Use of a penicillin allergy clinical decision rule to enable direct oral penicillin provocation: an international multicentre randomised control trial in an adult population (PALACE): study protocol

Introduction Penicillin allergies are highly prevalent in the healthcare setting and associated with the prescription of second-line inferior antibiotics. More than 85% of all penicillin allergy labels can be removed by skin testing and 96%–99% of low-risk penicillin allergy labels can be removed by direct oral challenge. An internally and externally validated clinical assessment tool for penicillin allergy, PEN-FAST, can identify a low-risk penicillin allergy without the need for skin testing; a score of less than 3 has a negative predictive value of 96.3% (95% CI, 94.1 to 97.8) for the presence of a penicillin allergy. It is hypothesised that PEN-FAST is a safe and effective tool for assessing penicillin allergy in an outpatient clinic setting. Methods and analysis This is an international, multicentre randomised control trial using the PEN-FAST tool to risk-stratify penicillin allergy labels in adult outpatients. The study’s primary objective is to evaluate the non-inferiority of using PEN-FAST score-guided management with direct oral challenge compared with standard care (defined as prick and intradermal skin testing followed by oral penicillin challenge). Participants will be randomised 1:1 to the intervention arm (direct oral penicillin challenge) or standard of care arm (skin testing followed by oral penicillin challenge, if skin testing is negative). The sample size of 380 randomised patients (190 per treatment arm) is required to demonstrate non-inferiority. Ethics and dissemination The study will be performed according to the guidelines of the Helsinki Declaration and is approved by the Austin Health Human Research Ethics Committee (HREC/62425/Austin-2020) in Melbourne Australia, Vanderbilt University Institutional Review Board (IRB #202174) in Tennessee, USA, Duke University Institutional Review Board (IRB #Pro00108461) in North Carolina, USA and McGill University Health Centre Research Ethics Board in Canada (PALACE/2022-7605). The results of this study will be published and presented in various scientific forums

Leucine-enriched whey protein supplementation,resistance-based exercise, and cardiometabolic healthin older adults: a randomized controlled trial

Background Increasing protein intake (above the Recommended Dietary Amount) alone or with resistance-based exercise is suggested to improve cardiometabolic health; however, randomized controlled trials (RCTs) are needed to confirm this. Methods The Liverpool Hope University-Sarcopenia Aging Trial (LHU-SAT) was a 16 week RCT (ClinicalTrials.gov Identifier: NCT02912130) of 100 community-dwelling older adults [mean age: 68.73 ± 5.80 years, body mass index: 27.06 ± 5.18 kg/m2 (52% women)] who were randomized to four independent groups [Control (C), Exercise (E), Exercise + Protein (EP), Protein (P)]. E and EP completed supervised and progressive resistance-based exercise (resistance exercise: two times per week, functional circuit exercise: once per week), while EP and P were supplemented with a leucine-enriched whey protein drink (three times per day) based on individual body weight (0.50 g/kg/meal, 1.50 g/kg/day). Outcome measures including arterial stiffness (pulse wave velocity), fasting plasma/serum biomarkers [glucose/glycated haemoglobin, total cholesterol, low-density lipoprotein (LDL), high-density lipoprotein, insulin, resistin, leptin, adiponectin, C-reactive protein, tumour necrosis factor-alpha, interleukin-6, cystatin-C, & ferritin], insulin resistance (HOMA-IR), and kidney function (eGFR) were measured before and after intervention. Results Total protein intake (habitual diet plus supplementation) increased to 1.55 ± 0.69 g/kg/day in EP and to 1.93 ± 0.72 g/kg/day in P, and remained significantly lower (P < 0.001) in unsupplemented groups (E: 1.08 ± 0.33 g/kg/day, C: 1.00 ± 0.26 g/kg/day). At 16 weeks, there was a group-by-time interaction whereby absolute changes in LDL-cholesterol were lower in EP [mean difference: �0.79 mmol/L, 95% confidence interval (CI): �1.29, �0.28, P = 0.002] and P (mean difference: �0.76 mmol/L, 95% CI: �1.26, �0.26, P = 0.003) vs. C. Serum insulin also showed group-by-time interactions at 16 weeks whereby fold changes were lower in EP (mean difference: �0.40, 95% CI: �0.65, �0.16, P = 0.001) and P (mean difference: �0.32, 95% CI: �0.56, �0.08, P = 0.009) vs. C, and fold changes in HOMA-IR improved in EP (mean difference: �0.37, 95% CI: �0.64, �0.10, P = 0.007) and P (mean difference: �0.27, 95% CI: �0.53, �0.00, P = 0.048) vs. C. Serum resistin declined in P only (group-by-time interaction at 16 weeks: P = 0.009). No other interactions were observed in outcome measures (P > 0.05), and kidney function (eGFR) remained unaltered. Conclusions Sixteen weeks of leucine-enriched whey protein supplementation alone and combined with resistance-based exercise improved cardiometabolic health markers in older adults. Keywords Aging; Insulin resistance; Inflammation; Lipoprotein

