Debridement for surgical wounds.

BACKGROUND: Surgical wounds that become infected are often debrided because clinicians believe that removal of this necrotic or infected tissue may expedite wound healing. There are numerous methods of debridement available, but no consensus on which one is most effective for surgical wounds. OBJECTIVES: To assess the effects of different methods of debridement on the rate of debridement and healing of surgical wounds. SEARCH METHODS: In October 2021, we searched the Cochrane Wounds Specialised Register, CENTRAL, MEDLINE, Embase, and CINAHL. To identify additional studies, we searched clinical trials registries for ongoing and unpublished studies, and scanned reference lists of relevant included studies, reviews, meta-analyses, and health technology reports. There were no restrictions on language, date of publication, or study setting. SELECTION CRITERIA: We included randomised controlled trials (RCTs) that enrolled people with a surgical wound that required debridement, and reported time to complete wound debridement or time to wound healing, or both. DATA COLLECTION AND ANALYSIS: Two review authors independently performed study selection, risk of bias assessment using the RoB 1 tool, data extraction, and GRADE assessment of the certainty of evidence. MAIN RESULTS: In this fourth update, we identified one additional study for inclusion. The review now includes six studies, with 265 participants, aged three to 91 years. Five studies were published between 1979 and 1990 and one published in 2014. The studies were carried out in hospital settings in China, Denmark, Belgium, and the UK. Six studies provided six comparisons. Due to the heterogeneity of studies, it was not appropriate to conduct meta-analyses. Four studies evaluated the effectiveness of dextranomer beads/paste; however, each study used a different comparator (Eusol-soaked dressings, 10% aqueous polyvinylpyrrolidone, 0.1% chloramine-soaked packs, and silicone foam elastomer dressing). One study compared streptokinase/streptodornase with saline-soaked dressings, and one compared endoscopic surgical debridement with conventional 'open' surgical debridement. Five studies reported time to complete debridement (reported as time to a clean wound bed) and three reported time to complete healing. One study reported effect estimates (surgical debridement via endoscopy versus surgical debridement) for time to a clean wound bed and time to complete wound healing, and it was possible to calculate effect estimates for one other study (dextranomer paste versus silicone foam elastomer) for time to complete wound healing. For the other four studies that did not report effect estimates, it was not possible to calculate time to a clean wound bed or time to complete wound healing due to missing variance and participant exclusions. None of the included studies reported outcomes pertaining to proportion of wounds completely healed, rate of reduction in wound size, rate of infection, or quality of life. All studies had unclear or high risk of bias for at least one key domain. Dextranomer paste/beads (autolytic debridement) compared with four different comparators Four studies compared dextranomer paste or beads with Eusol-soaked gauze (20 participants), 10% aqueous polyvinylpyrrolidone (40 participants), 0.1% chloramine-soaked dressings (28 participants), or silicone foam elastomer (50 participants). There is very low-certainty evidence that there may be no clear difference in time to a clean wound bed between dextranomer beads and Eusol gauze. The study did not report adverse events. There is very low-certainty evidence that there may be no difference in time to a clean wound bed between dextranomer paste and 10% aqueous polyvinylpyrrolidone gauze. There was low-certainty evidence that there may be no difference in deaths and serious adverse events. There may be a difference in time until the wounds were clinically clean and time to complete wound healing between dextranomer paste and 0.1% chloramine favouring 0.1% chloramine, but we are very uncertain. There is low-certainty evidence that there may be no difference in deaths and serious adverse events. There is very low-certainty evidence that there may be no difference in time to complete healing between dextranomer beads and silicone foam elastomer. The study did not report adverse events. Streptokinase/streptodornase solution (enzymatic) compared with saline-soaked dressings One study (21 participants) compared enzymatic debridement with saline-soaked dressings. There is low-certainty evidence that there may be no difference in time to a clean wound bed or secondary suture between streptokinase/streptodornase and saline-soaked dressings. There is very low-certainty evidence that there may be no difference in deaths and serious adverse events. Surgical debridement via endoscopic ('keyhole') surgery compared with surgical debridement by 'open' surgery (the wound is opened using a scalpel) One study (106 participants) reported time to complete wound healing and time to a clean wound bed. There is low-certainty evidence that there may be a reduction in time to complete wound healing and very low-certainty evidence that there may be no difference in time to a clean wound bed with surgical debridement via endoscopy compared to 'open' surgical debridement. The study did not report adverse events. Overall, the evidence was low to very low-certainty for all outcomes. Five included studies were published before 1991 and investigated treatments that are no longer available. Worldwide production of dextranomer products has been discontinued, except for dextranomer paste, which is currently only available in South Africa. Furthermore, Eusol, used in one study as the comparator to dextranomer, is rarely used due to risk of harmful effects on healthy tissue and the enzymatic agent streptokinase/streptodornase is no longer available worldwide. AUTHORS' CONCLUSIONS: Evidence for the effects of different methods of debridement on complete wound debridement and healing of surgical wounds remains unclear. Adequately powered, methodologically robust RCTs evaluating contemporary debridement interventions for surgical wounds are needed to guide clinical decision-making.

