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Calcific tendinitis, classified as enthesopathy, is a self-limiting disease that rarely involves the tendons of the gluteus maximus. We discuss a 52-year-old woman with a 1-year history of localized, reproducible posterolateral pain of her left hip, which was previously treated with steroid injection to her left greater trochanteric bursa without significant pain relief. Plain radiography and magnetic resonance imaging of the left hip revealed abnormal edema and calcifications at the insertion of the gluteus maximus tendon to the gluteal tuberosity, corresponding to the area of maximal tenderness on examination. This case report contributes to the growing medical literature for the rare presentation of calcific tendinitis of gluteus maximus insertion and reinforces the importance of the patient history, focused physical examination with special testing, and pertinent imaging for proper diagnosis and management.
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BACKGROUND: Medication nonadherence remains a significant health and economic burden in many high-income countries. Emerging smartphone interventions have started to use features such as gamification and financial incentives with varying degrees of effectiveness on medication adherence and health outcomes. A more consistent approach to applying these features, informed by patient perspectives, may result in more predictable and beneficial results from this type of intervention. OBJECTIVE: This qualitative study aims to identify patient perspectives on the use of gamification and financial incentives in mobile health (mHealth) apps for medication adherence in Australian patients taking medication for chronic conditions. METHODS: A total of 19 participants were included in iterative semistructured web-based focus groups conducted between May and December 2022. The facilitator used exploratory prompts relating to mHealth apps, gamification, and financial incentives, along with concepts raised from previous focus groups. Transcriptions were independently coded to develop a set of themes. RESULTS: Three themes were identified: purpose-driven design, trust-based standards, and personal choice. All participants acknowledged gamification and financial incentives as potentially effective features in mHealth apps for medication adherence. However, they also indicated that the effectiveness heavily depended on implementation and execution. Major concerns relating to gamification and financial incentives were perceived trivialization and potential for medication abuse, respectively. CONCLUSIONS: The study's findings provide a foundation for developers seeking to apply these novel features in an app intervention for a general cohort of patients. However, the study highlights the need for standards for mHealth apps for medication adherence, with particular attention to the use of gamification and financial incentives. Future research with patients and stakeholders across the mHealth app ecosystem should be explored to formalize and validate a set of standards or framework.
Subject(s)
Focus Groups , Medication Adherence , Mobile Applications , Motivation , Qualitative Research , Telemedicine , Humans , Mobile Applications/standards , Mobile Applications/statistics & numerical data , Focus Groups/methods , Male , Female , Medication Adherence/psychology , Medication Adherence/statistics & numerical data , Middle Aged , Adult , Australia , Telemedicine/methods , Telemedicine/standards , Aged , Video Games/standards , Video Games/psychologyABSTRACT
To date, thousands of SARS-CoV-2 samples from many vaccine developers have been tested within the CEPI-Centralized Laboratory Network. To convert data from each clinical assay to international standard units, the WHO international standard and the CEPI standard generated by the Medicines and Healthcare products Regulatory Agency were run in multiple facilities to determine the conversion factor for each assay. Reporting results in international units advances global understanding of SARS-CoV-2 immunity and vaccine efficacy, enhancing the quality, reliability, and utility of clinical assay data.
