Guiding safer risperidone prescribing in Alzheimer's disease with therapeutic drug monitoring.

Previous analysis of pharmacokinetic data on risperidone-treated patients with dementia predicted that 20% had concentration-to-dose (C/D) ratios of the active moiety (risperidone and 9-hydroxy(OH)-risperidone) above 14 ng/mL per mg/day, which were in turn associated with a greater risk of extrapyramidal side effects. This study aimed to further explore risperidone pharmacokinetics in a second dataset. Nonlinear mixed effects modelling, using a Bayesian approach, was applied to data from a randomized controlled trial of risperidone in people with dementia. Covariates included age and glomerular filtration rate (GFR). Age had a significant effect on risperidone clearance (ß = -1.5) and GFR on 9-OH-risperidone clearance (ß = 0.2). The model predicted that 26.2% (95% confidence interval 18.6-32.6%) had C/D ratios above 14 ng/mL per mg/day. These findings confirm the importance of age-related risperidone dose adjustments and argue strongly for therapeutic drug monitoring in the initial stages of treatment to identify those at greatest risk of toxicity.

International trade resilience and the Covid-19 pandemic.

The Covid-19 pandemic represents a low-probability, high-impact systemic risk that has severely disrupted international trade, reshaping the patterns of globalization. Drawing from the concept of supply chain resilience, which involves both the ability of a system to withstand an impact (robustness) and recover from it (responsiveness), we investigate country-level trade resilience during the 1st wave of the pandemic. By employing Fuzzy-set Qualitative Comparative Analysis (fsQCA), we identify configurations of country-level factors, i.e., country profiles, based on their effectiveness in engendering trade resilience. These factors include social and economic globalization, logistics performance, healthcare preparedness, national government response, and income level. The results show how these factors coalesced to strengthen (or weaken) international trade resilience, contributing to a holistic understanding of the impact of the pandemic on international trade. The findings inform the post-Covid-19 debate on international trade, with implications for managers and policymakers.

Overview of School-Based Telehealth Network Grant Program Services Delivered to Students in Rural Schools.

Telehealth can expand and enhance access to school-based health care, but its use has been relatively limited. Recognizing that school-based health care is still not reaching many students, the Health Resources and Services Administration (HRSA) funded the School Based Telehealth Network Grant Program to expand telehealth in rural school-based settings to help to increase the availability and use of these services. The 19 grantees delivered telehealth to over 200 schools across 17 states, choosing which services they would deliver and how. Looking across the services, these fell into three categories - primary/urgent care, behavioral health, and other more specialized services. The majority of grantees offered multiple telehealth services with the combination of behavioral health and primary/urgent care the most common. The current study adds to the literature by elucidating that telehealth in schools can address multiple clinical conditions through separate services even though doing so involves using various combinations of clinicians providing different services.

Multidisciplinary Care for Critical Limb Ischemia: Current Gaps and Opportunities for Improvement.

Critical limb ischemia (CLI), defined as ischemic rest pain or nonhealing ulceration due to arterial insufficiency, represents the most severe and limb-threatening manifestation of peripheral artery disease. A major challenge in the optimal treatment of CLI is that multiple specialties participate in the care of this complex patient population. As a result, the care of patients with CLI is often fragmented, and multidisciplinary societal guidelines have not focused specifically on the care of patients with CLI. Furthermore, multidisciplinary care has the potential to improve patient outcomes, as no single medical specialty addresses all the facets of care necessary to reduce cardiovascular and limb-related morbidity in this complex patient population. This review identifies current gaps in the multidisciplinary care of patients with CLI, with a goal toward increasing disease recognition and timely referral, defining important components of CLI treatment teams, establishing options for revascularization strategies, and identifying best practices for wound care post-revascularization.

Interactions of social, terrestrial, and marine sub-systems in the Galapagos Islands, Ecuador.

