The Effects of Applied Local Heat on Transdermal Drug Delivery Systems

Transdermal drug delivery systems have been developed over the past several decades and now include patches for birth control, nicotine addiction, and pain relief. The local application of heat can increase the diffusion coefficient of the drug in the skin and result in faster delivery of the drug and shorter time to reach a steady state concentration of the drug. While this procedure is desirable for some systems where a faster dose will aid in alleviating pain and/or symptoms, it can also be a cause of concern for some drugs. Fentanyl, a chronic pain relief drug, can cause accidental death by overdose. We report herein an analysis of the effects of various heating situations on transdermal fentanyl delivery based upon a model developed using COMSOL Multiphysics. The utilization of such a model allows for the determination of situations which may be potentially dangerous for fentanyl drug users, and enables the development of usage guidelines and safety mechanisms for transdermal delivery systems. Using the computer model, the following cases were simulated: no applied heat, ThermaCare heat pad, fever, and heating blanket. The heating blanket and ThermaCare heat pad simulations showed the most dangerous increases in fentanyl blood concentration above no-heat levels: about 180% and 100%, respectively, over 30 hours; by contrast, the patient fever model reported a 40% increase in fentanyl blood concentration. These simulations demonstrate the dangers of fentanyl transdermal pain patches when skin temperature is increased, and can be used to develop better patient guidelines for patch use and to improve fentanyl transdermal systems. Lastly, this computer model may be used to model other transdermal drug delivery systems for the improvement of patient guidelines and/or the development of new systems, thus decreasing the need for experimentation on subjects

Matrix Microarchitecture and Myosin II Determine Adhesion in 3D Matrices

SummaryBackgroundReports of adhesions in cells growing in 3D vary widely—from nonexistent to very large and elongated—and are often in apparent conflict, due largely to our minimal understanding of the underlying mechanisms that determine 3D cell phenotype. We address this problem directly by systematically identifying mechanisms that determine adhesion in 3D matrices and, from our observations, develop principles widely applicable across 2D and 3D substrates.ResultsWe demonstrate that nonmuscle myosin II activity guides adhesion phenotype in 3D as it does in 2D; however, in contrast to 2D, decreasing bulk matrix stiffness does not necessarily inhibit the formation of elongated adhesions. Even in soft 3D matrices, cells can form large adhesions in areas with appropriate local matrix fiber alignment. We further show that fiber orientation, apart from influencing local stiffness, modulates the available adhesive area and thereby determines adhesion size.ConclusionsThus adhesion in 3D is determined by both myosin activity and the immediate microenvironment of each adhesion, as defined by the local matrix architecture. Important parameters include not only the resistance of the fiber to pulling (i.e., stiffness) but also the orientation and diameter of the fiber itself. These principles not only clarify conflicts in the literature and point to adhesion modulating factors other than stiffness, but also have important implications for tissue engineering and studies of tumor cell invasion

Identification of Violence in the Home - Pediatric and Parental Reports

Objectives: To compare the rates of domestic violence reported by mothers with those identified by physicians, to compare the rates of harsh discipline practices reported by mothers with the rates of abuse identified by physicians, and to examine the relationship between reported domestic violence and harsh discipline practices. Design: Interviews with parents and pediatricians to compare pediatric detection of domestic violence and child abuse with parental reports of domestic violence and harsh discipline practices. Setting: Community-based pediatric practices in the 13-town greater New Haven, Conn, area. Participants: Of the 23 practices invited, 19 agreed to participate. Of the 2006 parents of eligible 4- to 8-year-olds asked to participate, 1886 (94%) completed the Child Behavior Checklist. Of those invited into the interview portion, 1148 (83%) completed the 90-minute in-person interview. Main Outcome Measures: Percentages of cases of domestic violence identified by pediatricians and reported by mothers. Percentages of cases of child abuse detected by pediatricians and percentages of mothers reporting that they have hit their children and left a mark. Results: Pediatricians detected domestic violence in 0.3% of the cases, but parents reported domestic violence in 4.2% (kappa = 0.106 [95% confidence interval, -0.007 to 0.219]). Pediatricians identified physical abuse of children in 0.5% of the cases, while mothers reported hitting their children and leaving a mark in 21.6% (kappa = 0.003 [95% confidence interval, -0.018 to 0.024]). Mothers reporting domestic violence were significantly more likely to report hitting hard enough to leave a mark (relative risk, 1.6 ([95% confidence interval, 1.09-2.38]) compared with those not reporting domestic violence. Physicians identifying domestic violence were not significantly more likely to report child abuse than those not identifying domestic violence. Conclusions: Parents report more cases of violence than pediatricians detect. Pediatricians should ask parents directly about domestic violence and harsh discipline

Does she think she’s supported? Maternal perceptions of their experiences in the neonatal intensive care unit

Parents’ involvement in the care of their infants in the neonatal intensive care unit (NICU) is critically important, leading many NICUs to implement policies and practices of family-centered care (FCC). Analyzing narrative interviews, we examined whether mothers of premature infants who participated in an intervention to help reduce anxiety, stress, and depression felt that their NICU experience reflected four key nursing behaviors previously identified as being necessary to achieving FCC. Fifty-six narratives derived from semi-structured interviews with the mothers were analyzed qualitatively and quantitatively to examine whether the women experienced emotional support, parent empowerment, welcoming environment, and parent education, as well as whether differences in reported experiences were related to sociodemographic factors or maternal coping styles. Overall, the mothers reported more negative than positive experiences with respect to the four behaviors, and those who had negative interactions with the hospital staff felt a sense of disenfranchisement and failure as mothers. Sociodemographic factors and coping styles were significantly associated with the mothers’ perceptions of their experiences, although these relationships were not consistent. Achieving actual FCC in the NICU may require parent-informed evidence-based changes in NICU personnel training and infrastructure

