Preliminary assessment of the subjective effects of electronic-cigarettes in young-adult low-dose electronic-cigarette users: Effects of nicotine dose and e-liquid flavor.

OBJECTIVE: The present study evaluated the effects of nicotine concentration (0-10 mg/ml) and flavor (gummy bear vs unflavored) on the subjective experiences of vaporized nicotine in young adult low-dose nicotine (3 mg/ml) ECIG users. PARTICIPANTS: Eight young adult ECIG users were recruited. METHODS: A single blinded crossover study was used. Participants were instructed to take ten 1.5 second puffs, each separated by 20 seconds. After self-administration, heart rate was recorded, and participants completed the Drug Effects, Direct Effects of Nicotine, and Direct Effects of ECIG questionnaires. RESULTS: ECIG user's standard daily nicotine dose influenced the rewarding and aversive effects of nicotine as the 10 mg/ml dose was found to be aversive in this user group. The combination of flavor and nicotine increased the subjective effects of ECIGs. CONCLUSIONS: Flavored e-liquids contribute to the reinforcing properties of nicotine by enhancing the subjective effects, which may lead to continued ECIG use.

Is the Sport Concussion Assessment Tool 5th Edition a useful concussion assessment tool in head-injured patients presenting to the emergency department?

OBJECTIVE: Concussion is a common ED complaint, but diagnosis is challenging as there are no validated objective measures. Use of concussion tools derived from sports medicine is common, but these tools are not well validated in ED settings. The aim of this study was to assess the ability of the Sport Concussion Assessment Tool 5th Edition (SCAT5) to identify concussion in ED patients presenting following head injury. METHODS: We conducted a prospective observational study of head-injured adult patients presenting to ED between March and July 2021. ED diagnosis of concussion was used as the diagnostic standard, and we assessed the diagnostic performance of the SCAT5 test and its three subsections (Standardised Assessment of Concussion (SAC), Post-Concussion Symptom Scale (PCSS) and Modified Balance Error Scoring System (mBESS)) against this. RESULTS: Thirty-two head-injured participants were enrolled, 19 of whom had a discharge diagnosis of concussion, alongside 17 controls. Median time for SCAT5 testing was 21 (interquartile range 16-27) min. Fifteen (30.6%) participants were interrupted during testing. Area under the curve (AUC) (95% confidence interval) for the SAC, PCSS and mBESS were 0.51 (0.34-0.68), 0.92 (0.84-0.99) and 0.66 (0.47-0.85), respectively. Sensitivity and specificity of sections were as follows: entire SCAT5 (100.0%, 20.0%), SAC (48.1%, 60.0%), PCSS (89.7%, 85.0%) and mBESS (83.3%, 58.8%). Using PCSS alone would have identified 17 of 19 concussions. CONCLUSION: The SCAT5 test had a low specificity, was long and was frequently interrupted. We suggest it is not an ideal assessment to use in ED. The PCSS score performed well and was easy to complete. It may be useful as a standalone tool to simplify ED concussion identification.

A New Risk Assessment Model for Hospital-Acquired Venous Thromboembolism in Critically Ill Children: A Report From the Children's Hospital-Acquired Thrombosis Consortium.

