Therapeutic applications of germline testing for cancer predisposition genes in Asia in the real world.

BACKGROUND: Germline genetic testing is traditionally carried out in patients suspected with hereditary cancer syndrome for enhanced cancer surveillance and/or preventive strategies, but is increasingly carried out for therapeutic indications. MATERIALS AND METHODS: We conducted a retrospective review of patients who underwent germline genetic testing at our centre to determine the prevalence of actionable pathogenic germline variants (PGV) and their clinical utility. RESULTS: From 2000 to 2022, 1154 cancer patients underwent germline testing, with the majority (945/1154) tested with multi-gene panels. Four hundred and eleven (35.6%) patients harboured a PGV and 334 (81%) were clinically actionable. BRCA1/2 accounted for 62.3% of actionable mutations, followed by mismatch repair (18%), and other homologous recombination repair (HRR) genes (19.7%). One hundred and fifty-two germline-positive patients have advanced cancers, and 79 received germline-directed therapies (poly ADP ribose polymerase inhibitors = 75; immunotherapy = 4). Median duration of immunotherapy and poly ADP ribose polymerase were 20.5 months (range 5-40 months) and 8 months (range 1-76 months), respectively. Among BRCA/HRR mutation carriers who received platinum-based chemotherapy, pathological complete response rate in the neoadjuvant setting was 53% (n = 17 breast cancers) and objective response rate was >80% in the advanced setting (n = 71). CONCLUSIONS: One-third of cancer patients tested carried a PGV and ∼80% were clinically actionable. Three-quarters of germline-positive advanced cancer patients received germline-directed therapies in the real world, underscoring the practical utility of germline testing to guide cancer therapeutics.

Deep-Level Structure of the Spin-Active Recombination Center in Dilute Nitrides.

A gallium interstitial defect is thought to be responsible for the spectacular spin-dependent recombination in GaAs_{1-x}N_{x} dilute nitrides. Current understanding associates this defect with at least two in-gap levels corresponding to the (+/0) and (++/+) charge-state transitions. Using a spin-sensitive photoinduced current transient spectroscopy, the in-gap electronic structure of a x=0.021 alloy is revealed. The (+/0) state lies ≈0.27 eV below the conduction band edge, and an anomalous, negative activation energy reveals the presence of not one but two other in-gap states. The observations are consistent with a (++/+) state ≈0.19 eV above the valence band edge, and a (+++/++) state ≈25 meV above the valence band edge.

Multiplicative Impact of Adverse Social Determinants of Health on Outcomes in Lupus Nephritis: A Meta-analysis and Systematic Review.

BACKGROUND: Social determinants of health (SDoH) likely contribute to outcome disparities in lupus nephritis (LN). Understanding the overall burden and contribution of each domain could guide future health-equity focused interventions to improve outcomes and reduce disparities in LN. Objectives of this meta-analysis were to: 1) determine the association of overall SDoH and specific SDoH domains on LN outcomes, and 2) develop a framework for the multidimensional impact of SDoH on LN outcomes. METHODS: We performed a comprehensive search of studies measuring associations between SDoH and LN outcomes. We examined pooled odds of poor LN outcomes including mortality, end-stage kidney disease, or cardiovascular disease in patients with and without adverse SDoH. Additionally, we calculated the pooled odds ratios of outcomes by four SDoH domains: individual (e.g., insurance), healthcare (e.g., fragmented care), community (e.g., neighborhood socioeconomic status), and health behaviors (e.g., smoking). RESULTS: Among 531 screened studies, 31 met inclusion and 13 studies with raw data were included in meta-analysis. Pooled odds of poor outcomes, were 1.47-fold higher in patients with any adverse SDoH. Patients with adverse SDoH in individual and healthcare domains had 1.64-fold and 1.77-fold higher odds of poor outcomes. We found a multiplicative impact of having ≥2 adverse SDoH on LN outcomes. Patients of Black Race with public insurance and fragmented care had 12-fold higher odds of poor LN outcomes. CONCLUSION: Adverse SDoH is associated with poor LN outcomes. Having ≥2 adverse SDoH, specifically in different SDoH domains, had a multiplicative impact leading to worse LN outcomes, widening disparities.