A Cross-sectional Survey of Comprehension and Satisfaction of Spanish-Reading Adults Regarding RÁPIDO as a Stroke Awareness Acronym.

ABSTRACT: BACKGROUND: Delay time to hospital arrival may be influenced by lack of recognition of stroke signs and the necessity to seek emergency medical, which in turn is influenced by language barriers to, a modifiable risk factor, stroke awareness education. The objective was to determine the comprehension and satisfaction of a Spanish stroke awareness acronym, RÁPIDO, among community-living, Hispanic and Latino, Spanish-reading adults. METHODS: A 33-item survey was completed by 166 adults. Data on sociodemographics, language preferences, stroke education, and comprehension and satisfaction with RÁPIDO were collected. Descriptive characteristics were calculated. Fisher exact tests were performed to determine whether reading language (group 1, only or predominantly reads in Spanish; group 2, reads in Spanish and English equally or reads predominately in English) influenced survey responses. Responses to open-ended questions were categorized. RESULTS: Sixty-nine percent of the participants were born outside of the United States, 82% currently resided in the United States, 34% read only or predominately in Spanish, and 7% had a stroke. Most participants thought RÁPIDO was informative, eye-catching, and easily remembered. Significant differences were found between reading language preference groups for correctly identifying RÁPIDO images for facial drooping (group 1, 80%; group 2, 95%; P ≤ .001) and dizziness/loss of balance (group 1, 54%; group 2, 73%; P = .027). Eighty percent or more of all participants were able to correctly interpret RÁPIDO images for facial drooping, blurry vision, impaired speech, and call emergency services. Adding "911" to the RÁPIDO image of the clock was a common suggestion. CONCLUSIONS: RÁPIDO was well received among the participants. Modifications to RÁPIDO images representing dizziness/loss of balance and arm weakness, and the addition of "911" may improve its usefulness. Obtaining more extensive feedback across the United States and testing the effect of RÁPIDO on increasing knowledge of stroke signs and retention of that knowledge are necessary next steps.

Changes in activities-specific balance confidence of active unilateral transtibial prosthesis users after provision of a self-aligning ankle foot.

BACKGROUND: Self-aligning ankle feet have an increased range of motion and are marketed to improve compliance over uneven terrain and increase function and balance; however, much of the existing literature focuses on the biomechanical aspect of these prostheses as opposed to patient-reported measures. OBJECTIVE: To compare activities-specific balance confidence (ABC), health-related quality of life (HR-QoL), perceived mobility, gait speed, and step length before and after provision of a self-aligning ankle foot in the active unilateral transtibial prosthesis user. STUDY DESIGN: Retrospective analysis of prospectively collected data. METHODS: Patient-reported and functional measures were captured for 85 users who were provided with a self-aligning ankle foot. Measures were recorded immediately before self-aligning ankle foot provision and again at 6 months afterward. The primary outcome was the ABC Score, along with the following secondary measures; HR-QoL using EQ-5D-5L Health Index Prosthetic Limb User Survey of Mobility and 10-meter timed walk test. RESULTS: The median age of the cohort was 55.2 years old and 71% were males, with the majority having their transtibial amputation due to trauma. There was a statistically significant improvement in ABC from 76 to 86% (p < 0.001) with a medium effect size. There was no statistically significant improvement in HR-QoL (p = 0.051), Prosthetic Limb User Survey of Mobility (p = 0.043), time taken to walk 10 m (p = 0.15) and step length (p = 0.003). CONCLUSIONS: Self aligning ankle feet increased ABC and step length with no detrimental effect on HR-QoL, perceived mobility or walking speed in those with a unilateral trans-tibial amputation.

A prospective study of MRI biomarkers in the brain and lower limb muscles for prediction of lower limb motor recovery following stroke.

