Identifying high risk medications causing potential drug-drug interactions in outpatients: A prescription database study based on an online surveillance system.

PubMed

Toivo, T M; Mikkola, J A V; Laine, K; Airaksinen, M

2016-01-01

Drug-drug interactions (DDIs) are a significant cause for adverse drug events (ADEs). DDIs are often predictable and preventable, but their prevention and management require systematic service development. Most DDI studies focus on interaction rates in hospitalized patients. Less is known of DDIs in outpatients, particularly how community pharmacists could contribute to DDI management by applying their surveillance systems for identifying high-risk medications. The study was related to the implementation of the first online DDI surveillance system in Finnish community pharmacies. The goal was to demonstrate how community pharmacies can utilize their prospective surveillance system 1) for identifying high risk medications causing potential DDIs in outpatients, 2) for collaborative service development with local physicians, and 3) for academic risk management research purposes. All DDI alerts given by the online surveillance system were collected during a one-month period in 16 out of 17 University Pharmacy outlets in Finland, covering approximately 10% of the national outpatient prescription volume. The surveillance system was based on the FASS database, which categorizes DDIs into four classes (A-D) according to their clinical significance. Potential drug-drug DDIs were analyzed for 276,891 dispensed community pharmacy prescriptions. Potential DDIs were associated with 10.8%, or 31,110 of these prescriptions. Clinically significant interaction alerts categorized as FASS classes D (most severe, should be avoided) and C (clinically significant but controllable) were associated with 0.5% and 7.0% of the prescriptions, respectively. Methotrexate and warfarin had the highest risk of causing potentially serious (class D) interactions. These interaction alerts were most frequently between methotrexate and NSAIDs and warfarin and NSAIDs. In general, NSAIDs were the most commonly interacting drugs in this study. This study demonstrates that community pharmacies can actively contribute to DDI risk management and systematically use their surveillance systems for identifying patients having clinically significant DDIs. The findings also indicate that the majority of potentially serious interactions in outpatients involve a limited number of drugs, particularly NSAIDs, warfarin and methotrexate. Further research should focus on community pharmacists' involvement in DDI risk management in collaboration with local health care providers. Copyright © 2015 Elsevier Inc. All rights reserved.

Development and evaluation of an interactive dental video game to teach dentin bonding.

PubMed

Amer, Rafat S; Denehy, Gerald E; Cobb, Deborah S; Dawson, Deborah V; Cunningham-Ford, Marsha A; Bergeron, Cathia

2011-06-01

Written and clinical tests compared the change in clinical knowledge and practical clinical skill of first-year dental students watching a clinical video recording of the three-step etch-and-rinse resin bonding system to those using an interactive dental video game teaching the same procedure. The research design was a randomized controlled trial with eighty first-year dental students enrolled in the preclinical operative dentistry course. Students' change in knowledge was measured through written examination using a pre-test and a post-test, as well as clinical tests in the form of a benchtop shear bond strength test. There was no statistically significant difference between teaching methods in regards to change in either knowledge or clinical skills, with one minor exception relating to the wetness of dentin following etching. Students expressed their preference for an interactive self-paced method of teaching.

Pharmacokinetic Interactions between Drugs and Botanical Dietary Supplements

PubMed Central

Sprouse, Alyssa A.

2016-01-01

The use of botanical dietary supplements has grown steadily over the last 20 years despite incomplete information regarding active constituents, mechanisms of action, efficacy, and safety. An important but underinvestigated safety concern is the potential for popular botanical dietary supplements to interfere with the absorption, transport, and/or metabolism of pharmaceutical agents. Clinical trials of drug–botanical interactions are the gold standard and are usually carried out only when indicated by unexpected consumer side effects or, preferably, by predictive preclinical studies. For example, phase 1 clinical trials have confirmed preclinical studies and clinical case reports that St. John’s wort (Hypericum perforatum) induces CYP3A4/CYP3A5. However, clinical studies of most botanicals that were predicted to interact with drugs have shown no clinically significant effects. For example, clinical trials did not substantiate preclinical predictions that milk thistle (Silybum marianum) would inhibit CYP1A2, CYP2C9, CYP2D6, CYP2E1, and/or CYP3A4. Here, we highlight discrepancies between preclinical and clinical data concerning drug–botanical interactions and critically evaluate why some preclinical models perform better than others in predicting the potential for drug–botanical interactions. Gaps in knowledge are also highlighted for the potential of some popular botanical dietary supplements to interact with therapeutic agents with respect to absorption, transport, and metabolism. PMID:26438626

Pharmacokinetic Interactions between Drugs and Botanical Dietary Supplements.

PubMed

Sprouse, Alyssa A; van Breemen, Richard B

2016-02-01

The use of botanical dietary supplements has grown steadily over the last 20 years despite incomplete information regarding active constituents, mechanisms of action, efficacy, and safety. An important but underinvestigated safety concern is the potential for popular botanical dietary supplements to interfere with the absorption, transport, and/or metabolism of pharmaceutical agents. Clinical trials of drug-botanical interactions are the gold standard and are usually carried out only when indicated by unexpected consumer side effects or, preferably, by predictive preclinical studies. For example, phase 1 clinical trials have confirmed preclinical studies and clinical case reports that St. John's wort (Hypericum perforatum) induces CYP3A4/CYP3A5. However, clinical studies of most botanicals that were predicted to interact with drugs have shown no clinically significant effects. For example, clinical trials did not substantiate preclinical predictions that milk thistle (Silybum marianum) would inhibit CYP1A2, CYP2C9, CYP2D6, CYP2E1, and/or CYP3A4. Here, we highlight discrepancies between preclinical and clinical data concerning drug-botanical interactions and critically evaluate why some preclinical models perform better than others in predicting the potential for drug-botanical interactions. Gaps in knowledge are also highlighted for the potential of some popular botanical dietary supplements to interact with therapeutic agents with respect to absorption, transport, and metabolism. Copyright © 2016 by The American Society for Pharmacology and Experimental Therapeutics.

Clinically significant drug-drug interactions involving opioid analgesics used for pain treatment in patients with cancer: a systematic review.

PubMed

Kotlinska-Lemieszek, Aleksandra; Klepstad, Pål; Haugen, Dagny Faksvåg

2015-01-01

Opioids are the most frequently used drugs to treat pain in cancer patients. In some patients, however, opioids can cause adverse effects and drug-drug interactions. No advice concerning the combination of opioids and other drugs is given in the current European guidelines. To identify studies that report clinically significant drug-drug interactions involving opioids used for pain treatment in adult cancer patients. Systematic review with searches in Embase, MEDLINE, and Cochrane Central Register of Controlled Trials from the start of the databases (Embase from 1980) through January 2014. In addition, reference lists of relevant full-text papers were hand-searched. Of 901 retrieved papers, 112 were considered as potentially eligible. After full-text reading, 17 were included in the final analysis, together with 15 papers identified through hand-searching of reference lists. All of the 32 included publications were case reports or case series. Clinical manifestations of drug-drug interactions involving opioids were grouped as follows: 1) sedation and respiratory depression, 2) other central nervous system symptoms, 3) impairment of pain control and/or opioid withdrawal, and 4) other symptoms. The most common mechanisms eliciting drug-drug interactions were alteration of opioid metabolism by inhibiting the activity of cytochrome P450 3A4 and pharmacodynamic interactions due to the combined effect on opioid, dopaminergic, cholinergic, and serotonergic activity in the central nervous system. Evidence for drug-drug interactions associated with opioids used for pain treatment in cancer patients is very limited. Still, the cases identified in this systematic review give some important suggestions for clinical practice. Physicians prescribing opioids should recognize the risk of drug-drug interactions and if possible avoid polypharmacy.

Medical biochemistry: Is it time to change the teaching style?

PubMed

Palocaren, Jeeji; Pillai, Lekha S; Celine, T M

2016-01-01

The Medical Council of India (MCI) recommendations on medical education suggest a shift from didactic lectures to more interactive lectures. This study assessed the effectiveness of different pedagogical methods in biochemistry and the perceptions of students and teachers about the shift from didactic to interactive lectures. An interventional crossover study was done with the topic divided into three biochemical modules and one clinical module. The students were divided into two batches, one of which was given didactic and the other, interactive lectures. They were assessed immediately after the lecture and four months later. Anonymous feedback was obtained to gauge the students' perceptions regarding the mode of teaching. The teachers' feedback on the use of both pedagogical styles was also obtained. There was no significant difference between the performance of the two groups in either examination in three of the modules. However, there was a statistically significant difference between the two groups' performance in the module that had clinical applications, with students from the interactive lecture group performing better. All students preferred interactive classes, irrespective of the topic taught. The teachers indicated that, although at the outset the interactive lectures were difficult to manage, both in terms of content and time, these drawbacks could be overcome with time and practice. Interactive lectures are an effective teaching method in biochemistry, especially in topics involving clinical application.

Clinical symptoms predict concurrent social and global functioning in an early psychosis sample.

PubMed

Cacciotti-Saija, Cristina; Langdon, Robyn; Ward, Philip B; Hickie, Ian B; Guastella, Adam J

2018-04-01

Although well established in chronic schizophrenia, the key determinants of functioning remain unknown during the early phase of a psychotic disorder. The aim of this study was to comprehensively examine the social cognitive, basic neurocognitive and clinical predictors of concurrent social functioning and global functioning in an early psychosis sample. This study examined the relationship between social cognition, basic neurocognition and clinical symptoms with concurrent functioning in 51 early psychosis individuals. Assessments included a range of self-report, observational and clinician-rated measures of cognitive, symptom severity and functioning domains. Results revealed a significant association between self-reported social function and lower levels of both social interaction anxiety and negative psychotic symptoms. A significant association was also observed between lower levels of negative psychotic symptoms and observed social functioning. Lastly, results demonstrated a significant association between reduced negative psychotic symptoms and clinician-rated global functioning. Clinical domains such as negative symptoms and social interaction anxiety significantly contribute to an optimal model predicting outcome during the early phase of a psychotic disorder. These clinical features may also provide useful markers of an individual's capacity for social participation. Clinical implications include the need for early targeted intervention to address social anxiety and negative psychotic symptoms to facilitate optimum patient outcome. © 2015 Wiley Publishing Asia Pty Ltd.

The effects of black pepper on the intestinal absorption and hepatic metabolism of drugs.

PubMed

Han, Hyo-Kyung

2011-06-01

There is currently a need for a better understanding of the mechanisms of food-drug interaction as well as the clinical implication to maximize the effectiveness and applicability of black pepper or its active component, piperine, as a bioavailability enhancer in the clinical arena. This review deals with the effects of black pepper and piperine on drug metabolizing enzymes as well as on intestinal drug absorption. The review provides the reader with a comprehensive update on the potential mechanisms and pharmacokinetic interactions of black pepper and piperine with co-administered medicines. The article also provides a comprehensive update on the current known issues with black pepper and piperine. The information provided is used to assess the clinical significance of black pepper and piperine and optimize their effectiveness as a bioavailability enhancer. For black pepper or piperine to be widely applicable in current medical practice, as a combination therapy, the clinical significance of food-drug interactions caused by concurrent use of black pepper or piperine should be carefully assessed with consideration for many compounding factors affecting the clinical outcome of pharmacokinetic interactions (e.g., dose, dosing regimen, genetic variation and species). Furthermore, the effective formulation strategy for the optimization of the pharmacokinetic characteristics of dietary components is crucial to improve their in vivo performance and ultimately maximize their effectiveness as a bioavailability enhancer.

Macrolides versus azalides: a drug interaction update.

PubMed

Amsden, G W

1995-09-01

To describe the current drug interaction profiles for all approved and investigational macrolide and azalide antimicrobials, and to comment on the clinical impact of these interactions when appropriate. MEDLINE was searched to identify all pertinent studies, review articles, and case reports from 1975 to 1995. When appropriate information was not available in the literature, data were obtained from the product manufacturers. All available data were reviewed to give an unbiased account of possible drug interactions. Data for some of the interactions were not available from the literature, but were available from abstracts or from company-supplied materials. Although the data were not always entirely explicative, the best attempt was made to deliver the pertinent information that clinical practitioners would need to formulate practice opinions. When more in-depth information was supplied in the form of a review or study report, a thorough explanation of pertinent methodology was supplied. Since the introduction of erythromycin into clinical practice, there have been several clinically significant drug interactions identified throughout the literature associated with this drug. These interactions have been caused mostly by inhibition of the CYP3A subclass of hepatic enzymes, thereby decreasing the metabolism of any other agent given concurrently that is also cleared through this mechanism. With the development and marketing of several new macrolides, it was hoped that the drug interaction profile associated with this class would improve. This has been met with variable success. Although some of the extensions of the 14-membered ring macrolides have shown an incidence of interactions equal to that of erythromycin, others have shown improved profiles. In contrast, the 16-membered ring macrolides have demonstrated a much improved, though not absent, interaction profile. The most success in avoiding drug interactions through structure modification has been accomplished with the development of the azalide class, of which azithromycin is the first to be approved for marketing. This agent has to date produced none of the classic drug interactions that most macrolides have demonstrated in patient care. The introduction of new 14- and 16-membered ring macrolides appears to have had a variable effect in modifying the incidence of drug interactions associated with this class. Azithromycin, a member of the new azalide class, has to date produced fewer clinically significant interactions than other azalides with any agent that is cleared through the CYP3A system.(ABSTRACT TRUNCATED AT 250 WORDS)

[The effectiveness of psychoanalytic-interactional therapy in borderline personality disorder: a study of clinical data].

PubMed

Leichsenring, Falk; Masuhr, Oliver; Jaeger, Ulrich; Dally, Andreas; Streeck, Ulrich

2007-01-01

Different methods are available for the psychotherapeutic treatment of patients with severe structural mental disorders. Psychoanalytic-interactional therapy is among those methods which have been clinically proven to be effective for many years. Psychoanalytic-interactional therapy was derived from analytic psychotherapy specifically to allow for the treatment of severely disturbed patients, e.g. patients with borderline personality disorders, prepsychotic disorders, addictions and perversions. In a naturalistic study, the effectiveness of psychoanalytic-interactional therapy was tested in a sample of patients with borderline personality disorders (N = 132). The patients were treated at the Clinic Tiefenbrunn near Goettingen, Germany. Standardized, reliable and valid diagnostic instruments were used to study the treatment effects. Psychoanalytic-interactional therapy was found to significantly improve target symptoms, general symptoms, interpersonal problems and life satisfaction. The results are discussed with regard to the treatment of severely disturbed patients.

Pharmacokinetic and pharmacodynamic drug interactions with ethanol (alcohol).

PubMed

Chan, Lingtak-Neander; Anderson, Gail D

2014-12-01

Ethanol (alcohol) is one of the most widely used legal drugs in the world. Ethanol is metabolized by alcohol dehydrogenase (ADH) and the cytochrome P450 (CYP) 2E1 drug-metabolizing enzyme that is also responsible for the biotransformation of xenobiotics and fatty acids. Drugs that inhibit ADH or CYP2E1 are the most likely theoretical compounds that would lead to a clinically significant pharmacokinetic interaction with ethanol, which include only a limited number of drugs. Acute ethanol primarily alters the pharmacokinetics of other drugs by changing the rate and extent of absorption, with more limited effects on clearance. Both acute and chronic ethanol use can cause transient changes to many physiologic responses in different organ systems such as hypotension and impairment of motor and cognitive functions, resulting in both pharmacokinetic and pharmacodynamic interactions. Evaluating drug interactions with long-term use of ethanol is uniquely challenging. Specifically, it is difficult to distinguish between the effects of long-term ethanol use on liver pathology and chronic malnutrition. Ethanol-induced liver disease results in decreased activity of hepatic metabolic enzymes and changes in protein binding. Clinical studies that include patients with chronic alcohol use may be evaluating the effects of mild cirrhosis on liver metabolism, and not just ethanol itself. The definition of chronic alcohol use is very inconsistent, which greatly affects the quality of the data and clinical application of the results. Our study of the literature has shown that a significantly higher volume of clinical studies have focused on the pharmacokinetic interactions of ethanol and other drugs. The data on pharmacodynamic interactions are more limited and future research addressing pharmacodynamic interactions with ethanol, especially regarding the non-central nervous system effects, is much needed.

Impact of pharmacist interventions in older patients: a prospective study in a tertiary hospital in Germany

PubMed Central

Cortejoso, L; Dietz, RA; Hofmann, G; Gosch, M; Sattler, A

2016-01-01

Background Inappropriate pharmacotherapy among older adults remains a critical issue in our health care systems. Besides polypharmacy and multiple comorbidities, the age-related pharmacokinetic and pharmacodynamic changes may increase the risk of adverse drug reactions and medication errors. Objective The main target of this study was to describe the characteristics of pharmaceutical interventions in two geriatric wards (orthogeriatric ward and geriatric day unit) of a general teaching hospital and to evaluate the clinical significance of the detected medication errors. Materials and methods The study was conducted between August 2014 and October 2015 and was based on a triple approach that included validation of medical orders, medication reconciliation at patients’ admission, and a predischarge planning appointment with the patient. The validation of medical orders was based on analyzing the suitability of the drugs prescribed, the drug dose depending on the patient’s characteristics, the presence of contraindications and interactions between drugs, and the proposal of alternative drugs included in the hospital formulary. Results A total of 2,307 interventions associated to a medication error in 15,282 medical orders for 1,859 older patients were recorded. The greater part of the interventions carried out on the orthogeriatric ward at admission and at discharge were due to omission of a drug in the medical order (20.0%) and clinically significant interactions requiring monitoring (30.4%), respectively. The main factor triggering pharmacist’s recommendations on the geriatric day unit was clinically significant interactions (21.1%). With regard to the clinical severity of the detected errors, 68.1% were considered significant, 24.8% were of minor significance, and 7.2% were clinically serious. Conclusion Our findings show the importance of clinical pharmacist involvement in the optimization of pharmacotherapy in older adults, ensuring that they receive effective, safe, and efficient drug therapy. PMID:27713625

Prevalence of statin-drug interactions in older people: a systematic review.

PubMed

Thai, Michele; Reeve, Emily; Hilmer, Sarah N; Qi, Katie; Pearson, Sallie-Anne; Gnjidic, Danijela

2016-05-01

Statins are among the most frequently prescribed medications internationally. Older people are commonly prescribed multiple medications and are at an increased risk of drug-drug interactions, including statin-drug interactions. The aim of this study was to conduct a systematic review of current evidence on the prevalence of statin-drug interactions in older people. A systematic search of observational studies in Embase, Medline, and PubMed was conducted. Articles were included if they were published in English during the period July 2000-July 2014 and reported on the prevalence of statin-drug interactions in people over 65 years of age. Two reviewers independently assessed the articles for eligibility and extracted the data. The search returned 1556 eligible articles. A total of 19 articles met the inclusion criteria. In studies (n = 7) that focused on statin users only, the prevalence of potential statin-drug interactions assessed using different measures ranged from 0.19 to 33.0 %. In studies that examined drug interactions across a population of both statin users and non-users (n = 12), the prevalence of potential statin-drug interactions ranged from 0.1 to 7.1 % (n = 8), and the prevalence of clinically relevant statin-drug interactions ranged from 1.5 to 4 % (n = 4). Current published evidence suggests substantial variations in the prevalence of statin-drug interactions and their clinical relevance. Further studies are necessary to provide a better understanding of the prevalence of clinically significant statin-drug interactions, the medications most frequently contributing to statin-drug interactions, and impact on relevant clinical outcomes in older people.

Hypericum perforatum: pharmacokinetic, mechanism of action, tolerability, and clinical drug-drug interactions.

PubMed

Russo, Emilio; Scicchitano, Francesca; Whalley, Benjamin J; Mazzitello, Carmela; Ciriaco, Miriam; Esposito, Stefania; Patanè, Marinella; Upton, Roy; Pugliese, Michela; Chimirri, Serafina; Mammì, Maria; Palleria, Caterina; De Sarro, Giovambattista

2014-05-01

Hypericum perforatum (HP) belongs to the Hypericaceae family and is one of the oldest used and most extensively investigated medicinal herbs. The medicinal form comprises the leaves and flowering tops of which the primary ingredients of interest are naphthodianthrones, xanthones, flavonoids, phloroglucinols (e.g. hyperforin), and hypericin. Although several constituents elicit pharmacological effects that are consistent with HP's antidepressant activity, no single mechanism of action underlying these effects has thus far been found. Various clinical trials have shown that HP has a comparable antidepressant efficacy as some currently used antidepressant drugs in the treatment of mild/moderate depression. Interestingly, low-hyperforin-content preparations are effective in the treatment of depression. Moreover, HP is also used to treat certain forms of anxiety. However, HP can induce various cytochrome P450s isozymes and/or P-glycoprotein, of which many drugs are substrates and which are the main origin of HP-drug interactions. Here, we analyse the existing evidence describing the clinical consequence of HP-drug interactions. Although some of the reported interactions are based on findings from in vitro studies, the clinical importance of which remain to be demonstrated, others are based on case reports where causality can, in some cases, be determined to reveal clinically significant interactions that suggest caution, consideration, and disclosure of potential interactions prior to informed use of HP. Copyright © 2013 John Wiley & Sons, Ltd.

The interaction between cannabis use and the Val158Met polymorphism of the COMT gene in psychosis: A transdiagnostic meta - analysis.

PubMed

Vaessen, Thomas Stephanus Johannes; de Jong, Lea; Schäfer, Annika Theresia; Damen, Thomas; Uittenboogaard, Aniek; Krolinski, Pauline; Nwosu, Chinyere Vicky; Pinckaers, Florentina Maria Egidius; Rotee, Iris Leah Marije; Smeets, Antonius Petrus Wilhelmus; Ermiş, Ayşegül; Kennedy, James L; Nieman, Dorien H; Tiwari, Arun; van Os, Jim; Drukker, Marjan

2018-01-01

Neither environmental nor genetic factors are sufficient to predict the transdiagnostic expression of psychosis. Therefore, analysis of gene-environment interactions may be productive. A meta-analysis was performed using papers investigating the interaction between cannabis use and catechol-O-methyl transferase (COMT) polymorphism Val158Met (COMTVal158Met). PubMed, Embase, PsychInfo. All observational studies assessing the interaction between COMTVal158Met and cannabis with any psychosis or psychotic symptoms measure as an outcome. A meta-analysis was performed using the Meta-analysis of Observational Studies in Epidemiology guidelines and forest plots were generated. Thirteen articles met the selection criteria: 7 clinical studies using a case-only design, 3 clinical studies with a dichotomous outcome, and 3 studies analysing a continuous outcome of psychotic symptoms below the threshold of psychotic disorder. The three study types were analysed separately. Validity of the included studies was assessed using "A Cochrane Risk of Bias Assessment Tool: for Non-Randomized Studies of Interventions". For case-only studies, a significant interaction was found between cannabis use and COMTVal158Met, with an OR of 1.45 (95% Confidence Interval = 1.05-2.00; Met/Met as the risk genotype). However, there was no evidence for interaction in either the studies including dichotomous outcomes (B = -0.51, 95% Confidence Interval -1.72, 0.70) or the studies including continuous outcomes (B = -0.04 95% Confidence Interval -0.16-0.08). A substantial part of the included studies used the case-only design, which has lower validity and tends to overestimate true effects. The interaction term between cannabis use and COMTVal158Met was only statistically significant in the case-only studies, but not in studies using other clinical or non-clinical psychosis outcomes. Future additional high quality studies might change current perspectives, yet currently evidence for the interaction remains unconvincing.

Effects of Pilates exercises on sensory interaction, postural control and fatigue in patients with multiple sclerosis.

PubMed

Soysal Tomruk, Melda; Uz, Muhammed Zahid; Kara, Bilge; İdiman, Egemen

2016-05-01

Decreased postural control, sensory integration deficits and fatigue are important problems that cause functional impairments in patients with multiple sclerosis (pwMS). To examine the effect of modified clinical Pilates exercises on sensory interaction and balance, postural control and fatigue in pwMS. Eleven patients with multiple sclerosis and 12 healthy matched controls were recruited in this study. Limits of stability and postural stability tests were used to evaluate postural control by Biodex Balance System and sensory interaction assessed. Fatigue was assessed by Modified Fatigue Impact Scale. Pilates exercises were applied two times a week for 10 weeks and measurements were repeated to pwMS after exercise training. Postural control and fatigue (except psychosocial parameter) of pwMS were significantly worser than healthy controls (p<0.05). Significant improvements occurred in sensory interaction (eyes open, foam surface) and total, physical and cognitive scores of fatigue after 10-week modified clinical Pilates training (p<0.05). No significant changes were detected in postural control after the pilates exercises (p>0.05). Ten-week Pilates training is effective to improve sensory interaction and to decrease fatigue. Pilates exercises can be applied safely in ambulatory pwMS for enhance sensory interaction and balance and combat fatigue. More investigations are needed. Copyright © 2016 Elsevier B.V. All rights reserved.

New Method for Insomnia Mongolian Mind-Body Interactive Psychotherapy in the Assessment of Chronic Insomnia: A Retrospective Study.

PubMed

He, Nagongbilige; Lan, Wu; Jiang, Aruna; Jia, Haserden; Bao, Shuzhi; Bao, Longmei; Qin, Altansha; Bao, Orgel; Bao, Shinjiltu; Wang, Nandin; Bao, Suyaltu; Dai, Shuangfu; Bao, Sarula; Arlud, Sarnai

2018-06-19

Insomnia is a common clinical complaint, and if not addressed it can increase the risk of developing other underlying diseases such as hypertension, depression and anxiety. The use of Mongolian mind-body interactive therapy as a comprehensive psychotherapeutic approach in chronic insomnia has been shown in this retrospective study. Subjects who had suffered insomnia for more than 1 month participated in the Mongolian mind-body interactive psychotherapy program between June 2012 and February 2014. They were interviewed by telephone at least 10 months before participating in the program. Their sleep was assessed using the Athens insomnia scale. Descriptive statistics, ANOVA and regression analysis were used for data analysis by SPSS software. Mongolian mind-body interactive psychotherapy significantly improved sleeping conditions. In ANOVA analysis, both short- and long-term outcomes were significantly affected by the treatment period. Patients who previously took medication and pre-treatment sleeping condition (ASI score) had a significant influence on long-term outcomes, as well as treatment time related to the duration of insomnia. Mongolian mind-body interactive psychotherapy is a new method for insomnia, and narrative therapy and hypnotic methods together improve the sleeping condition, However, a further controlled randomized clinical study is needed to understand the efficacy.

The role of hepatic transport and metabolism in the interactions between pravastatin or repaglinide and two rOatp inhibitors in rats.

PubMed

Badolo, Lassina; Bundgaard, Christoffer; Garmer, Mats; Jensen, Bente

2013-07-16

A change in the function or expression of hepatic drug transporters may have significant effect on the efficacy or safety of orally administered drugs. Although a number of clinical drug-drug interactions associated with hepatic transport proteins have been reported, in practice it is not always straightforward to discriminate other pathways (e.g. drug metabolism) from being involved in these interactions. The present study was designed to assess the interactions between organic anion transporting polypeptide (Oatp) substrates (pravastatin or repaglinide) and inhibitors (spironolactone or diphenhydramine) in vivo in rats. The mechanisms behind the interactions were then investigated using in vitro tools (isolated hepatocytes and rat liver microsomes). The results showed a significant increase in the systemic exposures of pravastatin (2.5-fold increase in AUC) and repaglinide (1.8-fold increase in AUC) after co-administration of spironolactone to rats. Diphenhydramine increased the AUC of repaglinide by 1.4-fold. The in vivo interactions observed in rats between Oatp substrates and inhibitors may a priori be classified as transport-mediated drug-drug interactions. However, mechanistic studies performed in vitro using both isolated rat hepatocytes and rat liver microsomes showed that the interaction between pravastatin and spironolactone may be solely linked to the inhibition of pravastatin uptake in liver. On the contrary, the inhibition of cytochrome P450 seemed to be the reason for the interactions observed between repaglinide and spironolactone. Although the function and structure of transport proteins may vary between rats and humans, the approach used in the present study can be applied to humans and help to understand the role of drug transport and drug metabolism in a given drug-drug interaction. This is important to predict and mitigate the risk of drug-drug interactions for a candidate drug in pre-clinical development, it is also important for the optimal design of drug-drug interactions studies in the clinic. Copyright © 2013 Elsevier B.V. All rights reserved.

What can paper-based clinical information systems tell us about the design of computerized clinical information systems (CIS) in the ICU?

PubMed

Miller, A; Pilcher, D; Mercaldo, N; Leong, T; Scheinkestel, C; Schildcrout, J

2010-08-01

Screen designs in computerized clinical information systems (CIS) have been modeled on their paper predecessors. However, limited understanding about how paper forms support clinical work means that we risk repeating old mistakes and creating new opportunities for error and inefficiency as illustrated by problems associated with computerized provider order entry systems. This study was designed to elucidate principles underlying a successful ICU paper-based CIS. The research was guided by two exploratory hypotheses: (1) paper-based artefacts (charts, notes, equipment, order forms) are used differently by nurses, doctors and other healthcare professionals in different (formal and informal) conversation contexts and (2) different artefacts support different decision processes that are distributed across role-based conversations. All conversations undertaken at the bedsides of five patients were recorded with any supporting artefacts for five days per patient. Data was coded according to conversational role-holders, clinical decision process, conversational context and artefacts. 2133 data points were analyzed using Poisson logistic regression analyses. Results show significant interactions between artefacts used during different professional conversations in different contexts (chi(2)((df=16))=55.8, p<0.0001). The interaction between artefacts used during different professional conversations for different clinical decision processes was not statistically significant although all two-way interactions were statistically significant. Paper-based CIS have evolved to support complex interdisciplinary decision processes. The translation of two design principles - support interdisciplinary perspectives and integrate decision processes - from paper to computerized CIS may minimize the risks associated with computerization. 2010 Australian College of Critical Care Nurses Ltd. Published by Elsevier Ltd. All rights reserved.

In Vitro, In Vivo, and Clinical Studies of Tedizolid To Assess the Potential for Peripheral or Central Monoamine Oxidase Interactions

PubMed Central

Bartizal, K.; Minassian, S. L.; Fang, E.; Prokocimer, P.

2013-01-01

Tedizolid phosphate is a novel oxazolidinone prodrug whose active moiety, tedizolid, has improved potency against Gram-positive pathogens and pharmacokinetics, allowing once-daily administration. Given linezolid warnings for drug-drug and drug-food interactions mediated by monoamine oxidase (MAO) inhibition, including sporadic serotonergic toxicity, these studies evaluated tedizolid for potential MAO interactions. In vitro, tedizolid and linezolid were reversible inhibitors of human MAO-A and MAO-B; the 50% inhibitory concentration (IC50) for tedizolid was 8.7 μM for MAO-A and 5.7 μM for MAO-B and 46.0 and 2.1 μM, respectively, with linezolid. Tedizolid phosphate was negative in the mouse head twitch model of serotonergic activity. Two randomized placebo-controlled crossover clinical studies assessed the potential of 200 mg/day tedizolid phosphate (at steady state) to enhance pressor responses to coadministered oral tyramine or pseudoephedrine. Sensitivity to tyramine was determined by comparing the concentration of tyramine required to elicit a ≥30-mmHg increase in systolic blood pressure (TYR30) when administered with placebo versus tedizolid phosphate. The geometric mean tyramine sensitivity ratio (placebo TYR30/tedizolid phosphate TYR30) was 1.33; a ratio of ≥2 is considered clinically relevant. In the pseudoephedrine study, mean maximum systolic blood pressure was not significantly different when pseudoephedrine was coadministered with tedizolid phosphate versus placebo. In summary, tedizolid is a weak, reversible inhibitor of MAO-A and MAO-B in vitro. Provocative testing in humans and animal models failed to uncover significant signals that would suggest potential for hypertensive or serotonergic adverse consequences at the therapeutic dose of tedizolid phosphate. Clinical studies are registered at www.clinicaltrials.gov as NCT01539473 (tyramine interaction study conducted at Covance Clinical Research Center, Evansville, IN) and NCT01577459 (pseudoephedrine interaction study conducted at Vince and Associates Clinical Research, Overland Park, KS). PMID:23612197

In vitro, in vivo, and clinical studies of tedizolid to assess the potential for peripheral or central monoamine oxidase interactions.

PubMed

Flanagan, S; Bartizal, K; Minassian, S L; Fang, E; Prokocimer, P

2013-07-01

Tedizolid phosphate is a novel oxazolidinone prodrug whose active moiety, tedizolid, has improved potency against Gram-positive pathogens and pharmacokinetics, allowing once-daily administration. Given linezolid warnings for drug-drug and drug-food interactions mediated by monoamine oxidase (MAO) inhibition, including sporadic serotonergic toxicity, these studies evaluated tedizolid for potential MAO interactions. In vitro, tedizolid and linezolid were reversible inhibitors of human MAO-A and MAO-B; the 50% inhibitory concentration (IC50) for tedizolid was 8.7 μM for MAO-A and 5.7 μM for MAO-B and 46.0 and 2.1 μM, respectively, with linezolid. Tedizolid phosphate was negative in the mouse head twitch model of serotonergic activity. Two randomized placebo-controlled crossover clinical studies assessed the potential of 200 mg/day tedizolid phosphate (at steady state) to enhance pressor responses to coadministered oral tyramine or pseudoephedrine. Sensitivity to tyramine was determined by comparing the concentration of tyramine required to elicit a ≥ 30-mmHg increase in systolic blood pressure (TYR30) when administered with placebo versus tedizolid phosphate. The geometric mean tyramine sensitivity ratio (placebo TYR30/tedizolid phosphate TYR30) was 1.33; a ratio of ≥ 2 is considered clinically relevant. In the pseudoephedrine study, mean maximum systolic blood pressure was not significantly different when pseudoephedrine was coadministered with tedizolid phosphate versus placebo. In summary, tedizolid is a weak, reversible inhibitor of MAO-A and MAO-B in vitro. Provocative testing in humans and animal models failed to uncover significant signals that would suggest potential for hypertensive or serotonergic adverse consequences at the therapeutic dose of tedizolid phosphate. Clinical studies are registered at www.clinicaltrials.gov as NCT01539473 (tyramine interaction study conducted at Covance Clinical Research Center, Evansville, IN) and NCT01577459 (pseudoephedrine interaction study conducted at Vince and Associates Clinical Research, Overland Park, KS).

Exploring the interaction between Salvia miltiorrhiza and human serum albumin: Insights from herb-drug interaction reports, computational analysis and experimental studies

NASA Astrophysics Data System (ADS)

Shao, Xin; Ai, Ni; Xu, Donghang; Fan, Xiaohui

2016-05-01

Human serum albumin (HSA) binding is one of important pharmacokinetic properties of drug, which is closely related to in vivo distribution and may ultimately influence its clinical efficacy. Compared to conventional drug, limited information on this transportation process is available for medicinal herbs, which significantly hampers our understanding on their pharmacological effects, particularly when herbs and drug are co-administrated as polytherapy to the ailment. Several lines of evidence suggest the existence of Salvia miltiorrhiza-Warfarin interaction. Since Warfarin is highly HSA bound in the plasma with selectivity to site I, it is critical to evaluate the possibility of HSA-related herb-drug interaction. Herein an integrated approach was employed to analyze the binding of chemicals identified in S. miltiorrhiza to HSA. Molecular docking simulations revealed filtering criteria for HSA site I compounds that include docking score and key molecular determinants for binding. For eight representative ingredients from the herb, their affinity and specificity to HSA site I was measured and confirmed fluorometrically, which helps to improve the knowledge of interaction mechanisms between this herb and HSA. Our results indicated that several compounds in S. miltiorrhiza were capable of decreasing the binding constant of Warfarin to HSA site I significantly, which may increase free drug concentration in vivo, contributing to the herb-drug interaction observed clinically. Furthermore, the significance of HSA mediated herb-drug interactions was further implied by manual mining on the published literatures on S. miltiorrhiza.

Potential pharmacokinetic interactions between antiretrovirals and medicinal plants used as complementary and African traditional medicines.

PubMed

Müller, Adrienne C; Kanfer, Isadore

2011-11-01

The use of traditional/complementary/alternate medicines (TCAMs) in HIV/AIDS patients who reside in Southern Africa is quite common. Those who use TCAMs in addition to antiretroviral (ARV) treatment may be at risk of experiencing clinically significant pharmacokinetic (PK) interactions, particularly between the TCAMs and the protease inhibitors (PIs) and non-nucleoside reverse transcriptase inhibitors (NNRTIs). Mechanisms of PK interactions include alterations to the normal functioning of drug efflux transporters, such as P-gp and/or CYP isoenzymes, such a CYP3A4 that mediate the absorption and elimination of drugs in the small intestine and liver. Specific mechanisms include inhibition and activation of these proteins and induction via the pregnane X receptor (PXR). Several clinical studies and case reports involving ARV-herb PK interactions have been reported. St John's Wort, Garlic and Cat's Claw exhibited potentially significant interactions, each with a PI or NNRTI. The potential for these herbs to induce PK interactions with drugs was first identified in reports of in vitro studies. Other in vitro studies have shown that several African traditional medicinal (ATM) plants and extracts may also demonstrate PK interactions with ARVs, through effects on CYP3A4, P-gp and PXR. The most complex effects were exhibited by Hypoxis hemerocallidea, Sutherlandia frutescens, Cyphostemma hildebrandtii, Acacia nilotica, Agauria salicifolia and Elaeodendron buchananii. Despite a high incidence of HIV/AIDs in the African region, only one clinical study, between efavirenz and Hypoxis hemerocallidea has been conducted. However, several issues/concerns still remain to be addressed and thus more studies on ATMs are warranted in order for more meaningful data to be generated and the true potential for such interactions to be determined. Copyright © 2011 John Wiley & Sons, Ltd.

Displacement of Drugs from Human Serum Albumin: From Molecular Interactions to Clinical Significance.

PubMed

Rimac, Hrvoje; Debeljak, Željko; Bojić, Mirza; Miller, Larisa

2017-01-01

Human serum albumin (HSA) is the most abundant protein in human serum. It has numerous functions, one of which is transport of small hydrophobic molecules, including drugs, toxins, nutrients, hormones and metabolites. HSA has the ability to interact with a wide variety of structurally different compounds. This promiscuous, nonspecific affinity can lead to sudden changes in concentrations caused by displacement, when two or more compounds compete for binding to the same molecular site. It is important to consider drug combinations and their binding to HSA when defining dosing regimens, as this can directly influence drug's free, active concentration in blood. In present paper we review drug interactions with potential for displacement from HSA, situations in which they are likely to occur and their clinical significance. We also offer guidelines in designing drugs with decreased binding to HSA. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

Childhood trauma and psychopathology among alcohol-dependent men: no interaction with temperament and character.

PubMed

Evren, Cuneyt; Sar, Vedat; Dalbudak, Ercan; Durkaya, Mine; Cetin, Rabia; Evren, Bilge; Cakmak, Duran; Ertem-Vehid, Hayriye

2011-01-01

The aim of this study was to evaluate possible interactions between childhood trauma, temperament, character, and psychopathology among alcohol-dependent men. Participants were 156 alcohol-dependent men consecutively admitted to a dependency treatment unit. The Childhood Abuse and Neglect Questionnaire, the Temperament and Character Inventory, and the Symptom Checklist-Revised were administered to all participants. Childhood abuse and neglect did not have any effect on temperament and character scores in multivariate analysis. Whereas childhood abuse had a significant main effect on all types of clinical psychopathology except depression and psychoticism scores, childhood neglect only had a significant main effect on depression scores. There was no interaction between childhood abuse and neglect on these analyses. Among alcohol-dependent men, childhood abuse and neglect contribute to general psychopathology through distinct clinical consequences, independently of temperamental and characterological features. Copyright © 2010 S. Karger AG, Basel.

[Predictive factors of clinically significant drug-drug interactions among regimens based on protease inhibitors, non-nucleoside reverse transcriptase inhibitors and raltegravir].

PubMed

Cervero, Miguel; Torres, Rafael; Jusdado, Juan José; Pastor, Susana; Agud, Jose Luis

2016-04-15

To determine the prevalence and types of clinically significant drug-drug interactions (CSDI) in the drug regimens of HIV-infected patients receiving antiretroviral treatment. retrospective review of database. Centre: Hospital Universitario Severo Ochoa, Infectious Unit. one hundred and forty-two participants followed by one of the authors were selected from January 1985 to December 2014. from their outpatient medical records we reviewed information from the last available visit of the participants, in relation to HIV infection, comorbidities, demographics and the drugs that they were receiving; both antiretroviral drugs and drugs not related to HIV infection. We defined CSDI from the information sheet and/or database on antiretroviral drug interactions of the University of Liverpool (http://www.hiv-druginteractions.org) and we developed a diagnostic tool to predict the possibility of CSDI. By multivariate logistic regression analysis and by estimating the diagnostic performance curve obtained, we identified a quick tool to predict the existence of drug interactions. Of 142 patients, 39 (29.11%) had some type of CSDI and in 11.2% 2 or more interactions were detected. In only one patient the combination of drugs was contraindicated (this patient was receiving darunavir/r and quetiapine). In multivariate analyses, predictors of CSDI were regimen type (PI or NNRTI) and the use of 3 or more non-antiretroviral drugs (AUC 0.886, 95% CI 0.828 to 0.944; P=.0001). The risk was 18.55 times in those receiving NNRTI and 27,95 times in those receiving IP compared to those taking raltegravir. Drug interactions, including those defined as clinically significant, are common in HIV-infected patients treated with antiretroviral drugs, and the risk is greater in IP-based regimens. Raltegravir-based prescribing, especially in patients who receive at least 3 non-HIV drugs could avoid interactions. Copyright © 2016 Elsevier España, S.L.U. All rights reserved.

Mother-child interactions in young children with excessive physical aggression and in typically developing young children.

PubMed

Urbain-Gauthier, Nadine; Wendland, Jaqueline

2017-07-01

Among the multiple risk factors, the emergence of conduct problems in young children may be linked to harsh parenting and child's temperamental difficulties, leading to a reciprocal early discordant relationship. Little is known about the characteristics of early parent-child interactions in young children with physical aggression. The purpose of the current study was to evaluate the characteristics of mother-child interactions in dyads referred for excessive physical aggression in young children under 5 years of age compared to mother-child interactions in typically developing young children. Mother-child interactions were assessed during a free-play session in both a clinical sample ( N = 70, child mean age  = 3.5 years) and a nonclinical sample ( N = 80, child mean age  = 3.5 years) by using the Rating Scale of Interaction Style (Clark and Seifer, adapted by Molitor and Mayes). Significant differences were found between several interactive features in clinical and nonclinical dyads. In clinical dyads, mothers' behaviors were often characterized by intrusiveness and criticism toward children, and poor facilitative positioning. Children with excessive aggressive behavior often displayed poor communication, initiation of bids, and poor responsiveness toward the mother. They displayed fewer sustained bouts of play than typically developing children did. In clinical dyads, strong positive correlations were found between child responsiveness and maternal interest in engagement ( r = .41, p < .001), while the child displaying sustained bouts of play was negatively correlated with the mother's attempts to intrude on the child's activity ( r = .64, p < .05). These data show that children with excessive aggressive behavior develop disrupted mother-infant interactions from a very young age. Several negative interactive features and correlations between child behavior and maternal behavior were found in clinical samples. The effects of these features add up and probably strengthen each other, thus leading to interactive difficulties from a very young age. More attention should be paid to early parent-child interactions in case of child behavioral problems. The recognition of these interactive dysfunctions is discussed in terms of clinical implications for therapeutic interventions.

Food-drug interactions.

PubMed

Schmidt, Lars E; Dalhoff, Kim

2002-01-01

Interactions between food and drugs may inadvertently reduce or increase the drug effect. The majority of clinically relevant food-drug interactions are caused by food-induced changes in the bioavailability of the drug. Since the bioavailability and clinical effect of most drugs are correlated, the bioavailability is an important pharmacokinetic effect parameter. However, in order to evaluate the clinical relevance of a food-drug interaction, the impact of food intake on the clinical effect of the drug has to be quantified as well. As a result of quality review in healthcare systems, healthcare providers are increasingly required to develop methods for identifying and preventing adverse food-drug interactions. In this review of original literature, we have tried to provide both pharmacokinetic and clinical effect parameters of clinically relevant food-drug interactions. The most important interactions are those associated with a high risk of treatment failure arising from a significantly reduced bioavailability in the fed state. Such interactions are frequently caused by chelation with components in food (as occurs with alendronic acid, clodronic acid, didanosine, etidronic acid, penicillamine and tetracycline) or dairy products (ciprofloxacin and norfloxacin), or by other direct interactions between the drug and certain food components (avitriptan, indinavir, itraconazole solution, levodopa, melphalan, mercaptopurine and perindopril). In addition, the physiological response to food intake, in particular gastric acid secretion, may reduce the bioavailability of certain drugs (ampicillin, azithromycin capsules, didanosine, erythromycin stearate or enteric coated, and isoniazid). For other drugs, concomitant food intake may result in an increase in drug bioavailability either because of a food-induced increase in drug solubility (albendazole, atovaquone, griseofulvin, isotretinoin, lovastatin, mefloquine, saquinavir and tacrolimus) or because of the secretion of gastric acid (itraconazole capsules) or bile (griseofulvin and halofantrine) in response to food intake. For most drugs, such an increase results in a desired increase in drug effect, but in others it may result in serious toxicity (halofantrine).

Clinical phenotype of bipolar disorder with comorbid binge eating disorder

PubMed Central

McElroy, Susan L.; Crow, Scott; Biernacka, Joanna M.; Winham, Stacey; Geske, Jennifer; Cuellar Barboza, Alfredo B.; Prieto, Miguel L.; Chauhan, Mohit; Seymour, Lisa R.; Mori, Nicole; Frye, Mark A.

2017-01-01

Background To explore the relationship between binge eating disorder (BED) and obesity in patients with bipolar disorder (BP). Methods 717 patients participating in the Mayo Clinic Bipolar Biobank completed structured diagnostic interviews and questionnaires for demographic and illness-related variables. They also had weight and height measured to determine body mass index (BMI). The effects of BED and obesity (BMI≥30 kg/m2), as well as their interaction, were assessed on one measure of general medical burden and six proxies of psychiatric illness burden. Results 9.5% of patients received a clinical diagnosis of BED and 42.8% were obese. BED was associated with a significantly elevated BMI. Both BED and obesity were associated with greater psychiatric and general illness burden, but illness burden profiles differed. After controlling for obesity, BED was associated with suicidality, psychosis, mood instability, anxiety disorder comorbidity, and substance abuse comorbidity. After controlling for BED status, obesity was associated with greater general medical comorbidity, but lower substance abuse comorbidity. There were no significant interaction effects between obesity and BED, or BMI and BED, on any illness burden outcome. Limitations There may have been insufficient power to detect interactions between BED and obesity. Conclusions: Among patients with BP, BED and obesity are highly prevalent and correlated, but associated with different profiles of enhanced illness burden. As the association of BED with greater psychiatric illness burden remained significant even after accounting for the effect of obesity, BP with BED may represent a clinically important sub-phenotype. PMID:23742827

Multiple Levels of Suffering

PubMed Central

Kiley, Kasey B.; Haywood, Carlton; Bediako, Shawn M.; Lanzkron, Sophie; Carroll, C. Patrick; Buenaver, Luis F.; Pejsa, Megan; Edwards, Robert R.; Haythornthwaite, Jennifer A.; Campbell, Claudia M.

2016-01-01

Objective: People living with sickle cell disease (SCD) experience severe episodic and chronic pain and frequently report poor interpersonal treatment within health-care settings. In this particularly relevant context, we examined the relationship between perceived discrimination and both clinical and laboratory pain. Methods: Seventy-one individuals with SCD provided self-reports of experiences with discrimination in health-care settings and clinical pain severity, and completed a psychophysical pain testing battery in the laboratory. Results: Discrimination in health-care settings was correlated with greater clinical pain severity and enhanced sensitivity to multiple laboratory-induced pain measures, as well as stress, depression, and sleep. After controlling for relevant covariates, discrimination remained a significant predictor of mechanical temporal summation (a marker of central pain facilitation), but not clinical pain severity or suprathreshold heat pain response. Furthermore, a significant interaction between experience with discrimination and clinical pain severity was associated with mechanical temporal summation; increased experience with discrimination was associated with an increased correlation between clinical pain severity and temporal summation of pain. Discussion: Perceived discrimination within health-care settings was associated with pain facilitation. These findings suggest that discrimination may be related to increased central sensitization among SCD patients, and more broadly that health-care social environments may interact with pain pathophysiology. PMID:26889615

Macrolide drug interactions: an update.

PubMed

Pai, M P; Graci, D M; Amsden, G W

2000-04-01

To describe the current drug interaction profiles for the commonly used macrolides in the US and Europe, and to comment on the clinical impact of these interactions. A MEDLINE search (1975-1998) was performed to identify all pertinent studies, review articles, and case reports. When appropriate information was not available in the literature, data were obtained from the product manufacturers. All available data were reviewed to provide an unbiased account of possible drug interactions. Data for some of the interactions were not available from the literature, but were available from abstracts or company-supplied materials. Although the data were not always explicit, the best attempt was made to deliver pertinent information that clinical practitioners would need to formulate practice opinions. When more in-depth information was supplied in the form of a review or study report, a thorough explanation of pertinent methodology was supplied. Several clinically significant drug interactions have been identified since the approval of erythromycin. These interactions usually were related to the inhibition of the cytochrome P450 enzyme systems, which are responsible for the metabolism of many drugs. The decreased metabolism by the macrolides has in some instances resulted in potentially severe adverse events. The development and marketing of newer macrolides are hoped to improve the drug interaction profile associated with this class. However, this has produced variable success. Some of the newer macrolides demonstrated an interaction profile similar to that of erythromycin; others have improved profiles. The most success in avoiding drug interactions related to the inhibition of cytochrome P450 has been through the development of the azalide subclass, of which azithromycin is the first and only to be marketed. Azithromycin has not been demonstrated to inhibit the cytochrome P450 system in studies using a human liver microsome model, and to date has produced none of the classic drug interactions characteristic of the macrolides. Most of the available data regarding macrolide drug interactions are from studies in healthy volunteers and case reports. These data suggest that clarithromycin appears to have an interaction profile similar to that of erythromycin. Given this similarity, it is important to consider the interaction profile of clarithromycin when using erythromycin. This is especially necessary as funds for further studies of a medication available in generic form (e.g., erythromycin) are limited. Azithromycin has produced few clinically significant interactions with any agent cleared through the cytochrome P450 enzyme system. Although the available data are promising, the final test should come from studies conducted in patients who are taking potentially interacting compounds on a chronic basis.

Intolerance of uncertainty and transdiagnostic group cognitive behavioral therapy for anxiety.

PubMed

Talkovsky, Alexander M; Norton, Peter J

2016-06-01

Recent evidence suggests intolerance of uncertainty (IU) is a transdiagnostic variable elevated across anxiety disorders. No studies have investigated IU's response to transdiagnostic group CBT for anxiety (TGCBT). This study evaluated IU outcomes following TGCBT across anxiety disorders. 151 treatment-seekers with primary diagnoses of social anxiety disorder, panic disorder, or GAD were evaluated before and after 12 weeks of TGCBT and completed self-report questionnaires at pre-, mid-, and post-treatment. IU decreased significantly following treatment. Decreases in IU predicted improvements in clinical presentation across diagnoses. IU interacted with time to predict improvement in clinical presentation irrespective of primary diagnosis. IU also interacted with time to predict improvement in clinical presentation although interactions of time with diagnosis-specific measures did not. IUS interacted with time to predict reduction in anxiety and fear symptoms, and inhibitory IU interacted with time to predicted reductions in anxiety symptoms but prospective IU did not. IU appears to be an important transdiagnostic variable in CBT implicated in both initial presentation and treatment change. Further implications are discussed. Published by Elsevier Ltd.

Drug-nutrient interactions.

PubMed

Chan, Lingtak-Neander

2013-07-01

Drug-nutrient interactions are defined as physical, chemical, physiologic, or pathophysiologic relationships between a drug and a nutrient. The causes of most clinically significant drug-nutrient interactions are usually multifactorial. Failure to identify and properly manage drug-nutrient interactions can lead to very serious consequences and have a negative impact on patient outcomes. Nevertheless, with thorough review and assessment of the patient's history and treatment regimens and a carefully executed management strategy, adverse events associated with drug-nutrient interactions can be prevented. Based on the physiologic sequence of events after a drug or a nutrient has entered the body and the mechanism of interactions, drug-nutrient interactions can be categorized into 4 main types. Each type of interaction can be managed using similar strategies. The existing data that guide the clinical management of most drug-nutrient interactions are mostly anecdotal experience, uncontrolled observations, and opinions, whereas the science in understanding the mechanism of drug-nutrient interactions remains limited. The challenge for researchers and clinicians is to increase both basic and higher level clinical research in this field to bridge the gap between the science and practice. The research should aim to establish a better understanding of the function, regulation, and substrate specificity of the nutrient-related enzymes and transport proteins present in the gastrointestinal tract, as well as assess how the incidence and management of drug-nutrient interactions can be affected by sex, ethnicity, environmental factors, and genetic polymorphisms. This knowledge can help us develop a true personalized medicine approach in the prevention and management of drug-nutrient interactions.

Interactive effects of specific fine particulate matter compositions and airborne pollen on frequency of clinic visits for pollinosis in Fukuoka, Japan.

PubMed

Phosri, Arthit; Ueda, Kayo; Tasmin, Saira; Kishikawa, Reiko; Hayashi, Masahiko; Hara, Keiichiro; Uehara, Yamato; Phung, Vera Ling Hui; Yasukouchi, Shusuke; Konishi, Shoko; Honda, Akiko; Takano, Hirohisa

2017-07-01

Previous studies have revealed the interactive effects of airborne pollen and particulate matter on the daily consultations for pollinosis, but it is uncertain which compositions are responsible. This study aimed to investigate the interactive effects of specific PM 2.5 compositions and airborne pollen on the daily number of clinic visits for pollinosis in Fukuoka. We obtained daily data on pollen concentrations, PM 2.5 compositions, PM 2.5 mass, gaseous pollutants (SO 2 , NO 2 , CO, and O 3 ), and weather variables monitored in Fukuoka between February and April, 2002-2012. In total, 73,995 clinic visits for pollinosis were made at 10 clinics in Fukuoka Prefecture during the study period. A time-stratified case-crossover design was applied to examine the interactive effects. The concentrations of PM 2.5 and its compositions were stratified into low (<15th percentile), moderate (15th-85th percentile), and high (>85th percentile) levels, and the association between airborne pollen and daily clinic visits for pollinosis was analyzed within each level. We found a significant interaction between specific PM 2.5 compositions and airborne pollen. Specifically, the odds ratio of daily clinic visits for pollinosis per interquartile increase in pollen concentration (39.8 grains/cm 2 ) at the average cumulative lag of 0 and 2 days during high levels of non-sea-salt Ca 2+ was 1.446 (95% CI: 1.323-1.581), compared to 1.075 (95% CI: 1.067-1.083) when only moderate levels were observed. This result remained significant when other air pollutants were incorporated into the model and was fairly persistent even when different percentile cut-off points were used. A similar interaction was found when we stratified the data according to non-sea-salt SO 4 2- levels. This finding differed from estimates made according to PM 2.5 and NO 3 - levels, which predicted that the effects of pollen were strongest in the lower levels. Associations between airborne pollen and daily clinic visits for pollinosis could be enhanced by high levels of specific PM 2.5 compositions, especially non-sea-salt Ca 2+ . Copyright © 2017 Elsevier Inc. All rights reserved.

Assessment of Pediatric Dysphagia and Feeding Disorders: Clinical and Instrumental Approaches

ERIC Educational Resources Information Center

Arvedson, Joan C.

2008-01-01

Assessment of infants and children with dysphagia (swallowing problems) and feeding disorders involves significantly more considerations than a clinical observation of a feeding. In addition to the status of feeding in the child, considerations include health status, broad environment, parent-child interactions, and parental concerns.…

Clinical features and functional significance of the P369S/R408Q variant in pyrin, the familial Mediterranean fever protein.

PubMed

Ryan, J G; Masters, S L; Booty, M G; Habal, N; Alexander, J D; Barham, B K; Remmers, E F; Barron, K S; Kastner, D L; Aksentijevich, I

2010-07-01

Familial Mediterranean fever (FMF) is caused by mutations in MEFV, which encodes pyrin. The nature of substitutions P369S and R408Q in exon 3 remains unclear. Exon 3 encoding pyrin's B-box domain is necessary for interactions with proline serine threonine phosphatase interacting protein 1 (PSTPIP1). The aim was to characterise the phenotype of patients with these substitutions and to determine their functional significance. A database of genetic tests undertaken at the US National Institutes of Health was interrogated. Symptoms and signs were classified according to Tel-Hashomer criteria. Coimmunoprecipitation techniques were employed to determine the variants' effects on pyrin/PSTPIP1 interactions. A total of 40 symptomatic and 4 asymptomatic family members with these substitutions were identified. P369S and R408Q were found in cis, and cosegregated in all patients sequenced. Clinical details were available on 22 patients. In all, 5 patients had symptoms and signs fulfilling a clinical diagnosis of FMF, and 15 received colchicine. In patients not achieving the criteria, trials of anti-tumour necrosis factor (TNF) agents resulted in partial or no benefit; resolution of symptoms was noted in those receiving anakinra. The carrier frequency was higher in the patient cohort than in controls but was not statistically significant. Coimmunoprecipitation studies demonstrated that these pyrin variants did not affect binding to PSTPIP1. P369S/R408Q substitutions are associated with a highly variable phenotype, and are infrequently associated with typical FMF symptoms, however a trial of colchicine is warranted in all. Functional and modelling studies suggest that these substitutions do not significantly affect pyrin's interaction with PSTPIP1. This study highlights the need for caution in interpreting genetic tests in patients with atypical symptoms.

The Effects of an Interactive Nursing Skills Mobile Application on Nursing Students' Knowledge, Self-efficacy, and Skills Performance: A Randomized Controlled Trial.

PubMed

Kim, Hyunsun; Suh, Eunyoung E

2018-03-01

Clinical nursing practice is important because it helps nursing students experience realities of clinical nursing that cannot be learned through theoretical education. This study aimed to evaluate the effect of an interactive nursing skills mobile application for nursing students. Sixty-six senior nursing students were randomly assigned to experimental or control groups. The experimental group used an interactive nursing skills mobile application for 1 week. The control group was provided with a mobile application containing noninteractive nursing video contents for 1 week. Before (pre-test) and 1 week after (post-test) using the mobile application, participants' knowledge of clinical nursing skills, self-efficacy of nursing practice, and nursing skills performance were assessed. The experimental group showed a significantly higher value for knowledge after 1 week of treatment via their mobile application than the control group (t = 3.34, p = .001). In addition, they showed significantly improved self-efficacy before and after intervention (t = 2.46, p = .017) than the control group. The experimental group's nursing skills performance was also significantly enhanced after intervention (t = 7.05, p < .001), with a significant difference in the degree of improvement (t = 4.47, p < .001). The interactive learner-centered nursing education mobile application with systematic contents was an effective method for students to experience practical nursing skills. Developing and applying a mobile application with other nursing contents that can be effectively used across all range of nursing students is recommended. Copyright © 2018. Published by Elsevier B.V.

An overview of bilastine metabolism during preclinical investigations.

PubMed

Lucero, María Luisa; Gonzalo, Ana; Mumford, Rory; Betanzos, Mónica; Alejandro, Ana

2012-06-01

Knowledge of the biotransformation of oral H₁ antihistamines is clinically important because it can define their pharmacokinetic profile through possible effects on absorption (i.e., first-pass metabolism) and elimination. Further, clinically significant interactions with inhibitors of cytochrome P450 (CYP) have previously been reported for drugs of this therapeutic group, such as terfenadine and astemizole, indicating the possibility of drug-drug interactions involving agents that share the same metabolic pathway. The aim of this article was to review the preclinical testing of a new antihistamine (i.e., bilastine) in terms of its biotransformation in various animal species, including humans, and to evaluate its potential for possible drug-drug interactions involving the CYP system. A wide array of preclinical experiments were reviewed, all of which demonstrated that bilastine undergoes minimal metabolism in all species tested to date, including humans. Further, bilastine did not interact significantly, either as an inhibitor or inducer, with the CYP enzyme system, suggesting a low propensity for involvement in drug-drug interactions. These characteristics demonstrate the potential for bilastine to be a good choice for allergic patients receiving treatment for other concomitant diseases, including those with renal or hepatic dysfunction.

An Interactive Platform to Visualize Data-Driven Clinical Pathways for the Management of Multiple Chronic Conditions.

PubMed

Zhang, Yiye; Padman, Rema

2017-01-01

Patients with multiple chronic conditions (MCC) pose an increasingly complex health management challenge worldwide, particularly due to the significant gap in our understanding of how to provide coordinated care. Drawing on our prior research on learning data-driven clinical pathways from actual practice data, this paper describes a prototype, interactive platform for visualizing the pathways of MCC to support shared decision making. Created using Python web framework, JavaScript library and our clinical pathway learning algorithm, the visualization platform allows clinicians and patients to learn the dominant patterns of co-progression of multiple clinical events from their own data, and interactively explore and interpret the pathways. We demonstrate functionalities of the platform using a cluster of 36 patients, identified from a dataset of 1,084 patients, who are diagnosed with at least chronic kidney disease, hypertension, and diabetes. Future evaluation studies will explore the use of this platform to better understand and manage MCC.

