Power Has Pitfalls: (In)accuracy of Administrative Data for Nonoperative Management of Appendicitis.

INTRODUCTION: Nonoperative management (NOM) of uncomplicated appendicitis is increasingly common. Effectiveness of NOM has been studied by identifying patients via International Classification of Diseases (ICD) 9/ICD-10 codes for uncomplicated appendicitis and no code for appendectomy. We sought to assess the accuracy of such administrative definitions. METHODS: We retrospectively identified patients with ICD-9/ICD-10 codes for appendicitis at five sites across the United States. Initial management plan and clinical severity were recorded by trained abstractors. We identified a gold standard cohort of patients with surgeon-diagnosed uncomplicated appendicitis and planned NOM. We defined two administrative cohorts with ICD-9/ICD-10 codes for uncomplicated appendicitis and either no surgery during initial admission (definition #1) or no surgery on day 0-1 of admission (definition #2). We compared each definition to the gold standard. RESULTS: Among 1224 patients with uncomplicated appendicitis, 72 (5.9%) underwent planned NOM. NOM patients were older (median [Q1-Q3] of 37 [27-56] versus 32 [25-44] y) and less frequently male (51.4% versus 54.9%), White (54.1% versus 67.6%), and privately insured (38.9% versus 50.2%) than patients managed operatively. Definition #1 had sensitivity of 0.81 and positive predictive value of 0.87 for NOM of uncomplicated appendicitis. Definition #2 had sensitivity of 0.83 and positive predictive value of 0.72. The gold standard cohort had a true failure/recurrence rate of 23.6%, compared with apparent rates of 25.4% and 39.8%, respectively. CONCLUSIONS: Administrative definitions are prone to misclassification in identifying planned NOM of uncomplicated appendicitis. This likely impacts outcomes in studies using administrative databases. Investigators should disclose how misclassification may affect results and select an administrative definition that optimally balances sensitivity and specificity for their research question.

Collective Intelligence-Based Participatory COVID-19 Surveillance in Accra, Ghana: Pilot Mixed Methods Study.

BACKGROUND: Infectious disease surveillance is difficult in many low- and middle-income countries. Information market (IM)-based participatory surveillance is a crowdsourcing method that encourages individuals to actively report health symptoms and observed trends by trading web-based virtual "stocks" with payoffs tied to a future event. OBJECTIVE: This study aims to assess the feasibility and acceptability of a tailored IM surveillance system to monitor population-level COVID-19 outcomes in Accra, Ghana. METHODS: We designed and evaluated a prediction markets IM system from October to December 2021 using a mixed methods study approach. Health care workers and community volunteers aged ≥18 years living in Accra participated in the pilot trading. Participants received 10,000 virtual credits to trade on 12 questions on COVID-19-related outcomes. Payoffs were tied to the cost estimation of new and cumulative cases in the region (Greater Accra) and nationwide (Ghana) at specified future time points. Questions included the number of new COVID-19 cases, the number of people likely to get the COVID-19 vaccination, and the total number of COVID-19 cases in Ghana by the end of the year. Phone credits were awarded based on the tally of virtual credits left and the participant's percentile ranking. Data collected included age, occupation, and trading frequency. In-depth interviews explored the reasons and factors associated with participants' user journey experience, barriers to system use, and willingness to use IM systems in the future. Trading frequency was assessed using trend analysis, and ordinary least squares regression analysis was conducted to determine the factors associated with trading at least once. RESULTS: Of the 105 eligible participants invited, 21 (84%) traded at least once on the platform. Questions estimating the national-level number of COVID-19 cases received 13 to 19 trades, and obtaining COVID-19-related information mainly from television and radio was associated with less likelihood of trading (marginal effect: -0.184). Individuals aged <30 years traded 7.5 times more and earned GH ¢134.1 (US $11.7) more in rewards than those aged >30 years (marginal effect: 0.0135). Implementing the IM surveillance was feasible; all 21 participants who traded found using IM for COVID-19 surveillance acceptable. Active trading by friends with communal discussion and a strong onboarding process facilitated participation. The lack of bidirectional communication on social media and technical difficulties were key barriers. CONCLUSIONS: Using an IM system for disease surveillance is feasible and acceptable in Ghana. This approach shows promise as a cost-effective source of information on disease trends in low- and middle-income countries where surveillance is underdeveloped, but further studies are needed to optimize its use.

