Role of RNA structural plasticity in modulating HIV-1 genome packaging and translation.

HIV-1 transcript function is controlled in part by twinned transcriptional start site usage, where 5' capped RNAs beginning with a single guanosine (1G) are preferentially packaged into progeny virions as genomic RNA (gRNA) whereas those beginning with three sequential guanosines (3G) are retained in cells as mRNAs. In 3G transcripts, one of the additional guanosines base pairs with a cytosine located within a conserved 5' polyA element, resulting in formation of an extended 5' polyA structure as opposed to the hairpin structure formed in 1G RNAs. To understand how this remodeling influences overall transcript function, we applied in vitro biophysical studies with in-cell genome packaging and competitive translation assays to native and 5' polyA mutant transcripts generated with promoters that differentially produce 1G or 3G RNAs. We identified mutations that stabilize the 5' polyA hairpin structure in 3G RNAs, which promote RNA dimerization and Gag binding without sequestering the 5' cap. None of these 3G transcripts were competitively packaged, confirming that cap exposure is a dominant negative determinant of viral genome packaging. For all RNAs examined, conformations that favored 5' cap exposure were both poorly packaged and more efficiently translated than those that favored 5' cap sequestration. We propose that structural plasticity of 5' polyA and other conserved RNA elements place the 5' leader on a thermodynamic tipping point for low-energetic (~3 kcal/mol) control of global transcript structure and function.

Risk of Suicidal Ideation and Behavior Following Early-Onset Idiopathic Restless Legs Syndrome Treatment.

PURPOSE: To estimate incidence rates of suicidal ideation and behavior following treatment initiation with gabapentinoids or dopamine agonists (DAs) in patients with newly diagnosed early-onset idiopathic restless legs syndrome (RLS) and to examine suicidal behavior risk, comparing between those receiving gabapentinoids and DAs. METHODS: A new user retrospective cohort study using MarketScan claims data from 2012 to 2019 was conducted. Exposures were monotherapy gabapentinoids or DAs initiated within 60 days of new RLS diagnosis. Three varying outcome measures of suicidality were examined and incidence rates were calculated for each. A log-binomial regression model the estimated relative risk (RR) of the outcomes with gabapentinoids. Propensity score weighting adjusted for baseline covariates, including age, substance use disorders, hyperlipidemia, antipsychotic use, hypnotic/sedative use, and mood stabilizer use, which were most imbalanced before weighting. RESULTS: The cohort included 6672 patients, with 4986 (74.7%) initiating a DA and 1686 (25.3%) initiating a gabapentinoid. Incidence rates for all outcome measures were higher in the gabapentinoid group (suicidality: 21.6 vs. 10.7 per 1000 person-years; suicidality with self-harm: 23.0 vs. 11.1 per 1000 person-years; overdose- and suicide-related events: 30.0 vs. 15.5 person-years). Associated risk of suicidality (adjusted RR, 1.27 [95% CI, 0.86-1.88]); suicidality with self-harm (adjusted RR, 1.30 [95% CI, 0.89-1.90]); or overdose- and suicide-related events (adjusted RR, 1.30 [95% CI, 0.93-1.80]) was not significant with gabapentinoids. CONCLUSIONS: Incidence rates for suicidal ideation and behavior were higher among the gabapentinoid group, although increased risk was not detected after adjustment. A possible signal cannot be ruled out given limitations of the data and rarity of the outcome.

Assessment of the Risk Evaluation and Mitigation Strategy (REMS) for Phentermine-Topiramate to Prevent Exposure During Pregnancy.