Study protocol: Australasian Registry of Severe Cutaneous Adverse Reactions (AUS-SCAR)

Introduction Severe cutaneous adverse reactions (SCAR) are a group of T cell-mediated hypersensitivities associated with significant morbidity, mortality and hospital costs. Clinical phenotypes include Stevens-Johnson syndrome (SJS), toxic epidermal necrolysis (TEN), drug reaction with eosinophilia and systemic symptoms (DRESS) and acute generalised exanthematous pustulosis (AGEP). In this Australasian, multicentre, prospective registry, we plan to examine the clinical presentation, drug causality, genomic predictors, potential diagnostic approaches, treatments and long-term outcomes of SCAR in Australia and New Zealand. Methods and analysis Adult and adolescent patients with SCAR including SJS, TEN, DRESS, AGEP and another T cell-mediated hypersensitivity, generalised bullous fixed drug eruption, will be prospectively recruited. A waiver of consent has been granted for some sites to retrospectively include cases which result in early mortality. DNA will be collected for all prospective cases. Blood, blister fluid and skin biopsy sampling is optional and subject to patient consent and site capacity. To develop culprit drug identification and prevention, genomic testing will be performed to confirm human leukocyte antigen (HLA) type and ex vivo testing will be performed via interferon-γ release enzyme linked immunospot assay using collected peripheral blood mononuclear cells. The long-term outcomes of SCAR will be investigated with a 12-month quality of life survey and examination of prescribing and mortality data. Ethics and dissemination This study was reviewed and approved by the Austin Health Human Research Ethics Committee (HREC/50791/Austin-19). Results will be published in peer-reviewed journals and presented at relevant conferences

Revision joint replacement surgeries of the hip and knee across geographic region and socioeconomic status in the western region of Victoria: a cross-sectional multilevel analysis of registry data

Background: Residents of rural and regional areas, compared to those in urban regions, are more likely to experience geographical difficulties in accessing healthcare, particularly specialist services. We investigated associations between region of residence, socioeconomic status (SES) and utilisation of all-cause revision hip replacement or revision knee replacement surgeries. Methods: Conducted in western Victoria, Australia, as part of the Ageing, Chronic Disease and Injury study, data from the Australian Orthopaedic Association National Joint Replacement Registry (2011–2013) for adults who underwent a revision hip replacement (n = 542; 54% female) or revision knee replacement (n = 353; 54% female) were extracted. We cross-matched residential addresses with 2011 census data from the Australian Bureau of Statistics (ABS), and using an ABS-derived composite index, classified region of residence according to local government areas (LGAs), and area-level SES into quintiles. For analyses, the control population (n = 591,265; 51% female) was ABS-determined and excluded adults already identified as cases. Mixed-effects logistic regression was performed. Results: We observed that 77% of revision hip surgeries and 83% of revision knee surgeries were performed for residents in the three most socially disadvantaged quintiles. In adjusted multilevel models, total variances contributed by the variance in LGAs for revisions of the hip or knee joint were only 1% (SD random effects ±0.01) and 3% (SD ± 0.02), respectively. No differences across SES or sex were observed. Conclusions: No differences in utilisation were identified between SES groups in the provision of revision surgeries of the hip or knee, independent of small between-LGA differences.Sharon L. Brennan-Olsen, Sara Vogrin, Stephen Graves, Kara L. Holloway-Kew, Richard S. Page, M. Amber Sajjad, Mark A. Kotowicz, Patricia M. Livingston, Mustafa Khasraw, Sharon Hakkennes, Trisha L. Dunning, Susan Brumby, Alasdair G. Sutherland, Jason Talevski, Darci Green, Thu-Lan Kelly, Lana J. Williams, and Julie A. Pasc