Improving Equity of Access to a Publicly Funded Bariatric Surgery Programme by Removal of Mandatory Weight Loss Targets.

INTRODUCTION: Obesity disproportionately affects 50.8% of Maori and 71.3% of Pacific adults in New Zealand, and these groups also have reduced access to bariatric surgery. Mandatory preoperative weight loss targets are a requirement of many bariatric surgery programmes globally; however, the evidence supporting their efficacy is inconclusive. In 2017, mandatory preoperative weight loss targets were eliminated from the bariatric surgery programme at Auckland City Hospital in New Zealand, with the aim to improve equity of access to bariatric surgery. This study will review postoperative patient outcomes following the elimination of preoperative weight loss targets from the programme. METHODS: A retrospective analysis of 231 patients who underwent bariatric surgery at Auckland City Hospital from 2018 to 2021 was performed. Nineteen patients were lost to follow up and 12 were excluded (revision surgery or pregnancy). The comparison group of 100 consecutive patients, retrospective from 2017, had been required to lose 10% of excess body weight preoperatively to qualify for surgery. Outcomes assessed were weight loss and diabetes resolution at 12 months, and postoperative complications within 90 days. RESULTS: Elimination of preoperative weight loss targets was associated with greater numbers of Maori and Pacific patients undergoing bariatric surgery. There was no significant difference in weight loss outcomes or postoperative complications. CONCLUSION: Elimination of preoperative weight loss targets improves access to bariatric surgery for Maori and Pacific patients, inequitably affected by obesity. Removal of preoperative weight loss targets does not adversely affect weight loss outcomes, or postoperative complications, thus supporting their elimination.

Combined Phacoemulsification and Hydrus Microstent Implantation in Asian Eyes with Moderate-to-Severe Normal Tension Glaucoma - 12-Month Outcomes.

PRECIS: This study reports 12-month outcomes of combined phacoemulsification and Hydrus Microstent implantation in Asian eyes with moderate-to-severe normal tension glaucoma, demonstrating a significant reduction in glaucoma medications with an excellent intra- and post-operative safety profile. PURPOSE: To evaluate the 12-month safety and efficacy outcomes of combined phacoemulsification and Hydrus Microstent (Ivantis Inc., Irvine, CA) implantation in Asian eyes with moderate to severe normal tension glaucoma (NTG). METHODS: Retrospective study of consecutive surgeries performed from August 2019 to August 2021 in a single tertiary eye centre in Singapore. Outcome measures included reduction in intraocular pressure (IOP), number of glaucoma medications, and intra- and post-operative complications. RESULTS: Data from 21 eyes of 21 subjects was analysed. All subjects were ethnic Chinese and majority were male (14, 66.7%). At baseline, mean IOP was 13.3 (2.3) mmHg, all eyes had a Humphrey Visual Field (HVF) mean deviation (MD) of ≥-6 dB [mean -13.9 (4.3) dB] and all eyes were on at least one glaucoma medication. There was no statistically significant reduction in IOP at all timepoints compared to baseline (all P>0.05). However, median number of medications was reduced from 2 to 0 at all timepoints, up to POM12 (all P<0.001). There were no intraoperative complications. No eyes underwent secondary glaucoma procedures nor lost any Snellen's line of visual acuity by POM12. One (4.8%) eye experienced numerical hypotony at POD1, which resolved conservatively. Two (9.5%) eyes underwent laser iridoplasty for stent occlusion by iris. There was no deterioration in HVF MD at POM12 compared to baseline (n=20, P>0.05). CONCLUSION: Combined phacoemulsification and Hydrus Microstent implantation was effective in reducing medication burden in Asian eyes with moderate to severe NTG, up to 12 months post-operatively.

Identifying and Characterizing the Transgender and Nonbinary Population Presenting to Pediatric Psychiatry Emergency Services.