OBJECTIVES: To create a risk model for hospital-acquired venous thromboembolism in critically ill children upon admission to an ICU. DESIGN: Case-control study. SETTING: ICUs from eight children's hospitals throughout the United States. SUBJECTS: Critically ill children with hospital-acquired venous thromboembolism (cases) 0-21 years old and similar children without hospital-acquired venous thromboembolism (controls) from January 2012 to December 2016. Children with a recent cardiac surgery, asymptomatic venous thromboembolism, or a venous thromboembolism diagnosed before ICU admission were excluded. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: The multi-institutional Children's Hospital-Acquired Thrombosis registry was used to identify cases and controls. Multivariable logistic regression was used to determine the association between hospital-acquired venous thromboembolism and putative risk factors present at or within 24 hours of ICU admission to develop the final model. A total of 548 hospital-acquired venous thromboembolism cases (median age, 0.8 yr; interquartile range, 0.1-10.2) and 187 controls (median age, 2.4 yr; interquartile range, 0.2-8.3) were analyzed. In the multivariable model, recent central venous catheter placement (odds ratio, 4.4; 95% CI, 2.7-7.1), immobility (odds ratio 3.6, 95% CI, 2.1-6.2), congenital heart disease (odds ratio 2.9, 95% CI, 1.7-4.7), length of hospital stay prior to ICU admission greater than or equal to 3 days (odds ratio, 2.5; 95% CI, 1.1-5.6), and history of autoimmune/inflammatory condition or current infection (odds ratio, 2.1; 95% CI, 1.2-3.4) were each independently associated with hospital-acquired venous thromboembolism. The risk model had an area under the receiver operating characteristic curve of 0.79 (95% CI, 0.73-0.84). CONCLUSIONS: Using the multicenter Children's Hospital-Acquired Thrombosis registry, we identified five independent risk factors for hospital-acquired venous thromboembolism in critically ill children, deriving a new hospital-acquired venous thromboembolism risk assessment model. A prospective validation study is underway to define a high-risk group for risk-stratified interventional trials investigating the efficacy and safety of prophylactic anticoagulation in critically ill children.

Comparison of a time-varying covariate model and a joint model of time-to-event outcomes in the presence of measurement error and interval censoring: application to kidney transplantation.

BACKGROUND: Tacrolimus (TAC) is an immunosuppressant drug given to kidney transplant recipients post-transplant to prevent antibody formation and kidney rejection. The optimal therapeutic dose for TAC is poorly defined and therapy requires frequent monitoring of drug trough levels. Analyzing the association between TAC levels over time and the development of potentially harmful de novo donor specific antibodies (dnDSA) is complex because TAC levels are subject to measurement error and dnDSA is assessed at discrete times, so it is an interval censored time-to-event outcome. METHODS: Using data from the University of Colorado Transplant Center, we investigated the association between TAC and dnDSA using a shared random effects (intercept and slope) model with longitudinal and interval censored survival sub-models (JM) and compared it with the more traditional interval censored survival model with a time-varying covariate (TVC). We carried out simulations to compare bias, level and power for the association parameter in the TVC and JM under varying conditions of measurement error and interval censoring. In addition, using Markov Chain Monte Carlo (MCMC) methods allowed us to calculate clinically relevant quantities along with credible intervals (CrI). RESULTS: The shared random effects model was a better fit and showed both the average TAC and the slope of TAC were associated with risk of dnDSA. The simulation studies demonstrated that, in the presence of heavy interval censoring and high measurement error, the TVC survival model underestimates the association between the survival and longitudinal measurement and has inflated type I error and considerably less power to detect associations. CONCLUSIONS: To avoid underestimating associations, shared random effects models should be used in analyses of data with interval censoring and measurement error.

Assessment and management of hypertension in transplant patients.

Hypertension in renal transplant recipients is common and ranges from 50% to 80% in adult recipients and from 47% to 82% in pediatric recipients. Cardiovascular morbidity and mortality and shortened allograft survival are important consequences of inadequate control of hypertension. In this review, we examine the epidemiology, pathophysiology, and management considerations of post-transplant hypertension. Donor and recipient factors, acute and chronic allograft injury, and immunosuppressive medications may each explain some of the pathophysiology of post-transplant hypertension. As observed in other patient cohorts, renal artery stenosis and adrenal causes of hypertension may be important contributing factors. Notably, BP treatment goals for renal transplant recipients remain an enigma because there are no adequate randomized controlled trials to support a benefit from targeting lower BP levels on graft and patient survival. The potential for drug-drug interactions and altered pharmacokinetics and pharmacodynamics of the different antihypertensive medications need to be carefully considered. To date, no specific antihypertensive medications have been shown to be more effective than others at improving either patient or graft survival. Identifying the underlying pathophysiology and subsequent individualization of treatment goals are important for improving long-term patient and graft outcomes in these patients.