Subject(s)
COVID-19 Vaccines , COVID-19 , SARS-CoV-2 , Humans , COVID-19 Vaccines/immunology , COVID-19/prevention & control , SARS-CoV-2/immunology , Reproducibility of Results , Vaccine Efficacy , World Health Organization , Clinical Laboratory Techniques/methods , Clinical Laboratory Techniques/standardsABSTRACT
Introduction: Immune checkpoint inhibitor-induced inflammatory arthritis (ICI-IA) poses a major clinical challenge to ICI therapy for cancer, with 13% of cases halting ICI therapy and ICI-IA being difficult to identify for timely referral to a rheumatologist. The objective of this study was to rapidly identify ICI-IA patients in clinical data and assess associated immune-related adverse events (irAEs) and risk factors. Methods: We conducted a retrospective study of the electronic health records (EHRs) of 89 patients who developed ICI-IA out of 2451 cancer patients who received ICI therapy at Northwestern University between March 2011 to January 2021. Logistic regression and random forest machine learning models were trained on all EHR diagnoses, labs, medications, and procedures to identify ICI-IA patients and EHR codes indicating ICI-IA. Multivariate logistic regression was then used to test associations between ICI-IA and cancer type, ICI regimen, and comorbid irAEs. Results: Logistic regression and random forest models identified ICI-IA patients with accuracies of 0.79 and 0.80, respectively. Key EHR features from the random forest model included ICI-IA relevant features (joint pain, steroid prescription, rheumatoid factor tests) and features suggesting comorbid irAEs (thyroid function tests, pruritus, triamcinolone prescription). Compared to 871 adjudicated ICI patients who did not develop arthritis, ICI-IA patients had higher odds of developing cutaneous (odds ratio [OR]=2.66; 95% Confidence Interval [CI] 1.63-4.35), endocrine (OR=2.09; 95% CI 1.15-3.80), or gastrointestinal (OR=2.88; 95% CI 1.76-4.72) irAEs adjusting for demographics, cancer type, and ICI regimen. Melanoma (OR=1.99; 95% CI 1.08-3.65) and renal cell carcinoma (OR=2.03; 95% CI 1.06-3.84) patients were more likely to develop ICI-IA compared to lung cancer patients. Patients on nivolumab+ipilimumab were more likely to develop ICI-IA compared to patients on pembrolizumab (OR=1.86; 95% CI 1.01-3.43). Discussion: Our machine learning models rapidly identified patients with ICI-IA in EHR data and elucidated clinical features indicative of comorbid irAEs. Patients with ICI-IA were significantly more likely to also develop cutaneous, endocrine, and gastrointestinal irAEs during their clinical course compared to ICI therapy patients without ICI-IA.
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Antineoplastic Agents, Immunological , Arthritis , Kidney Neoplasms , Melanoma , Humans , Antineoplastic Agents, Immunological/therapeutic use , Retrospective Studies , Arthritis/drug therapy , Melanoma/drug therapy , Kidney Neoplasms/drug therapyABSTRACT
BACKGROUND: Despite the high rates of cholecystectomy in Australia, there is minimal literature regarding the outcomes of cholecystectomy in rural Central Australia within the Northern Territory. This study aims to better characterize the outcomes for patients undergoing cholecystectomy in Central Australia and review clinical and patient characteristics, which may affect outcomes. METHOD: A retrospective case-control study was performed using data obtained from medical records for all patients undergoing cholecystectomy at Alice Springs Hospital in the Northern Territory from January 2018 until December 2022. Patient characteristics were gathered, and key outcomes examined included: inpatient mortality and 30-day mortality, bile duct injury, bile leak, return to theatre, conversion to open, duration of procedure, length of stay, and up-transfer to a tertiary referral centre. RESULTS: A total of 466 patients were included in this study. Majority of the patients were female and there was a large portion of Indigenous Australians (56%). There were no inpatient mortalities, or 30-day mortalities recorded. There were two bile leaks and/or bile duct injuries (0.4%) and two unplanned returned to theatres (0.4%). Indigenous Australians were more likely to require an emergency operation and had a longer median length of stay (P < 0.001). CONCLUSION: Cholecystectomy can be performed safely and to a high standard in Central Australia. Surgeons in Central Australia must appreciate the nuances in the management of patients who come from a significantly different socioeconomic background, with complex medical conditions when compared to metropolitan centres.
Subject(s)
Cholecystectomy , Length of Stay , Humans , Female , Male , Retrospective Studies , Cholecystectomy/statistics & numerical data , Middle Aged , Northern Territory/epidemiology , Case-Control Studies , Adult , Length of Stay/statistics & numerical data , Aged , Treatment Outcome , Postoperative Complications/epidemiology , Hospital Mortality/trendsABSTRACT
In a stack of atomically thin van der Waals layers, introducing interlayer twist creates a moiré superlattice whose period is a function of twist angle. Changes in that twist angle of even hundredths of a degree can dramatically transform the system's electronic properties. Setting a precise and uniform twist angle for a stack remains difficult; hence, determining that twist angle and mapping its spatial variation is very important. Techniques have emerged to do this by imaging the moiré, but most of these require sophisticated infrastructure, time-consuming sample preparation beyond stack synthesis, or both. In this work, we show that torsional force microscopy (TFM), a scanning probe technique sensitive to dynamic friction, can reveal surface and shallow subsurface structure of van der Waals stacks on multiple length scales: the moirés formed between bi-layers of graphene and between graphene and hexagonal boron nitride (hBN) and also the atomic crystal lattices of graphene and hBN. In TFM, torsional motion of an Atomic Force Microscope (AFM) cantilever is monitored as it is actively driven at a torsional resonance while a feedback loop maintains contact at a set force with the sample surface. TFM works at room temperature in air, with no need for an electrical bias between the tip and the sample, making it applicable to a wide array of samples. It should enable determination of precise structural information including twist angles and strain in moiré superlattices and crystallographic orientation of van der Waals flakes to support predictable moiré heterostructure fabrication.
