The utility of the irritability scale in Huntington's disease patients with evidence of irritability or aggression.

INTRODUCTION: Irritability, a common neuropsychiatric symptom in Huntington's disease (HD), lacks a standardized measurement. The Irritability Scale (IS), tailored for HD, has patient and informant versions, but variable interrater agreement has been reported frequently in previous studies. To enhance the clinical utility of the IS, this study aimed to identify the most reliable components estimating the underlying construct and develop a shortened version for time-limited contexts. METHODS: Participant and informant/observer concordance and the relationship of individual items to the complete IS scale were assessed. The short-form (SF) items were selected based on interrater agreement, exploratory factor analysis (EFA), and Item Response Theory (IRT) analysis results. Pair-wise correlation and covariance models were used to examine how SF predicted total IS score in 106 participants from the STAIR (Safety, Tolerability, and Activity of SRX246 in Irritable Subjects with Huntington's Disease) trial. Item Response Theory (IRT) analysis was used to evaluate the range and function of the selected items. RESULTS: IS interrater agreement was statistically significant (r = 0.33, p = .001). In combination with EFA factors and IRT analyses, five items were identified that showed good reliability and performance in differentiating levels of irritability. CONCLUSION: The proposed 5-item SF IS provided a reliable measure of the full scale and may be less burdensome for use in a clinical setting.

Negative allometry of leaf xylem conduit diameter and double-wall thickness: implications for implosion safety.

Xylem conduits have lignified walls to resist crushing pressures. The thicker the double-wall (T) relative to its diameter (D), the greater the implosion safety. Having safer conduits may incur higher costs and reduced flow, while having less resistant xylem may lead to catastrophic collapse under drought. Although recent studies have shown that conduit implosion commonly occurs in leaves, little is known about how leaf xylem scales T vs D to trade off safety, flow efficiency, mechanical support, and cost. We measured T and D in > 7000 conduits of 122 species to investigate how T vs D scaling varies across clades, habitats, growth forms, leaf, and vein sizes. As conduits become wider, their double-cell walls become proportionally thinner, resulting in a negative allometry between T and D. That is, narrower conduits, which are usually subjected to more negative pressures, are proportionally safer than wider ones. Higher implosion safety (i.e. higher T/D ratios) was found in asterids, arid habitats, shrubs, small leaves, and minor veins. Despite the strong allometry, implosion safety does not clearly trade off with other measured leaf functions, suggesting that implosion safety at whole-leaf level cannot be easily predicted solely by individual conduits' anatomy.

Early results of combined total ankle total talus replacement in the revision setting.

BACKGROUND: Revision of failed total ankle replacement (TAR) is challenging and associated with increased morbidity. Given the increased popularity of TAR in treating end-stage ankle arthritis (ESAA), viable revision options are needed. The objective of this case series is to present a minimum 2-year clinical and radiographic outcomes of patient-specific custom 3D-printed total ankle total talus (TATR) prostheses in this unique subset of patients. METHODS: 19 participants with ESAA and failed primary TAR who underwent TATR by a single surgeon at our institution from 2019 to 2021 were retrospectively identified. All participants were indicated for revision of primary STAR implant (Stryker, Kalamazoo, MI) and underwent replacement with 3D-printed titanium implants based on preoperative CT analysis (Additive Orthopaedics, Little Silver, NJ). Custom components included a mobile-bearing total talus and stemmed tibial system, performed through an anterior approach. Pre- and postoperative patient-reported outcomes were assessed using the Patient Reported Outcomes Measurement Information System (PROMIS). Pre- and postoperative implant alignment was assessed using medial distal tibial angle (MDTA) and tibiotalar angle (TTA) on anteroposterior, and sagittal tibial angle (STA) on lateral weight-bearing plain films. RESULTS: The average patient age was 60.6 (range, 39-77) years, with an average follow-up of 37.9 (range, 25.3-57.5) months. There was statistically significant improvement in all PROMIS domains. Short-term survivorship was 100%, with two participants (11.0%) requiring reoperation for postoperative complications: one underwent open reduction internal fixation of the tibia for a periprosthetic fracture, and another underwent medial gutter debridement and tarsal tunnel release for recurrent pain. There were no significant differences in pre- versus postoperative radiographic alignment measured by MDTA (89.9 vs 86.4), TTA (89.7 vs 88.1), or STA (85.2 vs 85.3). CONCLUSION: Custom 3D-printed TATR is a promising option for revision TAR. There was significant short-term improvement in pain and physical function, with excellent short-term survivorship and an acceptable postoperative complication rate.