Remission and low disease activity are associated with lower healthcare costs: results from the Systemic Lupus International Collaborating Clinics (SLICC) inception cohort.

OBJECTIVES: This study aims to determine the independent impact of definitions of remission/low disease activity (LDA) on direct/indirect costs (DCs, ICs) in a multicentre inception cohort. METHODS: Patients from 31 centres in 10 countries were enrolled within 15 months of diagnosis and assessed annually. Five mutually exclusive disease activity states (DAS) were defined as (1) remission off-treatment: clinical (c) SLEDAI-2K=0, without prednisone/immunosuppressants; (2) remission on-treatment: cSLEDAI-2K=0, prednisone ≤5 mg/day and/or maintenance immunosuppressants; (3) LDA-Toronto Cohort (TC): cSLEDAI-2K≤2, without prednisone/immunosuppressants; (4) modified lupus LDA state (mLLDAS): SLEDAI-2K≤4, no activity in major organs/systems, no new activity, prednisone ≤7.5 mg/day and/or maintenance immunosuppressants and (5) active: all remaining assessments.At each assessment, patients were stratified into the most stringent DAS fulfilled and the proportion of time in a DAS since cohort entry was determined. Annual DCs/ICs (2021 Canadian dollars) were based on healthcare use and lost workforce/non-workforce productivity over the preceding year.The association between the proportion of time in a DAS and annual DC/IC was examined through multivariable random-effects linear regressions. RESULTS: 1692 patients were followed a mean of 9.7 years; 49.0% of assessments were active. Remission/LDA (per 25% increase in time in a remission/LDA state vs active) were associated with lower annual DC/IC: remission off-treatment (DC -$C1372; IC -$C2507), remission on-treatment (DC -$C973; IC -$C2604,) LDA-TC (DC -$C1158) and mLLDAS (DC -$C1040). There were no cost differences between remission/LDA states. CONCLUSIONS: Our data suggest that systemic lupus erythematosus patients who achieve remission, both off and on-therapy, and reductions in disease activity incur lower costs than those experiencing persistent disease activity.

Informing Digital Programs for Lupus Self-Management Education: A Systematic Scoping Review.

OBJECTIVE: We describe the characteristics, content, and effectiveness of digital self-management (SM) education programs for lupus and other chronic conditions to identify gaps and inform the improvement of future programs in lupus. METHODS: Three bibliographic databases were searched for articles published between May 2012 and April 2022. The search was cast to capture the breadth of digital SM education programs in the following conditions: lupus, epilepsy, fibromyalgia, multiple sclerosis, sickle cell anemia, Sjögren syndrome, psoriatic arthritis, and rheumatoid arthritis. Title and abstract screening, as well as full-text review, was conducted by two independent reviewers. Data extraction was first completed by one author charting all studies and then, a second time, by four members of the research team charting collaboratively. RESULTS: Of the 1,969 articles identified through the search, 14 met inclusion criteria. Two additional articles were included following bibliography review. The 16 articles represented 12 unique digital SM education programs. Programs covered five conditions: epilepsy (n = 3), fibromyalgia (n = 2), multiple sclerosis (n = 4), lupus (n = 1), and rheumatoid arthritis (n = 2). Most programs were asynchronous and internet-based (n = 9) with a prescribed sequence of content (n = 8). Peer, technical, or specialist support was offered in seven programs. Most programs demonstrated statistically significant improvement of symptoms in the intervention group (n = 8). CONCLUSION: This scoping review summarizes the current landscape for digital SM education programs in lupus and similar conditions. In lupus, further investigation will fill in the gaps around digital SM education needs, user experience, and evaluation of outcomes.

Financial Hardship and Sleep Quality Among Black American Women With and Without Systemic Lupus Erythematosus.