Transgender and nonbinary (TGNB) individuals have an increased risk of certain mental health outcomes, such as depression and suicide attempts. This population skews younger in the United States and prior studies have not included TGNB patients for the entire pediatric age range in an emergency department (ED) setting. The present study aimed to examine gender identity documentation in the electronic health record and then use that information to identify and further characterize the pediatric TGNB population presenting to a psychiatric emergency service. Preliminary findings include a greater percentage of TGNB patients compared to non-TGNB individuals who had repeat visits to the ED for high acuity psychiatric concerns. A larger portion of TGNB patients also had at least one evaluation that included suicidal ideation. These results call for increased attention on the quality of mental healthcare for TGNB youth both inside and outside of the ED.

Digital droplet PCR analysis of organoids generated from mouse mammary tumors demonstrates proof-of-concept capture of tumor heterogeneity.

Breast cancer metastases exhibit many different genetic alterations, including copy number amplifications (CNA). CNA are genetic alterations that are increasingly becoming relevant to breast oncology clinical practice. Here we identify CNA in metastatic breast tumor samples using publicly available datasets and characterize their expression and function using a metastatic mouse model of breast cancer. Our findings demonstrate that our organoid generation can be implemented to study clinically relevant features that reflect the genetic heterogeneity of individual tumors.

Designathons in health research: a global systematic review.

INTRODUCTION: A designathon is a three-stage participatory activity informed by design thinking. There is a growing literature on designathons in health. This study synthesised designathons' effectiveness and implementation-related factors to address health challenges. METHODS: We searched Cochrane Library, Embase, PubMed, Scopus and the ClinicalTrials.gov registry for articles containing primary data on designathons for health from their dates of inception to 29 November 2022. We retrieved additional studies from citation searching and a complementary open call. We synthesised data on designathons' effectiveness (ie, engagement, outputs and implementation), required resources and implementation-related factors (ie, resources, facilitators, barriers, strengths and limitations). We assessed the risk of bias using a checklist adapted from Joanna Briggs Institute Critical Appraisal tools. RESULTS: In total, 4973 citations were identified, and 42 studies were included. In total, 26 studies (62%) were from high-income countries. The median number of total participants was 49, divided into a median of 8 teams. The duration of the intensive collaboration phase ranged from 3 hours to 7 days. Common evaluation criteria were feasibility, innovation and impact. Idea and prototype outputs included mobile phone applications, educational programmes and medical devices. Interventions developed from a designathon was estimated to be highly cost-effective. The most common facilitators were interdisciplinary participants and high-quality mentorship. The most common barriers were suboptimal execution of the events, difficulties in balancing interdisciplinary participants across teams and limited support for participants along the process. There were limited data on required resources and further implementation of solutions after designathons. CONCLUSION: Given designathons' adaptability in terms of budget, mode of delivery, type of output and involvement of diverse participants, including end users, designathons can be implemented in a wide range of contexts to address various health issues. PROSPERO REGISTRATION NUMBER: CRD42023389685.

Social innovation in health training to engage researchers in resource-limited settings: process description and evaluation.

Research on social innovations in health has increased in recent years. However, little training is geared toward enhancing social innovation research capacity. Most health training for low- and middle-income countries (LMICs) is developed by individuals in high-income countries, disregarding LMIC researchers' wisdom and insights and the communities' needs. Our team organized a multi-phase investigation involving a series of surveys and co-creation group discussions to assess individuals' training needs that directly informed a subsequent co-created training workshop series. We conducted a Hennessy-Hicks Training Needs Assessment among the Social Innovation in Health Initiative (SIHI) network and formed a co-creation group comprising SIHI fellows to design related training workshops. We ran a final evaluation survey and analyzed the workshop series' strengths, weaknesses and threats. Descriptive and thematic analysis were employed to analyze survey data and open-ended responses. The final evaluation survey captured data from 165 learners in 35 countries, including 26 LMICs. Most participants (67.3%, 111/165) rated the training workshop series as excellent, and 30.3% (50/165) rated it as good on a five-point scale. The need for writing research grants and manuscripts was rated the highest priority. Learners were interested in community-engaged research and diversity, equity and inclusion. This workshop illustrated how co-creation could be an effective tool for developing training materials tailored for LMIC researchers. We also offer a template for conducting a needs assessment and subsequent training workshops for LMICs. The ground-up, locally developed courses may be more effective than externally developed training programs intended for LMICs.