Determinants of long-term physical and mental health outcomes after intensive care admission for trauma survivors.

INTRODUCTION: Collectively, studies from medical and surgical intensive care units (ICU) suggest that long-term outcomes are poor for patients who have spent significant time in an ICU. We sought to identify determinants of post-intensive care physical and mental health outcomes 6-12 months after injury. METHODS: Adult trauma patients [ISS ≥9] admitted to one of three Level-1 trauma centers were interviewed 6-12 months post-injury to evaluate patient-reported outcomes. Patients requiring ICU admission â€‹≥ â€‹3 days ("ICU patients") were compared with those who did not require ICU admission ("non-ICU patients"). Multivariable regression models were built to identify factors associated with poor outcomes among ICU survivors. RESULTS: 2407 patients were followed [598 (25%) ICU and 1809 (75%) non-ICU patients]. Among ICU patients, 506 (85%) reported physical or mental health symptoms. Of them, 265 (52%) had physical symptoms only, 15 (3%) had mental symptoms only, and 226 (45%) had both physical and mental symptoms. In adjusted analyses, compared to non-ICU patients, ICU patients were more likely to have new limitations for ADLs (OR â€‹= â€‹1.57; 95% CI â€‹= â€‹1.21, 2.03), and worse SF-12 mental (mean Δ â€‹= â€‹-1.43; 95% CI â€‹= â€‹-2.79, -0.09) and physical scores (mean Δ â€‹= â€‹-2.61; 95% CI â€‹= â€‹-3.93, -1.28). Age, female sex, Black race, lower education level, polytrauma, ventilator use, history of psychiatric illness, and delirium during ICU stay were associated with poor outcomes in the ICU-admitted group. CONCLUSIONS: Physical impairment and mental health symptoms following ICU stay are highly prevalent among injury survivors. Modifiable ICU-specific factors such as early liberation from ventilator support and prevention of delirium are potential targets for intervention.

Differences in Serum miRNA Profiles by Race, Ethnicity, and Socioeconomic Status: Implications for Developing an Equitable Ovarian Cancer Screening Test.

Serum miRNAs are promising biomarkers for several clinical conditions, including ovarian cancer. To inform equitable implementation of these tests, we investigated the effects of race, ethnicity, and socioeconomic status on serum miRNA profiles. Serum samples from a large institutional biobank were analyzed using a custom panel of 179 miRNA species highly expressed in human serum, measured using the Abcam Fireplex assay via flow cytometry. Data were log-transformed prior to analysis. Differences in miRNA by race and ethnicity were assessed using logistic regression. Pairwise t tests analyzed racial and ethnic differences among eight miRNAs previously associated with ovarian cancer risk. Pearson correlations determined the relationship between mean miRNA expression and the social deprivation index (SDI) for Massachusetts residents. Of 1,586 patients (76.9% white, non-Hispanic), compared with white, non-Hispanic patients, those from other racial and ethnic groups were younger (41.9 years ± 13.2 vs. 51.3 ± 15.1, P < 0.01) and had fewer comorbidities (3.5 comorbidities ± 2.7 vs. 4.6 ± 2.8, P < 0.01). On logistic regression, miRNAs predicted race and ethnicity at an AUC of 0.69 (95% confidence interval, 0.66-0.72), which remained consistent when stratified by most comorbidities. Among eight miRNAs previously associated with ovarian cancer risk, seven significantly varied by race and ethnicity (all P < 0.01). There were no significant differences in SDI for any of these eight miRNAs. miRNA expression is significantly influenced by race and ethnicity, which remained consistent after controlling for confounders. Understanding baseline differences in biomarker test characteristics prior to clinical implementation is essential to ensure instruments perform comparably across diverse populations. PREVENTION RELEVANCE: This study aimed to understand factors affecting miRNA expression, to ensure we create equitable screening tests for ovarian cancer that perform well in diverse populations. The goal is to ensure that we are detecting ovarian cancer cases earlier (secondary prevention) in women of all races, ethnic backgrounds, and socioeconomic means.

