Investigating the outcomes of virus coinfection within and across host species.

Interactions between coinfecting pathogens have the potential to alter the course of infection and can act as a source of phenotypic variation in susceptibility between hosts. This phenotypic variation may influence the evolution of host-pathogen interactions within host species and interfere with patterns in the outcomes of infection across host species. Here, we examine experimental coinfections of two Cripaviruses-Cricket Paralysis Virus (CrPV), and Drosophila C Virus (DCV)-across a panel of 25 Drosophila melanogaster inbred lines and 47 Drosophilidae host species. We find that interactions between these viruses alter viral loads across D. melanogaster genotypes, with a ~3 fold increase in the viral load of DCV and a ~2.5 fold decrease in CrPV in coinfection compared to single infection, but we find little evidence of a host genetic basis for these effects. Across host species, we find no evidence of systematic changes in susceptibility during coinfection, with no interaction between DCV and CrPV detected in the majority of host species. These results suggest that phenotypic variation in coinfection interactions within host species can occur independently of natural host genetic variation in susceptibility, and that patterns of susceptibility across host species to single infections can be robust to the added complexity of coinfection.

The host phylogeny determines viral infectivity and replication across Staphylococcus host species.

Virus host shifts, where a virus transmits to and infects a novel host species, are a major source of emerging infectious disease. Genetic similarity between eukaryotic host species has been shown to be an important determinant of the outcome of virus host shifts, but it is unclear if this is the case for prokaryotes where anti-virus defences can be transmitted by horizontal gene transfer and evolve rapidly. Here, we measure the susceptibility of 64 strains of Staphylococcaceae bacteria (48 strains of Staphylococcus aureus and 16 non-S. aureus species spanning 2 genera) to the bacteriophage ISP, which is currently under investigation for use in phage therapy. Using three methods-plaque assays, optical density (OD) assays, and quantitative (q)PCR-we find that the host phylogeny explains a large proportion of the variation in susceptibility to ISP across the host panel. These patterns were consistent in models of only S. aureus strains and models with a single representative from each Staphylococcaceae species, suggesting that these phylogenetic effects are conserved both within and among host species. We find positive correlations between susceptibility assessed using OD and qPCR and variable correlations between plaque assays and either OD or qPCR, suggesting that plaque assays alone may be inadequate to assess host range. Furthermore, we demonstrate that the phylogenetic relationships between bacterial hosts can generally be used to predict the susceptibility of bacterial strains to phage infection when the susceptibility of closely related hosts is known, although this approach produced large prediction errors in multiple strains where phylogeny was uninformative. Together, our results demonstrate the ability of bacterial host evolutionary relatedness to explain differences in susceptibility to phage infection, with implications for the development of ISP both as a phage therapy treatment and as an experimental system for the study of virus host shifts.

Indirect treatment comparisons of the gene therapy etranacogene dezaparvovec versus extended half-life factor IX therapies for severe or moderately severe haemophilia B.

INTRODUCTION: Etranacogene dezaparvovec gene therapy for haemophilia B demonstrated superior efficacy at 24 months in reducing bleeds versus a ≥6-month lead-in period of prophylaxis with FIX products in the phase 3 trial, HOPE-B. In the absence of head-to-head comparisons of etranacogene dezaparvovec versus FIX products, indirect treatment comparisons (ITC) can be used. AIM: To compare the efficacy of etranacogene dezaparvovec versus rIX-FP, rFIXFc and N9-GP using ITC, and support HOPE-B results. METHODS: Data were leveraged from Phase 3 pivotal trials: HOPE-B, PROLONG-9FP, B-LONG and Paradigm 2. Annualised bleeding rates (ABR), spontaneous (AsBR) and joint (AjBR) bleeding rates, percentage of patients with no bleeds, and FIX consumption were assessed using inverse probability of treatment weighting and matching adjusted indirect comparisons. RESULTS: Etranacogene dezaparvovec demonstrated statistically significantly lower bleeding rates versus all comparators. Rate ratios for ABR, AsBR and AjBR versus rIX-FP were 0.19 (p < .0001), 0.08 (p < .0001) and 0.09 (p < .0001), respectively. Rate ratios for ABR, AsBR and AjBR versus rFIXFc were 0.14 (p < .0001), 0.13 (p = .0083) and 0.15 (p = .0111), respectively. Rate ratios for ABR and AsBR, versus N9-GP were 0.24 (p = .0231) and 0.13 (p = .0071), respectively. Etranacogene dezaparvovec demonstrated significantly higher percentage of patients with no bleeds versus rIX-FP and rFIXFc; odds ratios: 17.60 (p < .0001) and 5.65 (p = .0037), respectively. Etranacogene dezaparvovec resulted in significantly lower FIX consumption than all comparators. CONCLUSIONS: ITC suggests that etranacogene dezaparvovec offers patients with haemophilia B (≤2% of normal FIX expression) a single dose treatment that can significantly reduce bleeding rates and eliminate routine infusions associated with FIX therapies.