BACKGROUND: The U.S. Food and Drug Administration approved phentermine-topiramate for obesity in 2012 and required a Risk Evaluation and Mitigation Strategy (REMS) to prevent prenatal exposure. No such requirement was introduced for topiramate. OBJECTIVE: To evaluate the rate of prenatal exposure, contraceptive use, and pregnancy testing among patients with phentermine-topiramate compared with topiramate or other antiobesity medications (AOMs). DESIGN: Retrospective cohort study. SETTING: Nationwide health insurance claims database. PARTICIPANTS: Females aged 12 to 55 years with no infertility diagnosis or sterilization procedure. Patients with other indications for topiramate were excluded to identify a cohort that was likely treated for obesity. MEASUREMENTS: Patients initiated use of phentermine-topiramate, topiramate, or an AOM (liraglutide, lorcaserin, or bupropion-naltrexone). Pregnancy at treatment initiation, conception during treatment, contraceptive use, and pregnancy testing outcomes were ascertained. Measurable confounders were adjusted for, and extensive sensitivity analyses were done. RESULTS: A total of 156 280 treatment episodes were observed. Adjusted prevalence of pregnancy at treatment initiation was 0.9 versus 1.6 per 1000 episodes (prevalence ratio, 0.54 [95% CI, 0.31 to 0.95]) for phentermine-topiramate versus topiramate. The incidence rate of conception during treatment was 9.1 versus 15.0 per 1000 person-years (rate ratio, 0.61 [CI, 0.40 to 0.91]) for phentermine-topiramate versus topiramate. Both outcomes were similarly lower for phentermine-topiramate compared with AOM. Prenatal exposure was marginally lower in topiramate users compared with AOM users. Approximately 20% of patients in all cohorts had at least 50% of treatment days covered by contraceptives. Few patients had pregnancy tests before treatment (≤5%), but this was more common among phentermine-topiramate users. LIMITATIONS: Outcome misclassification; unmeasured confounding due to lack of prescriber data to account for possible clustering and spillover effects. CONCLUSION: Prenatal exposure seemed to be significantly lower among phentermine-topiramate users under the REMS. Pregnancy testing and contraceptive use appeared to be inadequate for all groups, which deserves attention to prevent the remaining potential exposures. PRIMARY FUNDING SOURCE: None.

Longitudinal Monitoring of Clinician-Patient Video Visits During the Peak of the COVID-19 Pandemic: Adoption and Sustained Challenges in an Integrated Health Care Delivery System.

BACKGROUND: Numerous prior opinion papers, administrative electronic health record data studies, and cross-sectional surveys of telehealth during the pandemic have been published, but none have combined assessments of video visit success monitoring with longitudinal assessments of perceived challenges to the rapid adoption of video visits during the pandemic. OBJECTIVE: This study aims to quantify (1) the use of video visits (compared with in-person and telephone visits) over time during the pandemic, (2) video visit successful connection rates, and (3) changes in perceived video visit challenges. METHODS: A web-based survey was developed for the dual purpose of monitoring and improving video visit implementation in our health care system during the COVID-19 pandemic. The survey included questions regarding rates of in-person, telephone, and video visits for clinician-patient encounters; the rate of successful connection for video visits; and perceived challenges to video visits (eg, software, hardware, bandwidth, and technology literacy). The survey was distributed via email to physicians, advanced practice professionals, and clinicians in May 2020. The survey was repeated in March 2021. Differences between the 2020 and 2021 responses were adjusted for within-respondent correlation across surveys and tested using generalized estimating equations. RESULTS: A total of 1126 surveys were completed (511 surveys in 2020 and 615 surveys in 2021). In 2020, only 21.7% (73/336) of clinicians reported no difficulty connecting with patients during video visits and 28.6% (93/325) of clinicians reported no difficulty in 2021. The distribution of the percentage of successfully connected video visits ("Over the past two weeks of scheduled visits, what percentage did you successfully connect with patients by video?") was not significantly different between 2020 and 2021 (P=.74). Challenges in conducting video visits persisted over time. Poor connectivity was the most common challenge reported by clinicians. This response increased over time, with 30.5% (156/511) selecting it as a challenge in 2020 and 37.1% (228/615) in 2021 (P=.01). Patients not having access to their electronic health record portals was also a commonly reported challenge (109/511, 21.3% in 2020 and 137/615, 22.3% in 2021, P=.73). CONCLUSIONS: During the pandemic, our health care delivery system rapidly adopted synchronous patient-clinician communication using video visits. As experience with video visits increased, the reported failure rate did not significantly decline, and clinicians continued to report challenges related to general network connectivity and patient access to technology.

A Pharmacoepidemiologic Approach to Evaluate Real-world Effectiveness of Hormonal Contraceptives in the Presence of Drug-drug Interactions.