LPHN3 and Attention-Deficit/Hyperactivity Disorder: Interaction with Maternal Stress during Pregnancy

ERIC Educational Resources Information Center

Choudhry, Zia; Sengupta, Sarojini M.; Grizenko, Natalie; Fortier, Marie-Eve; Thakur, Geeta A.; Bellingham, Johanne; Joober, Ridha

2012-01-01

Background: Attention-deficit/hyperactivity disorder (ADHD) is a heterogeneous behavioral disorder, complex both in etiology and clinical expression. Both genetic and environmental factors have been implicated, and it has been suggested that gene-environment interactions may play a pivotal role in the disorder. Recently, a significant association…

Cytochrome P450 enzyme mediated herbal drug interactions (Part 1)

PubMed Central

Wanwimolruk, Sompon; Prachayasittikul, Virapong

2014-01-01

It is well recognized that herbal supplements or herbal medicines are now commonly used. As many patients taking prescription medications are concomitantly using herbal supplements, there is considerable risk for adverse herbal drug interactions. Such interactions can enhance the risk for an individual patient, especially with regard to drugs with a narrow therapeutic index such as warfarin, cyclosporine A and digoxin. Herbal drug interactions can alter pharmacokinetic or/and pharmacodynamic properties of administered drugs. The most common pharmacokinetic interactions usually involve either the inhibition or induction of the metabolism of drugs catalyzed by the important enzymes, cytochrome P450 (CYP). The aim of the present article is to provide an updated review of clinically relevant metabolic CYP-mediated drug interactions between selected herbal supplements and prescription drugs. The commonly used herbal supplements selected include Echinacea, Ginkgo biloba, garlic, St. John's wort, goldenseal, and milk thistle. To date, several significant herbal drug interactions have their origins in the alteration of CYP enzyme activity by various phytochemicals. Numerous herbal drug interactions have been reported. Although the significance of many interactions is uncertain but several interactions, especially those with St. John’s wort, may have critical clinical consequences. St. John’s wort is a source of hyperforin, an active ingredient that has a strong affinity for the pregnane xenobiotic receptor (PXR). As a PXR ligand, hyperforin promotes expression of CYP3A4 enzymes in the small intestine and liver. This in turn causes induction of CYP3A4 and can reduce the oral bioavailability of many drugs making them less effective. The available evidence indicates that, at commonly recommended doses, other selected herbs including Echinacea, Ginkgo biloba, garlic, goldenseal and milk thistle do not act as potent or moderate inhibitors or inducers of CYP enzymes. A good knowledge of the mechanisms of herbal drug interactions is necessary for assessing and minimizing clinical risks. These processes help prediction of interactions between herbal supplements and prescription drugs. Healthcare professionals should remain vigilant for potential interactions between herbal supplements/medicines and prescription drugs, especially for drugs with a narrow therapeutic index are used. PMID:26417265

Effects of Job Burnout and Emotional Labor on Objective Structured Clinical Examination Performance Among Interns and Residents in Taiwan.

PubMed

Wang, Chen-Yu; Chen, Jen-De; Wang, Chih-Hung; Wang, Jong-Yi; Tai, Chih-Jaan; Hsieh, Tsu-Yi; Chen, Der-Yuan

2017-01-01

Medical education faces challenges concerning job burnout and emotional labor among junior physicians, which poses a potential threat to the quality of medical care. Although studies have investigated job burnout and emotional labor among physicians, empirical research on the association between job burnout, emotional labor, and clinical performance is lacking. This study investigated the effects of job burnout and emotional labor on clinical performance by using the objective structured clinical examination (OSCE) scores of interns and residents. Specifically, this cross-sectional study utilized the Maslach Burnout Inventory and the Emotional Labor Questionnaire as measurement instruments. A total of 225 interns and residents in central Taiwan answered structured questionnaires before beginning their OSCE. The major statistical analysis method employed was logistic regression. After adjustment for covariates, first-year residents were less likely than other residents to obtain high OSCE scores. The odds of high OSCE performance among interns and residents with high interaction component scores in emotional labor were significantly higher than those with low interaction scores. A high score in the interaction dimension of emotional labor was associated with strong clinical performance. The findings suggest that interventions which motivate positive attitudes and increase interpersonal interaction skills among physicians should receive higher priority.

An evaluation of learning clinical decision-making for early rehabilitation in the ICU via interactive education with audience response system.

PubMed

Toonstra, Amy L; Nelliot, Archana; Aronson Friedman, Lisa; Zanni, Jennifer M; Hodgson, Carol; Needham, Dale M

2017-06-01

Knowledge-related barriers to safely implement early rehabilitation programs in intensive care units (ICUs) may be overcome via targeted education. The purpose of this study was to evaluate the effectiveness of an interactive educational session on short-term knowledge of clinical decision-making for safe rehabilitation of patients in ICUs. A case-based teaching approach, drawing from published safety recommendations for initiation of rehabilitation in ICUs, was used with a multidisciplinary audience. An audience response system was incorporated to promote interaction and evaluate knowledge before vs. after the educational session. Up to 175 audience members, of 271 in attendance (129 (48%) physical therapists, 51 (19%) occupational therapists, 31 (11%) nursing, 14 (5%) physician, 46 (17%) other), completed both the pre- and post-test questions for each of the six unique patient cases. In four of six patient cases, there was a significant (p< 0.001) increase in identifying the correct answer regarding initiation of rehabilitation activities. This learning effect was similar irrespective of participants' years of experience and clinical discipline. An interactive, case-based, educational session may be effective for increasing short-term knowledge, and identifying knowledge gaps, regarding clinical decision-making for safe rehabilitation of patients in ICUs. Implications for Rehabilitation Lack of knowledge regarding the safety considerations for early rehabilitation of ICU patients is a barrier to implementing early rehabilitation. Interactive educational formats, such as the use of audience response systems, offer a new method of teaching and instantly assessing learning of clinically important information. In a small study, we have shown that an interactive, case-based educational format may be used to effectively teach clinical decision-making for the safe rehabilitation of ICU patients to a diverse audience of clinicians.

Patterns of mother-infant interaction from 3 to 12 months among dyads with substance abuse and psychiatric problems.

PubMed

Siqveland, Torill S; Haabrekke, Kristin; Wentzel-Larsen, Tore; Moe, Vibeke

2014-11-01

The aim of this study was to investigate the development of mother-infant interaction patterns from 3 to 12 months among three groups of mother-baby pairs recruited during pregnancy: one group from residential substance abuse treatment (n=28), a second group from psychiatric outpatient treatment (n=22), and a third group from well-baby clinics (n=30). The mother-infant interaction at 3 and 12 months was assessed by the Parent-Child Early Relational Assessment (PCERA), which consists of maternal, child and dyadic subscales (Clark, 2006). Linear mixed effects models were used to analyze group differences and the changes in mother-infant interaction from 3 to 12 months. At 3 months, pairwise comparisons showed that the group with psychiatric problems had significantly more difficulties in the mother-infant interaction than the two other groups. The group with substance abuse problems was not significantly different from the two other groups. At 12 months, the mother-infant pairs in the substance abuse group showed significantly more relational disturbances than the non-clinical pairs, as well as a poorer affective quality of interaction than the dyads in the group with psychiatric problems. Analysis of change from 3 to 12 months showed that difficulties in the interaction increased among the mother-baby pairs in the substance abuse group, while improvements were displayed in the two other groups. These results underline that mother-infant pairs at double risk due to maternal substance abuse and other non-optimal factors, are in need for long-term follow up in order to prevent the development of negative interactional patterns. Copyright © 2014 Elsevier Inc. All rights reserved.

The interaction between cannabis use and the Val158Met polymorphism of the COMT gene in psychosis: A transdiagnostic meta – analysis

PubMed Central

Schäfer, Annika Theresia; Damen, Thomas; Uittenboogaard, Aniek; Krolinski, Pauline; Nwosu, Chinyere Vicky; Pinckaers, Florentina Maria Egidius; Rotee, Iris Leah Marije; Ermiş, Ayşegül; Kennedy, James L.; Nieman, Dorien H.; Tiwari, Arun; van Os, Jim

2018-01-01

Background Neither environmental nor genetic factors are sufficient to predict the transdiagnostic expression of psychosis. Therefore, analysis of gene-environment interactions may be productive. Objective A meta-analysis was performed using papers investigating the interaction between cannabis use and catechol-O-methyl transferase (COMT) polymorphism Val158Met (COMTVal158Met). Data sources PubMed, Embase, PsychInfo. Study eligibility criteria All observational studies assessing the interaction between COMTVal158Met and cannabis with any psychosis or psychotic symptoms measure as an outcome. Study appraisal and synthesis methods A meta-analysis was performed using the Meta-analysis of Observational Studies in Epidemiology guidelines and forest plots were generated. Thirteen articles met the selection criteria: 7 clinical studies using a case-only design, 3 clinical studies with a dichotomous outcome, and 3 studies analysing a continuous outcome of psychotic symptoms below the threshold of psychotic disorder. The three study types were analysed separately. Validity of the included studies was assessed using "A Cochrane Risk of Bias Assessment Tool: for Non-Randomized Studies of Interventions". Results For case-only studies, a significant interaction was found between cannabis use and COMTVal158Met, with an OR of 1.45 (95% Confidence Interval = 1.05–2.00; Met/Met as the risk genotype). However, there was no evidence for interaction in either the studies including dichotomous outcomes (B = -0.51, 95% Confidence Interval -1.72, 0.70) or the studies including continuous outcomes (B = -0.04 95% Confidence Interval -0.16–0.08). Limitation A substantial part of the included studies used the case-only design, which has lower validity and tends to overestimate true effects. Conclusion The interaction term between cannabis use and COMTVal158Met was only statistically significant in the case-only studies, but not in studies using other clinical or non-clinical psychosis outcomes. Future additional high quality studies might change current perspectives, yet currently evidence for the interaction remains unconvincing. PMID:29444152

Content and Usability Evaluation of Patient Oriented Drug-Drug Interaction Websites.

PubMed

Adam, Terrence J; Vang, Joseph

Drug-Drug Interactions (DDI) are an important source of preventable adverse drug events and a common reason for hospitalization among patients on multiple drug therapy regimens. DDI information systems are important patient safety tools with the capacity to identify and warn health professionals of clinically significant DDI risk. While substantial research has been completed on DDI information systems in professional settings such as community, hospital, and independent pharmacies; there has been limited research on DDI systems offered through online websites directly for use by ambulatory patients. The focus of this project is to test patient oriented website capacity to correctly identify drug interactions among well established and clinically significant medication combinations and convey clinical risk data to patients. The patient education capability was assessed by evaluating website Information Capacity, Patient Usability and Readability. The study results indicate that the majority of websites identified which met the inclusion and exclusion criteria operated similarly, but vary in risk severity assessment and are not optimally patient oriented to effectively deliver risk information. The limited quality of information and complex medical term content complicate DDI risk data conveyance and the sites may not provide optimal information delivery to allow medication consumers to understand and manage their medication regimens.

Therapeutic Risk and Benefits of Concomitantly Using Herbal Medicines and Conventional Medicines: From the Perspectives of Evidence Based on Randomized Controlled Trials and Clinical Risk Management

PubMed Central

Zhang, Xiu-lai; Chen, Meng; Zhu, Ling-ling

2017-01-01

Despite increased awareness of the potential of herb-drug interactions (HDIs), the lack of rigorous clinical evidence regarding the significance provides a challenge for clinicians and consumers to make rational decisions about the safe combination of herbal and conventional medicines. This review addressed HDIs based on evidence from randomized controlled trials (RCTs). Literature was identified by performing a PubMed search till January 2017. Risk description and clinical risk management were described. Among 74 finally included RCTs, 17 RCTs (22.97%) simply addressed pharmacodynamic HDIs. Fifty-seven RCTs (77.03%) investigated pharmacokinetic HDIs and twenty-eight of them showed potential or actual clinical relevance. The extent of an HDI may be associated with the factors such as pharmacogenomics, dose of active ingredients in herbs, time course of interaction, characteristics of the object drugs (e.g., administration routes and pharmacokinetic profiles), modification of herbal prescription compositions, and coexistence of inducers and inhibitors. Clinical professionals should enhance risk management on HDIs such as increasing awareness of potential changes in therapeutic risk and benefits, inquiring patients about all currently used conventional medicines and herbal medicines and supplements, automatically detecting highly substantial significant HDI by computerized reminder system, selecting the alternatives, adjusting dose, reviewing the appropriateness of physician orders, educating patients to monitor for drug-interaction symptoms, and paying attention to follow-up visit and consultation. PMID:28491115

Assessment of pharmacy students' communication competence using the Roter Interaction Analysis System during objective structured clinical examinations.

PubMed

Kubota, Yoshie; Yano, Yoshitaka; Seki, Susumu; Takada, Kaori; Sakuma, Mio; Morimoto, Takeshi; Akaike, Akinori; Hiraide, Atsushi

2011-04-11

To determine the value of using the Roter Interaction Analysis System during objective structured clinical examinations (OSCEs) to assess pharmacy students' communication competence. As pharmacy students completed a clinical OSCE involving an interview with a simulated patient, 3 experts used a global rating scale to assess students' overall performance in the interview, and both the student's and patient's languages were coded using the Roter Interaction Analysis System (RIAS). The coders recorded the number of utterances (ie, units of spoken language) in each RIAS category. Correlations between the raters' scores and the number and types of utterances were examined. There was a significant correlation between students' global rating scores on the OSCE and the number of utterances in the RIAS socio-emotional category but not the RIAS business category. The RIAS proved to be a useful tool for assessing the socio-emotional aspect of students' interview skills.

A current review of cytochrome P450 interactions of psychotropic drugs.

PubMed

Madhusoodanan, Subramoniam; Velama, Umamaheswararao; Parmar, Jeniel; Goia, Diana; Brenner, Ronald

2014-05-01

The number of psychotropic drugs has expanded tremendously over the past few decades with a proportional increase in drug-drug interactions. The majority of psychotropic agents are biotransformed by hepatic enzymes, which can lead to significant drug-drug interactions. Most drug-drug interactions of psychotropics occur at metabolic level involving the hepatic cytochrome P450 enzyme system. We searched the National Library of Medicine, PsycINFO, and Cochrane reviews from 1981 to 2012 for original studies including clinical trials, double-blind, placebo-controlled studies, and randomized controlled trials. In addition, case reports, books, review articles, and hand-selected journals were utilized to supplement this review. Based on the clinical intensity of outcome, cytochrome interactions can be classified as severe, moderate, and mild. Severe interactions include effects that might be acutely life threatening. They are mainly inhibitory interactions with cardiovascular drugs. Moderate interactions include efficacy issues. Mild interactions include nonserious side effects, such as somnolence. Psychotropic drugs may interact with other prescribed medications used to treat concomitant medical illnesses. A thorough understanding of the most prescribed medications and patient education will help reduce the likelihood of potentially fatal drug-drug interactions.

Pre-Clinical Drug Prioritization via Prognosis-Guided Genetic Interaction Networks

PubMed Central

Xiong, Jianghui; Liu, Juan; Rayner, Simon; Tian, Ze; Li, Yinghui; Chen, Shanguang

2010-01-01

The high rates of failure in oncology drug clinical trials highlight the problems of using pre-clinical data to predict the clinical effects of drugs. Patient population heterogeneity and unpredictable physiology complicate pre-clinical cancer modeling efforts. We hypothesize that gene networks associated with cancer outcome in heterogeneous patient populations could serve as a reference for identifying drug effects. Here we propose a novel in vivo genetic interaction which we call ‘synergistic outcome determination’ (SOD), a concept similar to ‘Synthetic Lethality’. SOD is defined as the synergy of a gene pair with respect to cancer patients' outcome, whose correlation with outcome is due to cooperative, rather than independent, contributions of genes. The method combines microarray gene expression data with cancer prognostic information to identify synergistic gene-gene interactions that are then used to construct interaction networks based on gene modules (a group of genes which share similar function). In this way, we identified a cluster of important epigenetically regulated gene modules. By projecting drug sensitivity-associated genes on to the cancer-specific inter-module network, we defined a perturbation index for each drug based upon its characteristic perturbation pattern on the inter-module network. Finally, by calculating this index for compounds in the NCI Standard Agent Database, we significantly discriminated successful drugs from a broad set of test compounds, and further revealed the mechanisms of drug combinations. Thus, prognosis-guided synergistic gene-gene interaction networks could serve as an efficient in silico tool for pre-clinical drug prioritization and rational design of combinatorial therapies. PMID:21085674

[Potential antimicrobial drug interactions in clinical practice: consequences of polypharmacy and multidrug resistance].

PubMed

Martínez-Múgica, Cristina

2015-12-01

Polypharmacy is a growing problem nowadays, which can increase the risk of potential drug interactions, and result in a loss of effectiveness. This is particularly relevant to the anti-infective therapy, especially when infection is produced by resistant bacteria, because therapeutic options are limited and interactions can cause treatment failure. All antimicrobial prescriptions were retrospectively reviewed during a week in the Pharmacy Department, in order to detect potential drug-interactions and analysing their clinical significance. A total of 314 antimicrobial prescriptions from 151 patients were checked. There was at least one potential interaction detected in 40% of patients, being more frequent and severe in those infected with multidrug-resistant microorganisms. Drugs most commonly involved were quinolones, azoles, linezolid and vancomycin. Potential drug interactions with antimicrobial agents are a frequent problem that can result in a loss of effectiveness. This is why they should be detected and avoided when possible, in order to optimize antimicrobial therapy, especially in case of multidrug resistant infections.

Cumulative risk and AIDS-orphanhood: interactions of stigma, bullying and poverty on child mental health in South Africa.

PubMed

Cluver, Lucie; Orkin, Mark

2009-10-01

Research shows that AIDS-orphaned children are more likely to experience clinical-range psychological problems. Little is known about possible interactions between factors mediating these high distress levels. We assessed how food insecurity, bullying, and AIDS-related stigma interacted with each other and with likelihood of experiencing clinical-range disorder. In South Africa, 1025 adolescents completed standardised measures of depression, anxiety and post-traumatic stress. 52 potential mediators were measured, including AIDS-orphanhood status. Logistic regressions and hierarchical log-linear modelling were used to identify interactions among significant risk factors. Food insecurity, stigma and bullying all independently increased likelihood of disorder. Poverty and stigma were found to interact strongly, and with both present, likelihood of disorder rose from 19% to 83%. Similarly, bullying interacted with AIDS-orphanhood status, and with both present, likelihood of disorder rose from 12% to 76%. Approaches to alleviating psychological distress amongst AIDS-affected children must address cumulative risk effects.

Adding "Circle of Security - Parenting" to treatment as usual in three Swedish infant mental health clinics. Effects on parents' internal representations and quality of parent-infant interaction.

PubMed

Risholm Mothander, Pia; Furmark, Catarina; Neander, Kerstin

2018-06-01

This study presents effects of adding Circle of Security-Parenting (COS-P) to an already established comprehensive therapeutic model for early parent-child intervention in three Swedish infant mental health (IMH) clinics. Parents' internal representations and quality of parent-infant interaction were studied in a clinical sample comprised of 52 parent-infant dyads randomly allocated to two comparable groups. One group consisted of 28 dyads receiving treatment as usual (TAU) supplemented with COS-P in a small group format, and another group of 24 dyads receiving TAU only. Assessments were made at baseline (T1), 6 months after inclusion (T2) and 12 months after inclusion (T3). Changes over time were explored in 42 dyads. In the COS-P group, the proportion of balanced representations, as assessed with Working Model of the Child Interview (WMCI), significantly increased between T1 and T3. Further, the proportion of emotionally available interactions, as assessed with Emotional Availability scales (EA), significantly increased over time in the COS-P group. Improvements in the TAU-group were close to significant. Limitations of the study are mainly related to the small sample size. Strength is the real world character of the study, where COS-P was implemented in a clinical context not otherwise adapted to research. We conclude by discussing the value of supplementing TAU with COS-P in IMH treatment. © 2017 The Authors. Scandinavian Journal of Psychology published by Scandinavian Psychological Associations and John Wiley & Sons Ltd.

Impact of postgraduate training on communication skills teaching: a controlled study.

PubMed

Junod Perron, Noelle; Nendaz, Mathieu; Louis-Simonet, Martine; Sommer, Johanna; Gut, Anne; Cerutti, Bernard; van der Vleuten, Cees P; Dolmans, Diana

2014-04-14

Observation of performance followed by feedback is the key to good teaching of communication skills in clinical practice. The fact that it occurs rarely is probably due to clinical supervisors' perceived lack of competence to identify communication skills and give effective feedback. We evaluated the impact of a faculty development programme on communication skills teaching on clinical supervisors' ability to identify residents' good and poor communication skills and to discuss them interactively during feedback. We conducted a pre-post controlled study in which clinical supervisors took part to a faculty development program on teaching communication skills in clinical practice. Outcome measures were the number and type of residents' communication skills identified by supervisors in three videotaped simulated resident-patient encounters and the number and type of communication skills discussed interactively with residents during three feedback sessions. 48 clinical supervisors (28 intervention group; 20 control group) participated. After the intervention, the number and type of communication skills identified did not differ between both groups. There was substantial heterogeneity in the number and type of communication skills identified. However, trained participants engaged in interactive discussions with residents on a significantly higher number of communication items (effect sizes 0.53 to 1.77); communication skills items discussed interactively included both structural and patient-centered elements that were considered important to be observed by expert teachers. The faculty development programme did not increase the number of communication skills recognised by supervisors but was effective in increasing the number of communication issues discussed interactively in feedback sessions. Further research should explore the respective impact of accurate identification of communication skills and effective teaching skills on achieving more effective communication skills teaching in clinical practice.

Impact of postgraduate training on communication skills teaching: a controlled study

PubMed Central

2014-01-01

Background Observation of performance followed by feedback is the key to good teaching of communication skills in clinical practice. The fact that it occurs rarely is probably due to clinical supervisors’ perceived lack of competence to identify communication skills and give effective feedback. We evaluated the impact of a faculty development programme on communication skills teaching on clinical supervisors’ ability to identify residents’ good and poor communication skills and to discuss them interactively during feedback. Methods We conducted a pre-post controlled study in which clinical supervisors took part to a faculty development program on teaching communication skills in clinical practice. Outcome measures were the number and type of residents’ communication skills identified by supervisors in three videotaped simulated resident-patient encounters and the number and type of communication skills discussed interactively with residents during three feedback sessions. Results 48 clinical supervisors (28 intervention group; 20 control group) participated. After the intervention, the number and type of communication skills identified did not differ between both groups. There was substantial heterogeneity in the number and type of communication skills identified. However, trained participants engaged in interactive discussions with residents on a significantly higher number of communication items (effect sizes 0.53 to 1.77); communication skills items discussed interactively included both structural and patient-centered elements that were considered important to be observed by expert teachers. Conclusions The faculty development programme did not increase the number of communication skills recognised by supervisors but was effective in increasing the number of communication issues discussed interactively in feedback sessions. Further research should explore the respective impact of accurate identification of communication skills and effective teaching skills on achieving more effective communication skills teaching in clinical practice. PMID:24731477

Drug Interactions with Lithium: An Update.

PubMed

Finley, Patrick R

2016-08-01

Lithium has been used for the management of psychiatric illnesses for over 50 years and it continues to be regarded as a first-line agent for the treatment and prevention of bipolar disorder. Lithium possesses a narrow therapeutic index and comparatively minor alterations in plasma concentrations can have significant clinical sequelae. Several drug classes have been implicated in the development of lithium toxicity over the years, including diuretics and non-steroidal anti-inflammatory compounds, but much of the anecdotal and experimental evidence supporting these interactions is dated, and many newer medications and medication classes have been introduced during the intervening years. This review is intended to provide an update on the accumulated evidence documenting potential interactions with lithium, with a focus on pharmacokinetic insights gained within the last two decades. The clinical relevance and ramifications of these interactions are discussed.

Exploring the interaction of patient activation and message design variables: message frame and presentation mode influence on the walking behavior of patients with type 2 diabetes.

PubMed

Ledford, Christy J W

2012-10-01

Examining interpersonal (physician-patient) communication strategies for promoting walking exercise to patients with type 2 diabetes assigned to primary care clinics, the study evaluated two message design variables--frame and presentation mode--as influencers of communication and adoption success. The single-site, four-week, prospective intervention study followed a 2×3 factorial, non-equivalent comparison group quasi-experimental design. Results showed frame was significantly related to steps walked; however, when including patient activation as an interaction, frame was non-significant. The model including patient activation interactions, however, detected significant mode effects on behavior. Results provide evidence that statistics are most effectively used with activated patients.

Multiple Levels of Suffering: Discrimination in Health-Care Settings is Associated With Enhanced Laboratory Pain Sensitivity in Sickle Cell Disease.

PubMed

Mathur, Vani A; Kiley, Kasey B; Haywood, Carlton; Bediako, Shawn M; Lanzkron, Sophie; Carroll, C Patrick; Buenaver, Luis F; Pejsa, Megan; Edwards, Robert R; Haythornthwaite, Jennifer A; Campbell, Claudia M

2016-12-01

People living with sickle cell disease (SCD) experience severe episodic and chronic pain and frequently report poor interpersonal treatment within health-care settings. In this particularly relevant context, we examined the relationship between perceived discrimination and both clinical and laboratory pain. Seventy-one individuals with SCD provided self-reports of experiences with discrimination in health-care settings and clinical pain severity, and completed a psychophysical pain testing battery in the laboratory. Discrimination in health-care settings was correlated with greater clinical pain severity and enhanced sensitivity to multiple laboratory-induced pain measures, as well as stress, depression, and sleep. After controlling for relevant covariates, discrimination remained a significant predictor of mechanical temporal summation (a marker of central pain facilitation), but not clinical pain severity or suprathreshold heat pain response. Furthermore, a significant interaction between experience with discrimination and clinical pain severity was associated with mechanical temporal summation; increased experience with discrimination was associated with an increased correlation between clinical pain severity and temporal summation of pain. Perceived discrimination within health-care settings was associated with pain facilitation. These findings suggest that discrimination may be related to increased central sensitization among SCD patients, and more broadly that health-care social environments may interact with pain pathophysiology.

Are Pain-Related Temporomandibular Disorders the Product of an Interaction Between Psychological Factors and Self-Reported Bruxism?

PubMed

van Selms, Maurits Ka; Muzalev, Konstantin; Visscher, Corine M; Koutris, Michail; Bulut, Melike; Lobbezoo, Frank

2017-01-01

To investigate whether pain-related temporomandibular disorders (TMD) are the product of an interaction between psychological factors and self-reported bruxism activities. Patients referred to a specialized clinic for complaints of orofacial pain and dysfunction completed a digital questionnaire prior to the first clinical visit. The patient sample was then split into a case group consisting of 268 patients diagnosed with TMD pain according to the Diagnostic Criteria for Temporomandibular Disorders (85.8% women; mean ± standard deviation [SD] age = 40.1 ± 14.5 years) and a control group consisting of 254 patients without any pain in the orofacial area (50.8% women; 46.9 ± 13.6 years). The possible moderating roles of six psychological factors (depression, somatic symptoms, anxiety, stress, optimism, and prior psychological treatment) on the relationship between self-reported bruxism and the clinical presence of TMD pain were examined. Patients with TMD pain reported significantly more bruxism than patients without any report of orofacial pain. Furthermore, bruxism intensity was associated with a variety of psychological factors; however, there were no significant interactions between any of the psychological factors and bruxism with respect to the clinical presence of TMD pain. These findings do not support the view that the effect of bruxism on TMD pain is stronger in patients who experience higher levels of psychological distress compared to those with lower levels of distress.

Attitudinal effects of degrading themes and sexual explicitness in video materials.

PubMed

Golde, J A; Strassberg, D S; Turner, C M; Lowe, K

2000-07-01

This study examined the independent and interactive effects of sexual explicitness and degrading themes toward women on mens' attitudes following exposure to video presentations of male-female interactions. Subjects were 83 male college students who viewed video vignettes under one of four stimulus conditions: (a) sexually explicit/degrading, (b) sexually explicit/nondegrading, (c) nonexplicit/degrading, and (d) nonexplicit/nondegrading. Results revealed that men exposed to degrading material, regardless of explicitness, were significantly more likely to express attitudes supportive of rape, while explicitness had no significant main or interactive effect on these attitudes. Further, the interaction of explicitness with degradation was found to impact scores on a measure of sexual callousness. Theoretical and clinical implications of these findings are discussed.

Identification of GRB2 and GAB1 Coexpression as an Unfavorable Prognostic Factor for Hepatocellular Carcinoma by a Combination of Expression Profile and Network Analysis

PubMed Central

Yang, Mei; Wang, Danhua; Yu, Lingxiang; Guo, Chaonan; Guo, Xiaodong; Lin, Na

2013-01-01

Aim To screen novel markers for hepatocellular carcinoma (HCC) by a combination of expression profile, interaction network analysis and clinical validation. Methods HCC significant molecules which are differentially expressed or had genetic variations in HCC tissues were obtained from five existing HCC related databases (OncoDB.HCC, HCC.net, dbHCCvar, EHCO and Liverome). Then, the protein-protein interaction (PPI) network of these molecules was constructed. Three topological features of the network ('Degree', 'Betweenness', and 'Closeness') and the k-core algorithm were used to screen candidate HCC markers which play crucial roles in tumorigenesis of HCC. Furthermore, the clinical significance of two candidate HCC markers growth factor receptor-bound 2 (GRB2) and GRB2-associated-binding protein 1 (GAB1) was validated. Results In total, 6179 HCC significant genes and 977 HCC significant proteins were collected from existing HCC related databases. After network analysis, 331 candidate HCC markers were identified. Especially, GAB1 has the highest k-coreness suggesting its central localization in HCC related network, and the interaction between GRB2 and GAB1 has the largest edge-betweenness implying it may be biologically important to the function of HCC related network. As the results of clinical validation, the expression levels of both GRB2 and GAB1 proteins were significantly higher in HCC tissues than those in their adjacent nonneoplastic tissues. More importantly, the combined GRB2 and GAB1 protein expression was significantly associated with aggressive tumor progression and poor prognosis in patients with HCC. Conclusion This study provided an integrative analysis by combining expression profile and interaction network analysis to identify a list of biologically significant HCC related markers and pathways. Further experimental validation indicated that the aberrant expression of GRB2 and GAB1 proteins may be strongly related to tumor progression and prognosis in patients with HCC. The overexpression of GRB2 in combination with upregulation of GAB1 may be an unfavorable prognostic factor for HCC. PMID:24391994

Interactions between recreational drugs and antiretroviral agents.

PubMed

Antoniou, Tony; Tseng, Alice Lin-In

2002-10-01

To summarize existing data regarding potential interactions between recreational drugs and drugs commonly used in the management of HIV-positive patients. Information was obtained via a MEDLINE search (1966-August 2002) using the MeSH headings human immunodeficiency virus, drug interactions, cytochrome P450, medication names commonly prescribed for the management of HIV and related opportunistic infections, and names of commonly used recreational drugs. Abstracts of national and international conferences, review articles, textbooks, and references of all articles were also reviewed. Literature on pharmacokinetic interactions was considered for inclusion. Pertinent information was selected and summarized for discussion. In the absence of specific data, prediction of potential clinically significant interactions was based on pharmacokinetic and pharmacodynamic properties. All protease inhibitors (PIs) and nonnucleoside reverse transcriptase inhibitors are substrates and potent inhibitors or inducers of the cytochrome P450 system. Many classes of recreational drugs, including benzodiazepines, amphetamines, and opioids, are also metabolized by the liver and can potentially interact with antiretrovirals. Controlled interaction studies are often not available, but clinically significant interactions have been observed in a number of case reports. Overdoses secondary to interactions between the "rave" drugs methylenedioxymethamphetamine (MDMA) or gamma-hydroxybutyrate (GHB) and PIs have been reported. PIs, particularly ritonavir, may also inhibit metabolism of amphetamines, ketamine, lysergic acid diethylmide (LSD), and phencyclidine (PCP). Case series and pharmacokinetic studies suggest that nevirapine and efavirenz induce methadone metabolism, which may lead to symptoms of opiate withdrawal. A similar interaction may exist between methadone and the PIs ritonavir and nelfinavir, although the data are less consistent. Opiate metabolism can be inhibited or induced by concomitant PIs, and patients should be monitored for signs of toxicity and/or loss of analgesia. PIs should not be coadministered with midazolam and triazolam, since prolonged sedation may occur. Interactions between agents commonly prescribed for patients with HIV and recreational drugs can occur, and may be associated with serious clinical consequences. Clinicians should encourage open dialog with their patients on this topic, to avoid compromising antiretroviral efficacy and increasing the risk of drug toxicity.

Rapid Growth in Surgeons’ Use of Secure Messaging in a Patient Portal

PubMed Central

Shenson, Jared A.; Cronin, Robert M.; Davis, Sharon E.; Chen, Qingxia; Jackson, Gretchen Purcell

2016-01-01

Background Use of secure messaging through patient portals has risen substantially in recent years due to provider incentives and consumer demand. Secure messaging may increase patient satisfaction and improve outcomes, but also adds to physician workload. Most prior studies of secure messaging focused on primary care and medical specialties. We examined surgeons’ use of secure messaging and the contribution of messaging to outpatient interactions in a broadly-deployed patient portal. Methods We determined the number of clinic visits and secure messages for surgical providers in the first three years (2008–10) after patient portal deployment at an academic medical center. We calculated the proportion of outpatient interaction conducted through messaging for each specialty. Logistic regression models compared the likelihood of message-based versus clinic outpatient interaction across surgical specialties. Results Over the study period, surgical providers delivered care in 648,200 clinic visits and received 83,912 messages, with more than 200% growth in monthly message volume. Surgical specialties receiving the most messages were orthopedics/podiatry (25.1%), otolaryngology (20.1%), urology (10.8%), and general surgery (9.6%); vascular surgery (0.8%) and pediatric general surgery (0.2%) received the fewest. The proportion of outpatient interactions conducted through secure messaging increased significantly from 5.4% in 2008 to 15.3% in 2010 (p<0.001) with all specialties experiencing growth. Heart/lung transplantation (74.9%), liver/kidney/pancreas transplantation (69.5%), and general surgery (48.7%) had the highest proportion of message-based outpatient interaction by the end of the study. Conclusions This study demonstrates rapid adoption of online secure messaging across surgical specialties with significant growth in its use for outpatient interaction. Some specialties, particularly those with long-term follow-up, interacted with patients more through secure messaging than in person. As surgeons devote more time to secure messaging, additional research will be needed to understand the care delivered through online interactions and to develop models for reimbursement. PMID:26123340

[Molecular fundamentals of drug interactions in the therapy of colorectal cancer].

PubMed

Regulska, Katarzyna; Stanisz, Beata; Regulski, Miłosz; Gieremek, Paulina

2014-03-04

Rapid advances in the field of chemotherapy have resulted in the introduction of numerous antineoplastic drugs into clinical practice, which increased the efficiency of patient management. Also the prevalent use of combination treatment based on drug action synergy contributed to the improved clinical effect associated with cytotoxic drug administration. It seems, however, obvious that the multidirectional pharmacotherapy in oncology requires a thorough knowledge of drugs' pharmaceutical behavior in order to maximize their collective action and prevent the occurrence of unintended drug interactions that could potentially impair treatment effectiveness. In fact, drug interactions constitute a serious problem for current oncology primarily resulting from a narrow therapeutic index specific for the majority of anticancer drugs. This, in turn, indicates that even slight deviations of their pharmacokinetics could cause significant clinical consequences, manifested by alteration of the toxicological profile or reduction of therapeutic efficiency. Hence, the investigation of molecular aspects underlying the mechanisms of various drug interactions seems to be essential for proper and safe patient management. The present article is devoted to the extensive subject of drug interactions occurring in the therapy of colorectal cancer. It presents the available literature data on both positive and negative effects of interactions and it discusses their mechanisms complying with their classification into pharmacokinetic and pharmacodynamic ones.

Genetics and the Placebo Effect: the Placebome

PubMed Central

Hall, Kathryn T.; Loscalzo, Joseph; Kaptchuk, Ted J.

2015-01-01

Placebos are indispensable controls in randomized clinical trials (RCTs), and placebo responses significantly contribute to routine clinical outcomes. Recent neurophysiological studies reveal neurotransmitter pathways that mediate placebo effects. Evidence that genetic variations in these pathways can modify placebo effects raises the possibility of using genetic screening to identify placebo responders and thereby increase RCT efficacy and improve therapeutic care. Furthermore, the possibility of interaction between placebo and drug molecular pathways warrants consideration in RCT design. The study of genomic effects on placebo response, “the placebome”, is in its infancy. Here, we review evidence from placebo studies and RCTs to identify putative genes in the placebome, examine evidence for placebo-drug interactions, and discuss implications for RCTs and clinical care. PMID:25883069

“Everyone Needs a Friend Sometimes” – Social Predictors of Long-Term Remission In First Episode Psychosis

PubMed Central

Bjornestad, Jone; Joa, Inge; Larsen, Tor K.; Langeveld, Johannes; Davidson, Larry; ten Velden Hegelstad, Wenche; Anda, Liss G.; Veseth, Marius; Melle, Ingrid; Johannessen, Jan O.; Bronnick, Kolbjorn

2016-01-01

Background: Predictors of long-term symptomatic remission are crucial to the successful tailoring of treatment in first episode psychosis. There is lack of studies distinguishing the predictive effects of different social factors. This prevents a valid evaluating of their independent effects. Objectives: To test specific social baseline predictors of long-term remission. We hypothesized that first, satisfaction with social relations predicts remission; second, that frequency of social interaction predicts remission; and third, that the effect of friend relationship satisfaction and frequency will be greater than that of family relations satisfaction and frequency. Material and Methods: A sample of first episode psychosis (n = 186) completed baseline measures of social functioning, as well as clinical assessments. We compared groups of remitted and non-remitted individuals using generalized estimating equations analyses. Results: Frequency of social interaction with friends was a significant positive predictor of remission over a two-year period. Neither global perceived social satisfaction nor frequency of family interaction showed significant effects. Conclusions: The study findings are of particular clinical importance since frequency of friendship interaction is a possibly malleable factor. Frequency of interaction could be affected through behavioral modification and therapy already from an early stage in the course, and thus increase remission rates. PMID:27757090

Virtual patient instruction for dental students: can it improve dental care access for persons with special needs?

PubMed

Sanders, Carla; Kleinert, Harold L; Boyd, Sara E; Herren, Chris; Theiss, Lynn; Mink, John

2008-01-01

An interactive, virtual-patient module was produced on compact disc (CD-ROM) in response to the critical need to increase dental students' clinical exposure to patients with developmental disabilities. A content development team consisting of dental faculty members, parents of children with developmental disabilities, an individual with a developmental disability, and educational specialists developed the interactive, virtual-patient module. The module focused on a young man with congenital deafblindness presenting as a new patient with a painful molar. Students were required to make decisions regarding clinical interactions throughout the module. Differences in both comfort and knowledge level were measured pre- and post-module completion, as well as the dental students' overall satisfaction with the learning experience. Significant results were obtained in students' perceived comfort and knowledge base. Participants reported overall satisfaction using the modules. This study demonstrated that an interactive, multi-media (CD-ROM), virtual patient learning module for dental students could be an effective tool in providing students needed clinical exposure to patients with developmental disabilities.

Evaluation of potential interactions between mycophenolic acid derivatives and proton pump inhibitors.

PubMed

Gabardi, Steven; Olyaei, Ali

2012-01-01

To evaluate the incidence of gastrointestinal (GI) complications in solid organ transplant (SOT) recipients, impact of the complications on transplant outcomes, and the potential interactions between mycophenolic acid (MPA) derivatives and proton pump inhibitors (PPIs). An unrestricted literature search (1980-January 2012) was performed with MEDLINE and EMBASE using the following key words: drug-drug interaction, enteric-coated mycophenolic acid, GI complications, mycophenolate mofetil, solid organ transplant, and proton pump inhibitor, including individual agents within the class. Abstracts from scientific meetings were also evaluated. Additionally, reference citations from identified publications were reviewed. Relevant English-language, original research articles and review articles were evaluated if they focused on any of the topics identified in the search or included substantial content addressing GI complications in SOT recipients or drug interactions. GI complications are frequent among SOT recipients, with some studies showing prevalence rates as high as 70%. Transplant outcomes among renal transplant recipients are significantly impacted by GI complications, especially in patients requiring immunosuppressant dosage reductions or premature discontinuation. To this end, PPI use among patients receiving transplants is common. Recent data demonstrate that PPIs significantly reduce the overall exposure to MPA after oral administration of mycophenolate mofetil. Similar studies show this interaction does not exist between PPIs and enteric-coated mycophenolic acid (EC-MPA). Unfortunately, most of the available data evaluating this interaction are pharmacokinetic analyses that do not investigate the clinical impact of this interaction. A significant interaction exists between PPIs and mycophenolate mofetil secondary to reduced dissolution of mycophenolate mofetil in higher pH environments. EC-MPA is not absorbed in the stomach; therefore, low intragastric acidity does not impact EC-MPA and bioavailability is maintained with this formulation during PPI coadministration. The clinical impact of this interaction is unknown, yet one can theorize that reduced exposure to MPA in SOT recipients can increase the risk of allograft rejection and/or failure.

Identification of an Interaction between VWF rs7965413 and Platelet Count as a Novel Risk Marker for Metabolic Syndrome: An Extensive Search of Candidate Polymorphisms in a Case-Control Study

PubMed Central

Nakatochi, Masahiro; Ushida, Yasunori; Yasuda, Yoshinari; Yoshida, Yasuko; Kawai, Shun; Kato, Ryuji; Nakashima, Toru; Iwata, Masamitsu; Kuwatsuka, Yachiyo; Ando, Masahiko; Hamajima, Nobuyuki; Kondo, Takaaki; Oda, Hiroaki; Hayashi, Mutsuharu; Kato, Sawako; Yamaguchi, Makoto; Maruyama, Shoichi; Matsuo, Seiichi; Honda, Hiroyuki

2015-01-01

Although many single nucleotide polymorphisms (SNPs) have been identified to be associated with metabolic syndrome (MetS), there was only a slight improvement in the ability to predict future MetS by the simply addition of SNPs to clinical risk markers. To improve the ability to predict future MetS, combinational effects, such as SNP—SNP interaction, SNP—environment interaction, and SNP—clinical parameter (SNP × CP) interaction should be also considered. We performed a case-control study to explore novel SNP × CP interactions as risk markers for MetS based on health check-up data of Japanese male employees. We selected 99 SNPs that were previously reported to be associated with MetS and components of MetS; subsequently, we genotyped these SNPs from 360 cases and 1983 control subjects. First, we performed logistic regression analyses to assess the association of each SNP with MetS. Of these SNPs, five SNPs were significantly associated with MetS (P < 0.05): LRP2 rs2544390, rs1800592 between UCP1 and TBC1D9, APOA5 rs662799, VWF rs7965413, and rs1411766 between MYO16 and IRS2. Furthermore, we performed multiple logistic regression analyses, including an SNP term, a CP term, and an SNP × CP interaction term for each CP and SNP that was significantly associated with MetS. We identified a novel SNP × CP interaction between rs7965413 and platelet count that was significantly associated with MetS [SNP term: odds ratio (OR) = 0.78, P = 0.004; SNP × CP interaction term: OR = 1.33, P = 0.001]. This association of the SNP × CP interaction with MetS remained nominally significant in multiple logistic regression analysis after adjustment for either the number of MetS components or MetS components excluding obesity. Our results reveal new insight into platelet count as a risk marker for MetS. PMID:25646961

Identification of an interaction between VWF rs7965413 and platelet count as a novel risk marker for metabolic syndrome: an extensive search of candidate polymorphisms in a case-control study.

PubMed

Nakatochi, Masahiro; Ushida, Yasunori; Yasuda, Yoshinari; Yoshida, Yasuko; Kawai, Shun; Kato, Ryuji; Nakashima, Toru; Iwata, Masamitsu; Kuwatsuka, Yachiyo; Ando, Masahiko; Hamajima, Nobuyuki; Kondo, Takaaki; Oda, Hiroaki; Hayashi, Mutsuharu; Kato, Sawako; Yamaguchi, Makoto; Maruyama, Shoichi; Matsuo, Seiichi; Honda, Hiroyuki

2015-01-01

Although many single nucleotide polymorphisms (SNPs) have been identified to be associated with metabolic syndrome (MetS), there was only a slight improvement in the ability to predict future MetS by the simply addition of SNPs to clinical risk markers. To improve the ability to predict future MetS, combinational effects, such as SNP-SNP interaction, SNP-environment interaction, and SNP-clinical parameter (SNP × CP) interaction should be also considered. We performed a case-control study to explore novel SNP × CP interactions as risk markers for MetS based on health check-up data of Japanese male employees. We selected 99 SNPs that were previously reported to be associated with MetS and components of MetS; subsequently, we genotyped these SNPs from 360 cases and 1983 control subjects. First, we performed logistic regression analyses to assess the association of each SNP with MetS. Of these SNPs, five SNPs were significantly associated with MetS (P < 0.05): LRP2 rs2544390, rs1800592 between UCP1 and TBC1D9, APOA5 rs662799, VWF rs7965413, and rs1411766 between MYO16 and IRS2. Furthermore, we performed multiple logistic regression analyses, including an SNP term, a CP term, and an SNP × CP interaction term for each CP and SNP that was significantly associated with MetS. We identified a novel SNP × CP interaction between rs7965413 and platelet count that was significantly associated with MetS [SNP term: odds ratio (OR) = 0.78, P = 0.004; SNP × CP interaction term: OR = 1.33, P = 0.001]. This association of the SNP × CP interaction with MetS remained nominally significant in multiple logistic regression analysis after adjustment for either the number of MetS components or MetS components excluding obesity. Our results reveal new insight into platelet count as a risk marker for MetS.

Randomized Trial of a Web-Based Intervention to Address Barriers to Clinical Trials.

PubMed

Meropol, Neal J; Wong, Yu-Ning; Albrecht, Terrance; Manne, Sharon; Miller, Suzanne M; Flamm, Anne Lederman; Benson, Al Bowen; Buzaglo, Joanne; Collins, Michael; Egleston, Brian; Fleisher, Linda; Katz, Michael; Kinzy, Tyler G; Liu, Tasnuva M; Margevicius, Seunghee; Miller, Dawn M; Poole, David; Roach, Nancy; Ross, Eric; Schluchter, Mark D

2016-02-10

Lack of knowledge and negative attitudes have been identified as barriers to participation in clinical trials by patients with cancer. We developed Preparatory Education About Clinical Trials (PRE-ACT), a theory-guided, Web-based, interactive computer program, to deliver tailored video educational content to patients in an effort to overcome barriers to considering clinical trials as a treatment option. A prospective, randomized clinical trial compared PRE-ACT with a control condition that provided general clinical trials information produced by the National Cancer Institute (NCI) in text format. One thousand two hundred fifty-five patients with cancer were randomly allocated before their initial visit with an oncologist to PRE-ACT (n = 623) or control (n = 632). PRE-ACT had three main components: assessment of clinical trials knowledge and attitudinal barriers, values assessment with clarification back to patients, and provision of a video library tailored to address each patient's barriers. Outcomes included knowledge and attitudes and preparation for decision making about clinical trials. Both PRE-ACT and control interventions improved knowledge and attitudes (all P < .001) compared with baseline. Patients randomly allocated to PRE-ACT showed a significantly greater increase in knowledge (P < .001) and a significantly greater decrease in attitudinal barriers (P < .001) than did their control (text-only) counterparts. Participants in both arms significantly increased their preparedness to consider clinical trials (P < .001), and there was a trend favoring the PRE-ACT group (P < .09). PRE-ACT was also associated with greater patient satisfaction than was NCI text alone. These data show that patient education before the first oncologist visit improves knowledge, attitudes, and preparation for decision making about clinical trials. Both text and tailored video were effective. The PRE-ACT interactive video program was more effective than NCI text in improving knowledge and reducing attitudinal barriers. © 2015 by American Society of Clinical Oncology.

Effects of a dolphin interaction program on children with autism spectrum disorders – an exploratory research

PubMed Central

2012-01-01

Background Interaction programs involving dolphins and patients with various pathologies or developmental disorders (e.g., cerebral palsy, intellectual impairment, autism, atopic dermatitis, post-traumatic stress disorder, depression) have stimulated interest in their beneficial effects and therapeutic potential. However, the true effects observed in different clinical and psycho-educational setups are still controversial. Results An evaluation protocol consisting of the Childhood Autism Rating Scale (CARS), Psychoeducational Profile-Revised (PEP-R), Autism Treatment Evaluation Checklist (ATEC), Theory of Mind Tasks (ToM Tasks) and a custom-made Interaction Evaluation Grid (IEG) to evaluate behavioural complexity during in-pool interactions was applied to 10 children diagnosed with Autism Spectrum Disorders. The ATEC, ToM Tasks and CARS results show no benefits of the dolphin interaction program. Interestingly, the PEP-R suggests some statistically significant effects on ‘Overall development score’, as well as on their ‘Fine motor development’, ‘Cognitive performance’ and ‘Cognitive verbal development’. Also, a significant evolution in behavioural complexity was shown by the IEG. Conclusions This study does not support significant developmental progress resulting from the dolphin interaction program. PMID:22537536

Demographic and clinical correlates of autism symptom domains and autism spectrum diagnosis.

PubMed

Frazier, Thomas W; Youngstrom, Eric A; Embacher, Rebecca; Hardan, Antonio Y; Constantino, John N; Law, Paul; Findling, Robert L; Eng, Charis

2014-07-01

Demographic and clinical factors may influence assessment of autism symptoms. This study evaluated these correlates and also examined whether social communication and interaction and restricted/repetitive behavior provided unique prediction of autism spectrum disorder diagnosis. We analyzed data from 7352 siblings included in the Interactive Autism Network registry. Social communication and interaction and restricted/repetitive behavior symptoms were obtained using caregiver-reports on the Social Responsiveness Scale. Demographic and clinical correlates were covariates in regression models predicting social communication and interaction and restricted/repetitive behavior symptoms. Logistic regression and receiver operating characteristic curve analyses evaluated the incremental validity of social communication and interaction and restricted/repetitive behavior domains over and above global autism symptoms. Autism spectrum disorder diagnosis was the strongest correlate of caregiver-reported social communication and interaction and restricted/repetitive behavior symptoms. The presence of comorbid diagnoses also increased symptom levels. Social communication and interaction and restricted/repetitive behavior symptoms provided significant, but modest, incremental validity in predicting diagnosis beyond global autism symptoms. These findings suggest that autism spectrum disorder diagnosis is by far the largest determinant of quantitatively measured autism symptoms. Externalizing (attention deficit hyperactivity disorder) and internalizing (anxiety) behavior, low cognitive ability, and demographic factors may confound caregiver-report of autism symptoms, potentially necessitating a continuous norming approach to the revision of symptom measures. Social communication and interaction and restricted/repetitive behavior symptoms may provide incremental validity in the diagnosis of autism spectrum disorder. © The Author(s) 2013.

Demographic and clinical correlates of autism symptom domains and autism spectrum diagnosis

PubMed Central

Frazier, Thomas W; Youngstrom, Eric A; Embacher, Rebecca; Hardan, Antonio Y; Constantino, John N; Law, Paul; Findling, Robert L; Eng, Charis

2014-01-01

Demographic and clinical factors may influence assessment of autism symptoms. This study evaluated these correlates and also examined whether social communication and interaction and restricted/repetitive behavior provided unique prediction of autism spectrum disorder diagnosis. We analyzed data from 7352 siblings included in the Interactive Autism Network registry. Social communication and interaction and restricted/repetitive behavior symptoms were obtained using caregiver-reports on the Social Responsiveness Scale. Demographic and clinical correlates were covariates in regression models predicting social communication and interaction and restricted/repetitive behavior symptoms. Logistic regression and receiver operating characteristic curve analyses evaluated the incremental validity of social communication and interaction and restricted/repetitive behavior domains over and above global autism symptoms. Autism spectrum disorder diagnosis was the strongest correlate of caregiver-reported social communication and interaction and restricted/repetitive behavior symptoms. The presence of comorbid diagnoses also increased symptom levels. Social communication and interaction and restricted/repetitive behavior symptoms provided significant, but modest, incremental validity in predicting diagnosis beyond global autism symptoms. These findings suggest that autism spectrum disorder diagnosis is by far the largest determinant of quantitatively measured autism symptoms. Externalizing (attention deficit hyperactivity disorder) and internalizing (anxiety) behavior, low cognitive ability, and demographic factors may confound caregiver-report of autism symptoms, potentially necessitating a continuous norming approach to the revision of symptom measures. Social communication and interaction and restricted/repetitive behavior symptoms may provide incremental validity in the diagnosis of autism spectrum disorder. PMID:24104512

Systemic couple therapy for dysthymia.

PubMed

Montesano, Adrián; Feixas, Guillem; Muñoz, Dámaris; Compañ, Victoria

2014-03-01

We examined the effect of Systemic Couple Therapy on a patient diagnosed with dysthymic disorder and her partner. Marge and Peter, a middle-aged married couple, showed significant and meaningful changes in their pattern of interaction over the course of the therapy and, by the end of it, Marge no longer met the diagnostic criteria for dysthymic disorder. Her scores on the Structured Clinical Interview for DSM-IV Axis I Disorders (SCID-I) and Beck Depression Inventory, Second Edition (BDI-II) were in the clinical range before treatment and in the nonclinical one at the end of therapy. Although scores on Dyadic Adjustment Scale showed different patterns, both members reported significant improvement. The analysis of change in the alliance-related behaviors throughout the process concurred with change in couple's pattern of interaction. Treatment effects were maintained at 12-month follow-up. Highlights in the therapy process showed the importance of relational mechanisms of change, such as broadening the therapeutic focus into the couple's pattern of interaction, reducing expressed emotion and resentment, as well as increasing positive exchanges. The results of this evidence-based case study should prompt further investigation of couple therapy for dysthymia disorder. Randomized clinical trial design is needed to reach an evidence-based treatment status. (c) 2014 APA, all rights reserved.

Protein-engineered block-copolymers as stem cell delivery vehicles

NASA Astrophysics Data System (ADS)

Heilshorn, Sarah

2015-03-01

Stem cell transplantation is a promising therapy for a myriad of debilitating diseases and injuries; however, current delivery protocols are inadequate. Transplantation by direct injection, which is clinically preferred for its minimal invasiveness, commonly results in less than 5% cell viability, greatly inhibiting clinical outcomes. We demonstrate that mechanical membrane disruption results in significant acute loss of viability at clinically relevant injection rates. As a strategy to protect cells from these damaging forces, we show that cell encapsulation within hydrogels of specific mechanical properties will significantly improve viability. Building on these fundamental studies, we have designed a reproducible, bio-resorbable, customizable hydrogel using protein-engineering technology. In our Mixing-Induced Two-Component Hydrogel (MITCH), network assembly is driven by specific and stoichiometric peptide-peptide binding interactions. By integrating protein science methodologies with simple polymer physics models, we manipulate the polypeptide chain interactions and demonstrate the direct ability to tune the network crosslinking density, sol-gel phase behavior, and gel mechanics. This is in contrast to many other physical hydrogels, where predictable tuning of bulk mechanics from the molecular level remains elusive due to the reliance on non-specific and non-stoichiometric chain interactions for network formation. Furthermore, the hydrogel network can be easily modified to deliver a variety of bioactive payloads including growth factors, peptide drugs, and hydroxyapatite nanoparticles. Through a series of in vitro and in vivo studies, we demonstrate that these materials may significantly improve transplanted stem cell retention and function.

The interaction of hydroxyurea and ionizing radiation in human cervical carcinoma cells.

PubMed

Kuo, M L; Kunugi, K A; Lindstrom, M J; Kinsella, T J

1997-01-01

The results from prior in vitro and in vivo studies and recent phase 3 clinical trials suggest a significant potential role for hydroxyurea (HU) as a clinical radiosensitizer for cervix cancer. However, a detailed study of possible cellular mechanisms of radiosensitization in human cervix cancer cells as a consequence of dose and timing of HU and ionizing radiation (IR) has not been performed. This in vitro study analyses the interactions of HU and IR in a human cervical carcinoma cell line, Caski. Exponentially growing Caski cells were continuously exposed to clinically achievable but minimally cytotoxic concentrations of HU (0.3-3.0 mM) for various time intervals (6, 12, 18, 24, and 30 hours) up to one population doubling time either prior to or immediately following IR (2-8 Gy). The radiation survival data were analyzed using our modification of the linear-quadratic model to test for an interaction (greater than additive). The effects of HU alone, IR alone, and the combination on cell cycle progression and on apoptotic cell death in exponentially growing Caski cells were measured. We report a significant HU-IR interaction (radiosensitization) based on the sequence of HU exposure (post- > pre-IR) and with increasing concentrations of HU (0.3-3.0 mM), but no effect on radiosensitization with the duration of exposure to HU for up to one cell population doubling (6-30 hours). HU concentration has a significant effect on both alpha and beta linear-quadratic values in the post-IR sequences. Exposures of exponentially growing Caski cells to 1 mM and 3 mM HU alone result in a complete block in early S phase throughout the 30-hour exposure, while 0.3 mM HU causes a transient early S-phase block over the initial 12 to 18 hours of exposure. HU alone has no effect on cell cycle progression in G1 or G2/M populations but results in a large apoptotic population (31% following 1 mM HU x 30 hours), which appears to be the principal mechanism of drug cytotoxicity in these cells. IR alone (4 or 6 Gy) results in a significant G2 delay for 6 to 18 hours following IR but no G1 delay and a small apoptotic population at 30 hours post-IR (5.4% vs 2.1% in non-IR controls). The use of HU (0.3 or 1.0 mM) following IR (4 or 6 Gy) results in a significantly larger G2 delay compared with IR alone, but with only an additive effect on the apoptotic population. These in vitro data demonstrate that radiosensitization of Caski cells is more significant with post-IR exposures to clinically achievable concentrations of HU. This HU-IR interaction is associated with an increased G2 delay, suggesting a reduction in IR damage repair. However, this interaction appears to be independent of the cytotoxicity (principally by apoptosis) from HU alone.

Effect of pay-for-performance incentives on quality of care in small practices with electronic health records: a randomized trial.

PubMed

Bardach, Naomi S; Wang, Jason J; De Leon, Samantha F; Shih, Sarah C; Boscardin, W John; Goldman, L Elizabeth; Dudley, R Adams

2013-09-11

Most evaluations of pay-for-performance (P4P) incentives have focused on large-group practices. Thus, the effect of P4P in small practices, where many US residents receive care, is largely unknown. Furthermore, whether electronic health records (EHRs) with chronic disease management capabilities support small-practice response to P4P has not been studied. To assess the effect of P4P incentives on quality in EHR-enabled small practices in the context of an established quality improvement initiative. A cluster-randomized trial of small (<10 clinicians) primary care clinics in New York City from April 2009 through March 2010. A city program provided all participating clinics with the same EHR software with decision support and patient registry functionalities and quality improvement specialists offering technical assistance. Incentivized clinics were paid for each patient whose care met the performance criteria, but they received higher payments for patients with comorbidities, who had Medicaid insurance, or who were uninsured (maximum payments: $200/patient; $100,000/clinic). Quality reports were given quarterly to both the intervention and control groups. Comparison of differences in performance improvement, from the beginning to the end of the study, between control and intervention clinics for aspirin or antithrombotic prescription, blood pressure control, cholesterol control, and smoking cessation interventions. Mixed-effects logistic regression was used to account for clustering of patients within clinics, with a treatment by time interaction term assessing the statistical significance of the effect of the intervention. Participating clinics (n = 42 for each group) had similar baseline characteristics, with a mean of 4592 (median, 2500) patients at the intervention group clinics and 3042 (median, 2000) at the control group clinics. Intervention clinics had greater adjusted absolute improvement in rates of appropriate antithrombotic prescription (12.0% vs 6.1%, difference: 6.0% [95% CI, 2.2% to 9.7%], P = .001 for interaction term), blood pressure control (no comorbidities: 9.7% vs 4.3%, difference: 5.5% [95% CI, 1.6% to 9.3%], P = .01 for interaction term; with diabetes mellitus: 9.0% vs 1.2%, difference: 7.8% [95% CI, 3.2% to 12.4%], P = .007 for interaction term; with diabetes mellitus or ischemic vascular disease: 9.5% vs 1.7%, difference: 7.8% [95% CI, 3.0% to 12.6%], P = .01 for interaction term), and in smoking cessation interventions (12.4% vs 7.7%, difference: 4.7% [95% CI, -0.3% to 9.6%], P = .02 for interaction term). Intervention clinics performed better on all measures for Medicaid and uninsured patients except cholesterol control, but no differences were statistically significant. Among small EHR-enabled clinics, a P4P incentive program compared with usual care resulted in modest improvements in cardiovascular care processes and outcomes. Because most proposed P4P programs are intended to remain in place more than a year, further research is needed to determine whether this effect increases or decreases over time. clinicaltrials.gov Identifier: NCT00884013.

Rostral anterior cingulate cortex activity and early symptom improvement during treatment for major depressive disorder

PubMed Central

Korb, Alexander S.; Hunter, Aimee M.; Cook, Ian A.; Leuchter, Andrew F.

2011-01-01

In treatment trials for Major Depressive Disorder (MDD), early symptom improvement is predictive of eventual clinical response. Clinical response may also be predicted by elevated pretreatment theta (4-7 Hz) current density in the rostral anterior cingulate (rACC) and medial orbitofrontal cortex (mOFC). We investigated the relationship between pretreatment EEG and early improvement in predicting clinical outcome in 72 MDD subjects across three placebo-controlled treatment trials. Subjects were randomized to receive fluoxetine, venlafaxine, or placebo. Theta current density in the rACC and mOFC was computed with Low-Resolution Brain Electromagnetic Tomography (LORETA). An ANCOVA, examining week 8 Hamilton Depression Rating Scale (HamD) percent change, showed a significant effect of week-2-HamD-percent-change, and a significant three-way interaction of week-2-HamD-percent-change × Treatment × rACC. Medication subjects with robust early improvement showed almost no relationship between rACC theta current density and final clinical outcome. However, in subjects with little early improvement, rACC activity showed a strong relationship with clinical outcome. The model examining mOFC showed a trend in the three-way interaction. A combination of pretreatment rACC activity and early symptom improvement may be useful for predicting treatment response. PMID:21546222

Video-based sexually transmitted disease patient education: its impact on condom acquisition.