The Origin of Internal Genes Contributes to the Replication and Transmission Fitness of H7N9 Avian Influenza Virus.

H9N2 avian influenza viruses (AIVs) have donated internal gene segments during the emergence of zoonotic AIVs, including H7N9. We used reverse genetics to generate A/Anhui/1/13 (H7N9) and three reassortant viruses (2:6 H7N9) which contained the hemagglutinin and neuraminidase from Anhui/13 (H7N9) and the six internal gene segments from H9N2 AIVs belonging to (i) G1 subgroup 2, (ii) G1 subgroup 3, or (iii) BJ94 lineages, enzootic in different regions throughout Asia. Infection of chickens with the 2:6 H7N9 containing G1-like H9N2 internal genes conferred attenuation in vivo, with reduced shedding and transmission to contact chickens. However, possession of BJ94-like H9N2 internal genes resulted in more rapid transmission and significantly elevated cloacal shedding compared to the parental Anhui/13 H7N9. In vitro analysis showed that the 2:6 H7N9 with BJ94-like internal genes had significantly increased replication compared to the Anhui/13 H7N9 in chicken cells. In vivo coinfection experiments followed, where chickens were coinfected with pairs of Anhui/13 H7N9 and a 2:6 H7N9 reassortant. During ensuing transmission events, the Anhui/13 H7N9 virus outcompeted 2:6 H7N9 AIVs with internal gene segments of BJ94-like or G1-like H9N2 viruses. Coinfection did lead to the emergence of novel reassortant genotypes that were transmitted to contact chickens. Some of the reassortant viruses had a greater replication in chicken and human cells compared to the progenitors. We demonstrated that the internal gene cassette determines the transmission fitness of H7N9 viruses in chickens, and the reassortment events can generate novel H7N9 genotypes with increased virulence in chickens and enhanced zoonotic potential. IMPORTANCE H9N2 avian influenza viruses (AIVs) are enzootic in poultry in different geographical regions. The internal genes of these viruses can be exchanged with other zoonotic AIVs, most notably the A/Anhui/1/2013-lineage H7N9, which can give rise to new virus genotypes with increased veterinary, economic and public health threats to both poultry and humans. We investigated the propensity of the internal genes of H9N2 viruses (G1 or BJ94) in the generation of novel reassortant H7N9 AIVs. We observed that the internal genes of H7N9 which were derivative of BJ94-like H9N2 virus have a fitness advantage compared to those from the G1-like H9N2 viruses for efficient transmission among chickens. We also observed the generation of novel reassortant viruses during chicken transmission which infected and replicated efficiently in human cells. Therefore, such emergent reassortant genotypes may pose an elevated zoonotic threat.

Coinfection of Chickens with H9N2 and H7N9 Avian Influenza Viruses Leads to Emergence of Reassortant H9N9 Virus with Increased Fitness for Poultry and a Zoonotic Potential.