BACKGROUND: Accurate estimation of conception is critical in the assessment of the effects of drugs used during pregnancy or to prevent pregnancy. In a novel application, we studied the effectiveness of oral contraceptives (OCs), where misclassification of conception relative to OC exposure may obscure effect estimates. METHODS: We studied OC failure, in a large claims database, among women who used antiepileptic drugs with metabolizing enzyme-inducing properties (carbamazepine or oxcarbazepine), which reduce OC's effectiveness or enzyme-neutral properties (lamotrigine or levetiracetam), with no expected impact on OC effectiveness. We compared conception rates in women 12-48 years of age concomitantly using OCs and enzyme-inducing drugs with rates in concomitant users of OCs and enzyme-neutral drugs. We measured conception with a validated algorithm that estimates gestational age based on pregnancy endpoints. We estimated relative and attributable risk using generalized estimating equation models after standardized mortality ratio weighting. RESULTS: We identified 89,777 concomitant use episodes with adjusted contraceptive failure rates of 1.6 (95% confidence interval (CI) = 1.4, 1.8) per 100 person-years among users of enzyme-neutral drugs and 18,964 episodes with a rate of 2.3 (1.9, 2.8) among users of enzyme-inducing drugs. The relative risk of conception for enzyme-inducing group was 1.4 (1.1, 1.8), and the rate difference was 0.7 (0.2, 1.2). CONCLUSIONS: OCs in combination with antiepileptic drugs that interact with metabolic enzymes were associated with increased contraceptive failure rates. Measurement of conception in claims data had adequate accuracy to uncover a strong drug-drug interaction, offering promise for broader application in comparative effectiveness studies on hormonal contraceptives to inform clinical and regulatory decisionmaking.

Utilization Patterns of Skeletal Muscle Relaxants Among Commercially Insured Adults in the United States from 2006 to 2018.

OBJECTIVE: To examine the prevalence and duration of skeletal muscle relaxant (SMR) treatment among commercially insured adults in the United States. METHODS: We used the MarketScan Research Database to identify a cohort of adults 18 to 64 years who had ≥2-year continuous enrollment between 2005 and 2018. We estimated the prevalence of SMR treatment using a repeated cross-sectional design and derived treatment duration using the Kaplan-Meier method. Analyses were stratified by age group, sex, geographic region, individual SMR agent, and musculoskeletal disorder. RESULTS: 48.7 million individuals were included. Treatment prevalence ranged from 61.5 to 68.3 per 1,000. About one-third of users did not have a preceding musculoskeletal disorder diagnosis. Cyclobenzaprine was the dominant agent accounting for >50% of prescriptions. The considerable growth in the use of baclofen, tizanidine, and methocarbamol paralleled with a decline in carisoprodol and metaxalone use. The prevalence was highest in the South while lowest in the Northeast. The median treatment duration was 14 days with 4.0%, 1.9%, and 1.0% of individuals using SMRs for more than 90, 180, and 365 days, respectively. Compared with cyclobenzaprine, patients initiating baclofen, tizanidine, and carisoprodol had longer treatment duration. CONCLUSIONS: SMRs are widely used in the United States. Their use slightly increased in recent years, but trends varied among individual agents, patient groups, and geographic regions. Despite limited evidence to support efficacy, a sizable number of U.S. adults used SMRs for long-term and off-label conditions. Further study is needed to understand determinants of treatment as well as outcomes associated with such use.

Risk Factors Associated With 7- Versus 30-Day Readmission Among Patients With Heart Failure Using the Nationwide Readmission Database.