Inter-organ steroid hormone signaling promotes myoblast fusion via direct transcriptional regulation of a single key effector gene.

Steroid hormones regulate tissue development and physiology by modulating the transcription of a broad spectrum of genes. In insects, the principal steroid hormones, ecdysteroids, trigger the expression of thousands of genes through a cascade of transcription factors (TFs) to coordinate developmental transitions such as larval molting and metamorphosis. However, whether ecdysteroid signaling can bypass transcriptional hierarchies to exert its function in individual developmental processes is unclear. Here, we report that a single non-TF effector gene mediates the transcriptional output of ecdysteroid signaling in Drosophila myoblast fusion, a critical step in muscle development and differentiation. Specifically, we show that the 20-hydroxyecdysone (commonly referred to as "ecdysone") secreted from an extraembryonic tissue, amnioserosa, acts on embryonic muscle cells to directly activate the expression of antisocial (ants), which encodes an essential scaffold protein enriched at the fusogenic synapse. Not only is ants transcription directly regulated by the heterodimeric ecdysone receptor complex composed of ecdysone receptor (EcR) and ultraspiracle (USP) via ecdysone-response elements but also more strikingly, expression of ants alone is sufficient to rescue the myoblast fusion defect in ecdysone signaling-deficient mutants. We further show that EcR/USP and a muscle-specific TF Twist synergistically activate ants expression in vitro and in vivo. Taken together, our study provides the first example of a steroid hormone directly activating the expression of a single key non-TF effector gene to regulate a developmental process via inter-organ signaling and provides a new paradigm for understanding steroid hormone signaling in other developmental and physiological processes.

Strengths and challenges among Black and Latinx people living with HIV during COVID-19: A mixed-methods investigation of the translation of self-management across syndemic health crises.

Black and Latinx people are disproportionately impacted by HIV, COVID-19, and other syndemic health crises with similar underlying social determinants of health. Lessons learned from the HIV pandemic and COVID-19 response have been invoked to improve health equity at the systemic level in the face of other emergent health crises. However, few have examined the potential translation of strategies between syndemics at the individual level. The current mixed-methods study examined strategies used to manage HIV during the COVID-19 pandemic and the extent to which they were helpful in managing COVID-19 vulnerability among Black and Latinx people living with HIV. Participants (n = 30) were interviewed by telephone and completed demographic, mental health, alcohol and substance use, health literacy, and clinical measures in October and November 2020 in Los Angeles County. Rapid qualitative analysis, descriptive statistics, and mixed-methods merging were used to analyze the data. Qualitative results demonstrated that participants found HIV self-management strategies translated to aspects of the COVID-19 pandemic including hygiene and social distancing and coping with a health-related stressor. Although telemedicine provided continuity of HIV care for most participants, technology access and literacy posed a potential barrier, particularly to those facing other sociodemographic marginalization (i.e., low education, disability). Findings suggest providers can encourage leveraging individual HIV self-management strategies in response to other public health crises. However, these interventions must be culturally responsive and address intersecting social determinants of health. Future research should examine mechanisms that predict individual translation of HIV management strategies to other health concerns. (PsycInfo Database Record (c) 2024 APA, all rights reserved).

Projective light-sheet microscopy with flexible parameter selection.

Projection imaging accelerates volumetric interrogation in fluorescence microscopy, but for multi-cellular samples, the resulting images may lack contrast, as many structures and haze are summed up. Here, we demonstrate rapid projective light-sheet imaging with parameter selection (props) of imaging depth, position and viewing angle. This allows us to selectively image different sub-volumes of a sample, rapidly switch between them and exclude background fluorescence. Here we demonstrate the power of props by functional imaging within distinct regions of the zebrafish brain, monitoring calcium firing inside muscle cells of moving Drosophila larvae, super-resolution imaging of selected cell layers, and by optically unwrapping the curved surface of a Drosophila embryo. We anticipate that props will accelerate volumetric interrogation, ranging from subcellular to mesoscopic scales.