The aim of this prospective observational longitudinal study was to explore and decipher the predictive value of prospective MRI biomarkers in the brain and lower limb muscles for 3-month lower limb motor recovery following stroke. In the brain, we measured the integrity of the corticospinal tract (fractional anisotropy/"FA"). In the muscles, we measured volume, fatty replacement (fat fraction analysis and proton spectroscopy) and oedema. Measurements were taken at two time points: (1) within 4 weeks of stroke (baseline measurement, clinical and imaging) and (2) 3 months following stroke (follow up measurement, clinical only). Clinical measurements consisted of assessments of functional ability and strength (Fugl-Meyer score, motor NIHSS, Functional Ambulation Category/"FAC", and muscle dynamometry). Twenty-three patients completed imaging and clinical assessments at baseline and follow-up; five patients had partial imaging assessment. The results provided some evidence that damage to the corticospinal tract would result in less motor recovery: recovery of the Fugl-Meyer score and dynamometric ankle plantarflexion, ankle dorsiflexion, and knee extension correlated positively and significantly with fractional anisotropy (0.406-0.457; p = 0.034-p = 0.016). However, fractional anisotropy demonstrated a negative correlation with recovery of the Functional Ambulation Category (-0.359, p = 0.046). For the muscle imaging, significant inverse correlation was observed between vastus lateralis fat fraction vs. NIHSS recovery (-0.401, p = 0.04), and a strong positive correlation was observed between ratio of intra- to extra-myocellular lipid concentrations and the recovery of knee flexion (0.709, p = 0.007). This study supports previous literature indicating a positive correlation between the integrity of the corticospinal tract and motor recovery post-stroke, expanding the limited available literature describing this relationship specifically for the lower limb. However, recovery of functional ambulation behaved differently to other clinical recovery markers by demonstrating an inverse relationship with corticospinal tract integrity. The study also introduces some muscle imaging biomarkers as potentially valuable in the prediction of 3-month lower limb motor recovery following stroke.

Absent loading response knee flexion: The impact on gait kinetics and centre of mass motion in individuals with unilateral transfemoral amputation, and the effect of microprocessor controlled knee provision.

BACKGROUND: Individuals with unilateral transfemoral amputation walk with increased levels of asymmetry, and this is associated with reduced gait efficiency, back pain and overuse of the intact limb. This study investigated the effect of walking with a unilateral absence of loading response knee flexion on the symmetry of anterior-posterior kinetics and centre of mass accelerations. METHODS: A retrospective cohort study design was used, assessing three-dimensional gait data from individuals with unilateral transfemoral amputation (n = 56). The anterior-posterior gait variables analysed included; peak ground reaction forces, impulse, centre of mass acceleration, as well as rate of vertical ground reaction force increase in early stance. With respect to these variables, this study assessed the symmetry between intact and prosthetic limbs, compared intact limbs against a healthy unimpaired control group, and evaluated effect on symmetry of microprocessor controlled knee provision. FINDINGS: Significant between-limb asymmetries were found between intact and prosthetic limbs across all variables (p < 0.0001). Intact limbs showed excessive loading when compared with control group limbs after speed normalisation across all variables (p < 0.0001). No improvement in kinetic symmetry following microprocessor controlled knee provision was found. INTERPRETATION: The gait asymmetries for individuals with transfemoral amputation identified in this study suggest that more should be done by developers to address the resultant overloading of the intact limb, as this is thought to have negative long-term effects. The provision of microprocessor controlled knees did not appear to improve the asymmetries faced by individuals with transfemoral amputation, and clinicians should be aware of this when managing patient expectations.

Case report: Single-stage facial reanimation with bilateral lengthening temporalis myoplasties for immune dysregulation, polyendocrinopathy, enteropathy, X-linked (IPEX) syndrome related developmental facial palsy.

Immune dysregulation, polyendocrinopathy, enteropathy, X-linked (IPEX) syndrome is a rare primary immunodeficiency, typically associated with clinical features of intractable diarrhoea, type 1 diabetes mellitus and eczema. We present a case of IPEX syndrome referred to our regional facial palsy service for smile restoration surgery. The patient presented with dissatisfaction of facial appearance, including mask-like facies and no functional smile. Pre-operative electromyography confirmed normal temporalis muscle activation. Consequently, the patient was offered single-stage bilateral lengthening temporalis myoplasties. The patient reported improved satisfaction with facial appearance. Surgery resulted in good early resting and voluntary symmetry. Oral commissures were elevated at rest improving oral incompetence. This is the first description of facial animation surgery in the context of IPEX syndrome. With careful consideration and patient selection, successful surgical restoration of resting symmetry and dynamic commissural smile can be achieved in this complex cohort of patients.

Evaluation of cannabidiol nanoparticles and nanoemulsion biodistribution in the central nervous system after intrathecal administration for the treatment of pain.