OBJECTIVE: To compare dimensions of financial hardship and self-reported sleep quality among Black women with versus without systemic lupus erythematosus (SLE). METHODS: Participants were 402 Black women (50% with validated diagnosis of SLE) living in Georgia between 2017 and 2020. Black women with SLE were recruited from a population-based cohort established in Atlanta, and Black women without SLE were recruited to be of comparable age and from the same geographic areas as SLE women. Financial hardship was measured using three different scales: financial adjustments, financial setbacks, and financial strain. Sleep was assessed continuously using the Pittsburgh Sleep Quality Index (PSQI) scale. Each dimension of financial hardship was analyzed separately in SLE-stratified multivariable linear regression models and adjusted by sociodemographic and health status factors. RESULTS: Dimensions of financial hardship were similarly distributed across the two groups. Sleep quality was worse in Black women with, versus without, SLE (p < .001). Among Black women with SLE, financial adjustment was positively associated with a 0.40-unit increase in poor sleep quality (95% CI = 0.12-0.67, p = .005). When accounting for cognitive depressive symptoms, financial setbacks and strain were somewhat attenuated for Black women with SLE. Overall, no associations between financial hardships and sleep quality were observed for the women without SLE. CONCLUSIONS: Black women with SLE who experience financial hardships may be more at risk for poor sleep quality than Black women without SLE. Economic interventions targeting this population may help improve their overall health and quality of life.

Comparison of cognitive performance measures in individuals with systemic lupus erythematosus.

OBJECTIVE: Cognitive impairment is a common complaint in SLE, but approaches to measuring cognitive performance objectively vary. Leveraging data collected in a population-based cohort of individuals with validated SLE, we compared performance and potential impairment across multiple measures of cognition. METHODS: During a single study visit (October 2019-May 2022), times to complete the Trail Making Test B (TMTB; N=423) were recorded; potential impairment was defined as an age-corrected and education-corrected T-score <35 (>1.5 SD longer than the normative time). A clock drawing assessment (CLOX; N=435) with two parts (free clock draw (CLOX1) and copy (CLOX2)) was also performed (score range: 0-15; higher scores=better performance); potential impairment was defined as CLOX1 <10 or CLOX2 <12. Fluid cognition (N=199; in-person visits only) was measured via the National Institutes of Health (NIH) Toolbox Fluid Cognition Battery and expressed as age-corrected standard scores; potential impairment was defined by a score <77.5 (>1.5 SD lower the normative score). RESULTS: Participants (mean age 46 years; 92% female; 82% black) had a median (IQR) TMTB time of 96 (76-130) s; median (IQR) CLOX1 and CLOX2 scores of 12 (10-13) and 14 (13-15); and a mean (SD) fluid cognition standard score of 87.2 (15.6). TMTB time and fluid cognition score (ρ=-0.53, p<0.001) were the most highly intercorrelated measures. Overall, 65%, 55% and 28% were potentially impaired by the TMTB test, CLOX task and NIH Toolbox Fluid Cognition Battery, respectively. While there was overlap in potential impairment between TMTB and CLOX, more than half (58%) had impairment by only one of these assessments. Few (2%) had impairment in fluid cognition only. CONCLUSION: The TMTB, CLOX and NIH Fluid Cognition Battery each provided unique and potentially important information about cognitive performance in our SLE cohort. Future studies are needed to validate these measures in SLE and explore interventions that maintain or improve cognitive performance in this population.

Differences in Discounting Behavior and Brain Responses for Food and Money Reward.

Most neuroeconomic research seeks to understand how value influences decision-making. The influence of reward type is less well understood. We used functional magnetic resonance imaging (fMRI) to investigate delay discounting of primary (i.e., food) and secondary rewards (i.e., money) in 28 healthy, normal-weighted participants (mean age = 26.77; 18 females). To decipher differences in discounting behavior between reward types, we compared how well-different option-based statistical models (exponential, hyperbolic discounting) and attribute-wise heuristic choice models (intertemporal choice heuristic, dual reasoning and implicit framework theory, trade-off model) captured the reward-specific discounting behavior. Contrary to our hypothesis of different strategies for different rewards, we observed comparable discounting behavior for money and food (i.e., exponential discounting). Higher k values for food discounting suggest that individuals decide more impulsive if confronted with food. The fMRI revealed that money discounting was associated with enhanced activity in the right dorsolateral prefrontal cortex, involved in executive control; the right dorsal striatum, associated with reward processing; and the left hippocampus, involved in memory encoding/retrieval. Food discounting, instead, was associated with higher activity in the left temporoparietal junction suggesting social reinforcement of food decisions. Although our findings do not confirm our hypothesis of different discounting strategies for different reward types, they are in line with the notion that reward types have a significant influence on impulsivity with primary rewards leading to more impulsive choices.