Changes in Expression of Key Genes in Alzheimer's Disease: A Specific Brain Tissue Change.

Alzheimer's disease (AD) is an irreversible and neurodegenerative disorder. Its etiology is not clear, but the involvement of genetic components plays a central role in the onset of the disease. In the present study, the expression of 10 genes (APP, PS1 and PS2, APOE, APBA2, LRP1, GRIN2B, INSR, GJB1, and IDE) involved in the main pathways related to AD were analyzed in auditory cortices and cerebellum from 29 AD patients and 29 healthy older adults. Raw analysis revealed tissue-specific changes in genes LRP1, INSR, and APP. A correlation analysis showed a significant effect also tissue-specific AD in APP, GRIN2B, INSR, and LRP1. Furthermore, the E4 allele of the APOE gene revealed a significant correlation with change expression tissue-specific in ABPA2, APP, GRIN2B, LRP1, and INSR genes. To assess the existence of a correction between changes in target gene expression and a probability of AD in each tissue (auditory cortices and cerebellum) an analysis of the effect of expressions was realized and showed that the reduction in the expression of the APP in auditory cortex and GRIN2B cerebellum had a significant effect in increasing the probability of AD, in the same logic, our result also suggesting that increased expression of the LRP1 and INSR genes had a significant effect on increasing the probability of AD. Our results showed tissue-specific gene expression alterations associated with AD and certainly opened new perspectives to characterize factors involved in gene regulation and to obtain possible biomarkers for AD.

Characterizing Autism Spectrum Disorder and Predicting Suicide Risk for Pediatric Psychiatric Emergency Services Encounters.

Individuals diagnosed with autism spectrum disorder (ASD) are at a higher risk for mental health concerns including suicidal thoughts and behaviors (STB). Limited studies have focused on suicidal risk factors that are more prevalent or unique to the population with ASD. This study sought to characterize and classify youth presenting to the psychiatric emergency department (ED) for a chief complaint of STB. The results of this study validated that a high number of patients with ASD present to the ED with STB. There were important differences in clinical characteristics to those with ASD versus those without. Clinical features that showed important impact in predicting high suicide risk in the ASD cases include elements of the mental status exam such as affect, trauma symptoms, abuse history, and auditory hallucinations. Focused attention is needed on these unique differences in ASD cases so that suicide risk level can be appropriately and promptly addressed.

Associations of Cerebrovascular Metabolism Genotypes With Neuropsychiatric Symptoms and Age at Onset of Alzheimer's Disease Dementia

Objective: To study associations of cerebrovascular metabolism genotypes and haplotypes with age at Alzheimer’s disease dementia (AD) onset and with neuropsychiatric symptoms according to each dementia stage. Methods: Consecutive outpatients with late-onset AD were assessed for age at dementia onset and Neuropsychiatric Inventory scores according to Clinical Dementia Rating scores, apolipoprotein E gene (APOE) haplotypes, angiotensin-converting enzyme gene (ACE) variants rs1800764 and rs4291, low-density lipoprotein cholesterol receptor gene (LDLR) variants rs11669576 and rs5930, cholesteryl ester transfer protein gene (CETP) variants I422V and TaqIB, and liver X receptor beta gene (NR1H2) polymorphism rs2695121. Results: Considering 201 patients, only APOE-ɛ4 carriers had earlier dementia onset in multiple correlations, as well as less apathy, more delusions, and more aberrant motor behavior. Both ACE polymorphisms were associated with less intense frontally mediated behaviors. Regarding LDLR variants, carriers of the A allele of rs11669576 had less anxiety and more aberrant motor behavior, whereas carriers of the A allele of rs5930 had less delusions, less anxiety, more apathy, and more irritability. CETP variants that included G alleles of I422V and TaqIB were mostly associated with less intense frontally mediated behaviors, while severely impaired carriers of the T allele of rs2695121 had more anxiety and more aberrant motor behavior. Conclusion: Though only APOE haplotypes affected AD onset, cerebrovascular metabolism genotypes were associated with differences in several neuropsychiatric manifestations of AD.