Intraperitoneal and Hyperthermic Intraperitoneal Chemotherapy for the Treatment of Ovarian Cancer.

OPINION STATEMENT: In our clinical practice, we have shifted away from the use of adjuvant normothermic intraperitoneal (IP) chemotherapy, particularly following the publication of GOG 252. Our decision is rooted in the accumulating evidence indicating a lack of demonstrable superiority, alongside the recognized toxicities and logistical challenges associated with its administration. This strategic departure is also influenced by the rising utilization of maintenance therapies such as bevacizumab and PARP inhibitors, which present viable alternatives for improving patient outcomes. Our utilization of hyperthermic IP chemotherapy (HIPEC) is currently reserved for a specific cohort of patients, mirroring the patient population studied in the OVHIPEC-1 trial. Specifically, our HIPEC protocol applies to patients presenting with newly diagnosed stage IIIC high-grade epithelial ovarian cancer who are deemed ineligible for primary debulking surgery. Patients must exhibit at least stable disease with neoadjuvant platinum-based chemotherapy, maintain a favorable performance status (ECOG score 0-1), possess good nutritional reserves (with no evidence of protein-calorie malnutrition and an albumin level exceeding 3.5), and not have chronic kidney disease. When HIPEC is planned, it is administered at the time of interval debulking surgery, contingent upon the attainment of optimal surgical outcomes (< 1 cm of residual disease). Our HIPEC protocol adheres to the original OVHIPEC-1 trial guidelines, employing cisplatin at a dosage of 100 mg/m2. We administer at least two antiemetics, antihistamines, and sodium thiosulfate to mitigate known side effects. Postoperatively, patients are admitted to the general surgical floor, reserving the intensive care unit for those in critical condition. We follow Enhanced Recovery After Surgery principles, incorporating early ambulation and feeding into our postoperative care strategy. We have encountered encouraging results with this approach, with most patients having largely uncomplicated postoperative courses and resuming adjuvant chemotherapy within 3 to 4 weeks of surgery.

Bacterial Pneumonia and Stroke Risk: A Nationwide Longitudinal Followup Study.

BACKGROUND: Pneumonia causes significant morbidity and mortality and has been associated with cardiovascular complications. Our study aimed to investigate the incidence of ischemic and hemorrhagic strokes following bacterial pneumonia. METHODS: Between 1997 and 2012, 10,931 subjects with bacterial pneumonia and 109,310 controls were enrolled from the Taiwan National Health Insurance Research Database, and were followed up to the end of 2013. The risk of stroke was estimated in Cox regression analyses with hazard ratios (HRs) and 95% confidence intervals (CIs). RESULTS: When compared to the control group, subjects in the bacterial pneumonia group had a higher incidence of developing ischemic stroke (2.7% versus 0.4%, p <0.001) and hemorrhagic stroke (0.7% versus 0.1%, p <0.001). The risk of stroke increases with repeated hospitalizations due to bacterial pneumonia. Across bacterial etiologies, bacterial pneumonia was a significant risk factor among 775 subjects who developed ischemic stroke (HR, 5.72; 95% CI, 4.92-6.65) and 193 subjects who developed hemorrhagic stroke (HR, 5.33; 95% CI, 3.91-7.26). CONCLUSION: The risks of developing ischemic stroke and hemorrhagic stroke are significant following bacterial pneumonia infection. The risk factors, clinical outcomes, and the disease course should also be profiled to better inform the monitoring of stroke development and the clinical management of bacterial pneumonia patients.

Targeted indoor residual insecticide applications shift Aedes aegypti age structure and arbovirus transmission potential.