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We report kinetic energies (KE) of multiply charged atomic ions (MCAI) from interactions of moderately intense nanosecond lasers at 532 nm with argon containing clusters, including neat and doped clusters with a trace amount of trichlorobenzene. We develop a mathematical method to retrieve speed and thereby kinetic energy information from analyzing the time-of-flight profiles of the MCAI. This method should be generally applicable in detections of energetic charged particles with high velocities, a realm where velocity map imaging is inadequate. From this analysis, we discover that the KE of MCAI from doped clusters demonstrates a quadratic dependence on the charge of the atomic ions, while for neat clusters, the dependence is cubic. This result confirms the nature of the cluster disintegration process to be dominated by Coulomb explosion. This result bears more similarity to reports from extreme vacuum ultraviolet (EUV) fields with similar intensities, than to reports from near infrared (NIR) intense laser fields. However, the charge state distribution from our experiment is the opposite: we observe more higher charge state ions than reported in EUV fields, and our charge state distribution is actually similar to those reported in NIR fields. We also report a significant effect of the external electric field on the charge state distribution of the atomic ions: the presence of an electric field can significantly increase the charge from the atomic ions, as shown by a three-fold reduction in the average kinetic energy per charge. Although molecular dynamics simulations have been implemented for experiments in the EUV and NIR, our results allude to the need of a concerted effort in this regime of moderately intense nanosecond laser fields. The significant decrease in charge state distribution and the significant increase in KE from doped clusters, compared with neat clusters, is a telltale sign that the true interaction time between the laser field and the cluster may be substantially shorter than the duration of the laser, a welcome relief for molecular dynamics simulations.
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BACKGROUND: Accurate quantitation of immune markers is crucial for ensuring reliable assessment of vaccine efficacy against infectious diseases. This study was designed to confirm standardised performance of SARS-CoV-2 assays used to evaluate COVID-19 vaccine candidates at the initial seven laboratories (in North America, Europe, and Asia) of the Coalition for Epidemic Preparedness Innovations (CEPI) Centralized Laboratory Network (CLN). METHODS: Three ELISAs (pre-spike protein, receptor binding domain, and nucleocapsid), a microneutralisation assay (MNA), a pseudotyped virus-based neutralisation assay (PNA), and an IFN-γ T-cell ELISpot assay were developed, validated or qualified, and transferred to participating laboratories. Immune responses were measured in ELISA laboratory units (ELU) for ELISA, 50% neuralisation dilution (ND50) for MNA, 50% neutralisation titre (NT50) for PNA, and spot-forming units for the ELISpot assay. Replicate assay results of well characterised panels and controls of blood samples from individuals with or without SARS-CoV-2 infection were evaluated by geometric mean ratios, standard deviation, linear regression, and Spearman correlation analysis for consistency, accuracy, and linearity of quantitative measurements across all laboratories. FINDINGS: High reproducibility of results across all laboratories was demonstrated, with interlaboratory precision of 4·1-7·7% coefficient of variation for all three ELISAs, 3·8-19·5% for PNA, and 17·1-24·1% for MNA, over a linear range of 11-30 760 ELU per mL for the three ELISAs, 14-7876 NT50 per mL for PNA, and 21-25 587 ND50 per mL for MNA. The MNA was also adapted for detection of neutralising antibodies against the major SARS-CoV-2 variants of concern. The results of PNA and MNA (r=0·864) and of ELISA and PNA (r=0·928) were highly correlated. The IFN-γ ELISpot interlaboratory variability was 15·9-49·9% coefficient of variation. Sensitivity and specificity were close to 100% for all assays. INTERPRETATION: The CEPI CLN provides accurate quantitation of anti-SARS-CoV-2 immune response across laboratories to allow direct comparisons of different vaccine formulations in different geographical areas. Lessons learned from this programme will serve as a model for faster responses to future pandemic threats and roll-out of effective vaccines. FUNDING: CEPI.