PubMed Central

O'Donnell, L N; Doval, A S; Duran, R; O'Donnell, C

1995-01-01

OBJECTIVES. This study assessed the impact of video-based educational interventions on condom acquisition among men and women seeking services at a large sexually transmitted disease clinic in the South Bronx, New York. METHODS. During 1992, 3348 African American and Hispanic patients were enrolled in a clinical trial of video-based interventions designed to promote safer sex behaviors, including increased condom use. Patients were assigned to one of three groups: control, video, or video plus interactive group discussion. Subjects were given a coupon to redeem for free condoms at a pharmacy several blocks from the clinic. Rates of condom acquisition were assessed by level of intervention. RESULTS. In comparison with a control group, subjects who viewed videos were significantly more likely to redeem coupons for condoms (21.2% redemption rate vs 27.6%). However, participation in interactive sessions after video viewing augmented the positive effects of video viewing alone (27.6% redemption rate vs 36.9%). Gender and ethnicity were significantly associated with outcomes. CONCLUSIONS. The condom acquisition are almost doubled with the use of culturally appropriate, video-based interventions. Designed to present minimal disruption to clinical services, these interventions can be implemented in clinics servicing at-risk men and women. Images FIGURE 1 PMID:7762716

Quality of CPR: An important effect modifier in cardiac arrest clinical outcomes and intervention effectiveness trials.

PubMed

Yannopoulos, Demetris; Aufderheide, Tom P; Abella, Benjamin S; Duval, Sue; Frascone, Ralph J; Goodloe, Jeffrey M; Mahoney, Brian D; Nadkarni, Vinay M; Halperin, Henry R; O'Connor, Robert; Idris, Ahamed H; Becker, Lance B; Pepe, Paul E

2015-09-01

To determine if the quality of CPR had a significant interaction with the primary study intervention in the NIH PRIMED trial. The public access database from the NIH PRIMED trial was accessed to determine if there was an interaction between quality of CPR performance, intervention, and outcome (survival to hospital discharge with modified Rankin Score (mRS) ≤ 3). Multi-centered prehospital care systems across North America. Of 8719 adult patients enrolled, CPR quality was electronically recorded for compression rate, depth, and fraction in 6199 (71.1%), 3750 (43.0%) and 6204 (71.2%) subjects, respectively. "Acceptable" quality CPR was defined prospectively as simultaneous provision of a compression rate of 100/min (± 20%), depth of 5 cm (± 20%) and fraction of > 50%. Significant interaction was considered as p < 0.05. Standard CPR with an activated versus sham (inactivated) ITD. Overall, 848 and 827 patients, respectively, in the active and sham-ITD groups had "acceptable" CPR quality performed (n = 1675). There was a significant interaction between the active and sham-ITD and compression rate, depth and fraction as well as their combinations. The strongest interaction was seen with all three parameters combined (unadjusted and adjusted interaction p-value, < 0.001). For all presenting rhythms, when "acceptable" quality of CPR was performed, use of an active-ITD increased survival to hospital discharge with mRS ≤ 3 compared to sham (61/848 [7.2%] versus 34/827 [4.1%], respectively; p = 0.006). The opposite was true for patients that did not receive "acceptable" quality of CPR. In those patients, use of an active - ITD led to significantly worse survival to hospital discharge with mRS ≤ 3 compared to sham (34/1012 [3.4%] versus 62/1061 [5.8%], p = 0.007). There was a statistically significant interaction between the quality of CPR provided, intervention, and survival to hospital discharge with mRS ≤ 3 in the NIH PRIMED trial. Quality of CPR delivered can be an underestimated effect modifier in CPR clinical trials. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

[Formula: see text]Associations among parent-child relationships and cognitive and language outcomes in a clinical sample of preschool children.

PubMed

Leiser, Kara; Heffelfinger, Amy; Kaugars, Astrida

2017-02-01

To examine associations among parent-child relationship characteristics and child cognitive and language outcomes. Preschool children (n = 72) with early neurological insult completed assessments of cognitive and language functioning and participated in a parent-child semi-structured interaction. Quality of the parent-child relationship accounted for a significant amount of unique variance (12%) in predicting children's overall cognitive and language functioning. Impact of neurological insult was a significant predictor. Caregiver-child interactions that are harmonious and reciprocal as evidenced by affective and/or verbal exchanges support children's cognitive and language development. Observations of interactions can guide providers in facilitating child- and family-centered interventions.

Cobicistat Significantly Increases Tacrolimus Serum Concentrations in a Renal Transplant Recipient with Human Immunodeficiency Virus Infection.

PubMed

Han, Zhe; Kane, Brenna M; Petty, Lindsay A; Josephson, Michelle A; Sutor, Jozefa; Pursell, Kenneth J

2016-06-01

Cobicistat is a pharmacokinetic booster in several fixed-dose combination products for treatment of human immunodeficiency virus (HIV) infection. As a potent inhibitor of cytochrome P450 (CYP) 3A enzymes, significant drug-drug interactions are expected between cobicistat and medications that are metabolized primarily through the CYP3A pathway, including calcineurin inhibitors (e.g., tacrolimus and cyclosporine). We describe a case of tacrolimus toxicity due to supratherapeutic tacrolimus concentrations when Stribild (elvitegravir, cobicistat, emtricitabine, and tenofovir disoproxil fumarate) was initiated for newly diagnosed HIV infection in a 50-year-old renal transplant recipient who was previously receiving a stable tacrolimus regimen. Drug-drug interaction via CYP3A inhibition was acknowledged, and weekly labs were ordered to allow for close monitoring of renal function and tacrolimus serum concentrations as recommended by Stribild prescribing information. The patient reported headache, insomnia, stomachache, and decreased urine output within 1 week of starting Stribild and was found to have acute kidney injury (serum creatinine [S cr ]concentration increasing from 1.5-2.3 mg/dl) and a serum tacrolimus concentration of 111.2 ng/ml at 1 week follow-up (goal trough level 4-6 ng/ml). Both tacrolimus and Stribild were withheld. In 15 days, the patient's tacrolimus serum concentration returned to goal. In the interim, he required twice/week clinic visits for laboratory assessments and an emergency department visit for management of hyperkalemia (potassium 6.5 mEq/L). Triumeq (abacavir, dolutegravir, and lamivudine) was started about 4 weeks later after S cr returned to baseline, and his tacrolimus serum trough concentrations subsequently remained stable. To our knowledge, this is the first case report describing the extent, significance, and onset of cobicistat and tacrolimus drug-drug interaction in clinical practice. As more fixed-dose combination products including cobicistat as a pharmacokinetic booster come to market, clinicians should be reminded of its multitude of clinically significant drug-drug interactions. © 2016 Pharmacotherapy Publications, Inc.

A Drug Interactions Elective Course

PubMed Central

2009-01-01

Objectives To evaluate the impact of a drug interactions elective course on student knowledge and skills. Design A drug interactions elective which focused on assessment and application of drug interaction information and identification and management of commonly encountered drug interactions by therapeutic category was offered to third-year PharmD students. Students were expected to (1) determine whether a given interaction was clinically significant or required pharmacist intervention, and (2) make rational, scientifically sound, practical recommendations for management of drug interactions. Evaluation and Assessment Assessment included course evaluations, student self-assessments, and knowledge and skills assessments. Students who completed the course were more confident in their abilities relating to drug interactions than students who did not complete the course. Students who completed the course scored significantly better in all areas of the assessment compared to students who did not complete the course. Course evaluation results were also positive. Conclusion A course devoted to the identification and management of drug interactions improved PharmD students' knowledge and skills and could potentially improve the patient care they provide in the future. PMID:19657505

Clinically important drug interactions with zopiclone, zolpidem and zaleplon.

PubMed

Hesse, Leah M; von Moltke, Lisa L; Greenblatt, David J

2003-01-01

Insomnia, an inability to initiate or maintain sleep, affects approximately one-third of the American population. Conventional benzodiazepines, such as triazolam and midazolam, were the treatment of choice for short-term insomnia for many years but are associated with adverse effects such as rebound insomnia, withdrawal and dependency. The newer hypnosedatives include zolpidem, zaleplon and zopiclone. These agents may be preferred over conventional benzodiazepines to treat short-term insomnia because they may be less likely to cause significant rebound insomnia or tolerance and are as efficacious as the conventional benzodiazepines. This review aims to summarise the published clinical drug interaction studies involving zolpidem, zaleplon and zopiclone. The pharmacokinetic and pharmacodynamic interactions that may be clinically important are highlighted. Clinical trials have studied potential interactions of zaleplon, zolpidem and zopiclone with the following types of drugs: cytochrome P450 (CYP) inducers (rifampicin), CYP inhibitors (azoles, ritonavir and erythromycin), histamine H(2) receptor antagonists (cimetidine and ranitidine), antidepressants, antipsychotics, antagonists of benzodiazepines and drugs causing sedation. Rifampicin significantly induced the metabolism of the newer hypnosedatives and decreased their sedative effects, indicating that a dose increase of these agents may be necessary when they are administered with rifampicin. Ketoconazole, erythromycin and cimetidine inhibited the metabolism of the newer hypnosedatives and enhanced their sedative effects, suggesting that a dose reduction may be required. Addition of ethanol to treatment with the newer hypnosedatives resulted in additive sedative effects without altering the pharmacokinetic parameters of the drugs. Compared with some of the conventional benzodiazepines, fewer clinically important interactions appear to have been reported in the literature with zaleplon, zolpidem and zopiclone. The fact that these drugs are newer to the market and have not been as extensively studied as the conventional benzodiazepines may be the reason for this. Another explanation may be a difference in CYP metabolism. While triazolam and midazolam are biotransformed almost entirely via CYP3A4, the newer hypnosedatives are biotransformed by several CYP isozymes in addition to CYP3A4, resulting in CYP3A4 inhibitors and inducers having a lesser effect on their biotransformation.

Assessment of Pharmacy Students' Communication Competence Using the Roter Interaction Analysis System During Objective Structured Clinical Examinations

PubMed Central

Kubota, Yoshie; Seki, Susumu; Takada, Kaori; Sakuma, Mio; Morimoto, Takeshi; Akaike, Akinori; Hiraide, Atsushi

2011-01-01

Objective To determine the value of using the Roter Interaction Analysis System during objective structured clinical examinations (OSCEs) to assess pharmacy students' communication competence. Methods As pharmacy students completed a clinical OSCE involving an interview with a simulated patient, 3 experts used a global rating scale to assess students' overall performance in the interview, and both the student's and patient's languages were coded using the Roter Interaction Analysis System (RIAS). The coders recorded the number of utterances (ie, units of spoken language) in each RIAS category. Correlations between the raters' scores and the number and types of utterances were examined. Results There was a significant correlation between students' global rating scores on the OSCE and the number of utterances in the RIAS socio-emotional category but not the RIAS business category. Conclusions The RIAS proved to be a useful tool for assessing the socio-emotional aspect of students' interview skills. PMID:21655397

Gender and culture differences in the quality of life among Americans and Koreans with atrial fibrillation.

PubMed

Kang, Younhee

2009-09-01

This study examined the gender and culture differences in relation to the quality of life among Americans and Koreans with atrial fibrillation. It employed secondary data analysis and a descriptive comparative design. The settings were the cardiology outpatient clinics and the outpatient clinic in two urban hospitals in the USA and one university hospital in Korea. The quality of life was measured by the Short-Form Health Survey. The data from 129 subjects were analyzed by two-way ANCOVA and a post-hoc test. In relation to physical function, there was a statistically significant effect shown by gender, but no significant differences were found by the main effect of culture and the interaction effect of gender and culture. The significant interaction effect of gender and culture on mental health was shown. In conclusion, gender differences in the quality of life perceived by patients with atrial fibrillation varied with their cultural background. Thus, patients' cultural background should be considered in nursing practice.

The joint impact of smoking and exercise capacity on clinical outcomes among women with suspected myocardial ischemia: the WISE study.

PubMed

Linke, Sarah E; Rutledge, Thomas; Johnson, B Delia; Olson, Marian B; Bittner, Vera; Cornell, Carol E; Shaw, Leslee J; Eteiba, Wafia; Parashar, Susmita; Sheps, David S; Vido, Diane A; Mulukutla, Suresh; Bairey Merz, C Noel

2009-04-01

Although extensive research has been conducted on both smoking and low exercise capacity alone, few studies have examined the joint impact or interaction of these two risk factors. We examined the joint and interactive effects of smoking and self-reported exercise capacity on subsequent clinical events (heart failure, myocardial infarction [MI], stroke, and cardiovascular-related mortality) among women with suspected myocardial ischemia. At baseline (1996-1999), 789 women completed angiographic testing of coronary artery disease (CAD) severity and provided self-report information about their smoking history and exercise capacity as well as demographic and other risk factor data. Incidence of clinical events among the women was tracked for a median of 5.9 years; this analysis was conducted in 2008. In an adjusted survival analysis, women with a positive smoking history and self-reported low exercise capacity had the greatest risk of experiencing a clinical event (HR = 7.7, 95% CI 2.3, 25.5), followed by women with a positive smoking history and self-reported high exercise capacity (HR = 6.9, 95% CI 2.0, 24.6) and those with a negative smoking history and self-reported low exercise capacity (HR = 4.9, 95% CI 1.5, 15.8), relative to women with a negative smoking history and self-reported high exercise capacity. Additional analyses revealed a significant interaction between smoking history and exercise capacity, such that (1) women with a positive smoking history did not experience an additional significantly greater risk due to low exercise capacity, unlike those with a negative smoking history, and (2) all women experienced a significantly greater risk due to a positive smoking history regardless of their exercise capacity. Among women with suspected myocardial ischemia, the combined protective health effects of self-reported high exercise capacity and a negative smoking history remained significant after controlling for preexisting CAD severity and other established risk factors. These findings highlight the importance of studying behavioral risk factors in combination.

Psychosocial Correlates of Hepatitis C: Interaction and impact on quality of life

PubMed Central

Janke, E. Amy; McGraw, Sarah; Fraenkel, Liana; Garcia-Tsao, Guadalupe

2009-01-01

Despite demonstrated prevalence of psychosocial problems among hepatitis C (HCV) patients, little is known about how these problems develop, why they are sustained, and how clinical providers can effectively intervene. This study uses a qualitative approach to investigate the nature of psychosocial issues in HCV. Focus groups were conducted with HCV patients during which participants discussed significant feelings of anger, depression, and stigma associated with diagnosis. Participants noted these feelings/experiences isolated them from potential sources of social support. Results have important implications for clinical providers and suggest pathways by which HCV-related psychosocial factors interact and impact of quality of life. PMID:19122126

Recommended Approaches for Pharmacokinetic Natural Product-Drug Interaction Research: a NaPDI Center Commentary.

PubMed

Paine, Mary F; Shen, Danny D; McCune, Jeannine S

2018-05-07

Sales of botanical dietary supplements and other purported medicinal natural products (NPs) have escalated over the past ~25 years, increasing the potential for NPs to precipitate clinically significant pharmacokinetic interactions with United States Food and Drug Administration (FDA)-approved medications (NP-drug interactions or NPDIs). Published NPDI studies to date often lack consistency in design, implementation, and documentation, which present difficulties in assessing the clinical significance of the results. Common hurdles include large variability in the admixture composition of phytoconstituents between and within batches of a given NP, limited knowledge on the pharmacokinetics of precipitant NP constituents, and use of animal and/or in vitro models which, in some cases, are not mechanistically appropriate for extrapolation to humans. The National Center for Complementary and Integrative Health has created a Center of Excellence for Natural Product-Drug Interaction (NaPDI Center) to address these unmet research needs. The NaPDI Center has two overarching goals: 1) develop Recommended Approaches to guide researchers in the proper conduct of NPDI studies, which will evolve over time concurrent with emerging technologies and new research data; and 2) apply the Recommended Approaches in evaluating four model NPs as precipitants of NPDIs with clinically relevant object drugs. The major objectives of this commentary are to 1) explain the rationale for creating the NaPDI Center; 2) describe the Decision Trees developed by the NaPDI Center to enhance the planning, rigor, and consistency of NPDI studies; and 3) provide a framework for communicating results to the multidisciplinary scientists interested in the NaPDI Center&rsquo's Interaction Projects. The American Society for Pharmacology and Experimental Therapeutics.

Duration and structure of unaccompanied (dyadic) and accompanied (triadic) initial outpatient consultations in a specialist seizure clinic.

PubMed

Robson, Catherine; Drew, Paul; Reuber, Markus

2013-06-01

This study explores differences in the duration and structure of unaccompanied (dyadic) and accompanied (triadic) initial (diagnostic) outpatient consultations in a specialist seizure clinic. This is the first known study to explore this topic quantitatively by analyzing the discourse space taken up by the different participants in real clinical encounters. We did not observe significant differences between the duration of accompanied and unaccompanied interactions (p=0.589). Results suggest that patients occupy proportionally less discourse space (measured by the number of words produced) in accompanied interactions than in unaccompanied interactions (56.9% versus 28.3%, p ≤ 0.0001). In accompanied interactions, there is a weak negative correlation between the discourse space of patients and that of doctors (rs=-0.43, p=0.017) and a moderate to strong negative correlation with the discourse spaces of companions (rs=-0.64, p=0.001). These findings indicate that the presence of a companion may reduce opportunities for doctors to observe the interactional, linguistic, and topical features of seizure patient talk, whose differential diagnostic value has been described in a number of previous publications, or for patients to raise issues they want to talk about. Copyright © 2013 Elsevier Inc. All rights reserved.

Hyperforin in St. John's wort drug interactions.

PubMed

Madabushi, Rajanikanth; Frank, Bruno; Drewelow, Bernd; Derendorf, Hartmut; Butterweck, Veronika

2006-03-01

Recently, interactions of herbal medicines with synthetic drugs came into focus of particular interest. In the past 3 years, more than 50 papers were published regarding interactions between St. John's wort (Hypericum perforatum L.; SJW) and prescription drugs. Co-medication with SJW resulted in decreased plasma concentrations of a number of drugs including amitriptyline, cyclosporine, digoxin, indinavir, irinotecan, warfarin, phenprocoumon, alprazolam, dextrometorphane, simvastatin, and oral contraceptives. Sufficient evidence from interaction studies and case reports indicate that SJW is a potent inducer of cytochrome P450 enzymes (particularly CYP3A4) and/or P-glycoprotein. Recent studies could show that the degree of enzyme induction by SJW correlates strongly with the amount of hyperforin found in the product. Products that do not contain substantial amounts of hyperforin (<1%) have not been shown to produce clinically relevant enzyme induction. On the other hand, some evidence suggests that hyperforin may also contribute to the antidepressant activity of SJW. However, clinical studies using SJW preparations with a low hyperforin amount (<1%) clearly demonstrated the superiority of this plant extract over placebo and its equivalence to imipramine and fluoxetine in the treatment of mild to moderate forms of depression. In the present paper clinical significant SJW interactions are critically evaluated against the background of hyperforin.

[From stone-craved genes to Michelangelo: significance and different aspects of gene-environment interaction].

PubMed

Lazary, Judit

2017-12-01

Although genetic studies have improved a lot in recent years, without clinical relevance sometimes their significance is devalued. Reviewing the major milestones of psychogenomics it can be seen that break-through success is just a question of time. Investigations of direct effect of genetic variants on phenotypes have not yielded positive findings. However, an important step was taken by adapting the gene-environment interaction model. In this model genetic vulnerability stepped into the place of "stone craved" pathology. Further progress happened when studies of environmental factors were combined with genetic function (epigenetics). This model provided the possibility for investigation of therapeutic interventions as environmental factors and it was proven that effective treatments exert a modifying effect on gene expression. Moreover, recent developments focus on therapeutic manipulation of gene function (e.g. chemogenetics). Instead of "stone craved" genes up-to-date dynamically interacting gene function became the basis of psychogenomics in which correction of the expression is a potential therapeutic tool. Keeping in mind these trends and developments, there is no doubt that genetics will be a fundamental part of daily clinical routine in the future.

Association between social interaction and affect in nursing home residents with dementia.

PubMed

Jao, Ying-Ling; Loken, Eric; MacAndrew, Margaret; Van Haitsma, Kimberly; Kolanowski, Ann

2018-06-01

Social interactions that lead to positive affect are fundamental to human well-being. However, individuals with dementia are challenged to achieve positive social interaction. It is unclear how social interactions influence affect in people with dementia. This study examined the association between social interactions and affect in nursing home residents with dementia. This repeated measures study used baseline data from a clinical trial in which 126 residents from 12 nursing homes were enrolled. Participants were video recorded twice daily on five days. Ratings of social interaction and affect were taken from the videotapes using the Interacting with People subscale of the Passivity in Dementia and the Philadelphia Geriatric Center Apparent Affect Rating Scale. Linear mixed models were used for analysis. Social interaction was significantly related to higher interest and pleasure at within- and between-person levels. Social interaction significantly predicted anxiety and sadness at the between-person level only. Residents with higher cognitive function also displayed greater pleasure. Greater interest and anxiety was evident during the afternoon hours. This study supports the impact of social interactions on positive and negative affect. Findings can guide intervention development, aimed at promoting positive social interactions and improving affect for people with dementia.

Psychopathology and parenting: An examination of perceived and observed parenting in mothers with depression and PTSD

PubMed Central

Muzik, Maria; Morelen, Diana; Hruschak, Jessica; Rosenblum, Katherine Lisa; Bocknek, Erika; Beeghly, Marjorie

2016-01-01

Background The postpartum period represents a major transition in the lives of many women, a time when women are at increased risk for the emergence of psychopathology including depression and PTSD. The current study aimed to better understand the unique contributions of clinically significant postpartum depression, PTSD, and comorbid PTSD/depression on mother–infant bonding and observed maternal parenting behaviors (i.e., behavioral sensitivity, negative affect, positive affect) at 6 months postpartum. Methods Mothers (n=164; oversampled for history of childhood maltreatment given parent study's focus on perinatal mental health in women with trauma histories) and infants participated in 6-month home visit during which dyads engaged in interactional tasks varying in level of difficulties. Mothers also reported on their childhood abuse histories, current depression/PTSD symptoms, and bonding with the infant using standardized and validated instruments. Results Mothers with clinically significant depression had the most parenting impairment (self-report and observed). Mothers with clinically significant PTSD alone (due to interpersonal trauma that occurred predominately in childhood) showed similar interactive behaviors to those who were healthy controls or trauma-exposed but resilient (i.e., no postpartum psychopathology). Childhood maltreatment in the absence of postpartum psychopathology did not infer parenting risk. Limitations Findings are limited by (1) small cell sizes per clinical group, limiting power, (2) sample size and sample demographics prohibited examination of third variables that might also impact parenting (e.g., income, education), (3) self-report of symptoms rather than use of psychiatric interviews. Conclusions Findings show that in the context of child abuse history and/or current PTSD, clinically significant maternal depression was the most salient factor during infancy that was associated with parenting impairment at this level of analysis. PMID:27732922

Clinical features and functional significance of the P369S/R408Q variant in pyrin, the familial Mediterranean fever protein

PubMed Central

Ryan, JG; Masters, SL; Booty, MG; Habal, N; Alexander, JD; Barham, BK; Remmers, EF; Barron, KS; Kastner, DL; Aksentijevich, I

2013-01-01

Objectives Familial Mediterranean fever (FMF) is caused by mutations in MEFV, which encodes pyrin. The nature of substitutions P369S and R408Q in exon 3 remains unclear. Exon 3 encoding pyrin’s B-box domain is necessary for interactions with PSTPIP1. We aimed to characterize the phenotype of patients with these substitutions and to determine their functional significance. Methods A database of genetic tests undertaken in our institution was interrogated. Symptoms and signs were classified according to Tel-Hashomer criteria. Co-immunoprecipation techniques were employed to determine the variants’ effects on pyrin/PSTPIP1 interactions. Results We identified 40 symptomatic and 4 asymptomatic family members with these substitutions. P369S and R408Q were found in cis, and co-segregated in all patients sequenced. Clinical details were available on 22 patients. Five patients had symptoms and signs fulfilling a clinical diagnosis of FMF. Fourteen received colchicine. In patients not reaching the criteria, trials of anti-TNF agents resulted in partial or no benefit; resolution of symptoms was noted in those receiving anakinra. The carrier frequency was higher in the patient cohort than in controls but was not statistically significant. Co-immunoprecipitation studies demonstrated that these pyrin variants did not affect binding to PSTPIP1. Conclusions P369S/R408Q substitutions are associated with a highly variable phenotype, and are infrequently associated with typical FMF symptoms, however a trial of colchicine is warranted in all. Functional and modeling studies suggest that these substitutions do not significantly affect pyrin’s interaction with PSTPIP1. This study highlights the need for caution in interpreting genetic tests in patients with atypical symptoms. PMID:19934105

Interactive anatomical and surgical live stream lectures improve students' academic performance in applied clinical anatomy.

PubMed

Shiozawa, Thomas; Butz, Benjamin; Herlan, Stephan; Kramer, Andreas; Hirt, Bernhard

2017-01-01

Tuebingen's Sectio Chirurgica (TSC) is an innovative, interactive, multimedia, and transdisciplinary teaching method designed to complement dissection courses. The Tuebingen's Sectio Chirurgica (TSC) allows clinical anatomy to be taught via interactive live stream surgeries moderated by an anatomist. This method aims to provide an application-oriented approach to teaching anatomy that offers students a deeper learning experience. A cohort study was devised to determine whether students who participated in the TSC were better able to solve clinical application questions than students who did not participate. A total of 365 students participated in the dissection course during the winter term of the 2012/2013 academic year. The final examination contained 40 standard multiple-choice (S-MC) and 20 clinically-applied multiple-choice (CA-MC) items. The CA-MC items referred to clinical cases but could be answered solely using anatomical knowledge. Students who regularly participated in the TSC answered the CA-MC questions significantly better than the control group (75% and 65%, respectively; P < 0.05, Mann-Whitney U test). The groups exhibited no differences on the S-MC questions (85% and 82.5%, respectively; P > 0.05). The CA-MC questions had a slightly higher level of difficulty than the S-MC questions (0.725 and 0.801, respectively; P = 0.083). The discriminatory power of the items was comparable (S-MC median Pearson correlations: 0.321; CA-MC: 0.283). The TSC successfully teaches the clinical application of anatomical knowledge. Students who attended the TSC in addition to the dissection course were able to answer CA-MC questions significantly better than students who did not attend the TSC. Thus, attending the TSC in addition to the dissection course supported students' clinical learning goals. Anat Sci Educ 10: 46-52. © 2016 American Association of Anatomists. © 2016 American Association of Anatomists.

Designing and Evaluating an Interactive Multimedia Web-Based Simulation for Developing Nurses’ Competencies in Acute Nursing Care: Randomized Controlled Trial

PubMed Central

Wong, Lai Fun; Chan, Sally Wai-Chi; Ho, Jasmine Tze Yin; Mordiffi, Siti Zubaidah; Ang, Sophia Bee Leng; Goh, Poh Sun; Ang, Emily Neo Kim

2015-01-01

Background Web-based learning is becoming an increasingly important instructional tool in nursing education. Multimedia advancements offer the potential for creating authentic nursing activities for developing nursing competency in clinical practice. Objective This study aims to describe the design, development, and evaluation of an interactive multimedia Web-based simulation for developing nurses’ competencies in acute nursing care. Methods Authentic nursing activities were developed in a Web-based simulation using a variety of instructional strategies including animation video, multimedia instructional material, virtual patients, and online quizzes. A randomized controlled study was conducted on 67 registered nurses who were recruited from the general ward units of an acute care tertiary hospital. Following a baseline evaluation of all participants’ clinical performance in a simulated clinical setting, the experimental group received 3 hours of Web-based simulation and completed a survey to evaluate their perceptions of the program. All participants were re-tested for their clinical performances using a validated tool. Results The clinical performance posttest scores of the experimental group improved significantly (P<.001) from the pretest scores after the Web-based simulation. In addition, compared to the control group, the experimental group had significantly higher clinical performance posttest scores (P<.001) after controlling the pretest scores. The participants from the experimental group were satisfied with their learning experience and gave positive ratings for the quality of the Web-based simulation. Themes emerging from the comments about the most valuable aspects of the Web-based simulation include relevance to practice, instructional strategies, and fostering problem solving. Conclusions Engaging in authentic nursing activities using interactive multimedia Web-based simulation can enhance nurses’ competencies in acute care. Web-based simulations provide a promising educational tool in institutions where large groups of nurses need to be trained in acute nursing care and accessibility to repetitive training is essential for achieving long-term retention of clinical competency. PMID:25583029

Designing and evaluating an interactive multimedia Web-based simulation for developing nurses' competencies in acute nursing care: randomized controlled trial.

PubMed

Liaw, Sok Ying; Wong, Lai Fun; Chan, Sally Wai-Chi; Ho, Jasmine Tze Yin; Mordiffi, Siti Zubaidah; Ang, Sophia Bee Leng; Goh, Poh Sun; Ang, Emily Neo Kim

2015-01-12

Web-based learning is becoming an increasingly important instructional tool in nursing education. Multimedia advancements offer the potential for creating authentic nursing activities for developing nursing competency in clinical practice. This study aims to describe the design, development, and evaluation of an interactive multimedia Web-based simulation for developing nurses' competencies in acute nursing care. Authentic nursing activities were developed in a Web-based simulation using a variety of instructional strategies including animation video, multimedia instructional material, virtual patients, and online quizzes. A randomized controlled study was conducted on 67 registered nurses who were recruited from the general ward units of an acute care tertiary hospital. Following a baseline evaluation of all participants' clinical performance in a simulated clinical setting, the experimental group received 3 hours of Web-based simulation and completed a survey to evaluate their perceptions of the program. All participants were re-tested for their clinical performances using a validated tool. The clinical performance posttest scores of the experimental group improved significantly (P<.001) from the pretest scores after the Web-based simulation. In addition, compared to the control group, the experimental group had significantly higher clinical performance posttest scores (P<.001) after controlling the pretest scores. The participants from the experimental group were satisfied with their learning experience and gave positive ratings for the quality of the Web-based simulation. Themes emerging from the comments about the most valuable aspects of the Web-based simulation include relevance to practice, instructional strategies, and fostering problem solving. Engaging in authentic nursing activities using interactive multimedia Web-based simulation can enhance nurses' competencies in acute care. Web-based simulations provide a promising educational tool in institutions where large groups of nurses need to be trained in acute nursing care and accessibility to repetitive training is essential for achieving long-term retention of clinical competency.

Potential drug interactions in patients given antiretroviral therapy

PubMed Central

dos Santos, Wendel Mombaque; Secoli, Silvia Regina; Padoin, Stela Maris de Mello

2016-01-01

ABSTRACT Objective: to investigate potential drug-drug interactions (PDDI) in patients with HIV infection on antiretroviral therapy. Methods: a cross-sectional study was conducted on 161 adults with HIV infection. Clinical, socio demographic, and antiretroviral treatment data were collected. To analyze the potential drug interactions, we used the software Micromedex(r). Statistical analysis was performed by binary logistic regression, with a p-value of ≤0.05 considered statistically significant. Results: of the participants, 52.2% were exposed to potential drug-drug interactions. In total, there were 218 potential drug-drug interactions, of which 79.8% occurred between drugs used for antiretroviral therapy. There was an association between the use of five or more medications and potential drug-drug interactions (p = 0.000) and between the time period of antiretroviral therapy being over six years and potential drug-drug interactions (p < 0.00). The clinical impact was prevalent sedation and cardiotoxicity. Conclusions: the PDDI identified in this study of moderate and higher severity are events that not only affect the therapeutic response leading to toxicity in the central nervous and cardiovascular systems, but also can interfere in tests used for detection of HIV resistance to antiretroviral drugs. PMID:27878224

Increase in tiagabine serum concentration with coadministration of gemfibrozil.

PubMed

Burstein, Aaron H; Boudreau, Eilis A; Theodore, William H

2009-02-01

To report a case of possible acute tiagabine toxicity secondary to administration of gemfibrozil. A 39-year-old male was taking tiagabine 16 mg orally 3 times per day and carbamazepine 500 mg orally twice per day for complex partial seizures secondary to mesial temporal sclerosis. He was found to have type IV hypertriglyceridemia and was prescribed gemfibrozil. Because he reported severe confusion and altered consciousness shortly after a single 600-mg dose of gemfibrozil, he was admitted for controlled challenge with that drug. A single 300-mg dose of gemfibrozil resulted in lightheadedness and led to a 59% and 75% increase in total tiagabine serum concentrations at 2 and 5 hours, respectively, without significant change in baseline carbamazepine concentrations. This is the first report of an interaction between the widely used antihyperlipidemic drug gemfibrozil and tiagabine. Since tiagabine, which was originally developed as an antiepileptic medication, is now being used widely for a variety of other indications such as anxiety and depression, there is an increased risk for clinically significant interactions with gemfibrozil. Increased total and unbound tiagabine concentrations following a single 300-mg dose of gemfibrozil and reproduction of clinical symptoms with gemfibrozil rechallenge suggests the toxicity our patient experienced was due to a pharmacokinetic drug interaction. Use of the Horn Drug Interaction Probability Scale showed a probable interaction between gemfibrozil and tiagabine.

Adverse events caused by potential drug-drug interactions in an intensive care unit of a teaching hospital

PubMed Central

Alvim, Mariana Macedo; da Silva, Lidiane Ayres; Leite, Isabel Cristina Gonçalves; Silvério, Marcelo Silva

2015-01-01

Objective To evaluate the incidence of potential drug-drug interactions in an intensive care unit of a hospital, focusing on antimicrobial drugs. Methods This cross-sectional study analyzed electronic prescriptions of patients admitted to the intensive care unit of a teaching hospital between January 1 and March 31, 2014 and assessed potential drug-drug interactions associated with antimicrobial drugs. Antimicrobial drug consumption levels were expressed in daily doses per 100 patient-days. The search and classification of the interactions were based on the Micromedex® system. Results The daily prescriptions of 82 patients were analyzed, totaling 656 prescriptions. Antimicrobial drugs represented 25% of all prescription drugs, with meropenem, vancomycin and ceftriaxone being the most prescribed medications. According to the approach of daily dose per 100 patient-days, the most commonly used antimicrobial drugs were cefepime, meropenem, sulfamethoxazole + trimethoprim and ciprofloxacin. The mean number of interactions per patient was 2.6. Among the interactions, 51% were classified as contraindicated or significantly severe. Highly significant interactions (clinical value 1 and 2) were observed with a prevalence of 98%. Conclusion The current study demonstrated that antimicrobial drugs are frequently prescribed in intensive care units and present a very high number of potential drug-drug interactions, with most of them being considered highly significant. PMID:26761473

The interplay between individual social behavior and clinical symptoms in small clustered groups.

PubMed

Poletti, Piero; Visintainer, Roberto; Lepri, Bruno; Merler, Stefano

2017-07-26

Mixing patterns of human populations play a crucial role in shaping the spreading paths of infectious diseases. The diffusion of mobile and wearable devices able to record close proximity interactions represents a great opportunity for gathering detailed data on social interactions and mixing patterns in human populations. The aim of this study is to investigate how social interactions are affected by the onset of symptomatic conditions and to what extent the heterogeneity in human behavior can reflect a different risk of infection. We study the relation between individuals' social behavior and the onset of different symptoms, by making use of data collected in 2009 among students sharing a dormitory in a North America university campus. The dataset combines Bluetooth proximity records between study participants with self-reported daily records on their health state. Specifically, we investigate whether individuals' social activity significantly changes during different symptomatic conditions, including those defining Influenza-like illness, and highlight to what extent possible heterogeneities in social behaviors among individuals with similar age and daily routines may be responsible for a different risk of infection for influenza. Our results suggest that symptoms associated with Influenza-like illness can be responsible of a reduction of about 40% in the average duration of contacts and of 30% in the daily time spent in social interactions, possibly driven by the onset of fever. However, differences in the number of daily contacts were found to be not statistically significant. In addition, we found that individuals who experienced clinical influenza during the study period were characterized by a significantly higher social activity. In particular, both the number of person-to-person contacts and the time spent in social interactions emerged as significant risk factors for influenza infection. Our findings highlight that Influenza-like illness can remarkably reduce the social activity of individuals and strengthen the idea that the heterogeneity in social habits among individuals can significantly contribute in shaping differences among the individuals' risk of infection.

Pilot evaluation of parent-child interaction therapy delivered in an Australian community early childhood clinic setting.

PubMed

Phillips, Jane; Morgan, Susan; Cawthorne, Karen; Barnett, Bryanne

2008-08-01

Parent-child interaction therapy (PCIT) is a short-term, evidence-based parent training intervention used widely in the treatment of behaviourally disordered preschool-aged children. Outcome studies have shown PCIT to be associated with lasting improvements in child and sibling behaviours and in the interactional styles, stress levels, confidence, and psychological functioning of parents. To date, however, all outcome studies have been conducted in university research clinic settings, and therefore understanding about the effectiveness of PCIT applied in a real-world setting has been limited. The present study evaluated the effectiveness of PCIT delivered to families in an Australian community-based early childhood clinic. Participants included 43 families with children aged 19-52 months who were referred for treatment of disruptive child behaviours and who completed PCIT treatment at the Karitane Toddler Clinic, in Sydney, Australia. Parents provided pre- and post-treatment ratings of child behaviours, parental stress, parental psychopathology and parental attitudes to therapy. At the end of the programme, clinically and statistically significant improvements were seen in child behaviours and parental well-being, and parents reported high levels of satisfaction with treatment. Implications for the implementation of PCIT programmes in community-based settings are discussed and areas of further research are identified.

Using digital multimedia to improve parents' and children's understanding of clinical trials.

PubMed

Tait, Alan R; Voepel-Lewis, Terri; Levine, Robert

2015-06-01

Data show that many research subjects have difficulty understanding study information using traditional paper consent documents. This study, therefore, was designed to evaluate the effect of an interactive multimedia program on improving parents' and children's understanding of clinical trial concepts and participation. Parents (n=148) and children (n=135) were each randomised to receive information regarding clinical trials using either a traditional paper format (TF) or an interactive iPad program (IP) with inline exercises. Participants' understanding of the information was assessed using semistructured interviews prior to (pretest) and after (post-test) receiving the information. Participants also completed a short survey to assess their perceptions of information delivery and satisfaction with the process. Regardless of the mode of information delivery, all participants demonstrated improved pretest to post-test understanding. While there were no statistical differences in parents' post-test understanding between the TF and IP groups, children in the IP group had significantly greater post-test understanding compared with children in the TF group (11.65 (4.1) vs 8.85 (4.1) (2.8, 1.4, 4.2) 0-18 scale where 18=complete understanding). Furthermore, the IP was found to be significantly 'easier to follow' and 'more effective' in presenting information compared with the TF. Results demonstrated the importance of providing information regarding clinical trial concepts to parents and children. Importantly, the ability of interactive multimedia to improve understanding of clinical trial concepts and satisfaction with information delivery, particularly among children, supports this approach as a novel and effective vehicle for enhancing the informed consent process. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.

Fat-Soluble Vitamins: Clinical Indications and Current Challenges for Chromatographic Measurement

PubMed Central

Albahrani, Ali A.; Greaves, Ronda F.

2016-01-01

Fat-soluble vitamins, including vitamins A, D and E, are required for a wide variety of physiological functions. Over the past two decades, deficiencies of these vitamins have been associated with increased risk of cancer, type II diabetes mellitus and a number of immune system disorders. In addition, there is increasing evidence of interactions between these vitamins, especially between vitamins A and D. As a result of this enhanced clinical association with disease, translational clinical research and laboratory requests for vitamin measurements have significantly increased. These laboratory requests include measurement of 25-OHD (vitamin D), retinol (vitamin A) and α-tocopherol (vitamin E); the most accepted blood indicators for the assessment of body fat-soluble vitamin (FSV) status. There are significant obstacles to precise FSV measurement in blood. These obstacles include their physical and chemical properties, incomplete standardisation of measurement and limitations in the techniques that are currently used for quantification. The aim of this review is to briefly outline the metabolism and interactions of FSV as a prelude to identifying the current challenges for the quantification of blood vitamins A, D and E. PMID:27057076

Fat-Soluble Vitamins: Clinical Indications and Current Challenges for Chromatographic Measurement.

PubMed

Albahrani, Ali A; Greaves, Ronda F

2016-02-01

Fat-soluble vitamins, including vitamins A, D and E, are required for a wide variety of physiological functions. Over the past two decades, deficiencies of these vitamins have been associated with increased risk of cancer, type II diabetes mellitus and a number of immune system disorders. In addition, there is increasing evidence of interactions between these vitamins, especially between vitamins A and D. As a result of this enhanced clinical association with disease, translational clinical research and laboratory requests for vitamin measurements have significantly increased. These laboratory requests include measurement of 25-OHD (vitamin D), retinol (vitamin A) and α-tocopherol (vitamin E); the most accepted blood indicators for the assessment of body fat-soluble vitamin (FSV) status. There are significant obstacles to precise FSV measurement in blood. These obstacles include their physical and chemical properties, incomplete standardisation of measurement and limitations in the techniques that are currently used for quantification. The aim of this review is to briefly outline the metabolism and interactions of FSV as a prelude to identifying the current challenges for the quantification of blood vitamins A, D and E.

Organisational quality, nurse staffing and the quality of chronic disease management in primary care: observational study using routinely collected data.

PubMed

Griffiths, Peter; Maben, Jill; Murrells, Trevor

2011-10-01

An association between quality of care and staffing levels, particularly registered nurses, has been established in acute hospitals. Recently an association between nurse staffing and quality of care for several chronic conditions has also been demonstrated for primary care in English general practice. A smaller body of literature identifies organisational factors, in particular issues of human resource management, as being a dominant factor. However the literature has tended to consider staffing and organisational factors separately. We aim to determine whether relationships between the quality of clinical care and nurse staffing in general practice are attenuated or enhanced when organisational factors associated with quality of care are considered. We further aim to determine the relative contribution and interaction between these factors. We used routinely collected data from 8409 English general practices. The data, on organisational factors and the quality of clinical care for a range of long term conditions, is gathered as part of "Quality and Outcomes Framework" pay for performance system. Regression models exploring the relationship of staffing and organisational factors with care quality were fitted using MPLUS statistical modelling software. Higher levels of nurse staffing, clinical recording, education and reflection on the results of patient surveys were significantly associated with improved clinical care for COPD, CHD, Diabetes and Hypothyroidism after controlling for organisational factors. There was some evidence of attenuation of the estimated nurse staffing effect when organisational factors were considered, but this was small. The effect of staffing interacted significantly with the effect of organisational factors. Overall however, the characteristics that emerged as the strongest predictors of quality of clinical care were not staffing levels but the organisational factors of clinical recording, education and training and use of patient experience surveys. Organisational factors contribute significantly to observed variation in the quality of care in English general practices. Levels of nurse staffing have an independent association with quality but also interact with organisational factors. The observed relationships are not necessarily causal but a causal relationship is plausible. The benefits and importance of education, training and personal development of nursing and other practice staff was clearly indicated. Copyright © 2011. Published by Elsevier Ltd.

Development of Heat Shock Protein (Hsp90) Inhibitors To Combat Resistance to Tyrosine Kinase Inhibitors through Hsp90-Kinase Interactions.

PubMed

Wang, Meining; Shen, Aijun; Zhang, Chi; Song, Zilan; Ai, Jing; Liu, Hongchun; Sun, Liping; Ding, Jian; Geng, Meiyu; Zhang, Ao

2016-06-23

Heat shock protein 90 (Hsp90) is a ubiquitous chaperone of all of the oncogenic tyrosine kinases. Many Hsp90 inhibitors, alone or in combination, have shown significant antitumor efficacy against the kinase-positive naïve and mutant models. However, clinical trials of these inhibitors are unsuccessful due to insufficient clinical benefits and nonoptimal safety profiles. Recently, much progress has been reported on the Hsp90-cochaperone-client complex, which will undoubtedly assist in the understanding of the interactions between Hsp90 and its clients. Meanwhile, Hsp90 inhibitors have shown promise against patients' resistance caused by early generation tyrosine kinase inhibitors (TKIs), and at least 13 Hsp90 inhibitors are being reevaluated in the clinic. In this regard, the objectives of the current perspective are to summarize the structure and function of the Hsp90-cochaperone-client complex, to analyze the structural and functional insights into the Hsp90-client interactions to address several existing unresolved problems with Hsp90 inhibitors, and to highlight the preclinical and clinical studies of Hsp90 inhibitors as an effective treatment against resistance to tyrosine kinase inhibitors.

Assessment of Clinical Pharmacy Interventions to Reduce Outpatient Use of High-Risk Medications in the Elderly.

PubMed

Weddle, Sarah C; Rowe, A Shaun; Jeter, Julie W; Renwick, Rachel C; Chamberlin, Shaunta' M; Franks, Andrea S

2017-05-01

Use of high-risk medications in the elderly (HRME) and drug-disease (Rx-DIS) interactions in the elderly, as defined by the Healthcare Effectiveness Data and Information Set (HEDIS) Measures, are significantly associated with mortality, hospital admission, and need for emergency care. No published studies to date evaluate interventions to reduce the use of HEDIS-defined HRME, although many studies have postulated a beneficial effect of such interventions. To evaluate the effect of pharmacist interventions on use of HRME and Rx-DIS interactions in the outpatient elderly population. This retrospective cohort study was conducted in a resident-based family medicine clinic. Patients aged ≥ 65 years were prospectively screened for the use of HRME and Rx-DIS interactions before their visits with their primary care providers. If HRME or Rx-DIS interactions were noted, the clinical pharmacist sent messages to the physicians through the electronic medical record, alerting them of the findings with suggestions of safer alternative agents, if applicable. The recommendation acceptance rate was assessed and then compared with a historical control from a similar time frame. The primary outcome was assessed with a chi square analysis. Secondary outcomes were assessed with descriptive statistics, chi square test, and Fisher's exact test. HRME and/or Rx-DIS interactions were changed 25.9% of the time in the pharmacist intervention group compared with only 2.0% of the time in the historical control group (P = 0.001). The most frequently changed medication classes included skeletal muscle relaxants, benzodiazepines, and nonsteroidal anti-inflammatory drugs. Over 85% of the medication changes were preserved at the end of the study period. There was no difference between groups in the number of patients with HRME or Rx-DIS interactions. Clinical pharmacy interventions result in significant reductions in use of HRME and Rx-DIS interactions in the outpatient elderly population. Using electronic communication allows pharmacists to provide meaningful interventions for numerous patients receiving care in a high-volume family medicine clinic setting. There was no funding or sponsorship for this study. Rowe reports personal fees from The Medicines Company, outside the submitted work. The other authors have nothing to disclose. Study concept and design were contributed by Jeter, Chamberlin, and Weddle, with assistance from Rowe and Franks. Weddle and Renwick collected the data, and data interpretation was performed by Weddle and Rowe, with assistance from Franks. The manuscript was written by Weddle and Rowe and revised by Weddle and Franks, assisted by Chamberlin. The abstract for the completed study was presented at the American College of Clinical Pharmacy Global Conference, San Francisco, California, October 2015, and the Southeastern Residency Conference, Athens, Georgia, April 2015 (platform presentation). The research-in-progress abstract was presented at the Tennessee Society of Health System Pharmacists, Nashville, Tennessee, February 2015; the American Society of Health System Pharmacists Midyear Clinical Meeting, Anaheim, California, December 2014; and the University HealthSystem Consortium Pharmacy Council, Anaheim, California, December 2014.

Time and dose-dependent risk of pneumococcal pneumonia following influenza: a model for within-host interaction between influenza and Streptococcus pneumoniae

PubMed Central

Shrestha, Sourya; Foxman, Betsy; Dawid, Suzanne; Aiello, Allison E.; Davis, Brian M.; Berus, Joshua; Rohani, Pejman

2013-01-01

A significant fraction of seasonal and in particular pandemic influenza deaths are attributed to secondary bacterial infections. In animal models, influenza virus predisposes hosts to severe infection with both Streptococcus pneumoniae and Staphylococcus aureus. Despite its importance, the mechanistic nature of the interaction between influenza and pneumococci, its dependence on the timing and sequence of infections as well as the clinical and epidemiological consequences remain unclear. We explore an immune-mediated model of the viral–bacterial interaction that quantifies the timing and the intensity of the interaction. Taking advantage of the wealth of knowledge gained from animal models, and the quantitative understanding of the kinetics of pathogen-specific immunological dynamics, we formulate a mathematical model for immune-mediated interaction between influenza virus and S. pneumoniae in the lungs. We use the model to examine the pathogenic effect of inoculum size and timing of pneumococcal invasion relative to influenza infection, as well as the efficacy of antivirals in preventing severe pneumococcal disease. We find that our model is able to capture the key features of the interaction observed in animal experiments. The model predicts that introduction of pneumococcal bacteria during a 4–6 day window following influenza infection results in invasive pneumonia at significantly lower inoculum size than in hosts not infected with influenza. Furthermore, we find that antiviral treatment administered later than 4 days after influenza infection was not able to prevent invasive pneumococcal disease. This work provides a quantitative framework to study interactions between influenza and pneumococci and has the potential to accurately quantify the interactions. Such quantitative understanding can form a basis for effective clinical care, public health policies and pandemic preparedness. PMID:23825111

A clinical pharmacological assessment of doxazosin and enalapril in combination.

PubMed

Bainbridge, A D; Meredith, P A; Elliott, H L

1993-12-01

This study in 12 normotensive males investigated potential pharmacokinetic and pharmacodynamic interaction mechanisms resulting from the combination of enalapril and doxazosin. Blood pressure reductions were consistently greater with the combination but there was no evidence of a significant pharmacodynamic interaction (as determined by heart rate changes, renal function tests or by pressor responsiveness indices) and there was no evidence of a pharmacokinetic interaction with either drug. Responsiveness to each drug i.e. blood pressure reduction per unit drug concentration was not significantly altered in the combination regimen. In conclusion, these results suggest that the combination of enalapril and doxazosin produces a usefully additive hypotensive effect but there was no evidence of synergism i.e an effect which was more than additive.

Association between physicians’ interaction with pharmaceutical companies and their clinical practices: A systematic review and meta-analysis

PubMed Central

Al-Khaled, Lina; Kahale, Lara A.; Nas, Hala; El-Jardali, Fadi

2017-01-01

Background Pharmaceutical company representatives likely influence the prescribing habits and professional behaviors of physicians. The objective of this study was to systematically review the association between physicians’ interactions with pharmaceutical companies and their clinical practices. Methods We used the standard systematic review methodology. Observational and experimental study designs examining any type of targeted interaction between practicing physicians and pharmaceutical companies were eligible. The search strategy included a search of MEDLINE and EMBASE databases up to July 2016. Two reviewers selected studies, abstracted data, and assessed risk of bias in duplicate and independently. We assessed the quality of evidence using the GRADE approach. Results Twenty articles reporting on 19 studies met our inclusion criteria. All of these studies were conducted in high-income countries and examined different types of interactions, including detailing, industry-funded continuing medical education, and receiving free gifts. While all included studies assessed prescribing behaviors, four studies also assessed financial outcomes, one assessed physicians’ knowledge, and one assessed their beliefs. None of the studies assessed clinical outcomes. Out of the 19 studies, 15 found a consistent association between interactions promoting a medication, and inappropriately increased prescribing rates, lower prescribing quality, and/or increased prescribing costs. The remaining four studies found both associations and lack of significant associations for the different types of exposures and drugs examined in the studies. A meta-analysis of six of these studies found a statistically significant association between exposure and physicians’ prescribing behaviors (OR = 2.52; 95% CI 1.82–3.50). The quality of evidence was downgraded to moderate for risk of bias and inconsistency. Sensitivity analysis excluding studies at high risk of bias did not substantially change these results. A subgroup analysis did not find a difference by type of exposure. Conclusion There is moderate quality evidence that physicians’ interactions with pharmaceutical companies are associated with their prescribing patterns and quality. PMID:28406971

Predictive performance of three practical approaches for grapefruit juice-induced 2-fold or greater increases in AUC of concomitantly administered drugs.

PubMed

Takahashi, M; Onozawa, S; Ogawa, R; Uesawa, Y; Echizen, H

2015-02-01

Clinical pharmacists have a challenging task when answering patients' question about whether they can take specific drugs with grapefruit juice (GFJ) without risk of drug interaction. To identify the most practicable method for predicting clinically relevant changes in plasma concentrations of orally administered drugs caused by the ingestion of GFJ, we compared the predictive performance of three methods using data obtained from the literature. We undertook a systematic search of drug interactions associated with GFJ using MEDLINE and the Metabolism & Transport Drug Interaction Database (DIDB version 4.0). We considered an elevation of the area under the plasma concentration-time curve (AUC) of 2 or greater relative to the control value [AUC ratio (AUCR) ≥ 2.0] as a clinically significant interaction. The data from 74 drugs (194 data sets) were analysed. When the reported information of CYP3A involvement in the metabolism of a drug of interest was adopted as a predictive criterion for GFJ-drug interaction, the performance assessed by positive predictive value (PPV) was low (0.26), but that assessed by negative predictive value (NPV) and sensitivity was high (1.00 for both). When the reported oral bioavailability of ≤ 0.1 was used as a criterion, the PPV improved to 0.50 with an acceptable NPV of 0.81, but sensitivity was reduced to 0.21. When the reported AUCR was ≥ 10 after co-administration of a typical CYP3A inhibitor, the corresponding values were 0.64, 0.79 and 0.19, respectively. We consider that an oral bioavailability of ≤ 0.1 or an AUCR of ≥ 10 caused by a CYP3A inhibitor of a drug of interest may be a practical prediction criterion for avoiding significant interactions with GFJ. Information about the involvement of CYP3A in their metabolism should also be taken into account for drugs with narrow therapeutic ranges. © 2014 John Wiley & Sons Ltd.

Oxytocin response to youth–mother interactions in clinically anxious youth is associated with separation anxiety and dyadic behavior

PubMed Central

Lebowitz, Eli R.; Silverman, Wendy K.; Martino, Alyssa M.; Zagoory-Sharon, Orna; Feldman, Ruth; Leckman, James F.

2017-01-01

Background Anxiety disorders are common in youth and cause significant distress and impairment to the individual and family. Oxytocin (OT), a nine amino acid peptide, is implicated in anxiety regulation and modulation of close interpersonal and attachment behavior. Anxiety disorders have been linked to low levels of salivary OT in youth. Research has also linked oxytocinergic functioning to social support, warm contact, and bonding, and indicated that contact with attachment figures stimulates OT response. We examined OT response to a brief, positive youth–mother interaction in clinically anxious youth. We investigated whether quality of the youth–mother interaction as well as the presence of particular anxiety disorders, are associated with youth OT response. Method Salivary OT from 41 youth with primary DSM-5 anxiety disorders was assayed before and after a 7-min youth–mother interaction that was later systematically coded by two reliable coders. Youth and mothers also completed rating scales of youth anxiety symptoms. Results Affective touch, maternal sensitivity, maternal intrusiveness, youth engagement, and youth initiative all contributed significantly to predicting youth OT response. Repeated measures analyses showed that when affective touch was high youth had greater OT response. OT response was positively associated with the presence of separation anxiety disorder (SAD) and with child ratings of separation anxiety. Conclusions The findings highlight the importance of maternal and dyadic behavior patterns to oxytocinergic response in clinically anxious youth, shed light on the association between OT and SAD, and point to possible intervention strategies. PMID:28052452

The antinociceptive effect of zolpidem and zopiclone in mice.

PubMed

Pick, Chaim G; Chernes, Yakov; Rigai, Tova; Rice, Kenner C; Schreiber, Shaul

2005-07-01

Zolpidem and zopiclone are two of a newer hypno-sedative class of drugs, the "Z compounds". Their use for the treatment of short-term insomnia has been expanding constantly during the last two decades. The "Z compounds" are considered to cause less significant rebound insomnia or tolerance than the conventional hypnotic benzodiazepines. Their possible antinociceptive effect and interaction with the opioid system has not been studied yet. Our results demonstrate a significant difference between the antinociceptive properties of zopiclone and zolpidem when injected s.c. in the hotplate analgesic assay in mice. Zopiclone induced a weak, dose-dependent antinociceptive effect, antagonized only by the alpha2-adrenergic receptor antagonist yohimbine. Zolpidem induced a weak, biphasic dose-dependent antinociceptive effect, antagonized primarily by the non-selective opioid antagonist naloxone and by yohimbine. The weak antinociceptive effect of both drugs, evident only at very high doses (far beyond those used clinically to induce sleep), implies no clinical use for zopiclone or zolpidem in the management of pain. However, the possible interaction of zolpidem with the opioid system should be further investigated (in behavioral models, which do not overlap with the acute-pain antinociception model we used), both for possible side effects in special populations (i.e. elderly) and for possible drug-drug interactions, in order to minimize possible hazards and maximize clinical beneficial effects of its use for sleep.

Modeling eye gaze patterns in clinician-patient interaction with lag sequential analysis.

PubMed

Montague, Enid; Xu, Jie; Chen, Ping-Yu; Asan, Onur; Barrett, Bruce P; Chewning, Betty

2011-10-01

The aim of this study was to examine whether lag sequential analysis could be used to describe eye gaze orientation between clinicians and patients in the medical encounter. This topic is particularly important as new technologies are implemented into multiuser health care settings in which trust is critical and nonverbal cues are integral to achieving trust. This analysis method could lead to design guidelines for technologies and more effective assessments of interventions. Nonverbal communication patterns are important aspects of clinician-patient interactions and may affect patient outcomes. The eye gaze behaviors of clinicians and patients in 110 videotaped medical encounters were analyzed using the lag sequential method to identify significant behavior sequences. Lag sequential analysis included both event-based lag and time-based lag. Results from event-based lag analysis showed that the patient's gaze followed that of the clinician, whereas the clinician's gaze did not follow the patient's. Time-based sequential analysis showed that responses from the patient usually occurred within 2 s after the initial behavior of the clinician. Our data suggest that the clinician's gaze significantly affects the medical encounter but that the converse is not true. Findings from this research have implications for the design of clinical work systems and modeling interactions. Similar research methods could be used to identify different behavior patterns in clinical settings (physical layout, technology, etc.) to facilitate and evaluate clinical work system designs.

Modeling Eye Gaze Patterns in Clinician-Patient Interaction with Lag Sequential Analysis

PubMed Central

Montague, E; Xu, J; Asan, O; Chen, P; Chewning, B; Barrett, B

2011-01-01

Objective The aim of this study was to examine whether lag-sequential analysis could be used to describe eye gaze orientation between clinicians and patients in the medical encounter. This topic is particularly important as new technologies are implemented into multi-user health care settings where trust is critical and nonverbal cues are integral to achieving trust. This analysis method could lead to design guidelines for technologies and more effective assessments of interventions. Background Nonverbal communication patterns are important aspects of clinician-patient interactions and may impact patient outcomes. Method Eye gaze behaviors of clinicians and patients in 110-videotaped medical encounters were analyzed using the lag-sequential method to identify significant behavior sequences. Lag-sequential analysis included both event-based lag and time-based lag. Results Results from event-based lag analysis showed that the patients’ gaze followed that of clinicians, while clinicians did not follow patients. Time-based sequential analysis showed that responses from the patient usually occurred within two seconds after the initial behavior of the clinician. Conclusion Our data suggest that the clinician’s gaze significantly affects the medical encounter but not the converse. Application Findings from this research have implications for the design of clinical work systems and modeling interactions. Similar research methods could be used to identify different behavior patterns in clinical settings (physical layout, technology, etc.) to facilitate and evaluate clinical work system designs. PMID:22046723

Synergistic effect of cumulative corticosteroid dose and immunosuppressants on avascular necrosis in patients with systemic lupus erythematosus.

PubMed

Kwon, H H; Bang, S Y; Won, S; Park, Y; Yi, J H; Joo, Y B; Lee, H S; Bae, S C

2018-01-01

Objectives Avascular necrosis (AVN) is one of the most common causes of organ damage in patients with systemic lupus erythematosus (SLE) and often causes serious physical disability. The aims of this study were to investigate clinical risk factors associated with symptomatic AVN and to analyze their synergistic effects in a large SLE cohort in Korea. Methods Patients with SLE were enrolled and followed from 1998 to 2014 in the Hanyang BAE Lupus cohort, and damage was measured annually according to the Systemic Lupus International Collaborating Clinics/American College of Rheumatology Damage Index (SDI). AVN was confirmed by imaging study if patients had symptoms. To determine risk factors for AVN, clinical, laboratory and therapeutic variables were analyzed by logistic regression. Relative excess risk due to interaction (RERI), attributable proportion (AP), and synergy index (S) were calculated to measure interactions between significant variables. Results Among 1219 SLE patients, symptomatic AVN was the most common type of musculoskeletal damage (10.8%, n = 132). SLE patients with AVN showed an earlier onset age, demonstrated AVN more commonly in conjunction with certain other clinical manifestations such as renal and neuropsychiatric disorders, and received significantly higher total cumulative corticosteroid dose and immunosuppressive agents than did patients without AVN. However, in multivariable analysis, only two variables including use of a cumulative corticosteroid dose greater than 20 g (odds ratio (OR) 3.62, p = 0.015) and use of immunosuppressants including cyclophosphamide or mycophenolate mofetil (OR 4.51, p < 0.001) remained as significant risk factors for AVN. Patients with cumulative corticosteroid dose > 20 g and immunosuppressant use had a 15.44-fold increased risk for AVN, compared with patients without these risk factors ( p < 0.001). RERI, AP and S, which define the strength of interactions between two risk factors, were 9.01 (95% confidence interval (CI) 1.30-16.73), 0.58 (95% CI 0.36-0.81) and 2.66 (95% CI 1.42-4.99), respectively, supporting the presence of synergistic interactions in the development of symptomatic AVN in our Korean lupus cohort. Conclusions An individual risk assessment for AVN development should be made prior to and during treatment for SLE, especially in patients with high-dose corticosteroid and immunosuppressant use regardless of clinical manifestations and disease activity.

Anxiety symptoms and quality of interaction among oncology nurses: a correlational, cross-sectional study.