An H7N9 low-pathogenicity avian influenza virus (LPAIV) emerged in 2013 through genetic reassortment between H9N2 and other LPAIVs circulating in birds in China. This virus causes inapparent clinical disease in chickens, but zoonotic transmission results in severe and fatal disease in humans. To examine a natural reassortment scenario between H7N9 and G1 lineage H9N2 viruses predominant in the Indian subcontinent, we performed an experimental coinfection of chickens with A/Anhui/1/2013/H7N9 (Anhui/13) virus and A/Chicken/Pakistan/UDL-01/2008/H9N2 (UDL/08) virus. Plaque purification and genotyping of the reassortant viruses shed via the oropharynx of contact chickens showed H9N2 and H9N9 as predominant subtypes. The reassortant viruses shed by contact chickens also showed selective enrichment of polymerase genes from H9N2 virus. The viable "6+2" reassortant H9N9 (having nucleoprotein [NP] and neuraminidase [NA] from H7N9 and the remaining genes from H9N2) was successfully shed from the oropharynx of contact chickens, plus it showed an increased replication rate in human A549 cells and a significantly higher receptor binding to α2,6 and α2,3 sialoglycans compared to H9N2. The reassortant H9N9 virus also had a lower fusion pH, replicated in directly infected ferrets at similar levels compared to H7N9 and transmitted via direct contact. Ferrets exposed to H9N9 via aerosol contact were also found to be seropositive, compared to H7N9 aerosol contact ferrets. To the best of our knowledge, this is the first study demonstrating that cocirculation of H7N9 and G1 lineage H9N2 viruses could represent a threat for the generation of novel reassortant H9N9 viruses with greater virulence in poultry and a zoonotic potential. IMPORTANCE We evaluated the consequences of reassortment between the H7N9 and the contemporary H9N2 viruses of the G1 lineage that are enzootic in poultry across the Indian subcontinent and the Middle East. Coinfection of chickens with these viruses resulted in the emergence of novel reassortant H9N9 viruses with genes derived from both H9N2 and H7N9 viruses. The "6+2" reassortant H9N9 (having NP and NA from H7N9) virus was shed from contact chickens in a significantly higher proportion compared to most of the reassortant viruses, showed significantly increased replication fitness in human A549 cells, receptor binding toward human (α2,6) and avian (α2,3) sialic acid receptor analogues, and the potential to transmit via contact among ferrets. This study demonstrated the ability of viruses that already exist in nature to exchange genetic material, highlighting the potential emergence of viruses from these subtypes with zoonotic potential.

A large case series on the use of diphencyprone immunotherapy in the clearance of palmoplantar warts.

BACKGROUND: Palmoplantar viral warts are common, often affecting the quality of life of patients and present a major therapeutic challenge. Immunotherapy using diphencyprone (DCP) can be beneficial especially if first-line treatments fail. AIM: To determine the effectiveness of DCP in clearing viral warts, and to provide detail on the number of treatments required and any adverse effects (AEs). METHODS: This was a retrospective case series of 124 patients who had received DCP treatment in a UK private practice setting from 1991 to 2008, carried out by a dermatologist experienced in the procedure. All patients had been referred by other clinicians after failure of standard treatments. The study data were extracted from clinical records, with follow-up until wart clearance or treatment discontinuation. RESULTS: There was an equal distribution in sexes (63 females, 61 males), with 37% of patients having warts present for greater than 5 years. The majority (93%) of patients had already tried cryotherapy, which was unsuccessful in clearing warts completely in all cases. Following DCP treatment, 77% of patients achieved full eradication of their warts, including three patients who were immunosuppressed. The mean number of DCP treatments required to achieve full clearance was 4·7, and the mean concentration of DCP required was 4%. Only 12% of patients experienced AEs, which were mild, and included urticaria and blistering. CONCLUSION: We suggest that DCP immunotherapy is a safe and effective treatment for eradicating viral warts, especially in recalcitrant cases.

Management and treatment outcome of DRESS patients in Europe: An international multicentre retrospective study of 141 cases.