Subject(s)
COVID-19 , SARS-CoV-2 , Humans , SARS-CoV-2/genetics , COVID-19/prevention & control , COVID-19 Vaccines , Laboratories , Reproducibility of Results , Antibodies, Viral , ImmunityABSTRACT
There is a limited body of evidence for haploidentical hematopoietic stem cell transplantation (haplo-HSCT) in older patients. Previous studies have used a high proportion of bone marrow-derived grafts and a variety of conditioning regimens. In Australia and New Zealand, haplo-HCST is predominantly performed using peripheral blood (PB) with universal use of post-transplantation cyclophosphamide (PTCy). To characterize the outcomes of older recipients undergoing haplo-HSCT for acute myeloid leukemia (AML) and myelodysplastic syndromes (MDS). Data were collected through the Australasian Bone Marrow Transplant Recipient Registry (ABMTRR) for patients aged 65 or older receiving a PB haplo-HSCT for AML/MDS between January 2010 and July 2020. A total of 44 patients were included in the analysis. The median follow-up time was 377 days. The median age was 68 (range 65-74) with a median Karnofsky performance status of 90. Thirty patients (68.2%) had AML, whereas 14 (31.8%) had MDS. The median donor age was 40. The most common conditioning regimen was nonmyeloablative fludarabine, cyclophosphamide, and total body irradiation (75%); the remainder of the patients received either melphalan- or busulfan-based regimens, and the majority were reduced intensity, with only 2 patients undergoing myeloablative conditioning. All patients received post-transplantation cyclophosphamide and mycophenolate mofetil, with the majority also receiving tacrolimus (90.5%) and the remainder receiving cyclosporine (9.5%). No patients received anti-thymocyte globulin. Neutrophil engraftment was achieved in 97.6% of patients at a median of 18 days, whereas platelet engraftment was achieved in 92.7% of patients at a median of 28 days. The cumulative incidences of cytomegalovirus (CMV) reactivation and CMV disease were 52.5% and 5.1% at 1 year. The incidence of grade 2-4 acute Graft Versus Host Disease (GVHD) was 18.2%. The incidence of chronic GVHD at 2 years was 40.7%, with extensive chronic GVHD occurring in 17.7% of patients. The incidences of relapse and non-relapse mortality (NRM) at 2 years were 8.8% and 20.7% respectively. The leading causes of death were infection (64.7%) followed by relapse (14.2%). The 2-year overall survival was 74%. Relapse free survival and GVHD free, relapse free survival at 2 years was 70% and 48%. Haplo-HSCT using a peripheral blood graft and PTCy GVHD prophylaxis demonstrates long-term disease control with acceptable rates of NRM for older patients with AML/MDS.
Subject(s)
Cytomegalovirus Infections , Graft vs Host Disease , Hematopoietic Stem Cell Transplantation , Leukemia, Myeloid, Acute , Myelodysplastic Syndromes , Peripheral Blood Stem Cell Transplantation , Humans , Aged , New Zealand/epidemiology , Peripheral Blood Stem Cell Transplantation/adverse effects , Leukemia, Myeloid, Acute/drug therapy , Cyclophosphamide/therapeutic use , Hematopoietic Stem Cell Transplantation/adverse effects , Graft vs Host Disease/epidemiology , Graft vs Host Disease/prevention & control , Myelodysplastic Syndromes/therapy , RecurrenceABSTRACT
OBJECTIVE: To assess the application and utility of algorithms designed to detect features of SLE in electronic health record (EHR) data in a multisite, urban data network. METHODS: Using the Chicago Area Patient-Centered Outcomes Research Network (CAPriCORN), a Clinical Data Research Network (CDRN) containing data from multiple healthcare sites, we identified patients with at least one positively identified criterion from three SLE classification criteria sets developed by the American College of Rheumatology (ACR) in 1997, the Systemic Lupus International Collaborating Clinics (SLICC) in 2012, and the European Alliance of Associations for Rheumatology and the ACR in 2019 using EHR-based algorithms. To measure the algorithms' performance in this data setting, we first evaluated whether the number of clinical encounters for SLE was associated with a greater quantity of positively identified criteria domains using Poisson regression. We next quantified the amount of SLE criteria identified at a single healthcare institution versus all sites to assess the amount of SLE-related information gained from implementing the algorithms in a CDRN. RESULTS: Patients with three or more SLE encounters were estimated to have documented 2.77 (2.73 to 2.80) times the number of positive SLE attributes from the 2012 SLICC criteria set than patients without an SLE encounter via Poisson regression. Patients with three or more SLE-related encounters and with documented care from multiple institutions were identified with more SLICC criteria domains when data were included from all CAPriCORN sites compared with a single site (p<0.05). CONCLUSIONS: The positive association observed between amount of SLE-related clinical encounters and the number of criteria domains detected suggests that the algorithms used in this study can be used to help describe SLE features in this data environment. This work also demonstrates the benefit of aggregating data across healthcare institutions for patients with fragmented care.