Fractures in indigenous compared to non-indigenous populations: a systematic review of rates and aetiology

BackgroundCompared to non-indigenous populations, indigenous populations experience disproportionately greater morbidity, and a reduced life expectancy; however, conflicting data exist regarding whether a higher risk of fracture is experienced by either population. We systematically evaluate evidence for whether differences in fracture rates at any skeletal site exist between indigenous and non-indigenous populations of any age, and to identify potential risk factors that might explain these differences.MethodsOn 31 August 2016 we conducted a comprehensive computer-aided search of peer-reviewed literature without date limits. We searched PubMed, OVID, MEDLINE, CINAHL, EMBASE, and reference lists of relevant publications. The protocol for this systematic review is registered in PROSPERO, the International Prospective Register of systematic reviews (CRD42016043215). Using the World Health Organization reference population as standard, hip fracture incidence rates were re-standardized for comparability between countries.ResultsOur search yielded 3227 articles; 283 potentially eligible articles were cross-referenced against predetermined criteria, leaving 27 articles for final inclusion. Differences in hip fracture rates appeared as continent-specific, with lower rates observed for indigenous persons in all countries except for Canada and Australia where the opposite was observed. Indigenous persons consistently had higher rates of trauma-related fractures; the highest were observed in Australia where craniofacial fracture rates were 22-times greater for indigenous compared to non-indigenous women. After adjustment for socio-demographic and clinical risk factors, approximately a three-fold greater risk of osteoporotic fracture and five-fold greater risk of craniofacial fractures was observed for indigenous compared to non-indigenous persons; diabetes, substance abuse, comorbidity, lower income, locality, and fracture history were independently associated with an increased risk of fracture.ConclusionsThe observed paucity of data and suggestion of continent-specific differences indicate an urgent need for further research regarding indigenous status and fracture epidemiology and aetiology. Our findings also have implications for communities, governments and healthcare professionals to enhance the prevention of trauma-related fractures in indigenous persons, and an increased focus on modifiable lifestyle behaviours to prevent osteoporotic fractures in all populations

The diagnostic value of the Short Physical Performance Battery for sarcopenia

BACKGROUND: Sarcopenia is defined as the age-related loss of muscle mass, strength, and physical performance. The original European Working Group on Sarcopenia in Older Persons (EWGSOP1) definition, and its revision (EWGSOP2), provide new cut-points and alternate measures for sarcopenia diagnosis. However, sarcopenia is rarely diagnosed in clinical settings owing to its labor-intensive diagnostic process. Given the Short Physical Performance Battery (SPPB) is a quick, easily administrable, and objective measure of muscle strength and physical performance, both of which are key components of sarcopenia, this study examined the diagnostic value of the SPPB for this muscle disease. METHODS: A cross-sectional analysis of 294 community-dwelling older persons (≥65 years) was conducted. Appendicular lean body mass [(ALM) divided by height squared (ALM/h2)], muscle strength (handgrip/sit to stand), and physical performance [gait speed, timed up and go (TUG) and SPPB] were assessed using validated procedures, while participants were diagnosed with sarcopenia following the EWGSOP1 and EWGSOP2 criteria. Diagnostic ability of the SPPB independently and combined with ALM/h2 for sarcopenia was determined using area under the curve (AUC). Potential cut-points were identified, and sensitivity and specificity calculated. RESULTS: Prevalence of sarcopenia ranged from 4 to 16% depending on the definition. The SPPB demonstrated moderate (AUC = 0.644-0.770) value in diagnosing sarcopenia, and a cut-point of ≤8points in SPPB performance resulted in high sensitivity (82-100%) but low specificity (36-41%) for diagnosing those with severe sarcopenia. CONCLUSIONS: The SPPB displayed acceptable value in diagnosing older adults with severe sarcopenia. Moreover, the high sensitivity of the SPPB when using the cut-point of ≤8 suggests it may be a favorable screening tool for sarcopenia in clinical settings where ALM measurements are not available