While residual insecticide applications have the potential to decrease pathogen transmission by reducing the density of vectors and shifting the age structure of the adult mosquito population towards younger stages of development, this double entomological impact has not been documented for Aedes aegypti. Aedes collected from households enrolled in a cluster-randomized trial evaluating the epidemiological impact of targeted indoor residual spraying (TIRS) in Merida, Mexico, were dissected and their age structure characterized by the Polovodova combined with Christopher's ovariole growth methods. In total, 813 females were dissected to characterize age structure at 1, 3, 6, and 9 months post-TIRS. Significant differences in the proportion of nulliparous Ae. aegypti females between the treatment groups was found at one-month post-TIRS (control: 35% vs. intervention: 59%), three months (20% vs. 49%) but not at six or nine months post-TIRS. TIRS significantly shiftted Ae. aegypti age structure towards younger stages and led to a non-linear reduction in survivorship compared to the control arm. Reduced survivorship also reduced the number of arbovirus transmitting females (those who survived the extrinsic incubation period). Our findings provide strong evidence of the full entomological impact of TIRS, with important implications for quantifying the epidemiological impact of vector control methods.

Association of patient clinical and gut microbiota features with vancomycin-resistant enterococci environmental contamination in nursing homes: a retrospective observational study.

BACKGROUND: Preventing transmission is crucial for reducing infections with multidrug-resistant organisms (MDROs) in nursing homes. To identify resident characteristics associated with MDRO spread, we investigated associations between patient characteristics and contamination of their proximate room surfaces with vancomycin-resistant enterococci (VRE). METHODS: In this retrospective observational study, we used demographic and clinical data (including data on comorbidities, physical independence, catheter use within the past 30 days, and antibiotic exposure within the past 30 days) and surveillance cultures of patient body sites and room surfaces at enrolment and during weekly follow-up visits within the first month, and monthly thereafter (up to 6 months), in six US nursing homes collected in a previous clinical trial (September, 2016, to August, 2018). We did 16S rRNA gene sequencing on perirectal surveillance swabs to investigate the association between the gut microbiota and the culture status of participants and their rooms. FINDINGS: We included 245 participants (mean age 72·5 years [SD 13·6]; 111 [45%] were men, 134 [55%] were women, 132 [54%] were non-Hispanic white, and 112 [46%] were African American). We collected 2802 participant samples and 5592 environmental samples. At baseline, VRE colonisation was present in 49 (20%) participants, with environmental surfaces being contaminated in 36 (73%) of these patients. Hand contamination among VRE-colonised participants was more common in those with environmental contamination compared with those without (50 [51%] of 99 vs seven [13%] of 55; p<0·0001). We found a correlation between hand contamination and both groin and perirectal colonisation and contamination of various high-touch room surfaces (Cohen's κ 0·43). We found participant microbiota composition to be associated with antibiotic receipt within the past 30 days (high-risk antibiotics p=0·011 and low-risk antibiotics p=0·0004) and participant VRE colonisation status, but not environmental contamination among VRE-colonised participants (participant only vs uncolonised p=0·071, both participant and environment vs uncolonised p=0·025, and participant only vs participant and environment p=0·29). Multivariable analysis to identify independent factors associated with VRE-colonised participants contaminating their environment identified antibiotic exposure (adjusted odds ratio 2·75 [95% CI 1·22-6·16]) and male sex (2·75 [1·24-6·08]) as being associated with increased risk of environmental contamination, and physical dependence as being associated with a reduced risk of environmental contamination (0·91 [0·83-0·99]). INTERPRETATION: Our data support antibiotic use and interaction with proximal surfaces by physically independent nursing home residents as under-appreciated drivers of environmental contamination among VRE-colonised residents. Integrating resident hand-hygiene education and antimicrobial stewardship will strengthen efforts to reduce MDROs in nursing homes. FUNDING: US Centers for Disease Control and Prevention, National Institute of Health, Canadian Institutes of Health Research, and University of Michigan.

Safety and immunogenicity of a variant-adapted SARS-CoV-2 recombinant protein vaccine with AS03 adjuvant as a booster in adults primed with authorized vaccines: a phase 3, parallel-group study.