We investigated how the biodistribution of cannabidiol (CBD) within the central nervous system (CNS) is influenced by two different formulations, an oil-in-water (O/W) nanoemulsion and polymer-coated nanoparticles (PCNPs). We observed that both CBD formulations administered were preferentially retained in the spinal cord, with high concentrations reaching the brain within 10 min of administration. The CBD nanoemulsion reached Cmax in the brain at 210 ng/g within 120 min (Tmax), whereas the CBD PCNPs had a Cmax of 94 ng/g at 30 min (Tmax), indicating that rapid brain delivery can be achieved through the use of PCNPs. Moreover, the AUC0-4h of CBD in the brain was increased 3.7-fold through the delivery of the nanoemulsion as opposed to the PCNPs, indicating higher retention of CBD at this site. Both formulations exhibited immediate anti-nociceptive effects in comparison to the respective blank formulations.

Stroke in the young.

PURPOSE OF REVIEW: The purpose of this review is to review recent findings regarding stroke epidemiology, etiologies, and treatment in children and young adults. RECENT FINDINGS: Incidence in young adults is increasing, and incidence, recurrence, and survival is worse in patients with cryptogenic stroke and in developing countries. Careful consideration of patent foramen ovale closure is now recommended in young adults with cryptogenic stroke. Thrombectomy has recently been extended to carefully selected children with acute ischemic stroke, and two recent publications strongly suggest that it can be beneficial for children. Sickle cell is also an important global contributor to stroke burden, but hydroxyurea can be a cost effective medication for stroke prevention in children. Recent advances in genetic testing and treatments may improve outcomes for patients with monogenic causes of stroke, such as deficiency of adenosine deaminase 2, hemophilia, and Fabry's disease. SUMMARY: Stroke in children and young adults is a morbid disease responsible for enormous indirect societal costs and a high burden of years with disability per affected patient. Recent advances have improved access to care for children with large vessel occlusion and adults with rare causes of stroke. Future research may bring effective treatments for other monogenic causes of stroke as well as increasing access to hyperacute therapies for young stroke patients.

Evaluating patient and neurosurgeon perspectives on virtualisation of neurosurgery clinics in the COVID-19 era: a prospective mirror survey study.

BACKGROUND: The COVID-19 pandemic has compelled a global shift in healthcare service delivery towards virtualisation, including in Neurosurgery. Our study aims to elucidate the patient and neurosurgeon perceptions of virtual neurosurgery consultations (VNCs) and formulate a guidance algorithm based on our experience. METHODS: Between June 2020 and December 2020, we prospectively surveyed patients and neurosurgeons following their VNCs using a 10-item survey (four qualitative and six five-point Likert scale questions). Non-parametric hypothesis testing and grounded coding with inter-coder agreement was used to analyse quantitative and qualitative data, respectively. RESULTS: 106 patients and 10 neurosurgeons completed the survey. Wilcoxon rank-sum test revealed a statistically significant difference between the neurosurgeon and patient responses (p < 0.001). Patients perceived VNCs benefits to be enhanced efficiency (n = 142) and communication (28); and VNCs drawbacks as safety (46), technological (32), and administration (15) issues. Neurosurgeons perceived VNCs benefits to be enhanced efficiency (13), reduced COVID-19 exposure (2); and VNCs drawbacks as examination practicality (14), technological (6), and concerns for patients (6). Neurosurgeons perceived the relative indications for VNCs as postoperative follow-up clinics, and scan result discussions; and relative contraindications as neuro-oncology, new patients, and patients with worsening neurological symptoms. CONCLUSIONS: Our mirror-survey study provides preliminary evidence that VNCs render increased efficiency, communication, and safety in the current COVID-19 era. Going forward, we believe that further improvements in technology and administration are necessary, greater neurosurgeon appreciation of the patient-perceived benefits of VNCs is required, and neurosurgeons are to exercise clinical discernment on when to use VNCs.Key PointsWhat are the perceptions of patient and consultant neurosurgeons towards virtual neurosurgery consultations (VNCs)?Patient-perceived benefits of VNCs: enhanced efficiency/communication; VNC drawbacks: safety, technological, and administration issues. Neurosurgeon-perceived VNCs benefits of VNCs: enhanced efficiency, reduced COVID-19 exposure; VNC drawbacks: examination practicality, technological, and concerns for patients.Post-operative reviews and scan result discussions are perceived relative indications for VNCs; whereas new patient consultations, neuro-oncology and patients with new-onset neurological deficits are perceived relative contraindications for VNCs.Improvement in technology and administration is necessary; greater neurosurgeon appreciation of patient-perceived VNCs benefits is required, and neurosurgeons are to exercise clinical discernment on when to use VNCs.