BACKGROUND: Drug reaction with eosinophilia and systemic symptoms (DRESS) is a rare but potentially fatal drug hypersensitivity reaction. OBJECTIVE: To explore treatment approaches across Europe and their impact on the disease course, as well as prognostic factors and culprit drugs. METHODS: In this retrospective European multicentric study, we included patients with probable or certain DRESS (RegiSCAR score ≥ 4) between January 2016 and December 2020. Independent associations between clinical parameters and the risk of intensive care unit admission and mortality at three months were assessed using a multivariable-adjusted logistic regression model. RESULTS: A total of 141 patients from 8 tertiary centres were included. Morbilliform exanthem was the most frequent cutaneous manifestation (78.0%). The mean affected body surface area (BSA) was 67%, 42% of the patients presented with erythroderma, and 24.8% had mucosal involvement. Based on systemic involvement, 31.9% of the patients had a severe DRESS. Anticonvulsants (24.1%) and sulphonamides (22.0%) were the most frequent causative agents. In all, 73% of the patients were treated with systemic glucocorticoids, and 25.5% received topical corticosteroids as monotherapy. Few patients received antiviral drugs or anti-IL5. No patients received intravenous immunoglobulins. The overall mortality was 7.1%. Independent predictors of mortality were older age (≥57.0 years; fully adjusted OR, 9.80; 95% CI, 1.20-79.93; p = 0.033), kidney involvement (fully adjusted OR, 4.70; 95% CI, 1.00-24.12; p = 0.049), and admission in intensive care unit (fully adjusted OR, 8.12; 95% CI, 1.90-34.67; p = 0.005). Relapse of DRESS and delayed autoimmune sequelae occurred in 8.5% and 12.1% of patients, respectively. CONCLUSIONS: This study underlines the need for diagnostic and prognostic scores/markers as well as for prospective clinical trials of drugs with the potential to reduce mortality and complications of DRESS.

A randomised clinical trial comparing outcomes of a single digit volar plate injury - Buddy loops versus dorsal thermoplastic orthosis in a neutral position: study protocol.

BACKGROUND: Volar plate injuries are a common hand injury and complications associated with this injury such as a fixed flexion deformity, persistent pain and oedema can have a significant impact on a person's function. The literature reports these injuries are treated using various splinting materials such as thermoplastic, in varying degrees of proximal interphalangeal joint flexion or buddy loops. Despite volar plate injuries being reported as common, optimal non-surgical treatment of these injuries remains unclear. This study aims to investigate whether a dorsal blocking orthosis in a neutral position (00) is more effective than buddy loops for a volar plate injury to the proximal interphalangeal joint in preventing a fixed flexion deformity, reducing pain, managing oedema, and promoting function. METHODS: This study is a single-centre, prospective parallel-group, single blinded (assessor), randomised clinical trial. Patients between 18-65 years, who have sustained a volar plate injury to a single digit, have adequate cognitive functioning and give written informed consent will be invited to participate in this study. Patients will be randomised to either the control group where they will be fitted with buddy loops and commence early active motion exercises or the experimental group where they will receive a dorsal thermoplastic orthosis in a neutral position and commence early active motion exercises. The primary outcome measure is passive proximal interphalangeal joint extension and secondary outcome measures include passive range of motion, total passive motion, active range of motion, total active motion, grip strength, oedema, pain, function and adherence to treatment. Assessments will be completed until 8 weeks following commencement of treatment. The sample size calculation indicates that 23 patients is required in each group. With an expected dropout rate of 25% a total of 32 patients will be enrolled in each group. DISCUSSION: This study will assist in trying to improve treatment of volar plate injuries and assist in reducing complications associated with volar plate injuries, potentially reducing the need for prolonged hand therapy. TRIAL REGISTRATION: This trial has been registered with the Australian New Zealand Clinical Trials Registry (ACTRN12622001425785p). Ethical approval has been granted by the South Eastern Sydney Local Health District ethical committee (2022/ETH01697).

Randomized Trial of a Sexual Health Video Intervention for Black and Hispanic Adolescent Females.

Despite significant declines, adolescent birth rates in the USA are higher than other industrialized countries, with black and Hispanic youth disproportionately affected. This study assessed the efficacy of a single-session, entertainment-education sexual health video intervention for these populations. Using an individual-level randomized controlled trial, 1770 18- to 19-year-old black and Hispanic females were assigned to watch Plan A (n = 886) or a control video (n = 884) prior to a sexual reproductive health (SRH) visit. Participants self-reported data at baseline and 3 months post-baseline. Within an intent-to-treat framework, we estimated the average causal effect of assignment to Plan A on three confirmatory and five exploratory outcomes. We found that individuals assigned to Plan A had higher contraceptive knowledge, may be more likely to get sexually transmitted infection (STI) testing, and may have elevated HIV/STI risk perceptions 3 months post-video. Although we found no difference in long-acting reversible contraception (LARC) use nor frequency of condomless sex in the full sample, we did observe that first-time SRH visitors assigned to Plan A had a higher probability of using LARC than those in the control group. This study demonstrates that Plan A is a low-burden, inexpensive, and highly scalable video intervention for black and Hispanic adolescent females that has significant and borderline significant effects on protective sexual health behaviors and important antecedents. It adds to the evidence base of effective teen pregnancy prevention programs and the limited set of rigorous and causal studies investigating the effectiveness of entertainment-education interventions on sexual risk reduction. Registered in ClinicalTrials.gov (NCT03238313) on August 3, 2017.