Pharmacogenetic effects of angiotensin-converting enzyme inhibitors over age-related urea andcreatinine variations in patients with dementia due to Alzheimer disease / Efectos farmacogenéticos de inhibidores de la enzima convertidora de la angiotensina en variaciones de urea y creatinina asociadas con el envejecimiento en pacientes con demencia de la enfermedad de Alzheimer

Background: Renal function declines according to age and vascular risk factors, whereas few data are available regarding geneticallymediated effects of anti-hypertensives over renal function. Objective: To estimate urea and creatinine variations in dementia due to Alzheimer disease (AD) by way of a pharmacogenetic analysis of the anti-hypertensive effects of angiotensin-converting enzyme inhibitors (ACEis). Methods: Consecutive outpatients older than 60 years-old with AD and no history of kidney transplant or dialytic therapy were recruited for prospective correlations regarding variations in fasting blood levels of urea and creatinine in one year, considering ACE genotypes of rs1800764 and rs4291 and their respective haplotypes, and treatment with ACEis along with blood pressure variations. Results: For 190 patients, 152 had arterial hypertension, and 122 used ACEis. Minor allele frequencies were 0.492 for rs1800764-C and 0.337 for rs4291-T, both in Hardy-Weinberg equilibrium. There were no overall significant yearly variations in levels of urea and creatinine, but their concurrent variations were positively correlated (ρ <0.0001). Each A allele of rs4291 led to an yearly urea increase of 3.074 mg/ dL, and an yearly creatinine increase of 0.044 mg/dL, while the use of ACEis was protective regarding creatinine variations. The use of ACEis was also protective for carriers of rs1800764-CT/rs4291-AA, while carriers of rs1800764-CT/rs4291-AT had steeper reductions in creatinine levels, particularly when they were treated with ACEis. Conclusions: Effects of ACEis over creatinine variations are genetically mediated and independent of blood pressure variations in older people with AD.

Antecedentes: El deterioro de la función renal depende de la edad y los factores vasculares. La literatura sobre los efectos de fármacos antihipertensivos mediada genéticamente en la función renal es pobre. Objetivo: Estimar las variaciones de urea y creatinina a través del análisis farmacogenético de los efectos antihipertensivos de los inhibidores de la enzima convertidora de angiotensina (iECA) en pacientes con demencia debido a la enfermedad de Alzhaimer. Métodos: Fueron reclutados pacientes consecutivos mayores de 60 años de edad con enfermedad de Alzheimer y sin antecedentes de trasplante renal o diálisis. Se determinaron correlaciones prospectivas durante un año entre los cambios en los niveles sanguíneos de urea y creatinina, considerando genotipos y haplotipos de ACE (rs1800764 y rs4291) y el tratamiento con iECA a y las variaciones en la presión arterial. Resultados: De 190 pacientes, 152 presenaron hipertensión, 122 usaron iECA. Las frecuencias de alelos polimórficos fueron de 0.492 para rs1800764-C y 0.337 para rs4291-T, los dos alelos en equilibrio de Hardy-Weinberg. No se determinaron fluctuaciones anuales significativas en los niveles de urea o creatinina, pero sus variaciones concomitantes se asociaron fuertemente (ρ= <0.0001). Cada alelo A de rs4291 condujo a aumentos anuales de 3.074 mg/dL en urea y 0.044 mg/dL en creatinina, mientras que el uso de iECA fue protector para las variaciones en la creatinina. El uso de iECA también fue protector para las personas con rs1800764-CT/rs4291-AA, mientras que los portadores de rs1800764-CT/rs4291-AT tuvieron reducciones de creatinina más altas, particularmente cuando se usó iECA. Conclusión: Los efectos de iECA en la variación de la creatinina son genéticamente mediadas e independiente de las variaciones en la presión arterial en pacientes de edad avanzada con la enfermedad de Alzheimer.