Subject(s)
Lupus Erythematosus, Systemic , Rheumatology , Humans , United States , Lupus Erythematosus, Systemic/diagnosis , Lupus Erythematosus, Systemic/epidemiology , Severity of Illness Index , Medical Records , Patient Outcome AssessmentABSTRACT
Haploidentical hematopoietic stem cell transplant (haplo-HSCT) using posttransplant cyclophosphamide (PTCy) is appropriate for those who lack matched donors. Most studies using PTCy have been retrospective making conclusions difficult. ANZHIT-1 was a phase 2 study conducted at 6 Australian allogeneic HSCT centers. The primary end points were disease-free and overall survival at 2 years after HSCT. The reduced-intensity conditioning (RIC) included fludarabine, cyclophosphamide, and 200 cGy total body irradiation, and the myeloablative conditioning (MAC) was IV fludarabine and busulfan. PTCy, MMF and a calcineurin inhibitor (CNI) were used for graft-versus-host disease (GVHD) prophylaxis. CNIs were weaned and ceased by day +120 in eligible patients on day 60. Patients (n = 78) with hematological malignancies were included in the study, with a median follow-up of 732 days (range, 28-1728). HSCT was RIC in 46 patients and MAC in 32 patients. Disease-free survival probability at 2 years was 67.5% (95% [CI], 53.2-85.6) for MAC recipients and 68.3% (95% CI, 56.3-83.01) for RIC recipients. Transplant-related mortality (TRM) on day 100 and year 1 was 4.9% (95% CI, 1.6-15.3) and 17.9% (95% CI, 8.8-36.5), respectively, in the MAC group compared with 3.1% (95% CI, 0.8.1-12) and 11.6% (95% CI, 6-22.4), respectively, in the RIC group. The median time for elective cessation of CNI was day 142.5 days, with no excess chronic GVHD (cGVHD) or mortality. Of the evaluable patients, 71.6% discontinued immunosuppression 12 months after transplant. This prospective haplo-HSCT trial using PTCY demonstrated encouraging survival rates, indicating that early CNI withdrawal is feasible and safe.
Subject(s)
Graft vs Host Disease , Hematopoietic Stem Cell Transplantation , Peripheral Blood Stem Cell Transplantation , Humans , Australia , Calcineurin Inhibitors/therapeutic use , Cyclophosphamide/therapeutic use , Graft vs Host Disease/etiology , Graft vs Host Disease/prevention & control , Graft vs Host Disease/drug therapy , Hematopoietic Stem Cell Transplantation/adverse effects , Prospective Studies , Retrospective StudiesSubject(s)
Macular Edema , Retinal Vein Occlusion , Humans , Macular Edema/diagnosis , Macular Edema/drug therapy , Macular Edema/etiology , Retinal Vein Occlusion/complications , Retinal Vein Occlusion/diagnosis , Retinal Vein Occlusion/drug therapy , Tomography, Optical Coherence , Eye , BevacizumabABSTRACT
STUDY OBJECTIVE: The Geriatric Emergency Department Innovations (GEDI) program is a nurse-based geriatric assessment and care coordination program that reduces preventable admissions for older adults. Unfortunately, only 5% of older adults receive GEDI care because of resource limitations. The objective of this study was to predict the likelihood of hospitalization accurately and consistently with and without GEDI care using machine learning models to better target patients for the GEDI program. METHODS: We performed a cross-sectional observational study of emergency department (ED) patients between 2010 and 2018. Using propensity-score matching, GEDI patients were matched to other older adult patients. Multiple models, including random forest, were used to predict hospital admission. Multiple second-layer models, including random forest, were then used to predict whether GEDI assessment would change predicted hospital admission. Final model performance was reported as the area under the curve using receiver operating characteristic models. RESULTS: We included 128,050 patients aged over 65 years. The random forest ED disposition model had an area under the curve of 0.774 (95% confidence interval [CI] 0.741 to 0.806). In the random forest GEDI change-in-disposition model, 24,876 (97.3%) ED visits were predicted to have no change in disposition with GEDI assessment, and 695 (2.7%) ED visits were predicted to have a change in disposition with GEDI assessment. CONCLUSION: Our machine learning models could predict who will likely be discharged with GEDI assessment with good accuracy and thus select a cohort appropriate for GEDI care. In addition, future implementation through integration into the electronic health record may assist in selecting patients to be prioritized for GEDI care.