BACKGROUND: The 30-day all-cause readmission for heart failure (HF) is a standard measure to evaluate hospital performance. A recent study found that a shorter period after discharge may be more indicative of hospital quality. OBJECTIVE: To compare risk factors for 7- versus 30-day readmission in patients with HF. DESIGN: This is a retrospective cohort using the 2014 Nationwide Readmissions Database. SUBJECTS: Patients 65 years and older with Medicare coverage discharged after HF admission. MEASURES: The 7- or 30-day all-cause readmissions were the outcomes of interest. HF-related readmissions were secondary outcomes. Covariates included patient characteristics, hospital characteristics, and admission-related information. Hierarchical logistic regression evaluated the association between covariates and readmissions. RESULTS: There were N=15,039 all-cause readmissions within 7 days after discharge and N=47,896 within 30 days. Surgical service was a risk factor for 30-day but not 7-day all-cause readmission (odds ratio=1.10, 95% confidence interval=1.05-1.16). Depression, rheumatoid arthritis, liver disease, drug abuse, lymphoma, and psychosis were associated with an increased risk of 30-day all-cause readmission but not 7-day. Longer lengths of stay also had a higher likelihood of all-cause readmission within 30 days compared with 7 days. In contrast, smaller hospital bed size was associated with an increased risk of 7-day all-cause readmission (odds ratio=1.06, confidence interval=1.01-1.12) but not 30-day. Sensitivity analysis with using a 3-day readmission interval showed similar results. CONCLUSIONS: Risk factors for hospital readmission are slightly different dependent on the measurement interval. In general, hospital-related factors were associated with shorter readmissions intervals while patient factors were more associated with longer intervals.

Real-world adherence for direct oral anticoagulants in a newly diagnosed atrial fibrillation cohort: does the dosing interval matter?

BACKGROUND: Differences in adherence may represent drug properties (e.g. dosing interval) or patient experiences while on treatment. Adherence to direct oral anticoagulants (DOACs) in nonvalvular atrial fibrillation (NVAF) is important to maintain effectiveness over the course of treatment. METHODS: This was a retrospective cohort study using 2009-2015 Truven Health MarketScan Databases. New initiators of dabigatran, rivaroxaban, and apixaban with NVAF were identified. Twelve months of continuous enrollment before treatment was required to assess demographics and medical history. Proportion of days cover (PDC) was used to measure adherence at 3, 6, 9 and 12-month. Gaps in therapy and treatment switches were also evaluated. Logistic regression was used to compare high adherence (PDC ≥0.80). RESULTS: A total of 14,864 dabigatran, 16,005 rivaroxaban, and 8078 apixaban users were identified. Apixaban users had the highest adherence overall, with mean PDC at 3, 6, 9, and 12-months of 0.83, 0.76, 0.72, and 0.69, while dabigatran had the lowest adherence of 0.78, 0.67, 0.61, and 0.57. Adherence to DOACs increased with increased stroke risk scores. Adherence was also higher when first days supplied was > 30 days compared to 30 days and when filled via mail order pharmacies. Switching was highest among dabigatran users. Apixaban users were the most likely to have high adherence versus dabigatran (OR = 1.73, 95% CI = 1.60-1.88) and versus rivaroxaban (OR = 1.24, 95% CI = 1.14-1.34) at 12-months. CONCLUSIONS: Apixaban users had the highest overall adherence despite twice-daily dosing versus once-daily dosing for rivaroxaban. These findings can be useful for formulary decision-making and when assessing treatment options.

Transcriptional start site heterogeneity modulates the structure and function of the HIV-1 genome.

The promoter in HIV type 1 (HIV-1) proviral DNA contains three sequential guanosines at the U3-R boundary that have been proposed to function as sites for transcription initiation. Here we show that all three sites are used in cells infected with HIV-1 and that viral RNAs containing a single 5' capped guanosine (Cap1G) are specifically selected for packaging in virions, consistent with a recent report [Masuda et al. (2015) Sci Rep 5:17680]. In addition, we now show that transcripts that begin with two or three capped guanosines (Cap2G or Cap3G) are enriched on polysomes, indicating that RNAs synthesized from different transcription start sites have different functions in viral replication. Because genomes are selected for packaging as dimers, we examined the in vitro monomer-dimer equilibrium properties of Cap1G, Cap2G, and Cap3G 5'-leader RNAs in the NL4-3 strain of HIV-1. Strikingly, under physiological-like ionic conditions in which the Cap1G 5'-leader RNA adopts a dimeric structure, the Cap2G and Cap3G 5'-leader RNAs exist predominantly as monomers. Mutagenesis studies designed to probe for base-pairing interactions suggest that the additional guanosines of the 2G and 3G RNAs remodel the base of the PolyA hairpin, resulting in enhanced sequestration of dimer-promoting residues and stabilization of the monomer. Our studies suggest a mechanism through which the structure, function, and fate of the viral genome can be modulated by the transcriptionally controlled presence or absence of a single 5' guanosine.