Galapagos is often cited as an example of the conflicts that are emerging between resource conservation and economic development in island ecosystems, as the pressures associated with tourism threaten nature, including the iconic and emblematic species, unique terrestrial landscapes, and special marine environments. In this paper, two projects are described that rely upon dynamic systems models and agent-based models to examine human-environment interactions. We use a theoretical context rooted in complexity theory to guide the development of our models that are linked to social-ecological dynamics. The goal of this paper is to describe key elements, relationships, and processes to inform and enhance our understanding of human-environment interactions in the Galapagos Islands of Ecuador. By formalizing our knowledge of how systems operate and the manner in which key elements are linked in coupled human-natural systems, we specify rules, relationships, and rates of exchange between social and ecological features derived through statistical functions and/or functions specified in theory or practice. The processes described in our models also have practical applications in that they emphasize how political policies generate different human responses and model outcomes, many detrimental to the social-ecological sustainability of the Galapagos Islands.

Enhancing the prediction of acute kidney injury risk after percutaneous coronary intervention using machine learning techniques: A retrospective cohort study.

BACKGROUND: The current acute kidney injury (AKI) risk prediction model for patients undergoing percutaneous coronary intervention (PCI) from the American College of Cardiology (ACC) National Cardiovascular Data Registry (NCDR) employed regression techniques. This study aimed to evaluate whether models using machine learning techniques could significantly improve AKI risk prediction after PCI. METHODS AND FINDINGS: We used the same cohort and candidate variables used to develop the current NCDR CathPCI Registry AKI model, including 947,091 patients who underwent PCI procedures between June 1, 2009, and June 30, 2011. The mean age of these patients was 64.8 years, and 32.8% were women, with a total of 69,826 (7.4%) AKI events. We replicated the current AKI model as the baseline model and compared it with a series of new models. Temporal validation was performed using data from 970,869 patients undergoing PCIs between July 1, 2016, and March 31, 2017, with a mean age of 65.7 years; 31.9% were women, and 72,954 (7.5%) had AKI events. Each model was derived by implementing one of two strategies for preprocessing candidate variables (preselecting and transforming candidate variables or using all candidate variables in their original forms), one of three variable-selection methods (stepwise backward selection, lasso regularization, or permutation-based selection), and one of two methods to model the relationship between variables and outcome (logistic regression or gradient descent boosting). The cohort was divided into different training (70%) and test (30%) sets using 100 different random splits, and the performance of the models was evaluated internally in the test sets. The best model, according to the internal evaluation, was derived by using all available candidate variables in their original form, permutation-based variable selection, and gradient descent boosting. Compared with the baseline model that uses 11 variables, the best model used 13 variables and achieved a significantly better area under the receiver operating characteristic curve (AUC) of 0.752 (95% confidence interval [CI] 0.749-0.754) versus 0.711 (95% CI 0.708-0.714), a significantly better Brier score of 0.0617 (95% CI 0.0615-0.0618) versus 0.0636 (95% CI 0.0634-0.0638), and a better calibration slope of observed versus predicted rate of 1.008 (95% CI 0.988-1.028) versus 1.036 (95% CI 1.015-1.056). The best model also had a significantly wider predictive range (25.3% versus 21.6%, p < 0.001) and was more accurate in stratifying AKI risk for patients. Evaluated on a more contemporary CathPCI cohort (July 1, 2015-March 31, 2017), the best model consistently achieved significantly better performance than the baseline model in AUC (0.785 versus 0.753), Brier score (0.0610 versus 0.0627), calibration slope (1.003 versus 1.062), and predictive range (29.4% versus 26.2%). The current study does not address implementation for risk calculation at the point of care, and potential challenges include the availability and accessibility of the predictors. CONCLUSIONS: Machine learning techniques and data-driven approaches resulted in improved prediction of AKI risk after PCI. The results support the potential of these techniques for improving risk prediction models and identification of patients who may benefit from risk-mitigation strategies.

[Trichomycosis (trichobacteriosis) capitis in an infant: Microbiological, dermoscopic and ultrastructural features]. / Tricomicosis (tricobacteriosis) en un infante: Aspectos microbiológicos, dermatoscópicos y ultraestructurales.