Three cost-utility analyses of screening for intracranial hemorrhage in neonates with hemophilia.

BACKGROUND: Intracranial hemorrhage (ICH) in the newborn period is a potential cause of serious morbidity and mortality in individuals with hemophilia. The incidence of ICH is estimated to be 2% to 4%; however, depending on the mode of delivery, it may be considerably higher. Considering the varying sensitivities and costs of various imaging modalities, there remains controversy surrounding universal cranial imaging. Cost-utility analysis is the ideal tool to display the consequences of a decision made. METHODS: We constructed a decision tree to evaluate the direct and indirect costs, possible outcomes, and probabilities of ICH in neonates with hemophilia. We created 3 decision analysis models to evaluate the cost-utility of different screening modalities for ICH: ultrasound, computed tomography, and magnetic resonance imaging. Within each model, 3 different strategies were compared: screen all neonates; screen only neonates born by instrumented delivery; and not screen any neonates. A societal perspective was used for all models. The base case models were later reanalyzed in sensitivity analysis to account for uncertainties. RESULTS: Total costs for screening all neonates, screening only neonates born by instrumented delivery, and not screening any neonates were $9501, $9297, and $9347, respectively, for US, and $9761, $9351, and $9353, respectively, for CT. Screening instrumented deliveries using MRI had an incremental cost-effectiveness ratio of $12,440. CONCLUSIONS: Screening newborns born by an instrumented delivery appears to be the most cost-effective strategy irrespective of the imaging modality. Subsequent studies will require a longer time frame to factor in possible late effects of radiation, anesthesia, and the high cost of factor replacement and hospital admission.

Behavioral cues to expand a pain model of the cognitively impaired elderly in long-term care.

BACKGROUND: The purpose of this study was to determine the relationship between hypothesized pain behaviors in the elderly and a measurement model of pain derived from the Minimum Data Set-Resident Assessment Instrument (MDS-RAI) 2.0 items. METHODS: This work included a longitudinal cohort recruited from Medicare-certified longterm care facilities across the United States. MDS data were collected from 52,996 residents (mean age 83.7 years). Structural equation modeling was used to build a measurement model of pain to test correlations between indicators and the fit of the model by cognitive status. The model evaluates the theoretical constructs of pain to improve how pain is assessed and detected within cognitive levels. RESULTS: Using pain frequency and intensity as the only indicators of pain, the overall prevalence of pain was 31.2%; however, analysis by cognitive status showed that 47.7% of the intact group was in pain, while only 18.2% of the severely, 29.4% of the moderately, and 39.6% of the mildly cognitively impaired groups were experiencing pain. This finding supports previous research indicating that pain is potentially under-reported in severely cognitively impaired elderly nursing home residents. With adjustments to the measurement model, a revised format containing affective, behavioral, and inferred pain indicates a better fit of the data to include these domains, as a more complete measure of the pain construct. CONCLUSION: Pain has a significant effect on quality of life and long-term health outcomes in nursing home residents. Patients most at risk are those with mild to severe cognitive decline, or those unable to report pain verbally. Nursing homes are under great scrutiny to maintain standards of care and provide uniform high-quality care outcomes. Existing data from federally required resident surveys can serve as a valuable tool to identify indicators of pain and trends in care. Great responsibility lies in ensuring pain is included and monitored as a quality measure in long-term care, especially for residents unable to communicate their pain verbally.

Market turbulence creates financing opportunity.

The flight to high-quality assets resulting from Standard & Poor's downgrade of the U.S. government's credit rating has dropped the yield on U.S. Treasury securities as investors have sought refuge amid uncertain market conditions. Consequently, hospitals can now obtain mortgage insurance from the U.S. government to finance expansions and refinance their debt with GNMA securities at taxable interest rates that are often more favorable than tax-exempt bond fixed rates. Because GNMA certificates can be sold in a forward purchase transaction that locks in a fixed interest rate while avoiding payment of interest until construction funds are disbursed, they can help avoid the effects of negative arbitrage.