A study of hospitalized COVID-19 patients with AKI in a setting of multiracial developing country.

BACKGROUND: The commonest indication for hospitalization in COVID-19 patients is hypoxemia or severe respiratory symptoms. However, COVID-19 disease may result in extrapulmonary complications including kidney-related pathology. The reported incidence of renal involvement related to COVID infection varies based on geographical location. OBJECTIVE: This study aimed to assess the incidence rate of AKI in hospitalized COVID-19 patients and identify risk factors and prognostic predictors. METHOD: In this retrospective study, we recruited hospitalized COVID-19 patients from January 2021 until June 2021 at the University Malaya Medical Center. The inclusion criteria were hospitalized for ≥ 48 h with confirmed COVID-19 infection and at least 18 years old. Patient demographic and clinical data were collected from electronic medical records. The staging of AKI was based on criteria as per KDIGO guidelines. RESULTS: One thousand five hundred twenty-nine COVID patients fulfilled the inclusion criteria with a male-to-female ratio of 759 (49.6%) to 770 (50.3%). The median age was 55 (IQR: 36-66). 500 patients (32.7%) had diabetes, 621 (40.6%) had hypertension, and 5.6% (n = 85) had pre-existing chronic kidney disease (CKD). The incidence rate of AKI was 21.1% (n = 323). The percentage of COVID patients in different AKI stages of 1,2 and 3 were 16.3%, 2.1%, and 2.7%, respectively. Fifteen hospitalized patients (0.98%) required renal replacement therapy. 58.8% (n = 190) of AKI group had complete recovery of kidney function. Demographic factors included age (p < 0.001), diabetes (p < 0.001), hypertension (p < 0.012), CKD (p < 0.001), and vaccination status (p = 0.042) were associated with an increased risk of developing AKI. We found that the AKI cohort had statistically significant lower platelet counts and higher ferritin levels than the non-AKI cohort. AKI is a risk predictor of prolonged hospitalization (p < 0.001) and higher mortality rates (P < 0.001). CONCLUSION: AKI is a common clinical complication among hospitalized COVID-19 patients. The etiology of AKI is multifactorial and may have an adverse impact on patient morbidity and mortality.

Implementing a Staff-Led Smoking Cessation Intervention in a Diverse Safety-Net Rheumatology Clinic: A Pre-Post Scalability Study in a Low-Resource Setting.

OBJECTIVE: Quit Connect (QC), our specialty clinic smoking cessation intervention, supports clinic staff to check, advise, and connect willing patients to a state quit line or class. QC improved tobacco screening and quit line referrals 26-fold in a predominantly White academic health care system population. Implementing QC includes education, electronic health record (EHR) reminders, and periodic audit feedback. This study tested QC's feasibility and impact in a safety-net rheumatology clinic with a predominantly Black population. METHODS: In this pre-post study, adult rheumatology visits were analyzed 12 months before through 18 months after QC intervention (November 2019 through November 2021, omitting COVID-19 peak April through November 2020). EHR data compared process and clinical outcomes, including offers, referrals to resources, completed referrals, and documented cessation. Clinic staff engaged in pre-post focus groups and questionnaires regarding intervention feasibility and acceptability. Cost-effectiveness was also assessed. RESULTS: Visit-level patients who smoked were 89.8% Black and 69.5% women (n = 550). Before intervention, clinic staff rarely asked patients about readiness to cut back smoking (<10% assessment). After QC intervention, staff assessed quit readiness in 31.8% of visits with patients who smoked (vs 8.1% before); 58.9% of these patients endorsed readiness to cut back or quit. Of 102 accepting cessation services, 37% (n = 17) of those reached set a quit date. Staff found the intervention feasible and acceptable. Each quit attempt cost approximately $4 to $10. CONCLUSION: In a safety-net rheumatology clinic with a predominantly Black population, QC improved tobacco screening, readiness-to-quit assessment, and referrals and was also feasible and cost-effective.