Trichomycosis is a superficial infection caused by Corynebacterium flavescens, which regularly affects axillary, and to a a lesser extent, pubic, scrotal and intergluteal, and exceptionally, head hairs or trichomycosis capitis (TC). This condition is characterised by the formation of bacterial nodules. Clinically, it can be confused with white piedra or pediculosis. The diagnosis is made by microscopic and dermoscopic observation and confirmed by culture. OBJECTIVE: To present a case of TC in an infant and illustrate the microscopic, dermoscopic, and ultrastructural characteristics. CLINICAL CASE: A 6 month-old boy, otherwise healthy, with multiple yellowish concretions on the hairs of the head. TC was confirmed by yellow fluorescence with Wood’s light; white-yellowish beads, like “rosaries of crystalline stones’’ were observed on dermoscopy, direct examination showed bacterial masses, and Corynebacterium flavescens was identified by culture. A superficial infection, without perforation of the hairs, was confirmed by electron microscopy. Treatment with fusidic acid for 3 weeks achieved a clinical and microbiological cure. CONCLUSION: TC is a rare condition that affects children, and tends to be mistaken for other diseases of the hair, such as pediculosis and mycotic infections.

Impact of Glycoprotein IIb/IIIa Inhibitors Use on Outcomes After Lower Extremity Endovascular Interventions From Nationwide Inpatient Sample (2006-2011).

OBJECTIVE: The aim of our study was to study the impact of glycoprotein IIb/IIIa inhibitors (GPI) on in-hospital outcomes. BACKGROUND: There is paucity of data regarding the impact of GPI on the outcomes following peripheral endovascular interventions. METHODS: The study cohort was derived from Healthcare Cost and Utilization Project (HCUP) Nationwide Inpatient Sample (NIS) database between the years 2006 and 2011. Peripheral endovascular interventions and GPI utilization were identified using appropriate ICD-9 Diagnostic and procedural codes. Two-level hierarchical multivariate mixed models were created. The study outcomes were: primary (in-hospital mortality and amputation studied separately) and secondary (composite of in-hospital mortality and postprocedural complications). Hospitalization costs were also assessed. RESULTS: GPI utilization (OR, 95% CI, P-value) was independently predictive of lower amputation rates (0.36, 0.27-0.49, <0.001). There was no significant difference in terms of in-hospital mortality (0.59, 0.31-1.14, P 0.117), although GPI use predicted worse secondary outcomes (1.23, 1.03-1.47, 0.023). Following propensity matching, the amputation rate was lower (3.2% vs. 8%, P < 0.001), while hospitalization costs were higher in the cohort that received GPI ($21,091 ± 404 vs. 19,407 ± 133, P < 0.001). CONCLUSIONS: Multivariate analysis revealed GPI use in peripheral endovascular interventions to be suggestive of an increase in composite end-point of in-hospital mortality and postprocedural complications, no impact on in-hospital mortality alone, significantly lower rate of amputation, and increase in hospitalization costs. © 2016 Wiley Periodicals, Inc.

Intravascular Ultrasound in Lower Extremity Peripheral Vascular Interventions: Variation in Utilization and Impact on In-Hospital Outcomes From the Nationwide Inpatient Sample (2006-2011).

PURPOSE: To examine the impact of intravascular ultrasound (IVUS) utilization during lower limb endovascular interventions as regards postprocedural complications and amputation. METHODS: The study cohort was derived from the Healthcare Cost and Utilization Project Nationwide Inpatient Sample database between the years 2006 and 2011. Peripheral endovascular interventions were identified using appropriate ICD-9 procedure codes. Two-level hierarchical multivariate mixed models were created. The co-primary outcomes were in-hospital mortality and amputation; the secondary outcome was postprocedural complications. Model results are given as the odds ratio (OR) and 95% confidence interval (CI). Hospitalization costs were also assessed. RESULTS: Overall, among the 92,714 patients extracted from the database during the observation period, IVUS was used in 1299 (1.4%) patients. IVUS utilization during lower extremity peripheral vascular procedures was independently predictive of a lower rate of postprocedural complications (OR 0.80, 95% CI 0.66 to 0.99, p=0.037) as well as lower amputation rates (OR 0.59, 95% CI 0.45 to 0.77, p<0.001) without any significant impact on in-hospital mortality. Multivariate analysis also revealed IVUS utilization to be predictive of a nonsignificant increase in hospitalization costs ($1333, 95% CI -$167 to +$2833, p=0.082). CONCLUSION: IVUS use during lower limb endovascular interventions is predictive of lower postprocedural complication and amputation rates with a nonsignificant increase in hospitalization costs.