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Emergency Service, Hospital , Hospitalization , Aged , Humans , Cross-Sectional Studies , Machine Learning , Geriatric Assessment , HospitalsABSTRACT
BACKGROUND AND OBJECTIVE: To determine if age-related macular degeneration (AMD) status affects longitudinal retinal vessel changes. PATIENTS AND METHODS: Retrospective, cohort study of 125 eyes (75 patients) with AMD, following retinal vessel density (VD) and foveal avascular zone (FAZ) measurements using optical coherence tomography angiography (OCT-A) over 24 months. RESULTS: FAZ area (P < .001) and perimeter (P < .001) increased over 2 years, with no difference between nonexudative and exudative AMD (P = .134-.976). Eyes with geographic atrophy (GA) showed greater progressive VD loss (P = .023-.038), and greater increase in FAZ area (P = .044) and perimeter (P = .040) compared to eyes without GA. Neither baseline nor 2-year change in vascular parameters were associated with choroidal neovascularization (CNV) or GA incidence in nonexudative AMD, or anti-VEGF injection frequency in exudative AMD (P = .070-.952). CONCLUSION: AMD eyes with GA undergo more rapid loss of retinal vessel density and FAZ enlargement over 2 years, suggesting a relationship between the retinal vasculature and AMD pathophysiology. [Ophthalmic Surg Lasers Imaging Retina 2022;53:529-536.].
Subject(s)
Geographic Atrophy , Macular Degeneration , Cohort Studies , Fluorescein Angiography/methods , Humans , Macular Degeneration/diagnosis , Retinal Vessels , Retrospective Studies , Tomography, Optical Coherence/methodsABSTRACT
Monolayer hexagonal boron nitride (hBN) has attracted interest as an ultrathin tunnel barrier or environmental protection layer. Recently, wafer-scale hBN growth on Cu(111) was developed for semiconductor chip applications. For basic research and technology, understanding how hBN perturbs underlying electronically active layers is critical. Encouragingly, hBN/Cu(111) has been shown to preserve the Cu(111) surface state (SS), but it was unknown how tunneling into this SS through hBN varies spatially. Here, we demonstrate that the Cu(111) SS under wafer-scale hBN is homogeneous in energy and spectral weight over nanometer length scales and across atomic terraces. In contrast, a new spectral featureânot seen on bare Cu(111)âvaries with atomic registry and shares the spatial periodicity of the hBN/Cu(111) moiré. This work demonstrates that, for some 2D electron systems, an hBN overlayer can act as a protective yet remarkably transparent window on fragile low-energy electronic structure below.
Subject(s)
Boron Compounds , Semiconductors , Boron Compounds/chemistry , ElectronicsABSTRACT
Unrelated donors (UDs) are the commonest source for allogeneic transplantation (alloSCT), with higher non-relapse mortality (NRM) than siblings. We analyzed data from the Australasian Bone Marrow Transplant Recipient Registry from adults receiving a first UD alloSCT during 2001-2015, to determine whether and how NRM has changed. Predictors of outcome were determined using cox regression, accounting for time-interactions and competing risks. A total of 2308 patients met inclusion criteria. Changes over time included increasing age, utilization of peripheral blood cells, reduced intensity conditioning, and T-cell depletion. Three-year OS increased significantly from 44% in 2001-2005 to 58% in 2011-2015 (p < 0.001). This was attributed to a reduction in NRM from 35% to 24% (p < 0.001) with no change in relapse. Factors associated with increased NRM included age, male sex, CMV seropositivity, HLA mismatch, transplant more than 6 months from diagnosis, and T-cell depletion when administered during 2001-2005. Survival following UD SCT has improved by almost 15% over the past decade, driven by improvements in NRM. This has occurred despite increasing recipient age and appears to be due to better donor selection, reduced delays to transplantation, and improved prevention and management of GVHD.