Fluid Cognition Among Individuals With Systemic Lupus Erythematosus.

OBJECTIVE: We sought to describe fluid cognition and its correlates among individuals with systemic lupus erythematosus (SLE). METHODS: Participants (n = 199) were recruited from a population-based cohort for a single study visit (October 2019 to May 2022). Fluid cognition was measured via the National Institutes of Health Toolbox Fluid Cognition Battery (including episodic memory, working memory, attention and inhibitory control, processing speed, and cognitive flexibility domains) and expressed as age-corrected standard scores (mean 100, SD 15). Potential impairment was defined as a standard score >1.5 SD below the mean. Descriptive statistics were calculated and associations of various participant characteristics with the potential fluid cognition impairment were assessed with multivariable logistic regression. RESULTS: Participants' mean age was 46.1 years; most were female (87.4%), Black (86.4%), and non-Hispanic (95.0%). The mean overall fluid cognition score was 87.2; of the individual domains, the participants' mean score was lowest on attention and inhibitory control (82.0). Working status (odds ratio [OR] 0.30, 95% confidence interval [CI] 0.14-0.64) and higher self-reported physical functioning (OR 0.46, 95% CI 0.28-0.75) and physical performance (OR 0.72, 95% CI 0.59-0.87) were associated with lower odds of fluid cognition impairment; lower educational attainment was associated with higher odds (OR 3.82, 95% CI 1.67-8.75). Self-reported forgetfulness, neuropsychiatric damage, and depressive symptoms were not statistically significantly associated with potential impairment. CONCLUSION: Fluid cognition and, particularly, attention and inhibitory control were low in those with SLE relative to the general US population. Working status, higher physical functioning and performance, and higher educational attainment were associated with lower prevalence of potential impairment. Future work is needed to develop and implement interventions to help support cognition in individuals with SLE.

Co-delivery of HIV pre-exposure prophylaxis (PrEP) and HIV testing among publicly insured adolescents and young adults (AYA) receiving medication for opioid use disorder (MOUD).

BACKGROUND: Low rates of HIV pre-exposure prophylaxis (PrEP) prescribing contribute to the disproportionate burden of HIV in the United States. Among adolescent and young adults (AYA) with opioid use disorder, HIV testing and PrEP co-prescription rates are poorly characterized. METHODS: We performed a retrospective analysis involving deidentified data from Philadelphia's Medicaid beneficiaries ages 16-29 years who were prescribed medication for opioid use disorder (MOUD) from 2015 to 2020 and continuously Medicaid-enrolled for ≥6 months prior to that prescription. After identifying the presence of a qualifying diagnosis signifying a PrEP indication, we examined the outcome of appropriate PrEP co-prescriptions and HIV testing using generalized estimating equations (GEE) modeling. RESULTS: We identified 795 AYA Medicaid beneficiaries with 1269 qualified treatment episodes. We calculated a PrEP prescribing rate of 29.47 per 1000 person-years among AYA receiving MOUD. The HIV testing rate was 63.47 per 1000 person-years among AYA receiving MOUD. GEE modeling revealed that individuals receiving methadone were more likely (aOR=2.62, 95% CI=1.06-6.49) to receive HIV testing within 6 months after a PrEP-qualifying diagnosis compared to those receiving other MOUD medications. Those who only saw outpatient behavioral health providers were less likely (aOR=0.48, 95% CI=0.24-0.99) to have received an HIV test within 6 months after the PrEP-qualifying diagnosis compared to those receiving inpatient behavioral health services. CONCLUSIONS: Co-prescription of PrEP and HIV testing among AYA receiving MOUD was rare in this large urban publicly insured population. Interventions are needed to increase HIV prevention services for this key population of AYA at risk for HIV infection.