The ACCELERATE Plus (assessment and communication excellence for safe patient outcomes) Trial Protocol: a stepped-wedge cluster randomised trial, cost-benefit analysis, and process evaluation.

BACKGROUND: Nurses play an essential role in patient safety. Inadequate nursing physical assessment and communication in handover practices are associated with increased patient deterioration, falls and pressure injuries. Despite internationally implemented rapid response systems, falls and pressure injury reduction strategies, and recommendations to conduct clinical handovers at patients' bedside, adverse events persist. This trial aims to evaluate the effectiveness, implementation, and cost-benefit of an externally facilitated, nurse-led intervention delivered at the ward level for core physical assessment, structured patient-centred bedside handover and improved multidisciplinary communication. We hypothesise the trial will reduce medical emergency team calls, unplanned intensive care unit admissions, falls and pressure injuries. METHODS: A stepped-wedge cluster randomised trial will be conducted over 52 weeks. The intervention consists of a nursing core physical assessment, structured patient-centred bedside handover and improved multidisciplinary communication and will be implemented in 24 wards across eight hospitals. The intervention will use theoretically informed implementation strategies for changing clinician behaviour, consisting of: nursing executive site engagement; a train-the-trainer model for cascading facilitation; embedded site leads; nursing unit manager leadership training; nursing and medical ward-level clinical champions; ward nurses' education workshops; intervention tailoring; and reminders. The primary outcome will be a composite measure of medical emergency team calls (rapid response calls and 'Code Blue' calls), unplanned intensive care unit admissions, in-hospital falls and hospital-acquired pressure injuries; these measures individually will also form secondary outcomes. Other secondary outcomes are: i) patient-reported experience measures of receiving safe and patient-centred care, ii) nurses' perceptions of barriers to physical assessment, readiness to change, and staff engagement, and iii) nurses' and medical officers' perceptions of safety culture and interprofessional collaboration. Primary outcome data will be collected for the trial duration, and secondary outcome surveys will be collected prior to each step and at trial conclusion. A cost-benefit analysis and post-trial process evaluation will also be undertaken. DISCUSSION: If effective, this intervention has the potential to improve nursing care, reduce patient harm and improve patient outcomes. The evidence-based implementation strategy has been designed to be embedded within existing hospital workforces; if cost-effective, it will be readily translatable to other hospitals nationally. TRIAL REGISTRATION: Australian New Zealand Clinical Trials Registry ID: ACTRN12622000155796. Date registered: 31/01/2022.

A Barbed Proximal Femoral Nailing System for Isolated Intertrochanteric Femur Fractures: Operative Outcomes.

Intertrochanteric femur fractures are associated with high morbidity/mortality, necessitating strategies to limit time under anesthesia, blood loss, and additional trauma while achieving maximal fixation in osteopenic bone. The Orthopedic Designs North America, Inc. Talon DistalFix Femoral Nail System uses deployable barbs to maximize axial and rotational control without distal interlock screws. The purpose of this study was to evaluate perioperative features and postoperative outcomes in patients treated with the DistalFix Femoral Nailing System for isolated intertrochanteric femur fractures. Seventy-one consecutive patients underwent intramedullary fixation for isolated intertrochanteric fractures with the DistalFix system between January 2019-July 2020. Median operative time was 35 (33 - 40) minutes. Median estimated blood loss was 125 (75 - 150) cc. Median fluoroscopy time was 2.4 (2.2 - 2.9) minutes and dosage was 27.1 (18.0 - 35.2) mGy. Union occurred in 98% of patients; none experienced implant cutout, and 81.1% returned to previous mobility. The DistalFix system achieves a high rate of union and return to function while limiting operative risk factors. (Journal of Surgical Orthopaedic Advances 32(1):036-040, 2023).