Assessment of bisphenol A released from reusable plastic, aluminium and stainless steel water bottles.

Bisphenol A (BPA) is a ubiquitous high volume industrial chemical that is an estrogen and an environmental endocrine disrupting chemical. Bisphenol A is used extensively in the production of consumer goods, polycarbonate plastics, epoxy resins and coatings used to line metallic food and beverage cans. There is great concern regarding the possible harmful effects from exposures that result from BPA leaching into foods and beverages from packaging or storage containers. The objective of this study was to independently assess whether BPA contamination of water was occurring from different types of reusable drinking bottles marketed as alternatives to BPA-containing polycarbonate plastics. Using a sensitive and quantitative BPA-specific competitive enzyme-linked immunosorbent assay we evaluated whether BPA migrated into water stored in polycarbonate or copolyester plastic bottles, and different lined or unlined metallic reusable water bottles. At room temperature the concentration of BPA migrating from polycarbonate bottles ranged from 0.2 to 0.3 mg L⁻¹. Under identical conditions BPA migration from aluminium bottles lined with epoxy-based resins was variable depending on manufacturer ranging from 0.08 to 1.9 mg L⁻¹. Boiling water significantly increased migration of BPA from the epoxy lined bottles. No detectable BPA contamination was observed in water stored in bottles made from Tritan™ copolyester plastic, uncoated stainless steel, or aluminium lined with EcoCare™. The results from this study demonstrate that when used according to manufacturers' recommendations reusable water bottles constructed from "BPA-free" alternative materials are suitable for consumption of beverages free of BPA contamination.

A cost-effectiveness analysis of coagulation testing prior to tonsillectomy and adenoidectomy in children.

BACKGROUND: The American Society of Pediatric Otolaryngology recommends pre-operative coagulation testing only when indicated by history or physical exam. Nevertheless, many surgeons test all children scheduled for tonsillectomy and/or adenoidectomy (T&A). Studies of pre-operative screening have had conflicting results. A decision analysis model was constructed to address the costs and health outcome states of pre-operative screening strategies in children. PROCEDURE: A 14-day Markov model evaluated three strategies: (1) test all children for coagulation disorders; (2) test only those children with a pertinent history; and (3) perform no pre-operative testing. A literature search and a review of national databases estimated probabilities, costs, and utility data. Parameters then were varied widely in sensitivity analyses. Using a societal perspective and a cycle length of 1 day, we compared the strategies based on total costs and quality-adjusted life years (QALYs). RESULTS: Total costs for the strategies were $3,200 for testing all children, $3,083 for testing only those with a history finding, and $3,077 for not testing. Total utilities were 0.02579, 0.02654, and 0.02659 QALYs, respectively. Cost-effectiveness ratios were most sensitive to variation in the cost of post-operative care and the probability of post-operative bleeding. The strategy of not testing was dominant in all sensitivity analyses. CONCLUSIONS: Our results demonstrate that not performing preoperative testing is the most cost-effective strategy. This was persistent in sensitivity analyses, indicating that the model was robust. These data may be helpful to institutions and organizations to formulate policies regarding pre-operative coagulation for children without previous diagnoses of bleeding disorders.

Assessment and management of chronic pain in the older adult.

OBJECTIVE: To review the assessment and recommended management of mild to moderate chronic pain in the older adult. DATA SOURCES: Medline search using the terms pain, older adult, and analgesics, current national guidelines, and authors' case experiences. DATA SYNTHESIS: Assessing pain in cognitively intact and impaired older adults is essential to safe use of psychoactive medications. Following the guidelines of the American Geriatrics Society for persistent pain in the older adult provides guidance to the safe use of analgesics and other psychoactive drugs. Dosing of acetaminophen should be limited to avoid liver toxicity, and topical analgesics are preferred for focal pain. Full-dose nonsteroidal anti-inflammatory drugs should not be used for more than short periods, in order to avoid gastrointestinal, renal, and cardiovascular complications. Potentially inappropriate opioid analgesics and safer alternatives are encouraged. A description of other psychoactive medications for neuropathic pain and the role of vitamin D and depression in chronic pain is provided. CONCLUSION: The assessment of pain and use of analgesics in the older adult should benefit and not increase drug-related morbidity and mortality.