The hindbrain and cortico-reticular pathway in adolescent idiopathic scoliosis.

AIM: To characterise the corticoreticular pathway (CRP) in a case-control cohort of adolescent idiopathic scoliosis (AIS) patients using high-resolution slice-accelerated readout-segmented echo-planar diffusion tensor imaging (DTI) to enhance the discrimination of small brainstem nuclei in comparison to automated whole-brain volumetry and tractography and their clinical correlates. MATERIALS AND METHODS: Thirty-four participants (16 AIS patients, 18 healthy controls) underwent clinical and orthopaedic assessments and brain magnetic resonance imaging (MRI) on a 3 T MRI machine. Automated whole-brain volume-based morphometry, tract-based spatial statistics analysis, and manual CRP tractography by two independent raters were performed. Intra-rater and inter-rater agreement of DTI metrics from CRP tractography were assessed by intraclass correlation coefficient. Normalised structural brain volumes and DTI metrics were compared between groups using Student's t-tests. Linear correlation analysis between imaging parameters and clinical scores was also performed. RESULTS: AIS patients demonstrated a significantly larger pons volume compared to controls (p=0.006). Significant inter-side CRP differences in mean (p=0.02) and axial diffusivity (p=0.01) were found in patients only. Asymmetry in CRP fractional anisotropy significantly correlated with the Cobb angle (p=0.03). CONCLUSION: Relative pontine hypertrophy and asymmetry in CRP DTI metrics suggest central supranuclear inter-hemispheric imbalance in AIS, and support the role of the CRP in axial muscle tone. Longitudinal evaluation of CRP DTI metrics in the prediction of AIS progression may be clinically relevant.

Genomic epidemiology reveals geographical clustering of multidrug-resistant Escherichia coli ST131 associated with bacteraemia in Wales.

Antibiotic resistance is a significant global public health concern. Uropathogenic Escherichia coli sequence type (ST)131, a widely prevalent multidrug-resistant clone, is frequently associated with bacteraemia. This study investigates third-generation cephalosporin resistance in bloodstream infections caused by E. coli ST131. From 2013-2014 blood culture surveillance in Wales, 142 E. coli ST131 genomes were studied alongside global data. All three major ST131 clades were represented across Wales, with clade C/H30 predominant (n = 102/142, 71.8%). Consistent with global findings, Welsh strains of clade C/H30 contain ß-lactamase genes from the blaCTX-M-1 group (n = 65/102, 63.7%), which confer resistance to third-generation cephalosporins. Most Welsh clade C/H30 genomes belonged to sub-clade C2/H30Rx (58.3%). A Wales-specific sub-lineage, named GB-WLS.C2, diverged around 1996-2000. An introduction to North Wales around 2002 led to a localised cluster by 2009, depicting limited genomic diversity within North Wales. This investigation emphasises the value of genomic epidemiology, allowing the detection of genetically similar strains in local areas, enabling targeted and timely public health interventions.

Mycophenolate mofetil withdrawal in patients with systemic lupus erythematosus: a multicentre, open-label, randomised controlled trial.