PubMed

Karanikola, Maria Nk; Giannakopoulou, Margarita; Kalafati, Maria; Kaite, Charis P; Patiraki, Elisabeth; Mpouzika, Meropi; Papathanassoglou, Elisabeth E D; Middleton, Nicos

2016-01-01

To explore the severity of Anxiety Symptoms (AS) among Greek oncology nursing personnel, the degree of satisfaction from professional relationships, and potential association between them. A descriptive cross-sectional correlational study was performed in 2 Greek Oncology Hospitals, in 72 members of nursing personnel. Hamilton Anxiety Scale was used for the assessment of AS severity and the Index of Work Satisfaction subscale "Satisfaction from Interaction" for the degree of satisfaction from professional relationships among nursing personnel (NN) and between nursing personnel and physicians (NP). 11% of the sample reported clinical AS [≥26, scale range (SR): 0-52]. Satisfaction from NN [5.10 (SD: 1.04), SR: 1-7], and NP [4.21 (SD: 0.77), SR: 1-7] professional interaction were both moderate. Statistically significantly associations were observed between clinical AS and satisfaction from NN (p=0.014) and NP (p=0.013) professional interaction. Anxiety reduction interventions and improvement of professional relationships are essentials in order to reduce oncology nurses' psychological distress.

[Interactive workshops as a dissemination strategy in psychology].

PubMed

Martínez-Martínez, Kalina Isela; Carrascosa-Venegas, César; Ayala-Velázquez, Héctor

2003-01-01

To assess whether interactive workshops are an effective strategy for promoting a psychological intervention model among healthcare providers, to treat problem drinkers. The study was conducted between the years 1999 and 2000, among 206 healthcare providers at seven Instituto Mexicano del Seguro Social (Mexican Institute of Social Security, IMSS) clinics. Study subjects were selected by hospital executive officers. The study design is a quasi-experimental pre-test/post-test study. Data on providers' attitudes, interests, and knowledge were collected using a questionnaire. After that, interactive workshops were conducted, and the same questionnaire was applied again at the end of the workshops. Statistical analysis was carried out using Student's t test for matched samples. Statistically significant differences were found in participants' knowledge on alcoholism t (206, 205) = -9.234, p = 0.001, as well as in their interest t (206, 205) = -2.318, p = 0.021. Interactive workshops are an effective tool to disseminate the Guided Self-Help Program conducted in IMSS clinics. Healthcare providers can become change-inducing/promoting agents of psychological innovations.

Suicide, hopelessness, and social desirability: a test of an interactive model.

PubMed

Holden, R R; Mendonca, J D; Serin, R C

1989-08-01

We examined the relationships among suicidal indices, hopelessness, and social desirability. Both hopelessness and a measure of social desirability that reflected a sense of general capability were significant indicators of suicidal manifestations. In particular, hierarchical multiple regression procedures demonstrated that hopelessness and social desirability interacted in the prediction of suicide variables. Results generalized across various clinical diagnostic subgroups of psychiatric patients and a sample of prisoners and across different clinically evaluated and self-reported indices of suicidal behavior. Findings are interpreted to mean that a sense of general capability buffers the link of hopelessness to suicidal behavior. Implications for understanding the cognitions associated with suicide and for improving prediction of persons at risk are discussed.

Carbamazepine toxicity during combination therapy with levetiracetam: a pharmacodynamic interaction.

PubMed

Sisodiya, Sanjay M; Sander, Josemir W A S; Patsalos, Philip N

2002-02-01

Levetiracetam is a novel antiepileptic drug with an unknown mechanism of action. To-date levetiracetam is not known to be associated with any clinically significant pharmacokinetic interaction. Similarly, levetiracetam has not been associated with any pharmacodynamic interactions. We present four patients with severe refractory epilepsy in whom introduction of levetiracetam led to disabling symptoms compatible with carbamazepine toxicity requiring either carbamazepine dose reduction or levetiracetam withdrawal. As carbamazepine and carbamazepine-epoxide blood levels were not altered during levetiracetam co-medication, a pharmacodynamic interaction is suggested. Therefore, during levetiracetam co-medication with carbamazepine, patients should be monitored closely for symptoms of carbamazepine toxicity.

Statin-Induced Cardioprotection Against Ischemia-Reperfusion Injury: Potential Drug-Drug Interactions. Lesson to be Learnt by Translating Results from Animal Models to the Clinical Settings.

PubMed

Birnbaum, Gilad D; Birnbaum, Itamar; Ye, Yumei; Birnbaum, Yochai

2015-01-01

Numerous interventions have been shown to limit myocardial infarct size in animal models; however, most of these interventions have failed to have a significant effect in clinical trials. One potential explanation for the lack of efficacy in the clinical setting is that in bench models, a single intervention is studied without the background of other interventions or modalities. This is in contrast to the clinical setting in which new medications are added to the "standard of care" treatment that by now includes a growing number of medications. Drug-drug interaction may lead to alteration, dampening, augmenting or masking the effects of the intended intervention. We use the well described model of statin-induced myocardial protection to demonstrate potential interactions with agents which are commonly concomitantly used in patients with stable coronary artery disease and/or acute coronary syndromes. These interactions could potentially explain the reduced efficacy of statins in the clinical trials compared to the animal models. In particular, caffeine and aspirin could attenuate the infarct size limiting effects of statins; morphine could delay the onset of protection or mask the protective effect in patients with ST elevation myocardial infarction, whereas other anti-platelet agents (dipyridamole, cilostazol and ticagrelor) may augment (or mask) the effect due to their favorable effects on adenosine cell reuptake and intracellular cAMP levels. We recommend that after characterizing the effects of new modalities in single intervention bench research, studies should be repeated in the background of standard-of-care medications to assure that the magnitude of the effect is not altered before proceeding with clinical trials.

Antiretroviral Drug Interactions: Overview of Interactions Involving New and Investigational Agents and the Role of Therapeutic Drug Monitoring for Management

PubMed Central

Rathbun, R. Chris; Liedtke, Michelle D.

2011-01-01

Antiretrovirals are prone to drug-drug and drug-food interactions that can result in subtherapeutic or supratherapeutic concentrations. Interactions between antiretrovirals and medications for other diseases are common due to shared metabolism through cytochrome P450 (CYP450) and uridine diphosphate glucuronosyltransferase (UGT) enzymes and transport by membrane proteins (e.g., p-glycoprotein, organic anion-transporting polypeptide). The clinical significance of antiretroviral drug interactions is reviewed, with a focus on new and investigational agents. An overview of the mechanistic basis for drug interactions and the effect of individual antiretrovirals on CYP450 and UGT isoforms are provided. Interactions between antiretrovirals and medications for other co-morbidities are summarized. The role of therapeutic drug monitoring in the detection and management of antiretroviral drug interactions is also briefly discussed. PMID:24309307

Is the clinical relevance of drug-food and drug-herb interactions limited to grapefruit juice and Saint-John's Wort?

PubMed

Mouly, Stéphane; Lloret-Linares, Célia; Sellier, Pierre-Olivier; Sene, Damien; Bergmann, J-F

2017-04-01

An interaction of drug with food, herbs, and dietary supplements is usually the consequence of a physical, chemical or physiologic relationship between a drug and a product consumed as food, nutritional supplement or over-the-counter medicinal plant. The current educational review aims at reminding to the prescribing physicians that the most clinically relevant drug-food interactions may not be strictly limited to those with grapefruit juice and with the Saint John's Wort herbal extract and may be responsible for changes in drug plasma concentrations, which in turn decrease efficacy or led to sometimes life-threatening toxicity. Common situations handled in clinical practice such as aging, concomitant medications, transplant recipients, patients with cancer, malnutrition, HIV infection and those receiving enteral or parenteral feeding may be at increased risk of drug-food or drug-herb interactions. Medications with narrow therapeutic index or potential life-threatening toxicity, e.g., the non-steroidal anti-inflammatory drugs, opioid analgesics, cardiovascular medications, warfarin, anticancer drugs and immunosuppressants may be at risk of significant drug-food interactions to occur. Despite the fact that considerable effort has been achieved to increase patient' and doctor's information and ability to anticipate their occurrence and consequences in clinical practice, a thorough and detailed health history and dietary recall are essential for identifying potential problems in order to optimize patient prescriptions and drug dosing on an individual basis as well as to increase the treatment risk/benefit ratio. Copyright © 2016 Elsevier Ltd. All rights reserved.

[Medical rehabilitation group-programmes concerning health promotion, patient education and psychoeducation - a 2010 national survey].

PubMed

Reusch, A; Schug, M; Küffner, R; Vogel, H; Faller, H

2013-08-01

High quality demands are being placed on concepts of educational group programmes in medical rehabilitation as well as the related trainer qualifications. A nationwide survey of German medical rehabilitation clinics in 2005 had revealed a need for improving educational practice according to these quality criteria. An updated investigation was performed in 2010 aiming at describing group programmes used in medical rehabilitation. 1 473 inpatient and outpatient medical rehabilitation clinics were invited to participate. 908 clinics reported on their training programmes. Data from clinics caring for patients with somatic disorders could be compared to the 2005 survey. Data from clinics for both psychosomatic and substance abuse disorders was collected for the first time in 2010. Overall, psychologists and physicians were reported to be the most frequent conductors of educative programmes. In somatic clinics, psychologists, dieticians and occupational therapists or physiotherapists were the most common conductors. Two-thirds of the institutions reported no training prerequisites for staff members to perform patient education. 80% of the education programmes were categorized post hoc into 3 classes: "generic health education", "disorder-specific patient education", and "psychoeducational group programmes". Almost two-thirds of all programmes were carried out with 8-15 participants, and many used several interactive didactic methods. Programmes conducted in small groups (<8 participants) used significantly more interactive methods than those conducted in larger groups did (>15 participants). Only half of the programmes were manualized. Significantly more interactive methods were used in completely manualized programmes. Only about half of the programmes were evaluated, and only very few evaluation studies were published. The institutions wished additional support by workshops especially concerning qualification of their staff and concerning educational concepts. A need for further improvement and support exists relative to the training of educators and the development of manuals as well as evaluation and publication of the programmes. © Georg Thieme Verlag KG Stuttgart · New York.

Social anxiety and the interpretation of positive social events.

PubMed

Alden, Lynn E; Taylor, Charles T; Mellings, Tanna M J B; Laposa, Judith M

2008-05-01

We report four independent studies that examined the relationship between social interaction anxiety and the tendency to interpret positive social events in a threat-maintaining manner. Study 1 described the development of a scale that measures negative interpretations of positive social events, the interpretation of positive events scale (IPES). Study 2 cross-validated the structure of the IPES and established that social interaction anxiety explained significant variance in negative interpretations of positive social events beyond negative affect in general. Study 3 demonstrated that negative interpretation of positive events was significantly greater in a clinical sample of patients with generalized social anxiety disorder (GSAD) than a matched group of non-anxious community controls. In addition, within the GSAD group, the IPES was associated with negative social predictions following a positive interaction. Finally, study 4 confirmed that negative interpretations of positive social events mediated the relationship between social interaction anxiety and low positive affect.

Virtual Reality and Interactive Digital Game Technology: New Tools to Address Obesity and Diabetes

PubMed Central

“Skip” Rizzo, Albert; Lange, Belinda; Suma, Evan A; Bolas, Mark

2011-01-01

The convergence of the exponential advances in virtual reality (VR)-enabling technologies with a growing body of clinical research and experience has fueled the evolution of the discipline of clinical VR. This article begins with a brief overview of methods for producing and delivering VR environments that can be accessed by users for a range of clinical health conditions. Interactive digital games and new forms of natural movement-based interface devices are also discussed in the context of the emerging area of exergaming, along with some of the early results from studies of energy expenditure during the use of these systems. While these results suggest that playing currently available active exergames uses significantly more energy than sedentary activities and is equivalent to a brisk walk, these activities do not reach the level of intensity that would match playing the actual sport, nor do they deliver the recommended daily amount of exercise for children. However, these results provide some support for the use of digital exergames using the current state of technology as a complement to, rather than a replacement, for regular exercise. This may change in the future as new advances in novel full-body interaction systems for providing vigorous interaction with digital games are expected to drive the creation of engaging, low-cost interactive game-based applications designed to increase exercise participation in persons at risk for obesity. PMID:21527091

Membrane interaction and functional plasticity of inositol polyphosphate 5-phosphatases.

PubMed

Braun, Werner; Schein, Catherine H

2014-05-06

In this issue of Structure, Trésaugues and colleagues determined the interaction of membrane-bound phosphoinositides with three clinically significant human inositol polyphosphate 5-phosphatases (I5Ps). A comparison to the structures determined with soluble substrates revealed differences in the binding mode and suggested how the I5Ps and apurinic endonuclease (APE1) activities evolved from the same metal-binding active center. Copyright © 2014 Elsevier Ltd. All rights reserved.

Mindfulness-based stress reduction for chronic insomnia in adults older than 75 years: a randomized, controlled, single-blind clinical trial.

PubMed

Zhang, Jia-Xu; Liu, Xiao-Hui; Xie, Xin-Hui; Zhao, Dan; Shan, Mo-Shui; Zhang, Xi-Liang; Kong, Xiao-Ming; Cui, Hong

2015-01-01

To assess the effectiveness of mindfulness-based stress reduction (MBSR) for chronic insomnia and combined depressive or anxiety symptoms of older adults aged 75 years and over. A randomized, controlled, single-blind clinical trial. Participants included 60 adults aged 75 years and over with chronic insomnia. Participants were randomly assigned to the eight-week MBSR group or the wait-list control group. Assessments using the Pittsburgh Sleep Quality Index (PSQI), Self-rating Anxiety Sale (SAS), and Geriatric Depression Scale (GDS) were taken at baseline and post-treatment. For each outcome measure, a repeated measures analysis of variance was used to detect changes across assessments. There was a significant time × group interaction for the PSQI global score (P = .006); the MBSR group had a decrease in the PSQI global score (Cohen׳s d = 1.12), while the control group did not (Cohen׳s d = -0.06). Among the PSQI components, there was a significant time × group interaction for daytime dysfunction (P = .048); Cohen׳s d of the MBSR group was 0.76, while Cohen׳s d of control group was -0.04. There was no significant time × group interaction for the SAS score (P = .116), while for the GDS there was a significant time × group interaction (P = .039); the Cohen׳s d value for the MBSR group was 1.20, and it was 0.12 for the control group. This study demonstrated that the MBSR program could be a beneficial treatment for chronic insomnia in adults aged 75 years and older. Copyright © 2015 Elsevier Inc. All rights reserved.

The Dutch Social Interaction Anxiety Scale and the Social Phobia Scale: Reliability, Validity, and Clinical Utility

PubMed Central

Tielen, Deirdre; Wollmann, Lisa

2014-01-01

The social interaction anxiety scale (SIAS) and the social phobia scale (SPS) assess anxiety in social interactions and fear of scrutiny by others. This study examines the psychometric properties of the Dutch versions of the SIAS and SPS using data from a large group of patients with social phobia and a community-based sample. Confirmatory factor analysis revealed that the SIAS is unidimensional, whereas the SPS is comprised of three subscales. The internal consistency of the scales and subscales was good. The concurrent and discriminant validity was supported and the scales were well able to discriminate between patients and community-based respondents. Cut-off values with excellent sensitivity and specificity are presented. Of all self-report measures included, the SPS was the most sensitive for treatment effects. Normative data are provided which can be used to assess whether clinically significant change has occurred in individual patients. PMID:24701560

The dutch social interaction anxiety scale and the social phobia scale: reliability, validity, and clinical utility.

PubMed

de Beurs, Edwin; Tielen, Deirdre; Wollmann, Lisa

2014-01-01

The social interaction anxiety scale (SIAS) and the social phobia scale (SPS) assess anxiety in social interactions and fear of scrutiny by others. This study examines the psychometric properties of the Dutch versions of the SIAS and SPS using data from a large group of patients with social phobia and a community-based sample. Confirmatory factor analysis revealed that the SIAS is unidimensional, whereas the SPS is comprised of three subscales. The internal consistency of the scales and subscales was good. The concurrent and discriminant validity was supported and the scales were well able to discriminate between patients and community-based respondents. Cut-off values with excellent sensitivity and specificity are presented. Of all self-report measures included, the SPS was the most sensitive for treatment effects. Normative data are provided which can be used to assess whether clinically significant change has occurred in individual patients.

OTC analgesics and drug interactions: clinical implications

PubMed Central

Fendrick, A Mark; Pan, Deborah E; Johnson, Grace E

2008-01-01

The risk of drug interactions with concurrent use of multiple medications is a clinically relevant issue. Many patients are unaware that over-the-counter (OTC) analgesics can cause potentially serious adverse effects when used in combination with other common medications such as anticoagulants, corticosteroids, or antihypertensive agents. Of particular significance is the increased risk of upper abdominal gastrointestinal adverse events in patients who take traditional nonsteroidal anti-inflammatory drugs (NSAIDs). This risk is dose dependent and further increased in patients who take more than one NSAID or use NSAIDs in combination with certain other medications. Some NSAIDs may also mitigate the antiplatelet benefits of aspirin and may increase blood pressure in patients with hypertension. Clinicians should be aware of potential drug interactions with OTC analgesics when prescribing new medications. Additionally, patients should be properly counseled on the appropriate and safe use of OTC analgesics. PMID:18257920

The effects of levetiracetam, sumatriptan, and caffeine in a rat model of trigeminal pain: interactions in 2-component combinations.

PubMed

Tomić, Maja A; Pecikoza, Uroš B; Micov, Ana M; Popović, Božidar V; Stepanović-Petrović, Radica M

2015-06-01

Levetiracetam is an antiepileptic drug with analgesic efficacy shown in pain models and small clinical trials. Sumatriptan is used in acute migraine treatment. Caffeine is widely consumed in some beverages/foods and is also an adjuvant in analgesic formulations. We examined the effects of systemic levetiracetam, sumatriptan, and caffeine and their interactions in 2-component combinations in the rat orofacial formalin test, a model of trigeminal pain. Rats received a subcutaneous injection of formalin solution into the perinasal area, and the total time spent in nociceptive behavior (face rubbing) was quantified. The antinociceptive effect of drugs/drug combinations was assessed 1 hour after per os administration. The type of interaction between levetiracetam/sumatriptan and caffeine was examined by comparing the effects of a fixed, effective dose of levetiracetam/sumatriptan alone with the effects of the same dose applied with increasing, subeffective doses of caffeine. The type of interaction between levetiracetam and sumatriptan was determined by isobolographic analysis. Levetiracetam (1-50 mg/kg) and sumatriptan (0.5-5 mg/kg) produced significant and dose-dependent antinociceptive effects in both phases of the orofacial formalin test (P ≤ 0.001). Caffeine (7.5-100 mg/kg) produced significant antinociception in the second phase of the test (P = 0.04). Caffeine (1-7.5 mg/kg) significantly reduced the antinociceptive effects of levetiracetam (25 mg/kg) (first phase P = 0.002, second phase P < 0.001) and sumatriptan (2.5 mg/kg) (first phase P = 0.014, second phase P = 0.027); dose-dependent inhibition was observed in the second phase. Levetiracetam and sumatriptan exerted an additive interaction in the second phase of the orofacial formalin test. Results indicate that levetiracetam may be useful for treatment of pain in the trigeminal region. Dietary caffeine might decrease the effects of levetiracetam and sumatriptan; this needs to be considered in clinical settings. A levetiracetam-sumatriptan combination could also be useful in trigeminal pain treatment. Its efficacy and adverse effects should be examined clinically.

Ensemble survival tree models to reveal pairwise interactions of variables with time-to-events outcomes in low-dimensional setting

PubMed Central

Dazard, Jean-Eudes; Ishwaran, Hemant; Mehlotra, Rajeev; Weinberg, Aaron; Zimmerman, Peter

2018-01-01

Unraveling interactions among variables such as genetic, clinical, demographic and environmental factors is essential to understand the development of common and complex diseases. To increase the power to detect such variables interactions associated with clinical time-to-events outcomes, we borrowed established concepts from random survival forest (RSF) models. We introduce a novel RSF-based pairwise interaction estimator and derive a randomization method with bootstrap confidence intervals for inferring interaction significance. Using various linear and nonlinear time-to-events survival models in simulation studies, we first show the efficiency of our approach: true pairwise interaction-effects between variables are uncovered, while they may not be accompanied with their corresponding main-effects, and may not be detected by standard semi-parametric regression modeling and test statistics used in survival analysis. Moreover, using a RSF-based cross-validation scheme for generating prediction estimators, we show that informative predictors may be inferred. We applied our approach to an HIV cohort study recording key host gene polymorphisms and their association with HIV change of tropism or AIDS progression. Altogether, this shows how linear or nonlinear pairwise statistical interactions of variables may be efficiently detected with a predictive value in observational studies with time-to-event outcomes. PMID:29453930

Physicians' perceptions of physician-nurse interactions and information needs in China.

PubMed

Wen, Dong; Guan, Pengcheng; Zhang, Xingting; Lei, Jianbo

2018-01-01

Good communication between physicians and nurses is important for the understanding of disease status and treatment feedback; however, certain issues in Chinese hospitals could lead to suboptimal physician-nurse communication in clinical work. Convenience sampling was used to recruit participants. Questionnaires were sent to clinical physicians in three top tertiary Grade-A teaching hospitals in China and six hundred and seventeen physicians participated in the survey. (1) Common physician-nurse interactions were shift-change reports and provisional reports when needed, and interactions expected by physicians included face-to-face reports and communication via a phone or mobile device. (2) Most respondents believed that the need for information in physician-nurse interactions was high, information was moderately accurate and timely, and feedback regarding interaction time and satisfaction indicated that they were only average and required improvement. (3) Information needs in physician-nurse interactions differed significantly according to hospital category, role, workplace, and educational background (p < .05). There was a considerable need for information within physician-nurse interactions, and the level of satisfaction with the information obtained was average; requirements for the improvement of communication differed between physicians and nurses because of differences in their characteristics. Currently, the use of information technology in physician-nurse communication was less common but was highly expected by physicians.

Ensemble survival tree models to reveal pairwise interactions of variables with time-to-events outcomes in low-dimensional setting.

PubMed

Dazard, Jean-Eudes; Ishwaran, Hemant; Mehlotra, Rajeev; Weinberg, Aaron; Zimmerman, Peter

2018-02-17

Unraveling interactions among variables such as genetic, clinical, demographic and environmental factors is essential to understand the development of common and complex diseases. To increase the power to detect such variables interactions associated with clinical time-to-events outcomes, we borrowed established concepts from random survival forest (RSF) models. We introduce a novel RSF-based pairwise interaction estimator and derive a randomization method with bootstrap confidence intervals for inferring interaction significance. Using various linear and nonlinear time-to-events survival models in simulation studies, we first show the efficiency of our approach: true pairwise interaction-effects between variables are uncovered, while they may not be accompanied with their corresponding main-effects, and may not be detected by standard semi-parametric regression modeling and test statistics used in survival analysis. Moreover, using a RSF-based cross-validation scheme for generating prediction estimators, we show that informative predictors may be inferred. We applied our approach to an HIV cohort study recording key host gene polymorphisms and their association with HIV change of tropism or AIDS progression. Altogether, this shows how linear or nonlinear pairwise statistical interactions of variables may be efficiently detected with a predictive value in observational studies with time-to-event outcomes.

Patient satisfaction with doctor-patient interactions: a mixed methods study among diabetes mellitus patients in Pakistan.

PubMed

Jalil, Aisha; Zakar, Rubeena; Zakar, Muhammad Zakria; Fischer, Florian

2017-02-21

Patient satisfaction with doctor-patient interactions is an indicator of physicians' competence. The satisfaction of diabetes patients is rarely studied in public diabetes clinics of Pakistan. Thus, this study aims to analyse the association between patient satisfaction and five dimensions of medical interaction: technical expertise, interpersonal aspects, communication, consultation time, and access/availability. A cross-sectional mixed methods study was conducted during July and August 2015 in the largest public diabetes outpatient clinic in Punjab province. We used the criterion sampling method to identify 1164 patients who: (i) were adult (18 years and above), (ii) had diabetes mellitus, (iii) had made at least three previous visits to the same clinic. The data was collected through face-to-face interviews. The structured part of the questionnaire was based on demographic characteristics and the Patient Satisfaction Questionnaire (PSQ-III). We translated the questionnaire into Urdu and pretested it with 25 patients in a similar context. Data storage and analysis were carried out using SPSS (version 22.0). Bivariate analyses and multinomial logistic regression model were used to generate the quantitative findings. Out of the 1164 eligible patients approached for interviews, 1095 patients completed the structured questionnaire and 186 respondents provided qualitative information in comments section. We conducted a thematic content analysis of qualitative responses in order to explain the quantitative findings. Demographic characteristics such as gender, education and occupation were significantly associated with the levels of patient satisfaction. The dimensions of doctor-patient interaction were significantly associated with patient satisfaction: technical expertise (OR = .87; 95% CI = .84-.91), interpersonal aspects (OR = .82; 95% CI = .77-.87), communication (OR = .83; 95% CI = .78-.89), time dimension (OR = .90; 95% CI = .81-.99) and access/availability (OR = .78; 95% CI = .72-.84). Several factors involving doctors' incompetence, such as inappropriate handling of critical cases, inaccurate diagnose, excessive reliance on medical tests, absence of physical examination, non-availability of specialist doctors, and experimentation by trainee doctors were related to patient dissatisfaction. The findings of this study highlight a need to develop the interpersonal and clinical skills of doctors in order to improve the quality of doctor-patient interactions in public clinics for diabetes in Pakistan. Prospective researches should explore context-specific factors that form patient satisfaction.

Neuropathologic features associated with Alzheimer disease diagnosis

PubMed Central

Grinberg, L.T.; Miller, B.; Kawas, C.; Yaffe, K.

2011-01-01

Objective: To examine whether the association between clinical Alzheimer disease (AD) diagnosis and neuropathology and the precision by which neuropathology differentiates people with clinical AD from those with normal cognition varies by age. Methods: We conducted a cross-sectional analysis of 2,014 older adults (≥70 years at death) from the National Alzheimer's Coordinating Center database with clinical diagnosis of normal cognition (made ≤1 year before death, n = 419) or AD (at ≥65 years, n = 1,595) and a postmortem neuropathologic examination evaluating AD pathology (neurofibrillary tangles, neuritic plaques) and non-AD pathology (diffuse plaques, amyloid angiopathy, Lewy bodies, macrovascular disease, microvascular disease). We used adjusted logistic regression to analyze the relationship between clinical AD diagnosis and neuropathologic features, area under the receiver operating characteristic curve (c statistic) to evaluate how precisely neuropathology differentiates between cognitive diagnoses, and an interaction to identify effect modification by age group. Results: In a model controlling for coexisting neuropathologic features, the relationship between clinical AD diagnosis and neurofibrillary tangles was significantly weaker with increasing age (p < 0.001 for interaction). The aggregate of all neuropathologic features more strongly differentiated people with clinical AD from those without in younger age groups (70–74 years: c statistic, 95% confidence interval: 0.93, 0.89–0.96; 75–84 years: 0.95, 0.87–0.95; ≥85 years: 0.83, 0.80–0.87). Non-AD pathology significantly improved precision of differentiation across all age groups (p < 0.004). Conclusion: Clinical AD diagnosis was more weakly associated with neurofibrillary tangles among the oldest old compared to younger age groups, possibly due to less accurate clinical diagnosis, better neurocompensation, or unaccounted pathology among the oldest old. PMID:22031532

Infant Attachment Security and Early Childhood Behavioral Inhibition Interact to Predict Adolescent Social Anxiety Symptoms

PubMed Central

Lewis-Morrarty, Erin; Degnan, Kathryn A.; Chronis-Tuscano, Andrea; Pine, Daniel S.; Henderson, Heather A.; Fox, Nathan A.

2014-01-01

Insecure attachment and behavioral inhibition (BI) increase risk for internalizing problems, but few longitudinal studies have examined their interaction in predicting adolescent anxiety. This study included 165 adolescents (ages 14-17 years) selected based on their reactivity to novelty at 4 months. Infant attachment was assessed with the Strange Situation. Multi-method BI assessments were conducted across childhood. Adolescents and their parents independently reported on anxiety. The interaction of attachment and BI significantly predicted adolescent anxiety symptoms, such that BI and anxiety were only associated among adolescents with histories of insecure attachment. Exploratory analyses revealed that this effect was driven by insecure-resistant attachment and that the association between BI and social anxiety was significant only for insecure males. Clinical implications are discussed. PMID:25522059

Interactive effects of C-reactive protein levels on the association between APOE variants and triglyceride levels in a Taiwanese population.

PubMed

Wu, Semon; Hsu, Lung-An; Teng, Ming-Sheng; Lin, Jeng-Feng; Chou, Hsin-Hua; Lee, Ming-Cheng; Wu, Yi-Ming; Su, Cheng-Wen; Ko, Yu-Lin

2016-05-13

Apolipoprotein E (APOE) plays a major role in lipid metabolism and inflammation. However, the association between APOE gene polymorphisms and serum triglyceride levels remains controversial. We tested the effects of APOE variants on triglyceride levels and their interactions with the inflammatory marker C-reactive protein (CRP) in a Taiwanese population. Two APOE single nucleotide polymorphisms (SNPs) rs429358 and rs7412 were genotyped by TaqMan Assay using real time PCR in 595 healthy subjects attending the clinic for routine visits. After adjustment for clinical covariates, subjects carrying the rs429358-TT genotype and non-ε4 alleles were found to have higher CRP levels, whereas those with rs7412-CC genotype and non-ε2 alleles had significantly higher total and low-density lipoprotein cholesterol levels (all P < 0.01). Using subgroup and interaction analyses, we observed significantly lower triglyceride levels in subjects carrying the rs429358-TT genotype and non-ε4 alleles in the low CRP group (P = 2.71 × 10(-4) and P = 4.32 × 10(-4), respectively), but not in those in the high CRP group (interaction P = 0.013 and 0.045, respectively). In addition, multivariate stepwise linear regression analysis showed that subjects carrying the rs429358-TT genotype and non-ε4 alleles with low CRP levels had significantly lower triglyceride levels (P < 0.001 and P < 0.001, respectively). In addition, when combined with the risk alleles of GCKR, APOA5 and LPL gene variants, we observed that triglyceride levels increased significantly with the number of risk alleles (P = 2.9 × 10(-12)). The combination of SNPs and ε alleles at the APOE locus is involved in managing lipid and CRP levels in the Taiwanese population. APOE polymorphisms interact with CRP to regulate triglyceride levels, thus triglyceride concentration is influenced by both the genetic background of the APOE locus and the inflammatory status of a subject.

Advances in the understanding of the clinically relevant genetic pathways and molecular aspects of canine mammary tumours. Part 2: invasion, angiogenesis, metastasis and therapy.

PubMed

Santos, A A; Matos, A J F

2015-08-01

Significant advances have been made recently in the understanding of the molecular events and critical pathways associated with and driving cancer of the mammary gland in humans and dogs. The study of canine mammary tumour biology, particularly the interactions of neoplastic cells with stromal and immune cells, is crucial for the development of novel effective therapeutic agents and strategies. This second part of a two-part review discusses some of the latest advances in the understanding of the clinically relevant genetic and molecular pathways involved in metastasis and in the interactions between tumour and stromal cells, including inflammatory and immune cells, cancer-associated fibroblasts, and endothelial cells. Recent experimental data on the role of matrix-degrading proteases and angiogenic factors are also discussed. Finally, the clinical utility of different non-surgical therapeutic modalities is reviewed. Copyright © 2015 Elsevier Ltd. All rights reserved.

Drug-nutrient interactions: a broad view with implications for practice.

PubMed

Boullata, Joseph I; Hudson, Lauren M

2012-04-01

The relevance of drug?nutrient interactions in daily practice continues to grow with the widespread use of medication. Interactions can involve a single nutrient, multiple nutrients, food in general, or nutrition status. Mechanistically, drug?nutrient interactions occur because of altered intestinal transport and metabolism, or systemic distribution, metabolism and excretion, as well as additive or antagonistic effects. Optimal patient care includes identifying, evaluating, and managing these interactions. This task can be supported by a systematic approach for categorizing interactions and rating their clinical significance. This review provides such a broad framework using recent examples, as well as some classic drug?nutrient interactions. Pertinent definitions are presented, as is a suggested approach for clinicians. This important and expanding subject will benefit tremendously from further clinician involvement. Copyright © 2012 Academy of Nutrition and Dietetics. Published by Elsevier Inc. All rights reserved.

Adherence to drug-drug interaction alerts in high-risk patients: a trial of context-enhanced alerting.

PubMed

Duke, Jon D; Li, Xiaochun; Dexter, Paul

2013-05-01

Drug-drug interaction (DDI) alerting is an important form of clinical decision support, yet physicians often fail to attend to critical DDI warnings due to alert fatigue. We previously described a model for highlighting patients at high risk of a DDI by enhancing alerts with relevant laboratory data. We sought to evaluate the effect of this model on alert adherence in high-risk patients. A 6-month randomized controlled trial involving 1029 outpatient physicians was performed. The target interactions were all DDIs known to cause hyperkalemia. Alerts in the intervention group were enhanced with the patient's most recent potassium and creatinine levels. The control group received unmodified alerts. High -risk patients were those with baseline potassium >5.0 mEq/l and/or creatinine ≥1.5 mg/dl (132 μmol/l). We found no significant difference in alert adherence in high-risk patients between the intervention group (15.3%) and the control group (16.8%) (p=0.71). Adherence in normal risk patients was significantly lower in the intervention group (14.6%) than in the control group (18.6%) (p<0.01). In neither group did physicians increase adherence in patients at high risk. Physicians adhere poorly to hyperkalemia-associated DDI alerts even in patients with risk factors for a clinically significant interaction, and the display of relevant laboratory data in these alerts did not improve adherence levels in the outpatient setting. Further research is necessary to determine optimal strategies for conveying patient-specific DDI risk.

Evolution of Emotional Symptoms Over Time Among Daughters of Patients With Breast Cancer.

PubMed

Wellisch, David K; Ormseth, Sarah R; Aréchiga, Adam E

2015-01-01

This study longitudinally profiled anxiety and depressive symptoms of daughters of patients with breast cancer and examined the mother׳s survival status, the daughter׳s age at the time of mother׳s diagnosis, and the style of family communication about breast cancer as moderators of change in symptomatology across participants׳ first 3 appointments at the University of California, Los Angeles Revlon Breast Center High Risk Clinic. We evaluated the effects of hypothesized predictors on change in anxiety and depressive symptoms, 3 (symptomatology at first, second, and third clinic visits) × 2 (mother survived or died) × 2 (<20 or ≥20y old at diagnosis) × 2 (open or closed family communication) repeated-measures analyses of variance were employed. There was a main effect for time of diagnosis on state anxiety, demonstrating a significant reduction in anxiety across clinic visits overall (p < 0.001). There were also significant 3-way interactions. For state anxiety, mother׳s survival status moderated the time of diagnosis × age at diagnosis and time of diagnosis × family communication interaction effects. For daughters whose mothers died, decreased anxiety was observed in those who were younger at the time of diagnosis (p = 0.001). For daughters whose mothers survived, anxiety was decreased for those with closed family communication styles (p = 0.001). The time of diagnosis × mother׳s survival × age at diagnosis interaction was also significant for depressive symptoms (p = 0.001). Among daughters whose mothers died, those who were younger showed decreases in symptoms (p = 0.004). These daughters appeared to benefit from the high-risk program as demonstrated by decreased symptomatology, particularly daughters whose mothers died who were younger at the time of diagnosis. Copyright © 2015 The Academy of Psychosomatic Medicine. Published by Elsevier Inc. All rights reserved.

Pharmacokinetics and Drug Interactions Determine Optimum Combination Strategies in Computational Models of Cancer Evolution.

PubMed

Chakrabarti, Shaon; Michor, Franziska

2017-07-15

The identification of optimal drug administration schedules to battle the emergence of resistance is a major challenge in cancer research. The existence of a multitude of resistance mechanisms necessitates administering drugs in combination, significantly complicating the endeavor of predicting the evolutionary dynamics of cancers and optimal intervention strategies. A thorough understanding of the important determinants of cancer evolution under combination therapies is therefore crucial for correctly predicting treatment outcomes. Here we developed the first computational strategy to explore pharmacokinetic and drug interaction effects in evolutionary models of cancer progression, a crucial step towards making clinically relevant predictions. We found that incorporating these phenomena into our multiscale stochastic modeling framework significantly changes the optimum drug administration schedules identified, often predicting nonintuitive strategies for combination therapies. We applied our approach to an ongoing phase Ib clinical trial (TATTON) administering AZD9291 and selumetinib to EGFR-mutant lung cancer patients. Our results suggest that the schedules used in the three trial arms have almost identical efficacies, but slight modifications in the dosing frequencies of the two drugs can significantly increase tumor cell eradication. Interestingly, we also predict that drug concentrations lower than the MTD are as efficacious, suggesting that lowering the total amount of drug administered could lower toxicities while not compromising on the effectiveness of the drugs. Our approach highlights the fact that quantitative knowledge of pharmacokinetic, drug interaction, and evolutionary processes is essential for identifying best intervention strategies. Our method is applicable to diverse cancer and treatment types and allows for a rational design of clinical trials. Cancer Res; 77(14); 3908-21. ©2017 AACR . ©2017 American Association for Cancer Research.

Impact of Interactive e-Learning Modules on Appropriateness of Imaging Referrals: A Multicenter, Randomized, Crossover Study.

PubMed

Velan, Gary M; Goergen, Stacy K; Grimm, Jane; Shulruf, Boaz

2015-11-01

Health care expenditure on diagnostic imaging investigations is increasing, and many tests are ordered inappropriately. Validated clinical decision rules (CDRs) for certain conditions are available to aid in assessing the need for imaging. However, awareness and utilization of CDRs are lacking. This study compared the efficacy and perceived impact of interactive e-learning modules versus static versions of CDRs, for learning about appropriate imaging referrals. A multicenter, randomized, crossover trial was performed; participants were volunteer medical students and recent graduates. In week 1, group 1 received an e-learning module on appropriate imaging referrals for pulmonary embolism; group 2 received PDF versions of relevant CDRs, and an online quiz with feedback. In week 2, the groups crossed over, focusing on imaging referrals for cervical spine trauma in adults. Online assessments were administered to both groups at the end of each week, and participants completed an online questionnaire at the end of the trial. Group 1 (e-learning module) performed significantly better on the pulmonary embolism knowledge assessment. After the crossover, participants in group 2 (e-learning module) were significantly more likely to improve their scores in the assessment of cervical spine trauma knowledge. Both groups gave positive evaluations of the e-learning modules. Interactive e-learning was significantly more effective for learning in this cohort, compared with static CDRs. We believe that the authentic clinical scenarios, feedback, and integration provided by the e-learning modules contributed to their impact. This study has implications for implementation of e-learning tools to facilitate appropriate referrals for imaging investigations in clinical practice. Crown Copyright © 2015. Published by Elsevier Inc. All rights reserved.

An introductory orientation to clinical pathology core and on-call responsibilities.

PubMed

Pappas, A A; Drew, M J; Flick, J; Fink, L; Fuller, G L; Hough, A J

1994-05-01

An introductory 4-week orientation for clinical pathology is described. There were 76 hours of lectures, 74 hours of conferences, and 68 hours of laboratories for a total of 221 hours. During the orientation, all calls handled by the residents were evaluated as to resolution, patient outcome, and interaction required. Eighty calls were received during the orientation from 57 technologists (71%), 16 physicians (20%), and seven nurses (9%). The calls originated concerning the following: blood banking, 37 (46%); hematology, 21 (27%); chemistry, 14 (18%); microbiology, five (6%); and administration, three (4%). Sixty percent of the calls were consultative and 40% were supervisory. Ninety-nine percent were handled appropriately by the residents. Patient outcome was moderately or significantly affected in 44% of all calls, divided between 67% of all consultative calls and 9% of all supervisory calls. Significant pathologist interaction was required in 49% of all calls, divided between 71% of the consultative calls and 16% of the supervisory calls. Using this integrated, dynamic system of resident instruction, on-call experience, and evaluation, residents quickly gain confidence in handling call, didactic clinical consultation, and patient management. The orientation and on-call system described provides for a relevant and dynamic system for resident education.

Parent-child reading interactions among English and English as a second language speakers in an underserved pediatric clinic in Hawai'i.

PubMed

Kitabayashi, Kristyn M; Huang, Gary Y; Linskey, Katy R; Pirga, Jason; Bane-Terakubo, Teresa; Lee, Meta T

2008-10-01

The purpose of this study was to compare reading patterns between English-speaking and English as a Second Language (ESL) families in a health care setting in Hawai'i. A cross-sectional study was performed at an underserved pediatric primary care clinic in Hawai'i. Caregivers of patients between the ages of 6 months to 5 years were asked questions regarding demographics and parent-child reading interactions. Respondents were categorized into English-speaking or ESL groups based on primary language spoken at home. Pearson chi2 tests and Fisher exact tests were performed to compare demographic differences, reading frequency, and reading attitudes between groups. One-hundred three respondents completed the survey Fifty percent were ESL. All ESL respondents were of Asian-Pacific Islander (API) or mixed Asian ethnicity. All Caucasians in the study (n = 9) were in the English-speaking group. Between the English-speaking (n = 52) and ESL (n = 51) groups, there were no significant statistical differences in age or gender of the child, reading attitudes, or parent's educational status. Parents in the ESL group read to their children significantly fewer days per week than their English-speaking counterparts, had significantly fewer books in the home, and lived significantly fewer years in the United States. The findings suggest that API immigrant families share similar attitudes about reading as English-speaking families in Hawai'i but have significantly fewer books in their household and read significantly less frequently Physicians working with API populations should be aware that immigrant children may have fewer reading interactions and should counsel parents on the importance of reading daily.

Quadratic function between arterial partial oxygen pressure and mortality risk in sepsis patients: an interaction with simplified acute physiology score.

PubMed

Zhang, Zhongheng; Ji, Xuqing

2016-10-13

Oxygen therapy is widely used in emergency and critical care settings, while there is little evidence on its real therapeutic effect. The study aimed to explore the impact of arterial oxygen partial pressure (PaO 2 ) on clinical outcomes in patients with sepsis. A large clinical database was employed for the study. Subjects meeting the diagnostic criteria of sepsis were eligible for the study. All measurements of PaO 2 were extracted. The primary endpoint was death from any causes during hospital stay. Survey data analysis was performed by using individual ICU admission as the primary sampling unit. Quadratic function was assumed for PaO 2 and its interaction with other covariates were explored. A total of 199,125 PaO 2 samples were identified for 11,002 ICU admissions. Each ICU stay comprised 18 PaO 2 samples in average. The fitted multivariable model supported our hypothesis that the effect of PaO 2 on mortality risk was in quadratic form. There was significant interaction between PaO 2 and SAPS-I (p = 0.007). Furthermore, the main effect of PaO 2 on SOFA score was nonlinear. The study shows that the effect of PaO 2 on mortality risk is in quadratic function form, and there is significant interaction between PaO 2 and severity of illness.

Are Low Patient Satisfaction Scores Always Due to the Provider?: Determinants of Patient Satisfaction Scores During Spine Clinic Visits.

PubMed

Bible, Jesse E; Shau, David N; Kay, Harrison F; Cheng, Joseph S; Aaronson, Oran S; Devin, Clinton J

2018-01-01

A prospective study. The aim of this study was to investigate the impact of various components on patient satisfaction scores SUMMARY OF BACKGROUND DATA.: Patient satisfaction has become an important component of quality assessments. However, with many of these sources collecting satisfaction data reluctant to disclose detailed information, little remains known about the potential determinants of patient satisfaction. Two hundred patients were contacted via phone within 3 weeks of new patient encounter with 11 spine providers. Standardized patient satisfaction phone survey consisting of 25 questions (1-10 rating scale) was administered. Questions inquired about scheduling, parking, office staff, teamwork, wait-time, radiology, provider interactions/behavior, treatment, and follow-up communication. Potential associations between these factors and three main outcome measures were investigated: (1) provider satisfaction, (2) overall clinic visit satisfaction, and (3) quality of care. Significant associations (P < 0.0001) with provider satisfaction, overall clinic visit satisfaction, and perceived overall quality of care were found with appointment scheduling, parking, office staff, teamwork, wait time, radiology, provider interactions/behavior, treatment, and follow-up communication. Nurse-practitioner/resident involvement was positively associated with scores (P ≤ 0.03). A "candy-man" effect was not noted, as pain medication prescribing did not play a significant role in satisfaction (P > 0.05).In multivariate regression analysis, explanation of medical condition/treatment (P = 0.002) and provider empathy (P = 0.04) were significantly associated with provider satisfaction scores, while the amount of time spent with the provider was not. Conversely, teamwork of staff/provider and follow-up communication were significantly associated with both overall clinic visit satisfaction and quality of care (P ≤ 0.03), while provider behaviors or satisfaction were not. Satisfaction with the provider was associated with better explanations of the spine condition/treatment plan and provider empathy, but was not a significant factor in either overall clinic visit satisfaction or perceived quality of care. Patients' perception of teamwork between staff and providers along with reliable follow-up communication were found to be significant determinants of overall patient satisfaction and perceived quality of care. 3.

Assessing the clinical outcome of Vim radiosurgery with voxel-based morphometry: visual areas are linked with tremor arrest!

PubMed

Tuleasca, Constantin; Witjas, Tatiana; Najdenovska, Elena; Verger, Antoine; Girard, Nadine; Champoudry, Jerome; Thiran, Jean-Philippe; Van de Ville, Dimitri; Cuadra, Meritxell Bach; Levivier, Marc; Guedj, Eric; Régis, Jean

2017-11-01

Radiosurgery (RS) is an alternative to open standard stereotactic procedures (deep-brain stimulation or radiofrequency thalamotomy) for drug-resistant essential tremor (ET), aiming at the same target (ventro-intermediate nucleus, Vim). We investigated the Vim RS outcome using voxel-based morphometry by evaluating the interaction between clinical response and time. Thirty-eight patients with right-sided ET benefited from left unilateral Vim RS. Targeting was performed using 130 Gy and a single 4-mm collimator. Neurological and neuroimaging assessment was completed at baseline and 1 year. Clinical responders were considered those with at least 50% improvement in tremor score on the treated hand (TSTH). Interaction between clinical response and time showed the left temporal pole and occipital cortex (Brodmann area 19, including V4, V5 and the parahippocampal place area) as statistically significant. A decrease in gray matter density (GMD) 1 year after Vim RS correlated with higher TSTH improvement (Spearman = 0.01) for both anatomical areas. Higher baseline GMD within the left temporal pole correlated with better TSTH improvement (Spearman = 0.004). Statistically significant structural changes in the relationship to clinical response after Vim RS are present in remote areas, advocating a distant neurobiological effect. The former regions are mainly involved in locomotor monitoring toward the local and distant environment, suggesting the recruiting requirement in targeting of the specific visuomotor networks.

Pituitary volume and clinical trajectory in young relatives at risk for schizophrenia.

PubMed

Shah, J L; Tandon, N; Howard, E R; Mermon, D; Miewald, J M; Montrose, D M; Keshavan, M S

2015-10-01

Stress and vulnerability likely interact to play a major role in psychosis. While much has been written about the neural diathesis-stress model in psychosis and its clinical risk states, little is known about HPA axis biomarkers in non-help-seeking individuals at familial high risk (FHR). We sought to prospectively measure pituitary volume (PV) in adolescents and young adults at FHR for schizophrenia and to follow their emerging sub-clinical psychotic symptoms and clinical trajectories. Forty healthy controls and 38 relatives of patients with schizophrenia or schizoaffective disorder were identified in Pittsburgh, USA. PV was derived from baseline 1.5 T magnetic resonance imaging. Chapman's schizotypy scales were acquired at baseline, and structured clinical interviews for DSM-IV-TR Axis I diagnoses were attempted annually for up to 3 years. Seven individuals converted to psychosis. PV did not differ between FHR and control groups overall. Within the FHR group, PV was positively correlated with Chapman's positive schizotypy (Magical Ideation and Perceptual Aberration) scores, and there was a significant group × PV interaction with schizotypy. PV was significantly higher in FHR subjects carrying any baseline Axis I diagnosis (p = 0.004), and higher still in individuals who went on to convert to psychosis (p = 0.0007). Increased PV is a correlate of early positive schizotypy, and may predict trait vulnerability to subsequent psychosis in FHR relatives. These preliminary findings support a model of stress-vulnerability and HPA axis activation in the early phases of psychosis.

Effects of Interaction Between DRD4 Methylation and Prenatal Maternal Stress on Methylphenidate-Induced Changes in Continuous Performance Test Performance in Youth with Attention-Deficit/Hyperactivity Disorder.

PubMed

Kim, Johanna Inhyang; Kim, Jae-Won; Shin, Inkyung; Kim, Bung-Nyun

2018-06-15

Environmental factors may interact with genetic factors via the epigenetic process, and this interaction can contribute to inter-individual variability in the treatment response. The purpose of this study was to investigate the interaction effects between dopamine receptor D4 (DRD4) methylation and prenatal maternal stress on the methylphenidate (MPH) response of youth with attention-deficit/hyperactivity disorder (ADHD). This study was an 8-week open-label trial of MPH that included 74 ADHD youth. We investigated the associations between MPH treatment response, which was defined as a score ≤2 on the Clinical Global Impressions-Improvement (CGI-I) scale, and the methylation of 28 cytosine-guanine dinucleotide (CpG) sites of DRD4. Additionally, the interaction effects between DRD4 methylation and prenatal maternal stress on changes in Continuous Performance Test (CPT) scores after MPH treatment were investigated. Although there were no significant sites that showed significant association with treatment response, there was a significant interaction effect of the methylation of CpG7 and prenatal maternal stress on changes in omission errors of the CPT following treatment (p = 0.0001). The present findings indicate that the interaction between methylation of CpG7 of DRD4 and prenatal maternal stress may be predictive of the treatment response to MPH in youth with ADHD.

Impact of an Onsite Clinic on Utilization of Preventive Services.

PubMed

Ostovari, Mina; Yu, Denny; Yih, Yuehwern; Steele-Morris, Charlotte Joy

2017-07-01

To assess impact of an onsite clinic on healthcare utilization of preventive services for employees of a public university and their dependents. Descriptive statistics, logistic regression and classification tree techniques were used to assess health claim data to identify changes in patterns of healthcare utilization and factors impacting usage of onsite clinic. Utilization of preventive services significantly increased for women and men employees by 9% and 14% one year after implementation of the onsite clinic. Hourly-paid employees, employees without diabetes, employees with spouse opt out or no coverage were more likely to go to the onsite clinic. Adapted framework for assessing performance of onsite clinics based on usage of health informatics would help to identify health utilization patterns and interaction between onsite clinic and offsite health providers.

Immunosuppressive Interactions among Calcium Channel Antagonists and Selected Corticosteroids and Macrolides Using Human whole Blood Lymphocytes

PubMed Central

Chow, Fung-Sing; Jusko, William J.

2014-01-01

Summary The immunosuppressive interactions of calcium channel antagonists [diltiazem (Dil), verapamil (Ver) and nifedipine (Nif)], with corticosteroids [methylprednisolone (Mpl), prednisolone (Prd)], and macrolides [tacrolimus (Tac) and sirolnnus (Sir)] were examined in human whole blood lymphocyte cultures. Gender-related differences in responses in the interactions between these drug classes were studied using blood from 6 males and 6 females. The nature and intensity of interactions were determined using an extended Loewe additivity model. All immunosuppressants exhibited higher potency than the calcium channel antagonists with mean IC50 values of: Dil (mM)Ver (mM)Nif (mM)Mpl (nM)Prd (nM)Tac (nM)Sir (nM)Male13541.921312.118.6150327Female11431.847.44.68.8111106 Gender-related differences in responses to Mpl and Prd were observed while the others were not significant. Additive interactions were found among calcium channel antagonists and corticosteroids. Significant synergistic interactions were observed between calcium channel antagonists and tacrolimus and sirolimus, although these are unlikely to be of clinical importance. These studies demonstrate diverse drug interactions in the examination of an important array of immunosuppressant drug combinations. PMID:15681895

Proton pump inhibitors and potential interactions with clopidogrel: an update.

PubMed

Gerson, Lauren B

2013-06-01

Clopidogrel, an antiplatelet agent, is increasingly prescribed for patients with recent stroke, myocardial infarction, acute coronary syndrome, and/or patients post-coronary stent insertion to prevent recurrent cardiovascular events. Since clopidogrel can increase the risk of gastrointestinal hemorrhage, co-administration of proton pump inhibitors (PPIs) has been recommended, particularly in patients at high risk. In 2009, the FDA issued warnings about potential interactions between clopidogrel and PPIs, given the fact that both drugs are metabolized via the cytochrome P450 pathway. Prior studies have demonstrated significant reduction in platelet inhibition when PPI therapy is administered to subjects on clopidogrel therapy. Two meta-analyses were published in 2010 and 2011, the first suggesting association of PPIs with adverse cardiovascular events when observational studies were examined, but noting that the results were limited by the presence of significant heterogeneity. The second meta-analysis did not find a significant increase in the risk of adverse primary events (which included all cause mortality, cardiovascular death, myocardial infarction, or stroke), and concluded that analysis of the data from two randomized controlled trials yielded a risk difference of zero. An updated literature search was performed to assess clinical studies describing interactions between PPIs and clopidogrel published from 2011-2012. The majority of these studies did not show significant interactions when primary cardiac outcomes were considered. More importantly, the newer data demonstrated that PPI usage independently was a risk factor for adverse CV outcomes, since most PPI users were older patients who were more likely to have concomitant co-morbid conditions. Two updated reviews also concluded that the presence of confounding factors likely explained differences in results between studies, and that there were no significant differences in effects on clopidogrel between individual proton pump inhibitors. Overall, clinicians can assure their patients that combination therapy is safe when indicated in a patient at high risk of GI bleeding, but they should also stop PPI therapy if it is not clinically indicated.

A peer learning intervention for nursing students in clinical practice education: A quasi-experimental study.

PubMed

Pålsson, Ylva; Mårtensson, Gunilla; Swenne, Christine Leo; Ädel, Eva; Engström, Maria

2017-04-01

Studies of peer learning indicate that the model enables students to practice skills useful in their future profession, such as communication, cooperation, reflection and independence. However, so far most studies have used a qualitative approach and none have used a quasi-experimental design to study effects of nursing students' peer learning in clinical practice. To investigate the effects of peer learning in clinical practice education on nursing students' self-rated performance. Quasi-experimental. The study was conducted during nursing students' clinical practice. All undergraduate nursing students (n=87) attending their first clinical practice were approached. Seventy students out of 87 answered the questionnaires at both baseline and follow-up (42 of 46 in the intervention group and 28 of 39 in the comparison group). During the first two weeks of the clinical practice period, all students were supervised traditionally. Thereafter, the intervention group received peer learning the last two weeks, and the comparison group received traditional supervision. Questionnaire data were collected on nursing students' self-rated performance during the second (baseline) and last (follow-up) week of their clinical practice. Self-efficacy was improved in the intervention group and a significant interaction effect was found for changes over time between the two groups. For the other self-rated variables/tests, there were no differences in changes over time between the groups. Studying each group separately, the intervention group significantly improved on thirteen of the twenty variables/tests over time and the comparison group improved on four. The results indicate that peer learning is a useful method which improves nursing students' self-efficacy to a greater degree than traditional supervision does. Regarding the other self-rated performance variables, no interaction effects were found. Copyright © 2017 The Authors. Published by Elsevier Ltd.. All rights reserved.

Semiautomated segmentation of head and neck cancers in 18F-FDG PET scans: A just-enough-interaction approach.

PubMed

Beichel, Reinhard R; Van Tol, Markus; Ulrich, Ethan J; Bauer, Christian; Chang, Tangel; Plichta, Kristin A; Smith, Brian J; Sunderland, John J; Graham, Michael M; Sonka, Milan; Buatti, John M

2016-06-01

The purpose of this work was to develop, validate, and compare a highly computer-aided method for the segmentation of hot lesions in head and neck 18F-FDG PET scans. A semiautomated segmentation method was developed, which transforms the segmentation problem into a graph-based optimization problem. For this purpose, a graph structure around a user-provided approximate lesion centerpoint is constructed and a suitable cost function is derived based on local image statistics. To handle frequently occurring situations that are ambiguous (e.g., lesions adjacent to each other versus lesion with inhomogeneous uptake), several segmentation modes are introduced that adapt the behavior of the base algorithm accordingly. In addition, the authors present approaches for the efficient interactive local and global refinement of initial segmentations that are based on the "just-enough-interaction" principle. For method validation, 60 PET/CT scans from 59 different subjects with 230 head and neck lesions were utilized. All patients had squamous cell carcinoma of the head and neck. A detailed comparison with the current clinically relevant standard manual segmentation approach was performed based on 2760 segmentations produced by three experts. Segmentation accuracy measured by the Dice coefficient of the proposed semiautomated and standard manual segmentation approach was 0.766 and 0.764, respectively. This difference was not statistically significant (p = 0.2145). However, the intra- and interoperator standard deviations were significantly lower for the semiautomated method. In addition, the proposed method was found to be significantly faster and resulted in significantly higher intra- and interoperator segmentation agreement when compared to the manual segmentation approach. Lack of consistency in tumor definition is a critical barrier for radiation treatment targeting as well as for response assessment in clinical trials and in clinical oncology decision-making. The properties of the authors approach make it well suited for applications in image-guided radiation oncology, response assessment, or treatment outcome prediction.

The Aerobic and Cognitive Exercise Study (ACES) for Community-Dwelling Older Adults With or At-Risk for Mild Cognitive Impairment (MCI): Neuropsychological, Neurobiological and Neuroimaging Outcomes of a Randomized Clinical Trial.

PubMed

Anderson-Hanley, Cay; Barcelos, Nicole M; Zimmerman, Earl A; Gillen, Robert W; Dunnam, Mina; Cohen, Brian D; Yerokhin, Vadim; Miller, Kenneth E; Hayes, David J; Arciero, Paul J; Maloney, Molly; Kramer, Arthur F

2018-01-01

Prior research has found that cognitive benefits of physical exercise and brain health in older adults may be enhanced when mental exercise is interactive simultaneously, as in exergaming. It is unclear whether the cognitive benefit can be maximized by increasing the degree of mental challenge during exercise. This randomized clinical trial (RCT), the Aerobic and Cognitive Exercise Study (ACES) sought to replicate and extend prior findings of added cognitive benefit from exergaming to those with or at risk for mild cognitive impairment (MCI). ACES compares the effects of 6 months of an exer-tour (virtual reality bike rides) with the effects of a more effortful exer-score (pedaling through a videogame to score points). Fourteen community-dwelling older adults meeting screening criteria for MCI (sMCI) were adherent to their assigned exercise for 6 months. The primary outcome was executive function, while secondary outcomes included memory and everyday cognitive function. Exer-tour and exer-score yielded significant moderate effects on executive function (Stroop A/C; d 's = 0.51 and 0.47); there was no significant interaction effect. However, after 3 months the exer-tour revealed a significant and moderate effect, while exer-score showed little impact, as did a game-only condition. Both exer-tour and exer-score conditions also resulted in significant improvements in verbal memory. Effects appear to generalize to self-reported everyday cognitive function. Pilot data, including salivary biomarkers and structural MRI, were gathered at baseline and 6 months; exercise dose was associated with increased BDNF as well as increased gray matter volume in the PFC and ACC. Improvement in memory was associated with an increase in the DLPFC. Improved executive function was associated with increased expression of exosomal miRNA-9. Interactive physical and cognitive exercise (both high and low mental challenge) yielded similarly significant cognitive benefit for adherent sMCI exercisers over 6 months. A larger RCT is needed to confirm these findings. Further innovation and clinical trial data are needed to develop accessible, yet engaging and effective interventions to combat cognitive decline for the growing MCI population. ClinicalTrials.gov ID: NCT02237560.

The Aerobic and Cognitive Exercise Study (ACES) for Community-Dwelling Older Adults With or At-Risk for Mild Cognitive Impairment (MCI): Neuropsychological, Neurobiological and Neuroimaging Outcomes of a Randomized Clinical Trial

PubMed Central

Anderson-Hanley, Cay; Barcelos, Nicole M.; Zimmerman, Earl A.; Gillen, Robert W.; Dunnam, Mina; Cohen, Brian D.; Yerokhin, Vadim; Miller, Kenneth E.; Hayes, David J.; Arciero, Paul J.; Maloney, Molly; Kramer, Arthur F.

2018-01-01

Prior research has found that cognitive benefits of physical exercise and brain health in older adults may be enhanced when mental exercise is interactive simultaneously, as in exergaming. It is unclear whether the cognitive benefit can be maximized by increasing the degree of mental challenge during exercise. This randomized clinical trial (RCT), the Aerobic and Cognitive Exercise Study (ACES) sought to replicate and extend prior findings of added cognitive benefit from exergaming to those with or at risk for mild cognitive impairment (MCI). ACES compares the effects of 6 months of an exer-tour (virtual reality bike rides) with the effects of a more effortful exer-score (pedaling through a videogame to score points). Fourteen community-dwelling older adults meeting screening criteria for MCI (sMCI) were adherent to their assigned exercise for 6 months. The primary outcome was executive function, while secondary outcomes included memory and everyday cognitive function. Exer-tour and exer-score yielded significant moderate effects on executive function (Stroop A/C; d's = 0.51 and 0.47); there was no significant interaction effect. However, after 3 months the exer-tour revealed a significant and moderate effect, while exer-score showed little impact, as did a game-only condition. Both exer-tour and exer-score conditions also resulted in significant improvements in verbal memory. Effects appear to generalize to self-reported everyday cognitive function. Pilot data, including salivary biomarkers and structural MRI, were gathered at baseline and 6 months; exercise dose was associated with increased BDNF as well as increased gray matter volume in the PFC and ACC. Improvement in memory was associated with an increase in the DLPFC. Improved executive function was associated with increased expression of exosomal miRNA-9. Interactive physical and cognitive exercise (both high and low mental challenge) yielded similarly significant cognitive benefit for adherent sMCI exercisers over 6 months. A larger RCT is needed to confirm these findings. Further innovation and clinical trial data are needed to develop accessible, yet engaging and effective interventions to combat cognitive decline for the growing MCI population. ClinicalTrials.gov ID: NCT02237560 PMID:29780318

Identification of Staphylococcal Nuclease Domain-containing 1 (SND1) as a Metadherin-interacting Protein with Metastasis-promoting Functions*

PubMed Central

Blanco, Mario Andres; Alečković, Maša; Hua, Yuling; Li, Tuo; Wei, Yong; Xu, Zhen; Cristea, Ileana M.; Kang, Yibin

2011-01-01

Metastasis is the deadliest and most poorly understood feature of malignant diseases. Recent work has shown that Metadherin (MTDH) is overexpressed in over 40% of breast cancer patients and promotes metastasis and chemoresistance in experimental models of breast cancer progression. Here we applied mass spectrometry-based screen to identify staphylococcal nuclease domain-containing 1 (SND1) as a candidate MTDH-interacting protein. After confirming the interaction between SND1 and MTDH, we tested the role of SND1 in breast cancer and found that it strongly promotes lung metastasis. SND1 was further shown to promote resistance to apoptosis and to regulate the expression of genes associated with metastasis and chemoresistance. Analyses of breast cancer clinical microarray data indicated that high expression of SND1 in primary tumors is strongly associated with reduced metastasis-free survival in multiple large scale data sets. Thus, we have uncovered SND1 as a novel MTDH-interacting protein and shown that it is a functionally and clinically significant mediator of metastasis. PMID:21478147

Insight and illness perception in Mexican patients with psychosis.