An evaluation of pelvic floor disorders in a public and private healthcare setting.

INTRODUCTION AND HYPOTHESIS: The objectives were to determine whether a difference exists in the duration of pelvic floor disorder (PFD) symptoms among patients presenting to urogynecologists in two healthcare systems: private and county; and to elucidate differences in baseline characteristics, type of PFDs, symptom severity and management, stratified by healthcare plans. METHODS: A multi-center retrospective study was conducted including new patients presenting to three urogynecology clinics between March 2016 and May 2018: one private clinic (site A) and two public clinics in the same county healthcare system (sites B and C). Baseline data included age, race, BMI, parity, and comorbidities. Primary outcome was "time to presentation" defined as PFD duration in months. Secondary outcomes were symptom severity and PFD management, analyzed by healthcare setting and insurance type. RESULTS: A total of 1,055 private and 439 public patients were included. Patients in the public setting were younger (54 vs 61 years, p<0.001), largely Hispanic (76% vs 14%, p<0.001), of higher parity (4 vs 3, p=0.001), and had more comorbidities, with a predominance of county-funded healthcare plans. There was no difference in duration of symptoms between the public and private groups respectively (54 vs 56 months, p=0.94). Patients in the public setting had more severe urinary incontinence (3 vs 2 pads/day, p<0.001) and prolapse (stages 3-4, 71% vs 61%, p=0.004); however, they had lower rates of surgical management for stress incontinence and prolapse. Differences in fecal incontinence could not be evaluated owing to small sample size. CONCLUSIONS: Public patients presented younger with more severe symptoms but had lower rates of surgery for PFDs traditionally managed surgically.

Comparison of patient-reported and functional outcomes after transition from traditional upper limb prosthetics to multiarticulating hands in the user with a unilateral transradial amputation.

BACKGROUND: Multiarticulating hands (MAHs) have been commercially available for over 15 years. Despite this, their cost remains significantly higher than traditional electric hands, and they are not routinely available in many countries. The Scottish Specialist Prosthetic Service within the National Health Service has been prescribing MAHs since 2014. However, the benefits of MAHs provided in clinical settings are not well known. OBJECTIVES: This study aimed to compare patient-reported and functional measures in unilateral transradial prosthetic users transitioning from a body-powered or traditional myoelectric prosthesis to a MAH. STUDY DESIGN: This was a retrospective cohort analysis of individuals with a unilateral transradial amputation provided with a MAH. METHODS: Of 38 users provided with MAHs, 20 had complete data sets of patient-reported and functional measures before and 6 months after provision. These included Disabilities of the Arm, Shoulder, and Hand; Southampton Hand Assessment Procedure Index of Function; health-related quality of life (EQ-5D-5L Health Index); Trinity Amputation and Prosthesis Experience Scales satisfaction; and Box and Block Test. RESULTS: The mean age was 44 years (SD 16) (n = 20), and 75% were male. There were an 8-unit mean reduction in the Disabilities of the Arm, Shoulder, and Hand ( P = .01) and a 9.5-unit improvement in the Southampton Hand Assessment Procedure IOF ( P = .007) at 6 months after provision. Health-related quality of life did not change ( P = .581). Users reported a four-point improvement in their Trinity Amputation and Prosthesis Experience Scales ( P = .004) and transferred 3.3 blocks more completing the Box and Block Test ( P = .001). CONCLUSIONS: The evidence clearly supports continued provision of MAHs to this group of moderate users: the more function the user achieves, the less of a disability they perceive to have.

Development of nanoparticle loaded microneedles for drug delivery to a brain tumour resection site.

Systemic drug delivery to the central nervous system (CNS) has been historically impeded by the presence of the blood brain barrier rendering many therapies inefficacious to any cancer cells residing within the brain. Therefore, local drug delivery systems are being developed to overcome this shortfall. Here we have manufactured polymeric microneedle (MN) patches, which can be anchored within a resection cavity site following surgical removal of a tumour such as isocitrate dehydrogenase wild type glioblastoma (GBM). These MN patches have been loaded with polymer coated nanoparticles (NPs) containing cannabidiol (CBD) or olaparib (OLA) and applied to an in vitro brain simulant and ex vivo rat brain tissue to assess drug release and distance of penetration. MN patches loaded with methylene blue dye were placed into a cavity of 0.6 % agarose to simulate brain tissue. The results showed that clear channels were generated by the MNs and the dye spread laterally throughout the agarose. When loaded with CBD-NPs, the agarose showed a CBD concentration of 12.5 µg/g at 0.5 cm from the MN insertion site. Furthermore, high performance liquid chromatography of ex vivo brain tissue following CBD-NP/MN patch insertion showed successful delivery of 59.6 µg/g into the brain tissue. Similarly, OLA-NP loaded MN patches showed delivery of 5.2 µg/g OLA into agarose gel at 0.5 cm distance from the insertion site. Orbitrap secondary ion mass spectrometry (OrbiSIMS) analysis confirmed the presence of OLA and the MN patch at up to 6 mm away from the insertion site following its application to a rat brain hemisphere. This data has provided insight into the capabilities and versatility of MN patches for use in local brain drug delivery, giving promise for future research.