BACKGROUND: Mycophenolate mofetil is an immunosuppressant commonly used to treat systemic lupus erythematosus (SLE) and lupus nephritis. It is a known teratogen associated with significant toxicities, including an increased risk of infections and malignancies. Mycophenolate mofetil withdrawal is desirable once disease quiescence is reached, but the timing of when to do so and whether it provides a benefit has not been well-studied. We aimed to determine the effects of mycophenolate mofetil withdrawal on the risk of clinically significant disease reactivation in patients with quiescent SLE on long-term mycophenolate mofetil therapy. METHODS: This multicenter, open-label, randomised trial was conducted in 19 centres in the USA. Eligible patients were aged between 18 and 70 years old, met the American College of Rheumatology (ACR) 1997 SLE criteria, and had a clinical SLEDAI score of less than 4 at screening. Mycophenolate mofetil therapy was required to be stable or decreasing for 2 years or more if initiated for renal indications, or for 1 year or more for non-renal indications. Participants were randomly allocated in a 1:1 ratio to a withdrawal group, who tapered off mycophenolate mofetil over 12 weeks, or a maintenance group who maintained their baseline dose (1-3g per day) for 60 weeks. Adaptive random allocation ensured groups were balanced for study site, renal versus non-renal disease, and baseline mycophenolate mofetil dose (≥2 g per day vs <2 g per day). Clinically significant disease reactivation by week 60 following random allocation, requiring increased doses or new immunosuppressive therapy was the primary endpoint, in the modified intention-to-treat population (all randomly allocated participants who began study-provided mycophenolate mofetil). Non-inferiority was evaluated using an estimation-based approach. The trial was registered at ClinicalTrials.gov (NCT01946880) and is completed. FINDINGS: Between Nov 6, 2013, and April 27, 2018, 123 participants were screened, of whom 102 were randomly allocated to the maintenance group (n=50) or the withdrawal group (n=52). Of the 100 participants included in the modified intention-to-treat analysis (49 maintenance, 51 withdrawal), 84 (84%) were women, 16 (16%) were men, 40 (40%) were White, 41 (41%) were Black, and 76 (76%) had a history of lupus nephritis. The average age was 42 (SD 12·7). By week 60, nine (18%) of 51 participants in the withdrawal group had clinically significant disease reactivation, compared to five (10%) of 49 participants in the maintenance group. The risk of clinically significant disease reactivation was 11% (95% CI 5-24) in the maintenance group and 18% (10-32) in the withdrawal group. The estimated increase in the risk of clinically significant disease reactivation with mycophenolate mofetil withdrawal was 7% (one-sided upper 85% confidence limit 15%). Similar rates of adverse events were observed in the maintenance group (45 [90%] of 50 participants) and the withdrawal group (46 [88%] of 52 participants). Infections were more frequent in the mycophenolate mofetil maintenance group (32 [64%]) compared with the withdrawal group (24 [46%]). INTERPRETATIONS: Mycophenolate mofetil withdrawal is not significantly inferior to mycophenolate mofetil maintenance. Estimates for the rates of disease reactivation and increases in risk with withdrawal can assist clinicians in making informed decisions on withdrawing mycophenolate mofetil in patients with stable SLE. FUNDING: The National Institute of Allergy and Infectious Diseases and the National Institute of Arthritis and Musculoskeletal and Skin Diseases.

Appendectomy and asthma: a search for an association in older subjects.

INTRODUCTION: Several risk factors found to be associated with postoperative complications and cancer surgery, which carry a significant morbidity risk to cancer patients. Therefore, prehabilitation is necessary to improve the functional capability and nutritional status of a patient prior to surgery, so that the patient can withstand any postoperative activity and associated deterioration. Thus, this study aims to assess the effectiveness of prehabilitation interventions on the functional status of patients with gastric and oesophageal cancer who underwent esophagectomy and gastrectomy. MATERIAL AND METHODS: An interventional study was carried out among oesophageal and gastric cancer patients who had undergone surgery at the National Cancer Institute of Malaysia. The prehabilitation process took a maximum of two weeks, depending on the patient's optimisation before surgery. The prehabilitation is based on functional capacity (ECOG performance status), muscle function (handgrip strength), cardio-respiratory function (peak flow meter) and nutritional status (calorie and protein). Postoperative outcomes are measured based on the length of hospital stay, complications, and Clavien-Dindo Classification. RESULTS: Thirty-one patients were recruited to undergo a prehabilitation intervention prior to gastrectomy (n=21) and esophagectomy (n=10). Demographically, most of the cancer patients were males (67.7%) with an ideal mean of BMI (23.5±6.0). Physically, the majority of them had physical class (ASA grade) Grade 2 (67.7%), ECOG performance status of 1 (61.3%) and SGA grade B (51.6%). The functional capacity and nutritional status showed a significant improvement after one week of prehabilitation interventions: peak expiratory flow meter (p<0.001), handgrip (p<0.001), ECOG performance (p<0.001), walking distance (p<0.001), incentive spirometry (p<0.001), total body calorie (p<0.001) and total body protein (p=0.004). However, those patients who required two weeks of prehabilitation for optimization showed only significant improvement in peak expiratory flow meter (p<0.001), handgrip (p<0.001), and incentive spirometry (p<0.001). Prehabilitation is significantly associated postoperatively with the length of hospital stay (p=0.028), complications (p=0.011) and Clavien-Dindo Classification (p=0.029). CONCLUSION: Prehabilitation interventions significantly increase the functional capacity and nutritional status of cancer patients preoperatively; concurrently reducing hospital stays and complications postoperatively. However, certain cancer patients might require over two weeks of prehabilitation to improve the patient's functional capacity and reduce complications postoperatively.