PubMed

Gómez-de-Regil, Lizzette

2015-03-01

Insight and illness perception are two concepts of interest in the study of factors related to clinical outcome in patients with psychosis. Insight implies a risk of emotional distress for the patient. Illness perceptions, regardless of their accuracy, might be favorable or not to illness. Literature provides evidence of significant correlates of these factors with clinical outcome, but they are rarely included in a single study. 1) assessing insight and illness perception in a sample of Mexican patients who have experienced psychosis and, 2) analyzing how insight and illness perception relate to each other and how they relate to clinical status (i.e., positive, negative, and general psychopathology, depression, and anxiety). Sixty-one participants (55.7% females) were recruited from a public psychiatric hospital; insight and illness perceptions were assessed with the SUMD and the Brief-IPQ, respectively. Clinical status was assessed with the PANSS, CDS and BAI scales. Participants showed good insight, favorable illness perceptions for the cognitive and comprehension dimensions, but unfavorable for the emotional dimension. Clinical status of sample was characterized by mild symptoms. Poor insight related to positive symptoms and general psychopathology. Cognitive and emotional perceptions of illness were significantly associated to most clinical status parameters, whereas comprehension showed no significant results. The study not only replicates the significant association on insight and illness perception with clinical outcome, but shows how their patterns of interactions are different, reinforcing the idea that they are two distinct factors worthy of being habitually acknowledged in research and clinical practice.

Virtual reality and interactive digital game technology: new tools to address obesity and diabetes.

PubMed

Skip Rizzo, Albert; Lange, Belinda; Suma, Evan A; Bolas, Mark

2011-03-01

The convergence of the exponential advances in virtual reality (VR)-enabling technologies with a growing body of clinical research and experience has fueled the evolution of the discipline of clinical VR. This article begins with a brief overview of methods for producing and delivering VR environments that can be accessed by users for a range of clinical health conditions. Interactive digital games and new forms of natural movement-based interface devices are also discussed in the context of the emerging area of exergaming, along with some of the early results from studies of energy expenditure during the use of these systems. While these results suggest that playing currently available active exergames uses significantly more energy than sedentary activities and is equivalent to a brisk walk, these activities do not reach the level of intensity that would match playing the actual sport, nor do they deliver the recommended daily amount of exercise for children. However, these results provide some support for the use of digital exergames using the current state of technology as a complement to, rather than a replacement, for regular exercise. This may change in the future as new advances in novel full-body interaction systems for providing vigorous interaction with digital games are expected to drive the creation of engaging, low-cost interactive game-based applications designed to increase exercise participation in persons at risk for obesity. © 2011 Diabetes Technology Society.

Training experiences immediately after medical school.

PubMed

Roche, A M; Sanson-Fisher, R W; Cockburn, J

1997-01-01

Trainees in all teaching hospitals in New South Wales were surveyed using a self-completion, postal questionnaire to assess perceptions of the quality and extent of training received for interactional and technical skills. The response rate was 67.1%. Mean age was 25.4 years and 38.8% were female. Overall, training was found to be generally poor in terms of time and educational strategies used. Interactional skills were found to receive lower levels of training than technical skills both prior to and during the intern year with significantly fewer (P < 0.000) educational strategies reported for training received in interactional skills than for technical skills. Trainees' perceptions of the adequacy of training was significantly more negative for interactional than technical skills (P < 0.001). Assessment of competence was also significantly lower for interactional than technical skills (P < 0.001). On average, fewer than one in three trainees considered themselves to be competent in interactional skills compared to two-thirds who reported themselves as competent for technical skills. The findings of this study highlight the need for improved efforts with regard to both the quality and quantity of training provided during the intern year. Considerable scope exists for improved educational experiences for both interactional and technical skill areas, but particularly for interactional skills. Overall, greater use of a range of basic educational strategies such as the provision of 'observation' and 'critical feedback' is indicated. Efforts also need to be directed toward the training of clinical educators to optimize the potential of the preregistration period.

Confidence and Information Access in Clinical Decision-Making: An Examination of the Cognitive Processes that affect the Information-seeking Behavior of Physicians.

PubMed

Uy, Raymonde Charles; Sarmiento, Raymond Francis; Gavino, Alex; Fontelo, Paul

2014-01-01

Clinical decision-making involves the interplay between cognitive processes and physicians' perceptions of confidence in the context of their information-seeking behavior. The objectives of the study are: to examine how these concepts interact, to determine whether physician confidence, defined in relation to information need, affects clinical decision-making, and if information access improves decision accuracy. We analyzed previously collected data about resident physicians' perceptions of information need from a study comparing abstracts and full-text articles in clinical decision accuracy. We found that there is a significant relation between confidence and accuracy (φ=0.164, p<0.01). We also found various differences in the alignment of confidence and accuracy, demonstrating the concepts of underconfidence and overconfidence across years of clinical experience. Access to online literature also has a significant effect on accuracy (p<0.001). These results highlight possible CDSS strategies to reduce medical errors.

Exercise for Breast Cancer Survivors: Research Evidence and Clinical Guidelines.

ERIC Educational Resources Information Center

Courneya, Kerry S.; Mackey, John R.; McKenzie, Donald C.

2002-01-01

Exercise can significantly benefit breast cancer survivors during and after treatment. Moderate intensity aerobic exercise as well as resistance training are important. Psychological health is optimized by enjoyable exercise that develops new skills, incorporates social interaction, and occurs in a stimulating environment. Several conditions…

Association of FKBP5 Polymorphisms and Childhood Abuse With Risk of Posttraumatic Stress Disorder Symptoms in Adults

PubMed Central

Binder, Elisabeth B.; Bradley, Rebekah G.; Liu, Wei; Epstein, Michael P.; Deveau, Todd C.; Mercer, Kristina B.; Tang, Yilang; Gillespie, Charles F.; Heim, Christine M.; Nemeroff, Charles B.; Schwartz, Ann C.; Cubells, Joseph F.; Ressler, Kerry J.

2008-01-01

Context In addition to trauma exposure, other factors contribute to risk for development of posttraumatic stress disorder (PTSD) in adulthood. Both genetic and environmental factors are contributory, with child abuse providing significant risk liability. Objective To increase understanding of genetic and environmental risk factors as well as their interaction in the development of PTSD by gene × environment interactions of child abuse, level of non–child abuse trauma exposure, and genetic polymorphisms at the stress-related gene FKBP5. Design, Setting, and Participants A cross-sectional study examining genetic and psychological risk factors in 900 non psychiatric clinic patients (762 included for all genotype studies) with significant levels of childhood abuse as well as non–child abuse trauma using a verbally presented survey combined with single-nucleotide polymorphism (SNP) genotyping. Participants were primarily urban, low-income, black (>95%) men and women seeking care in the general medical care and obstetrics-gynecology clinics of an urban public hospital in Atlanta, Georgia, between 2005 and 2007. Main Outcome Measures Severity of adult PTSD symptomatology, measured with the modified PTSD Symptom Scale, non–child abuse (primarily adult) trauma exposure and child abuse measured using the traumatic events inventory and 8 SNPs spanning the FKBP5 locus. Results Level of child abuse and non–child abuse trauma each separately predicted level of adult PTSD symptomatology (mean [SD], PTSD Symptom Scale for no child abuse, 8.03 [10.48] vs ≥2 types of abuse, 20.93 [14.32]; and for no non–child abuse trauma, 3.58 [6.27] vs ≥4 types, 16.74 [12.90]; P<.001). Although FKBP5 SNPs did not directly predict PTSD symptom outcome or interact with level of non–child abuse trauma to predict PTSD symptom severity, 4 SNPs in the FKBP5 locus significantly interacted (rs9296158, rs3800373, rs1360780, and rs9470080; minimum P=.0004) with the severity of child abuse to predict level of adult PTSD symptoms after correcting for multiple testing. This gene × environment interaction remained significant when controlling for depression severity scores, age, sex, levels of non–child abuse trauma exposure, and genetic ancestry. This genetic interaction was also paralleled by FKBP5 genotype-dependent and PTSD-dependent effects on glucocorticoid receptor sensitivity, measured by the dexamethasone suppression test. Conclusions Four SNPs of the FKBP5 gene interacted with severity of child abuse as a predictor of adult PTSD symptoms. There were no main effects of the SNPs on PTSD symptoms and no significant genetic interactions with level of non–child abuse trauma as predictor of adult PTSD symptoms, suggesting a potential gene-childhood environment interaction for adult PTSD. PMID:18349090

Canine and Human Atopic Dermatitis: Two Faces of the Same Host-Microbe Interaction.

PubMed

Santoro, Domenico; Rodrigues Hoffmann, Aline

2016-06-01

Host-microbe interaction has been suggested to play a critical role in the pathogenesis of atopic dermatitis. The dog has been shown to be the best model to study both pathogenesis and microbiome modifications in atopic dermatitis. Bradley et al. show a significant correlation between microbiome diversity, clinical signs, and skin barrier function in atopic dogs before, during, and after antimicrobial therapy. Copyright © 2016 The Authors. Published by Elsevier Inc. All rights reserved.

Phage Therapy: Beyond Antibacterial Action.

PubMed

Górski, Andrzej; Jończyk-Matysiak, Ewa; Międzybrodzki, Ryszard; Weber-Dąbrowska, Beata; Łusiak-Szelachowska, Marzanna; Bagińska, Natalia; Borysowski, Jan; Łobocka, Małgorzata B; Węgrzyn, Alicja; Węgrzyn, Grzegorz

2018-01-01

Until recently, phages were considered as mere "bacteria eaters" with potential for use in combating antimicrobial resistance. The real value of phage therapy assessed according to the standards of evidence-based medicine awaits confirmation by clinical trials. However, the progress in research on phage biology has shed more light on the significance of phages. Accumulating data indicate that phages may also interact with eukaryotic cells. How such interactions could be translated into advances in medicine (especially novel means of therapy) is discussed herein.

Sex moderates the effects of positive and negative affect on clinical pain in patients with knee osteoarthritis.

PubMed

Speed, Traci J; Richards, Jessica M; Finan, Patrick H; Smith, Michael T

2017-07-01

Sex differences in clinical pain severity and response to experimental pain are commonly reported, with women generally showing greater vulnerability. Affect, including state (a single rating) and stable (average daily ratings over two weeks) positive affect and negative affect has also been found to impact pain sensitivity and severity, and research suggests that affect may modulate pain differentially as a function of sex. The current study aimed to examine sex as a moderator of the relationships between affect and pain-related outcomes among participants with knee osteoarthritis (KOA). One hundred and seventy-nine participants (59 men) with KOA completed electronic diaries assessing clinical pain, positive affect, and negative affect. A subset of participants (n=120) underwent quantitative sensory testing, from which a single index of central sensitization to pain was derived. We used multiple regression models to test for the interactive effects of sex and affect (positive versus negative and stable versus state) on pain-related outcomes. We used mixed effects models to test for the moderating effects of sex on the relationships between state affect and pain over time. Sex differences in affect and pain were identified, with men reporting significantly higher stable positive affect and lower central sensitization to pain indexed by quantitative sensory testing, as well as marginally lower KOA-specific clinical pain compared to women. Moreover, there was an interaction between stable positive affect and sex on KOA-specific clinical pain and average daily non-specific pain ratings. Post hoc analyses revealed that men showed trends towards an inverse relationship between stable positive affect and pain outcomes, while women showed no relationship between positive affect and pain. There was also a significant interaction between sex and stable negative affect and sex on KOA-specific pain such that men showed a significantly stronger positive relationship between stable negative affect and KOA-specific pain than women. Sex did not interact with state affect on pain outcomes. Findings suggest that men may be particularly sensitive to the effects of stable positive affect and negative affect on clinical pain. Future work with larger samples is needed in order to identify potential mechanisms driving the sex-specific effects of affect on pain. The current study provides novel data that suggesting that the association of positive affect, negative affect, and pain are different in men versus women with KOA. Further understanding of the difference in affective expression between men and women may lead to the development of novel therapeutic interventions and help to identify additional modifiable factors in the prevention and management of pain. Copyright © 2017 Scandinavian Association for the Study of Pain. Published by Elsevier B.V. All rights reserved.

MMP Inhibitors: Past, present and future.

PubMed

Cathcart, Jillian M; Cao, Jian

2015-06-01

  Development of inhibitors of matrix metalloproteinases (MMPs) has been fraught with challenges. Early compounds largely failed due to poor selectivity and bioavailability. Dose-limiting side effects, off-target interactions, and improperly designed clinical trials significantly impeded clinical success. As information becomes available and technology evolves, tools to combat these obstacles have been developed. Improved methods for high throughput screening and drug design have led to identification of compounds exhibiting high potency, binding affinity, and favorable pharmacokinetic profiles. Current research into MMP inhibitors employs innovative approaches for drug delivery methods and allosteric inhibitors. Such innovation is key for development of clinically successful compounds.

Pharmacokinetic and pharmacodynamic drug interactions of carbamazepine and glibenclamide in healthy albino Wistar rats

PubMed Central

Prashanth, S.; Kumar, A. Anil; Madhu, B.; Rama, N.; Sagar, J. Vidya

2011-01-01

Aims: To find out the pharmacokinetic and pharmacodynamic drug interaction of carbamazepine, a protype drug used to treat painful diabetic neuropathy with glibenclamide in healthy albino Wistar rats following single and multiple dosage treatment. Materials and Methods: Therapeutic doses (TD) of glibenclamide and TD of carbamazepine were administered to the animals. The blood glucose levels were estimated by GOD/POD method and the plasma glibenclamide concentrations were estimated by a sensitive RP HPLC method to calculate pharmacokinetic parameters. Results: In single dose study the percentage reduction of blood glucose levels and glibenclamide concentrations of rats treated with both carbamazepine and glibenclamide were significantly increased when compared with glibenclamide alone treated rats and the mechanism behind this interaction may be due to inhibition of P-glycoprotein mediated transport of glibenclamide by carbamazepine, but in multiple dose study the percentage reduction of blood glucose levels and glibenclamide concentrations were reduced and it may be due to inhibition of P-glycoprotein mediated transport and induction of CYP2C9, the enzyme through which glibenclamide is metabolised. Conclusions: In the present study there is a pharmacokinetic and pharmacodynamic interaction between carbamazepine and glibenclamide was observed. The possible interaction involves both P-gp and CYP enzymes. To investigate this type of interactions pre-clinically are helpful to avoid drug-drug interactions in clinical situation. PMID:21701639

Optimizing prognosis-related key miRNA-target interactions responsible for cancer metastasis.

PubMed

Zhao, Hongying; Yuan, Huating; Hu, Jing; Xu, Chaohan; Liao, Gaoming; Yin, Wenkang; Xu, Liwen; Wang, Li; Zhang, Xinxin; Shi, Aiai; Li, Jing; Xiao, Yun

2017-12-12

Increasing evidence suggests that the abnormality of microRNAs (miRNAs) and their downstream targets is frequently implicated in the pathogenesis of human cancers, however, the clinical benefit of causal miRNA-target interactions has been seldom studied. Here, we proposed a computational method to optimize prognosis-related key miRNA-target interactions by combining transcriptome and clinical data from thousands of TCGA tumors across 16 cancer types. We obtained a total of 1,956 prognosis-related key miRNA-target interactions between 112 miRNAs and 1,443 their targets. Interestingly, these key target genes are specifically involved in tumor progression-related functions, such as 'cell adhesion' and 'cell migration'. Furthermore, they are most significantly correlated with 'tissue invasion and metastasis', a hallmark of metastasis, in ten distinct types of cancer through the hallmark analysis. These results implicated that the prognosis-related key miRNA-target interactions were highly associated with cancer metastasis. Finally, we observed that the combination of these key miRNA-target interactions allowed to distinguish patients with good prognosis from those with poor prognosis both in most TCGA cancer types and independent validation sets, highlighting their roles in cancer metastasis. We provided a user-friendly database named miRNATarget (freely available at http://biocc.hrbmu.edu.cn/miRNATar/), which provides an overview of the prognosis-related key miRNA-target interactions across 16 cancer types.

Drug-drug interactions as a result of co-administering Δ9-THC and CBD with other psychotropic agents.

PubMed

Rong, Carola; Carmona, Nicole E; Lee, Yena L; Ragguett, Renee-Marie; Pan, Zihang; Rosenblat, Joshua D; Subramaniapillai, Mehala; Shekotikhina, Margarita; Almatham, Fahad; Alageel, Asem; Mansur, Rodrigo; Ho, Roger C; McIntyre, Roger S

2018-01-01

To determine, via narrative, non-systematic review of pre-clinical and clinical studies, whether the effect of cannabis on hepatic biotransformation pathways would be predicted to result in clinically significant drug-drug interactions (DDIs) with commonly prescribed psychotropic agents. Areas covered: A non-systematic literature search was conducted using the following databases: PubMed, PsycInfo, and Scopus from inception to January 2017. The search term cannabis was cross-referenced with the terms drug interactions, cytochrome, cannabinoids, cannabidiol, and medical marijuana. Pharmacological, molecular, and physiologic studies evaluating the pharmacokinetics of Δ 9 -tetrahydrocannabinol (Δ 9 -THC) and cannabidiol (CBD), both in vitro and in vivo, were included. Bibliographies were also manually searched for additional citations that were relevant to the overarching aim of this paper. Expert opinion: Δ 9 -Tetrahydrocannabinol and CBD are substrates and inhibitors of cytochrome P450 enzymatic pathways relevant to the biotransformation of commonly prescribed psychotropic agents. The high frequency and increasing use of cannabis invites the need for healthcare providers to familiarize themselves with potential DDIs in persons receiving select psychotropic agents, and additionally consuming medical marijuana and/or recreational marijuana.

Problem solving moderates the effects of life event stress and chronic stress on suicidal behaviors in adolescence.

PubMed

Grover, Kelly E; Green, Kelly L; Pettit, Jeremy W; Monteith, Lindsey L; Garza, Monica J; Venta, Amanda

2009-12-01

The present study examined the unique and interactive effects of stress and problem-solving skills on suicidal behaviors among 102 inpatient adolescents. As expected, life event stress and chronic stress each significantly predicted suicidal ideation and suicide attempt. Problem solving significantly predicted suicidal ideation, but not suicide attempt. Problem solving moderated the associations between life event stress and suicidal behaviors, as well as between chronic stress and suicidal ideation, but not chronic stress and suicide attempt. At high levels of stress, adolescents with poor problem-solving skills experienced elevated suicidal ideation and were at greater risk of making a nonfatal suicide attempt. The interactive effects decreased to non-significance after controlling for depressive symptoms and hopelessness. Clinical implications are discussed.

Parents who hit and scream: interactive effects of verbal and severe physical aggression on clinic-referred adolescents' adjustment.

PubMed

LeRoy, Michelle; Mahoney, Annette; Boxer, Paul; Gullan, Rebecca Lakin; Fang, Qijuan

2014-05-01

The goals of this study were first, to delineate the co-occurrence of parental severe physical aggression and verbal aggression toward clinic-referred adolescents, and second, to examine the interactive effects of parental severe physical aggression and verbal aggression on adolescent externalizing and internalizing behavior problems. This research involved 239 referrals of 11- to 18-year-old youth and their dual-parent families to a non-profit, private community mental health center in a semi-rural Midwest community. Multiple informants (i.e., adolescents and mothers) were used to assess parental aggression and adolescent behavior problems. More than half of clinic-referred adolescents (51%) experienced severe physical aggression and/or high verbal aggression from one or both parents. A pattern of interactive effects of mother-to-adolescent severe physical aggression and verbal aggression on adolescent behavior problems emerged, indicating that when severe physical aggression was present, mother-to-adolescent verbal aggression was positively associated with greater adolescent behavior problems whereas when severe physical aggression was not present, the links between verbal aggression and behavior problems was no longer significant. No interactive effects were found for father-to-adolescent severe physical aggression and verbal aggression on adolescent adjustment; however, higher father-to-adolescent verbal aggression was consistently linked to behavior problems above and beyond the influence of severe physical aggression. The results of this study should promote the practice of routinely assessing clinic-referred adolescents and their parents about their experiences of verbal aggression in addition to severe physical aggression and other forms of abuse. Copyright © 2013 Elsevier Ltd. All rights reserved.

Monitoring daily affective symptoms and memory function using interactive voice response in outpatients receiving electroconvulsive therapy.

PubMed

Fazzino, Tera L; Rabinowitz, Terry; Althoff, Robert R; Helzer, John E

2013-12-01

Recently, there has been a gradual shift from inpatient-only electroconvulsive therapy (ECT) toward outpatient administration. Potential advantages include convenience and reduced cost. But providers do not have the same opportunity to monitor treatment response and adverse effects as they do with inpatients. This can obviate some of the potential advantages of outpatient ECT, such as tailoring treatment intervals to clinical response. Scheduling is typically algorithmic rather than empirically based. Daily monitoring through an automated telephone, interactive voice response (IVR), is a potential solution to this quandary. To test feasibility of clinical monitoring via IVR, we recruited 26 patients (69% female; mean age, 51 years) receiving outpatient ECT to make daily IVR reports of affective symptoms and subjective memory for 60 days. The IVR also administered a word recognition task daily to test objective memory. Every seventh day, a longer IVR weekly interview included questions about suicidal ideation. Overall daily call compliance was high (mean, 80%). Most participants (96%) did not consider the calls to be time-consuming. Longitudinal regression analysis using generalized estimating equations revealed that participant objective memory functioning significantly improved during the study (P < 0.05). Of 123 weekly IVR interviews, 41 reports (33%) in 14 patients endorsed suicidal ideation during the previous week. Interactive voice response monitoring of outpatient ECT can provide more detailed clinical information than standard outpatient ECT assessment. Interactive voice response data offer providers a comprehensive, longitudinal picture of patient treatment response and adverse effects as a basis for treatment scheduling and ongoing clinical management.

Examining weight suppression as a predictor of eating disorder symptom trajectories in anorexia nervosa.

PubMed

Bodell, Lindsay P; Racine, Sarah E; Wildes, Jennifer E

2016-08-01

Research in individuals with bulimia nervosa has highlighted the clinical significance of weight suppression (WS), defined as the difference between one's highest and current weight. More recently, studies have suggested that WS also may play a role in symptom maintenance and weight gain during treatment in anorexia nervosa (AN) and that the influence of WS on AN outcomes may depend on an individual's body mass index (BMI). However, no study has investigated whether WS or the interaction between WS and BMI is associated with the longer-term course of eating pathology following treatment discharge in patients with AN. The current study examined a sample of females with AN (N = 180) who completed interviews and self-report questionnaires at discharge from intensive treatment and at 3, 6, and 12-months after discharge. Latent growth curve models tested whether WS, BMI, or the WS by BMI interaction significantly predicted the trajectory of eating disorder symptoms (i.e., Eating Disorder Examination global score, BMI, frequency of loss of control eating, frequency of purging) over the year following discharge. WS at discharge predicted change in BMI, and the interaction between WS and BMI predicted growth in eating disorder severity and purging frequency over time. Neither WS nor its interaction with BMI predicted growth in loss of control eating frequency. Results provide further support for the clinical significance of WS in AN symptom maintenance, but suggest that the influence of WS likely depends on an individual's BMI as well as the outcome being measured. © 2016 Wiley Periodicals, Inc.(Int J Eat Disord 2016; 49:753-763). © 2016 Wiley Periodicals, Inc.

A laboratory medicine residency training program that includes clinical consultation and research.

PubMed

Spitzer, E D; Pierce, G F; McDonald, J M

1990-04-01

We describe a laboratory medicine residency training program that includes ongoing interaction with both clinical laboratories and clinical services as well as significant research experience. Laboratory medicine residents serve as on-call consultants in the interpretation of test results, design of testing strategies, and assurance of test quality. The consultative on-call beeper system was evaluated and is presented as an effective method of clinical pathology training that is well accepted by the clinical staff. The research component of the residency program is also described. Together, these components provide training in real-time clinical problem solving and prepare residents for the changing technological environment of the clinical laboratory. At the completion of the residency, the majority of the residents are qualified laboratory subspecialists and are also capable of running an independent research program.

Developmental disabilities: improving competence in care using virtual patients.

PubMed

Sanders, Carla L; Kleinert, Harold L; Free, Teresa; King, Pam; Slusher, Ida; Boyd, Sara

2008-02-01

Nurse practitioners (NPs) have an increasingly important role in health care provision in the United States. However, most nurses report that they receive little or no clinical training in the area of developmental disabilities. A core development team consisting of NP faculty members from three universities, one physician assistant faculty member, the parents of children with developmental disabilities, and educational specialists developed two multimedia interactive pediatric instructional modules in CD-ROM format: one involving a child with Down syndrome and the other, an infant born at 26 weeks gestation. Participants were required to make decisions about proper clinical interaction throughout the cases. The modules on CD were piloted with NP students at three universities. Effectiveness study results demonstrated significant gains in both knowledge and comfort level regarding the care of patients with developmental disabilities.

Does Brain Reserve Protect Older Women from Vascular Depression?

PubMed Central

2014-01-01

Objectives. Brain reserve theory, typically discussed in relation to dementia, was examined with regard to late-life depression symptomatology and cerebrovascular burden (CVB) in older-old women. Method. It was predicted that in a 6-year longitudinal sample (Health and Retirement Study) of 1,355 stroke-free women aged 80 years and older, higher levels of depressive symptomatology (8-item Center for Epidemiologic Studies-Depression score) would be predicted by high CVB, less educational attainment, and the education × CVB interaction after controlling for age and cognitive functioning (Telephone Interview for Cognitive Status). A latent growth curve model was used to identify differences in depression symptomatology at baseline and over time. Logistic regression analyses were used to predict clinically significant depressive symptomatology at each wave based on CVB, education, and the education × CVB interaction. Results. Results indicate that among older women, greater educational attainment predicted fewer depression symptoms at baseline, but this advantage was partially eroded over time. The education × CVB interaction predicted clinically significant depressive symptoms at baseline when the benefits of education were most robust. Discussion. Brain reserve, characterized by educational attainment, may counterbalance the effect of high CVB with respect to depressive symptoms, thereby preserving mood in late life. These findings support the application of brain reserve theory to late-life depression. PMID:23448867

DNase I enzyme-aided fluorescence signal amplification based on graphene oxide-DNA aptamer interactions for colorectal cancer exosome detection.

PubMed

Wang, Hui; Chen, Hui; Huang, Zhipeng; Li, Tengda; Deng, Anmei; Kong, Jilie

2018-07-01

Exosomes have proved to be an effective cancer biomarker with significant potential, and several cell-specific molecules have been found in colorectal cancer (CRC) exosomes. Nevertheless, it is challenging to use exosomes in clinical lab diagnostics due to their nanoscale and the lack of a convenient and effective detection platform. Here, we developed a DNase I enzyme-aided fluorescence amplification method for CRC exosome detection, based on graphene oxide (GO)-DNA aptamer (CD63 and EpCAM aptamers) interactions. The fluorescence of fluorophore-labeled aptamers quenched by GO, recovered after incubation with samples containing CRC exosomes. The DNase I enzyme digested the single-stranded DNA aptamers on the exosome surface and the exosomes were able to interact with more fluorescent aptamer probes, resulting in an increase of signal amplification. The limit of detection for CRC exosomes is 2.1 × 10 4 particles/μl. Consequently, a rapid and effective method with high sensitivity was established. The method was verified in 19 clinical blood serum samples to distinguish healthy and CRC patients, showing significant diagnostic power. Moreover, it can be expanded to other kinds of cancer exosomes, in addition to CRC. Copyright © 2018 Elsevier B.V. All rights reserved.

Effects of external electrical and magnetic fields on pacemakers and defibrillators: from engineering principles to clinical practice.

PubMed

Beinart, Roy; Nazarian, Saman

2013-12-24

The overall risk of clinically significant adverse events related to EMI in recipients of CIEDs is very low. Therefore, no special precautions are needed when household appliances are used. Environmental and industrial sources of EMI are relatively safe when the exposure time is limited and distance from the CIEDs is maximized. The risk of EMI-induced events is highest within the hospital environment. Physician awareness of the possible interactions and methods to minimize them is warranted.

Hot flushes, coronary heart disease, and hormone therapy in postmenopausal women

PubMed Central

Huang, Alison J.; Sawaya, George F.; Vittinghoff, Eric; Lin, Feng; Grady, Deborah

2010-01-01

Objective The aim of this study was to examine interactions between hot flushes, estrogen plus progestogen therapy (EPT), and coronary heart disease (CHD) events in postmenopausal women with CHD. Methods We analyzed data from the Heart and Estrogen/Progestin Replacement Study, a randomized, placebo-controlled trial of 0.625 mg conjugated equine estrogens plus 2.5 mg medroxyprogesterone acetate in 2,763 postmenopausal women with CHD. Hot flushes were assessed at baseline using self-administered questionnaires; women reporting bothersome hot flushes “some” to ”all” of the time were considered to have clinically significant flushing. Cox regression models were used to examine the effect of EPT on risk of CHD events among women with and without significant flushing at baseline. Results The mean age of participants was 66.7 ± 6.8 years, and 89% (n = 2,448) were white. Sixteen percent (n = 434) of participants reported clinically significant hot flushes at baseline. Among women with baseline flushing, EPT increased risk of CHD events nine-fold in the first year compared with placebo (hazard ratio = 9.01; 95% CI, 1.15-70.35); among women without baseline flushing, treatment did not significantly affect CHD event risk in the first year (hazard ratio = 1.32; 95% CI, 0.86-2.03; P = 0.07 for interaction of hot flushes with treatment). The trend toward differential effects of EPT on risk for CHD among women with and without baseline flushing did not persist after the first year of treatment. Conclusions Among older postmenopausal women with CHD, EPT may increase risk of CHD events substantially in the first year of treatment among women with clinically significant hot flushes but not among those without hot flushes. PMID:19325499

Senior physiotherapy students as standardised patients for junior students enhances self-efficacy and satisfaction in both junior and senior students.

PubMed

Mandrusiak, Allison M; Isles, Rosemary; Chang, Angela T; Choy, Nancy L Low; Toppenberg, Rowena; McCook, Donna; Smith, Michelle D; O'Leary, Karina; Brauer, Sandra G

2014-05-23

Standardised patients are used in medical education to expose students to clinical contexts and facilitate transition to clinical practice, and this approach is gaining momentum in physiotherapy programs. Expense and availability of trained standardised patients are factors limiting widespread adoption, and accessing clinical visits with real patients can be challenging. This study addressed these issues by engaging senior students as standardised patients for junior students. It evaluated how this approach impacted self-reported constructs of both the junior and senior students. Learning activities for undergraduate physiotherapy students were developed in five courses (Neurology, Cardiorespiratory and three Musculoskeletal courses) so that junior students (Year 2 and 3) could develop skills and confidence in patient interview, physical examination and patient management through their interaction with standardised patients played by senior students (Year 4). Surveys were administered before and after the interactions to record junior students' self-reported confidence, communication, preparedness for clinic, and insight into their abilities; and senior students' confidence and insight into what it is like to be a patient. Satisfaction regarding this learning approach was surveyed in both the junior and senior students. A total of 253 students completed the surveys (mean 92.5% response rate). Across all courses, junior students reported a significant (all P < 0.037) improvement following the standardised patient interaction in their: preparedness for clinic, communication with clients, confidence with practical skills, and understanding of their strengths and weaknesses in relation to the learning activities. Senior students demonstrated a significant improvement in their confidence in providing feedback and insight into their own learning (P < 0.001). All students reported high satisfaction with this learning experience (mean score 8.5/10). This new approach to peer-assisted learning using senior students as standardised patients resulted in positive experiences for both junior and senior students across a variety of physiotherapy areas, activities, and stages within a physiotherapy program. These findings support the engagement of senior students as standardised patients to enhance learning within physiotherapy programs, and may have application across other disciplines to address challenges associated with accessing real patients via clinical visits or utilising actors as standardised patients.

Validation of SURE, a four-item clinical checklist for detecting decisional conflict in patients.

PubMed

Ferron Parayre, Audrey; Labrecque, Michel; Rousseau, Michel; Turcotte, Stéphane; Légaré, France

2014-01-01

We sought to determine the psychometric properties of SURE, a 4-item checklist designed to screen for clinically significant decisional conflict in clinical practice. This study was a secondary analysis of a clustered randomized trial assessing the effect of DECISION+2, a 2-hour online tutorial followed by a 2-hour interactive workshop on shared decision making, on decisions to use antibiotics for acute respiratory infections. Patients completed SURE and also the Decisional Conflict Scale (DCS), as the gold standard, after consultation. We evaluated internal consistency of SURE using the Kuder-Richardson 20 coefficient (KR-20). We compared DCS and SURE scores using the Spearman correlation coefficient. We assessed sensitivity and specificity of SURE scores (cut-off score ≤3 out of 4) by identifying patients with and without clinically significant decisional conflict (DCS score >37.5 on a scale of 0-100). Of the 712 patients recruited during the trial, 654 completed both tools. SURE scores showed adequate internal consistency (KR-20 coefficient of 0.7). There was a significant correlation between DCS and SURE scores (Spearman's ρ = -0.45, P < 0.0001). The prevalence of clinically significant decisional conflict as estimated by the DCS was 5.2% (95% CI 3.7-7.3). Sensitivity and specificity of SURE ≤3 were 94.1% (95% CI 78.9-99.0) and 89.8% (95% CI 87.1-92.0), respectively. SURE shows adequate psychometric properties in a primary care population with a low prevalence of clinically significant decisional conflict. SURE has the potential to be a useful screening tool for practitioners, responding to the growing need for detecting clinically significant decisional conflict in patients.

Using video-annotation software to identify interactions in group therapies for schizophrenia: assessing reliability and associations with outcomes.

PubMed

Orfanos, Stavros; Akther, Syeda Ferhana; Abdul-Basit, Muhammad; McCabe, Rosemarie; Priebe, Stefan

2017-02-10

Research has shown that interactions in group therapies for people with schizophrenia are associated with a reduction in negative symptoms. However, it is unclear which specific interactions in groups are linked with these improvements. The aims of this exploratory study were to i) develop and test the reliability of using video-annotation software to measure interactions in group therapies in schizophrenia and ii) explore the relationship between interactions in group therapies for schizophrenia with clinically relevant changes in negative symptoms. Video-annotation software was used to annotate interactions from participants selected across nine video-recorded out-patient therapy groups (N = 81). Using the Individual Group Member Interpersonal Process Scale, interactions were coded from participants who demonstrated either a clinically significant improvement (N = 9) or no change (N = 8) in negative symptoms at the end of therapy. Interactions were measured from the first and last sessions of attendance (>25 h of therapy). Inter-rater reliability between two independent raters was measured. Binary logistic regression analysis was used to explore the association between the frequency of interactive behaviors and changes in negative symptoms, assessed using the Positive and Negative Syndrome Scale. Of the 1275 statements that were annotated using ELAN, 1191 (93%) had sufficient audio and visual quality to be coded using the Individual Group Member Interpersonal Process Scale. Rater-agreement was high across all interaction categories (>95% average agreement). A higher frequency of self-initiated statements measured in the first session was associated with improvements in negative symptoms. The frequency of questions and giving advice measured in the first session of attendance was associated with improvements in negative symptoms; although this was only a trend. Video-annotation software can be used to reliably identify interactive behaviors in groups for schizophrenia. The results suggest that proactive communicative gestures, as assessed by the video-analysis, predict outcomes. Future research should use this novel method in larger and clinically different samples to explore which aspects of therapy facilitate such proactive communication early on in therapy.

Blockade of neuronal dopamine D2 receptor attenuates morphine tolerance in mice spinal cord.

PubMed

Dai, Wen-Ling; Xiong, Feng; Yan, Bing; Cao, Zheng-Yu; Liu, Wen-Tao; Liu, Ji-Hua; Yu, Bo-Yang

2016-12-22

Tolerance induced by morphine remains a major unresolved problem and significantly limits its clinical use. Recent evidences have indicated that dopamine D2 receptor (D2DR) is likely to be involved in morphine-induced antinociceptive tolerance. However, its exact effect and molecular mechanism remain unknown. In this study we examined the effect of D2DR on morphine antinociceptive tolerance in mice spinal cord. Chronic morphine treatment significantly increased levels of D2DR in mice spinal dorsal horn. And the immunoreactivity of D2DR was newly expressed in neurons rather than astrocytes or microglia both in vivo and in vitro. Blockade of D2DR with its antagonist (sulpiride and L-741,626, i.t.) attenuated morphine antinociceptive tolerance without affecting basal pain perception. Sulpiride (i.t.) also down-regulated the expression of phosphorylation of NR1, PKC, MAPKs and suppressed the activation of astrocytes and microglia induced by chronic morphine administration. Particularly, D2DR was found to interact with μ opioid receptor (MOR) in neurons, and chronic morphine treatment enhanced the MOR/D2DR interactions. Sulpiride (i.t.) could disrupt the MOR/D2DR interactions and attenuate morphine tolerance, indicating that neuronal D2DR in the spinal cord may be involved in morphine tolerance possibly by interacting with MOR. These results may present new opportunities for the treatment and management of morphine-induced antinociceptive tolerance which often observed in clinic.

Pharmacokinetic interactions and safety evaluations of coadministered tafenoquine and chloroquine in healthy subjects.

PubMed

Miller, Ann K; Harrell, Emma; Ye, Li; Baptiste-Brown, Sharon; Kleim, Jőrg-Peter; Ohrt, Colin; Duparc, Stephan; Möhrle, Jörg J; Webster, Alison; Stinnett, Sandra; Hughes, Arlene; Griffith, Sandy; Beelen, Andrew P

2013-12-01

The long-acting 8-aminoquinoline tafenoquine (TQ) coadministered with chloroquine (CQ) may radically cure Plasmodium vivax malaria. Coadministration therapy was evaluated for a pharmacokinetic interaction and for pharmacodynamic, safety and tolerability characteristics. Healthy subjects, 18-55 years old, without documented glucose-6-phosphate dehydrogenase deficiency, received CQ alone (days 1-2, 600 mg; and day 3, 300 mg), TQ alone (days 2 and 3, 450 mg) or coadministration therapy (day 1, CQ 600 mg; day 2, CQ 600 mg + TQ 450 mg; and day 3, CQ 300 mg + TQ 450 mg) in a randomized, double-blind, parallel-group study. Blood samples for pharmacokinetic and pharmacodynamic analyses and safety data, including electrocardiograms, were collected for 56 days. The coadministration of CQ + TQ had no effect on TQ AUC0-t , AUC0-∞ , Tmax or t1/2 . The 90% confidence intervals of CQ + TQ vs. TQ for AUC0-t , AUC0-∞ and t1/2 indicated no drug interaction. On day 2 of CQ + TQ coadministration, TQ Cmax and AUC0-24 increased by 38% (90% confidence interval 1.27, 1.64) and 24% (90% confidence interval 1.04, 1.46), respectively. The pharmacokinetics of CQ and its primary metabolite desethylchloroquine were not affected by TQ. Coadministration had no clinically significant effect on QT intervals and was well tolerated. No clinically significant safety or pharmacokinetic/pharmacodynamic interactions were observed with coadministered CQ and TQ in healthy subjects. © 2013 The British Pharmacological Society.

An Overview of the Evidence and Mechanisms of Herb–Drug Interactions

PubMed Central

Fasinu, Pius S.; Bouic, Patrick J.; Rosenkranz, Bernd

2012-01-01

Despite the lack of sufficient information on the safety of herbal products, their use as alternative and/or complementary medicine is globally popular. There is also an increasing interest in medicinal herbs as precursor for pharmacological actives. Of serious concern is the concurrent consumption of herbal products and conventional drugs. Herb–drug interaction (HDI) is the single most important clinical consequence of this practice. Using a structured assessment procedure, the evidence of HDI presents with varying degree of clinical significance. While the potential for HDI for a number of herbal products is inferred from non-human studies, certain HDIs are well established through human studies and documented case reports. Various mechanisms of pharmacokinetic HDI have been identified and include the alteration in the gastrointestinal functions with consequent effects on drug absorption; induction and inhibition of metabolic enzymes and transport proteins; and alteration of renal excretion of drugs and their metabolites. Due to the intrinsic pharmacologic properties of phytochemicals, pharmacodynamic HDIs are also known to occur. The effects could be synergistic, additive, and/or antagonistic. Poor reporting on the part of patients and the inability to promptly identify HDI by health providers are identified as major factors limiting the extensive compilation of clinically relevant HDIs. A general overview and the significance of pharmacokinetic and pharmacodynamic HDI are provided, detailing basic mechanism, and nature of evidence available. An increased level of awareness of HDI is necessary among health professionals and drug discovery scientists. With the increasing number of plant-sourced pharmacological actives, the potential for HDI should always be assessed in the non-clinical safety assessment phase of drug development process. More clinically relevant research is also required in this area as current information on HDI is insufficient for clinical applications. PMID:22557968

Static and Dynamic Cognitive Reserve Proxy Measures: Interactions with Alzheimer’s Disease Neuropathology and Cognition

PubMed Central

Malek-Ahmadi, Michael; Lu, Sophie; Chan, YanYan; Perez, Sylvia E; Chen, Kewei; Mufson, Elliott J

2018-01-01

Objective Years of education are the most common proxy for measuring cognitive reserve (CR) when assessing the relationship between Alzheimer’s disease (AD) neuropathology and cognition. However, years of education may be limited as a CR proxy given that it represents a specific timeframe in early life and is static. Studies suggest that measures of intellectual function provide a dynamic estimate of CR that is superior to years of education since it captures the effect of continued learning over time. The present study determined whether dynamic measures of CR were better predictors of episodic memory and executive function in the presence of AD pathology than a static measure of CR. Methods Subjects examined died with a pre-mortem clinical diagnosis of no cognitive impaired, mild cognitive impairment and mild to moderate AD. CERAD and Braak stage were used to stratify the sample by AD pathology severity. Linear regression analyses using CR by CERAD and CR by Braak stage interaction terms were used to determine whether Extended Range Vocabulary Test (ERVT) scores or years of education were significantly associated with episodic memory composite (EMC) and executive function composite (EFC) performance. All models were adjusted for clinical diagnosis, age at death, gender, APOE e4 carrier status and Braak stage. Results For episodic memory, years of education by CERAD interaction were not statistically significant (β=-0.01, SE=0.01, p=0.53). By contrast, ERVT interaction with CERAD diagnosis was statistically significant (β=-0.03, SE=0.01, p=0.004). Among the models using Braak stages, none of the CR by pathology interactions were associated with EMC or EFC. Conclusion Results suggest that a dynamic rather than a static measure is a better indicator of CR and that the relationship between CR and cognition is dependent upon the severity of select AD criteria. PMID:29423338

Clinical Drug-Drug Pharmacokinetic Interaction Potential of Sucralfate with Other Drugs: Review and Perspectives.

PubMed

Sulochana, Suresh P; Syed, Muzeeb; Chandrasekar, Devaraj V; Mullangi, Ramesh; Srinivas, Nuggehally R

2016-10-01

Sucralfate, a complex of aluminium hydroxide with sulfated sucrose, forms a strong gastrointestinal tract (GIT) mucosal barrier with excellent anti-ulcer property. Because sucralfate does not undergo any significant oral absorption, sucralfate resides in the GIT for a considerable length of time. The unabsorbed sucralfate may alter the pharmacokinetics of the oral drugs by impeding its absorption and reducing the oral bioavailability. Because of the increased use of sucralfate, it was important to provide a reappraisal of the published clinical drug-drug interaction studies of sucralfate with scores of drugs. This review covers several category of drugs such as non-steroidal anti-inflammatory drugs, fluoroquinolones, histamine H2-receptor blockers, macrolides, anti-fungals, anti-diabetics, salicylic acid derivatives, steroidal anti-inflammatory drugs and provides pharmacokinetic data summary along with study design, objectives and key remarks. While the loss of oral bioavailability was significant for the fluoroquinolone class, it generally varied for other classes of drugs, suggesting that impact of the co-administration of sucralfate is manageable in clinical situations. Given the technology advancement in formulation development, it may be in order feasible to develop appropriate formulation strategies to either avoid or minimize the absorption-related issues when co-administered with sucralfate. It is recommended that consideration of both in vitro and preclinical studies may be in order to gauge the level of interaction of a drug with sucralfate. Such data may aid in the development of appropriate strategies to navigate the co-administration of sucralfate with other drugs in this age of polypharmacy.

Emergent processes in cognitive-emotional interactions

PubMed Central

Pessoa, Luiz

2010-01-01

Emotion and cognition have been viewed as largely separate entities in the brain. Within this framework, significant progress has been made in understanding specific aspects of behavior. Research in the past two decades, however, has started to paint a different picture of brain organization, one in which network interactions are key to understanding complex behaviors. From both basic and clinical perspectives, the characterization of cognitive-emotional interactions constitutes a fundamental issue in the investigation of the mind and brain. This review will highlight the interactive and integrative potential that exists in the brain to bring together the cognitive and emotional domains. First, anatomical evidence will be provided, focusing on structures such as hypothalamus, basal forebrain, amygdala, cingulate cortex, orbitofrontal cortex, and insula. Data on functional interactions will then be discussed, followed by a discussion of a dual competition framework, which describes cognitive-emotional interactions in terms of perceptual and cognitive competition mechanisms. PMID:21319489

Manual therapy in osteoarthritis of the hip: outcome in subgroups of patients.

PubMed

Hoeksma, H L; Dekker, J; Ronday, H K; Breedveld, F C; Van den Ende, C H M

2005-04-01

To investigate whether manual therapy has particular benefit in subgroups of patients defined on the basis of hip function, range of joint motion, pain and radiological deterioration. The study was performed in the out-patient clinic of physical therapy of a large hospital. Data on 109 patients with OA of the hip (clinical ACR criteria) participating in a randomized clinical trial on the effects of manual therapy were used. The outcomes for hip function (Harris hip score), range of joint motion (ROM) and pain (VAS) were compared for specific subgroups. Subgroups were assigned by the median split method. The interaction effect between subgroup and treatment was tested using multiple regression analysis. No differences were observed in the effect of manual therapy in specific subgroups of patients defined on the basis of baseline levels of hip function, pain and ROM. On the basis of radiological grading of osteoarthritis (OA), we found that patients with severe radiological grading of OA had significantly worse outcome on ROM as a result of manual therapy than patients with mild or moderate radiological grading of OA. A significant interaction effect was found for only 1 out of 12 hypotheses investigated. Therefore, we conclude that there is no evidence for the particular benefit of manual therapy in subgroups of patients.

Infant attachment security and early childhood behavioral inhibition interact to predict adolescent social anxiety symptoms.

PubMed

Lewis-Morrarty, Erin; Degnan, Kathryn A; Chronis-Tuscano, Andrea; Pine, Daniel S; Henderson, Heather A; Fox, Nathan A

2015-01-01

Insecure attachment and behavioral inhibition (BI) increase risk for internalizing problems, but few longitudinal studies have examined their interaction in predicting adolescent anxiety. This study included 165 adolescents (ages 14-17 years) selected based on their reactivity to novelty at 4 months. Infant attachment was assessed with the Strange Situation. Multimethod BI assessments were conducted across childhood. Adolescents and their parents independently reported on anxiety. The interaction of attachment and BI significantly predicted adolescent anxiety symptoms, such that BI and anxiety were only associated among adolescents with histories of insecure attachment. Exploratory analyses revealed that this effect was driven by insecure-resistant attachment and that the association between BI and social anxiety was significant only for insecure males. Clinical implications are discussed. © 2014 The Authors. Child Development © 2014 Society for Research in Child Development, Inc.

Aortic dissection simulation models for clinical support: fluid-structure interaction vs. rigid wall models.

PubMed

Alimohammadi, Mona; Sherwood, Joseph M; Karimpour, Morad; Agu, Obiekezie; Balabani, Stavroula; Díaz-Zuccarini, Vanessa

2015-04-15

The management and prognosis of aortic dissection (AD) is often challenging and the use of personalised computational models is being explored as a tool to improve clinical outcome. Including vessel wall motion in such simulations can provide more realistic and potentially accurate results, but requires significant additional computational resources, as well as expertise. With clinical translation as the final aim, trade-offs between complexity, speed and accuracy are inevitable. The present study explores whether modelling wall motion is worth the additional expense in the case of AD, by carrying out fluid-structure interaction (FSI) simulations based on a sample patient case. Patient-specific anatomical details were extracted from computed tomography images to provide the fluid domain, from which the vessel wall was extrapolated. Two-way fluid-structure interaction simulations were performed, with coupled Windkessel boundary conditions and hyperelastic wall properties. The blood was modelled using the Carreau-Yasuda viscosity model and turbulence was accounted for via a shear stress transport model. A simulation without wall motion (rigid wall) was carried out for comparison purposes. The displacement of the vessel wall was comparable to reports from imaging studies in terms of intimal flap motion and contraction of the true lumen. Analysis of the haemodynamics around the proximal and distal false lumen in the FSI model showed complex flow structures caused by the expansion and contraction of the vessel wall. These flow patterns led to significantly different predictions of wall shear stress, particularly its oscillatory component, which were not captured by the rigid wall model. Through comparison with imaging data, the results of the present study indicate that the fluid-structure interaction methodology employed herein is appropriate for simulations of aortic dissection. Regions of high wall shear stress were not significantly altered by the wall motion, however, certain collocated regions of low and oscillatory wall shear stress which may be critical for disease progression were only identified in the FSI simulation. We conclude that, if patient-tailored simulations of aortic dissection are to be used as an interventional planning tool, then the additional complexity, expertise and computational expense required to model wall motion is indeed justified.

Increasing Reasoning Awareness: Video Analysis of Students' Two-Party Virtual Patient Interactions.

PubMed

Edelbring, Samuel; Parodis, Ioannis; Lundberg, Ingrid E

2018-02-27

Collaborative reasoning occurs in clinical practice but is rarely developed during education. The computerized virtual patient (VP) cases allow for a stepwise exploration of cases and thus stimulate active learning. Peer settings during VP sessions are believed to have benefits in terms of reasoning but have received scant attention in the literature. The objective of this study was to thoroughly investigate interactions during medical students' clinical reasoning in two-party VP settings. An in-depth exploration of students' interactions in dyad settings of VP sessions was performed. For this purpose, two prerecorded VP sessions lasting 1 hour each were observed, transcribed in full, and analyzed. The transcriptions were analyzed using thematic analysis, and short clips from the videos were selected for subsequent analysis in relation to clinical reasoning and clinical aspects. Four categories of interactions were identified: (1) task-related dialogue, in which students negotiated a shared understanding of the task and strategies for information gathering; (2) case-related insights and perspectives were gained, and the students consolidated and applied preexisting biomedical knowledge into a clinical setting; (3) clinical reasoning interactions were made explicit. In these, hypotheses were followed up and clinical examples were used. The researchers observed interactions not only between students and the VP but also (4) interactions with other resources, such as textbooks. The interactions are discussed in relation to theories of clinical reasoning and peer learning. The dyad VP setting is conducive to activities that promote analytic clinical reasoning. In this setting, components such as peer interaction, access to different resources, and reduced time constraints provided a productive situation in which the students pursued different lines of reasoning. ©Samuel Edelbring, Ioannis Parodis, Ingrid E Lundberg. Originally published in JMIR Medical Education (http://mededu.jmir.org), 27.02.2018.

Increasing Reasoning Awareness: Video Analysis of Students’ Two-Party Virtual Patient Interactions

PubMed Central

Parodis, Ioannis; Lundberg, Ingrid E

2018-01-01

Background Collaborative reasoning occurs in clinical practice but is rarely developed during education. The computerized virtual patient (VP) cases allow for a stepwise exploration of cases and thus stimulate active learning. Peer settings during VP sessions are believed to have benefits in terms of reasoning but have received scant attention in the literature. Objective The objective of this study was to thoroughly investigate interactions during medical students’ clinical reasoning in two-party VP settings. Methods An in-depth exploration of students’ interactions in dyad settings of VP sessions was performed. For this purpose, two prerecorded VP sessions lasting 1 hour each were observed, transcribed in full, and analyzed. The transcriptions were analyzed using thematic analysis, and short clips from the videos were selected for subsequent analysis in relation to clinical reasoning and clinical aspects. Results Four categories of interactions were identified: (1) task-related dialogue, in which students negotiated a shared understanding of the task and strategies for information gathering; (2) case-related insights and perspectives were gained, and the students consolidated and applied preexisting biomedical knowledge into a clinical setting; (3) clinical reasoning interactions were made explicit. In these, hypotheses were followed up and clinical examples were used. The researchers observed interactions not only between students and the VP but also (4) interactions with other resources, such as textbooks. The interactions are discussed in relation to theories of clinical reasoning and peer learning. Conclusions The dyad VP setting is conducive to activities that promote analytic clinical reasoning. In this setting, components such as peer interaction, access to different resources, and reduced time constraints provided a productive situation in which the students pursued different lines of reasoning. PMID:29487043

Genetic Variants in the Bone Morphogenic Protein Gene Family Modify the Association between Residential Exposure to Traffic and Peripheral Arterial Disease

PubMed Central

Ward-Caviness, Cavin K.; Neas, Lucas M.; Blach, Colette; Haynes, Carol S.; LaRocque-Abramson, Karen; Grass, Elizabeth; Dowdy, Elaine; Devlin, Robert B.; Diaz-Sanchez, David; Cascio, Wayne E.; Lynn Miranda, Marie; Gregory, Simon G.; Shah, Svati H.; Kraus, William E.; Hauser, Elizabeth R.

2016-01-01

There is a growing literature indicating that genetic variants modify many of the associations between environmental exposures and clinical outcomes, potentially by increasing susceptibility to these exposures. However, genome-scale investigations of these interactions have been rarely performed particularly in the case of air pollution exposures. We performed race-stratified genome-wide gene-environment interaction association studies on European-American (EA, N = 1623) and African-American (AA, N = 554) cohorts to investigate the joint influence of common single nucleotide polymorphisms (SNPs) and residential exposure to traffic (“traffic exposure”)—a recognized vascular disease risk factor—on peripheral arterial disease (PAD). Traffic exposure was estimated via the distance from the primary residence to the nearest major roadway, defined as the nearest limited access highways or major arterial. The rs755249-traffic exposure interaction was associated with PAD at a genome-wide significant level (P = 2.29x10-8) in European-Americans. Rs755249 is located in the 3’ untranslated region of BMP8A, a member of the bone morphogenic protein (BMP) gene family. Further investigation revealed several variants in BMP genes associated with PAD via an interaction with traffic exposure in both the EA and AA cohorts; this included interactions with non-synonymous variants in BMP2, which is regulated by air pollution exposure. The BMP family of genes is linked to vascular growth and calcification and is a novel gene family for the study of PAD pathophysiology. Further investigation of BMP8A using the Genotype Tissue Expression Database revealed multiple variants with nominally significant (P < 0.05) interaction P-values in our EA cohort were significant BMP8A eQTLs in tissue types highlight relevant for PAD such as rs755249 (tibial nerve, eQTL P = 3.6x10-6) and rs1180341 (tibial artery, eQTL P = 5.3x10-6). Together these results reveal a novel gene, and possibly gene family, associated with PAD via an interaction with traffic air pollution exposure. These results also highlight the potential for interactions studies, particularly at the genome scale, to reveal novel biology linking environmental exposures to clinical outcomes. PMID:27082954

Co-morbidity and clinically significant interactions between antiepileptic drugs and other drugs in elderly patients with newly diagnosed epilepsy.

PubMed

Bruun, Emmi; Virta, Lauri J; Kälviäinen, Reetta; Keränen, Tapani

2017-08-01

A study was conducted to investigate the frequency of potential pharmacokinetic drug-to-drug interactions in elderly patients with newly diagnosed epilepsy. We also investigated co-morbid conditions associated with epilepsy. From the register of Kuopio University Hospital (KUH) we identified community-dwelling patients aged 65 or above with newly diagnosed epilepsy and in whom use of the first individual antiepileptic drug (AED) began in 2000-2013 (n=529). Furthermore, register data of the Social Insurance Institution of Finland were used for assessing potential interactions in a nationwide cohort of elderly subjects with newly diagnosed epilepsy. We extracted all patients aged 65 or above who had received special reimbursement for the cost of AEDs prescribed on account of epilepsy in 2012 where their first AED was recorded in 2011-2012 as monotherapy (n=1081). Clinically relevant drug interactions (of class C or D) at the time of starting of the first AED, as assessed via the SFINX-PHARAO database, were analysed. Hypertension (67%), dyslipidemia (45%), and ischaemic stroke (32%) were the most common co-morbid conditions in the hospital cohort of patients. In these patients, excessive polypharmacy (more than 10 concomitant drugs) was identified in 27% of cases. Of the patients started on carbamazepine, 52 subjects (32%) had one class-C or class-D drug interaction and 51 (31%) had two or more C- or D-class interactions. Only 2% of the subjects started on valproate exhibited a class-C interaction. None of the subjects using oxcarbazepine displayed class-C or class-D interactions. Patients with 3-5 (OR 4.22; p=0.05) or over six (OR 8.86; p=0.003) other drugs were more likely to have C- or D-class interaction. The most common drugs with potential interactions with carbamazepine were dihydropyridine calcium-blockers, statins, warfarin, and psychotropic drugs. Elderly patients with newly diagnosed epilepsy are at high risk of clinically relevant pharmacokinetic interactions with other drugs, especially if exposed to carbamazepine, but these interactions can be controlled via rational drug choices and with prediction of the possible drug-to-drug interactions. Patients on dihydropyridine calcium-channel blockers, statins, warfarin, and risperidone face the highest risk of interactions. Copyright © 2017 Elsevier Inc. All rights reserved.

Working together: Using a unique approach to evaluate an interactive and clinic-based longitudinal interprofessional education experience with 13 professions.

PubMed

Thompson, Britta M; Bratzler, Dale W; Fisher, Mark J; Torres, Amie; Faculty, Epic; Sparks, Rhonda A

2016-11-01

Interprofessional education (IPE) involving an interactive and longitudinal clinic experience at an inner-city charitable clinic from September to May 2013/2014 was evaluated. Pre-, mid-, and post-intervention data were collected from students in 13 different professions including medicine (medical and physician assistant), dentistry (dental and dental hygiene), nursing (undergraduate and clinical nurse specialist), public health, pharmacy, physical therapy, occupational therapy, nutritional sciences, speech and language pathology, and social work. To evaluate their interprofessional attitudes, students completed the TeamSTEPPS Teamwork Attitudes Questionnaire (T-TAQ) and Readiness for Interprofessional Learning Scale (RIPLS). They also completed a unique measure, healthcare professionals circles diagrams (HPCDs), that indicated student conceptualisation of a healthcare team caring for a complex patient, along with perception of their team's progress towards meeting patient goals. Results from the T-TAQ and RIPLS scores indicated small but significant increases from pre- to post-intervention (p = 0.005 and 0.012, respectively). Analysis of the HPCDs revealed significant increases in students' perceptions of the types of interprofessional team members, relationships, and communication between professions to provide medical care to patients (p < 0.01). Most HPCDs included pharmacists, nurses, and physicians as part of the care team at all time points. Students significantly increased their inclusion of dentistry, public health, social work, and physician assistants as members of the healthcare team from pre- to post-intervention. Implications of our data indicated the importance of IPE interventions that include not only classroom-based sessions, but actual patient care experiences within interprofessional teams. It also reinforced the importance of new and unique methods to assess IPE.

Molecular interactions between general anesthetics and the 5HT2B receptor.

PubMed

Matsunaga, Felipe; Gao, Lu; Huang, Xi-Ping; Saven, Jeffery G; Roth, Bryan L; Liu, Renyu

2015-01-01

Serotonin modulates many processes through a family of seven serotonin receptors. However, no studies have screened for interactions between general anesthetics currently in clinical use and serotonergic G-protein-coupled receptors (GPCRs). Given that both intravenous and inhalational anesthetics have been shown to target other classes of GPCRs, we hypothesized that general anesthetics might interact directly with some serotonin receptors and thus modify their function. Radioligand binding assays were performed to screen serotonin receptors for interactions with propofol and isoflurane as well as for affinity determinations. Docking calculations using the crystal structure of 5-HT2B were performed to computationally confirm the binding assay results and locate anesthetic binding sites. The 5-HT2B class of receptors interacted significantly with both propofol and isoflurane in the primary screen. The affinities for isoflurane and propofol were determined to be 7.78 and .95 μM, respectively, which were at or below the clinical concentrations for both anesthetics. The estimated free energy derived from docking calculations for propofol (-6.70 kcal/mol) and isoflurane (-5.10 kcal/mol) correlated with affinities from the binding assay. The anesthetics were predicted to dock at a pharmacologically relevant binding site of 5HT2B. The molecular interactions between propofol and isoflurane with the 5-HT2B class of receptors were discovered and characterized. This finding implicates the serotonergic GPCRs as potential anesthetic targets.

The interaction between rejection sensitivity and emotional maltreatment in borderline personality disorder.