Mixed Method Designs in Implementation Research

This paper describes the application of mixed method designs in implementation research in 22 mental health services research studies published in peer-reviewed journals over the last 5 years. Our analyses revealed 7 different structural arrangements of qualitative and quantitative methods, 5 different functions of mixed methods, and 3 different ways of linking quantitative and qualitative data together. Complexity of design was associated with number of aims or objectives, study context, and phase of implementation examined. The findings provide suggestions for the use of mixed method designs in implementation research

Predicting climate-sensitive water-related disease trends based on health, seasonality and weather data in Fiji

Leptospirosis, typhoid and dengue are three water-related diseases influenced by environmental factors. We examined whether seasonality and rainfall predict reported syndromes associated with leptospirosis, typhoid and dengue in Fiji. Poisson generalised linear models were fitted with s6 early warning, alert and response system (EWARS) syndromic conditions from March 2016 until December 2020, incorporating seasonality, temperature and rainfall. Watery diarrhoea, prolonged fever and suspected dengue displayed seasonal trends with peaks corresponding with the rainy season, while bloody diarrhoea, acute fever with rash and acute jaundice syndrome did not. Seasonality was the most common predictor for watery and bloody diarrhoea, prolonged fever, suspected dengue, and acute fever plus rash in those aged 5 and over, explaining between 0.4 % – 37.8 % of the variation across all conditions. Higher rainfall was the most common predictor for acute fever plus rash and acute jaundice syndrome in children under 5, explaining between 1.0 % – 7.6 % variation across all conditions. Each EWARS syndromic condition case peak was associated with a different rainfall lag, varying between 0 and 11 weeks. The relationships between EWARS, rainfall and seasonality show that it is possible to predict when outbreaks will occur by following seasonality and rainfall. Pre-positioning of diagnostic and treatment resources could then be aligned with seasonality and rainfall peaks to plan and address water-related disease outbreaks

Early-Onset Bipolar Spectrum Disorders: Diagnostic Issues

Since the mid 1990s, early-onset bipolar spectrum disorders (BPSDs) have received increased attention in both the popular press and scholarly press. Rates of diagnosis of BPSD in children and adolescents have increased in inpatient, outpatient, and primary care settings. BPSDs remain difficult to diagnose, particularly in youth. The current diagnostic system makes few modifications to accommodate children and adolescents. Researchers in this area have developed specific BPSD definitions that affect the generalizability of their findings to all youth with BPSD. Despite knowledge gains from the research, BPSDs are still difficult to diagnose because clinicians must: (1) consider the impact of the child’s developmental level on symptom presentation (e.g., normative behavior prevalence, environmental limitations on youth behavior, pubertal status, irritability, symptom duration); (2) weigh associated impairment and course of illness (e.g., neurocognitive functioning, failing to meet full DSM criteria, future impairment); and (3) make decisions about appropriate assessment (differentiating BPSD from medical illnesses, medications, drug use, or other psychiatric diagnoses that might better account for symptoms; comorbid disorders; informant characteristics and assessment measures to use). Research findings concerning these challenges and relevant recommendations are offered. Areas for further research to guide clinicians’ assessment of children with early-onset BPSD are highlighted

The memorialization of southern poor white men's labor in rick bragg's memoir trilogy

This article explores the ways that Rick Bragg memorializes poor white men's labor across his memoir trilogy, examining the tensions that arise as he attempts to bring poor whites into the center of the southern community. I consider the neo-Agrarian strains within his work, as well as Bragg's responses to the globalization of the region. The work addresses the absences within the South's memorial landscape, and questions the extent to which Bragg's work addresses those gaps. © 2012 Cambridge University Press

Improving Clinical Prediction of Bipolar Spectrum Disorders in Youth.

This report evaluates whether classification tree algorithms (CTA) may improve the identification of individuals at risk for bipolar spectrum disorders (BPSD). Analyses used the Longitudinal Assessment of Manic Symptoms (LAMS) cohort (629 youth, 148 with BPSD and 481 without BPSD). Parent ratings of mania symptoms, stressful life events, parenting stress, and parental history of mania were included as risk factors. Comparable overall accuracy was observed for CTA (75.4%) relative to logistic regression (77.6%). However, CTA showed increased sensitivity (0.28 vs. 0.18) at the expense of slightly decreased specificity and positive predictive power. The advantage of CTA algorithms for clinical decision making is demonstrated by the combinations of predictors most useful for altering the probability of BPSD. The 24% sample probability of BPSD was substantially decreased in youth with low screening and baseline parent ratings of mania, negative parental history of mania, and low levels of stressful life events (2%). High screening plus high baseline parent-rated mania nearly doubled the BPSD probability (46%). Future work will benefit from examining additional, powerful predictors, such as alternative data sources (e.g., clinician ratings, neurocognitive test data); these may increase the clinical utility of CTA models further

Development of Alcohol and Drug Use in Youth With Manic Symptoms

This analysis examined alcohol and drug use over a six-year follow-up of children in the Longitudinal Assessment of Manic Symptoms (LAMS) study