Assessment of the safety, pharmacokinetics and pharmacodynamics of GSK3335065, an inhibitor of kynurenine monooxygenase, in a randomised placebo-controlled first-in-human study in healthy volunteers.

GSK3335065 is an inhibitor of kynurenine monooxygenase (KMO) being developed for the treatment of acute pancreatitis. Healthy male volunteers were administered ascending doses of GSK3335065 or matched placebo as a single intravenous bolus injection to assess safety, tolerability, pharmacokinetics and pharmacodynamics. GSK3335065 displayed an apparent volume of distribution between 20.6 L and 44.6 L, a clearance between 0.462 L/h and 0.805 L/hr and a terminal half-life between 31.3 and 34.5 hr. In the single subject who received 1.3 mg GSK3335065, changes in tryptophan pathway metabolites were observed consistent with the changes seen in preclinical species suggesting that KMO enzyme activity was partially inhibited. However, a broad complex ventricular tachycardia was observed in this subject, which was judged to be a Serious Adverse Event (SAE) and resulted in early termination of the study. While development of GSK3335065 was subsequently discontinued, significant confounding factors hinder a clear interpretation that the tachycardia was directly related to administration of the compound.

Acquired Acrodermatitis enteropathica - an unusual cause of vulva ulceration in a post-operative patient: a case report.

Acrodermatitis enteropathica (AE) is a rare disorder which can be congenital or acquired. The main features are peri-orificial dermatitis, gastrointestinal symptom in the form of diarrhoea, acral dermatitis and alopecia, among others. This report aims to highlight that AE is an important differential diagnosis to consider, when managing older patients with mucosal infections or ulcerations. Here, we present the case of a 68-year-old female with end-stage liver disease who presented with a right inter-trochanteric femoral fracture following a fall and was noted, on admission, to have non-healing mucosal ulcers.

Resistant starch-An accessible fiber ingredient acceptable to the Western palate.

Dietary fiber intakes in Western societies are concerningly low and do not reflect global recommended dietary fiber intakes for chronic disease prevention. Resistant starch (RS) is a fermentable dietary fiber that has attracted research interest. As an isolated ingredient, its fine particle size, relatively bland flavor, and white appearance may offer an appealing fiber source to the Western palate, accustomed to highly refined, processed grains. This review aims to provide a comprehensive insight into the current knowledge (classification, production methods, and characterization methods), health benefits, applications, and acceptability of RS. It further discusses the present market for commercially available RS ingredients and products containing ingredients high in RS. The literature currently highlights beneficial effects for dietary RS supplementation with respect to glucose metabolism, satiety, blood lipid profiles, and colonic health. An exploration of the market for commercial RS ingredients indicates a diverse range of products (from isolated RS2, RS3, and RS4) with numerous potential applications as partial or whole substitutes for traditional flour sources. They may increase the nutritional profile of a food product (e.g., by increasing the fiber content and lowering energy values) without significantly compromising its sensory and functional properties. Incorporating RS ingredients into staple food products (such as bread, pasta, and sweet baked goods) may thus offer an array of nutritional benefits to the consumer and a highly accessible functional ingredient to be greater exploited by the food industry.

A compact instrument for gamma-ray burst detection on a CubeSat platform II: Detailed design, assembly and validation.

The Gamma-ray Module, GMOD, is a miniaturised novel gamma-ray detector which will be the primary scientific payload on the Educational Irish Research Satellite (EIRSAT-1) 2U CubeSat mission. GMOD comprises a compact (25 mm × 25 mm × 40 mm) cerium bromide scintillator coupled to a tiled array of 4 × 4 silicon photomultipliers, with front-end readout provided by the IDE3380 SIPHRA. This paper presents the detailed GMOD design and the accommodation of the instrument within the restrictive CubeSat form factor. The electronic and mechanical interfaces are compatible with many off-the-shelf CubeSat systems and structures. The energy response of the GMOD engineering qualification model has been determined using radioactive sources, and an energy resolution of 5.4% at 662 keV has been measured. EIRSAT-1 will perform on-board processing of GMOD data. Trigger results, including light-curves and spectra, will be incorporated into the spacecraft beacon and transmitted continuously. Inexpensive hardware can be used to decode the beacon signal, making the data accessible to a wide community. GMOD will have scientific capability for the detection of gamma-ray bursts, in addition to the educational and technology demonstration goals of the EIRSAT-1 mission. The detailed design and measurements to date demonstrate the capability of GMOD in low Earth orbit, the scalability of the design for larger CubeSats and as an element of future large gamma-ray missions.

