Healthcare Encounters and Outcomes of Filipino Patients with Systemic Lupus Erythematosus Managed at a Tertiary COVID-19 Referral Center.

Objective: The coronavirus disease 2019 (COVID-19) pandemic has limited healthcare delivery for patients with chronic diseases, including Systemic Lupus Erythematosus (SLE). This study aims to describe the outcomes of patients with SLE in a national COVID-19 referral center in the Philippines. Methods: A review of records of all adult patients with SLE seen in the University of the Philippines-Philippine General Hospital (UP-PGH) from March 2020 to December 2021 was done. Data about patient characteristics, health encounters, and outcomes before and after the first visit during the study period were extracted. Descriptive statistics were employed. Results: Our population of 403 patients was predominantly young (mean age 34.53 ± 11.14 years), female, and unemployed. This consisted of 370 known cases of SLE, 92 were diagnosed in institutions outside UP-PGH, and 33 new patients. Over the 22-month study period, there were 2,093 medical encounters, most of which were teleconsultations (81.70%). During an average gap of 53.6 ± 26.7 weeks between the last consultation and the first visit within the pandemic study period, 84 patients (22.70%) discontinued at least one of their SLE control medications, 68 (18.38%) patients developed a lupus flare, and 79 (21.35%) were hospitalized for various reasons. On their return to the rheumatology clinic during the pandemic, 37.47% were in lupus flare, 28.29% needed to be hospitalized, and 20 died. However, 86.75% of flares were controlled. During subsequent health encounters, 48 patients had a new flare (43 of these were controlled) and 20 died. The most common reason for hospitalization (n=160) was lupus disease flare and the most common cause of death (n=40) was pneumonia. Sixty patients acquired COVID-19 infection from which most recovered and four died. Conclusion: Audio teleconsultation was the most common method used by our lupus cohort to interact with their doctors during the pandemic. There was an average of a year-long interruption in medical care for 62.70%. More than a third developed a disease flare and 15% acquired COVID-19 but outcomes were good in more than 85%. Despite the challenges posed by the pandemic, the majority of our lupus cohort who were able to continue their treatment had favorable outcomes.

A fibroblast-dependent TGFß1/sFRP2 noncanonical Wnt signaling axis promotes epithelial metaplasia in idiopathic pulmonary fibrosis.

Reciprocal interactions between alveolar fibroblasts and epithelial cells are crucial for lung homeostasis, injury repair, and fibrogenesis, but underlying mechanisms remain unclear. To investigate, we administered the fibroblast-selective TGFß1 signaling inhibitor, epigallocatechin gallate (EGCG), to Interstitial Lung Disease (ILD) patients undergoing diagnostic lung biopsy and conducted single-cell RNA sequencing on spare tissue. Biopsies from untreated patients showed higher fibroblast TGFß1 signaling compared to non-disease donor or end-stage ILD tissues. In vivo, EGCG downregulated TGFß1 signaling and several pro-inflammatory and stress pathways in biopsy samples. Notably, EGCG reduced fibroblast secreted frizzle-like receptor protein 2 (sFRP2), an unrecognized TGFß1 fibroblast target gene induced near type II alveolar epithelial cells (AEC2s) in situ. Using AEC2-fibroblast coculture organoids and precision cut lung slices (PCLS) from non-diseased donors, we found TGFß1 signaling promotes a spread AEC2 KRT17+ basaloid state, whereupon sFRP2 then activates a mature Krt5+ basal cell program. Wnt-receptor Frizzled 5 (Fzd5) expression and downstream calcineurin signaling were required for sFRP2-induced nuclear NFATc3 accumulation and KRT5 expression. These findings highlight stage-specific TGFß1 signaling in ILD, the therapeutic potential of EGCG in reducing IPF-related transcriptional changes, and identify TGFß1-non-canonical Wnt pathway crosstalk via sFRP2 as a novel mechanism for dysfunctional epithelial signaling in Idiopathic Pulmonary Fibrosis/ILD.

Knowledge, Attitudes, and Beliefs About Opioid Use Disorder Treatment in Primary Care.

This survey study assesses the US public's perception and awareness regarding medication for opioid use disorder and its availability in primary care settings.

Update on the assessment of resistance to antidepressant treatment: Rationale for the Antidepressant Treatment History Form: Short Form-2 (ATHF-SF2).

