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Abstract Drug-related errors are a leading cause of preventable patient harm in the clinical setting. We present the first wearable camera system to automatically detect potential errors, prior to medication delivery. We demonstrate that using deep learning algorithms, our system can detect and classify drug labels on syringes and vials in drug preparation events recorded in real-world operating rooms. We created a first-of-its-kind large-scale video dataset from head-mounted cameras comprising 4K footage across 13 anesthesiology providers, 2 hospitals and 17 operating rooms over 55 days. The system was evaluated on 418 drug draw events in routine patient care and a controlled environment and achieved 99.6% sensitivity and 98.8% specificity at detecting vial swap errors. These results suggest that our wearable camera system has the potential to provide a secondary check when a medication is selected for a patient, and a chance to intervene before a potential medical error.

Background: Donation after circulatory death with thoracoabdominal normothermic regional perfusion (DCD-NRP) for cardiac transplant has promising results, though data for lung transplant is lacking. This study evaluates lung transplant outcomes using DCD-NRP allografts. Methods: All patients who underwent lung transplantation (LT) from June 1, 2020, to July 5, 2023, at a single institution were evaluated. Recipients received organs from DCD-NRP or brain dead (control) donors (donation after brain death (DBD)). All DCD-NRP were adult, primary bilateral LT (BLT) without preoperative extracorporeal membrane oxygenation (ECMO). Inclusion criteria for controls were age >18 years, BLT, no preoperative ECMO, and primary transplantation. Comparison was separated by LT or heart-lung transplant (HLT). The primary outcome was primary graft dysfunction (PGD) grade 3 at 72 hours. Results: There were 8 LT and 3 HLT in the DCD-NRP cohort, and 138 BLT and 7 HL DBD controls. PGD grade 3 at 72 hours was 0% in the entire DCD-NRP cohort (vs control: 9.4% LT and 0% HLT). There were no statistically significant differences in donor and recipient characteristics, though DCD-NRP HLT had significantly shorter ischemic time (85 vs 200 minutes, p

Introduction: There are scant data on implementation of large-scale direct-acting antiviral treatment for hepatitis C virus in jails in the U.S. New York City Health + Hospitals/Correctional Health Services aimed to scale up hepatitis C virus treatment in the New York City jail system. This study describes the trends in annual hepatitis C virus treatment in New York City jails compared with those in Medicaid-funded treatment in the New York City community from 2014 to 2020. Methods: In this observational study, we extracted annual counts of direct-acting antiviral prescriptions for hepatitis C virus for those (1) in the New York City community who were covered by Medicaid and (2) those detained in New York City jails for 2014–2020. Data sources were New York City Department of Health and Mental Hygiene annual reports and Correctional Health Services treatment records, respectively. We used linear regression analysis to test for significant trends in annual treatment in these 2 cohorts during 2015–2019. Results: From 2015 to 2019, treatments started in New York City jails increased annually (p=0.001), whereas Medicaid-funded prescriptions in the New York City community declined since a peak in 2015 (p

Abstract Background To determine the safety and efficacy of biological agents used in the treatment of systemic lupus erythematosus (SLE) in adults. Methods Systematic review and meta-analysis following PRISMA guidelines. Data sources MEDLINE (through Pubmed), EMBASE, Cochrane library, Clinicaltrials.gov, Australianclinicaltrials.gov.au, ANZCTR.org.au and WHO International Clinical Trials Registry Platform for studies published from 20 May 2021 and 15 years prior. A grey literature search was performed and completed on 31 May 2021. Study criteria Phase II, III or quasi randomised controlled trials, studies with only cerebral or cutaneous lupus were excluded. Data extraction: Two authors independently screened studies for eligibility, extracted, reviewed data for accuracy, and used the Cochrane tool to assess risk of bias. Results Forty-four studies were identified, consisting of 15 groups of drugs and 25 different biological agents, totalling 16,889 patients. The main outcomes assessed included Systemic Lupus Erythematosus Responder Index (SRI), BILAG-Based Composite Lupus Assessment (BICLA) and combined combined/partial renal remission (CRR/PRR). Four groups of biologics were found to improve outcomes. Anti-interferons: Anifrolumab increased BICLA response and SRI 5 to 8, decreased prednisone dosages, with increased herpes zoster infections, but fewer serious adverse events. Sifalimumab improved SRI but also increased herpes zoster infections. Anti BAFF/BLyS and/or APRIL: Belimumab consistently improved SRI 4, decreased prednisone dosages, increased combined CRR/PRR, and had no adverse safety outcomes. Tabalumab increased SRI 5 at 52 weeks with no steroid sparing effect but was associated with increased infusion related adverse events. Telitacicept improved SRI 4 at 52 weeks, with no increased adverse events, though data was rather sparse. Anti CD-20 monoclonal antibody, Obinutuzumab increased combined CRR/PRR at 1 and 2 years. Anti IL12/23 monoclonal antibody, Ustekinumab, increased SRI 4 to 6, but not BICLA at 24 weeks, with no concerning safety outcomes. Conclusion Multiple biologic agents are shown in high quality studies to have a significant therapeutic impact on outcomes in SLE.