A scoping review of physical activity interventions for older adults.

BACKGROUND: To inform implementation and future research, this scoping review investigates the volume of evidence for physical activity interventions among adults aged 60+. Our research questions are: (1) what is the evidence regarding interventions designed to increase total physical activity in adults aged 60+ years, in accordance with three of the four strategic objectives of GAPPA (active societies, active environments, active people); (2) what is the current evidence regarding the effectiveness of physical activity programmes and services designed for older adults?; and (3) What are the evidence gaps requiring further research? METHODS: We searched PEDro, MEDLINE, CINAHL and Cochrane from 1 January 2010 to 1 November 2020 for systematic reviews and meta-analyses of physical activity interventions in adults aged 60+. We identified interventions designed to: (1) increase physical activity; and (2) deliver physical activity programmes and services in home, community or outpatient settings. We extracted and coded data from eligible reviews according to our proposed framework informed by TIDieR, Prevention of Falls Network Europe (PROFANE), and WHO's International Classification of Functioning, Disability and Health (ICF). We classified the overall findings as positive, negative or inconclusive. RESULTS: We identified 39 reviews of interventions to increase physical activity and 342 reviews of programmes/services for older adults. Interventions were predominantly structured exercise programmes, including balance strength/resistance training, and physical recreation, such as yoga and tai chi. There were few reviews of health promotion/coaching and health professional education/referral, and none of sport, workplace, sociocultural or environmental interventions. Fewer reported outcomes of total physical activity, social participation and quality of life/well-being. We noted insufficient coverage in diverse and disadvantaged samples and low-middle income countries. CONCLUSIONS: There is a modest but growing volume of evidence regarding interventions designed to increase total physical activity in older adults, although more interventional studies with long term follow-up are needed, particularly for GAPPA 1. Active Societies and GAPPA 2. Active Environments. By comparison, there is abundant evidence for GAPPA 3. specific programmes and services, but coverage of sport and workplace interventions, and diverse samples and settings is lacking. Comprehensive reviews of individual studies are now needed as well as research targeting neglected outcomes, populations and settings.

Noise heterogeneity in attenuation-corrected cardiac SPECT images increases perfusion value uncertainty near the base of the heart.

BACKGROUND: Dedicated cardiac SPECT cameras which employ multi-pinhole detectors have variable photon sensitivity within the camera's field-of-view such that a lower number of photon counts is typically detected from the base of the heart than from the apex. Consequently, the noise in a reconstructed image is expected to be higher at the base than at the apex of the heart. METHODS: Patient emission images were resampled to create statistical replicates which were reconstructed with and without attenuation correction. Noise images were computed using one standard deviation of the replicated images. These were evaluated for 93 patients with normal study results, each imaged with both a dual-headed parallel-hole camera and a multi-pinhole camera. Statistics for a normal database (NDB) of images from the 93 patients were also calculated. RESULTS: Image noise (1.7-fold) and NDB uncertainty (1.3-fold) increase significantly from the apex-to-the base of the heart in attenuation-corrected multi-pinhole SPECT images. The differences for non-attenuation-corrected images or those acquired with a parallel-hole camera were not significant. CONCLUSIONS: For best interpretation of attenuation-corrected images acquired with multi-pinhole cameras, knowledge of NDB uncertainty gradients should be taken into consideration.

Patient-specific SPECT imaging protocols to standardize image noise.