Mass Casualty Shooting Venues, Types of Firearms, and Age of Perpetrators in the United States, 1982-2018.

OBJECTIVES: To evaluate the association between mass casualty shooting venues, types of firearms, and the age of perpetrators in the United States. METHODS: We analyzed data on mass casualty (≥ 3 fatalities) shootings for August 1982 through February 14, 2018. We describe data overall, specifically by school venues and the weapons used. We categorized perpetrators by ages of younger than 18 years, 18 to 20 years, and 21 years and older. We described the number of victims (fatalities plus injuries) by medians and average per event. RESULTS: Of 97 events, the median perpetrator age was 35 years and 21 years for school shootings. Four of 16 school events were committed by those aged 18 to 20 years, and all of those events included long guns. Victims of perpetrators aged 18 to 20 years made up 9.0% of all victims and 31.1% of victims of school shootings. CONCLUSIONS: Persons aged 18 to 20 years perpetrated about 1 in 8 shootings, accounting for about 1 in 3 victims of school shootings. Public Health Implications. Legislation to prevent mass casualty events must be multifaceted, including age restrictions, restrictions on certain types of firearms, and improved resources for mental health, with particular emphasis on mental health and firearm restrictions for young adults.

Payer and Pharmaceutical Manufacturer Considerations for Outcomes-Based Agreements in the United States.

BACKGROUND: Considerable interest exists among health care payers and pharmaceutical manufacturers in designing outcomes-based agreements (OBAs) for medications for which evidence on real-world effectiveness is limited at product launch. OBJECTIVES: To build hypothetical OBA models in which both payer and manufacturer can benefit. METHODS: Models were developed for a hypothetical hypercholesterolemia OBA, in which the OBA was assumed to increase market access for a newly marketed medication. Fixed inputs were drug and outcome event costs from the literature over a 1-year OBA period. Model estimates were developed using a range of inputs for medication effectiveness, medical cost offsets, and the treated population size. Positive or negative feedback to the manufacturer was incorporated on the basis of expectations of drug performance through changes in the reimbursement level. Model simulations demonstrated that parameters had the greatest impact on payer cost and manufacturer reimbursement. RESULTS: Models suggested that changes in the size of the population treated and drug effectiveness had the largest influence on reimbursement and costs. Despite sharing risk for potential product underperformance, manufacturer reimbursement increased relative to having no OBA, if the OBA improved market access for the new product. Although reduction in medical costs did not fully offset the cost of the medication, the payer could still save on net costs per patient relative to having no OBA by tying reimbursement to drug effectiveness. CONCLUSIONS: Pharmaceutical manufacturers and health care payers have demonstrated interest in OBAs, and under a certain set of assumptions both may benefit.

A Review of Interventions to Increase Vena Cava Filter Retrieval Rates.

BACKGROUND: Inferior vena cava filters (IVCFs) are indicated for therapeutic and prophylactic treatment of venous thromboembolism in patients when anticoagulation has failed or is contraindicated. Retrievable IVCFs are not always retrieved despite clinical recommendations. The purpose of this review is to compare results in the literature regarding interventions and to improve IVCF retrieval rates. METHODS: Articles were identified via the search terms "vena cava filters" and "inferior vena cava filters" in conjunction with "retrieval." Searches were repeated in MEDLINE/PubMed, Google Scholar, and Cochrane database. Exclusion criteria included duplicates, misidentified subject matter, study period before 2008, and lack of control group. Two independent reviewers screened key elements in the identified manuscripts, including the targeted intervention population, study design, IVCF retrieval rates, and other outcomes. A third reviewer corroborated results and consolidated findings. RESULTS: Seventeen articles were identified for review. Of these, 12 were physician-targeted interventions, and 8 were patient-targeted interventions (3 studies included both). IVCF retrieval rates varied substantially for each study, but all reviewed studies reported improvement in retrieval rate following intervention. Only 5 studies reported decreased IVCF indwell times in intervention groups. Reported complication rates from IVCF retrievals were low, ranging from 0 to 2%. CONCLUSIONS: IVCF retrieval rates were improved by all interventions in the reviewed studies. Findings suggest that IVCF retrieval rates can be best improved by tracking patients typically lost to follow-up. Literature suggests that successful tracking requires an individual or team of individuals who have been assigned dedicated clinical responsibility for coordinating care following IVCF placement.