Subject(s)
Graft vs Host Disease , Hematopoietic Stem Cell Transplantation , Adult , Graft vs Host Disease/etiology , Hematopoietic Stem Cell Transplantation/adverse effects , Humans , Infant , Male , New Zealand/epidemiology , Recurrence , Retrospective Studies , Transplantation Conditioning , Unrelated DonorsABSTRACT
Sleep disorders and chronic sleep disturbances are common and are associated with cardio-metabolic diseases and neuropsychiatric disorders. Several genetic pathways and neuronal mechanisms that regulate sleep have been described in animal models, but the genes underlying human sleep variation and sleep disorders are largely unknown. Identifying these genes is essential in order to develop effective therapies for sleep disorders and their associated comorbidities. To address this unmet health problem, genome-wide association studies (GWAS) have identified numerous genetic variants associated with human sleep traits and sleep disorders. However, in most cases, it is unclear which gene is responsible for a sleep phenotype that is associated with a genetic variant. As a result, it is necessary to experimentally validate candidate genes identified by GWAS using an animal model. Rodents are ill-suited for this endeavor due to their poor amenability to high-throughput sleep assays and the high costs associated with generating, maintaining, and testing large numbers of mutant lines. Zebrafish (Danio rerio), an alternative vertebrate model for studying sleep, allows for the rapid and cost-effective generation of mutant lines using the CRISPR/Cas9 system. Numerous zebrafish mutant lines can then be tested in parallel using high-throughput behavioral assays to identify genes whose loss affects sleep. This process identifies a gene associated with each GWAS hit that is likely responsible for the human sleep phenotype. This strategy is a powerful complement to GWAS approaches and holds great promise to identify the genetic basis for common human sleep disorders.
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Background: Production of affordable coronavirus disease 2019 (COVID-19) vaccines in low- and middle-income countries is needed. NDV-HXP-S is an inactivated egg-based recombinant Newcastle disease virus vaccine expressing the spike (S) protein of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). It's being developed by public sector manufacturers in Thailand, Vietnam, and Brazil; herein are initial results from Thailand. Methods: This phase 1 stage of a randomised, dose-escalation, observer-blind, placebo-controlled, phase 1/2 trial was conducted at the Vaccine Trial Centre, Mahidol University (Bangkok). Healthy males and non-pregnant females, aged 18-59 years and negative for SARS-CoV-2 antibodies, were eligible. Participants were randomised to receive one of six treatments by intramuscular injection twice, 28 days apart: 1 µg, 1 µg+CpG1018 (a toll-like receptor 9 agonist), 3 µg, 3 µg+CpG1018, 10 µg, or placebo. Participants and personnel assessing outcomes were masked to treatment. The primary outcomes were solicited and spontaneously reported adverse events (AEs) during 7 and 28 days after each vaccination, respectively. Secondary outcomes were immunogenicity measures (anti-S IgG and pseudotyped virus neutralisation). An interim analysis assessed safety at day 57 in treatment-exposed individuals and immunogenicity through day 43 per protocol. ClinicalTrials.gov (NCT04764422). Findings: Between March 20 and April 23, 2021, 377 individuals were screened and 210 were enroled (35 per group); all received dose one; five missed dose two. The most common solicited AEs among vaccinees, all predominantly mild, were injection site pain (<63%), fatigue (<35%), headache (<32%), and myalgia (<32%). The proportion reporting a vaccine-related AE ranged from 5·7% to 17·1% among vaccine groups and was 2·9% in controls; there was no vaccine-related serious adverse event. The 10 µg formulation's immunogenicity ranked best, followed by 3 µg+CpG1018, 3 µg, 1 µg+CpG1018, and 1 µg formulations. On day 43, the geometric mean concentrations of 50% neutralising antibody ranged from 122·23 international units per mL (IU/mL; 1 µg, 95% confidence interval (CI) 86·40-172·91) to 474·35 IU/mL (10 µg, 95% CI 320·90-701·19), with 93·9% to 100% of vaccine groups attaining a ≥ 4-fold increase over baseline. Interpretation: NDV-HXP-S had an acceptable safety profile and potent immunogenicity. The 3 µg and 3 µg+CpG1018 formulations advanced to phase 2. Funding: National Vaccine Institute (Thailand), National Research Council (Thailand), Bill & Melinda Gates Foundation, National Institutes of Health (USA).