Impact of PPAM aid use on the time to prosthetic limb delivery in patients with unilateral transtibial amputation: A retrospective analysis.

BACKGROUND: The pneumatic postamputation mobility (PPAM) aid is the most commonly used early walking aid in the United Kingdom in transtibial amputation (TTA) and promotes wound healing and prepares the stump for prosthetic limb fitting. Optimal guidelines for PPAM aid use and how these factors affect achievement of rehabilitation milestones have not yet been conclusively established. OBJECTIVE: To investigate the relationship between PPAM aid use and the time taken to achieve rehabilitation milestones in patients undergoing unilateral TTA. STUDY DESIGN: Retrospective case note analysis. METHODS: Case notes of patients from one National Health Service amputation rehabilitation center who were identified as having a unilateral TTA in 2017-2018 and fitted with a prosthesis were reviewed. RESULTS: One hundred seven patients (67.5% male; mean age of 59.9 years) were identified. Use of PPAM aid during inpatient physiotherapy was associated with the days to reach referral, casting, delivery of prosthetic limb, and inpatient discharge dates (r (105) =-0.345; -0.400; -0.423; 0.546, respectively, all P < 0.05). Frequency of PPAM aid use was associated with the time to reach casting (r (105) =-0.533, P < 0.05) and delivery (r (105) =-0.513, P < 0.05). The days to being PPAM aid use and the frequency of PPAM aid use were predictive of the days to reach referral, casting, delivery, and inpatient discharge. CONCLUSIONS: The use of the PPAM aid is associated with a reduction in the time taken to reach rehabilitation milestones. Early and more frequent use of PPAM aid during rehabilitation will decrease the time fit and delivery of the prosthetic limb.

Testing Variational Bias Correction of Satellite Radiance Data in the ACCESS-C: Australian Convective-Scale NWP System.

Radiance observations are typically affected by biases that come mainly from instrument error (scanning or calibration) and inaccuracies of the radiative transfer model. These biases need to be removed for successful assimilation, so a bias correction scheme is crucial in the Numerical Weather Prediction (NWP) system. Today, most NWP centres, including the Bureau of Meteorology (hereafter, "the Bureau"), correct the biases through variational bias correction (VarBC) schemes, which were originally developed for global models. However, there are difficulties in estimating the biases in a limited-area model (LAM) domain. As a result, the Bureau's regional NWP system, ACCESS-C (Australian Community Climate and Earth System Simulator-City), uses variational bias coefficients obtained directly from its global NWP system ACCESS-G (Global). This study investigates independent radiance bias correction in the data assimilation system for ACCESS-C. We assessed the impact of using independent bias correction for the LAM compared with the operational bias coefficients derived in ACCESS-G between February and April 2020. The results from our experiment show no significant difference between the control and test, suggesting a neutral impact on the forecast. Our findings point out that the VarBC-LAM strategy should be further explored with different settings of predictors and adaptivity for a more extended period and over additional domains.

The clinical and translational prospects of microneedle devices, with a focus on insulin therapy for diabetes mellitus as a case study.

Microneedles have the clinical advantage of being able to deliver complex drugs across the skin in a convenient and comfortable manner yet haven't successfully transitioned to medical practice. Diabetes mellitus is a complicated disease, which is commonly treated with multiple daily insulin injections, contributing to poor treatment adherence. Firstly, this review determines the clinical prospect of microneedles, alongside considerations that ought to be addressed before microneedle technology can be translated from bench to bedside. Thereafter, we use diabetes as a case study to consider how microneedle-based-technology may be successfully harnessed. Here, publications referring to insulin microneedles were evaluated to understand whether insertion efficiency, angle of insertion, successful dose delivery, dose adjustability, material biocompatibility and therapeutic stability are being addressed in early stage research. Moreover, over 3,000 patents from 1970 to 2019 were reviewed with the search term '"microneedle" AND "insulin"' to understand the current status of the field. In conclusion, the reporting of early stage microneedle research demonstrated a lack of consistency relating to the translational factors addressed. Additionally, a more rational design, based on a patient-centred approach is required before microneedle-based delivery systems can be used to revolutionise the lives of people living with diabetes following regulatory approval.