Physical Performance in a Diverse, Population-Based Cohort of Individuals With Systemic Lupus Erythematosus.

OBJECTIVE: To report the burden and correlates of poor physical performance in a diverse cohort of individuals with systemic lupus erythematosus (SLE). METHODS: In this single-visit study of 446 individuals with SLE from a population-based metropolitan Atlanta cohort, we measured physical performance via the Short Physical Performance Battery (score range 0-12; intermediate-low [<10] vs high [≥10]). We also collected demographic, clinical, and psychosocial variables and examined the associations (adjusted odds ratios [aORs]) of intermediate-low versus high physical performance with these characteristics via multivariable logistic regression. RESULTS: We found that more than half (59.6%) of our participants had poorer (intermediate-low) overall physical performance. Only 7% of the cohort received the maximum score on the lower body strength task versus 90% and 76% receiving the maximum scores on balance and gait speed tasks. Current employment status (aOR 0.69, 95% confidence interval [CI] 0.45-1.05) and higher cognitive functioning (aOR 0.57, 95% CI 0.42-0.77) were strongly associated with lower odds of intermediate-low physical performance. Higher body mass index (aOR 1.25, 95% CI 1.01-1.56), disease activity (aOR 1.59, 95% CI 1.27-1.98), and disease burden (aOR 1.38, 95% CI 1.08-1.77) were associated with poorer performance, as were higher depressive symptoms, perceived stress scores, and lower educational attainment (not statistically significant). CONCLUSION: In our population-based, primarily Black cohort, we found that individuals with SLE commonly had poor physical performance. We identified both SLE- and non-SLE-specific factors that could help clinicians identify those most at risk for poor physical performance and intervene to improve, maintain, and support physical performance among those with SLE.

The pharmacokinetics of 38% silver diamine fluoride in healthy children with dental caries: a quasi-experimental study.

PURPOSE: Silver diamine fluoride (SDF) is a medication used for the arrestment of dental caries. This study aims to determine the pharmacokinetics (PK) of silver and fluoride following SDF application in healthy children with dental caries. METHODS: A total of 15 subjects, aged 4 to 10 years, with at least one cavity on a primary tooth, were recruited for this study. Urine samples were collected at baseline, first 24 h (F1) and second 24 h (F2) after SDF treatment for analysis of silver and fluoride content. Hair samples were also collected at baseline and at 7, 14, 30, 60, 75, and 90 days after SDF treatment to analyze silver content. RESULTS: Participants with under or over-collection of urine, or failure to provide urine collection were excluded for fluoride analysis. As a result, eight subjects' urine samples were eligible for fluoride analysis. Significant correlations were observed between baseline urinary fluoride levels and F1/F2 levels. Pairwise comparisons from Friedman's test showed significant differences between baseline and F1 fluoride levels. For silver analysis, 15 subjects were studied. F1 urinary silver levels were higher than baseline and F2 levels. Subsequent to SDF treatment, hair silver levels displayed fluctuations around the baseline. None of the participants reported adverse effects, and all caries teeth ceased progression within 30 days. CONCLUSIONS: The urinary fluoride levels after SDF treatment, although higher, were not clinically significant. Urinary and hair silver levels were negligible. Therefore, SDF appears safe to be used among children.