PubMed

Chesin, Megan; Fertuck, Eric; Goodman, Jeanne; Lichenstein, Sarah; Stanley, Barbara

2015-01-01

Borderline personality disorder (BPD) is a prevalent psychiatric disorder associated with significant distress, dysfunction, and treatment utilization. Though, theoretically, BPD is posited to arise from a combination of trait and environmental risk factors, few studies have tested trait-by-environment interactions in BPD. We investigated the roles of rejection sensitivity (RS) and childhood emotional neglect and abuse (ENA) as well as their interaction in BPD. Eighty-five adults with a lifetime mood disorder who were recruited for outpatient studies in a psychiatric clinic were assessed for ENA using the Childhood Trauma Questionnaire and for RS with the Adult Rejection Sensitivity Questionnaire. BPD diagnoses were made by consensus using data collected on the Structured Clinical Interview for DSM-IV. Hierarchical logistic regression was used to test associations between RS, ENA, their interaction and BPD. RS and ENA interacted to predict co-occurring BPD in our sample of mood-disordered patients, with the strength of the relationship between RS and BPD depending on the severity of ENA. In the context of little or no ENA, RS and BPD were more strongly related than when ENA was more severe. Our results extend previous findings suggesting RS and ENA are risk factors for BPD. They also provide preliminary support for contemporary theories of BPD positing trait-by-environment interactions in the development of BPD. Prospective studies are needed to confirm these findings. © 2014 S. Karger AG, Basel.

Updates on the Clinical Evidenced Herb-Warfarin Interactions

PubMed Central

Ge, Beikang; Zhang, Zhen; Zuo, Zhong

2014-01-01

Increasing and inadvertent use of herbs makes herb-drug interactions a focus of research. Concomitant use of warfarin, a highly efficacious oral anticoagulant, and herbs causes major safety concerns due to the narrow therapeutic window of warfarin. This paper presents an update overview of clinical findings regarding herb-warfarin interaction, highlighting clinical outcomes, severity of documented interactions, and quality of clinical evidence. Among thirty-eight herbs, Cannabis, Chamomile, Cranberry, Garlic, Ginkgo, Grapefruit, Lycium, Red clover, and St. John's wort were evaluated to have major severity interaction with warfarin. Herbs were also classified on account of the likelihood of their supporting evidences for interaction. Four herbs were considered as highly probable to interact with warfarin (level I), three were estimated as probable (level II), and ten and twenty-one were possible (level III) and doubtful (level IV), respectively. The general mechanism of herb-warfarin interaction almost remains unknown, yet several pharmacokinetic and pharmacodynamic factors were estimated to influence the effectiveness of warfarin. Based on limited literature and information reported, we identified corresponding mechanisms of interactions for a small amount of “interacting herbs.” In summary, herb-warfarin interaction, especially the clinical effects of herbs on warfarin therapy should be further investigated through multicenter studies with larger sample sizes. PMID:24790635

Role of regulatory agencies in translating pharmacogenetics to the clinics

PubMed Central

Prasad, Krishna

2009-01-01

Overall, the regulators (here the term is used in the broad sense including competent authorities, the national departments of health and the European commission) have a significant role in translating pharmacogenomics into clinical practice. The first objective is to establish the role of the genomic information that is available, and this should be data driven. Conduct of robust clinical trials that are sound both scientifically and from a regulatory perspective should be encouraged. Significant interaction between Academia, Pharma industry and the regulator is essential with the overall aim of improving public health. Conceptually, this would involve the triumvirate (Academia, industry and regulators) as an orchestra with the regulators perhaps taking the role of the conductor while the significant players would be those that generate data (Academia and industry). The regulators also need to ensure that clear guidance is available for use of the information and the tests with a significant level of uniformity between the ICH regions. The commercial availability of the test will have considerable impact on the use of pharmacogenomics, but this is currently beyond the scope of this paper. PMID:22461095

Past, Present, and Future Trends in Teaching Clinical Skills through Web-Based Learning Environments

ERIC Educational Resources Information Center

Coe Regan, Jo Ann R.; Youn, Eric J.

2008-01-01

Distance education in social work has grown significantly due to the use of interactive television and computer networks. Given the recent developments in delivering distance education utilizing Web-based technology, this article presents a literature review focused on identifying generational trends in the development of Web-based learning…

The protolobar structure of the human kidney: Its biologic and clinical significance

DOE Office of Scientific and Technical Information (OSTI.GOV)

Inke, G.

This book depicts the uniqueness of each kidney as a result of the interaction of the process of nephronogenesis with the random variability of vascular channels within the bounds of a limited space. The fields of anatomy, developmental biology, comparative morphology, embryology, nephrology, pathology, physiology, radiology, and urologic surgery are treated.

A Comparison of Therapeutic Factors in Two Group Treatment Modalities: Verbal and Art Therapy.

ERIC Educational Resources Information Center

Shechtman, Zipora; Perl-Dekel, Ofra

2000-01-01

Compares therapeutic factors in verbal and art group psychotherapy in a psychiatric day-treatment clinic in Israel. Results only partly support the differences between modalities, but do reveal significant differences between participants with only a few interactions between participants and modalities. All therapeutic factors appear in both…

[Interaction of mental health and forced married migrants in Germany].

PubMed

Kizilhan, Jan

2015-11-01

The study examines the interaction of the forced married migrants and the frequency of the psychological illness. Forced-married and not forced-married migrants are compared concerning her psychological illness in psychosomatic clinics in Germany. Forced-married women reported significantly more about psychological illness and have undertaken on average at least four times a suicide attempt. Forced-married women suffer lifelong from this event and need, with taking into account cultural migration-specific aspects, special support in the psychosocial consultation and medical-therapeutic treatment. © Georg Thieme Verlag KG Stuttgart · New York.

Clinical physiology grand rounds.

PubMed

Richards, Jeremy; Schwartzstein, Richard; Irish, Julie; Almeida, Jacqueline; Roberts, David

2013-04-01

Clinical Physiology Grand Rounds (CPGR) is an interactive, case-based conference for medical students designed to: (1) integrate preclinical and clinical learning; (2) promote inductive clinical reasoning; and (3) emphasise students as peer teachers. CPGR specifically encourages mixed learning level student interactions and emphasises the use of concept mapping. We describe the theoretical basis and logistical considerations for an interactive, integrative, mixed-learner environment such as CPGR. In addition, we report qualitative data regarding students' attitudes towards and perceptions of CPGR. Medical students from first to fourth year participate in a monthly, interactive conference. The CPGR was designed to bridge gaps and reinforce linkages between basic science and clinical concepts, and to incorporate interactive vertical integration between preclinical and clinical students. Medical education and content experts use Socratic, interactive teaching methods to develop real-time concept maps to emphasise the presence and importance of linkages across curricula. Student focus groups were held to assess attitudes towards and perceptions of the mixed-learner environment and concept maps in CPGR. Qualitative analyses of focus group transcripts were performed to develop themes and codes describing the students' impressions of CPGR. CPGR is a case-based, interactive conference designed to help students gain an increased appreciation of linkages between basic science and clinical medicine concepts, and an increased awareness of clinical reasoning thought processes. Success is dependent upon explicit attention being given to goals for students' integrated learning. © Blackwell Publishing Ltd 2013.

Attachment styles and clinical communication performance in trainee doctors.

PubMed

Fletcher, Ian; McCallum, Rachel; Peters, Sarah

2016-11-01

To investigate the relationship between trainee doctors' attachment style and their performance in qualifying clinical and communication skills assessments. Participants were 190 undergraduate medical students whose performance was assessed by examiners across two areas (communication and clinical skills) during their qualifying Objective Structured Clinical Examination (OSCE). Simulated patients also rated communication skills. Participants' attachment style was rated across two dimensions, avoidance and anxiety, using the Relationship Questionnaire (RQ). Lower levels of attachment avoidance and anxiety significantly predicted higher performance in both communication and clinical skills. Trainee doctors' attachment styles are associated with patient communication and clinical performance. Further research is needed to investigate the impact of attachment on consultations between doctors and patients within clinical settings. Attachment theory can inform our understanding why, for some student doctors, interacting with patients may be particularly challenging and require additional support by medical educators. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

Interaction between Helicobacter pylori infection, nonsteroidal anti-inflammatory drugs and/or low-dose aspirin use: Old question new insights

PubMed Central

Sostres, Carlos; Gargallo, Carla Jerusalen; Lanas, Angel

2014-01-01

Previous reports clearly demonstrated that Helicobacter pylori (H. pylori) infection, nonsteroidal anti-inflammatory drugs (NSAID) or low dose aspirin (ASA) use significantly and independently increased the risk for the development of peptic ulcer disease. Today, the presence of H. pylori infection associated with low dose ASA and/or NSAID use in the same patient is becoming more frequent and therefore the potential interaction between these factors and the consequences of it has important implications. Whether NSAID intake in the presence of H. pylori infection may further increase the risk of peptic ulcer carried by the presence of only one risk factor is still a matter of debate. Studies on the interaction between the two risk factors yielded conflicting data and no consensus has been reached in the last years. In addition, the interaction between H. pylori infection and low-dose ASA remains even more controversial. In real clinical practice, we can find different clinical scenarios involving these three factors associated with the presence of different gastrointestinal and cardiovascular risk factors. These huge variety of possible combinations greatly hinder the decision making process of physicians. PMID:25071338

Routine drug and food interactions during antihelminthic treatment of neurocysticercosis: a reason for the variable efficacy of albendazole and praziquantel?

PubMed

Romo, Matthew L; Carpio, Arturo; Kelvin, Elizabeth A

2014-04-01

Neurocysticercosis (NC) or infection of the central nervous system with Taenia solium larvae is a leading cause of preventable seizures and epilepsy in endemic regions across the globe. Albendazole and praziquantel are commonly used antihelminthic agents to treat NC; however, viable cysts persist in the majority of patients, putting them at risk for future seizures and other neurological complications. Because of their pharmacokinetic profiles, albendazole and praziquantel have the potential to interact with many different drugs. During antihelminthic treatment, antiepileptic drugs and corticosteroids are commonly co-administered to manage seizures and cerebral edema; however, the most commonly used agents from these drug classes are known to significantly alter plasma concentrations of albendazole and praziquantel. The overarching issue with drug interactions during the treatment of NC is whether or not they have clinical relevance, as the plasma concentrations of albendazole and praziquantel have not been directly linked with eradication of viable cysts. Future studies should attempt to evaluate the validity of a causal relationship between antihelminthic plasma concentrations and outcomes so that drug interactions can be better understood and managed and so that treatment can be optimized. © 2014, The American College of Clinical Pharmacology.

Molecular dynamics approach to probe PKCβII-ligand interactions and influence of crystal water molecules on these interactions.

PubMed

Grewal, Baljinder K; Bhat, Jyotsna; Sobhia, Masilamani Elizabeth

2015-01-01

PKCβII is a potential target for therapeutic intervention against pandemic diabetic complications. Present study probes the molecular interactions of PKCβII with its clinically important ligands, viz. ruboxistaurin, enzastaurin and co-crystallized ligand, 2-methyl-1H-indol-3-yl-BIM-1. The essentials of PKCβII-ligand interaction, crystal water-induced alterations in these interactions and key interacting flexible residues are analyzed. Computational methodologies, viz. molecular docking and molecular simulation coupled with molecular mechanics-Poisson-Boltzmann surface area and generalized born surface area (MM-PB[GB]SA) are employed. The structural changes in the presence and absence of crystal water molecules in PKCβII ATP binding site residues, and its interaction with bound ligand, are identified. Difference in interaction of selective and nonselective ligand with ATP binding site residues of PKCβII is reported. The study showed that the nonbonding interactions contribute significantly in PKCβII-ligand binding and presence of crystal water molecules affects the interactions. The findings of present work may integrate the new aspects in the drug design process of PKCβII inhibitors.

Non-obvious correlations to disease management unraveled by Bayesian artificial intelligence analyses of CMS data.

PubMed

Vemulapalli, Vijetha; Qu, Jiaqi; Garren, Jeonifer M; Rodrigues, Leonardo O; Kiebish, Michael A; Sarangarajan, Rangaprasad; Narain, Niven R; Akmaev, Viatcheslav R

2016-11-01

Given the availability of extensive digitized healthcare data from medical records, claims and prescription information, it is now possible to use hypothesis-free, data-driven approaches to mine medical databases for novel insight. The goal of this analysis was to demonstrate the use of artificial intelligence based methods such as Bayesian networks to open up opportunities for creation of new knowledge in management of chronic conditions. Hospital level Medicare claims data containing discharge numbers for most common diagnoses were analyzed in a hypothesis-free manner using Bayesian networks learning methodology. While many interactions identified between discharge rates of diagnoses using this data set are supported by current medical knowledge, a novel interaction linking asthma and renal failure was discovered. This interaction is non-obvious and had not been looked at by the research and clinical communities in epidemiological or clinical data. A plausible pharmacological explanation of this link is proposed together with a verification of the risk significance by conventional statistical analysis. Potential clinical and molecular pathways defining the relationship between commonly used asthma medications and renal disease are discussed. The study underscores the need for further epidemiological research to validate this novel hypothesis. Validation will lead to advancement in clinical treatment of asthma & bronchitis, thereby, improving patient outcomes and leading to long term cost savings. In summary, this study demonstrates that application of advanced artificial intelligence methods in healthcare has the potential to enhance the quality of care by discovering non-obvious, clinically relevant relationships and enabling timely care intervention. Copyright © 2016 The Authors. Published by Elsevier B.V. All rights reserved.

Social skills as a mediator between anxiety symptoms and peer interactions among children and adolescents.

PubMed

Motoca, Luci M; Williams, Sandra; Silverman, Wendy K

2012-01-01

The present study used a cross-sectional design to examine the relations among youth anxiety symptoms, positive and negative peer interactions, and social skills. Also examined was the mediating role of social skills in the relations between youth anxiety symptoms and positive and negative peer interactions. Youth sex and age were examined as moderators. The sample consisted of 397 children and adolescents (M = 10.11 years; 53.4% boys; 74.8% Hispanic Latino) referred to an anxiety disorders clinic. Anxiety symptoms, positive and negative peer interactions, and social skills were assessed using youth and parent ratings. Structural equation modeling results indicated that for youth ratings only, youth anxiety symptoms were negatively related to positive peer interactions controlling for primary social phobia and comorbid depressive disorders. For both youth and parent ratings, youth anxiety symptoms were positively related to negative peer interactions and negatively related to social skills. Also for both youth and parent ratings, social skills mediated the relations between youth anxiety symptoms and positive and negative peer interactions. For parent ratings only, the effects of youth anxiety symptoms and social skills on peer interactions were significantly moderated by youth age. Youth sex was not a significant moderator using youth and parent ratings. Findings suggest that difficulties with social skills and peer interactions are problematic features of youth referred for anxiety problems. Findings highlight the need to improve understanding of anxiety symptoms, social skills, and peer interactions in this population.

Social Skills as a Mediator between Anxiety Symptoms and Peer Interactions among Children and Adolescents

PubMed Central

Motoca, Luci M.; Williams, Sandra; Silverman, Wendy K.

2012-01-01

Objective The present study used a cross-sectional design to examine the relations among youth anxiety symptoms, positive and negative peer interactions, and social skills. Also examined was the mediating role of social skills in the relations between youth anxiety symptoms and positive and negative peer interactions. Youth sex and age were examined as moderators. Method The sample consisted of 397 children and adolescents (M = 10.11 years; 53.4% boys; 74.8% Hispanic Latino) referred to an anxiety disorders clinic. Anxiety symptoms, positive and negative peer interactions, and social skills were assessed using youth and parent ratings. Results Structural equation modeling results indicated that for youth ratings only, youth anxiety symptoms were negatively related to positive peer interactions controlling for primary social phobia and comorbid depressive disorders. For both youth and parent ratings, youth anxiety symptoms were positively related to negative peer interactions and negatively related to social skills. Also for both youth and parent ratings, social skills mediated the relations between youth anxiety symptoms and positive and negative peer interactions. For parent ratings only, the effects of youth anxiety symptoms and social skills on peer interactions were significantly moderated by youth age. Youth sex was not a significant moderator using youth and parent ratings. Conclusions Findings suggest difficulties with social skills and peer interactions are problematic features of youth referred for anxiety problems. Findings highlight the need to improve understanding of anxiety symptoms, social skills, and peer interactions in this population. PMID:22471319

Sociodemographic and Substance Use Disorder Determinants of HIV Sexual Risk Behavior in Men and Women in Outpatient Drug Treatment in the NIDA National Drug Abuse Treatment Clinical Trials Network.

PubMed

Kidd, Jeremy D; Tross, Susan; Pavlicova, Martina; Hu, Mei-Chen; Campbell, Aimee N C; Nunes, Edward V

2017-06-07

Sexual risk behavior is now the primary vector of HIV transmission among substance users in the United States with gender as a crucial moderator of risk behavior. The purpose of this study was to examine gender differences in factors (age, race/ethnicity, education) that predict main-partner unprotected sexual occasions (USO) using the unique platform of two parallel NIDA National Drug Abuse Treatment Clinical Trials Network gender-specific safer sex intervention trials. Baseline assessments of male (N = 430) and female (N = 377) participants included demographic characteristics; past 3-month sexual activity; and a diagnostic assessment for alcohol, cocaine/stimulant, and opioid use disorders. Using mixed effects generalized linear modeling of the main outcome USO, two-way interactions of gender with age, race/ethnicity, and education were evaluated and adjusted by alcohol, cocaine/stimulant, or opioid use disorder. When adjusted for alcohol use disorder, the interaction of education and gender was significant. For men, a high school or greater education was significantly associated with more USO compared to men with less than high school. For women, greater than high school education was significantly associated with less USO compared to women with a high school education. None of the other interactions were significant when adjusted for cocaine/stimulant or opioid use disorder. Conclusions/Importance: This study demonstrates gender differences in the relationship of education, alcohol use disorder, and main-partner USO in individuals in substance abuse treatment. This underscores the importance of considering demographic and substance use factors in HIV sexual risk behavior and in crafting prevention messages for this population.

Verbal Play as an Interactional Discourse Resource in Early Stage Alzheimer’s Disease

PubMed Central

Shune, Samantha; Duff, Melissa C.

2012-01-01

Background Verbal play, the creative and playful use of language to make puns, rhyme words, and tease, is a pervasive and enjoyable component of social communication and serves important interpersonal functions. The current study examines the use of verbal play in the communicative interactions of individuals with Alzheimer’s disease as part of a broader program of research on language-and-memory-in-use. Aims To document the frequency of verbal play in the communicative interactions of individuals with very mild Alzheimer’s disease (AD) and their familiar communication partners. To characterize the interactional forms, resources, and functions of playful episodes. Methods Using quantitative group comparisons and detailed discourse analysis, we analyzed verbal play in the interactional discourse of five participants with very mild AD and five healthy (demographically matched) comparison participants. Each participant interacted with a familiar partner while completing a collaborative referencing task, and with a researcher between task trials. Results A total of 1,098 verbal play episodes were coded. Despite being in the early stages of AD, all the AD participants used verbal play. There were no significant group differences in the frequency of verbal play episodes or in the interactional forms, resources, or functions of those playful episodes between AD and healthy comparison pair sessions. Conclusions The successful use of verbal play in the interactions of individuals with very mild AD and their partners highlights an area of preserved social communication. These findings represent an important step, both clinically and for research, in documenting the rich ways that individuals with early stage AD orchestrate interactionally meaningful communication with their partners through the use of interactional discourse resources like verbal play. This work also offers a promising clinical tool for tracking and targeting verbal play across disease progression. PMID:23129879

A comparison of the biological properties of small molecular weight agonists and antagonists of CD200:CD200R interactions.

PubMed

Gorczynski, Reg; Boudakov, Ivo; Khatri, Ismat

2008-11-01

Our laboratory and others have documented in some detail the immunological consequences which follow from interaction of the ubiquitously expressed molecule CD200 with its receptor(s) CD200R (expressed predominantly on cells of myeloid and lymphoid origin). In particular, there is evidence that these interactions lead to immunosuppressive signals which modulate graft rejection responses; decrease the manifestations of arthritis in rodent models; diminish mast cell mediator release in models of allergic disease; and favour the growth of tumors in both mice and humans. The development of small molecular weight agonists (and/or antagonists) of these interactions would thus likely have significant clinical importance. The data reported herein characterizes several such molecules in a number of rodent models.

Pursuing Improvement in Clinical Reasoning: Development of the Clinical Coaching Interactions Inventory.

PubMed

Jessee, Mary Ann; Tanner, Christine A

2016-09-01

Clinical coaching has been identified as a signature pedagogy in nursing education. Recent findings indicate that clinical coaching interactions in the clinical learning environment fail to engage students in the higher order thinking skills believed to promote clinical reasoning. The Clinical Coaching Interactions Inventory (CCII) was based on evidence of supervisor questioning techniques, the Tanner clinical judgment model, Bloom's Taxonomy, and simulation evaluation tools. Content validity was established with expert assessment, student testing for clarity, and calculation of scale-content validity index/average (S-CVI/Ave). Reliability was established with Kuder-Richardson Formula 20 (KR-20). CVI (S-CVI/Ave) was .91, and KR-20 was .70. The CCII identified differences in clinical coaching behaviors in university faculty supervisors and staff nurse preceptor supervisors. The CCII advances the measurement of clinical coaching interactions from qualitative to quantitative. Ultimately, results from use of this inventory may facilitate the design of prelicensure clinical coaching strategies that promote the improvement of students' clinical reasoning skill. [J Nurs Educ. 2016;55(9):495-504.]. Copyright 2016, SLACK Incorporated.

Just enough, but not too much interactivity leads to better clinical skills performance after a computer assisted learning module.

PubMed

Kalet, A L; Song, H S; Sarpel, U; Schwartz, R; Brenner, J; Ark, T K; Plass, J

2012-01-01

Well-designed computer-assisted instruction (CAI) can potentially transform medical education. Yet little is known about whether specific design features such as direct manipulation of the content yield meaningful gains in clinical learning. We designed three versions of a multimedia module on the abdominal exam incorporating different types of interactivity. As part of their physical diagnosis course, 162 second-year medical students were randomly assigned (1:1:1) to Watch, Click or Drag versions of the abdominal exam module. First, students' prior knowledge, spatial ability, and prior experience with abdominal exams were assessed. After using the module, students took a posttest; demonstrated the abdominal exam on a standardized patient; and wrote structured notes of their findings. Data from 143 students were analyzed. Baseline measures showed no differences among groups regarding prior knowledge, experience, or spatial ability. Overall there was no difference in knowledge across groups. However, physical exam scores were significantly higher for students in the Click group. A mid-range level of behavioral interactivity was associated with small to moderate improvements in performance of clinical skills. These improvements were likely mediated by enhanced engagement with the material, within the bounds of learners' cognitive capacity. These findings have implications for the design of CAI materials to teach procedural skills.

Interaction of different antidepressants with acute and chronic methadone in mice, and possible clinical implications.

PubMed

Schreiber, Shaul; Barak, Yonatan; Hostovsky, Avner; Baratz-Goldstein, Renana; Volis, Ina; Rubovitch, Vardit; Pick, Chaim G

2014-04-01

We studied the interaction of a single dose of different antidepressant medications with a single (acute) dose or implanted mini-pump (chronic) methadone administration in mice, using the hotplate assay. For the acute experiment, subthreshold doses of six antidepressant drugs were administered separately with a single dose of methadone. The addition of a subthreshold dose of desipramine or clomipramine to methadone produced significant augmentation of the methadone effect with each drug (p < 0.05). Fluvoxamine given at a fixed subthreshold dose induced a synergistic effect only with a low methadone dose. Escitalopram, reboxetine and venlafaxine given separately, each at a fixed subthreshold dose, induced no interaction. Possible clinical implications of these findings are that while escitalopram, reboxetine and venlafaxine do not affect methadone's antinociception in mice and are safe to be given together with methadone when indicated, fluvoxamine, clomipramine and desipramine considerably augment methadone-induced effects and should be avoided in this population due to the risk of inducing opiate overdose. For the chromic experiment, when a subthreshold dose of either escitalopram, desipramine or clomipramine was injected to mice following 2 weeks of methadone administration with the mini-pump, none of the antidepressant drugs strengthened methadone's analgesic effect. Further studies are needed before possible clinical implications can be drawn.

Laboratory Exercises to Teach Clinically Relevant Chemistry of Antibiotics

PubMed Central

Chelette, Candace T.

2014-01-01

Objectives. To design, implement, and evaluate student performance on clinically relevant chemical and spectral laboratory exercises on antibiotics. Design. In the first of 2 exercises, second-year pharmacy students enrolled in an integrated laboratory sequence course studied the aqueous stability of ß-lactam antibiotics using a spectral visual approach. In a second exercise, students studied the tendency of tetracycline, rifamycins, and fluoroquinolones to form insoluble chelate complexes (turbidity) with polyvalent metals. Assessment. On a survey to assess achievement of class learning objectives, students agreed the laboratory activities helped them better retain important information concerning antibiotic stability and interactions. A significant improvement was observed in performance on examination questions related to the laboratory topics for 2012 and 2013 students compared to 2011 students who did not complete the laboratory. A 1-year follow-up examination question administered in a separate course showed >75% of the students were able to identify rifamycins-food interactions compared with <25% of students who had not completed the laboratory exercises. Conclusion. The use of spectral visual approaches allowed students to investigate antibiotic stability and interactions, thus reinforcing the clinical relevance of medicinal chemistry. Students’ performance on questions at the 1-year follow-up suggested increased retention of the concepts learned as a result of completing the exercises. PMID:24672070

Laboratory exercises to teach clinically relevant chemistry of antibiotics.

PubMed

El Sayed, Khalid A; Chelette, Candace T

2014-03-12

To design, implement, and evaluate student performance on clinically relevant chemical and spectral laboratory exercises on antibiotics. In the first of 2 exercises, second-year pharmacy students enrolled in an integrated laboratory sequence course studied the aqueous stability of ß-lactam antibiotics using a spectral visual approach. In a second exercise, students studied the tendency of tetracycline, rifamycins, and fluoroquinolones to form insoluble chelate complexes (turbidity) with polyvalent metals. On a survey to assess achievement of class learning objectives, students agreed the laboratory activities helped them better retain important information concerning antibiotic stability and interactions. A significant improvement was observed in performance on examination questions related to the laboratory topics for 2012 and 2013 students compared to 2011 students who did not complete the laboratory. A 1-year follow-up examination question administered in a separate course showed >75% of the students were able to identify rifamycins-food interactions compared with <25% of students who had not completed the laboratory exercises. The use of spectral visual approaches allowed students to investigate antibiotic stability and interactions, thus reinforcing the clinical relevance of medicinal chemistry. Students' performance on questions at the 1-year follow-up suggested increased retention of the concepts learned as a result of completing the exercises.

Geographic Proximity and Racial Disparities in Cancer Clinical Trial Participation

PubMed Central

Kanarek, Norma F.; Tsai, Hua-Ling; Metzger-Gaud, Sharon; Damron, Dorothy; Guseynova, Alla; Klamerus, Justin F.; Rudin, Charles M.

2011-01-01

This study assessed the effects of race and place of residence on clinical trial participation by patients seen at a designated NCI comprehensive cancer center. Clinical trial accrual to cancer case ratios were evaluated using a database of residents at the continental United States seen at The Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins from 2005 to 2007. Place of residence was categorized into 3 nonoverlapping geographic areas: Baltimore City, non–Baltimore City catchment area, and non–catchment area. Controlling for age, sex, county poverty level, and cancer site, significant race and place of residence differences were seen in therapeutic or nontherapeutic clinical trials participation. White non–Baltimore City catchment area residents, the designated reference group, achieved the highest participation rate. Although the test of interaction (control group compared with all others) was not significant, some race–geographic area group differences were detected. In therapeutic trials, most race–place of residence group levels were statistically lower and different from reference; in nontherapeutic trials, race-specific Baltimore City groups participated at levels similar to reference. Baltimore City residents had lower participation rates only in therapeutic trials, irrespective of race. County poverty level was not significant but was retained as a confounder. Place of residence and race were found to be significant predictors of participation in therapeutic and nontherapeutic clinical trials, although patterns differed somewhat between therapeutic and nontherapeutic trials. Clinical trial accruals are not uniform across age, sex, race, place of residence, cancer site, or trial type, underscoring that cancer centers must better understand their source patients to enhance clinical trial participation. PMID:21147901

Development and evaluation of learning module on clinical decision-making in Prosthodontics.

PubMed

Deshpande, Saee; Lambade, Dipti; Chahande, Jayashree

2015-01-01

Best practice strategies for helping students learn the reasoning skills of problem solving and critical thinking (CT) remain a source of conjecture, particularly with regard to CT. The dental education literature is fundamentally devoid of research on the cognitive components of clinical decision-making. This study was aimed to develop and evaluate the impact of blended learning module on clinical decision-making skills of dental graduates for planning prosthodontics rehabilitation. An interactive teaching module consisting of didactic lectures on clinical decision-making and a computer-assisted case-based treatment planning software was developed Its impact on cognitive knowledge gain in clinical decision-making was evaluated using an assessment involving problem-based multiple choice questions and paper-based case scenarios. Mean test scores were: Pretest (17 ± 1), posttest 1 (21 ± 2) and posttest 2 (43 ± 3). Comparison of mean scores was done with one-way ANOVA test. There was overall significant difference in between mean scores at all the three points (P < 0.001). A pair-wise comparison of mean scores was done with Bonferroni test. The mean difference is significant at the 0.05 level. The pair-wise comparison shows that posttest 2 score is significantly higher than posttest 1 and posttest 1 is significantly higher than pretest that is, pretest 2 > posttest 1 > pretest. Blended teaching methods employing didactic lectures on the clinical decision-making as well as computer assisted case-based learning can be used to improve quality of clinical decision-making in prosthodontic rehabilitation for dental graduates.

New era in drug interaction evaluation: US Food and Drug Administration update on CYP enzymes, transporters, and the guidance process.

PubMed

Huang, Shiew-Mei; Strong, John M; Zhang, Lei; Reynolds, Kellie S; Nallani, Srikanth; Temple, Robert; Abraham, Sophia; Habet, Sayed Al; Baweja, Raman K; Burckart, Gilbert J; Chung, Sang; Colangelo, Philip; Frucht, David; Green, Martin D; Hepp, Paul; Karnaukhova, Elena; Ko, Hon-Sum; Lee, Jang-Ik; Marroum, Patrick J; Norden, Janet M; Qiu, Wei; Rahman, Atiqur; Sobel, Solomon; Stifano, Toni; Thummel, Kenneth; Wei, Xiao-Xiong; Yasuda, Sally; Zheng, Jenny H; Zhao, Hong; Lesko, Lawrence J

2008-06-01

Predicting clinically significant drug interactions during drug development is a challenge for the pharmaceutical industry and regulatory agencies. Since the publication of the US Food and Drug Administration's (FDA's) first in vitro and in vivo drug interaction guidance documents in 1997 and 1999, researchers and clinicians have gained a better understanding of drug interactions. This knowledge has enabled the FDA and the industry to progress and begin to overcome these challenges. The FDA has continued its efforts to evaluate methodologies to study drug interactions and communicate recommendations regarding the conduct of drug interaction studies, particularly for CYP-based and transporter-based drug interactions, to the pharmaceutical industry. A drug interaction Web site was established to document the FDA's current understanding of drug interactions (http://www.fda.gov/cder/drug/drugInteractions/default.htm). This report provides an overview of the evolution of the drug interaction guidances, includes a synopsis of the steps taken by the FDA to revise the original drug interaction guidance documents, and summarizes and highlights updated sections in the current guidance document, Drug Interaction Studies-Study Design, Data Analysis, and Implications for Dosing and Labeling.

Detection of Significant Pneumococcal Meningitis Biomarkers by Ego Network.

PubMed

Wang, Qian; Lou, Zhifeng; Zhai, Liansuo; Zhao, Haibin

2017-06-01

To identify significant biomarkers for detection of pneumococcal meningitis based on ego network. Based on the gene expression data of pneumococcal meningitis and global protein-protein interactions (PPIs) data recruited from open access databases, the authors constructed a differential co-expression network (DCN) to identify pneumococcal meningitis biomarkers in a network view. Here EgoNet algorithm was employed to screen the significant ego networks that could accurately distinguish pneumococcal meningitis from healthy controls, by sequentially seeking ego genes, searching candidate ego networks, refinement of candidate ego networks and significance analysis to identify ego networks. Finally, the functional inference of the ego networks was performed to identify significant pathways for pneumococcal meningitis. By differential co-expression analysis, the authors constructed the DCN that covered 1809 genes and 3689 interactions. From the DCN, a total of 90 ego genes were identified. Starting from these ego genes, three significant ego networks (Module 19, Module 70 and Module 71) that could predict clinical outcomes for pneumococcal meningitis were identified by EgoNet algorithm, and the corresponding ego genes were GMNN, MAD2L1 and TPX2, respectively. Pathway analysis showed that these three ego networks were related to CDT1 association with the CDC6:ORC:origin complex, inactivation of APC/C via direct inhibition of the APC/C complex pathway, and DNA strand elongation, respectively. The authors successfully screened three significant ego modules which could accurately predict the clinical outcomes for pneumococcal meningitis and might play important roles in host response to pathogen infection in pneumococcal meningitis.

Drug interaction between celecoxib and methotrexate in organic anion transporter 3-transfected renal cells and in rats in vivo.

PubMed

Maeda, Akimitsu; Tsuruoka, Shuichi; Ushijima, Kentarou; Kanai, Yoshikatsu; Endou, Hitoshi; Saito, Kazuyuki; Miyamoto, Etsuko; Fujimura, Akio

2010-08-25

Methotrexate has a clinically important pharmacokinetic interaction with nonsteroidal anti-inflammatory drugs (NSAIDs) mainly through its competition for tubular secretion via the renal organic anion transporter 3 (OAT3). We have previously reported the usefulness of OAT3-transfected renal tubular cells for screening of the drugs which interfere with the pharmacokinetics of methotrexate. Celecoxib, a cyclooxygenase (COX) 2 inhibitor, has not been reported to interact with methotrexate, but the mechanisms are unclear why the interaction did not occur. The purpose of this study was to evaluate the effect of celecoxib on methotrexate tubular secretion using a renal cell line stably expressing human OAT3 (S2-hOAT3), and to evaluate the pharmacokinetic interaction of the two drugs in rats. [3H]methotrexate uptake into S2-hOAT3 cells was significantly inhibited by celecoxib in a concentration-dependent manner and the Ki value was 35.3 microM. However, methotrexate serum concentrations and urinary excretion of methotrexate over 24 h in rats were not affected by celecoxib (50, 200 mg/kg). Celecoxib serum concentrations were increased by the increase in celecoxib dosage and the maximum drug concentration (Cmax) was 20.6 microM (celecoxib 200 mg/kg), which did not reach the Ki value obtained in the in vitro study. These results indicated that celecoxib inhibited the secretion of methotrexate via hOAT3, which suggested that celecoxib was a substrate of hOAT3. However, co-administration of the two drugs at clinical dosage did not affect the pharmacokinetics of methotrexate, because the serum concentrations did not reach the Ki value. Although the accumulation study using S2-hOAT3 cells was useful to predict the interaction between the new drug and methotrexate in vivo, a comparison of the Ki value with the Cmax in clinical dosage was necessary to evaluate the degree of this interaction. Copyright (c) 2010 Elsevier B.V. All rights reserved.

A Systematic Approach to Evaluate Herb-Drug Interaction Mechanisms: Investigation of Milk Thistle Extracts and Eight Isolated Constituents as CYP3A Inhibitors

PubMed Central

Brantley, Scott J.; Graf, Tyler N.; Oberlies, Nicholas H.

2013-01-01

Despite increasing recognition of potential untoward interactions between herbal products and conventional medications, a standard system for prospective assessment of these interactions remains elusive. This information gap was addressed by evaluating the drug interaction liability of the model herbal product milk thistle (Silybum marianum) with the CYP3A probe substrate midazolam. The inhibitory effects of commercially available milk thistle extracts and isolated constituents on midazolam 1′-hydroxylation were screened using human liver and intestinal microsomes. Relative to vehicle, the extract silymarin and constituents silybin A, isosilybin A, isosilybin B, and silychristin at 100 μM demonstrated >50% inhibition of CYP3A activity with at least one microsomal preparation, prompting IC50 determination. The IC50s for isosilybin B and silychristin were ∼60 and 90 μM, respectively, whereas those for the remaining constituents were >100 μM. Extracts and constituents that contained the 1,4-dioxane moiety demonstrated a >1.5-fold shift in IC50 when tested as potential mechanism-based inhibitors. The semipurified extract, silibinin, and the two associated constituents (silybin A and silybin B) demonstrated mechanism-based inhibition of recombinant CYP3A4 (KI, ∼100 μM; kinact, ∼0.20 min−1) but not microsomal CYP3A activity. The maximum predicted increases in midazolam area under the curve using the static mechanistic equation and recombinant CYP3A4 data were 1.75-fold, which may necessitate clinical assessment. Evaluation of the interaction liability of single herbal product constituents, in addition to commercially available extracts, will enable elucidation of mechanisms underlying potential clinically significant herb-drug interactions. Application of this framework to other herbal products would permit predictions of herb-drug interactions and assist in prioritizing clinical evaluation. PMID:23801821

A systematic approach to evaluate herb-drug interaction mechanisms: investigation of milk thistle extracts and eight isolated constituents as CYP3A inhibitors.

PubMed

Brantley, Scott J; Graf, Tyler N; Oberlies, Nicholas H; Paine, Mary F

2013-09-01

Despite increasing recognition of potential untoward interactions between herbal products and conventional medications, a standard system for prospective assessment of these interactions remains elusive. This information gap was addressed by evaluating the drug interaction liability of the model herbal product milk thistle (Silybum marianum) with the CYP3A probe substrate midazolam. The inhibitory effects of commercially available milk thistle extracts and isolated constituents on midazolam 1'-hydroxylation were screened using human liver and intestinal microsomes. Relative to vehicle, the extract silymarin and constituents silybin A, isosilybin A, isosilybin B, and silychristin at 100 μM demonstrated >50% inhibition of CYP3A activity with at least one microsomal preparation, prompting IC50 determination. The IC50s for isosilybin B and silychristin were ∼60 and 90 μM, respectively, whereas those for the remaining constituents were >100 μM. Extracts and constituents that contained the 1,4-dioxane moiety demonstrated a >1.5-fold shift in IC50 when tested as potential mechanism-based inhibitors. The semipurified extract, silibinin, and the two associated constituents (silybin A and silybin B) demonstrated mechanism-based inhibition of recombinant CYP3A4 (KI, ∼100 μM; kinact, ∼0.20 min(-1)) but not microsomal CYP3A activity. The maximum predicted increases in midazolam area under the curve using the static mechanistic equation and recombinant CYP3A4 data were 1.75-fold, which may necessitate clinical assessment. Evaluation of the interaction liability of single herbal product constituents, in addition to commercially available extracts, will enable elucidation of mechanisms underlying potential clinically significant herb-drug interactions. Application of this framework to other herbal products would permit predictions of herb-drug interactions and assist in prioritizing clinical evaluation.

Mechanisms of peripheral immune-cell-mediated analgesia in inflammation: clinical and therapeutic implications.

PubMed

Hua, Susan; Cabot, Peter J

2010-09-01

Peripheral mechanisms of endogenous pain control are significant. In peripheral inflamed tissue, an interaction between immune-cell-derived opioids and opioid receptors localized on sensory nerve terminals results in potent, clinically measurable analgesia. Opioid peptides and the mRNA encoding their precursor proteins are present in immune cells. These cells 'home' preferentially to injured tissue, where they secrete opioids to reduce pain. Investigation of the mechanisms underlying the migration of opioid-containing immune cells to inflamed tissue is an active area of research, with recent data demonstrating the importance of cell adhesion molecules in leukocyte adhesion to both the endothelium in vascular transmigration and to neurons within peripheral inflamed tissue. This review summarizes the physiological mechanisms and clinical significance of this unique endogenous peripheral analgesic pathway and discusses therapeutic implications for the development of novel targeted peripheral analgesics. Copyright 2010 Elsevier Ltd. All rights reserved.

Clinical utility of the Rorschach with African Americans.

PubMed

Presley, G; Smith, C; Hilsenroth, M; Exner, J

2001-12-01

In this study we sought to identify Rorschach differences between African Americans and White Americans and to understand these differences within a social and cultural framework. Data from the Exner (1993) Comprehensive System normative sample (N = 700) was used to form a group of 44 African Americans and 44 White Americans matched for age, sex, education, and socioeconomic status. Twenty-three Rorschach variables were chosen a priori and group differences were analyzed. The only clinically significant difference found was that African Americans offered significantly less cooperative movement. This lower frequency of cooperative movement may suggest African Americans do not anticipate cooperative interactions with others as a routine event. This may reflect a shared feeling among African Americans that most members of our society are less likely to be sensitive to or responsive to their needs relative to others. However, the study demonstrates a striking similarity between the groups, supporting the clinical use of the Rorschach with African Americans.

A Comprehensive Pan-Cancer Molecular Study of Gynecologic and Breast Cancers. | Office of Cancer Genomics

Cancer.gov

We analyzed molecular data on 2,579 tumors from The Cancer Genome Atlas (TCGA) of four gynecological types plus breast. Our aims were to identify shared and unique molecular features, clinically significant subtypes, and potential therapeutic targets. We found 61 somatic copy-number alterations (SCNAs) and 46 significantly mutated genes (SMGs). Eleven SCNAs and 11 SMGs had not been identified in previous TCGA studies of the individual tumor types. We found functionally significant estrogen receptor-regulated long non-coding RNAs (lncRNAs) and gene/lncRNA interaction networks.

Centralized Research Recruitment—Evolving a Local Clinical Research Recruitment Web Application to Better Meet User Needs

PubMed Central

Dwyer‐White, Molly; Doshi, Aalap; Hill, Mary; Pienta, Kenneth J.

2011-01-01

Abstract  Recruiting volunteers into clinical research remains a significant challenge for many clinical research study teams, thus the Michigan Institute for Clinical and Health Research (MICHR) at the University of Michigan developed UMClinicalStudies (http://www.UMClinicalStudies.org)—a Web application that links the community to a single gateway for clinical research. UMClinicalStudies (formerly named “Engage”) is an integral piece of MICHR’s efforts to increase clinical research participation in order to advance medical discoveries. Despite the initial success of the application, barriers to research participation remain, including the applications accessibility for potential research volunteers and study team members. In response, new initiatives were instigated to identify user needs, in order to broaden the ability to simultaneously assist researchers in recruitment activities, while also aiding potential volunteers in the exploration of and participation in clinical research opportunities. To do this, improvements to the interface and functionality were identified and implemented for both the public and the research audiences through extensive system analysis, and through the application of human computer interactivity processes, resulting in significant improvements in usability and ultimately research volunteerism, indicating that utilizing such technology is pivotal in reaching broader audiences for clinical trial participation. Clin Trans Sci 2011; Volume 4: 363–368 PMID:22029810

A proposed clinical decision support architecture capable of supporting whole genome sequence information.

PubMed

Welch, Brandon M; Loya, Salvador Rodriguez; Eilbeck, Karen; Kawamoto, Kensaku

2014-04-04

Whole genome sequence (WGS) information may soon be widely available to help clinicians personalize the care and treatment of patients. However, considerable barriers exist, which may hinder the effective utilization of WGS information in a routine clinical care setting. Clinical decision support (CDS) offers a potential solution to overcome such barriers and to facilitate the effective use of WGS information in the clinic. However, genomic information is complex and will require significant considerations when developing CDS capabilities. As such, this manuscript lays out a conceptual framework for a CDS architecture designed to deliver WGS-guided CDS within the clinical workflow. To handle the complexity and breadth of WGS information, the proposed CDS framework leverages service-oriented capabilities and orchestrates the interaction of several independently-managed components. These independently-managed components include the genome variant knowledge base, the genome database, the CDS knowledge base, a CDS controller and the electronic health record (EHR). A key design feature is that genome data can be stored separately from the EHR. This paper describes in detail: (1) each component of the architecture; (2) the interaction of the components; and (3) how the architecture attempts to overcome the challenges associated with WGS information. We believe that service-oriented CDS capabilities will be essential to using WGS information for personalized medicine.

A Proposed Clinical Decision Support Architecture Capable of Supporting Whole Genome Sequence Information

PubMed Central

Welch, Brandon M.; Rodriguez Loya, Salvador; Eilbeck, Karen; Kawamoto, Kensaku

2014-01-01

Whole genome sequence (WGS) information may soon be widely available to help clinicians personalize the care and treatment of patients. However, considerable barriers exist, which may hinder the effective utilization of WGS information in a routine clinical care setting. Clinical decision support (CDS) offers a potential solution to overcome such barriers and to facilitate the effective use of WGS information in the clinic. However, genomic information is complex and will require significant considerations when developing CDS capabilities. As such, this manuscript lays out a conceptual framework for a CDS architecture designed to deliver WGS-guided CDS within the clinical workflow. To handle the complexity and breadth of WGS information, the proposed CDS framework leverages service-oriented capabilities and orchestrates the interaction of several independently-managed components. These independently-managed components include the genome variant knowledge base, the genome database, the CDS knowledge base, a CDS controller and the electronic health record (EHR). A key design feature is that genome data can be stored separately from the EHR. This paper describes in detail: (1) each component of the architecture; (2) the interaction of the components; and (3) how the architecture attempts to overcome the challenges associated with WGS information. We believe that service-oriented CDS capabilities will be essential to using WGS information for personalized medicine. PMID:25411644

Prognostic and predictive value of tumor-infiltrating lymphocytes in a phase III randomized adjuvant breast cancer trial in node-positive breast cancer comparing the addition of docetaxel to doxorubicin with doxorubicin-based chemotherapy: BIG 02-98.

PubMed

Loi, Sherene; Sirtaine, Nicolas; Piette, Fanny; Salgado, Roberto; Viale, Giuseppe; Van Eenoo, Françoise; Rouas, Ghizlane; Francis, Prudence; Crown, John P A; Hitre, Erika; de Azambuja, Evandro; Quinaux, Emmanuel; Di Leo, Angelo; Michiels, Stefan; Piccart, Martine J; Sotiriou, Christos

2013-03-01

Previous preclinical and clinical data suggest that the immune system influences prognosis and response to chemotherapy (CT); however, clinical relevance has yet to be established in breast cancer (BC). We hypothesized that increased lymphocytic infiltration would be associated with good prognosis and benefit from immunogenic CT-in this case, anthracycline-only CT-in selected BC subtypes. We investigated the relationship between quantity and location of lymphocytic infiltrate at diagnosis with clinical outcome in 2009 node-positive BC samples from the BIG 02-98 adjuvant phase III trial comparing anthracycline-only CT (doxorubicin followed by cyclophosphamide, methotrexate, and fluorouracil [CMF] or doxorubicin plus cyclophosphamide followed by CMF) versus CT combining doxorubicin and docetaxel (doxorubicin plus docetaxel followed by CMF or doxorubicin followed by docetaxel followed by CMF). Readings were independently performed by two pathologists. Disease-free survival (DFS), overall survival (OS), and interaction with type of CT associations were studied. Median follow-up was 8 years. There was no significant prognostic association in the global nor estrogen receptor (ER) -positive/human epidermal growth factor receptor 2 (HER2) -negative population. However, each 10% increase in intratumoral and stromal lymphocytic infiltrations was associated with 17% and 15% reduced risk of relapse (adjusted P = .1 and P = .025), respectively, and 27% and 17% reduced risk of death in ER-negative/HER2-negative BC regardless of CT type (adjusted P = .035 and P = .023), respectively. In HER2-positive BC, there was a significant interaction between increasing stromal lymphocytic infiltration (10% increments) and benefit with anthracycline-only CT (DFS, interaction P = .042; OS, P = .018). In node-positive, ER-negative/HER2-negative BC, increasing lymphocytic infiltration was associated with excellent prognosis. Further validation of the clinical utility of tumor-infiltrating lymphocytes in this context is warranted. Our data also support the evaluation of immunotherapeutic approaches in selected BC subtypes.

Self-transcendence and nurse-patient interaction in cognitively intact nursing home patients.

PubMed

Haugan, Gørill; Rannestad, Toril; Hanssen, Brith; Espnes, Geir A

2012-12-01

The aim of this study was to test whether nurse-patient interaction affects cognitively intact nursing home patients' interpersonal and intrapersonal self-transcendence, as well as testing the psychometric properties of the Nurse-Patient Interaction Scale (NPIS). Self-transcendence is considered a spiritual developmental process of maturity in adulthood, and a vital resource of well-being at the end of life. The concept of self-transcendence has previously been explored in various populations, yet the nurse-patient interactions' potential influence on self-transcendence in nursing home patients has not been published previously. A cross-sectional design employing the Self-Transcendence Scale and the NPIS was adopted. A sample of 202 cognitively well-functioning nursing home patients in Norway was selected. The statistical analyses were carried out using lisrel 8.8 and structural equation modelling. Structural equation modelling-analysis indicates statistical significant effect of nurse-patient interaction on the patients' self-transcendence. Direct influence on the intrapersonal and indirect influence on the interpersonal self-transcendence aspects was disclosed. Nurse-patient interaction significantly affected both interpersonal and intrapersonal self-transcendence among cognitively intact nursing home patients. Hence, facilitating caring interventions can be significantly beneficial to older patients' self-transcendence and thereby well-being, both emotional and physical. Caring behaviour signifies the vital and ultimate qualitative nursing behaviour, which promotes self-transcendence and thereby well-being. These findings are important for clinical nursing that intends to increase patients' well-being. © 2012 Blackwell Publishing Ltd.

A decision tree-based combination of ezrin-interacting proteins to estimate the prognostic risk of patients with esophageal squamous cell carcinoma.

PubMed

He, Jian-Zhong; Wu, Zhi-Yong; Wang, Shao-Hong; Ji, Xia; Yang, Cui-Xia; Xu, Xiu-E; Liao, Lian-Di; Wu, Jian-Yi; Li, En-Min; Zhang, Kai; Xu, Li-Yan

2017-08-01

Our previous studies have highlighted the importance of ezrin in esophageal squamous cell carcinoma (ESCC). Here our objective was to explore the clinical significance of ezrin-interacting proteins, which would provide a theoretical basis for understanding the function of ezrin and potential therapeutic targets for ESCC. We used affinity purification and mass spectrometry to identify PDIA3, CNPY2, and STMN1 as potential ezrin-interacting proteins. Confocal microscopy and coimmunoprecipitation analysis further confirmed the colocalization and interaction of ezrin with PDIA3, CNPY2, and STMN1. Tissue microarray data of ESCC samples (n=263) showed that the 5-year overall survival (OS) and disease-free survival (DFS) were significantly lower for the CNPY2 (OS, P=.003; DFS, P=.011) and STMN1 (OS, P=.010; DFS, P=.002) high-expression groups compared with the low-expression groups. By contrast, overexpression of PDIA3 was significantly correlated with favorable survival (OS, P<.001; DFS, P=.001). Cox regression demonstrated the prognostic value of PDIA3, CNPY2, and STMN1 in ESCC. Furthermore, decision tree analysis revealed that the resulting classifier of both ezrin and its interacting proteins could be used to better predict OS and DFS of patients with ESCC. In conclusion, a signature of ezrin-interacting proteins accurately predicts ESCC patient survival or tumor recurrence. Copyright © 2017 Elsevier Inc. All rights reserved.

Searching for the synergistic effect between aclidinium and formoterol: From bench to bedside.

PubMed

Cazzola, Mario; Calzetta, Luigino; Ora, Josuel; Puxeddu, Ermanno; Rogliani, Paola; Matera, Maria Gabriella

2015-10-01

Aim of our study was to understand if the interaction between aclidinium and formoterol administered at therapeutic doses leads to a synergistic rather than additive broncholytic effect. We tested the type of effect ex vivo on isolated human bronchi and then in vivo in COPD patients. The analysis of the interaction between aclidinium and formoterol in vitro was measured by applying the Unified Theory, whereas that in COPD patients was measured by applying the Bliss Independence criterion. Aclidinium and formoterol administered alone completely relaxed human isolated bronchial tissues sub-maximally pre-contracted with ACh in a concentration-dependent manner with similar potency (EC50: aclidinium 4.64 ± 0.78 nM, formoterol 2.71 ± 0.21), whereas the interaction of aclidinium plus formoterol produced moderate to strong synergism. Changes in FEV1 values showed that inhaled aclidinium and formoterol induced a significant and time-dependent bronchodilatory effect during the study time. The inhalation of aclidinium and formoterol in combination significantly anticipated at 5 min post-administration the bronchodilatory effect of FEV1, compared with the effect of drugs administered alone. There was a synergistic interaction for FEV1 at 5 min and from 120 min to 240 min post-inhalation, whereas from 30 min to 60 min post-administration the drug interaction was additive. This study shows that aclidinium and formoterol can produce a significant synergistic interaction that may have a role also in the clinic setting. Copyright © 2015 Elsevier Ltd. All rights reserved.

Effect of blueberry juice on clearance of buspirone and flurbiprofen in human volunteers

PubMed Central

Hanley, Michael J; Masse, Gina; Harmatz, Jerold S; Cancalon, Paul F; Dolnikowski, Gregory G; Court, Michael H; Greenblatt, David J

2013-01-01

Aim The present study evaluated the possibility of drug interactions involving blueberry juice (BBJ) and substrate drugs whose clearance is dependent on cytochromes P4503A (CYP3A) and P4502C9 (CYP2C9). Methods A 50:50 mixture of lowbush and highbush BBJ was evaluated in vitro as an inhibitor of CYP3A activity (hydroxylation of triazolam and dealkylation of buspirone) and of CYP2C9 activity (flurbiprofen hydroxylation) using human liver microsomes. In clinical studies, clearance of oral buspirone and oral flurbiprofen was studied in healthy volunteers with and without co-treatment with BBJ. Results BBJ inhibited CYP3A and CYP2C9 activity in vitro, with 50% inhibitory concentrations (IC50) of less than 2%, but without evidence of mechanism-based (irreversible) inhibition. Grapefruit juice (GFJ) also inhibited CYP3A activity, but inhibitory potency was increased by pre-incubation, consistent with mechanism-based inhibition. In clinical studies, GFJ significantly increased area under the plasma concentration−time curve (AUC) for the CYP3A substrate buspirone. The geometric mean ratio (GMR = AUC with GFJ divided by AUC with water) was 2.12. In contrast, the effect of BBJ (GMR = 1.39) was not significant. In the study of flurbiprofen (CYP2C9 substrate), the positive control inhibitor fluconazole significantly increased flurbiprofen AUC (GMR = 1.71), but BBJ had no significant effect (GMR = 1.03). Conclusion The increased buspirone AUC associated with BBJ is quantitatively small and could have occurred by chance. BBJ has no effect on flurbiprofen AUC. The studies provide no evidence for concern about clinically important pharmacokinetic drug interactions of BBJ with substrate drugs metabolized by CYP3A or CYP2C9. PMID:22943633

An approach to evaluating drug-nutrient interactions.

PubMed

Santos, Cristina A; Boullata, Joseph I

2005-12-01

Although the significance of interactions between drugs is widely appreciated, little attention has been given to interactions between drugs and nutrients. Pharmacists are challenged to remember documented interactions involving available drugs, and they face the possibility that each newly approved therapeutic agent may be involved not only in unrecognized drug-drug interactions but in drug-nutrient interactions as well. A more consistent approach to evaluating drug-nutrient interactions is needed. The approach must be systematic in order to assess the influence of nutritional status, food, or specific nutrients on a drug's pharmacokinetics and pharmacodynamics, as well as the influence of a drug on overall nutritional status or on the status of a specific nutrient. We provide such a process, using several recently approved drugs as working examples. Risk factors and clinical relevance are described, with distinctions made between documented and potential interactions. Application of this process by the pharmacist to any drug will help increase their expertise. Furthermore, full consideration by pharmacists of all possible interactions of the drug regimens used in practice can allow for improved patient care.

The correlation between organizational justice and trust among employees of rehabilitation clinics in hospitals of Ahvaz, Iran

PubMed Central

Khiavi, Farzad Faraji; Shakhi, Kamal; Dehghani, Roohallah; Zahiri, Mansour

2016-01-01

Introduction Organizational justice is an intricate concept that refers to fair and ethical conduct of individuals within organizations. No research has been conducted on the variables associated with organizational justice in rehabilitation clinics. Thus, the aim of this research was to determine the correlation between organizational justice and organizational trust among the employees of rehabilitation clinics in hospitals of Ahvaz, Iran. Methods This was a cross-sectional research, and it was conducted on 140 rehabilitation staff members of hospital clinics in Ahvaz. The data were gathered using organizational justice and trust questionnaires. The data were analyzed using the independent-samples t-test, ANOVA, and Pearson’s product-moment correlation SPSS software. Results Significant correlations between procedure and interaction justice and organizational trust were identified (p < 0.001). Distributive justice showed small correlation with trust (r = 0.25, p < 0.021). Organizational justice was significantly associated with organizational trust (r = 0.42, p < 0.001). Organizational justice was not significantly related to any demographic variable (p > 0.05). Conclusion There was a positive, medium, and significant correlation between organizational justice and trust. It is suggested that rehabilitation clinics’ managers develop plans to increase their organizational justice subscales in order to develop organizational trust among their employees. PMID:27053997

Food-drug interactions: grapefruit juice.

PubMed

Diaconu, Camelia Harapu; Cuciureanu, Magdalena; Vlase, L; Cuciureanu, Rodica

2011-01-01

Food-drug interactions are increasingly recognized as important clinical events which may change significantly the bioavailability of oral administrated drugs. Grapefruit juice (GFJ) demonstrated multiple interactions with drugs leading to loss of the therapeutic effects or increased side-effects. GFJ decreases pre-systemic metabolism through a) competitive or mechanism-based inhibition of gut wall CYP3A4 isoenzymes and b) P-glycoprotein (P-gp), c) multidrug resistance protein-2 (MRP2) or d) organic anion-transporting polypeptide (OATP) inhibition. Although, GFJ presents high amounts of flavonoids (e.g. naringin, naringenin), furanocoumarins (e.g. 6',7'-dihydroxybergamottin, bergamottin) are the main chemicals involved in the pharmacokinetic interactions. As compounds of GFJ show additive or synergistic effects, all the major furanocoumarins are necessary for the maximal inhibitory effect. Also, related citrus fruits (sweeties, pummelo and sour orange) or various plants containing furanocoumarins may present pharmacological interactions, yet to be discovered.

Internet-enabled interactive multimedia asthma education program: a randomized trial.

PubMed

Krishna, Santosh; Francisco, Benjamin D; Balas, E Andrew; König, Peter; Graff, Gavin R; Madsen, Richard W

2003-03-01

To determine whether health outcomes of children who have asthma can be improved through the use of an Internet-enabled interactive multimedia asthma education program. Two hundred twenty-eight children with asthma visiting a pediatric pulmonary clinic were randomly assigned to control and intervention groups. Children and caregivers in both groups received traditional patient education based on the National Asthma Education and Prevention Program. Intervention group participants received additional self-management education through the Interactive Multimedia Program for Asthma Control and Tracking. Pediatric Asthma Care Knowledge Survey, Pediatric Asthma Caregiver's Quality of Life Questionnaire, asthma symptom history, spirometry, and health services utilization data were collected at the initial visit and at 3 and 12 months. Interactive Multimedia Program for Asthma Control and Tracking significantly increased asthma knowledge of children and caregivers, decreased asthma symptom days (81 vs 51 per year), and decreased number of emergency department visits (1.93 vs 0.62 per year) among the intervention group participants. The intervention group children were also using a significantly lower average daily dose of inhaled corticosteroids (434 vs 754 micro g [beclomethasone equivalents]) at visit 3. Asthma knowledge of all 7- to 17-year-old children correlated with fewer urgent physician visits (r = 0.37) and less frequent use of quick-relief medicines (r = 0.30). Supplementing conventional asthma care with interactive multimedia education can significantly improve asthma knowledge and reduce the burden of childhood asthma.

Guilt is more strongly associated with suicidal ideation among military personnel with direct combat exposure.

PubMed

Bryan, Craig J; Ray-Sannerud, Bobbie; Morrow, Chad E; Etienne, Neysa

2013-05-15

Suicide rates in the U.S. military have been rising rapidly in the past decade. Research suggests guilt is a significant predictor of suicidal ideation among military personnel, and may be especially pronounced among those who have been exposure to combat-related traumas. The current study explored the interactive effect of direct combat exposure and guilt on suicidal ideation in a clinical sample of military personnel. Ninety-seven active duty U.S. Air Force personnel receiving outpatient mental health treatment at two military clinics completed self-report symptom measures of guilt, depression, hopelessness, perceived burdensomeness, posttraumatic stress disorder, and suicidal ideation. Generalized multiple regression analyses indicated a significant interaction of guilt and direct combat exposure (B=.124, SE=.053, p=.020), suggesting a stronger relationship of guilt with suicidal ideation among participants who had direct combat exposure as compared to those who had not. The interactions of direct combat exposure with depression (B=.004, SE=.040, p=.926), PTSD symptoms (B=.016, SE=.018, p=.382), perceived burdensomeness (B=.159, SE=.152, p=.300) and hopelessness (B=.069, SE=.036, p=.057) were nonsignificant. Although guilt is associated with more severe suicidal ideation in general among military personnel, it is especially pronounced among those who have had direct combat exposure. Copyright © 2013 Elsevier B.V. All rights reserved.

Social Fears and Social Phobia in the United States: Results from the National Comorbidity Survey Replication

PubMed Central

Ruscio, Ayelet Meron; Brown, Timothy A.; Chiu, Wai Tat; Sareen, Jitender; Stein, Murray B.; Kessler, Ronald C.

2008-01-01

Background Despite heightened awareness of the clinical significance of social phobia, information is still lacking about putative subtypes, functional impairment, and treatment-seeking. New epidemiologic data on these topics are presented from the National Comorbidity Survey Replication (NCS-R). Methods The NCS-R is a nationally representative household survey fielded in 2001–2003. The WHO Composite International Diagnostic Interview (CIDI 3.0) was used to assess 14 performance and interactional fears and DSM-IV social phobia. Results The estimated lifetime and 12-month prevalence of social phobia are 12.1% and 7.1%. Performance and interactional fears load onto a single latent factor, and there is little evidence for distinct subtypes based either on the content or number of fears. Social phobia is associated with significant psychiatric comorbidity, role impairment, and treatment-seeking, all of which have a dose-response relationship with number of social fears. However, social phobia is the focus of clinical attention in only about half of cases where treatment is obtained. Among non-comorbid cases, those with the most fears were least likely to receive social phobia treatment. Conclusions Social phobia is a common, under-treated disorder that leads to significant functional impairment. Increasing numbers of social fears are associated with increasingly severe manifestations of the disorder. PMID:17976249

Trajectories of Social Anxiety in Children: Influence of Child Cortisol Reactivity and Parental Social Anxiety.