Medication interventions for fall prevention in the older adult.

OBJECTIVE: To review fall epidemiology, risk factors, assessments and intervention methods, and outcomes in order to provide guidance to pharmacists. DATA SOURCES: Recently published articles listed in Medline and resources on the Agency for Healthcare Research and Quality website (www.ahrq.gov) identified using the search terms falls, medications and falls, fall risk factors, and falls interventions and outcomes; personal data in preparation for publication consideration by the authors; and bibliographies from gathered articles. DATA SYNTHESIS: Falls may result from multiple risk factors that should be considered to both prevent falls and intervene when a fall has occurred. Careful consideration of the total psychoactive drug load, especially psychotropic drugs, and well-planned recommendations for tapering, discontinuing, and/or replacing drugs implicated in increasing fall risk are presented. A fall risk assessment method that incorporates fall history and risk factors, current disease states and conditions, and medications that may increase fall risk is provided. Two cases with interventions and outcomes are detailed. Because anemia may increase fall risk, adequate assessment of the cause(s) of anemia and conservative recommendations to correct it may decrease fall risk. Adequate vitamin D and calcium intake also may be essential to both decrease falls and fall-related fracture risk. Suggested alternatives and tapering for drugs implicated in increasing falls are considered. Osteoporosis risk assessment is a further area requiring delineation for possible pharmacist assistance to the patient and prescriber to reduce the risk of both fall-related and nontrauma fractures. Interventions to change medications may reduce falls by up to 70%. Additional fall-related resources on the Internet are provided. CONCLUSION: Pharmacists can play an important role by identifying patients who may have fall risk factors and history and by providing information for drug changes that may reduce fall risk.

Assessment of psychotropic and psychoactive drug loads and falls in nursing facility residents.

OBJECTIVE: To determine if there were any differences in fall risk and actual falls between those who were prescribed and those who were not prescribed psychotropic and psychoactive medications in a skilled nursing facility. DESIGN: An observational, retrospective cohort study of prospective patient data in a skilled nursing facility. SETTING: A public skilled nursing facility of more than 100 beds. PATIENTS: Patient charts and consultant pharmacists' drug regimen review monthly report records for 177 patients who were residents for 30 or more days over a 19-month period during 1996-1997 were tabulated. INTERVENTIONS: A fall risk using an assessment method that incorporated patient fall history, conditions, diseases, and medications associated with falls was performed on each resident. MAIN OUTCOME MEASURES: Patient demographics, medication usage, fall risk, and fall occurrences. RESULTS: Falls occurred in 107 of 177 (60.5%) residents over the study period. There were 428 documented falls. Fall rates appeared to be directly related to the number of psychotropic drugs, but not other psychoactive medications, until two or more were used concurrently. CONCLUSIONS: Preliminary evidence suggests multiple psychotropic and psychoactive drugs may increase the risk of falls in a skilled nursing facility in proportion to the total load of these agents. Minimization of inappropriate prescribing of psychotropic and psychoactive medications in elderly nursing facility residents, as mandated by current federal guidelines, may affect the risk of falls in nursing facility patients.

Depressive symptoms in older people predict nursing home admission.