Background: In a parallel-group, international, phase 3 study (ClinicalTrials.govNCT04762680), we evaluated prototype (D614) and Beta (B.1.351) variant recombinant spike protein booster vaccines with AS03-adjuvant (CoV2 preS dTM-AS03). Methods: Adults, previously primed with mRNA (BNT162b2, mRNA-1273), adenovirus-vectored (Ad26.CoV2.S, ChAdOx1nCoV-19) or protein (CoV2 preS dTM-AS03 [monovalent D614; MV(D614)]) vaccines were enrolled between 29 July 2021 and 22 February 2022. Participants were stratified by age (18-55 and ≥ 56 years) and received one of the following CoV2 preS dTM-AS03 booster formulations: MV(D614) (n = 1285), MV(B.1.351) (n = 707) or bivalent D614 + B.1.351 (BiV; n = 625). Unvaccinated adults who tested negative on a SARS-CoV-2 rapid diagnostic test (control group, n = 479) received two primary doses, 21 days apart, of MV(D614). Anti-D614G and anti-B.1.351 antibodies were evaluated using validated pseudovirus (lentivirus) neutralization (PsVN) assay 14 days post-booster (day [D]15) in 18-55-year-old BNT162b2-primed participants and compared with those pre-booster (D1) and on D36 in 18-55-year-old controls (primary immunogenicity endpoints). PsVN titers to Omicron BA.1, BA.2 and BA.4/5 subvariants were also evaluated. Safety was evaluated over a 12-month follow-up period. Planned interim analyses are presented up to 14 days post-last vaccination for immunogenicity and over a median duration of 5 months for safety. Findings: All three boosters elicited robust anti-D614G or -B.1.351 PsVN responses for mRNA, adenovirus-vectored and protein vaccine-primed groups. Among BNT162b2-primed adults (18-55 years), geometric means of the individual post-booster versus pre-booster titer ratio (95% confidence interval [CI]) were: for MV (D614), 23.37 (18.58-29.38) (anti-D614G); for MV(B.1.351), 35.41 (26.71-46.95) (anti-B.1.351); and for BiV, 14.39 (11.39-18.28) (anti-D614G) and 34.18 (25.84-45.22 (anti-B.1.351). GMT ratios (98.3% CI) versus post-primary vaccination GMTs in controls, were: for MV(D614) booster, 2.16 (1.69; 2.75) [anti-D614G]; for MV(B.1.351), 1.96 (1.54; 2.50) [anti-B.1.351]; and for BiV, 2.34 (1.84; 2.96) [anti-D614G] and 1.39 (1.09; 1.77) [anti-B.1.351]. All booster formulations elicited cross-neutralizing antibodies against Omicron BA.2 (across priming vaccine subgroups), Omicron BA.1 (BNT162b2-primed participants) and Omicron BA.4/5 (BNT162b2-primed participants and MV D614-primed participants). Similar patterns in antibody responses were observed for participants aged ≥56 years. Reactogenicity tended to be transient and mild-to-moderate severity in all booster groups. No safety concerns were identified. Interpretation: CoV2 preS dTM-AS03 boosters demonstrated acceptable safety and elicited robust neutralizing antibodies against multiple variants, regardless of priming vaccine. Funding: Sanofi and Biomedical Advanced Research and Development Authority (BARDA).

Sertoli-Leydig cell tumor associated with a germline DICER1 pathogenic variant diagnosed during pregnancy: Considerations for treatment, surveillance, and prevention.

•This is the first report of a germline DICER1-associated Sertoli-Leydig cell tumor (SLCT) diagnosed in pregnancy.•SLCT is linked to DICER1 pathogenic variants, but little is known about management of DICER1-associated SLCT.•There is an extended risk for metachronous SLCT in patients with germline DICER1 pathogenic variants who retain an ovary.•Prophylactic contralateral salpingo-oophorectomy may be offered with shared decision making to patients with inherited SLCT.•Genetic testing for DICER1 should be offered to all patients with moderately or poorly differentiated SLCT.

Comparison of multiple 3D scanners to capture foot, ankle, and lower leg morphology.