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BACKGROUND: Emerging health care strategies addressing medication adherence include the use of direct-to-patient incentives or elements adapted from computer games. However, there is currently no published evidence synthesis on the use of gamification or financial incentives in mobile apps to improve medication adherence. OBJECTIVE: The aim of this scoping review is to synthesize and appraise the literature pertaining to the use of mobile apps containing gamification or financial incentives for medication adherence. There were two objectives: to explore the reported effectiveness of these features and to describe and appraise the design and development process, including patient involvement. METHODS: The following databases were searched for relevant articles published in English from database inception to September 24, 2020: Embase, MEDLINE, PsycINFO, CINAHL, and Web of Science. The framework by Arksey and O'Malley and the PRISMA-ScR (Preferred Reporting Items for Systematic Reviews and Meta-Analyses extension for Scoping Reviews) checklist guided this scoping review. Using a systematic screening process, studies were included if incentives or game features were used within mobile apps to specifically address medication adherence. An appraisal using risk of bias tools was also applied to their respective study design. RESULTS: A total of 11 studies from the initial 691 retrieved articles were included in this review. Across the studies, gamification alone (9/11, 82%) was used more than financial incentives (1/11, 9%) alone or a combination of the two (1/11, 9%). The studies generally reported improved or sustained optimal medication adherence outcomes; however, there was significant heterogeneity in the patient population, methodology such as outcome measures, and reporting of these studies. There was considerable variability in the development process and evaluation of the apps, with authors opting for either the waterfall or agile methodology. App development was often guided by a theory, but across the reviewed studies, there were no common theories used. Patient involvement was not commonly evident in predevelopment phases but were generally reserved for evaluations of feasibility, acceptance, and effectiveness. Patient perspectives on gamified app features indicated a potential to motivate positive health behaviors such as medication adherence along with critical themes of repetitiveness and irrelevance of certain features. The appraisal indicated a low risk of bias in most studies, although concerns were identified in potential confounding. CONCLUSIONS: To effectively address medication adherence via gamified and incentivized mobile apps, an evidence-based co-design approach and agile methodology should be used. This review indicates some adoption of an agile approach in app development; however, patient involvement is lacking in earlier stages. Further research in a generalized cohort of patients living with chronic conditions would facilitate the identification of barriers, potential opportunities, and the justification for the use of gamification and financial incentives in mobile apps for medication adherence.
Subject(s)
Mobile Applications , Telemedicine , Gamification , Humans , Medication Adherence , Motivation , Telemedicine/methodsABSTRACT
BACKGROUND: Production of affordable coronavirus disease 2019 (COVID-19) vaccines in low- and middle-income countries is needed. NDV-HXP-S is an inactivated egg-based Newcastle disease virus vaccine expressing the spike protein of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). It's being developed in Thailand, Vietnam, and Brazil; herein are initial results from Thailand. METHODS: This phase 1 stage of a randomised, dose-escalation, observer-blind, placebo-controlled, phase 1/2 trial was conducted at the Vaccine Trial Centre, Mahidol University (Bangkok). Healthy adults aged 18-59 years, non-pregnant and negative for SARS-CoV-2 antibodies were eligible. Participants were block randomised to receive one of six treatments by intramuscular injection twice, 28 days apart: 1 µg±CpG1018 (a toll-like receptor 9 agonist), 3 µg±CpG1018, 10 µg, or placebo. Participants and personnel assessing outcomes were masked to treatment. The primary outcomes were solicited and spontaneously reported adverse events (AEs) during 7 and 28 days after each vaccination, respectively. Secondary outcomes were immunogenicity measures (anti-S IgG and pseudotyped virus neutralisation). An interim analysis assessed safety at day 57 in treatment-exposed individuals and immunogenicity through day 43 per protocol. ClinicalTrials.gov ( NCT04764422 ). FINDINGS: Between March 20 and April 23, 2021, 377 individuals were screened and 210 were enrolled (35 per group); all received dose one; five missed dose two. The most common solicited AEs among vaccinees, all predominantly mild, were injection site pain (<63%), fatigue (<35%), headache (<32%), and myalgia (<32%). The proportion reporting a vaccine-related AE ranged from 5·7% to 17·1% among vaccine groups and was 2·9% in controls; there was no vaccine-related serious adverse event. The 10 µg formulation's immunogenicity ranked best, followed by 3 µg+CpG1018, 3 µg, 1 µg+CpG1018, and 1 µg formulations. On day 43, the geometric mean concentrations of 50% neutralising antibody ranged from 122·23 IU/mL (1 µg, 95% CI 86·40-172·91) to 474·35 IU/mL (10 µg, 95% CI 320·90-701·19), with 93·9% to 100% of vaccine groups attaining a ≥4-fold increase over baseline. INTERPRETATION: NDV-HXP-S had an acceptable safety profile and potent immunogenicity. The 3 µg and 3 µg+CpG1018 formulations advanced to phase 2. FUNDING: National Vaccine Institute (Thailand), National Research Council (Thailand), Bill & Melinda Gates Foundation, National Institutes of Health (USA).