Abstract Intrinsically Disordered Proteins (IDPs) play crucial roles in numerous diseases like Alzheimer's and ALS by forming irreversible amyloid fibrils. The effectiveness of force fields (FFs) developed for globular proteins and their modified versions for IDPs varies depending on the specific protein. This study assesses 13 FFs, including AMBER and CHARMM, by simulating the R2 region of the FUS-LC domain (R2-FUS-LC region), an IDP implicated in ALS. Due to the flexibility of the region, we show that utilizing multiple measures, which evaluate the local and global conformations, and combining them together into a final score are important for a comprehensive evaluation of force fields. The results suggest c36m2021s3p with mTIP3p water model is the most balanced FF, capable of generating various conformations compatible with known ones. In addition, the mTIP3P water model is computationally more efficient than those of top-ranked AMBER FFs with four-site water models. The evaluation also reveals that AMBER FFs tend to generate more compact conformations compared to CHARMM FFs but also more non-native contacts. The top-ranking AMBER and CHARMM FFs can reproduce intra-peptide contacts but underperform for inter-peptide contacts, indicating there is room for improvement.

Background: In May 2022, New York City (NYC) experienced a large outbreak of human mpox (clade IIb). Data on mpox transmission following exposure in healthcare facilities in nonendemic settings are limited. Because mpox was previously not seen in NYC, our healthcare staff may not always recognize a suspected case and therefore may neglect to implement timely infection prevention and control measures, leading to infectious exposures. The risk of transmission from unrecognized mpox may be higher in inpatient psychiatric units where direct physical contact is more common in the setting of common spaces for patients. In July 2022, a patient was admitted to NYC Health + Hospitals–Bellevue (Bellevue) psychiatry with signs and symptoms of mpox that were not recognized for 4 days, at which point the patient was tested for mpox and was isolated. We describe the investigation of staff and patients exposed during the 4 days prior to diagnosis and isolation of the index patient, and we report on the outcome mpox infection among those exposed. Methods: This study was a retrospective chart review of adult patients admitted to and staff working on an inpatient psychiatric unit where the patient with mpox was admitted to Bellevue, the largest municipal hospital in NYC. Each individual was classified regarding degree of exposure, based on criteria from the CDC, and was offered postexposure mpox vaccination where indicated. We describe the nature of contact with the patient for those with high-risk exposures. The outcome of interest was development of mpox infection during 21 days after last exposure. Results: In total, 29 patients and 84 staff members were identified to have been on the psychiatric unit prior to isolation of the index case of mpox. All exposed individuals were monitored for signs and symptoms of mpox for 21 days after last exposure. The exposed and unexposed patients were kept apart in the psychiatric unit. All patients who had contact were classified as having a low-to-intermediate risk exposure. Among 23 staff members exposed, 8 had high-risk exposures, 4 had intermediate-risk exposures, and 11 had low-risk exposures. Those with high-risk exposures were offered Jynneos as postexposure vaccination, but they declined. None of the exposed staff or patients developed mpox during the follow-up period. Conclusions: Mpox transmission was not observed despite several exposures in a congregate psychiatry unit. Given limited data, further studies are needed to better understand transmission risk in congregate healthcare settings.

Chan et al. develop an open-source smartphone-based tympanometer to evaluate middle ear function. The authors test their device in a group of paediatric patients at an audiology clinic and report a high level of agreement in audiologists’ classification of tympanograms produced using this device compared with a commercial device.

Therapy with anticoagulants requires frequent monitoring. Here the authors describe a proof-of-concept study of a simple and affordable blood clot test that uses a smartphone’s vibration motor and camera to track micro-movements in a single drop of blood.

During the 2022 mpox outbreak, tecovirimat was accessed through an expanded access investigational new drug (EA-IND) protocol. We leveraged a unique public/private hospital partnership in New York City to create a novel infrastructure to navigate the EA-IND’s regulatory requirements and rapidly provide tecovirimat to patients.