PubMed

Poole, Kristie L; Van Lieshout, Ryan J; McHolm, Angela E; Cunningham, Charles E; Schmidt, Louis A

2017-12-19

Few studies have examined the interactive effect of intra- and extra-individual vulnerability factors on the trajectory of social anxiety in children. In this study, we examined the joint influence of familial vulnerability (i.e., parental social anxiety) and child biological stress vulnerability (i.e., cortisol reactivity) on trajectories of social anxiety. Children (N = 112 (57 males), M age  = 8.14 years, S.D. = 2.25) were followed over three visits spanning approximately three years. Parental social anxiety was assessed using the Social Phobia and Anxiety Inventory, children's behavior and salivary cortisol reactivity were measured in response to a speech task, and children's social anxiety was assessed at all three visits using the Screen for Child Related Emotional Disorders (SCARED; Parent-report). A growth curve analysis was used to examine trajectories of child social anxiety as predicted by children's cortisol reactivity and parental social anxiety, adjusting for covariates. We found a significant interaction between parental social anxiety and child cortisol reactivity in predicting child social anxiety across time. Having a socially anxious parent coupled with heightened cortisol reactivity predicted the highest levels of child social anxiety, with scores that remained above clinically significant levels for social anxiety across all visits. Children with familial risk for social anxiety and who also exhibit high stress-reactivity appear to be at risk for persistent, clinically significant social anxiety. This highlights the importance of considering the interaction between both biological and contextual factors when considering the development, maintenance, and treatment of social anxiety in children across time.

Interactive wiimote gaze stabilization exercise training system for patients with vestibular hypofunction

PubMed Central

2012-01-01

Background Peripheral vestibular hypofunction is a major cause of dizziness. When complicated with postural imbalance, this condition can lead to an increased incidence of falls. In traditional clinical practice, gaze stabilization exercise is commonly used to rehabilitate patients. In this study, we established a computer-aided vestibular rehabilitation system by coupling infrared LEDs to an infrared receiver. This system enabled the subjects’ head-turning actions to be quantified, and the training was performed using vestibular exercise combined with computer games and interactive video games that simulate daily life activities. Methods Three unilateral and one bilateral vestibular hypofunction patients volunteered to participate in this study. The participants received 30 minutes of computer-aided vestibular rehabilitation training 2 days per week for 6 weeks. Pre-training and post-training assessments were completed, and a follow-up assessment was completed 1 month after the end of the training period. Results After 6 weeks of training, significant improvements in balance and dynamic visual acuity (DVA) were observed in the four participants. Self-reports of dizziness, anxiety and depressed mood all decreased significantly. Significant improvements in self-confidence and physical performance were also observed. The effectiveness of this training was maintained for at least 1 month after the end of the training period. Conclusion Real-time monitoring of training performance can be achieved using this rehabilitation platform. Patients demonstrated a reduction in dizziness symptoms after 6 weeks of training with this short-term interactive game approach. This treatment paradigm also improved the patients’ balance function. This system could provide a convenient, safe and affordable treatment option for clinical practitioners. PMID:23043886

Interactive wiimote gaze stabilization exercise training system for patients with vestibular hypofunction.

PubMed

Chen, Po-Yin; Hsieh, Wan-Ling; Wei, Shun-Hwa; Kao, Chung-Lan

2012-10-09

Peripheral vestibular hypofunction is a major cause of dizziness. When complicated with postural imbalance, this condition can lead to an increased incidence of falls. In traditional clinical practice, gaze stabilization exercise is commonly used to rehabilitate patients. In this study, we established a computer-aided vestibular rehabilitation system by coupling infrared LEDs to an infrared receiver. This system enabled the subjects' head-turning actions to be quantified, and the training was performed using vestibular exercise combined with computer games and interactive video games that simulate daily life activities. Three unilateral and one bilateral vestibular hypofunction patients volunteered to participate in this study. The participants received 30 minutes of computer-aided vestibular rehabilitation training 2 days per week for 6 weeks. Pre-training and post-training assessments were completed, and a follow-up assessment was completed 1 month after the end of the training period. After 6 weeks of training, significant improvements in balance and dynamic visual acuity (DVA) were observed in the four participants. Self-reports of dizziness, anxiety and depressed mood all decreased significantly. Significant improvements in self-confidence and physical performance were also observed. The effectiveness of this training was maintained for at least 1 month after the end of the training period. Real-time monitoring of training performance can be achieved using this rehabilitation platform. Patients demonstrated a reduction in dizziness symptoms after 6 weeks of training with this short-term interactive game approach. This treatment paradigm also improved the patients' balance function. This system could provide a convenient, safe and affordable treatment option for clinical practitioners.

Short-term effects of kinesio taping versus cervical thrust manipulation in patients with mechanical neck pain: a randomized clinical trial.

PubMed

Saavedra-Hernández, Manuel; Castro-Sánchez, Adelaida M; Arroyo-Morales, Manuel; Cleland, Joshua A; Lara-Palomo, Inmaculada C; Fernández-de-Las-Peñas, César

2012-08-01

Randomized clinical trial. To compare the effectiveness of cervical spine thrust manipulation to that of Kinesio Taping applied to the neck in individuals with mechanical neck pain, using self-reported pain and disability and cervical range of motion as measures. The effectiveness of cervical manipulation has received considerable attention in the literature. However, because some patients cannot tolerate cervical thrust manipulation, alternative therapeutic options should be investigated. Eighty patients (36 women) were randomly assigned to 1 of 2 groups: the manipulation group, which received 2 cervical thrust manipulations, and the tape group, which received Kinesio Taping applied to the neck. Neck pain (11-point numeric pain rating scale), disability (Neck Disability Index), and cervical-range-of-motion data were collected at baseline and 1 week after the intervention by an assessor blinded to the treatment allocation of the patients. Mixed-model analyses of variance were used to examine the effects of the treatment on each outcome variable, with group as the between-subjects variable and time as the within-subjects variable. The primary analysis was the group-by-time interaction. No significant group-by-time interactions were found for pain (F = 1.892, P = .447) or disability (F = 0.115, P = .736). The group-by-time interaction was statistically significant for right (F = 7.317, P = .008) and left (F = 9.525, P = .003) cervical rotation range of motion, with the patients who received the cervical thrust manipulation having experienced greater improvement in cervical rotation than those treated with Kinesio Tape (P<.01). No significant group-by-time interactions were found for cervical spine range of motion for flexion (F = 0.944, P = .334), extension (F = 0.122, P = .728), and right (F = 0.220, P = .650) and left (F = 0.389, P = .535) lateral flexion. Patients with mechanical neck pain who received cervical thrust manipulation or Kinesio Taping exhibited similar reductions in neck pain intensity and disability and similar changes in active cervical range of motion, except for rotation. Changes in neck pain surpassed the minimal clinically important difference, whereas changes in disability did not. Changes in cervical range of motion were small and not clinically meaningful. Because we did not include a control or placebo group in this study, we cannot rule out a placebo effect or natural changes over time as potential reasons for the improvements measured in both groups. Therapy, level 1b.

Synchronization within, and interactions between, the default mode and dorsal attention networks in relapsing-remitting multiple sclerosis.

PubMed

Huang, Muhua; Zhou, Fuqing; Wu, Lin; Wang, Bo; Wan, Hui; Li, Fangjun; Zeng, Xianjun; Gong, Honghan

2018-01-01

The effects of the interactions between the default mode network (DMN) and the dorsal attention network (DAN), which present anticorrelated behaviors, in relapsing-remitting multiple sclerosis (RRMS) are poorly understood. This study used resting-state functional connectivity (FC) and the Granger causality test (GCT) to examine changes in the undirected and effective functional network connectivity (FNC) between the two networks during the remitting phase in RRMS patients. Thirty-three patients experiencing a clinically diagnosed remitting phase of RRMS and 33 well-matched healthy control subjects participated in this study. First, an independent component (IC) analysis was performed to preprocess the functional magnetic resonance imaging data and select resting-state networks. Then, an FNC analysis and the GCT were combined to examine the temporal correlations between the ICs of the DMN and DAN and to identify correlations with clinical markers. Compared with the healthy subjects, the RRMS patients in the remitting phase showed the following: 1) significantly decreased FC within the DAN in the postcentral gyrus and decreased FC within the DMN in several regions except the parahippocampal gyrus, where increased FC was observed; 2) a relatively stable interaction between the two anticorrelated networks as well as a driving connectivity from the DAN to DMN (IC15); and 3) significantly positive correlations between the connectivity coefficient of the right superior temporal gyrus and the Modified Fatigue Impact Scale score ( ρ = 0.379, p = 0.036). Adaptive mechanisms that maintain stable interactions might occur between the DMN and DAN during the remitting phase in RRMS patients.

Pharmacokinetic interactions and safety evaluations of coadministered tafenoquine and chloroquine in healthy subjects

PubMed Central

Miller, Ann K; Harrell, Emma; Ye, Li; Baptiste-Brown, Sharon; Kleim, Jőrg-Peter; Ohrt, Colin; Duparc, Stephan; Möhrle, Jörg J; Webster, Alison; Stinnett, Sandra; Hughes, Arlene; Griffith, Sandy; Beelen, Andrew P

2013-01-01

Aims The long-acting 8-aminoquinoline tafenoquine (TQ) coadministered with chloroquine (CQ) may radically cure Plasmodium vivax malaria. Coadministration therapy was evaluated for a pharmacokinetic interaction and for pharmacodynamic, safety and tolerability characteristics. Methods Healthy subjects, 18–55 years old, without documented glucose-6-phosphate dehydrogenase deficiency, received CQ alone (days 1–2, 600 mg; and day 3, 300 mg), TQ alone (days 2 and 3, 450 mg) or coadministration therapy (day 1, CQ 600 mg; day 2, CQ 600 mg + TQ 450 mg; and day 3, CQ 300 mg + TQ 450 mg) in a randomized, double-blind, parallel-group study. Blood samples for pharmacokinetic and pharmacodynamic analyses and safety data, including electrocardiograms, were collected for 56 days. Results The coadministration of CQ + TQ had no effect on TQ AUC0–t, AUC0–∞, Tmax or t1/2. The 90% confidence intervals of CQ + TQ vs. TQ for AUC0–t, AUC0–∞ and t1/2 indicated no drug interaction. On day 2 of CQ + TQ coadministration, TQ Cmax and AUC0–24 increased by 38% (90% confidence interval 1.27, 1.64) and 24% (90% confidence interval 1.04, 1.46), respectively. The pharmacokinetics of CQ and its primary metabolite desethylchloroquine were not affected by TQ. Coadministration had no clinically significant effect on QT intervals and was well tolerated. Conclusions No clinically significant safety or pharmacokinetic/pharmacodynamic interactions were observed with coadministered CQ and TQ in healthy subjects. PMID:23701202

Potential drug interactions and chemotoxicity in older patients with cancer receiving chemotherapy.

PubMed

Popa, Mihaela A; Wallace, Kristie J; Brunello, Antonella; Extermann, Martine; Balducci, Lodovico

2014-07-01

Increased risk of drug interactions due to polypharmacy and aging-related changes in physiology among older patients with cancer is further augmented during chemotherapy. No previous studies examined potential drug interactions (PDIs) from polypharmacy and their association with chemotherapy tolerance in older patients with cancer. This study is a retrospective medical chart review of 244 patients aged 70+ years who received chemotherapy for solid or hematological malignancies. PDI among all drugs, supplements, and herbals taken with the first chemotherapy cycle were screened for using the Drug Interaction Facts software, which classifies PDIs into five levels of clinical significance with level 1 being the highest. Descriptive and correlative statistics were used to describe rates of PDI. The association between PDI and severe chemotoxicity was tested with logistic regressions adjusted for baseline covariates. A total of 769 PDIs were identified in 75.4% patients. Of the 82 level 1 PDIs identified among these, 32 PDIs involved chemotherapeutics. A large proportion of the identified PDIs were of minor clinical significance. The risk of severe non-hematological toxicity almost doubled with each level 1 PDI (OR=1.94, 95% CI: 1.22-3.09), and tripled with each level 1 PDI involving chemotherapeutics (OR=3.08, 95% CI: 1.33-7.12). No association between PDI and hematological toxicity was found. In this convenience sample of older patients with cancer receiving chemotherapy we found notable rates of PDI and a substantial adjusted impact of PDI on risk of non-hematological toxicity. These findings warrant further research to optimize chemotherapy outcomes. Copyright © 2014 Elsevier Inc. All rights reserved.

Valerian: no evidence for clinically relevant interactions.

PubMed

Kelber, Olaf; Nieber, Karen; Kraft, Karin

2014-01-01

In recent popular publications as well as in widely used information websites directed to cancer patients, valerian is claimed to have a potential of adverse interactions with anticancer drugs. This questions its use as a safe replacement for, for example, benzodiazepines. A review on the interaction potential of preparations from valerian root (Valeriana officinalis L. root) was therefore conducted. A data base search and search in a clinical drug interaction data base were conducted. Thereafter, a systematic assessment of publications was performed. Seven in vitro studies on six CYP 450 isoenzymes, on p-glycoprotein, and on two UGT isoenzymes were identified. However, the methodological assessment of these studies did not support their suitability for the prediction of clinically relevant interactions. In addition, clinical studies on various valerian preparations did not reveal any relevant interaction potential concerning CYP 1A2, 2D6, 2E1, and 3A4. Available animal and human pharmacodynamic studies did not verify any interaction potential. The interaction potential of valerian preparations therefore seems to be low and thereby without clinical relevance. We conclude that there is no specific evidence questioning their safety, also in cancer patients.

Valerian: No Evidence for Clinically Relevant Interactions

PubMed Central

Nieber, Karen; Kraft, Karin

2014-01-01

In recent popular publications as well as in widely used information websites directed to cancer patients, valerian is claimed to have a potential of adverse interactions with anticancer drugs. This questions its use as a safe replacement for, for example, benzodiazepines. A review on the interaction potential of preparations from valerian root (Valeriana officinalis L. root) was therefore conducted. A data base search and search in a clinical drug interaction data base were conducted. Thereafter, a systematic assessment of publications was performed. Seven in vitro studies on six CYP 450 isoenzymes, on p-glycoprotein, and on two UGT isoenzymes were identified. However, the methodological assessment of these studies did not support their suitability for the prediction of clinically relevant interactions. In addition, clinical studies on various valerian preparations did not reveal any relevant interaction potential concerning CYP 1A2, 2D6, 2E1, and 3A4. Available animal and human pharmacodynamic studies did not verify any interaction potential. The interaction potential of valerian preparations therefore seems to be low and thereby without clinical relevance. We conclude that there is no specific evidence questioning their safety, also in cancer patients. PMID:25093031

Effects of long-term treatment with angiotensin-converting-enzyme inhibitors in the presence or absence of aspirin: a systematic review.

PubMed

Teo, Koon K; Yusuf, Salim; Pfeffer, Marc; Torp-Pedersen, Christian; Kober, Lars; Hall, Alistair; Pogue, Janice; Latini, Roberto; Collins, Rory

2002-10-05

Results from a retrospective analysis of the Studies of Left Ventricular Dysfunction (SOLVD) study suggest that angiotensin-converting-enzyme (ACE) inhibitors may be less effective in patients receiving aspirin. We aimed to confirm or refute this theory. We used the Peto-Yusuf method to undertake a systematic overview of data for 22060 patients from six long-term randomised trials of ACE inhibitors to assess whether aspirin altered the effects of ACE inhibitor therapy on major clinical outcomes (composite of death, myocardial infarction, stroke, hospital admission for congestive heart failure, or revascularisation). Baseline characteristics, and prognosis in patients allocated placebo, differed strikingly between those who were and were not taking aspirin at baseline. Results from analyses of all trials, except SOLVD, did not suggest any significant differences between the proportional reductions in risk with ACE inhibitor therapy in the presence or absence of aspirin for the major clinical outcomes (p=0.15), or in any of its individual components, except myocardial infarction (interaction p=0.01). Overall, ACE inhibitor therapy significantly reduced the risk of the major clinical outcomes by 22% (p<0.0001), with clear reductions in risk both among those receiving aspirin at baseline (odds ratio 0.80, [99% CI 0.73-0.88]) and those who were not (0.71 [99% CI 0.62-0.81], interaction p=0.07). Considering the totality of evidence on all major vascular outcomes in these trials, there is only weak evidence of any reduction in the benefit of ACE-inhibitor therapy when added to aspirin. However, there is definite evidence of clinically important benefits with respect to these major clinical outcomes with ACE-inhibitor therapy, irrespective of whether concomitant aspirin is used.

Impact of gender-age interaction on the outcome of ischemic stroke in an Italian cohort of patients treated according to a standardized clinical pathway.

PubMed

Denti, Licia; Artoni, Andrea; Scoditti, Umberto; Caminiti, Caterina; Giambanco, Fabiola; Casella, Monica; Ceda, Gian Paolo

2013-12-01

Stroke outcome has been reported as worse in women, especially in terms of disability. As for mortality, the data are conflicting, with some reports suggesting a female advantage. Our objective was to explore such issues in an Italian cohort of patients managed by a standardized clinical pathway (CPW) and, as such, homogeneous in terms of clinical management. Data from a cohort of 1993 patients (987 women and 1006 men) with first-ever ischemic stroke, consecutively referred to an in-hospital Clinical Pathway Program from January 1, 2001 to December 31, 2009, were retrospectively analyzed. The relationship between female gender and one-month outcome was assessed with adjustment for age, stroke severity and premorbid disability. The outcome was worse in women in terms of disability (age-adjusted odds ratio 2.03, 95% CI 1.69-2.46), while no difference was found for mortality. In multivariate models, female gender turned out to be associated with a lower case-fatality rate (adjusted hazard ratio 0.65, 95% CI 0.48-0.89, P=0.007), whereas the odds ratio for disability decreased but remained significant (OR 1.30; 95% CI 1.01-1.69). We found a significant interaction between gender and age in the case-fatality rate, and a female survival advantage was apparent only below 50 years. Our study confirms the excess risk of disability after stroke in women, although it is mostly explained by the occurrence of the most severe clinical syndromes. As for mortality, female gender seems to play a protective role, at least in the short-term and in younger patients. © 2013.

Exergaming and older adult cognition: a cluster randomized clinical trial.

PubMed

Anderson-Hanley, Cay; Arciero, Paul J; Brickman, Adam M; Nimon, Joseph P; Okuma, Naoko; Westen, Sarah C; Merz, Molly E; Pence, Brandt D; Woods, Jeffrey A; Kramer, Arthur F; Zimmerman, Earl A

2012-02-01

Dementia cases may reach 100 million by 2050. Interventions are sought to curb or prevent cognitive decline. Exercise yields cognitive benefits, but few older adults exercise. Virtual reality-enhanced exercise or "exergames" may elicit greater participation. To test the following hypotheses: (1) stationary cycling with virtual reality tours ("cybercycle") will enhance executive function and clinical status more than traditional exercise; (2) exercise effort will explain improvement; and (3) brain-derived neurotrophic growth factor (BDNF) will increase. Multi-site cluster randomized clinical trial (RCT) of the impact of 3 months of cybercycling versus traditional exercise, on cognitive function in older adults. Data were collected in 2008-2010; analyses were conducted in 2010-2011. 102 older adults from eight retirement communities enrolled; 79 were randomized and 63 completed. A recumbent stationary ergometer was utilized; virtual reality tours and competitors were enabled on the cybercycle. Executive function (Color Trails Difference, Stroop C, Digits Backward); clinical status (mild cognitive impairment; MCI); exercise effort/fitness; and plasma BDNF. Intent-to-treat analyses, controlling for age, education, and cluster randomization, revealed a significant group X time interaction for composite executive function (p=0.002). Cybercycling yielded a medium effect over traditional exercise (d=0.50). Cybercyclists had a 23% relative risk reduction in clinical progression to MCI. Exercise effort and fitness were comparable, suggesting another underlying mechanism. A significant group X time interaction for BDNF (p=0.05) indicated enhanced neuroplasticity among cybercyclists. Cybercycling older adults achieved better cognitive function than traditional exercisers, for the same effort, suggesting that simultaneous cognitive and physical exercise has greater potential for preventing cognitive decline. This study is registered at Clinicaltrials.gov NCT01167400. Copyright © 2012 American Journal of Preventive Medicine. Published by Elsevier Inc. All rights reserved.

Stressful Life Events in a Clinical Sample of Depressed Children in Hungary

PubMed Central

Mayer, László; Lopez-Duran, Nestor L.; Kovacs, Maria; George, Charles; Baji, Ildikó; Kapornai, Krisztina; Kiss, Enikő; Vetró, Ágnes

2009-01-01

Background There is limited information on the characteristics of stressful life events in depressed pediatric clinical populations and the extent to which sex, age, and their interactions may influence the relations of life events and depression. Using a very large clinical sample of children and adolescents with major depressive disorder (MDD), we therefore examined life events in various ways as well as their relations to age and sex. Method The study included a clinic-based sample of 434 children (ages 7–14) with a DSM-IV diagnosis of MDD and their mothers, and a school-based comparison sample of 724 children and their mothers. Life event information was obtained from the mothers. Results Children with MDD had twice the number of lifetime stressful events than did the comparison group, with very high levels of stressors by the age of 7–9 that stabilized across adolescence. In contrast, the comparison sample experienced a gradual increase in stressful life events as a function of age up to mid-adolescence. Parental health events, death of close relatives, and intra-familial events were significantly associated with MDD diagnosis. There were significantly stronger associations between parental health- as well as death-event clusters and MDD diagnosis among younger children than adolescents. Limitations Geographical differences between the clinical and comparison samples, as well as possible parental reporting biases may affect the generalizability of these findings. Conclusion The association between some stressful life events and MDD seems to be moderated by age, underscoring the need to examine specific events, as well as clusters of events. Better understanding of such interactions may facilitate early identification of possible risk factors for pediatric MDD. PMID:18845343

Stressful life events in a clinical sample of depressed children in Hungary.

PubMed

Mayer, László; Lopez-Duran, Nestor L; Kovacs, Maria; George, Charles J; Baji, Ildikó; Kapornai, Krisztina; Kiss, Eniko; Vetró, Agnes

2009-05-01

There is limited information on the characteristics of stressful life events in depressed pediatric clinical populations and the extent to which sex, age, and their interactions may influence the relations of life events and depression. Using a very large clinical sample of children and adolescents with major depressive disorder (MDD), we therefore examined life events in various ways, as well as their relations to age and sex. The study included a clinic-based sample of 434 children (ages 7-14) with a DSM-IV diagnosis of MDD and their mothers, and a school-based comparison sample of 724 children and their mothers. Life event information was obtained from the mothers. Children with MDD had twice the number of lifetime stressful events than did the comparison group, with very high levels of stressors by the age of 7-9 that stabilized across adolescence. In contrast, the comparison sample experienced a gradual increase in stressful life events as a function of age up to mid-adolescence. Parental health events, death of close relatives, and intrafamilial events were significantly associated with MDD diagnosis. There were significantly stronger associations between parental health- as well as death-event clusters and MDD diagnosis among younger children than adolescents. Geographical differences between the clinical and comparison samples, as well as possible parental reporting biases may affect the generalizability of these findings. The association between some stressful life events and MDD seems to be moderated by age, underscoring the need to examine specific events, as well as clusters of events. Better understanding of such interactions may facilitate early identification of possible risk factors for pediatric MDD.

Association of lung function genes with chronic obstructive pulmonary disease.

PubMed

Kim, Woo Jin; Lim, Myoung Nam; Hong, Yoonki; Silverman, Edwin K; Lee, Ji-Hyun; Jung, Bock Hyun; Ra, Seung Won; Choi, Hye Sook; Jung, Young Ju; Park, Yong Bum; Park, Myung Jae; Lee, Sei Won; Lee, Jae Seung; Oh, Yeon-Mok; Lee, Sang Do

2014-08-01

Spirometric measurements of pulmonary function are important in diagnosing and determining the severity of chronic obstructive pulmonary disease (COPD). We performed this study to determine whether candidate genes identified in genome-wide association studies of spirometric measurements were associated with COPD and if they interacted with smoking intensity. The current analysis included 1,000 COPD subjects and 1,000 controls recruited from 24 hospital-based pulmonary clinics. Thirteen SNPs, chosen based on genome-wide association studies of spirometric measurements in the Korean population cohorts, were genotyped. Genetic association tests were performed, adjusting for age, sex, and smoking intensity, using models including a SNP-by-smoking interaction term. PID1 and FAM13A were significantly associated with COPD susceptibility. There were also significant interactions between SNPs in ACN9 and FAM13A and smoking pack-years, and an association of ACN9 with COPD in the lowest smoking tertile. The risk allele of FAM13A was associated with increased expression of FAM13A in the lung. We have validated associations of FAM13A and PID1 with COPD. ACN9 showed significant interaction with smoking and is a potential candidate gene for COPD. Significant associations of genetic variants of FAM13A with gene expression levels suggest that the associated loci may act as genetic regulatory elements for FAM13A gene expression.

Prevalence and Clinical Significance of Diabetes in Asian Versus White Patients With Heart Failure.

PubMed

Bank, Ingrid E M; Gijsberts, Crystel M; Teng, Tiew-Hwa K; Benson, Lina; Sim, David; Yeo, Poh Shuan Daniel; Ong, Hean Yee; Jaufeerally, Fazlur; Leong, Gerard K T; Ling, Lieng H; Richards, A Mark; de Kleijn, Dominique P V; Dahlström, Ulf; Lund, Lars H; Lam, Carolyn S P

2017-01-01

The study sought to compare the prevalence, clinical correlates and prognostic impact of diabetes in Southeast Asian versus white patients with heart failure (HF) with preserved or reduced ejection fraction. Diabetes mellitus is common in HF and is associated with impaired prognosis. Asia is home to the majority of the world's diabetic population, yet data on the prevalence and clinical significance of diabetes in Asian patients with HF are sparse, and no studies have directly compared Asian and white patients. Two contemporary population-based HF cohorts were combined: from Singapore (n = 1,002, median [25th to 75th percentile] age 62 [54 to 70] years, 76% men, 19.5% obesity) and Sweden (n = 19,537, 77 [68 to 84] years, 60% men, 24.8% obesity). The modifying effect of ethnicity on the relationship between diabetes and clinical correlates or prognosis (HF hospitalization and all-cause mortality) was examined using interaction terms. Diabetes was present in 569 (57%) Asian patients versus 4,680 (24%) white patients (p < 0.001). Adjusting for clinical covariates, obesity was more strongly associated with diabetes in white patients (odds ratio [OR]: 3.45; 95% confidence interval [CI]: 2.86 to 4.17) than in Asian patients (OR: 1.82; 95% CI: 1.13 to 2.96; p interaction  = 0.026). Diabetes was more strongly associated with increased HF hospitalization and all-cause mortality in Asian patients (hazard ratio: 1.50; 95% CI: 1.21 to 1.87) than in white patients (hazard ratio: 1.29; 95% CI: 1.22 to 1.36; p interaction  = 0.045). Diabetes was 3-fold more common in Southeast Asian compared to white patients with HF, despite younger age and less obesity, and more strongly associated with poor outcomes in Asian patients than white patients. These results underscore the importance of ethnicity-tailored aggressive strategies to prevent diabetes and its complications. Copyright © 2017 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.

Neuropsychological deficits associated with heavy prenatal alcohol exposure are not exacerbated by ADHD.

PubMed

Glass, Leila; Ware, Ashley L; Crocker, Nicole; Deweese, Benjamin N; Coles, Claire D; Kable, Julie A; May, Philip A; Kalberg, Wendy O; Sowell, Elizabeth R; Jones, Kenneth Lyons; Riley, Edward P; Mattson, Sarah N

2013-11-01

Neuropsychological functioning of individuals with attention-deficit/hyperactivity disorder (ADHD) or heavy prenatal alcohol exposure has been well documented independently. This study examined the interaction between both factors on cognitive performance in children. As part of a multisite study, 344 children (8-16 y, M = 12.28, SD = 2.52) completed a comprehensive neuropsychological battery. Four subject groups were tested: children with histories of heavy prenatal alcohol exposure (AE) and ADHD (AE+, n = 90), alcohol-exposed without ADHD, (AE-, n = 38), nonexposed with ADHD (ADHD, n = 80), and nonexposed without ADHD (CON, n = 136). Separate 2(AE) × 2(ADHD) MANCOVAs revealed significant main and interactive effects of ADHD and AE on overall WISC-IV, D-KEFS, and CANTAB performance. Individual ANOVAs revealed significant interactions on 2 WISC-IV indices [Verbal Comprehension (VCI), Perceptual Reasoning (PRI)], and four D-KEFS and CANTAB subtests [Design Fluency, Verbal Fluency, Trail Making, Spatial Working Memory]. Follow-up analyses demonstrated no difference between AE+ and AE- groups on these measures. The combined AE+/- group demonstrated more severe impairment than the ADHD group on VCI and PRI, but there were no other differences between clinical groups. These results support a combined AE+/- group for neuropsychological research and indicate that, in some cases, the neuropsychological effects seen in ADHD are altered by prenatal alcohol exposure. The effects of alcohol exposure on verbal comprehension and perceptual reasoning were greater than those related to having ADHD without alcohol exposure, although both conditions independently resulted in cognitive impairment compared to controls. Clinically, these findings demonstrate task-dependent patterns of impairment across clinical disorders. PsycINFO Database Record (c) 2013 APA, all rights reserved.

Interactive cervical motion kinematics: sensitivity, specificity and clinically significant values for identifying kinematic impairments in patients with chronic neck pain.

PubMed

Sarig Bahat, Hilla; Chen, Xiaoqi; Reznik, David; Kodesh, Einat; Treleaven, Julia

2015-04-01

Chronic neck pain has been consistently shown to be associated with impaired kinematic control including reduced range, velocity and smoothness of cervical motion, that seem relevant to daily function as in quick neck motion in response to surrounding stimuli. The objectives of this study were: to compare interactive cervical kinematics in patients with neck pain and controls; to explore the new measures of cervical motion accuracy; and to find the sensitivity, specificity, and optimal cutoff values for defining impaired kinematics in those with neck pain. In this cross-section study, 33 patients with chronic neck pain and 22 asymptomatic controls were assessed for their cervical kinematic control using interactive virtual reality hardware and customized software utilizing a head mounted display with built-in head tracking. Outcome measures included peak and mean velocity, smoothness (represented by number of velocity peaks (NVP)), symmetry (represented by time to peak velocity percentage (TTPP)), and accuracy of cervical motion. Results demonstrated significant and strong effect-size differences in peak and mean velocities, NVP and TTPP in all directions excluding TTPP in left rotation, and good effect-size group differences in 5/8 accuracy measures. Regression results emphasized the high clinical value of neck motion velocity, with very high sensitivity and specificity (85%-100%), followed by motion smoothness, symmetry and accuracy. These finding suggest cervical kinematics should be evaluated clinically, and screened by the provided cut off values for identification of relevant impairments in those with neck pain. Such identification of presence or absence of kinematic impairments may direct treatment strategies and additional evaluation when needed. Copyright © 2014 Elsevier Ltd. All rights reserved.

Simultaneous Assessment of Transporter-Mediated Drug-Drug Interactions Using a Probe Drug Cocktail in Cynomolgus Monkey.

PubMed

Kosa, Rachel E; Lazzaro, Sarah; Bi, Yi-An; Tierney, Brendan; Gates, Dana; Modi, Sweta; Costales, Chester; Rodrigues, A David; Tremaine, Larry M; Varma, Manthena V

2018-06-07

We aim to establish an in vivo preclinical model to enable simultaneous assessment of inhibition potential of an investigational drug on clinically relevant drug transporters, organic anion transporting polypeptide (OATP)1B, breast cancer resistance protein (BCRP), P-glycoprotein (P-gp) and organic anion transporter (OAT)3. Pharmacokinetics of substrate cocktail consisting of pitavastatin (OATP1B substrate), rosuvastatin (OATP1B/BCRP/OAT3), sulfasalazine (BCRP) and talinolol (P-gp) were obtained in cynomolgus monkey - alone or in combination with transporter inhibitors. Single dose rifampicin (30 mg/kg) significantly (p<0.01) increased the plasma exposure of all four drugs, with a marked effect on pitavastatin and rosuvastatin (AUC ratio ~21-39). Elacridar, BCRP/P-gp inhibitor, increased the AUC of sulfasalazine, talinolol, as well as rosuvastatin and pitavastatin. An OAT1/3 inhibitor (probenecid) significantly (p<0.05) impacted the renal clearance of rosuvastatin (~8-fold). In vitro, rifampicin (10μM) inhibited uptake of pitavastatin, rosuvastatin and sulfasalazine by monkey and human primary hepatocytes. Transport studies using membrane vesicles suggested that all probe substrates, except talinolol, are transported by cynoBCRP; while talinolol is a cynoP-gp substrate. Elacridar and rifampicin inhibited both cynoBCRP and cynoP-gp in vitro, indicating potential for in vivo intestinal efflux inhibition. In conclusion, a probe substrate cocktail was validated to simultaneously evaluate perpetrator impact on multiple clinically relevant transporters using the cynomolgus monkey. The results support the use of the cynomolgus monkey as a model that could enable drug-drug interaction risk assessment, before advancing a new molecular entity into clinical development, as well as providing mechanistic insights on transporter-mediated interactions. The American Society for Pharmacology and Experimental Therapeutics.

Azathioprine-Induced Warfarin Resistance

PubMed Central

Vazquez, Sara R; Rondina, Matthew T; Pendleton, Robert C

2011-01-01

OBJECTIVE To describe a case of azathioprine-induced warfarin resistance, present a literature review on warfarin–azathioprine interactions, and provide recommendations on appropriate management of this clinically significant interaction. CASE SUMMARY A 29-year-old female with Cogan’s syndrome experienced thrombosis of the left internal carotid artery. She was treated with an average weekly warfarin dose of 39 mg (5.5 mg daily) prior to beginning azathioprine therapy. Three weeks following initiation of azathioprine 150 mg daily, the international normalized ratio (INR) decreased from 1.9 (prior to the medication change) to 1.0 without any change in the warfarin dose or other relevant factors. Over several weeks, the patient’s warfarin dose was titrated up to 112 mg weekly (16 mg daily) to achieve an INR of 2.5 (a 188%, or 2.9-fold dose increase). Because of elevated liver enzyme levels, the azathioprine dosage was decreased to 100 mg daily. Within 2 weeks following that decrease, warfarin requirements decreased to 105 mg weekly (15 mg daily). DISCUSSION Azathioprine was the probable causative agent of warfarin resistance according to the Naranjo probability scale, and a possible causative agent according to the Drug Interaction Probability Scale. A literature search (PubMed, 1966–December 2007) revealed 8 case reports of this drug interaction and 2 cases involving a similar effect with 6-mercaptopurine, the active metabolite of azathioprine. The exact mechanism of the interaction remains unknown. Previously published case reports point to a rapid onset and offset of the warfarin–azathioprine interaction and a dose-dependent increase of at least 2.5-fold in warfarin dose requirement with the initiation of azathioprine 75–200 mg daily. CONCLUSIONS This case report and several others point toward azathioprine as a clinically significant inducer of warfarin resistance. Providers should anticipate the need for higher warfarin doses, warfarin dose adjustment, and close INR monitoring in patients receiving azathioprine or its active metabolite, 6-mercaptopurine. PMID:18505911

Clinical analysis of genome next-generation sequencing data using the Omicia platform

PubMed Central

Coonrod, Emily M; Margraf, Rebecca L; Russell, Archie; Voelkerding, Karl V; Reese, Martin G

2013-01-01

Aims Next-generation sequencing is being implemented in the clinical laboratory environment for the purposes of candidate causal variant discovery in patients affected with a variety of genetic disorders. The successful implementation of this technology for diagnosing genetic disorders requires a rapid, user-friendly method to annotate variants and generate short lists of clinically relevant variants of interest. This report describes Omicia’s Opal platform, a new software tool designed for variant discovery and interpretation in a clinical laboratory environment. The software allows clinical scientists to process, analyze, interpret and report on personal genome files. Materials & Methods To demonstrate the software, the authors describe the interactive use of the system for the rapid discovery of disease-causing variants using three cases. Results & Conclusion Here, the authors show the features of the Opal system and their use in uncovering variants of clinical significance. PMID:23895124

Interaction effects among IFN-γ+874, IL-2-330, IL-10-1082, IL-10-592 and IL-4-589 polymorphisms on the clinical progression of subjects infected with hepatitis B virus and/or hepatitis C virus: a retrospective nested case–control study

PubMed Central

Gao, Qiu-Ju; Xie, Jia-Xin; Wang, Li-Min; Zhou, Qiang; Zhang, Shi-Yong

2017-01-01

Background The natural outcomes of hepatitis B virus (HBV) and/or hepatitis C virus (HCV) infections vary considerably among individuals The infection may heal naturally, or patients may succumb to chronic liver diseases, including chronic hepatitis, liver cirrhosis and hepatocellular carcinoma. The mechanism is not fully understood. Objectives To evaluate the interaction among four single nucleotide polymorphisms (SNPs) and their influence on different clinical outcomes. Methods 277 individuals infected with HBV and/or HCV, including 81 patients with chronic hepatitis B and C, 122 asymptomatic HBV and/or HCV carriers and 74 controls who cleared HBV and HCV spontaneously, were involved in this study. The SNPs of four genes (rs2069762/−330 G/T of IL-2, rs2430561/+874A>T of IFN-γ, rs1800896/−1082G>A and rs1800872/−592C>A of IL-10 and rs2243250/−589C>T of IL-4) were analysed using restriction fragment length polymorphism-polymerase chain reaction or sequence-specific primer PCR. The gene–gene interactions were assessed using the multifactor-dimensionality reduction method. Results Interleukin (IL)-10-592 AC and IL-4-589 CC/CT showed a synergistic effect on liver inflammatory injury (p<0.01), whereas interferon (IFN)-γ+874  AA and IL-2-330 TT had a synergistic impact (p<0.05). IFN-γ+874  AA and IL-10-1082 AA had an antagonistic effect (p<0.01) on the clinical progression, including asymptomatic HBV and HCV carriers and chronic hepatitis. IL-2-330 TT and IL-10-1082 AA synergistically influenced the clinical outcome (p<0.05). IFN-γ+874 AA, IL-2-330 TT and IL-10-1082 AA interactively affected the clinical outcome including asymptomatic HBV and HCV carriers and chronic hepatitis (p<0.05). Conclusions Interactions among polymorphisms of IFN-γ+874 AA, IL-2-330 TT, IL-10-1082 AA, IL10-−592 AC and IL-4-589 CC/CT significantly influenced the clinical progression of the subjects with HBV and/or HCV infection. PMID:28838891

Interaction effects among IFN-γ+874, IL-2-330, IL-10-1082, IL-10-592 and IL-4-589 polymorphisms on the clinical progression of subjects infected with hepatitis B virus and/or hepatitis C virus: a retrospective nested case-control study.

PubMed

Gao, Qiu-Ju; Xie, Jia-Xin; Wang, Li-Min; Zhou, Qiang; Zhang, Shi-Yong

2017-08-23

The natural outcomes of hepatitis B virus (HBV) and/or hepatitis C virus (HCV) infections vary considerably among individuals The infection may heal naturally, or patients may succumb to chronic liver diseases, including chronic hepatitis, liver cirrhosis and hepatocellular carcinoma. The mechanism is not fully understood. To evaluate the interaction among four single nucleotide polymorphisms (SNPs) and their influence on different clinical outcomes. 277 individuals infected with HBV and/or HCV, including 81 patients with chronic hepatitis B and C, 122 asymptomatic HBV and/or HCV carriers and 74 controls who cleared HBV and HCV spontaneously, were involved in this study. The SNPs of four genes ( rs2069762/-330 G/T of IL-2 , rs2430561/+874A>T of IFN-γ, rs1800896/-1082G>A  and rs1800872/-592C>A of IL-10 and rs2243250/ -589 C>T of IL-4 ) were analysed using restriction fragment length polymorphism-polymerase chain reaction or sequence-specific primer PCR. The gene-gene interactions were assessed using the multifactor-dimensionality reduction method. Interleukin (IL)-10-592 AC and IL-4-589 CC/CT showed a synergistic effect on liver inflammatory injury (p<0.01), whereas interferon (IFN)-γ+874  AA and IL-2-330 TT had a synergistic impact (p<0.05). IFN-γ+874  AA and IL-10-1082 AA had an antagonistic effect (p<0.01) on the clinical progression, including asymptomatic HBV and HCV carriers and chronic hepatitis. IL-2-330 TT and IL-10-1082 AA synergistically influenced the clinical outcome (p<0.05). IFN-γ+874 AA, IL-2-330 TT and IL-10-1082 AA interactively affected the clinical outcome including asymptomatic HBV and HCV carriers and chronic hepatitis (p<0.05). Interactions among polymorphisms of IFN-γ+874 AA, IL-2-330 TT, IL-10-1082 AA, IL10--592 AC and IL-4-589 CC/CT significantly influenced the clinical progression of the subjects with HBV and/or HCV infection. © Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2017. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

Genetic interactions within inositol-related pathways are associated with longitudinal changes in ventricle size

PubMed Central

Koran, Mary Ellen I.; Hohman, Timothy J.; Meda, Shashwath A.; Thornton-Wells, Tricia A.

2013-01-01

The genetic etiology of late onset Alzheimer disease (LOAD) has proven complex, involving clinical and genetic heterogeneity and gene-gene interactions. Recent genome wide association studies (GWAS) in LOAD have led to the discovery of novel genetic risk factors; however, the investigation of gene-gene interactions has been limited. Conventional genetic studies often use binary disease status as the primary phenotype, but for complex brain-based diseases, neuroimaging data can serve as quantitative endophenotypes that correlate with disease status and closely reflect pathological changes. In the Alzheimer's Disease Neuroimaging Initiative (ADNI) cohort, we tested for association of genetic interactions with longitudinal MRI measurements of the inferior lateral ventricles (ILVs), which have repeatedly shown a relationship to LOAD status and progression. We performed linear regression to evaluate the ability of pathway-derived SNP-SNP pairs to predict the slope of change in volume of the ILVs. After Bonferroni correction, we identified four significant interactions in the right ILV (RILV) corresponding to gene-gene pairs SYNJ2-PI4KA, PARD3-MYH2, PDE3A-ABHD12B and OR2L13-PRKG1 and one significant interaction in the left ILV (LILV) corresponding to SYNJ2-PI4KA. The SNP-SNP interaction corresponding to SYNJ2-PI4KA was identical in the RILV and LILV and was the most significant interaction in each (RILV: p=9.10×10−12; LILV: p=8.20×10−13). Both genes belong to the inositol phosphate signaling pathway which has been previously associated with neurodegeneration in AD and we discuss the possibility that perturbation of this pathway results in a down-regulation of the Akt cell survival pathway and, thereby, decreased neuronal survival, as reflected by increased volume of the ventricles. PMID:24077433

Talk in Interaction in the Speech-Language Pathology Clinic: Bringing Theory to Practice through Discourse

ERIC Educational Resources Information Center

Leaby, Margaret M.; Walsh, Irene P.

2008-01-01

The importance of learning about and applying clinical discourse analysis to enhance the talk in interaction in the speech-language pathology clinic is discussed. The benefits of analyzing clinical discourse to explicate therapy dynamics are described.

A method for developing standardised interactive education for complex clinical guidelines

PubMed Central

2012-01-01

Background Although systematic use of the Perinatal Society of Australia and New Zealand internationally endorsed Clinical Practice Guideline for Perinatal Mortality (PSANZ-CPG) improves health outcomes, implementation is inadequate. Its complexity is a feature known to be associated with non-compliance. Interactive education is effective as a guideline implementation strategy, but lacks an agreed definition. SCORPIO is an educational framework containing interactive and didactic teaching, but has not previously been used to implement guidelines. Our aim was to transform the PSANZ-CPG into an education workshop to develop quality standardised interactive education acceptable to participants for learning skills in collaborative interprofessional care. Methods The workshop was developed using the construct of an educational framework (SCORPIO), the PSANZ-CPG, a transformation process and tutor training. After a pilot workshop with key target and stakeholder groups, modifications were made to this and subsequent workshops based on multisource written observations from interprofessional participants, tutors and an independent educator. This participatory action research process was used to monitor acceptability and educational standards. Standardised interactive education was defined as the attainment of content and teaching standards. Quantitative analysis of positive expressed as a percentage of total feedback was used to derive a total quality score. Results Eight workshops were held with 181 participants and 15 different tutors. Five versions resulted from the action research methodology. Thematic analysis of multisource observations identified eight recurring education themes or quality domains used for standardisation. The two content domains were curriculum and alignment with the guideline and the six teaching domains; overload, timing, didacticism, relevance, reproducibility and participant engagement. Engagement was the most challenging theme to resolve. Tutors identified all themes for revision whilst participants identified a number of teaching but no content themes. From version 1 to 5, a significant increasing trend in total quality score was obtained; participants: 55%, p=0.0001; educator: 42%, p=0.0004; tutor peers: 57%, p=0.0001. Conclusions Complex clinical guidelines can be developed into a workshop acceptable to interprofessional participants. Eight quality domains provide a framework to standardise interactive teaching for complex clinical guidelines. Tutor peer review is important for content validity. This methodology may be useful for other guideline implementation. PMID:23131137

A method for developing standardised interactive education for complex clinical guidelines.

PubMed

Vaughan, Janet I; Jeffery, Heather E; Raynes-Greenow, Camille; Gordon, Adrienne; Hirst, Jane; Hill, David A; Arbuckle, Susan

2012-11-06

Although systematic use of the Perinatal Society of Australia and New Zealand internationally endorsed Clinical Practice Guideline for Perinatal Mortality (PSANZ-CPG) improves health outcomes, implementation is inadequate. Its complexity is a feature known to be associated with non-compliance. Interactive education is effective as a guideline implementation strategy, but lacks an agreed definition. SCORPIO is an educational framework containing interactive and didactic teaching, but has not previously been used to implement guidelines. Our aim was to transform the PSANZ-CPG into an education workshop to develop quality standardised interactive education acceptable to participants for learning skills in collaborative interprofessional care. The workshop was developed using the construct of an educational framework (SCORPIO), the PSANZ-CPG, a transformation process and tutor training. After a pilot workshop with key target and stakeholder groups, modifications were made to this and subsequent workshops based on multisource written observations from interprofessional participants, tutors and an independent educator. This participatory action research process was used to monitor acceptability and educational standards. Standardised interactive education was defined as the attainment of content and teaching standards. Quantitative analysis of positive expressed as a percentage of total feedback was used to derive a total quality score. Eight workshops were held with 181 participants and 15 different tutors. Five versions resulted from the action research methodology. Thematic analysis of multisource observations identified eight recurring education themes or quality domains used for standardisation. The two content domains were curriculum and alignment with the guideline and the six teaching domains; overload, timing, didacticism, relevance, reproducibility and participant engagement. Engagement was the most challenging theme to resolve. Tutors identified all themes for revision whilst participants identified a number of teaching but no content themes. From version 1 to 5, a significant increasing trend in total quality score was obtained; participants: 55%, p=0.0001; educator: 42%, p=0.0004; tutor peers: 57%, p=0.0001. Complex clinical guidelines can be developed into a workshop acceptable to interprofessional participants. Eight quality domains provide a framework to standardise interactive teaching for complex clinical guidelines. Tutor peer review is important for content validity. This methodology may be useful for other guideline implementation.

Development and initial evaluation of a treatment decision dashboard.

PubMed

Dolan, James G; Veazie, Peter J; Russ, Ann J

2013-04-21

For many healthcare decisions, multiple alternatives are available with different combinations of advantages and disadvantages across several important dimensions. The complexity of current healthcare decisions thus presents a significant barrier to informed decision making, a key element of patient-centered care.Interactive decision dashboards were developed to facilitate decision making in Management, a field marked by similarly complicated choices. These dashboards utilize data visualization techniques to reduce the cognitive effort needed to evaluate decision alternatives and a non-linear flow of information that enables users to review information in a self-directed fashion. Theoretically, both of these features should facilitate informed decision making by increasing user engagement with and understanding of the decision at hand. We sought to determine if the interactive decision dashboard format can be successfully adapted to create a clinically realistic prototype patient decision aid suitable for further evaluation and refinement. We created a computerized, interactive clinical decision dashboard and performed a pilot test of its clinical feasibility and acceptability using a multi-method analysis. The dashboard summarized information about the effectiveness, risks of side effects and drug-drug interactions, out-of-pocket costs, and ease of use of nine analgesic treatment options for knee osteoarthritis. Outcome evaluations included observations of how study participants utilized the dashboard, questionnaires to assess usability, acceptability, and decisional conflict, and an open-ended qualitative analysis. The study sample consisted of 25 volunteers - 7 men and 18 women - with an average age of 51 years. The mean time spent interacting with the dashboard was 4.6 minutes. Mean evaluation scores on scales ranging from 1 (low) to 7 (high) were: mechanical ease of use 6.1, cognitive ease of use 6.2, emotional difficulty 2.7, decision-aiding effectiveness 5.9, clarification of values 6.5, reduction in decisional uncertainty 6.1, and provision of decision-related information 6.0. Qualitative findings were similarly positive. Interactive decision dashboards can be adapted for clinical use and have the potential to foster informed decision making. Additional research is warranted to more rigorously test the effectiveness and efficiency of patient decision dashboards for supporting informed decision making and other aspects of patient-centered care, including shared decision making.

Sex differences in mortality following acute coronary syndromes.

PubMed

Berger, Jeffrey S; Elliott, Laine; Gallup, Dianne; Roe, Matthew; Granger, Christopher B; Armstrong, Paul W; Simes, R John; White, Harvey D; Van de Werf, Frans; Topol, Eric J; Hochman, Judith S; Newby, L Kristin; Harrington, Robert A; Califf, Robert M; Becker, Richard C; Douglas, Pamela S

2009-08-26

Conflicting information exists about whether sex differences modulate short-term mortality following acute coronary syndromes (ACS). To investigate the relationship between sex and 30-day mortality in ACS, and to determine whether this relationship was modified by clinical syndrome or coronary anatomy using a large database across the spectrum of ACS and adjusting for potentially confounding clinical covariates. A convenience sample of patients pooled from 11 independent, international, randomized ACS clinical trials between 1993 and 2006 whose databases are maintained at the Duke Clinical Research Institute, Durham, North Carolina. Of 136 247 patients, 38 048 (28%) were women; 102 004 (26% women) with ST-segment elevation myocardial infarction (STEMI), 14 466 (29% women) with non-STEMI (NSTEMI), and 19 777 (40% women) with unstable angina. Thirty-day mortality following ACS. Thirty-day mortality was 9.6% in women and 5.3% in men (odds ratio [OR], 1.91; 95% confidence interval [CI], 1.83-2.00). After multivariable adjustment, mortality was not significantly different between women and men (adjusted OR, 1.06; 95% CI, 0.99-1.15). A significant sex by type of ACS interaction was demonstrated (P < .001). In STEMI, 30-day mortality was higher among women (adjusted OR, 1.15; 95% CI, 1.06-1.24), whereas in NSTEMI (adjusted OR, 0.77; 95% CI, 0.63-0.95) and unstable angina, mortality was lower among women (adjusted OR, 0.55; 95% CI, 0.43-0.70). In a cohort of 35 128 patients with angiographic data, women more often had nonobstructive (15% vs 8%) and less often had 2-vessel (25% vs 28%) and 3-vessel (23% vs 26%) coronary disease, regardless of ACS type. After additional adjustment for angiographic disease severity, 30-day mortality among women was not significantly different than men, regardless of ACS type. The relationship between sex and 30-day mortality was similar across the levels of angiographic disease severity (P for interaction = .70). Sex-based differences existed in 30-day mortality among patients with ACS and vary depending on clinical presentation. However, these differences appear to be largely explained by clinical differences at presentation and severity of angiographically documented disease.

Interaction of CYP2C19, P2Y12, and GPIIIa Variants Associates With Efficacy of Clopidogrel and Adverse Events on Patients With Ischemic Stroke.

PubMed

Yi, Xingyang; Wang, Yanfen; Lin, Jing; Cheng, Wen; Zhou, Qiang; Wang, Chun

2017-10-01

Clopidogrel is a clinically important oral antiplatelet agent for the treatment or prevention of cerebrovascular disease. However, different individuals have different sensitivities to clopidogrel. This study assessed variants of different genes for association with response to clopidogrel, clinical outcome, and side effects in patients with ischemic stroke (IS). We consecutively enrolled 375 patients with IS after they received clopidogrel therapy, and venous blood samples were subjected to genotyping allelic variants of genes modulating clopidogrel absorption (ATP binding cassette subfamily B1, ABCB1), metabolic activation (cytochrome P450[CYP] 3A and CYP2C19), and biologic activity (platelet membrane receptor [ P2Y12, P2Y1)], and glycoprotein IIIa [ GPIIIa]) and statistically analyzing their interactions with clopidogrel sensitivity (CS) and adverse events, risk of IS recurrence, myocardial infarction, and death during 6 months of follow-up. Adverse events occurred in 37 patients (31 had IS recurrence, 4 died, and 2 had myocardial infarction) during the first 6 months of follow-up. Single locus analysis showed that only the CYP2C19*2(rs4244285) variant was independently associated with CS and risk of adverse events after adjusting covariates. However, there was significant gene-gene interaction among CYP2C19*2(rs4244285), P2Y12(rs16863323), and GPIIIa (rs2317676) analyzed by generalized multifactor dimensionality reduction methods. The rate of adverse events among patients with the 3-loci interaction was 2.82 times the rate among those with no interaction (95% confidence interval: 2.04-8.63). Sensitivity of patients with IS to clopidogrel and clopidogrel-induced adverse clinical events may be multifactorial but is not determined by single gene polymorphisms.

Shared polymorphisms and modifiable behavior factors for myocardial infarction and high cholesterol in a retrospective population study

PubMed Central

Liang, Yulan; Kelemen, Arpad

2017-01-01

Abstract Genetic and environmental (behavior, clinical, and demographic) factors are associated with increased risks of both myocardial infarction (MI) and high cholesterol (HC). It is known that HC is major risk factor that may cause MI. However, whether there are common single nucleotide polymorphism (SNPs) associated with both MI and HC is not firmly established, and whether there are modulate and modified effects (interactions of genetic and known environmental factors) on either HC or MI, and whether these joint effects improve the predictions of MI, is understudied. The purpose of this study is to identify novel shared SNPs and modifiable environmental factors on MI and HC. We assess whether SNPs from a metabolic pathway related to MI may relate to HC; whether there are moderate effects among SNPs, lifestyle (smoke and drinking), HC, and MI after controlling other factors [gender, body mass index (BMI), and hypertension (HTN)]; and evaluate prediction power of the joint and modulate genetic and environmental factors influencing the MI and HC. This is a retrospective study with residents of Erie and Niagara counties in New York with a history of MI or with no history of MI. The data set includes environmental variables (demographic, clinical, lifestyle). Thirty-one tagSNPs from a metabolic pathway related to MI are genotyped. Generalized linear models (GLMs) with imputation-based analysis are conducted for examining the common effects of tagSNPs and environmental exposures and their interactions on having a history of HC or MI. MI, BMI, and HTN are significant risk factors for HC. HC shows the strongest effect on risk of MI in addition to HTN; gender and smoking status while drinking status shows protective effect on MI. rs16944 (gene IL-1β) and rs17222772 (gene ALOX) increase the risks of HC, while rs17231896 (gene CETP) has protective effects on HC either with or without the clinical, behavioral, demographic factors with different effect sizes that may indicate the existence of moderate or modifiable effects. Further analysis with the inclusions of gene–gene and gene–environmental interactions shows interactions between rs17231896 (CETP) and rs17222772 (ALOX); rs17231896 (CETP) and gender. rs17237890 (CETP) and rs2070744 (NOS3) are found to be significantly associated with risks of MI adjusted by both SNPs and environmental factors. After multiple testing adjustments, these effects diminished as expected. In addition, an interaction between drinking and smoking status is significant. Overall, the prediction power in successfully classifying MI status is increased to 80% with inclusions of all significant tagSNPs and environmental factors and their interactions compared with environmental factors only (72%). Having a history of either HC or MI has significant effects on each other in both directions, in addition to HTN and gender. Genes/SNPs identified from this analysis that are associated with HC may be potentially linked to MI, which could be further examined and validated through haplotype-pairs analysis with appropriate population stratification corrections, and function/pathway regulation analysis to eliminate the limitations of the current analysis. PMID:28906356

Shared polymorphisms and modifiable behavior factors for myocardial infarction and high cholesterol in a retrospective population study.

PubMed

Liang, Yulan; Kelemen, Arpad

2017-09-01

Genetic and environmental (behavior, clinical, and demographic) factors are associated with increased risks of both myocardial infarction (MI) and high cholesterol (HC). It is known that HC is major risk factor that may cause MI. However, whether there are common single nucleotide polymorphism (SNPs) associated with both MI and HC is not firmly established, and whether there are modulate and modified effects (interactions of genetic and known environmental factors) on either HC or MI, and whether these joint effects improve the predictions of MI, is understudied.The purpose of this study is to identify novel shared SNPs and modifiable environmental factors on MI and HC. We assess whether SNPs from a metabolic pathway related to MI may relate to HC; whether there are moderate effects among SNPs, lifestyle (smoke and drinking), HC, and MI after controlling other factors [gender, body mass index (BMI), and hypertension (HTN)]; and evaluate prediction power of the joint and modulate genetic and environmental factors influencing the MI and HC.This is a retrospective study with residents of Erie and Niagara counties in New York with a history of MI or with no history of MI. The data set includes environmental variables (demographic, clinical, lifestyle). Thirty-one tagSNPs from a metabolic pathway related to MI are genotyped. Generalized linear models (GLMs) with imputation-based analysis are conducted for examining the common effects of tagSNPs and environmental exposures and their interactions on having a history of HC or MI.MI, BMI, and HTN are significant risk factors for HC. HC shows the strongest effect on risk of MI in addition to HTN; gender and smoking status while drinking status shows protective effect on MI. rs16944 (gene IL-1β) and rs17222772 (gene ALOX) increase the risks of HC, while rs17231896 (gene CETP) has protective effects on HC either with or without the clinical, behavioral, demographic factors with different effect sizes that may indicate the existence of moderate or modifiable effects. Further analysis with the inclusions of gene-gene and gene-environmental interactions shows interactions between rs17231896 (CETP) and rs17222772 (ALOX); rs17231896 (CETP) and gender. rs17237890 (CETP) and rs2070744 (NOS3) are found to be significantly associated with risks of MI adjusted by both SNPs and environmental factors. After multiple testing adjustments, these effects diminished as expected. In addition, an interaction between drinking and smoking status is significant. Overall, the prediction power in successfully classifying MI status is increased to 80% with inclusions of all significant tagSNPs and environmental factors and their interactions compared with environmental factors only (72%).Having a history of either HC or MI has significant effects on each other in both directions, in addition to HTN and gender. Genes/SNPs identified from this analysis that are associated with HC may be potentially linked to MI, which could be further examined and validated through haplotype-pairs analysis with appropriate population stratification corrections, and function/pathway regulation analysis to eliminate the limitations of the current analysis.

Common genetic variation within miR-146a predicts disease onset and relapse in multiple sclerosis.

PubMed

Zhou, Yuan; Chen, Ming; Simpson, Steve; Lucas, Robyn M; Charlesworth, Jac C; Blackburn, Nicholas; van der Mei, Ingrid; Ponsonby, Anne-Louise; Taylor, Bruce V

2018-02-01

Despite extensive studies focusing on the changes in expression of microRNAs (miRNAs) in multiple sclerosis (MS) compared to healthy controls, few studies have evaluated the association of genetic variants of miRNAs with MS clinical course. We investigated whether a functional polymorphism in the MS associated miR-146a gene predicted clinical course (hazard of conversion to MS and of relapse, and annualized change in disability), using a longitudinal cohort study of persons with a first demyelinating event followed up to their 5-year review. We found the genotype (GC+CC) of rs2910164 predicted relapse compared with the GG genotype (HR=2.09 (95% CI 1.42, 3.06), p=0.0001), as well as a near-significant (p=0.07) association with MS conversion risk. Moreover, we found a significant additive interaction between rs2910164 and baseline anti-EBNA-1 IgG titers predicting risk of conversion to MS (relative excess risk due to interaction [RERI] 2.39, p=0.00002) and of relapse (RERI 1.20, p=0.006). Supporting these results, similar results were seen for the other EBV-correlated variables: anti-EBNA-2 IgG titers and past history of infectious mononucleosis. There was no association of rs2910164 genotype for disability progression. Our findings provide evidence for miR-146a and EBV infection in modulating MS clinical course.

Sex modifies the APOE-related risk of developing Alzheimer disease.

PubMed

Altmann, Andre; Tian, Lu; Henderson, Victor W; Greicius, Michael D

2014-04-01

The APOE4 allele is the strongest genetic risk factor for sporadic Alzheimer disease (AD). Case-control studies suggest the APOE4 link to AD is stronger in women. We examined the APOE4-by-sex interaction in conversion risk (from healthy aging to mild cognitive impairment (MCI)/AD or from MCI to AD) and cerebrospinal fluid (CSF) biomarker levels. Cox proportional hazards analysis was used to compute hazard ratios (HRs) for an APOE-by-sex interaction on conversion in controls (n = 5,496) and MCI patients (n = 2,588). The interaction was also tested in CSF biomarker levels of 980 subjects from the Alzheimer's Disease Neuroimaging Initiative. Among controls, male and female carriers were more likely to convert to MCI/AD, but the effect was stronger in women (HR = 1.81 for women; HR = 1.27 for men; interaction: p = 0.011). The interaction remained significant in a predefined subanalysis restricted to APOE3/3 and APOE3/4 genotypes. Among MCI patients, both male and female APOE4 carriers were more likely to convert to AD (HR = 2.16 for women; HR = 1.64 for men); the interaction was not significant (p = 0.14). In the subanalysis restricted to APOE3/3 and APOE3/4 genotypes, the interaction was significant (p = 0.02; HR = 2.17 for women; HR = 1.51 for men). The APOE4-by-sex interaction on biomarker levels was significant for MCI patients for total tau and the tau-to-Aβ ratio (p = 0.009 and p = 0.02, respectively; more AD-like in women). APOE4 confers greater AD risk in women. Biomarker results suggest that increased APOE-related risk in women may be associated with tau pathology. These findings have important clinical implications and suggest novel research approaches into AD pathogenesis. © 2014 American Neurological Association.