BACKGROUND: In addition to acquired photon counts, image noise depends on the image reconstruction algorithm. This work develops patient-specific activity or acquisition time protocols to standardize the average noise in a reconstructed image for different patients, cameras, and reconstruction algorithms. METHODS: Image noise was calculated for images from 43 patients acquired on both a conventional and a multiple-pinhole cardiac SPECT camera. Functions were found to relate image noise to radiotracer activity, scan time, and body mass and were validated by normalizing the image noise in a test set of 58 patients. RESULTS: There was a 3.6-fold difference in photon sensitivity between the two cameras but a 16-fold difference in activity-scan time was necessary to match the noise levels. Image noise doubled from 45 to 128 kg for the conventional camera (12.8 minutes) and tripled for the multiple-pinhole camera (5 minutes) for 350 MBq (9.5 mCi) 99mTc-tetrofosmin. It was 16.3% and 6.1% respectively for an average sized patient. CONCLUSIONS: A linear scaling of activity with respect to the patient weight normalizes image noise but the scaling factors depend on the choice of camera and image reconstruction parameters. Therefore, equivalent numbers of acquired photon counts are not sufficient to guarantee equivalent image noise.

Discriminating minor and major forms of drug reaction with eosinophilia and systemic symptoms: Facial edema aligns to the severe phenotype.

BACKGROUND: Drug reaction with eosinophilia and systemic symptoms (DRESS) is a cutaneous and systemic drug allergy disorder. Patients exist on a severity spectrum, with some experiencing a mild form of the disorder that fails to meet the Registry of Severe Cutaneous Adverse Reactions (SCAR) to Drugs diagnostic criteria for DRESS. OBJECTIVE: We sought to determine whether there were any cutaneous or dermatopathologic features that discriminate between the mild form of DRESS (DRESS minor) and the severe phenotype (DRESS major). METHODS: Hospitalized patients from a single center with a diagnosis of DRESS were prospectively recruited over a 7-year period. Clinical and dermatopathologic features were analyzed to discriminate between DRESS minor and DRESS major. RESULTS: Forty-five patients were included, of whom 19 had a Registry of Severe Cutaneous Adverse Reactions (SCAR) to Drugs score of ≤3 (DRESS minor) and 26 had a score of ≥4 (DRESS major). The mean latency period (P = .001), fever >38.5 °C (P = .001), and a reaction lasting >15 days (P = .010) discriminated DRESS major from DRESS minor. Facial edema was the sole discerning cutaneous feature (P = .025). Discriminating histopathologic features included basal squamatization (P = .005), dermal red blood cell extravasation (P = .009), and interface inflammation (P = .005). CONCLUSION: We propose a new classification system-DRESS minor-to distinguish the milder illness from the severe form, DRESS major. Facial edema and certain histopathologic features can help discriminate between major and minor versions.

Balloon flight test of a CeBr3 detector with silicon photomultiplier readout.

Recent advances in silicon photomultiplier (SiPM) technology and new scintillator materials allow for the creation of compact high-performance gamma-ray detectors which can be deployed on small low-cost satellites. A small number of such satellites can provide full sky coverage and complement, or in some cases replace the existing gamma-ray missions in detection of transient gamma-ray events. The aim of this study is to test gamma-ray detection using a novel commercially available CeBr3 scintillator combined with SiPM readout in a near-space environment and inform further technology development for a future space mission. A prototype gamma-ray detector was built using a CeBr3 scintillator and an array of 16 J-Series SiPMs by ON Semiconductor. SiPM readout was performed using SIPHRA, a radiation-tolerant low-power integrated circuit developed by IDEAS. The detector was flown as a piggyback payload on the Advanced Scintillator Compton Telescope balloon flight from Columbia Scientific Balloon Facility. The payload included the detector, a Raspberry Pi on-board computer, a custom power supply board, temperature and pressure sensors, a Global Navigation Satellite System receiver and a satellite modem. The balloon delivered the detector to 37 km altitude where its detection capabilities and readout were tested in the radiation-intense near-space environment. The detector demonstrated continuous operation during the 8-hour flight and after the landing. It performed spectral measurements in an energy range of 100 keV to 8 MeV and observed the 511 keV gamma-ray line arising from positron annihilation in the atmosphere with full width half maximum of 6.8%. During ascent and descent, the detector count rate peaked at an altitude of 16 km corresponding to the point of maximum radiation intensity in the atmosphere. Despite several engineering issues discovered after the flight test, the results of this study confirm the feasibility of using CeBr3 scintillator, SiPMs, and SIPHRA in future space missions.