Abstract Introduction Neutrophil‐to‐lymphocyte ratio (NLR) is a routinely available biomarker that reflects systemic inflammation. The study evaluated the predictive value of NLR for ischemic stroke and atrial fibrillation (AF) in patients with type 2 diabetes mellitus. Methods This was a population‐based cohort study of patients with type 2 diabetes mellitus and complete blood count tests at baseline between 1 January 1st, 2009, and 31 December, 2009, at government‐funded hospitals/clinics in Hong Kong. Follow‐up was until 31 December, 2019, or death. Results A total of 85,351 patients (age = 67.6 ± 13.2 years old, male = 48.8%, follow‐up = 3101 ± 1441 days) were included. Univariable Cox regression found that increased NLR at quartiles 2, 3 and 4 was significantly associated with higher risks of new‐onset ischemic stroke (hazard ratio [HR]: 1.28 [1.20–1.37], p

Abstract Overdoses from non-medical use of opioids can lead to hypoxemic/hypercarbic respiratory failure, cardiac arrest, and death when left untreated. Opioid toxicity is readily reversed with naloxone, a competitive antagonist that can restore respiration. However, there remains a critical need for technologies to administer naloxone in the event of unwitnessed overdose events. We report a closed-loop wearable injector system that measures respiration and apneic motion associated with an opioid overdose event using a pair of on-body accelerometers, and administers naloxone subcutaneously upon detection of an apnea. Our proof-of-concept system has been evaluated in two environments: (i) an approved supervised injection facility (SIF) where people self-inject opioids under medical supervision and (ii) a hospital environment where we simulate opioid-induced apneas in healthy participants. In the SIF (n = 25), our system identified breathing rate and post-injection respiratory depression accurately when compared to a respiratory belt. In the hospital, our algorithm identified simulated apneic events and successfully injected participants with 1.2 mg of naloxone. Naloxone delivery was verified by intravenous blood draw post-injection for all participants. A closed-loop naloxone injector system has the potential to complement existing evidence-based harm reduction strategies and, in the absence of bystanders, help make opioid toxicity events functionally witnessed and in turn more likely to be successfully resuscitated.

In the spring of 2022, mpox spread to non-endemic countries, including the United States. In New York City (NYC), vaccine demand grew as quickly as case counts. With the leadership of the Regional Emerging Special Pathogens Treatment Center (RESPTC) at NYC Health and Hospitals/Bellevue (NYC H+H)—part of the largest public hospital system in the United States—an innovative vaccination model was established that overcame challenges involving health inequities, inadequate access, and lack of vaccine uptake, to successfully administer JYNNEOS vaccines to over 12,000 patients. Transmission has slowed since its peak in August 2022, which has been attributed to successful vaccination campaigns, infection-induced immunity, and behavioral changes among those at highest risk; however, a Centers for Disease Control and Prevention (CDC) assessment released on 4 April 2023 suggests jurisdictions with low vaccination levels (

Abstract Background This systematic review aimed to explore the process of decision-making for nutrition and hydration for people living with dementia from the perspectives and experiences of all involved. Methods We searched CINAHL, the Cochrane Library, EMBASE, MEDLINE and PsycINFO databases. Search terms were related to dementia, decision-making, nutrition and hydration. Qualitative, quantitative and case studies that focused on decision-making about nutrition and hydration for people living with dementia were included. The CASP and Murad tools were used to appraise the quality of included studies. Data extraction was guided by the Interprofessional Shared Decision Making (IP-SDM) model. We conducted a narrative synthesis using thematic analysis. PROSPERO registration number CRD42019131497. Results Forty-five studies were included (20 qualitative, 15 quantitative and 10 case studies), comprising data from 17 countries and 6020 patients, family caregivers and practitioners. The studies covered a range of decisions from managing oral feeding to the use of tube feeding. We found that decisions about nutrition and hydration for people living with dementia were generally too complex to be mapped onto the precise linear steps of the existing decision-making model. Decision-making processes around feeding for people living with dementia were largely influenced by medical evidence, personal values, cultures and organizational routine. Although the process involved multiple people, family caregivers and non-physician practitioners were often excluded in making a final decision. Upon disagreement, nutrition interventions were sometimes delivered with conflicting feelings concealed by family caregivers or practitioners. Most conflicts and negative feelings were resolved by good relationship, honest communication, multidisciplinary team meetings and renegotiation. Conclusions The decision-making process regarding nutrition and hydration for people living with dementia does not follow a linear process. It needs an informed, value-sensitive, and collaborative process. However, it often characterized by unclear procedures and with a lack of support. Decisional support is needed and should be approached in a shared and stepwise manner.