The relative burden of community-acquired pneumonia hospitalizations in older adults: a retrospective observational study in the United States.

BACKGROUND: The risk of community-acquired pneumonia (CAP) increases with age and significantly impacts morbidity and mortality in the elderly population. The burden of illness and cost of preventing CAP has not been compared to other serious diseases. METHODS: This retrospective analysis used claims data from 2014 to 2015 and compared hospitalizations for CAP, myocardial infarction (MI), stroke, and osteoporotic fractures (OF) in adults aged ≥65 years enrolled in a Medicare Advantage insurance plan. Individuals who had not already been hospitalized for one of these conditions and did not have evidence of long-term care were included in the study. Hospitalizations for each condition were described by length of stay, readmissions, mortality, and total costs. Preventive measures included vaccinations for CAP and medications for MI, stroke, and OF. RESULTS: A total of 1,949,352 individuals were included in the cohort. In 2015, the rate of CAP-related hospitalizations was the highest at 846.7 per 100,000 person-years compared to 405 for MI, 278.9 for stroke, and 343.9 for OF. Vaccination costs for CAP were $40.2 million including $14.1 million for pneumococcal and $26.1 million for influenza vaccines. The cost of preventive medications for MI and stroke reached over $661 million and OF totaled $169 million. CONCLUSIONS: Although CAP has a higher burden of hospitalization and total costs than MI, stroke, and OF in the elderly population, prevention efforts were disproportionately smaller for CAP. Prioritization of CAP prevention is needed to substantially reduce the burden of CAP.

Hospital Variation and Patient Characteristics Associated With Vena Cava Filter Utilization.

INTRODUCTION: There is a wide variation in the use of vena cava filter (VCF). OBJECTIVE: This study assessed the hospital and patient characteristics associated with VCF use in deep vein thrombosis (DVT) and pulmonary embolism (PE). METHODS: Inpatient discharge data from all acute care hospitals with DVT/PE during 2008-2014 in Kentucky were used. Hierarchical logistic regression models were used to evaluate the relationships of study variables with VCF use. RESULTS: During the study period, 81,922 discharges for DVT/PE were observed and 10.5% of these received a VCF. This included 12,083 cases of PE+DVT, 18,571 cases of PE only, and 51,268 cases of DVT only. VCF use among these groups was 22.7%, 6.0%, and 7.8%, respectively. In adjusted analyses, VCF use was associated with increasing age, indicating that those over age 65 were twice as likely to receive a filter compared with the reference (21-25 y old) group. Significant comorbidities associated with VCF use included cancer, liver disease, cerebrovascular disease, atrial fibrillation, anemia, and concurrent bleeding. Lower extremity, proximal DVTs, and patients receiving thrombolytic therapy or embolectomy, those having surgery, and those who were unstable or had trauma, were also more likely to receive a filter. Among cancer types, brain and metastatic tumors were significantly associated with VCF use. Between-hospital variation after controlling for all covariates was 7.1%. CONCLUSIONS: There was high variation in the use of VCFs. Several high-risk subgroups were more likely to use VCFs including older adults and those with cancer and concurrent bleeding.

Therapeutic Assessment in Psychological Triage Using the PAI.

This case illustrates the utility of incorporating therapeutic assessment in a triage context that typically involves a focus on gathering information. A man referred to our clinic by a local mental health center was seen by our assessment team for a triage that includes the administration of a single psychological test, the Personality Assessment Inventory (PAI). Although this triage must rapidly gather information to determine client suitability and treatment assignment, we still attempt to work with clients to collaboratively develop goals for this assessment that include addressing questions that are central concerns for the clients. In this case, the test results suggested a severe disorder that accounted for many phenomena that he had been experiencing but had apparently been reluctant to share. The information gathered led to a referral to a different treatment program that could provide pharmacological and more intensive forms of treatment. However, the collaborative bond formed between the assessor and the client during this triage was sufficiently strong that it was our assessor to whom the client turned in a subsequent crisis precipitated by a symptomatic exacerbation. This case illustrates complementary information gathering and therapeutic goals of assessment even in the context of a brief assessment.