BACKGROUND: 3D scanning of the foot and ankle is gaining popularity as an alternative method to traditional plaster casting to fabricate ankle-foot orthoses (AFOs). However, comparisons between different types of 3D scanners are limited. OBJECTIVES: The aim of this study was to evaluate the accuracy and speed of seven 3D scanners to capture foot, ankle, and lower leg morphology to fabricate AFOs. STUDY DESIGN: Repeated-measures design. METHODS: The lower leg region of 10 healthy participants (mean age 27.8 years, standard deviation [SD] 9.3) was assessed with 7 different 3D scanners: Artec Eva (Eva), Structure Sensor (SS I), Structure Sensor Mark II (SS II), Sense 3D Scanner (Sense), Vorum Spectra (Spectra), Trnio 3D Scanner App on iPhone 11 (Trnio 11), and Trnio 3D Scanner App on iPhone 12 (Trnio 12). The reliability of the measurement protocol was confirmed initially. The accuracy was calculated by comparing the digital scan with clinical measures. A percentage difference of #5% was considered acceptable. Bland and Altman plots were used to show the mean bias and limit of agreement (LoA) for each 3D scanner. Speed was the time needed for 1 complete scan. RESULTS: The mean accuracy ranged from 6.4% (SD 10.0) to 230.8% (SD 8.4), with the SS I (21.1%, SD 6.8), SS II (21.7%, SD 7.5), and Eva (2.5%, SD 4.5) within an acceptable range. Similarly, Bland and Altman plots for Eva, SS I, and SS II showed the smallest mean bias and LoA 21.7 mm (LoA 25.8 to 9.3), 21.0 mm (LoA 210.3 to 8.3), and 0.7 mm (LoA 213 to 11.5), respectively. The mean speed of the 3D scanners ranged from 20.8 seconds (SD 8.1, SS I) to 329.6 seconds (SD 200.2, Spectra). CONCLUSIONS: Eva, SS I, and SS II appear to be the most accurate and fastest 3D scanners for capturing foot, ankle, and lower leg morphology, which could be used for AFO fabrication.

Nostalgia in Tourism.

Tourism research has recognized nostalgia as an intrinsic motive, an emotion that tourists may experience at or after visiting a destination, and an effective appeal to market destinations. This article reviews the multifaceted roles of nostalgia in four domains: heritage tourism, sport tourism, film tourism, and contemporary tourism. The former three tourism domains have distinctive attractions that inspire nostalgia, suiting for corresponding scales for nostalgia as a motive. Moreover, nostalgia contributes to sustainable tourism and can be applied in virtual reality. Furthermore, research has uncovered nostalgia's restorative function and provided evidence of its mediating effects on the linkage between COVID-19 reactions (perceived severity, travel constraints, and the need to belong) on behavioral outcomes.

Suitability of Automated Writing Measures for Clinical Trial Outcome in Writer's Cramp.

BACKGROUND: Writer's cramp (WC) dystonia is a rare disease that causes abnormal postures during the writing task. Successful research studies for WC and other forms of dystonia are contingent on identifying sensitive and specific measures that relate to the clinical syndrome and achieve a realistic sample size to power research studies for a rare disease. Although prior studies have used writing kinematics, their diagnostic performance remains unclear. OBJECTIVE: This study aimed to evaluate the diagnostic performance of automated measures that distinguish subjects with WC from healthy volunteers. METHODS: A total of 21 subjects with WC and 22 healthy volunteers performed a sentence-copying assessment on a digital tablet using kinematic and hand recognition softwares. The sensitivity and specificity of automated measures were calculated using a logistic regression model. Power analysis was performed for two clinical research designs using these measures. The test and retest reliability of select automated measures was compared across repeat sentence-copying assessments. Lastly, a correlational analysis with subject- and clinician-rated outcomes was performed to understand the clinical meaning of automated measures. RESULTS: Of the 23 measures analyzed, the measures of word legibility and peak accelerations distinguished subjects with WC from healthy volunteers with high sensitivity and specificity and demonstrated smaller sample sizes suitable for rare disease studies, and the kinematic measures showed high reliability across repeat visits, while both word legibility and peak accelerations measures showed significant correlations with the subject- and clinician-rated outcomes. CONCLUSIONS: Novel automated measures that capture key aspects of the disease and are suitable for use in clinical research studies of WC dystonia were identified. © 2022 International Parkinson and Movement Disorder Society.

CMS Initiative to Reduce Potentially Avoidable Hospitalizations Among Long-Stay Nursing Facility Residents: Lessons Learned.