All definitions of treatment-resistant depression (TRD) require that patients have experienced insufficient benefit from one or more adequate antidepressant trials. Thus, identifying "failed, adequate trials" is key to the assessment of TRD. The Antidepressant Treatment History Form (ATHF) was one of the first and most widely used instruments that provided objective criteria in making these assessments. The original ATHF was updated in 2018 to the ATHF-SF, changing to a checklist format for scoring, and including specific pharmacotherapy, brain stimulation, and psychotherapy interventions as potentially adequate antidepressant treatments. The ATHF-SF2, presented here, is based on the consensus of the ATHF workgroup about the novel interventions introduced since the last revision and which should/should not be considered effective treatments for major depressive episodes. This document describes the rationale for these choices and, for each intervention, the minimal criteria for determining the adequacy of treatment administration. The Supplementary Material that accompanies this article provide the Scoring Checklist, Data Collection Forms (current episode and composite of previous episodes), and Instruction Manual for the ATHF-SF2.

A registered report of a two-site study of variations of the flanker task: ERN experimental effects and data quality.

Error-related negativity is a widely used measure of error monitoring, and many projects are independently moving ERN recorded during a flanker task toward standardization, optimization, and eventual clinical application. However, each project uses a different version of the flanker task and tacitly assumes ERN is functionally equivalent across each version. The routine neglect of a rigorous test of this assumption undermines efforts to integrate ERN findings across tasks, optimize and standardize ERN assessment, and widely apply ERN in clinical trials. The purpose of this registered report was to determine whether ERN shows similar experimental effects (correct vs. error trials) and data quality (intraindividual variability) during three commonly used versions of a flanker task. ERN was recorded from 172 participants during three versions of a flanker task across two study sites. ERN scores showed numerical differences between tasks, raising questions about the comparability of ERN findings across studies and tasks. Although ERN scores from all three versions of the flanker task yielded high data quality and internal consistency, one version did outperform the other two in terms of the size of experimental effects and the data quality. Exploratory analyses of the error positivity (Pe) provided tentative support for the other two versions of the task over the paradigm that appeared optimal for ERN. The present study provides a roadmap for how to statistically compare psychometric characteristics of ERP scores across paradigms and gives preliminary recommendations for flanker tasks to use for ERN- and Pe-focused studies.

A contact binary satellite of the asteroid (152830) Dinkinesh.

Asteroids with diameters less than about 5 km have complex histories because they are small enough for radiative torques (that is, YORP, short for the Yarkovsky-O'Keefe-Radzievskii-Paddack effect)1 to be a notable factor in their evolution2. (152830) Dinkinesh is a small asteroid orbiting the Sun near the inner edge of the main asteroid belt with a heliocentric semimajor axis of 2.19 AU; its S-type spectrum3,4 is typical of bodies in this part of the main belt5. Here we report observations by the Lucy spacecraft6,7 as it passed within 431 km of Dinkinesh. Lucy revealed Dinkinesh, which has an effective diameter of only 720 m, to be unexpectedly complex. Of particular note is the presence of a prominent longitudinal trough overlain by a substantial equatorial ridge and the discovery of the first confirmed contact binary satellite, now named (152830) Dinkinesh I Selam. Selam consists of two near-equal-sized lobes with diameters of 210 m and 230 m. It orbits Dinkinesh at a distance of 3.1 km with an orbital period of about 52.7 h and is tidally locked. The dynamical state, angular momentum and geomorphologic observations of the system lead us to infer that the ridge and trough of Dinkinesh are probably the result of mass failure resulting from spin-up by YORP followed by the partial reaccretion of the shed material. Selam probably accreted from material shed by this event.

Clinical characteristics and treatment exposure of patients with marked treatment-resistant unipolar major depressive disorder: A RECOVER trial report.

BACKGROUND: RECOVER is a randomized sham-controlled trial of vagus nerve stimulation and the largest such trial conducted with a psychiatric neuromodulation intervention. OBJECTIVE: To describe pre-implantation baseline clinical characteristics and treatment history of patients with unipolar, major depressive disorder (MDD), overall and as a function of exposure to interventional psychiatric treatments (INTs), including electroconvulsive therapy, transcranial magnetic stimulation, and esketamine. METHODS: Medical, psychiatric, and treatment records were reviewed by study investigators and an independent Study Eligibility Committee prior to study qualification. Clinical characteristics and treatment history (using Antidepressant Treatment History [Short] Form) were compared in those qualified (N = 493) versus not qualified (N = 228) for RECOVER, and among the qualified group as a function of exposure to INTs during the current major depressive episode (MDE). RESULTS: Unipolar MDD patients who qualified for RECOVER had marked TRD (median of 11.0 lifetime failed antidepressant treatments), severe disability (median WHODAS score of 50.0), and high rate of baseline suicidality (77% suicidal ideation, 40% previous suicide attempts). Overall, 71% had received at least one INT. Compared to the no INT group, INT recipients were younger and more severely depressed (QIDS-C, QIDS-SR), had greater suicidal ideation, earlier diagnosis of MDD, and failed more antidepressant medication trials. CONCLUSIONS: RECOVER-qualified unipolar patients had marked TRD and marked treatment resistance with most failing one or more prior INTs. Treatment with ≥1 INTs in the current MDE was associated with earlier age of MDD onset, more severe clinical presentation, and greater treatment resistance relative to patients without a history of INT. TRIAL REGISTRATION: ClinicalTrials.gov Identifier NCT03887715.