Prediction of hydrogen and carbon chemical shifts from RNA using database mining and support vector regression.

The Biological Magnetic Resonance Data Bank (BMRB) contains NMR chemical shift depositions for over 200 RNAs and RNA-containing complexes. We have analyzed the (1)H NMR and (13)C chemical shifts reported for non-exchangeable protons of 187 of these RNAs. Software was developed that downloads BMRB datasets and corresponding PDB structure files, and then generates residue-specific attributes based on the calculated secondary structure. Attributes represent properties present in each sequential stretch of five adjacent residues and include variables such as nucleotide type, base-pair presence and type, and tetraloop types. Attributes and (1)H and (13)C NMR chemical shifts of the central nucleotide are then used as input to train a predictive model using support vector regression. These models can then be used to predict shifts for new sequences. The new software tools, available as stand-alone scripts or integrated into the NMR visualization and analysis program NMRViewJ, should facilitate NMR assignment and/or validation of RNA (1)H and (13)C chemical shifts. In addition, our findings enabled the re-calibration a ring-current shift model using published NMR chemical shifts and high-resolution X-ray structural data as guides.

ResearchConnect.info: An Interactive Web-Based Platform for Building Academic Collaborations.

RATIONALE AND OBJECTIVES: Radiology is a rapidly evolving field that benefits from continuous innovation and research participation among trainees. Traditional methods for involving residents in research are often inefficient and limited, usually due to the absence of a standardized approach to identifying available research projects. A centralized online platform can enhance networking and offer equal opportunities for all residents. MATERIALS AND METHODS: Research Connect is an online platform built with PHP, SQL, and JavaScript. Features include project and collaboration listing as well as advertisement of project openings to medical/undergraduate students, residents, and fellows. The automated system maintains project data and sends notifications for new research opportunities when they meet user preference criteria. Both pre- and post-launch surveys were used to assess the platform's efficacy. RESULTS: Before the introduction of Research Connect, 69% of respondents used informal conversations as their primary method of discovering research opportunities. One year after its launch, Research Connect had 141 active users, comprising 63 residents and 41 faculty members, along with 85 projects encompassing various radiology subspecialties. The platform received a median satisfaction rating of 4 on a 1-5 scale, with 54% of users successfully locating projects of interest through the platform. CONCLUSION: Research Connect addresses the need for a standardized method and centralized platform with active research projects and is designed for scalability. Feedback suggests it has increased the visibility and accessibility of radiology research, promoting greater trainee involvement and academic collaboration.

End-of-Life Healthcare Utilization in Lewy Body Dementia.

Background: Lewy body dementia (LBD) is the second most common neurodegenerative dementia in the US, presenting unique end-of-life challenges. Objective: This study examined healthcare utilization and care continuity in the last year of life in LBD. Methods: Medicare claims for enrollees with LBD, continuously enrolled in the year preceding death, were examined from 2011-2018. We assessed hospital stays, emergency department (ED) visits, intensive care unit (ICU) admissions, life-extending procedures, medications, and care continuity. Results: We identified 45,762 LBD decedents, predominantly female (51.8%), White (85.9%), with average age of 84.1 years (SD 7.5). There was a median of 2 ED visits (IQR 1-5) and 1 inpatient stay (IQR 0-2). Higher age was inversely associated with ICU stays (Odds Ratio [OR] 0.96; 95% Confidence Interval [CI] 0.96-0.97) and life-extending procedures (OR 0.96; 95% CI 0.95-0.96). Black and Hispanic patients experienced higher rates of ED visits, inpatient hospitalizations, ICU admissions, life-extending procedures, and in-hospital deaths relative to White patients. On average, 15 (7.5) medications were prescribed in the last year. Enhanced care continuity correlated with reduced hospital (OR 0.72; 95% CI 0.70-0.74) and ED visits (OR 0.71; 95% CI 0.69-0.87) and fewer life-extending procedures (OR 0.71; 95% CI 0.64-0.79). Conclusions: This study underscored the complex healthcare needs of people with LBD during their final year, which was influenced by age and race. Care continuity may reduce hospital and ED visits and life-extending procedures.