Carotid artery stenting versus carotid endarterectomy.

Stroke remains a significant contributor to morbidity and mortality in developed countries. Carotid artery stenosis is a major cause of stroke. Advances in medical therapy, surgical technique and endovascular maturation has resulted in options for the treatment of carotid stenosis. Here, we present a review of carotid artery stenting and carotid endarterectomy as it applies to trials comparing and contrasting the two treatment options. We also explore the intricacies surrounding reimbursement of these treatment strategies in the USA.

Superficial Mycoses Associated with Diaper Dermatitis.

Diapers create particular conditions of moisture and friction, and with urine and feces come increased pH and irritating enzymes (lipases and proteases). Fungi can take advantage of all these factors. Candida yeasts, especially C. albicans, are responsible for the most frequent secondary infections and are isolated in more than 80 % of cases. Correct diagnosis is important for ensuring the correct prescription of topical antimycotics. Nystatin, imidazoles and ciclopirox are effective. It is important to realize there are resistant strains. Dermatophytes can infect the diaper area, with the most common agent being Epidermophyton floccosum. The clinical characteristics of dermatophytosis are different from those of candidiasis, and it can be diagnosed and treated simply. Malassezia yeasts can aggravate conditions affecting the diaper area, such as seborrheic dermatitis, atopic dermatitis, and inverse psoriasis. Additional treatment is recommended in this case, because they usually involve complement activation and increased specific IgE levels. Erythrasma is a pseudomycosis that is indistinguishable from candidiasis and may also occur in large skin folds. It is treated with topical antibacterial products and some antimycotics.

Local delivery of paclitaxel in the treatment of peripheral arterial disease.

BACKGROUND: Despite advancements from balloon angioplasty to drug-eluting stents, primary patency rates after endovascular revascularization of peripheral artery disease have remained inferior compared to surgery. Endovascular revascularization has been limited by restenosis and mechanical stent failure. Thus, there is increased research into other nonstent-based local drug delivery modalities, which can provide an active drug to inhibit restenosis focally and avoid the risk of systemic adverse effects. METHODS: This review will summarize the unique properties of paclitaxel and studies on paclitaxel local delivery for the treatment of peripheral artery disease. A MEDLINE search for relevant peer-reviewed scientific literature published in English was conducted. Search terms included but were not limited to paclitaxel pharmacodynamics, paclitaxel local drug delivery, and drug eluting balloons, with a focus on the use of paclitaxel in the context of coronary and peripheral vascular disease. RESULTS: The primary search produced 182 results of which 51 papers were relevant. Of the 51 relevant papers, 27 were original research papers and 24 were either review papers, commentary or opinion papers. CONCLUSIONS: Paclitaxel has several chemical properties, which make it ideal for local drug delivery including its hydrophobicity, ability to concentrate into the arterial intima layer and prolonged effect on cells even after brief exposure periods. Local delivery of paclitaxel via injection catheters, balloon catheters and coated balloons has shown encouraging results in terms of efficacy and safety in small-scale animal and clinical studies. Additional preclinical and clinical studies are needed to determine the long-term efficacy and safety of these treatments in humans.

Dysautonomic responses during percutaneous carotid intervention: principles of physiology and management.

Percutaneous carotid artery stenting (CAS) has emerged as a less invasive alternative to carotid endarterectomy for the treatment of carotid atherosclerotic disease. The main risk of CAS is the occurrence of neuro-vascular complications; however, carotid artery stenting-related dysautonomia (CAS-D) (hypertension, hypotension, and bradycardia) is the most frequently reported problem occurring in the periprocedural period. Alterations in autonomic homeostasis result from baroreceptor stimulation, which occurs particularly at the time of balloon inflation in the region of the carotid sinus. The response can be profound enough to induce asystole or even complete cessation of postganglionic sympathetic nerve activity. Frequency and factors predisposing a patient to CAS-D have been investigated in several studies; however, there are significant discrepancies in results among reports. Lack of consistent findings may arise from using different methods and definitions, as well as other factors discussed in detail in this review. Furthermore, a correlation of CAS-D with short and long-term outcomes has been investigated only in small and mostly retrospective studies, explaining why its prognostic significance remains uncertain. In this manuscript, we have focused on risk factors, pathophysiology and management of periprocedural autonomic dysfunction. As there is no standardized approach to the treatment of CAS-D, we present an algorithm for the periprocedural management of patients undergoing CAS. The proposed algorithm was developed based on our procedural experience as well as data from the available literature. The Yale Algorithm was successfully implemented at our institution and we are currently collecting data for short- and long-term safety. © 2014 Wiley Periodicals, Inc.