Post-operative Patient Portal Messaging is Associated With Return to the Emergency Department After Lumbar Spine Surgery.

STUDY DESIGN: Retrospective study. OBJECTIVE: To explore the association between patients undergoing lumbar spine surgery who message their care team via an electronic patient portal (EPP) post-operatively and emergency department (ED) visits within 90 days of surgery. SUMMARY OF BACKGROUND DATA: Secure patient messaging through electronic patient portals has grown over recent years. Despite its frequent utilization by patients to engage with their care team, its association with clinical outcomes remains unknown in spine surgery. METHODS: This study was approved by our Institutional Review Board. Inclusion criteria were adults who underwent single-stage lumbar spine surgery between January 2016-June 2023. Patients with incomplete information, multi-stage surgeries, and those who died within 90 days of surgery were excluded. Patient sociodemographic, surgical, hospital readmission, and patient-provider engagement data were collected. RESULTS: A total of 13,135 patients were included. A total of 1,711 patients (13%) had a post-operative ED visit, and 4,791 patients (36%) used the patient portal to send a message after surgery. Sending a post-operative patient message after undergoing lumbar spine surgery was associated with an increased likelihood of having an ED visit that does not lead to readmission (1.29 (1.10-1.53), P = 0.002). Patients with high school degrees were more likely to have an ED visit without readmission (1.33 (1.08-1.65), P = 0.008). CONCLUSION: Patients at a higher risk of presenting to the ED post-operatively should be identified and may benefit from additional counseling and access to the care team virtually to limit unnecessary healthcare utilization. Focusing on patients who reach out via EPP messaging post-operatively may be a good target patient group to address first. Future research is needed to investigate the possible health literacy and other socioeconomic barriers affecting these patients so that appropriate, more cost-effective resources can be utilized to avoid clinically unnecessary and costly ED visits.

Assessing the variation and drivers of cost in 1-level lumbar fusion: a time-driven activity-based costing analysis.

BACKGROUND CONTEXT: As value-based health care arrangements gain traction in spine care, understanding the true cost of care becomes critical. Historically, inaccurate cost proxies have been used, including negotiated reimbursement rates or list prices. However, time-driven activity-based costing (TDABC) allows for a more accurate cost assessment, including a better understanding of the primary drivers of cost in 1-level lumbar fusion. PURPOSE: To determine the variation of total hospital cost, differences in characteristics between high-cost and non-high-cost patients, and to identify the primary drivers of total hospital cost in a sample of patients undergoing 1-level lumbar fusion. STUDY DESIGN/SETTING: Retrospective, multicenter (one academic medical center, one community-based hospital), observational study. PATIENT SAMPLE: A total of 383 patients undergoing elective 1-level lumbar fusion for degenerative spine conditions between November 2, 2021 and December 2, 2022. OUTCOME MEASURES: Total hospital cost of care (normalized); preoperative, intraoperative, and postoperative cost of care (normalized); ratio of most to least expensive 1-level lumbar fusion. METHODS: Patients undergoing a 1-level lumbar fusion between November 2, 2021 and December 2, 2022 were identified at two hospitals (one quaternary referral academic medical center and one community-based hospital) within our health system. TDABC was used to calculate total hospital cost, which was also broken up into: pre-, intra-, and postoperative timeframes. Operating surgeon and patient characteristics were also collected and compared between high- and non-high-cost patients. The correlation of surgical time and cost was determined. Multivariable linear regression was used to determine factors associated with total hospital cost. RESULTS: The most expensive 1-level lumbar fusion was 6.8x more expensive than the least expensive 1-level lumbar fusion, with the intraoperative period accounting for 88% of total cost. On average. the implant cost accounted for 30% of the total, but across the patient sample, the implant cost accounted for a range of 6% to 44% of the total cost. High-cost patients were younger (55 years [SD: 13 years] vs.63 years [SD: 13 years], p=.0002), more likely to have commercial health insurance (24 out of 38 (63%) vs. 181 out of 345 (52%), p=.003). There was a poor correlation between time of surgery (i.e., incision to close) and total overall cost (ρ: .26, p<.0001). Increase age (RC: -0.003 [95% CI: -0.006 to -0.000007], p=.049) was associated with decreased cost. Surgery by certain surgeons was associated with decreased total cost when accounting for other factors (p<.05). CONCLUSIONS: A large variation exists in the total hospital cost for patients undergoing 1-level lumbar fusion, which is primarily driven by surgeon-level decisions and preferences (e.g., implant and technology use). Also, being a "fast" surgeon intraoperatively does not mean your total cost is meaningfully lower. As efforts continue to optimize patient value through ensuring appropriate clinical outcomes while also reducing cost, spine surgeons must use this knowledge to lead, or at least be active participants in, any discussions that could impact patient care.