Associations Between Postdischarge Care and Cognitive Impairment-Related Hospital Readmissions for Ketoacidosis and Severe Hypoglycemia in Adults With Diabetes.

OBJECTIVE: Patients with severe hypoglycemia (SH) or diabetic ketoacidosis (DKA) experience high hospital readmission after being discharged. Cognitive impairment (CI) may further increase the risk, especially in those experiencing an interruption of medical care after discharge. This study examined the effect modification role of postdischarge care (PDC) on CI-associated readmission risk among U.S. adults with diabetes initially admitted for DKA or SH. RESEARCH DESIGN AND METHODS: We used the Nationwide Readmissions Database (NRD) (2016-2018) to identify individuals hospitalized with a diagnosis of DKA or SH. Multivariate Cox regression was used to compare the all-cause readmission risk at 30 days between those with and without CI identified during the initial hospitalization. We assessed the CI-associated readmission risk in the patients with and without PDC, an effect modifier with the CI status. RESULTS: We identified 23,775 SH patients (53.3% women, mean age 65.9 ± 15.3 years) and 140,490 DKA patients (45.8% women, mean age 40.3 ± 15.4 years), and 2,675 (11.2%) and 1,261 (0.9%), respectively, had a CI diagnosis during their index hospitalization. For SH and DKA patients discharged without PDC, CI was associated with a higher readmission risk of 23% (adjusted hazard ratio [aHR] 1.23, 95% confidence interval 1.08-1.40) and 35% (aHR 1.35, 95% confidence interval 1.08-1.70), respectively. However, when patients were discharged with PDC, we found PDC was an effect modifier to mitigate CI-associated readmission risk for both SH and DKA patients (P < 0.05 for all). CONCLUSIONS: Our results suggest that PDC can potentially mitigate the excessive readmission risk associated with CI, emphasizing the importance of postdischarge continuity of care for medically complex patients with comorbid diabetes and CI.

Comparison of Pimavanserin Versus Quetiapine for Hospitalization and Mortality Risk Among Medicare Beneficiaries with Parkinson's Disease Psychosis.

Background: Pimavanserin is currently the only antipsychotic approved for Parkinson's disease (PD) psychosis, yet its relative safety compared with treatment alternatives has not been thoroughly assessed. Objectives: This study aimed to compare hospitalization and mortality risk in Medicare beneficiaries with PD receiving new prescriptions of pimavanserin or quetiapine for PD psychosis. Methods: The study identified new users of pimavanserin and quetiapine from a 15% national sample of Medicare fee-for-service claims collected between May 1, 2016, and December 30, 2018. All-cause hospitalization and mortality were assessed in time-to-event regression models. Standardized mortality ratio weighting balanced pimavanserin and quetiapine users on baseline characteristics. Follow-up was censored at discontinuation, switch, disenrollment, or the end of the study period. Results: There were 844 new pimavanserin users and 2505 new quetiapine users. The adjusted hazard ratios (95% confidence intervals [CIs]) for hospitalization at 30, 90, 180, and 365 days for pimavanserin versus quetiapine users were 0.59 (0.43-0.81), 0.56 (0.44-0.72), 0.63 (0.52-0.77), and 0.70 (0.60-0.83). The most common reasons for hospitalization were traumatic injury and sepsis. Hospitalizations for heart-related issues were higher with pimavanserin (P < 0.05). The adjusted hazard ratios (95% CIs) for all-cause mortality at 90, 180, and 365 days for pimavanserin versus quetiapine users were 0.73 (0.48-1.13), 0.80 (0.58-1.10), and 0.94 (0.74-1.19). Conclusions: Risk of hospitalization was lower in pimavanserin users compared with quetiapine, and no difference in mortality was observed between pimavanserin and quetiapine. An active comparator analyses with treatment alternatives provided the most clinically relevant information for patients and physicians.