A validated agent-based model to study the spatial and temporal heterogeneities of malaria incidence in the rainforest environment.

BACKGROUND: The Amazon environment has been exposed in the last decades to radical changes that have been accompanied by a remarkable rise of both Plasmodium falciparum and Plasmodium vivax malaria. The malaria transmission process is highly influenced by factors such as spatial and temporal heterogeneities of the environment and individual-based characteristics of mosquitoes and humans populations. All these determinant factors can be simulated effectively trough agent-based models. METHODS: This paper presents a validated agent-based model of local-scale malaria transmission. The model reproduces the environment of a typical riverine village in the northern Peruvian Amazon, where the malaria transmission is highly seasonal and apparently associated with flooding of large areas caused by the neighbouring river. Agents representing humans, mosquitoes and the two species of Plasmodium (P. falciparum and P. vivax) are simulated in a spatially explicit representation of the environment around the village. The model environment includes: climate, people houses positions and elevation. A representation of changes in the mosquito breeding areas extension caused by the river flooding is also included in the simulation environment. RESULTS: A calibration process was carried out to reproduce the variations of the malaria monthly incidence over a period of 3 years. The calibrated model is also able to reproduce the spatial heterogeneities of local scale malaria transmission. A "what if" eradication strategy scenario is proposed: if the mosquito breeding sites are eliminated through mosquito larva habitat management in a buffer area extended at least 200 m around the village, the malaria transmission is eradicated from the village. CONCLUSIONS: The use of agent-based models can reproduce effectively the spatiotemporal variations of the malaria transmission in a low endemicity environment dominated by river floodings like in the Amazon.

Role of access to parks and markets with anthropometric measurements, biological markers, and a healthy lifestyle.

BACKGROUND: This study examined the association between access to urban green spaces and markets with anthropometric measurements, biological markers, sociodemographic, and healthy lifestyle. METHODS: Geographic information systems were used to establish a correlation between environmental features and cardiovascular risk parameters. A total number of 832 (age range 18-74 years) individuals were selected for this study. RESULTS: Body mass index was significantly and positively related to the distance to parks (ρ = 0.079, p < 0.05), but negatively related to the distance to markets (ρ = -0.125, p < 0.05). In addition, waist circumference was similar and positively related to distance to parks (ρ = 0.097, p < 0.05) and negatively related to distance to markets (ρ = -0.092, p < 0.05). With respect to biochemical parameters, when there was an increase in the distance to markets, high-density lipoprotein cholesterol increased and glycemia decreased. CONCLUSION: The results of this study suggest the importance of the role of environmental factors such as parks and markets in the development of cardiovascular risk.

Mucormycosis in children: a study of 22 cases in a Mexican hospital.

We present a single-centre, retrospective study (1985-2012) of 22 cases of mucormycosis in children. A total of 158 mucormycosis cases were identified, of which 22 (13.96%) were children. The mean age of the children was 10.3 years (range: 6 months-18 years), and 59% of the infections occurred in males. The rhinocerebral form was the main clinical presentation (77.27%), followed by the primary cutaneous and pulmonary patterns. The major underlying predisposing factors were diabetes mellitus in 68.18% of the patients and haematologic diseases in 27.7% of the patients. The cases were diagnosed by mycological tests, with positive cultures in 95.4% of the patients. Rhizopus arrhizus was the foremost aetiologic agent in 13/22 cases (59.1%). In 21 cultures, the aetiologic agents were identified morphologically and by molecular identification. In 10 cultures, the internal transcribed spacer region of the ribosomal DNA was sequenced. Clinical cure and mycological cure were achieved in 27.3% cases, which were managed with amphotericin B deoxycholate and by treatment of the underlying conditions.

Carotid stent deformation: sonographic findings and CT correlation.