Use of in-network insurance benefits is critical for improving retention in telehealth-based buprenorphine treatment.

An empiric evidence base is lacking regarding the relationship between insurance status, payment source, and outcomes among patients with opioid use disorder (OUD) on telehealth platforms. Such information gaps may lead to unintended impacts of policy changes. Following the phase-out of the COVID-19 Public Health Emergency, states were allowed to redetermine Medicaid eligibility and disenroll individuals. Yet, financial barriers remain a common and significant hurdle for patients with OUD and are associated with worse outcomes. We studied 3842 patients entering care in 2022 at Ophelia Health, one of the nation's largest OUD telehealth companies, to assess associations between insurance status and 6-month retention. In multivariable analyses, in-network patients who could use insurance benefits were more likely to be retained compared with cash-pay patients (adjusted risk ratio [aRR]: 1.50; 95% CI: 1.40-1.62; P < .001). Among a subsample of 882 patients for whom more detailed insurance data were available (due to phased-in electronic health record updates), in-network patients were also more likely to be retained at 6 months compared with insured, yet out-of-network patients (aRR: 1.86; 95% CI: 1.54-2.23; P < .001). Findings show that insurance status, and specifically the use of in-network benefits, is associated with superior retention and suggest that Medicaid disenrollment and insurance plan hesitation to engage with telehealth providers may undermine the nation's response to the opioid crisis.

Towards understanding sex differences in autism spectrum disorders.

Autism Spectrum Disorder (ASD) is a neurodevelopmental condition characterized by social deficits, repetitive behaviours and lack of empathy. Its significant genetic heritability and potential comorbidities often lead to diagnostic and therapeutic challenges. This review addresses the biological basis of ASD, focusing on the sex differences in gene expression and hormonal influences. ASD is more commonly diagnosed in males at a ratio of 4:1, indicating a potential oversight in female-specific ASD research and a risk of underdiagnosis in females. We consider how ASD manifests differently across sexes by exploring differential gene expression in female and male brains and consider how variations in steroid hormones influence ASD characteristics. Synaptic function, including excitation/inhibition ratio imbalance, is influenced by gene mutations and this is explored as a key factor in the cognitive and behavioural manifestations of ASD. We also discuss the role of micro RNAs (miRNAs) and highlight a novel mutation in miRNA-873, which affects a suite of key synaptic genes, neurexin, neuroligin, SHANK and post-synaptic density proteins, implicated in the pathology of ASD. Our review suggests that genetic predisposition, sex differences in brain gene expression, and hormonal factors significantly contribute to the presentation, identification and severity of ASD, necessitating sex-specific considerations in diagnosis and treatments. These findings advocate for personalized interventions to improve the outcomes for individuals with ASD.

When to hold and when to fold: Early prediction of nonresponse to transcranial magnetic stimulation in major depressive disorder.

BACKGROUND: Determining when to recommend a change in treatment regimen due to insufficient improvement is a common challenge in therapeutics. METHODS: In a sample of 7215 patients with major depressive disorder treated with transcranial magnetic stimulation (TMS) and with PHQ-9 scores before, during and after the course, 3 groups were identified based on number of acute course sessions: exactly 36 sessions (N = 3591), more than 36 sessions (N = 975), and less than 36 sessions (N = 2649). Two techniques were used to determine thresholds for percentage change in PHQ-9 scores at assessments after 10, 20, and 30 sessions that optimized prediction of endpoint response status: the Youden index and fixing the false positive rate at 10%. Positive and negative predictive values were calculated to assess the accuracy of identifying final nonresponders and responders, respectively. RESULTS: There was greater accuracy in predicting final response than nonresponse, especially in the groups that had at least 36 sessions. Substantial proportions of patients with low levels of early improvement were classified as responders at the end of treatment. LIMITATIONS: The findings should be validated with clinician ratings using a more comprehensive depression severity scale. CONCLUSIONS: Manifesting clinical improvement early in the TMS course is strongly predictive of final status as a responder, while lack of early improvement is a relatively poor indicator of final nonresponse status. The predictive value of lack of early symptomatic improvement is too low to make reliable recommendations regarding changes in treatment regimen.