Background and Aim While weight gain during infliximab therapy in inflammatory bowel disease (IBD) is common, there has been limited research evaluating its impact on infliximab efficacy. Methods Primary aims of this study were to determine the frequency of excess weight gain (body mass index [BMI] > 25 kg/m2) in children with IBD on maintenance infliximab and evaluate the impact on infliximab dosing, serum trough levels, and treatment failure. Secondary aims were to determine differences in weight gain, treatment characteristics, and clinical/biochemical variables between patients with therapeutic and subtherapeutic maintenance therapy trough levels. We performed a retrospective study of 253 pediatric IBD (75.1% Crohn's disease, 23.3% ulcerative colitis, 1.6% IBD‐unclassified) patients on infliximab followed at BC Children's Hospital between January 2013 and January 2018. Results Median age at infliximab initiation was 13.9 years, median length of follow up was 56.9 months, and 55.7% were males; 10.3% of the cohort demonstrated excess weight gain (7.5% overweight, 2.8% obese). Average mg/kg dosing was not statistically different between groups (normal, overweight, and obese: 6.7, 6.4, and 6.7 mg/kg, respectively, P = 0.52). Median BMI of patients with therapeutic and subtherapeutic trough levels was similar at 19.9 kg/m2 (interquartile range [IQR], 17.3–23.8) and 19.7 kg/m2 (IQR, 17.4–21.9), respectively. BMI had no effect on secondary loss of response to infliximab, with no significant difference between normal and high BMI subgroups (13.4 vs. 16.7%, P = 0.9). Conclusions In a subgroup of pediatric IBD patients on maintenance infliximab, excess weight gain was not associated with higher weight‐based dosing, lower serum trough levels, or increased risk of treatment failure.

ABSTRACTJamestown Canyon virus (JCV) is a neuroinvasive arbovirus that is found throughout North America and increasingly recognized as a public health concern. From 2004 to 2012, an average of 1.7 confirmed cases were reported annually in the United States, whereas from 2013 to 2018 this figure increased over seventeen-fold to 29.2 cases per year. The rising number of reported human infections highlights the need for better understanding of the clinical manifestations and epidemiology of JCV. Here, we describe nine patients diagnosed with neuroinvasive JCV infection in Massachusetts from 2013, the year of the first reported case in the state, to 2017. Because current diagnostic testing relies on serology, which is complicated by cross-reactivity with related orthobunyaviruses and can be negative in immunosuppressed patients, we developed and evaluated an RT-qPCR assay for detection of JCV RNA. We tested this on the available archived serum from two patients, but did not detect viral RNA. JCV is transmitted by multiple mosquito species and its primary vector in Massachusetts is unknown, so we additionally applied the RT-qPCR assay and confirmatory RNA sequencing to assess JCV prevalence in a vector candidate, Ochlerotatus canadensis. We identified JCV in 0.6% of mosquito pools, a similar prevalence to neighboring Connecticut. We assembled the first Massachusetts JCV genome directly from a mosquito sample, finding high identity to JCV isolates collected over a 60-year period. Further studies are needed to reconcile the low vector prevalence and low rate of viral evolutionary change with the increasing number of reported cases.

Airway epithelial damage is a common feature in respiratory diseases such as COPD and has been suggested to drive inflammation and progression of disease. These features manifest as remodeling and destruction of lung epithelial characteristics including loss of small airways which contributes to chronic airway inflammation. Histone deacetylase 6 (HDAC6) has been shown to play a role in epithelial function and dysregulation, such as in cilia disassembly, epithelial to mesenchymal transition (EMT) and oxidative stress responses, and has been implicated in several diseases. We thus used ACY-1083, an inhibitor with high selectivity for HDAC6, and characterized its effects on epithelial function including epithelial disruption, cytokine production, remodeling, mucociliary clearance and cell characteristics. Primary lung epithelial air-liquid interface cultures from COPD patients were used and the impacts of TNF, TGF-β, cigarette smoke and bacterial challenges on epithelial function in the presence and absence of ACY-1083 were tested. Each challenge increased the permeability of the epithelial barrier whilst ACY-1083 blocked this effect and even decreased permeability in the absence of challenge. TNF was also shown to increase production of cytokines and mucins, with ACY-1083 reducing the effect. We observed that COPD-relevant stimulations created damage to the epithelium as seen on immunohistochemistry sections and that treatment with ACY-1083 maintained an intact cell layer and preserved mucociliary function. Interestingly, there was no direct effect on ciliary beat frequency or tight junction proteins indicating other mechanisms for the protected epithelium. In summary, ACY-1083 shows protection of the respiratory epithelium during COPD-relevant challenges which indicates a future potential to restore epithelial structure and function to halt disease progression in clinical practice.