Policy Points Misaligned incentives between Medicare and Medicaid may result in avoidable hospitalizations among long-stay nursing home residents. Providing nursing homes with clinical staff, such as nurse practitioners, was more effective in reducing resident hospitalizations than providing Medicare incentive payments alone. CONTEXT: In 2012, the Centers for Medicare and Medicaid Services implemented the Initiative to Reduce Avoidable Hospitalizations Among Nursing Facility Residents. In Phase 1 (2012 to 2016), clinical or education-based interventions (Clinical-Only) aimed to reduce hospitalizations among long-stay nursing home residents. In Phase 2 (2016 to 2020), the Initiative also included a Medicare payment incentive for treating residents with certain conditions within the nursing home. Nursing homes participating in Phase 1 continued their previous interventions and received the incentive (Clinical + Payment) and others received the incentive only (Payment-Only). METHODS: Mixed methods were used to determine the effectiveness of the Initiative and explore facilitators of and barriers to implementation that participating nursing homes experienced. We used telephone and in-person interviews to investigate aspects of implementation and a difference-in-differences regression model framework comparing residents in participating and nonparticipating nursing homes to determine the effect of the Initiative on measures of utilization, expenditures, and quality. FINDINGS: Three key components were necessary for successful implementation of the Initiative-staff retention and leadership stability, leadership and staff support, and provider engagement and support. Nursing homes that lacked one or more of these three components experienced greater challenges. The Clinical-Only intervention in Phase 1 was successful in reducing hospitalizations. We did not find evidence that the Clinical + Payment or Payment-Only interventions were successful in reducing hospitalizations. CONCLUSIONS: Reducing hospitalizations among nursing home residents hinges upon the availability and support of clinical staff who can provide ongoing education to direct-care staff in the nursing home, as well as hands-on care. Use of Medicare payment incentives alone to encourage on-site treatment of residents was insufficient to reduce hospitalizations. Unless nursing homes are adequately staffed to treat residents with acute care needs, further reductions in hospitalizations will be difficult to achieve.

In-hospital Outcomes for COVID-19 Patients in the Military Health System: Comparison of Military and Civilian Facility Treatment.

INTRODUCTION: Beneficiaries of TRICARE, an insurance program of the military health system, can choose to receive care within the private sector (fee-for-service) or direct (budget-based facilities with salaried providers) care setting. Previous studies in several specialties have shown that there are disparities in both resource utilization and outcomes between the two settings. In this study, we sought to determine differences in outcomes between coronavirus disease 2019 (COVID-19) patients treated in the private sector versus direct care. MATERIALS AND METHODS: Using TRICARE claims data, we identified patients admitted to the hospital for COVID-19 between March and September 2020. Cases were classified, according to the facility where they were admitted for treatment, as private sector or direct care. We abstracted patient sociodemographic characteristics, comorbid conditions, and outcomes including in-hospital mortality, intensive care unit (ICU) admission, ventilator use, in-hospital complications, and 30-day readmission. We used multivariable regression models, adjusted for covariates, to determine the association between health care settings and outcomes. RESULTS: A total of 3,177 patients were included. Of these, 2,147 (68%) and 1,030 (32%) received care in the private sector and direct care settings, respectively. The average age of the study cohort was 52 years (SD = 21), and 84% had at least one medical comorbidity. In adjusted analyses, we found significant differences in the rates of ICU admission, with patients treated in private sector care having lower odds of being admitted to the ICU (odds ratio, 0.64; 95% CI, 0.53-0.76). There were no significant differences in the rates of in-hospital mortality, ventilator use, in-hospital complications, and 30-day readmissions. CONCLUSION: With the exception of ICU admission rates, which are higher in the direct care setting, we encountered comparable hospital-based outcomes for patients treated for COVID-19 within the military health system, whether care was received under private sector or direct care.

Identification of essential genes in Mycobacterium avium subsp. paratuberculosis genome for persistence in dairy calves.