Factors Related to the Development of Infective Endocarditis in Hemodialysis Patients in a Third-Level Hospital in Panama.

INTRODUCTION: Venous access for hemodialysis (HD) makes patients more susceptible to transient bacteremia, predisposing them to the development of infective endocarditis (IE). Among the risk factors observed in this population are temporary access to HD, hypoalbuminemia, diabetes mellitus, female gender, anemia, and colonization by methicillin-resistant Staphylococcus aureus (MRSA). METHODOLOGY: A retrospective case-control study with a one-to-two ratio was carried out on patients with chronic kidney disease (CKD) undergoing renal replacement therapy with at least one vascular access for HD at Complejo Hospitalario Dr. Arnulfo Arias Madrid (CHDrAAM) from 2010 to 2020. Sociodemographic variables, past medical history, and data on current HD were studied. The odds ratio (OR) and adjusted odds ratio (aOR) were calculated for the collected variables. RESULTS: No statistically significant differences between the groups were observed in sociodemographic variables. In terms of past medical history, the cases showed a predominance of coronary disease (47.6% vs 4.8%; OR: 37.27), valvular disease (23.8% vs 0%), and heart failure (33.3% vs 4.8%; OR: 10). In the cases, the use of a temporary catheter was more prevalent (61.9% vs 33.3%; OR: 3.25), and subclavian access was more frequently recorded (28.6% vs 2.4%; OR: 14.4). A short duration of venous access (<30 days) was found in a greater proportion of cases (23.8% vs 4.8%; OR: 6.25). The main pathogen isolated was S. aureus (33.3%), and the most affected valve was the aortic valve (59.1%). Fever was found in 100% of the reported cases, and up to 47.6% presented with a recent murmur. DISCUSSION: Similar to previous studies conducted in other countries, we identified a history of pre-existing valve disease, the use of a temporary catheter, and recent venous access as risk factors. Contrary to what has been reported in the literature, this study did not find female sex, diabetes mellitus, and hypoalbuminemia as risks. CONCLUSION: Factors such as a history of coronary artery disease, heart failure, preexisting valvular disease, the use of a temporary catheter, subclavian venous access, and short duration of venous access (<30 days) were identified as risk factors for the development of IE in patients with CKD on HD.

Predictors of mental health among U.S. adults during COVID-19 early pandemic, mid- pandemic, and post-vaccine eras.

BACKGROUND: A collective trauma like COVID-19 impacts individuals differently due to socio-contextual and individual characteristics. Younger adults, minorities, affiliates of certain political parties, and residents of some regions of the United States reported experiencing poorer mental health during the pandemic. Being diagnosed with COVID-19, or losing a friend/family to it, was related to more adverse mental health symptoms. While the negative impact of COVID-19 on health outcomes has been studied, mental health changes during this pandemic need further exploration. METHODS: In a study of 8,612 U.S. households, using three surveys collected from a nationally representative panel between May 2020 and October 2021, using a repeated cross-sectional design, a linear mixed effect regression model was performed to investigate factors associated with the mental health status, based on the Mental Health Inventory-5, of individuals throughout different phases of the COVID-19 pandemic, and whether an improvement over time, especially after vaccines became available, was observed. RESULTS: An overall improvement in mental health was observed after vaccines became available. Individuals with no COVID-related death in their household, those not wearing masks, those identifying as members of the Republican Party, race/ethnicities other than Asian, men, older adults, and residents of the South were less likely than others to report mental health challenges. CONCLUSIONS: Our results highlight the need for widespread mental health interventions and health promotion to address challenges during the COVID-19 pandemic and beyond. Due to the worse mental health observed among Asians, younger adults, women, low-income families, those with a higher level of concern for COVID-19, people who lost someone to COVID-19, and/or individuals with histories of opioid use disorder and criminal legal involvement, over the period of this study, targeted attention needs to be given to the mental health of these groups.

Closing Gaps in Public Services for US Residents With Intellectual and Developmental Disabilities.

This Viewpoint describes existing public health and social service systems for persons with intellectual and developmental disabilities as they transition to adult care, barriers and opportunities faced in service access, and potential actions to narrow these gaps and enhance equity.