OBJECTIVES: To evaluate the power of several self-reported depressive symptoms to predict nursing home admission (NHA). DESIGN: A Cox proportional hazards model was used to estimate the risk of NHA. SETTING: Data were from the Health Outcomes Survey (a national random sample of 137,000 Medicare + Choice enrollees aged 65 and older), the Nursing Home Minimum Data Set, and the Medicare Enrollment Database. PARTICIPANTS: Medicare beneficiaries aged 65 and older enrolled in a Medicare Managed Care Plan who were self-respondents to the questionnaire and were not institutionalized at the time of the survey. MEASUREMENTS: Variables were self-reported functional status, chronic health conditions, demographics, and several mood-related questions. RESULTS: After controlling for age, race, sex, marital status, home ownership, functional status, and comorbid conditions, individuals who identified themselves as feeling sad or depressed much of the time over the previous year were at significantly higher risk of NHA. CONCLUSION: A single question about depressive symptoms can be used to identify individuals at higher risk of NHA. There may be benefit from better screening and treatment of depression in community-based older people. Depression and social support may be linked. This study was targeted and did not attempt to explain everything that affects NHA. Investigation of the relationship between social support, depression, and NHA should be considered in future research.

Pharmacist interventions in geriatric nursing facility NSAID therapy: a one-year follow-up study of costs and outcomes.

OBJECTIVES: To document costs and outcomes occurring with acceptance or rejection of ongoing pharmacists' interventions regarding therapy with a nonsteroidal anti-inflammatory drug (NSAID) versus acetaminophen (APAP) therapy in treating osteoarthritis in a long-term care facility in the sixth year of observation. DESIGN: A nonrandomized observational prospective cohort study with all patients resident for 30 or more days over the 12-month study period receiving NSAID or APAP therapy for osteoarthritis. SETTING: A skilled nursing facility with more than 100 beds. PATIENTS: All patients had a monthly drug regimen review, receiving full-dose NSAIDs (not low-dose aspirin alone) on a continuous basis, and were selected for intervention. A control group of patients receiving APAP on a continuous basis also was selected for comparison of outcomes. INTERVENTIONS: Patients receiving NSAIDs had (1) periodic hemoglobin and hematocrit determinations; (2) physical assessment of lower eyelid, nailbed, and stool color; (3) and a recommendation to replace NSAID with APAP or to add gastroprotective pharmacotherapy if the NSAID was continued. Patients not receiving an NSAID for osteoarthritis and continuously taking APAP served as a control group. MAIN OUTCOMES MEASURES: Cost-analysis calculations were performed for existing regimens versus cost savings that would be experienced with recommended pharmacotherapeutic interventions. RESULTS: Fourteen intervention subjects and sixteen control patients were identified. In the three patients for whom the pharmacist's recommendations were accepted within three months (11 NSAID-use months), there were three substitutions of APAP therapy observed over an additional 26 patient-months. Five of 11 patients in the NSAID group for whom pharmacists' recommendations were rejected developed gastrointestional (GI) bleeding, necessitating six hospitalizations. Two of these patients died over the study period. No group for whom APAP was accepted nor control-group patients experienced suspected GI bleeding. Total costs of the control group analgesic therapy was $756.74, or $47.30 per patient. Cost savings for APAP substitution in the intervention rejection group would exceed $91,000, while cost savings with the addition of hemoglobin and hematocrit determinations would exceed $84,200. Cost savings from addition of gastroprotectives to the NSAID would have been misoprostol, $73,000; omeprazole, $71,400. CONCLUSIONS: Refusal to accept pharmacists' intervention recommendations regarding alternatives to NSAID pharmacotherapy in this nursing facility population is associated with sustained and considerable costs, morbidity, and mortality.

Sadness predicts death in older people.

OBJECTIVE: To determine if a question about symptoms of depression in a mail survey predicts mortality after adjusting for a large number of covariates. DESIGN: National cross-sectional survey of 141,589 enrollees in Medicare, age 65 and older. Analyses used multivariate logistic regression models with death as the outcome. RESULTS: Response to a question about sadness or anhedonia was associated with death in 2 years (OR = 1.32; 95% CI = 1.2, 1.4). Results were consistent across age, gender, and presence/absence of known heart disease. Other responses associated with death were older age, male gender, and self-reported cancers, shortness of breath, heart failure, smoking, and other characteristics. Higher education and being married appeared to protect from death. DISCUSSION: A single survey question about feelings of sadness or anhedonia is predictive of death in 2 years.