To cause disease Mycobacterium avium subsp. paratuberculosis needs to enter mammalian cells, arrest phagosomal maturation and manipulate the host immune system. The genetic basis of the bacterial capacity to achieve these outcomes remains largely unknown. Identifying these genes would allow us to gain a deeper understanding of MAP's pathogenesis and potentially develop a live attenuated Johne's disease vaccine by knocking out these genes. MAP genes demonstrated to be essential for colonization in the natural host, ruminants, are unknown. Genome-wide transposon mutagenesis and high-throughput sequencing were combined to evaluate the essentiality of each coding region in the bacterial genome to survive in dairy calves. A saturated library of 3,852 MAP Tn mutants, with insertions in 56% of TA sites, interrupting 88% of genes, was created using a MycoMarT7 phagemid containing a mariner transposon. Six calves were inoculated with a high dose of a library of MAP mutants, 1011 CFUs, (input) at 2 weeks of age. Following 2 months of incubation, MAP cells were isolated from the ileum, jejunum, and their associated lymph nodes of calves, resulting in approximately 100,000 colonies grown on solid media across 6 animals (output). Targeted next-generation sequencing was used to identify the disrupted genes in all the mutants in the input pool and the output pool recovered from the tissues to identify in vivo essential genes. Statistical analysis for the determination of essential genes was performed by a Hidden Markov Model (HMM), categorizing genes into essential genes that are devoid of insertions and growth-defect genes whose disruption impairs the growth of the organism. Sequence analysis identified 430 in vivo essential and 260 in vivo growth-defect genes. Gene ontology enrichment analysis of the in vivo essential and growth-defect genes with the highest reduction in the tissues revealed a high representation of genes involved in metabolism and respiration, cell wall and cell processing, virulence, and information pathway processes. This study has systematically identified essential genes for the growth and persistence of MAP in the natural host body.

Clinical applications of machine learning in predicting 3D shapes of the human body: a systematic review.

BACKGROUND: Predicting morphological changes to anatomical structures from 3D shapes such as blood vessels or appearance of the face is a growing interest to clinicians. Machine learning (ML) has had great success driving predictions in 2D, however, methods suitable for 3D shapes are unclear and the use cases unknown. OBJECTIVE AND METHODS: This systematic review aims to identify the clinical implementation of 3D shape prediction and ML workflows. Ovid-MEDLINE, Embase, Scopus and Web of Science were searched until 28th March 2022. RESULTS: 13,754 articles were identified, with 12 studies meeting final inclusion criteria. These studies involved prediction of the face, head, aorta, forearm, and breast, with most aiming to visualize shape changes after surgical interventions. ML algorithms identified were regressions (67%), artificial neural networks (25%), and principal component analysis (8%). Meta-analysis was not feasible due to the heterogeneity of the outcomes. CONCLUSION: 3D shape prediction is a nascent but growing area of research in medicine. This review revealed the feasibility of predicting 3D shapes using ML clinically, which could play an important role for clinician-patient visualization and communication. However, all studies were early phase and there were inconsistent language and reporting. Future work could develop guidelines for publication and promote open sharing of source code.

Risk of retinal disease in patients with autism spectrum disorder.

BACKGROUND: Ocular abnormalities and visual dysfunction have been associated with autism spectrum disorder (ASD). Our study assessed the risks of developing retinal diseases in individuals with ASD. METHODS: In all, 18 874 patients with ASD and 188 740 controls were selected from the Taiwan National Health Insurance Research Database between 2001 and 2009. The control group was matched based on demographic characteristics and medical and ophthalmological comorbidities. The hazard ratios (HRs) with 95% confidence intervals were calculated with Cox-regression analyses adjusted for selected confounders. RESULTS: Individuals with ASD had a higher incidence of developing retinal diseases (1.48‰ vs 0.73‰, P < .001), and the diagnosis of retinal diseases occurred earlier than the controls (3.73 vs 6.28 years, P < .001). When compared to the control group, the HR of developing retinal diseases in the ASD group was 1.75 (95%: 1.04-2.94) and 7.84 (95%: 3.51-17.47) for retinal detachment. There was no association between the cumulative daily dose of atypical antipsychotics and the incidence of retinal diseases in the ASD group. CONCLUSION: Individuals with ASD have a higher risk of developing retinal detachment and are diagnosed with retinal diseases earlier than controls. Future research is needed to elucidate the mechanisms mediating the progression of retinal diseases in the ASD population.