Carotid artery dissection is a rare but potentially serious complication of endovascular procedures in the carotid arteries. Stent deformation or incomplete expansion may occur following endovascular repair of an iatrogenic carotid artery dissection and may mimic stent fracture. We report an unusual case of deformation of a common carotid artery open cell design stent following endovascular repair of an iatrogenic dissection, which resulted in persistent blood flow between the stent and the wall of the common carotid artery. Sonographic features are described and correlation with intravascular ultrasound and CT is provided.

The atlas of unburnable oil for supply-side climate policies.

To limit the increase in global mean temperature to 1.5 °C, CO2 emissions must be drastically reduced. Accordingly, approximately 97%, 81%, and 71% of existing coal and conventional gas and oil resources, respectively, need to remain unburned. This article develops an integrated spatial assessment model based on estimates and locations of conventional oil resources and socio-environmental criteria to construct a global atlas of unburnable oil. The results show that biodiversity hotspots, richness centres of endemic species, natural protected areas, urban areas, and the territories of Indigenous Peoples in voluntary isolation coincide with 609 gigabarrels (Gbbl) of conventional oil resources. Since 1524 Gbbl of conventional oil resources are required to be left untapped in order to keep global warming under 1.5 °C, all of the above-mentioned socio-environmentally sensitive areas can be kept entirely off-limits to oil extraction. The model provides spatial guidelines to select unburnable fossil fuels resources while enhancing collateral socio-environmental benefits.

Study protocol: improving response to malaria in the Amazon through identification of inter-community networks and human mobility in border regions of Ecuador, Peru and Brazil.

INTRODUCTION: Understanding human mobility's role in malaria transmission is critical to successful control and elimination. However, common approaches to measuring mobility are ill-equipped for remote regions such as the Amazon. This study develops a network survey to quantify the effect of community connectivity and mobility on malaria transmission. METHODS: We measure community connectivity across the study area using a respondent driven sampling design among key informants who are at least 18 years of age. 45 initial communities will be selected: 10 in Brazil, 10 in Ecuador and 25 in Peru. Participants will be recruited in each initial node and administered a survey to obtain data on each community's mobility patterns. Survey responses will be ranked and the 2-3 most connected communities will then be selected and surveyed. This process will be repeated for a third round of data collection. Community network matrices will be linked with each country's malaria surveillance system to test the effects of mobility on disease risk. ETHICS AND DISSEMINATION: This study protocol has been approved by the institutional review boards of Duke University (USA), Universidad San Francisco de Quito (Ecuador), Universidad Peruana Cayetano Heredia (Peru) and Universidade Federal Minas Gerais (Brazil). Results will be disseminated in communities by the end of the study.

Carotid revascularization: a systematic review of the evidence.

OBJECTIVE AND BACKGROUND: The aim of this study is to provide an evidence-based review of the periprocedural safety and long-term effectiveness of carotid artery stenting (CAS) compared to carotid endarterectomy (CEA), with particular attention paid to the use of embolic protection devices and patients at high risk for CEA. METHODS: Electronic databases (Ovid Medline, Cochrane central register of controlled trials, Pubmed, and Embase) were searched to identify: (1) randomized controlled trials (RCT) comparing outcomes of CEA and CAS, and (2) prospective clinical trials assessing the safety of CAS in patients at high surgical risk. Pooled incidence rates and one-sided 95% confidence interval for the periprocedural and long-term composite end-point of stroke, myocardial infarction, or death among high surgical risk patients were generated and compared to objective performance criteria (OPC) reported by previous trials. RESULTS: Six RCTs and 14 prospective clinical trials met our search criteria. Selected RCTs showed inconsistency in reported periprocedural and long-term outcome rates. Pooled incidence rates of the periprocedural and long-term composite end-point of stroke, myocardial infarction or death in high surgical risk candidates were 5.59% and 7.92%, respectively. These results were noninferior to selected OPCs (P-value <0.001). CONCLUSIONS: CAS represents a safe and effective stroke prevention strategy in high surgical risk patients when compared with CEA. The inconsistent results from the RCTs and the improved outcomes in the prospective clinical trials are likely related to variability in operator experience, use of embolic protection devices, and patient selection strategies.