Water T2 could predict functional decline in patients with dysferlinopathy.

BACKGROUND: Water T2 (T2H2O ) mapping is increasingly being used in muscular dystrophies to assess active muscle damage. It has been suggested as a surrogate outcome measure for clinical trials. Here, we investigated the prognostic utility of T2H2O to identify changes in muscle function over time in limb girdle muscular dystrophies. METHODS: Patients with genetically confirmed dysferlinopathy were assessed as part of the Jain Foundation Clinical Outcomes Study in dysferlinopathy. The cohort included 18 patients from two sites, both equipped with 3-tesla magnetic resonance imaging (MRI) systems from the same vendor. T2H2O value was defined as higher or lower than the median in each muscle bilaterally. The degree of deterioration on four functional tests over 3 years was assessed in a linear model against covariates of high or low T2H2O at baseline, age, disease duration, and baseline function. RESULTS: A higher T2H2O at baseline significantly correlated with a greater decline on functional tests in 21 out of 35 muscles and was never associated with slower decline. Higher baseline T2H2O in adductor magnus, vastus intermedius, vastus lateralis, and vastus medialis were the most sensitive, being associated bilaterally with greater decline in multiple timed tests. Patients with a higher than median baseline T2H2O (>40.6 ms) in the right vastus medialis deteriorated 11 points more on the North Star Ambulatory Assessment for Dysferlinopathy and lost an additional 86 m on the 6-min walk than those with a lower T2H2O (<40.6 ms). Optimum sensitivity and specificity thresholds for predicting decline were 39.0 ms in adductor magnus and vastus intermedius, 40.0 ms in vastus medialis, and 40.5 ms in vastus lateralis from different sites equipped with different MRI systems. CONCLUSIONS: In dysferlinopathy, T2H2O did not correlate with current functional ability. However, T2H2O at baseline was higher in patients who worsened more rapidly on functional tests. This suggests that inter-patient differences in functional decline over time may be, in part, explained by different severities of the active muscle damage, assessed by T2H2O measure at baseline. Significant challenges remain in standardizing T2H2O values across sites to allow determining globally applicable thresholds. The results from the present work are encouraging and suggest that T2H2O could be used to improve prognostication, patient selection, and disease modelling for clinical trials.

Three-year quantitative magnetic resonance imaging and phosphorus magnetic resonance spectroscopy study in lower limb muscle in dysferlinopathy.

BACKGROUND: Natural history studies in neuromuscular disorders are vital to understand the disease evolution and to find sensitive outcome measures. We performed a longitudinal assessment of quantitative magnetic resonance imaging (MRI) and phosphorus magnetic resonance spectroscopy (31 P MRS) outcome measures and evaluated their relationship with function in lower limb skeletal muscle of dysferlinopathy patients. METHODS: Quantitative MRI/31 P MRS data were obtained at 3 T in two different sites in 54 patients and 12 controls, at baseline, and three annual follow-up visits. Fat fraction (FF), contractile cross-sectional area (cCSA), and muscle water T2 in both global leg and thigh segments and individual muscles and 31 P MRS indices in the anterior leg compartment were assessed. Analysis included comparisons between patients and controls, assessments of annual changes using a linear mixed model, standardized response means (SRM), and correlations between MRI and 31 P MRS markers and functional markers. RESULTS: Posterior muscles in thigh and leg showed the highest FF values. FF at baseline was highly heterogeneous across patients. In ambulant patients, median annual increases in global thigh and leg segment FF values were 4.1% and 3.0%, respectively (P < 0.001). After 3 years, global thigh and leg FF increases were 9.6% and 8.4%, respectively (P < 0.001). SRM values for global thigh FF were over 0.8 for all years. Vastus lateralis muscle showed the highest SRM values across all time points. cCSA decreased significantly after 3 years with median values of 11.0% and 12.8% in global thigh and global leg, respectively (P < 0.001). Water T2 values in ambulant patients were significantly increased, as compared with control values (P < 0.001). The highest water T2 values were found in the anterior part of thigh and leg. Almost all 31 P MRS indices were significantly different in patients as compared with controls (P < 0.006), except for pHw , and remained, similar as to water T2 , abnormal for the whole study duration. Global thigh water T2 at baseline was significantly correlated to the change in FF after 3 years (ρ = 0.52, P < 0.001). There was also a significant relationship between the change in functional score and change in FF after 3 years in ambulant patients (ρ = -0.55, P = 0.010). CONCLUSIONS: This multi-centre study has shown that quantitative MRI/31 P MRS measurements in a heterogeneous group of dysferlinopathy patients can measure significant changes over the course of 3 years. These data can be used as reference values in view of future clinical trials in dysferlinopathy or comparisons with quantitative MRI/S data obtained in other limb-girdle muscular dystrophy subtypes.