Balance training using virtual reality improves balance and physical performance in older adults at high risk of falls

Purpose: Exercise programs designed for falls prevention have been proven effective in reducing falls by approximately 21%. Virtual reality may provide a viable alternative intervention for falls prevention. This study compared the effects of virtual reality training using the Balance Rehabilitation Unit (BRU) versus exercise using a modified Otago Exercise Programme (EX) on improving balance and physical performance in the short-term restorative care setting of the Gait and Balance Gym (Gabagym). Patients and methods: This was a pre- and post-intervention study of 195 participants (median age 78 years, IQR 73-84; 67% female) who presented with a risk and/or history of falls. Participants were assigned to either EX (n=82) or BRU (n=63). Supervised sessions occurred twice a week for 6 weeks. Participants receiving interventions were compared to a separate group (n=50) with similar characteristics who did not receive any intervention. Balance and physical performance were assessed at initial and final attendance and included the 5 Times Sit to Stand (5STS) test, Timed Up and Go (TUG), gait speed and posturography assessment using the BRU. Fear of falling was assessed using the Falls Efficacy Scale. Handgrip strength and adherence were also monitored. Results: Post-intervention, EX and BRU groups achieved similar improvements and reported similar adherence rates (71% vs 72%, respectively). Both intervention groups improved in balance and physical performance measures. Both interventions showed significantly better improvement than the non-intervention group in TUG (p<0.001), gait speed (p=0.021), limits of stability in posturography assessment (p=0.008), FES-I score (p=0.013) and handgrip strength (p=0.021). Only the BRU group improved control of static posture in the eyes closed (p=0.002) and foam eyes closed (p=0.006) tasks. Conclusion: This study highlights the potential use of virtual reality as a practical alternative to improve outcomes of balance training for reduction of falls risk in older adults

Degree of hippocampal atrophy is not related to a history of febrile seizures in patients with proved hippocampal sclerosis

OBJECTIVES—To examine the degree of hippocampal atrophy in patients with temporal lobe epilepsy and proved hippocampal sclerosis to determine whether or not patients with febrile seizures have more severe hippocampal atrophy. To determine whether or not there is a relation between age of seizure onset, duration of temporal lobe epilepsy, or seizure frequency, and severity of hippocampal atrophy.
METHODS—Hippocampal volumes were measured from volumetrically acquired MR images in 77 consecutive surgical patients with temporal lobe epilepsy (37 febrile seizures (FS)+, 40 FS−) with proved hippocampal sclerosis, and compared with 98controls.
RESULTS—Ipsilateral and contralateral hippocampal volumes were not significantly different between the FS+ and FS− groups. There was no difference in the age of onset of habitual seizures, duration of epilepsy, or age at the time of surgery, between these groups. No clinically significant correlations were found between hippocampal volumes and age of onset of first non-febrile seizure, duration of temporal lobe epilepsy, or complex partial and secondarily generalised seizure frequency, in patients with and without febrile seizures.
CONCLUSIONS—Although febrile seizures was associated with hippocampal sclerosis in 48% of patients in this surgical series, the degree of MRI determined hippocampal atrophy was not related to a history of such seizures. The results do not support the view that febrile seizures cause more severe hippocampal sclerosis and are consistent with the hypothesis that hippocampal sclerosis is a pre-existing abnormality.