Abstract Background Hospitalisation is often harmful for people with dementia and results in high societal costs, so avoidance of unnecessary admissions is a global priority. However, no intervention has yet reduced admissions of community-dwelling people with dementia. We therefore aimed to examine hospitalisation rates of people with dementia and whether these differ from people without dementia and to identify socio-demographic and clinical predictors of hospitalisation. Methods We searched MEDLINE, Embase, and PsycINFO from inception to 9 May 2019. We included observational studies which (1) examined community-dwelling people with dementia of any age or dementia subtype, (2) diagnosed dementia using validated diagnostic criteria, and (3) examined all-cause general (i.e. non-psychiatric) hospital admissions. Two authors screened abstracts for inclusion and independently extracted data and assessed included studies for risk of bias. Three authors graded evidence strength using Cochrane’s GRADE approach, including assessing for evidence of publication bias using Begg’s test. We used random effects meta-analysis to pool estimates for hospitalisation risk in people with and without dementia. Results We included 34 studies of 277,432 people with dementia: 17 from the USA, 15 from Europe, and 2 from Asia. The pooled relative risk of hospitalisation for people with dementia compared to those without was 1.42 (95% confidence interval 1.21, 1.66) in studies adjusted for age, sex, and physical comorbidity. Hospitalisation rates in people with dementia were between 0.37 and 1.26/person-year in high-quality studies. There was strong evidence that admission is associated with older age, and moderately strong evidence that multimorbidity, polypharmacy, and lower functional ability are associated with admission. There was strong evidence that dementia severity alone is not associated. Conclusions People with dementia are more frequently admitted to hospital than those without dementia, independent of physical comorbidities. Future interventions to reduce unnecessary hospitalisations should target potentially modifiable factors, such as polypharmacy and functional ability, in high-risk populations.

Background: High patient turnover presents challenges and opportunity to provide hepatitis C virus (HCV) care in US jails (remand facilities). This study describes the HCV care cascade in the New York City (NYC) jail system during the direct-acting antiviral (DAA) treatment era. Methods: Patients admitted to the NYC jail system from January 2014 through December 2017 were included in this retrospective cohort analysis. We describe rates of screening, diagnosis, linkage to jail-based care, and treatment among the overall cohort, and among subgroups with long jail stays (≥120 days) or frequent stays (≥10 admissions). The study protocol was approved by a third-party institutional review board (BRANY, Lake Success, NY). Findings: Among the 121,371 patients in our analysis, HCV screening was performed in 40,219 (33%), 4665 (12%) of whom were viremic, 1813 (39%) seen by an HCV clinician in jail, and 248 (5% of viremic patients) started on treatment in jail. Having a long stay (adjusted risk ratio [aRR] 8·11, 95% confidence interval [CI] 6·98, 9·42) or frequent stays (aRR 1·51, 95% CI 1·04, 2·18) were significantly associated with being seen by an HCV clinician. Patients with long stays had a higher rate of treatment (14% of viremic patients). Sustained virologic response at 12 weeks was achieved in 147/164 (90%) of patients with available virologic data. Interpretation: Jail health systems can reach large numbers of HCV-infected individuals. The high burden of HCV argues for universal screening in jail settings. Length of stay was strongly associated with being seen by an HCV clinician in jail. Treatment is feasible among those with longer lengths of stay. Funding: None.

The basolateral amygdala (BLA) is critical for associating initially neutral cues with appetitive and aversive stimuli and receives dense neuromodulatory acetylcholine (ACh) projections. We measured BLA ACh signaling and activity of neurons expressing CaMKIIα (a marker for glutamatergic principal cells) in mice during cue-reward learning using a fluorescent ACh sensor and calcium indicators. We found that ACh levels and nucleus basalis of Meynert (NBM) cholinergic terminal activity in the BLA (NBM-BLA) increased sharply in response to reward-related events and shifted as mice learned the cue-reward contingency. BLA CaMKIIα neuron activity followed reward retrieval and moved to the reward-predictive cue after task acquisition. Optical stimulation of cholinergic NBM-BLA terminal fibers led to a quicker acquisition of the cue-reward contingency. These results indicate BLA ACh signaling carries important information about salient events in cue-reward learning and provides a framework for understanding how ACh signaling contributes to shaping BLA responses to emotional stimuli.