Building community resilience in a context of climate change: The role of social capital.

Social capital is considered important for resilience across social levels, including communities, yet insights are scattered across disciplines. This meta-synthesis of 187 studies examines conceptual and empirical understandings of how social capital relates to resilience, identifying implications for community resilience and climate change practice. Different conceptualisations are highlighted, yet also limited focus on underlying dimensions of social capital and proactive types of resilience for engaging with the complex climate change challenge. Empirical insights show that structural and socio-cultural aspects of social capital, multiple other factors and formal actors are all important for shaping the role of social capital for guiding resilience outcomes. Thus, finding ways to work with these different elements is important. Greater attention on how and why outcomes emerge, interactions between factors, approaches of formal actors and different socio-cultural dimensions will advance understandings about how to nurture social capital for resilience in the context of climate change.

Characteristics and outcome of patients transported by police to emergency departments under section 351 of the Mental Health Act 2014 (Vic).

OBJECTIVE: To determine characteristics, precipitating circumstances, clinical care, outcome and disposition of patients brought to the ED under section 351 (s351, police detention and transport) powers of the Mental Health Act 2014 (Vic) (MHAV). METHODS: This is an observational cohort study conducted in two metropolitan teaching hospitals in Victoria. Participants were adult patients brought to ED under s351 of the MHAV. Data collected included demographics, event circumstances, pre-hospital and ED interventions and outcome. Analyses are descriptive. RESULTS: The present study included 438 patient encounters. Median age was 34 years. In 84% of encounters (368/438) patients were co-transported with ambulance. The most common primary reason for detainment was suicide risk/intent (296/438, 67.6%) followed by abnormal behaviour without threat to self or others (92/438, 21%). In ED, parenteral sedation was administered in 11% (48/438). Physical restraint was applied in 17.6% (77/438). Psychiatric admission was required in 23.5% (103/438). In 63 cases, psychiatric admission was involuntary (14.4%). Most patients (297/438, 67.8%) were discharged home. A subset of patients had recurrent s351 presentations. Eighteen (5.6%) patients accounted for 22% (96/438) of all events. CONCLUSION: Most patients brought to ED under s351 of the MHAV had expressed intention to self-harm, did not require medical intervention and were discharged home. It could be questioned whether the current application of s351 is consistent with the least restrictive principles of the MHAV, especially as there is no apparent monitoring or reporting of the use of these powers. There were a concerning number of patients with multiple s351 events over a short period.

The impact of COVID-19 infection on hip fracture 30-day mortality.

Introduction: A novel virus, SARS-CoV-2, has caused a fatal global pandemic which particularly affects the elderly and those with comorbidities. Hip fractures affect elderly populations, necessitate hospital admissions and place this group at particular risk from COVID-19 infection. This study investigates the effect of COVID-19 infection on 30-day hip fracture mortality. Method: Data related to 75 adult hip fractures admitted to two units during March and April 2020 were reviewed. The mean age was 83.5 years (range 65-98 years), and most (53, 70.7%) were women. The primary outcome measure was 30-day mortality associated with COVID-19 infection. Results: The COVID-19 infection rate was 26.7% (20 patients), with a significant difference in the 30-day mortality rate in the COVID-19-positive group (10/20, 50%) compared to the COVID-19-negative group (4/55, 7.3%), with mean time to death of 19.8 days (95% confidence interval: 17.0-22.5). The mean time from admission to surgery was 43.1 h and 38.3 h, in COVID-19-positive and COVID-19-negative groups, respectively. All COVID-19-positive patients had shown symptoms of fever and cough, and all 10 cases who died were hypoxic. Seven (35%) cases had radiological lung findings consistent of viral pneumonitis which resulted in mortality (70% of mortality). 30% (n = 6) contracted the COVID-19 infection in the community, and 70% (n = 14) developed symptoms after hospital admission. Conclusion: Hip fractures associated with COVID-19 infection have a high 30-day mortality. COVID-19 testing and chest X-ray for patients presenting with hip fractures help in early planning of high-risk surgeries and allow counselling of the patients and family using realistic prognosis.