Upregulation of toll-like receptors in chronic enteropathies in dogs.

PubMed

Burgener, I A; König, A; Allenspach, K; Sauter, S N; Boisclair, J; Doherr, M G; Jungi, T W

2008-01-01

Inflammatory bowel disease (IBD) is thought to result from a dysregulated interaction between the host immune system and commensal microflora. Toll-like receptors (TLRs) recognize microbe-associated molecular patterns (MAMPs), but their role in enteropathies in dogs is unknown. That there is a dysregulation of TLRs recognizing bacterial MAMPs in dogs with IBD. Sixteen healthy beagles and 12 dogs with steroid-treated (ST) and 23 dogs with food-responsive (FR) diarrhea. Prospective, observational study. mRNA expression of canine TLR2, 4, and 9 was evaluated by quantitative real-time RT-PCR in duodenal and colonic biopsies obtained before and after standard therapy. Samples from control dogs were taken at necropsy, with additional biopsies of stomach, jejunum, ileum, and mesenteric lymph node in 6 dogs. There were significant differences (P< or = .017) in expression of TLR2, 4, and 9 between the 6 sampled locations in healthy control dogs (lymph node > small intestine > or = colon). Before therapy, ST expressed more mRNA than control dogs for all 3 receptors (P < .05). There were no significant differences between pretreatment and posttreatment values, even though 32/35 dogs improved clinically. No associations were found when comparing receptor mRNA expression with either histology or clinical activity scores. Bacteria-responsive TLR2, 4, and 9 are upregulated in duodenal and colonic mucosa in IBD. This might lead to increased inflammation through interaction with the commensal flora. The absence of significant changes after therapy despite clinical improvement might point toward the existence of a genetic predisposition to IBD as described in human IBD.

Creating learning momentum through overt teaching interactions during real acute care episodes.

PubMed

Piquette, Dominique; Moulton, Carol-Anne; LeBlanc, Vicki R

2015-10-01

Clinical supervisors fulfill a dual responsibility towards patient care and learning during clinical activities. Assuming such roles in today's clinical environments may be challenging. Acute care environments present unique learning opportunities for medical trainees, as well as specific challenges. The goal of this paper was to better understand the specific contexts in which overt teaching interactions occurred in acute care environments. We conducted a naturalistic observational study based on constructivist grounded theory methodology. Using participant observation, we collected data on the teaching interactions occurring between clinical supervisors and medical trainees during 74 acute care episodes in the critical care unit of two academic centers, in Toronto, Canada. Three themes contributed to a better understanding of the conditions in which overt teaching interactions among trainees and clinical supervisors occurred during acute care episodes: seizing emergent learning opportunities, coming up against challenging conditions, and creating learning momentum. Our findings illustrate how overt learning opportunities emerged from certain clinical situations and how clinical supervisors and trainees could purposefully modify unfavorable learning conditions. None of the acute care episodes encountered in the critical care environment represented ideal conditions for learning. Yet, clinical supervisors and trainees succeeded in engaging in overt teaching interactions during many episodes. The educational value of these overt teaching interactions should be further explored, as well as the impact of interventions aimed at increasing their use in acute care environments.

The Attachment Doll Play Assessment: Predictive Validity with Concurrent Mother-Child Interaction and Maternal Caregiving Representations

PubMed Central

George, Carol; Solomon, Judith

2016-01-01

Attachment is central to the development of children’s regulatory processes. It has been associated with developmental and psychiatric health across the life span, especially emotional and behavioral regulation of negative affect when stressed (Schore, 2001; Schore and Schore, 2008). Assessment of attachment patterns provides a critical frame for understanding emerging developmental competencies and formulating treatment and intervention. Play-based attachment assessments provide access to representational models of attachment, which are regarded in attachment theory as the central organizing mechanisms associated with stability or change (Bowlby, 1969/1982; Bretherton and Munholland, 2008). The Attachment Doll Play Assessment (ADPA, George and Solomon, 1990–2016; Solomon et al., 1995) is a prominent established representational attachment measure for children aged early latency through childhood. This study examines the predictive validity of the ADPA to caregiving accessibility and responsiveness assessed from mother-child interaction and maternal representation. Sixty nine mothers and their 5–7-year-old children participated in this study. Mother-child interaction was observed during a pre-separation dyadic interaction task. Caregiving representations were rated from the Caregiving Interview (George and Solomon, 1988/1993/2005/2007). Child security with mother was associated with positive dyadic interaction and flexibly integrated maternal caregiving representations. Child controlling/disorganized attachments were significantly associated with problematic dyadic interaction and dysregulated-helpless maternal caregiving representations. The clinical implications and the use of the ADPA in clinical and educational settings are discussed. PMID:27803683

The Attachment Doll Play Assessment: Predictive Validity with Concurrent Mother-Child Interaction and Maternal Caregiving Representations.

PubMed

George, Carol; Solomon, Judith

2016-01-01

Attachment is central to the development of children's regulatory processes. It has been associated with developmental and psychiatric health across the life span, especially emotional and behavioral regulation of negative affect when stressed (Schore, 2001; Schore and Schore, 2008). Assessment of attachment patterns provides a critical frame for understanding emerging developmental competencies and formulating treatment and intervention. Play-based attachment assessments provide access to representational models of attachment, which are regarded in attachment theory as the central organizing mechanisms associated with stability or change (Bowlby, 1969/1982; Bretherton and Munholland, 2008). The Attachment Doll Play Assessment (ADPA, George and Solomon, 1990-2016; Solomon et al., 1995) is a prominent established representational attachment measure for children aged early latency through childhood. This study examines the predictive validity of the ADPA to caregiving accessibility and responsiveness assessed from mother-child interaction and maternal representation. Sixty nine mothers and their 5-7-year-old children participated in this study. Mother-child interaction was observed during a pre-separation dyadic interaction task. Caregiving representations were rated from the Caregiving Interview (George and Solomon, 1988/1993/2005/2007). Child security with mother was associated with positive dyadic interaction and flexibly integrated maternal caregiving representations. Child controlling/disorganized attachments were significantly associated with problematic dyadic interaction and dysregulated-helpless maternal caregiving representations. The clinical implications and the use of the ADPA in clinical and educational settings are discussed.

TP53 mutations, expression and interaction networks in human cancers

PubMed Central

Wang, Xiaosheng; Sun, Qingrong

2017-01-01

Although the associations of p53 dysfunction, p53 interaction networks and oncogenesis have been widely explored, a systematic analysis of TP53 mutations and its related interaction networks in various types of human cancers is lacking. Our study explored the associations of TP53 mutations, gene expression, clinical outcomes, and TP53 interaction networks across 33 cancer types using data from The Cancer Genome Atlas (TCGA). We show that TP53 is the most frequently mutated gene in a number of cancers, and its mutations appear to be early events in cancer initiation. We identified genes potentially repressed by p53, and genes whose expression correlates significantly with TP53 expression. These gene products may be especially important nodes in p53 interaction networks in human cancers. This study shows that while TP53-truncating mutations often result in decreased TP53 expression, other non-truncating TP53 mutations result in increased TP53 expression in some cancers. Survival analyses in a number of cancers show that patients with TP53 mutations are more likely to have worse prognoses than TP53-wildtype patients, and that elevated TP53 expression often leads to poor clinical outcomes. We identified a set of candidate synthetic lethal (SL) genes for TP53, and validated some of these SL interactions using data from the Cancer Cell Line Project. These predicted SL genes are promising candidates for experimental validation and the development of personalized therapeutics for patients with TP53-mutated cancers. PMID:27880943

TP53 mutations, expression and interaction networks in human cancers.

PubMed

Wang, Xiaosheng; Sun, Qingrong

2017-01-03

Although the associations of p53 dysfunction, p53 interaction networks and oncogenesis have been widely explored, a systematic analysis of TP53 mutations and its related interaction networks in various types of human cancers is lacking. Our study explored the associations of TP53 mutations, gene expression, clinical outcomes, and TP53 interaction networks across 33 cancer types using data from The Cancer Genome Atlas (TCGA). We show that TP53 is the most frequently mutated gene in a number of cancers, and its mutations appear to be early events in cancer initiation. We identified genes potentially repressed by p53, and genes whose expression correlates significantly with TP53 expression. These gene products may be especially important nodes in p53 interaction networks in human cancers. This study shows that while TP53-truncating mutations often result in decreased TP53 expression, other non-truncating TP53 mutations result in increased TP53 expression in some cancers. Survival analyses in a number of cancers show that patients with TP53 mutations are more likely to have worse prognoses than TP53-wildtype patients, and that elevated TP53 expression often leads to poor clinical outcomes. We identified a set of candidate synthetic lethal (SL) genes for TP53, and validated some of these SL interactions using data from the Cancer Cell Line Project. These predicted SL genes are promising candidates for experimental validation and the development of personalized therapeutics for patients with TP53-mutated cancers.

Antiepileptic drug therapy: clinical laboratory significance.

PubMed

Naradzay, J F; Olshaker, J S

1996-01-01

When evaluating a patient who is taking an antiepileptic medication, it is important for the emergency physician to correlate the clinical presentation with the antiepileptic drug level. Therapeutic ranges have been suggested for most antiepileptic medications, but these must be interpreted in light of clinical efficacy and patient tolerance. When considering the efficacy of anti-epileptic medications, it is necessary to consider the patient's unique metabolism, side-effect tolerance, and overall response to therapy. Suggested therapeutic ranges should be the first reference for the emergency physician. The purpose of this report is to discuss the laboratory values of commonly prescribed antiepileptic medications. Therapeutic ranges, side-effects, and common medication interactions are discussed concerning phenytoin, phenobarbital, carbamezapine, and valproic acid.

Using an International Medical Advisory Board to guide clinical governance in a corporate refractive surgery model.

PubMed

Vukich, John A

2009-07-01

To describe the role played by the International Medical Advisory Board (IMAB) in clinical and corporate governance at Optical Express, a corporate provider of refractive surgery. A review of goals, objectives, and actions of the IMAB. The IMAB has contributed to study design, data analysis, and selection of instruments and procedures. Through interactions with Optical Express corporate and clinical staff, the IMAB has supported management's effort to craft a corporate culture focused on continuous improvement in the safety and visual outcomes of refractive surgery. The IMAB has fashioned significant changes in corporate policies and procedures and has had an impact on corporate culture at Optical Express.

Fluorescence study on the interaction of human serum albumin with Butein in liposomes

NASA Astrophysics Data System (ADS)

Toprak, Mahmut

2016-02-01

The interaction of Butein with human serum albumin in L-egg lecithin phosphatidycholine (PC) liposome has been investigated by fluorescence and absorption spectroscopy. The results of the fluorescence measurement indicated that Butein effectively quenched the intrinsic fluorescence of HSA via static quenching. The Stern-Volmer plots in all the liposome solutions showed a positive deviation from the linearity. According to the thermodynamic parameters, the hydrophobic interactions appeared be the major interaction forces between Butein and HSA. The effect of Butein on the conformation of HSA was also investigated by the synchronous fluorescence under the same experimental conditions. In addition, the partition coefficient of the Butein in the PC liposomes was also determined by using the fluorescence quenching process. The obtained results can be of biological significance in pharmacology and clinical medicine.

The effects of racial attitudes on affect and engagement in racially discordant medical interactions between non-Black physicians and Black patients.

PubMed

Hagiwara, Nao; Dovidio, John F; Eggly, Susan; Penner, Louis A

2016-07-01

The association between physicians' and patients' racial attitudes and poorer patient-physician communication in racially discordant medical interactions is well-documented. However, it is unclear how physicians' and patients' racial attitudes independently and jointly affect their behaviors during these interactions. In a secondary analysis of video-recorded medical interactions between non-Black physicians and Black patients, we examined how physicians' explicit and implicit racial bias and patients' perceived past discrimination influenced their own as well as one another's affect and level of engagement. Affect and engagement were assessed with a "thin slice" method. For physicians, the major findings were significant three-way interactions: physicians' affect and engagement were influenced by their implicit and explicit racial bias (i.e., aversive racism), but only when they interacted with patients who reported any incidence of prior discrimination. In contrast, patients' affect was influenced only by perceived discrimination. Theoretical and clinical implications of current findings are discussed.

Virus-Bacteria Interactions: Implications and Potential for the Applied and Agricultural Sciences.

PubMed

Moore, Matthew D; Jaykus, Lee-Ann

2018-02-02

Eukaryotic virus-bacteria interactions have recently become an emerging topic of study due to multiple significant examples related to human pathogens of clinical interest. However, such omnipresent and likely important interactions for viruses and bacteria relevant to the applied and agricultural sciences have not been reviewed or compiled. The fundamental basis of this review is that these interactions have importance and deserve more investigation, as numerous potential consequences and applications arising from their discovery are relevant to the applied sciences. The purpose of this review is to highlight and summarize eukaryotic virus-bacteria findings in the food/water, horticultural, and animal sciences. In many cases in the agricultural sciences, mechanistic understandings of the effects of virus-bacteria interactions remain unstudied, and many studies solely focus on co-infections of bacterial and viral pathogens. Given recent findings relative to human viral pathogens, further research related to virus-bacteria interactions would likely result in numerous discoveries and beneficial applications.

The effects of racial attitudes on affect and engagement in racially discordant medical interactions between non-Black physicians and Black patients

PubMed Central

Hagiwara, Nao; Dovidio, John F.; Eggly, Susan; Penner, Louis A.

2016-01-01

The association between physicians’ and patients’ racial attitudes and poorer patient–physician communication in racially discordant medical interactions is well-documented. However, it is unclear how physicians’ and patients’ racial attitudes independently and jointly affect their behaviors during these interactions. In a secondary analysis of video-recorded medical interactions between non-Black physicians and Black patients, we examined how physicians’ explicit and implicit racial bias and patients’ perceived past discrimination influenced their own as well as one another’s affect and level of engagement. Affect and engagement were assessed with a “thin slice” method. For physicians, the major findings were significant three-way interactions: physicians’ affect and engagement were influenced by their implicit and explicit racial bias (i.e., aversive racism), but only when they interacted with patients who reported any incidence of prior discrimination. In contrast, patients’ affect was influenced only by perceived discrimination. Theoretical and clinical implications of current findings are discussed. PMID:27642254

The use of PC based VR in clinical medicine: the VREPAR projects.

PubMed

Riva, G; Bacchetta, M; Baruffi, M; Borgomainerio, E; Defrance, C; Gatti, F; Galimberti, C; Fontaneto, S; Marchi, S; Molinari, E; Nugues, P; Rinaldi, S; Rovetta, A; Ferretti, G S; Tonci, A; Wann, J; Vincelli, F

1999-01-01

Virtual reality (VR) is an emerging technology that alters the way individuals interact with computers: a 3D computer-generated environment in which a person can move about and interact as if he actually was inside it. Given to the high computational power required to create virtual environments, these are usually developed on expensive high-end workstations. However, the significant advances in PC hardware that have been made over the last three years, are making PC-based VR a possible solution for clinical assessment and therapy. VREPAR - Virtual Reality Environments for Psychoneurophysiological Assessment and Rehabilitation - are two European Community funded projects (Telematics for health - HC 1053/HC 1055 - http://www.psicologia.net) that are trying to develop a modular PC-based virtual reality system for the medical market. The paper describes the rationale of the developed modules and the preliminary results obtained.

Prescription drug therapy in the podiatric outpatient population: interactions and precautions.

PubMed

Dickinson, B D; Alley, P; Price, T W; Simeone, L A

1988-04-01

A survey of 2,000 outpatients at the clinic of the Dr. William M. Scholl College of Podiatric Medicine was conducted analyzing both medications reported by the patients at the time of treatment and drugs by the attending podiatrist. The major groups of medications already used by the patients included diuretics, vitamins and minerals, nonsteroidal antiinflammatory drugs, cardiovascular medications, insulin and oral hypoglycemics, estrogen and thyroid hormone replacement, and antibiotics. Patients with asthma, ulcers, epilepsy, affective disorders and Parkinsonism represented significant subgroups. The major drugs used by podiatrists in the outpatient clinic included analgesics and antiinflammatory agents, local anesthetics, antibiotics, sedative-hypnotics, and a variety of topical agents. These two sources of medication serve as the basis for a review of drug interactions in the podiatric outpatient population. In addition, precautions for the use of drugs commonly administered by podiatrists are reviewed.

The effectiveness of psychoanalytic-interactional psychotherapy in borderline personality disorder.

PubMed

Leichsenring, Falk; Masuhr, Oliver; Jaeger, Ulrich; Dally, Andreas; Streeck, Ulrich

2010-01-01

Different methods are available for the psychotherapeutic treatment of patients with severe personality disorders. In Germany, a special form of dynamically oriented therapy called psychoanalytic-interactional psychotherapy or method (PiM) has been clinically applied for many years. PiM was derived from psychoanalytic therapy and has been specifically adapted for the treatment of severely disordered patients, for example, patients with borderline personality disorders, prepsychotic disorders, addictions, and perversions. In a naturalistic study, the effectiveness of PiM was tested in a sample of patients with borderline personality disorders (N = 132). The patients were treated in the Clinic Tiefenbrunn near Göettingen. Standardized, reliable, and valid diagnostic instruments were used to study the treatment effects. According to the results, PiM achieved significant improvements in target symptoms, general symptoms, interpersonal problems, and contentedness with life. The results are discussed with regard to the treatment of severely disordered patients.

Genotyping for Severe Drug Hypersensitivity

PubMed Central

Karlin, Eric; Phillips, Elizabeth

2014-01-01

Over the past decade, there have been significant advances in our understanding of the immunopathogenesis and pharmacogenomics of severe immunologically-mediated adverse drug reactions. Such T-cell-mediated adverse drug reactions such as Stevens-Johnson syndrome/toxic epidermal necrolysis (SJS/TEN), drug-induced liver disease (DILI) and other drug hypersensitivity syndromes have more recently been shown to be mediated through interactions with various class I and II HLA alleles. Key examples have included the associations of HLA-B*15:02 and carbamazepine induced SJS/TEN in Southeast Asian populations and HLA-B*57:01 and abacavir hypersensitivity. HLA-B*57:01 screening to prevent abacavir hypersensitivity exemplifies a successful translational roadmap from pharmacogenomic discovery through to widespread clinical implementation. Ultimately, our increased understanding of the interaction between drugs and the MHC could be used to inform drug design and drive pre-clinical toxicity programs to improve drug safety. PMID:24429903

Nuclear Mechanics and Stem Cell Differentiation.

PubMed

Mao, Xinjian; Gavara, Nuria; Song, Guanbin

2015-12-01

Stem cells are characterized by their self-renewal and multi-lineage differentiation potential. Stem cell differentiation is a prerequisite for the application of stem cells in regenerative medicine and clinical therapy. In addition to chemical stimulation, mechanical cues play a significant role in regulating stem cell differentiation. The integrity of mechanical sensors is necessary for the ability of cells to respond to mechanical signals. The nucleus, the largest and stiffest cellular organelle, interacts with the cytoskeleton as a key mediator of cell mechanics. Nuclear mechanics are involved in the complicated interactions of lamins, chromatin and nucleoskeleton-related proteins. Thus, stem cell differentiation is intimately associated with nuclear mechanics due to its indispensable role in mechanotransduction and mechanical response. This paper reviews several main contributions of nuclear mechanics, highlights the hallmarks of the nuclear mechanics of stem cells, and provides insight into the relationship between nuclear mechanics and stem cell differentiation, which may guide clinical applications in the future.

Paraoxonase 1 (PON1) Q192R genotypes and their interaction with smoking strongly increase atherogenicity and the Framingham risk score.

PubMed

Souza-Nogueira, Andre de; Camargo, Alissana Ester; Remondi, Felipe Assan; Paoliello, Monica Maria Bastos; Richter, Rebecca J; Furlong, Clement E; Barbosa, Decio Sabbatini; Maes, Michael; Moreira, Estefania Gastaldello

2016-10-01

Paraoxonase 1 (PON1) polymorphisms are associated with an increased susceptibility to cardiovascular disease. PON1 Q192R polymorphism (rs662) partially determine PON1 hydrolytic activity and protect against oxidation of LDL and HDL. This study aimed to delineate the association of PON1 status (functional 192 genotype and plasma activity levels) and atherogenicity in urbans residents aged 40 years or more. Anthropometric data, lipid profiles, the atherogenic index of the plasma (AIP) and Framingham score risk were measured. Three kinetic assays were conducted to assay PON1 status using phenylacetate and 4-(chloromethyl)phenyl acetate as substrates. Smoking per se did not significantly impact the AIP but the interaction PON1 genotype by smoking significantly increased the AIP. In subjects with the RR genotype smoking increased the AIP index from (estimated mean ± SEM) -0.038 ± 0.039 to 0.224 ± 0.094. The QR genotype increased the Framingham risk index by around 1.3 points. Smoking by RR genotype carriers significantly increased the Framingham risk score (17.23 ± 2.04) as compared to smoking (13.00 ± 1.06) and non-smoking (7.79 ± 0.70) by QQ+QR genotype carriers. The interaction RR genotype by smoking was a more important predictor (odds ratio = 7.90) of an increased Framingham risk score (> 20) than smoking per se (odds ratio = 2.73). The interaction smoking by RR genotype carriers significantly increased triglycerides and lowered HDL cholesterol. Smoking per se has no (AIP) or a mild (Framingham risk score) effect on atherogenicity, while the interaction smoking by PON1 RR genotype has a clinically highly significant impact on atherogenicity.

Senior physiotherapy students as standardised patients for junior students enhances self-efficacy and satisfaction in both junior and senior students

PubMed Central

2014-01-01

Background Standardised patients are used in medical education to expose students to clinical contexts and facilitate transition to clinical practice, and this approach is gaining momentum in physiotherapy programs. Expense and availability of trained standardised patients are factors limiting widespread adoption, and accessing clinical visits with real patients can be challenging. This study addressed these issues by engaging senior students as standardised patients for junior students. It evaluated how this approach impacted self-reported constructs of both the junior and senior students. Methods Learning activities for undergraduate physiotherapy students were developed in five courses (Neurology, Cardiorespiratory and three Musculoskeletal courses) so that junior students (Year 2 and 3) could develop skills and confidence in patient interview, physical examination and patient management through their interaction with standardised patients played by senior students (Year 4). Surveys were administered before and after the interactions to record junior students’ self-reported confidence, communication, preparedness for clinic, and insight into their abilities; and senior students’ confidence and insight into what it is like to be a patient. Satisfaction regarding this learning approach was surveyed in both the junior and senior students. Results A total of 253 students completed the surveys (mean 92.5% response rate). Across all courses, junior students reported a significant (all P < 0.037) improvement following the standardised patient interaction in their: preparedness for clinic, communication with clients, confidence with practical skills, and understanding of their strengths and weaknesses in relation to the learning activities. Senior students demonstrated a significant improvement in their confidence in providing feedback and insight into their own learning (P < 0.001). All students reported high satisfaction with this learning experience (mean score 8.5/10). Conclusion This new approach to peer-assisted learning using senior students as standardised patients resulted in positive experiences for both junior and senior students across a variety of physiotherapy areas, activities, and stages within a physiotherapy program. These findings support the engagement of senior students as standardised patients to enhance learning within physiotherapy programs, and may have application across other disciplines to address challenges associated with accessing real patients via clinical visits or utilising actors as standardised patients. PMID:24885224

Genders of patients and clinicians and their effect on shared decision making: a participant-level meta-analysis.

PubMed

Wyatt, Kirk D; Branda, Megan E; Inselman, Jonathan W; Ting, Henry H; Hess, Erik P; Montori, Victor M; LeBlanc, Annie

2014-09-02

Gender differences in communication styles between clinicians and patients have been postulated to impact patient care, but the extent to which the gender dyad structure impacts outcomes in shared decision making remains unclear. Participant-level meta-analysis of 775 clinical encounters within 7 randomized trials where decision aids, shared decision making tools, were used at the point of care. Outcomes analysed include decisional conflict scale scores, satisfaction with the clinical encounter, concordance between stated decision and action taken, and degree of patient engagement by the clinician using the OPTION scale. An estimated minimal important difference was used to determine if nonsignificant results could be explained by low power. We did not find a statistically significant interaction between clinician/patient gender mix and arm for decisional conflict, satisfaction with the clinical encounter or patient engagement. A borderline significant interaction (p = 0.05) was observed for one outcome: concordance between stated decision and action taken, where encounters with female clinician/male patient showed increased concordance in the decision aid arm compared to control (8% more concordant encounters). All other gender dyads showed decreased concordance with decision aid use (6% fewer concordant encounters for same-gender, 16% fewer concordant encounters for male clinician/female patient). In this participant-level meta-analysis of 7 randomized trials, decision aids used at the point of care demonstrated comparable efficacy across gender dyads. Purported barriers to shared decision making based on gender were not detected when tested for a minimum detected difference. ClinicalTrials.gov NCT00888537, NCT01077037, NCT01029288, NCT00388050, NCT00578981, NCT00949611, NCT00217061.

Posaconazole exposure-response relationship: evaluating the utility of therapeutic drug monitoring.

PubMed

Dolton, Michael J; Ray, John E; Marriott, Deborah; McLachlan, Andrew J

2012-06-01

Posaconazole has become an important part of the antifungal armamentarium in the prophylaxis and salvage treatment of invasive fungal infections (IFIs). Structurally related to itraconazole, posaconazole displays low oral bioavailability due to poor solubility, with significant drug interactions and gastrointestinal disease also contributing to the generally low posaconazole plasma concentrations observed in patients. While therapeutic drug monitoring (TDM) of plasma concentrations is widely accepted for other triazole antifungal agents such as voriconazole, the utility of TDM for posaconazole is controversial due to debate over the relationship between posaconazole exposure in plasma and clinical response to therapy. This review examines the available evidence for a relationship between plasma concentration and clinical efficacy for posaconazole, as well as evaluating the utility of TDM and providing provisional target concentrations for posaconazole therapy. Increasing evidence supports an exposure-response relationship for plasma posaconazole concentrations for prophylaxis and treatment of IFIs; a clear relationship has not been identified between posaconazole concentration and toxicity. Intracellular and intrapulmonary concentrations have been studied for posaconazole but have not been correlated to clinical outcomes. In view of the high mortality and cost associated with the treatment of IFIs, increasing evidence of an exposure-response relationship for posaconazole efficacy in the prevention and treatment of IFIs, and the common finding of low posaconazole concentrations in patients, TDM for posaconazole is likely to be of significant clinical utility. In patients with subtherapeutic posaconazole concentrations, increased dose frequency, administration with high-fat meals, and withdrawal of interacting medications from therapy are useful strategies to improve systemic absorption.

Preferences for a third-trimester ultrasound scan in a low-risk obstetric population: a discrete choice experiment.

PubMed

Lynn, Fiona A; Crealey, Grainne E; Alderdice, Fiona A; McElnay, James C

2015-10-01

Establish maternal preferences for a third-trimester ultrasound scan in a healthy, low-risk pregnant population. Cross-sectional study incorporating a discrete choice experiment. A large, urban maternity hospital in Northern Ireland. One hundred and forty-six women in their second trimester of pregnancy. A discrete choice experiment was designed to elicit preferences for four attributes of a third-trimester ultrasound scan: health-care professional conducting the scan, detection rate for abnormal foetal growth, provision of non-medical information, cost. Additional data collected included age, marital status, socio-economic status, obstetric history, pregnancy-specific stress levels, perceived health and whether pregnancy was planned. Analysis was undertaken using a mixed logit model with interaction effects. Women's preferences for, and trade-offs between, the attributes of a hypothetical scan and indirect willingness-to-pay estimates. Women had significant positive preference for higher rate of detection, lower cost and provision of non-medical information, with no significant value placed on scan operator. Interaction effects revealed subgroups that valued the scan most: women experiencing their first pregnancy, women reporting higher levels of stress, an adverse obstetric history and older women. Women were able to trade on aspects of care and place relative importance on clinical, non-clinical outcomes and processes of service delivery, thus highlighting the potential of using health utilities in the development of services from a clinical, economic and social perspective. Specifically, maternal preferences exhibited provide valuable information for designing a randomized trial of effectiveness and insight for clinical and policy decision makers to inform woman-centred care. © 2013 Blackwell Publishing Ltd.

Moderating effects of race in clinical trial participation and outcomes among marijuana-dependent young adults.

PubMed

Montgomery, LaTrice; Petry, Nancy M; Carroll, Kathleen M

2012-12-01

Few studies have examined clinical trial participation rates and treatment outcomes among underserved young adults who are dependent on marijuana, the most commonly abused illicit drug. The present study was a secondary analysis of a trial of court-referred marijuana-dependent young adults (ages 18-25) randomized to one of four treatment conditions: Motivational Enhancement Therapy/Cognitive Behavioral Therapy (MET/CBT), MET/CBT+Contingency Management (CM), Drug Counseling (DC) or DC+CM. African American (N=81) participants were compared to White (N=31) participants with respect to rates of participation in phases of treatment and substance use outcomes. In addition, the interaction of race and treatment condition was examined to ascertain if the interventions yielded different effects based on race. Among those who started treatment, African American young adults were significantly less likely to complete the treatment and posttreatment phases of the clinical trial than their White counterparts. Irrespective of treatment type, substance use outcomes (i.e., percentage of marijuana-negative specimens and longest duration of continuous abstinence) did not vary by race. However, there was a significant interaction effect between treatment type and race; African American young adults did not benefit differentially from any specific type of treatment, but CM was effective in reducing proportion of marijuana positive samples among White young adults. Findings suggest that clinical trial treatment and posttreatment completion rates vary by race in this population, as does response to specific treatment types. More treatment research focusing specifically on African American marijuana-dependent young adults is warranted. Copyright © 2012 Elsevier Ireland Ltd. All rights reserved.

Comprehensive process model of clinical information interaction in primary care: results of a "best-fit" framework synthesis.

PubMed

Veinot, Tiffany C; Senteio, Charles R; Hanauer, David; Lowery, Julie C

2018-06-01

To describe a new, comprehensive process model of clinical information interaction in primary care (Clinical Information Interaction Model, or CIIM) based on a systematic synthesis of published research. We used the "best fit" framework synthesis approach. Searches were performed in PubMed, Embase, the Cumulative Index to Nursing and Allied Health Literature (CINAHL), PsycINFO, Library and Information Science Abstracts, Library, Information Science and Technology Abstracts, and Engineering Village. Two authors reviewed articles according to inclusion and exclusion criteria. Data abstraction and content analysis of 443 published papers were used to create a model in which every element was supported by empirical research. The CIIM documents how primary care clinicians interact with information as they make point-of-care clinical decisions. The model highlights 3 major process components: (1) context, (2) activity (usual and contingent), and (3) influence. Usual activities include information processing, source-user interaction, information evaluation, selection of information, information use, clinical reasoning, and clinical decisions. Clinician characteristics, patient behaviors, and other professionals influence the process. The CIIM depicts the complete process of information interaction, enabling a grasp of relationships previously difficult to discern. The CIIM suggests potentially helpful functionality for clinical decision support systems (CDSSs) to support primary care, including a greater focus on information processing and use. The CIIM also documents the role of influence in clinical information interaction; influencers may affect the success of CDSS implementations. The CIIM offers a new framework for achieving CDSS workflow integration and new directions for CDSS design that can support the work of diverse primary care clinicians.

Differential effects of synthetic progestagens on neuron survival and estrogen neuroprotection in cultured neurons.

PubMed

Jayaraman, Anusha; Pike, Christian J

2014-03-25

Progesterone and other progestagens are used in combination with estrogens for clinical purposes, including contraception and postmenopausal hormone therapy. Progesterone and estrogens have interactive effects in brain, however interactions between synthetic progestagens and 17β-estradiol (E2) in neurons are not well understood. In this study, we investigated the effects of seven clinically relevant progestagens on estrogen receptor (ER) mRNA expression, E2-induced neuroprotection, and E2-induced BDNF mRNA expression. We found that medroxyprogesterone acetate decreased both ERα and ERβ expression and blocked E2-mediated neuroprotection and BDNF expression. Conversely, levonorgestrel and nesterone increased ERα and or ERβ expression, were neuroprotective, and failed to attenuate E2-mediated increases in neuron survival and BDNF expression. Other progestagens tested, including norethindrone, norethindrone acetate, norethynodrel, and norgestimate, had variable effects on the measured endpoints. Our results demonstrate a range of qualitatively different actions of progestagens in cultured neurons, suggesting significant variability in the neural effects of clinically utilized progestagens. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

Measuring treatment effects on dual-task performance: a framework for research and clinical practice

PubMed Central

Plummer, Prudence; Eskes, Gail

2015-01-01

The relevance of dual-task walking to everyday ambulation is widely acknowledged, and numerous studies have demonstrated that dual-task interference can significantly impact recovery of functional walking in people with neurological disorders. The magnitude and direction of dual-task interference is influenced by the interaction between the two tasks, including how individuals spontaneously prioritize their attention. Therefore, to accurately interpret and characterize dual-task interference and identify changes over time, it is imperative to evaluate single and dual-task performance in both tasks, as well as the tasks relative to each other. Yet, reciprocal dual-task effects (DTE) are frequently ignored. The purpose of this perspective paper is to present a framework for measuring treatment effects on dual-task interference, specifically taking into account the interactions between the two tasks and how this can provide information on whether overall dual-task capacity has improved or a different attentional strategy has been adopted. In discussing the clinical implications of using this framework, we provide specific examples of using this method and provide some explicit recommendations for research and clinical practice. PMID:25972801

The effect of oxytocin nasal spray on social interaction deficits observed in young children with autism: a randomized clinical crossover trial.

PubMed

Yatawara, C J; Einfeld, S L; Hickie, I B; Davenport, T A; Guastella, A J

2016-09-01

Interventions for autism are limited. The synthetic hormone oxytocin may provide a potential treatment to improve core social and behavioral difficulties in autism, but its efficacy has yet to be evaluated in young children who potentially may benefit to a greater extent. We investigated the efficacy, tolerability and safety of oxytocin treatment in young children with autism using a double-blind, randomized, placebo-controlled, crossover, clinical trial. Thirty-one children with autism received 12 International Units (IU) of oxytocin and placebo nasal spray morning and night (24 IU per day) for 5 weeks, with a 4-week washout period between each treatment. Compared with placebo, oxytocin led to significant improvements on the primary outcome of caregiver-rated social responsiveness. Overall, nasal spray was well tolerated, and the most common reported adverse events were thirst, urination and constipation. This study is the first clinical trial to support the potential of oxytocin as an early intervention for young children with autism to help improve social interaction deficits.

The effect of oxytocin nasal spray on social interaction deficits observed in young children with autism: a randomized clinical crossover trial

PubMed Central

Yatawara, C J; Einfeld, S L; Hickie, I B; Davenport, T A; Guastella, A J

2016-01-01

Interventions for autism are limited. The synthetic hormone oxytocin may provide a potential treatment to improve core social and behavioral difficulties in autism, but its efficacy has yet to be evaluated in young children who potentially may benefit to a greater extent. We investigated the efficacy, tolerability and safety of oxytocin treatment in young children with autism using a double-blind, randomized, placebo-controlled, crossover, clinical trial. Thirty-one children with autism received 12 International Units (IU) of oxytocin and placebo nasal spray morning and night (24 IU per day) for 5 weeks, with a 4-week washout period between each treatment. Compared with placebo, oxytocin led to significant improvements on the primary outcome of caregiver-rated social responsiveness. Overall, nasal spray was well tolerated, and the most common reported adverse events were thirst, urination and constipation. This study is the first clinical trial to support the potential of oxytocin as an early intervention for young children with autism to help improve social interaction deficits. PMID:26503762

Do Family Responsibilities and a Clinical Versus Research Faculty Position Affect Satisfaction with Career and Work-Life Balance for Medical School Faculty?

PubMed

Beckett, Laurel; Nettiksimmons, Jasmine; Howell, Lydia Pleotis; Villablanca, Amparo C

2015-06-01

Balancing career and family obligations poses challenges to medical school faculty and contributes to dissatisfaction and attrition from academics. We examined the relationship between family setting and responsibilities, rank, and career and work-life satisfaction for faculty in a large U.S. medical school. Baseline faculty surveys were analyzed from the first year of a 4-year National Institutes of Health-funded study to evaluate awareness, knowledge, attitudes, and use of family friendly policies and career satisfaction. The study focus was on the impact of family responsibilities and characteristics of the faculty position (rank, clinical vs. nonclinical, and academic series) in multivariate comparisons between primary predictors and outcomes of interest. Both clinical and family responsibilities for children under 18 play a major and interacting role in satisfaction with career and work-life balance. Clinical faculty respondents without children at home reported significantly greater career satisfaction and better work-life balance than their nonclinical counterparts. Nonclinical faculty respondents with children reported greater satisfaction and better balance than counterparts without family responsibilities. However, the advantage in career satisfaction and work-life balance for clinical faculty respondents disappeared for those with responsibility for young children. No gender-based differences were noted in the results or across faculty rank for respondents; however, for women, reaching associate professor resulted in greater career satisfaction. This study suggests that both work-related factors and family responsibilities influence satisfaction with career and work-life balance, but the predictors appear to interact in complex and nuanced ways. Further research is needed to delineate more clearly these interactions and to explore other factors that may play important additional roles.

Do Family Responsibilities and a Clinical Versus Research Faculty Position Affect Satisfaction with Career and Work–Life Balance for Medical School Faculty?

PubMed Central

Beckett, Laurel; Nettiksimmons, Jasmine; Howell, Lydia Pleotis

2015-01-01

Abstract Background: Balancing career and family obligations poses challenges to medical school faculty and contributes to dissatisfaction and attrition from academics. We examined the relationship between family setting and responsibilities, rank, and career and work–life satisfaction for faculty in a large U.S. medical school. Methods: Baseline faculty surveys were analyzed from the first year of a 4-year National Institutes of Health–funded study to evaluate awareness, knowledge, attitudes, and use of family friendly policies and career satisfaction. The study focus was on the impact of family responsibilities and characteristics of the faculty position (rank, clinical vs. nonclinical, and academic series) in multivariate comparisons between primary predictors and outcomes of interest. Results: Both clinical and family responsibilities for children under 18 play a major and interacting role in satisfaction with career and work–life balance. Clinical faculty respondents without children at home reported significantly greater career satisfaction and better work–life balance than their nonclinical counterparts. Nonclinical faculty respondents with children reported greater satisfaction and better balance than counterparts without family responsibilities. However, the advantage in career satisfaction and work–life balance for clinical faculty respondents disappeared for those with responsibility for young children. No gender-based differences were noted in the results or across faculty rank for respondents; however, for women, reaching associate professor resulted in greater career satisfaction. Conclusion: This study suggests that both work-related factors and family responsibilities influence satisfaction with career and work–life balance, but the predictors appear to interact in complex and nuanced ways. Further research is needed to delineate more clearly these interactions and to explore other factors that may play important additional roles. PMID:26070036

Social support and conscientiousness in hemodialysis adherence.

PubMed

Moran, P J; Christensen, A J; Lawton, W J

1997-01-01

Previous conclusions regarding the role of social support in hemodialysis adherence are inconsistent, suggesting that other factors may moderate this relationship. Using the Five-Factor Model of Personality, we examined the hypothesis that conscientiousness would interact with social support in predicting fluid-intake and medication adherence in a sample of 56 chronic hemodialysis patients. Hierarchical regression analyses (controlling for demographic, clinical, and other personality variables) revealed a significant interaction between social support and conscientiousness. However, inconsistent with prediction, high support among patients with low conscientiousness was associated with poorer fluid-intake adherence, while support had little effect on fluid-intake adherence among high conscientiousness patients. No main or interactive effects were found for support or conscientiousness on a measure of medication adherence.

Teaching veterinary obstetrics using three-dimensional animation technology.

PubMed

Scherzer, Jakob; Buchanan, M Flint; Moore, James N; White, Susan L

2010-01-01

In this three-year study, test scores for students taught veterinary obstetrics in a classroom setting with either traditional media (photographs, text, and two-dimensional graphical presentations) were compared with those for students taught by incorporating three-dimensional (3D) media (linear animations and interactive QuickTime Virtual Reality models) into the classroom lectures. Incorporation of the 3D animations and interactive models significantly increased students' scores on essay questions designed to assess their comprehension of the subject matter. This approach to education may help to better prepare students for dealing with obstetrical cases during their final clinical year and after graduation.

APOA2 -256T>C polymorphism interacts with saturated fatty acids intake to affect anthropometric and hormonal variables in type 2 diabetic patients.

PubMed

Basiri, Marjan Ghane; Sotoudeh, Gity; Alvandi, Ehsan; Djalali, Mahmood; Eshraghian, Mohammad Reza; Noorshahi, Neda; Koohdani, Fariba

2015-05-01

Recent studies have established the interaction between APOA2 -256T>C polymorphism and dietary saturated fatty acids intake in relation to obesity on healthy individuals. In the current study, we investigate the effects of this interaction on anthropometric variables and serum levels of leptin and ghrelin in patients with type 2 diabetes. In this cross-sectional study, 737 patients with type 2 diabetes mellitus (290 males and 447 females) were recruited from diabetes clinics in Tehran. The usual dietary intake of all participants during the last year was obtained by validated semiquantitative food frequency questionnaire. APOA2 genotyping was performed by real-time PCR on genomic DNA. No significant relation was obtained by univariate analysis between anthropometric variables and APOA2 genotypes. However, after adjusting for age, gender, physical activity and total energy intake, we identified a significant interaction between APOA2-saturated fatty acids intake and body mass index (BMI). After adjusting for potential confounders, serum levels of ghrelin in CC genotype patients were significantly higher than T allele carriers (p = 0.03), whereas the case with leptin did not reveal a significant difference. The result of this study confirmed the interaction between APOA2 -256T>C polymorphism and SFAs intake with BMI in type 2 diabetic patients. In fact, homozygous patients for the C allele with high saturated fatty acids intake had higher BMI. The APOA2 -256T>C polymorphism was associated with elevated levels of serum ghrelin.

Community-based early intervention for language delay: a preliminary investigation.

PubMed

Ciccone, Natalie; Hennessey, Neville; Stokes, Stephanie F

2012-01-01

A trial parent-focused early intervention (PFEI) programme for children with delayed language development is reported in which current research evidence was translated and applied within the constraints of available of clinical resources. The programme, based at a primary school, was run by a speech-language pathologist with speech-language pathology students. To investigate the changes in child language development and parent and child interactions following attendance at the PFEI. Eighteen parents and their children attended six, weekly group sessions in which parents were provided with strategies to maximize language learning in everyday contexts. Pre- and post-programme assessments of vocabulary size and measures of parent-child interaction were collected. Parents and children significantly increased their communicative interactions from pre- to post-treatment. Children's expressive vocabulary size and language skills increased significantly. Large-effect sizes were observed. The positive outcomes of the intervention programme contribute to the evidence base of intervention strategies and forms of service delivery for children at risk of language delay. © 2012 Royal College of Speech and Language Therapists.

Does adult ADHD interact with COMT val (158) met genotype to influence working memory performance?

PubMed

Biehl, Stefanie C; Gschwendtner, Kathrin M; Guhn, Anne; Müller, Laura D; Reichert, Susanne; Heupel, Julia; Reif, Andreas; Deckert, Jürgen; Herrmann, Martin J; Jacob, Christian P

2015-03-01

Both attention-deficit/hyperactivity disorder (ADHD) and catechol-O-methyltransferase (COMT) genotype have been linked to altered dopaminergic transmission and possible impairment in frontal lobe functioning. This study offers an investigation of a possible interaction between ADHD diagnosis and COMT genotype on measures of working memory and executive function. Thirty-five adults with ADHD, who were recruited from the ADHD outpatient clinic at the Department of Psychiatry, Psychosomatics and Psychotherapy, University of Würzburg, and thirty-five matched healthy controls completed the Digit Span test and the Stroop Color Word Test. While there were no main effects of ADHD or COMT, the two factors interacted on both Digit Span subtests with the two groups' met/met carriers showing significantly different performance on the Digit Span Forward subtest and the val/val carriers showing significantly different performance on the Digit Span Backward subtest. Findings provide preliminary support for a differential impact of COMT genotype on working memory measures in adult patients with ADHD compared to healthy controls.

SFINX-a drug-drug interaction database designed for clinical decision support systems.

PubMed

Böttiger, Ylva; Laine, Kari; Andersson, Marine L; Korhonen, Tuomas; Molin, Björn; Ovesjö, Marie-Louise; Tirkkonen, Tuire; Rane, Anders; Gustafsson, Lars L; Eiermann, Birgit

2009-06-01

The aim was to develop a drug-drug interaction database (SFINX) to be integrated into decision support systems or to be used in website solutions for clinical evaluation of interactions. Key elements such as substance properties and names, drug formulations, text structures and references were defined before development of the database. Standard operating procedures for literature searches, text writing rules and a classification system for clinical relevance and documentation level were determined. ATC codes, CAS numbers and country-specific codes for substances were identified and quality assured to ensure safe integration of SFINX into other data systems. Much effort was put into giving short and practical advice regarding clinically relevant drug-drug interactions. SFINX includes over 8,000 interaction pairs and is integrated into Swedish and Finnish computerised decision support systems. Over 31,000 physicians and pharmacists are receiving interaction alerts through SFINX. User feedback is collected for continuous improvement of the content. SFINX is a potentially valuable tool delivering instant information on drug interactions during prescribing and dispensing.

Use of Digital Rectal Examination as an Adjunct to Prostate Specific Antigen in the Detection of Clinically Significant Prostate Cancer.

PubMed

Halpern, Joshua A; Oromendia, Clara; Shoag, Jonathan E; Mittal, Sameer; Cosiano, Michael F; Ballman, Karla V; Vickers, Andrew J; Hu, Jim C

2018-04-01

Guidelines from the NCCN ® (National Comprehensive Cancer Network®) advocate digital rectal examination screening only in men with elevated prostate specific antigen. We investigated the effect of prostate specific antigen on the association of digital rectal examination and clinically significant prostate cancer in a large American cohort. We evaluated the records of the 35,350 men who underwent digital rectal examination in the screening arm of the Prostate, Lung, Colorectal and Ovarian Cancer Screening trial for the development of clinically significant prostate cancer (Gleason 7 or greater). Followup was 343,273 person-years. The primary outcome was the rate of clinically significant prostate cancer among men with vs without suspicious digital rectal examination. We performed competing risks regression to evaluate the interaction between time varying suspicious digital rectal examination and prostate specific antigen. A total of 1,713 clinically significant prostate cancers were detected with a 10-year cumulative incidence of 5.9% (95% CI 5.6-6.2). Higher risk was seen for suspicious vs nonsuspicious digital rectal examination. Increases in absolute risk were small and clinically irrelevant for normal (less than 2 ng/ml) prostate specific antigen (1.5% vs 0.7% risk of clinically significant prostate cancer at 10 years), clinically relevant for elevated (3 ng/ml or greater) prostate specific antigen (23.0% vs 13.7%) and modestly clinically relevant for equivocal (2 to 3 ng/ml) prostate specific antigen (6.5% vs 3.5%). Digital rectal examination demonstrated prognostic usefulness when prostate specific antigen was greater than 3 ng/ml, limited usefulness for less than 2 ng/ml and marginal usefulness for 2 to 3 ng/ml. These findings support the restriction of digital rectal examination to men with higher prostate specific antigen as a reflex test to improve specificity. It should not be used as a primary screening modality to improve sensitivity. Copyright © 2018 American Urological Association Education and Research, Inc. Published by Elsevier Inc. All rights reserved.

painACTION-back pain: a self-management website for people with chronic back pain.

PubMed

Chiauzzi, Emil; Pujol, Lynette A; Wood, Mollie; Bond, Kathleen; Black, Ryan; Yiu, Elizabeth; Zacharoff, Kevin

2010-07-01

To determine whether an interactive self-management Website for people with chronic back pain would significantly improve emotional management, coping, self-efficacy to manage pain, pain levels, and physical functioning compared with standard text-based materials. The study utilized a pretest-posttest randomized controlled design comparing Website (painACTION-Back Pain) and control (text-based material) conditions at baseline and at 1-, 3, and 6-month follow-ups. Two hundred and nine people with chronic back pain were recruited through dissemination of study information online and at a pain treatment clinic. The 6-month follow-up rates for the Website and control groups were 73% and 84%, respectively. Measures were based on the recommendations of the Initiative on Methods, Measurement, and Pain Assessment in Clinical Trials and included measures of pain intensity, physical functioning, emotional functioning, coping, self-efficacy, fear-avoidance, perceived improvement with treatment, self-efficacy, and catastrophizing. Compared with controls, painACTION-Back Pain participants reported significantly: 1) lower stress; 2) increased coping self-statements; and 3) greater use of social support. Comparisons between groups suggested clinically significant differences in current pain intensity, depression, anxiety, stress, and global ratings of improvement. Among participants recruited online, those using the Website reported significantly: 1) lower "worst" pain; 2) lower "average" pain; and 3) increased coping self-statements, compared with controls. Participants recruited through the pain clinic evidenced no such differences. An online self-management program for people with chronic back pain can lead to improvements in stress, coping, and social support, and produce clinically significant differences in pain, depression, anxiety, and global rates of improvement.

Parent Depression and Anger in Peer-Delivered Parent Support Services

PubMed Central

Shen, Sa; Rodriguez, James; Radigan, Marleen; Burton, Geraldine; Hoagwood, Kimberly E.

2017-01-01

Knowledge about parents who seek peer-delivered parent support services in children’s mental health is limited. In this prospective study, characteristics of 124 parents who sought peer parent advocate services related to their children’s behavioral difficulties are described. This urban sample consisted primarily of low-income mothers of color, 80% of whom were caring for children with clinically significant behavioral problems. Of these parents, 64% endorsed clinically significant levels of depressive symptoms at baseline. Linear mixed effects models were used to examine associations between parent depression and anger expression with working alliances with peer advocates. No independent or combined effects of parent depression or anger expression on working alliance were found. However, adjusting for family demographic factors, caregiver strain and child symptoms, parent depression interacted with anger expression to influence working alliances, primarily around agreement and mutual engagement on goals. Among parents who endorsed clinically significant depressive symptoms, anger expression did not influence working alliance but among non-depressed parents, anger expression was negatively associated with working alliance. Implications for training peer parent advocates to more effectively engage low income parents are discussed. PMID:28775660

Parent Depression and Anger in Peer-Delivered Parent Support Services.

PubMed

Olin, S Serene; Shen, Sa; Rodriguez, James; Radigan, Marleen; Burton, Geraldine; Hoagwood, Kimberly E

2015-11-01

Knowledge about parents who seek peer-delivered parent support services in children's mental health is limited. In this prospective study, characteristics of 124 parents who sought peer parent advocate services related to their children's behavioral difficulties are described. This urban sample consisted primarily of low-income mothers of color, 80% of whom were caring for children with clinically significant behavioral problems. Of these parents, 64% endorsed clinically significant levels of depressive symptoms at baseline. Linear mixed effects models were used to examine associations between parent depression and anger expression with working alliances with peer advocates. No independent or combined effects of parent depression or anger expression on working alliance were found. However, adjusting for family demographic factors, caregiver strain and child symptoms, parent depression interacted with anger expression to influence working alliances, primarily around agreement and mutual engagement on goals. Among parents who endorsed clinically significant depressive symptoms, anger expression did not influence working alliance but among non-depressed parents, anger expression was negatively associated with working alliance. Implications for training peer parent advocates to more effectively engage low income parents are discussed.

Selexipag in Pulmonary Arterial Hypertension: Most Updated Evidence From Recent Preclinical and Clinical Studies.

PubMed

Ghosh, Raktim K; Ball, Somedeb; Das, Avash; Bandyopadhyay, Dhrubajyoti; Mondal, Samhati; Saha, Debjit; Gupta, Anjan

2017-05-01

Pulmonary arterial hypertension (PAH) is a relatively rare disease that, due to its chronic nature, has always been difficult to treat effectively. Selexipag is an oral prostacyclin (PGI 2 ) agonist that was approved by US Food and Drug Administration (US FDA) in December 2015 for the treatment of PAH. After its success in phase 1 and phase 2 clinical trials regarding the convenient oral twice-daily dosing and low side-effect profile, selexipag raised the hope of controlling the disease progression in PAH patients. In the recently completed multicentered phase 3 study (GRIPHON), selexipag has been shown to reduce death and hospitalization due to PAH significantly, an effect that was consistent across different ranges of maintenance dose. In the same study selexipag use was also associated with an increase in 6-minute walk distance (a measure of symptom severity) from baseline, but no significant improvement in all-cause mortality could be observed. The results of the ongoing phase 3 studies (TRITON and TRANSIT-1) are expected to throw some more light on the safety and efficacy of this novel molecule across various treatment scenarios. Hence, our article aims to summarize all the available information from preclinical and clinical studies published to date on the pharmacodynamics, pharmacokinetics, efficacy, safety (in general and in scenarios such as hepatic and renal function impairment), significant drug interactions (with warfarin and antiretroviral drugs), and clinical significance of oral selexipag in patients with PAH. © 2016, The American College of Clinical Pharmacology.

Thrombus aspiration and prehospital ticagrelor administration in ST-elevation myocardial infarction: Findings from the ATLANTIC trial.

PubMed

Kilic, Sinem; Fabris, Enrico; Van't Hof, Arnoud W J; Hamm, Christian W; Lapostolle, Frédéric; Lassen, Jens Flensted; Tsatsaris, Anne; Diallo, Abdourahmane; Vicaut, Eric; Montalescot, Gilles

2018-02-01

The potential interactions between prehospital (pre-H) ticagrelor administration and thrombus aspiration (TA) in patients with ST-elevation myocardial infarction (STEMI) treated with primary percutaneous coronary intervention (PCI) have never been studied. Therefore, we evaluated the potential benefit of TA and pre-H ticagrelor treatment in patients enrolled in the ATLANTIC trial (NCT01347580). This analysis included 1,630 patients who underwent primary PCI. Multivariate analysis was used to explore the potential association of TA and pre-H treatment to clinical outcomes. Potential interactions between TA and pre-H ticagrelor were also explored. A total of 941 (57.7%) patients underwent TA. In adjusted multivariate logistic model, pre-H ticagrelor treatment was significantly associated with less frequent new MI or definite stent *thrombosis (ST) (odds ratio [OR] 0.43, 95% CI 0.20-0.92, P=.031), or definite ST (OR 0.26, 95% CI 0.07-0.91, P=.036) at 30 days. Patients treated with TA had higher frequency of Thrombolysis in Myocardial Infarction (TIMI) flow 0-1 compared with no-TA group (80.7% vs 51.9%, P<.0001). TA when also adjusted for TIMI flow 0-1 showed significant association only for higher bailout use of glycoprotein IIb/IIIa inhibitors (OR 1.72, 95% CI 1.18-2.50, P=.004) and more frequent 30-day TIMI major bleeding (OR 2.92, 95% CI 1.10-7.76, P=.032). No significant interactions between TA and pre-H ticagrelor were present for the explored end points. TA when left to physicians' discretion was used in high-risk patients, was associated with bailout use of glycoprotein IIb/IIIa inhibitors and TIMI major bleeding, and had no impact on 30-day clinical outcomes. Conversely, pre-H ticagrelor treatment predicted lower 30-day rates of ST or new MI without interaction with TA. Copyright © 2017 The Authors. Published by Elsevier Inc. All rights reserved.

A Comprehensive Pan-Cancer Molecular Study of Gynecologic and Breast Cancers.

PubMed

Berger, Ashton C; Korkut, Anil; Kanchi, Rupa S; Hegde, Apurva M; Lenoir, Walter; Liu, Wenbin; Liu, Yuexin; Fan, Huihui; Shen, Hui; Ravikumar, Visweswaran; Rao, Arvind; Schultz, Andre; Li, Xubin; Sumazin, Pavel; Williams, Cecilia; Mestdagh, Pieter; Gunaratne, Preethi H; Yau, Christina; Bowlby, Reanne; Robertson, A Gordon; Tiezzi, Daniel G; Wang, Chen; Cherniack, Andrew D; Godwin, Andrew K; Kuderer, Nicole M; Rader, Janet S; Zuna, Rosemary E; Sood, Anil K; Lazar, Alexander J; Ojesina, Akinyemi I; Adebamowo, Clement; Adebamowo, Sally N; Baggerly, Keith A; Chen, Ting-Wen; Chiu, Hua-Sheng; Lefever, Steve; Liu, Liang; MacKenzie, Karen; Orsulic, Sandra; Roszik, Jason; Shelley, Carl Simon; Song, Qianqian; Vellano, Christopher P; Wentzensen, Nicolas; Weinstein, John N; Mills, Gordon B; Levine, Douglas A; Akbani, Rehan

2018-04-09

We analyzed molecular data on 2,579 tumors from The Cancer Genome Atlas (TCGA) of four gynecological types plus breast. Our aims were to identify shared and unique molecular features, clinically significant subtypes, and potential therapeutic targets. We found 61 somatic copy-number alterations (SCNAs) and 46 significantly mutated genes (SMGs). Eleven SCNAs and 11 SMGs had not been identified in previous TCGA studies of the individual tumor types. We found functionally significant estrogen receptor-regulated long non-coding RNAs (lncRNAs) and gene/lncRNA interaction networks. Pathway analysis identified subtypes with high leukocyte infiltration, raising potential implications for immunotherapy. Using 16 key molecular features, we identified five prognostic subtypes and developed a decision tree that classified patients into the subtypes based on just six features that are assessable in clinical laboratories. Copyright © 2018 Elsevier Inc. All rights reserved.

Family support, self-esteem, and perceived racial discrimination among Asian American male college students.

PubMed

Wei, Meifen; Yeh, Christine Jean; Chao, Ruth Chu-Lien; Carrera, Stephanie; Su, Jenny C

2013-07-01

This study was conducted to examine under what situation (i.e., when individuals used more or less family support) and for whom (i.e., those with high or low self-esteem) perceived racial discrimination would or would not have a significant positive association with psychological distress. A total of 95 Asian American male college students completed an online survey. A hierarchical regression analysis indicated a significant 3-way interaction of family support, self-esteem, and perceived racial discrimination in predicting psychological distress after controlling for perceived general stress. A simple effect analysis was used to explore the nature of the interaction. When Asian American male college students used more family support to cope with racial discrimination, the association between perceived racial discrimination and psychological distress was not significant for those with high or low self-esteem. The result from the simple interaction indicated that, when more family support was used, the 2 slopes for high and low self-esteem were not significantly different from each other. Conversely, when they used less family support, the association between perceived racial discrimination and psychological distress was not significant for those with high self-esteem, but was significantly positive for those with low self-esteem. The result from the simple interaction indicated that, when less family support was used, the slopes for high and low self-esteem were significantly different. The result suggested that low use of family support may put these male students with low self-esteem at risk for psychological distress. Limitations, future research directions, and clinical implications were discussed. PsycINFO Database Record (c) 2013 APA, all rights reserved.

The role of organizational context in moderating the effect of research use on pain outcomes in hospitalized children: a cross sectional study.

PubMed

Yamada, Janet; Squires, Janet E; Estabrooks, Carole A; Victor, Charles; Stevens, Bonnie

2017-01-23

Despite substantial research on pediatric pain assessment and management, health care professionals do not adequately incorporate this knowledge into clinical practice. Organizational context (work environment) is a significant factor in influencing outcomes; however, the nature of the mechanisms are relatively unknown. The objective of this study was to assess how organizational context moderates the effect of research use and pain outcomes in hospitalized children. A cross-sectional survey was undertaken with 779 nurses in 32 patient care units in 8 Canadian pediatric hospitals, following implementation of a multifaceted knowledge translation intervention, Evidence-based Practice for Improving Quality (EPIQ). The influence of organizational context was assessed in relation to pain process (assessment and management) and clinical (pain intensity) outcomes. Organizational context was measured using the Alberta Context Tool that includes: leadership, culture, evaluation, social capital, informal interactions, formal interactions, structural and electronic resources, and organizational slack (staff, space, and time). Marginal modeling estimated the effects of instrumental research use (direct use of research knowledge) and conceptual research use (indirect use of research knowledge) on pain outcomes while examining the effects of context. Six of the 10 organizational context factors (culture, social capital, informal interactions, resources, and organizational slack [space and time]) significantly moderated the effect of instrumental research use on pain assessment; four factors (culture, social capital, resources and organizational slack time) moderated the effect of conceptual research use and pain assessment. Only two factors (evaluation and formal interactions) moderated the effect of instrumental research use on pain management. All organizational factors except slack space significantly moderated the effect of instrumental research use on pain intensity; informal interactions and organizational slack space moderated the effect of conceptual research use and pain intensity. Many aspects of organizational context consistently moderated the effects of instrumental research use on pain assessment and pain intensity, while only a few influenced conceptual use of research on pain outcomes. Organizational context factors did not generally influence the effect of research use on pain management. Further research is required to further explore the relationships between organizational context and pain management outcomes.

3D nitrogen-doped graphene/β-cyclodextrin: host-guest interactions for electrochemical sensing

NASA Astrophysics Data System (ADS)

Liu, Jilun; Leng, Xuanye; Xiao, Yao; Hu, Chengguo; Fu, Lei

2015-07-01

Host-guest interactions, especially those between cyclodextrins (CDs, including α-, β- and γ-CD) and various guest molecules, exhibit a very high supramolecular recognition ability. Thus, they have received considerable attention in different fields. These specific interactions between host and guest molecules are promising for biosensing and clinical detection. However, there is a lack of an ideal electrode substrate for CDs to increase their performance in electrochemical sensing. Herein, we propose a new 3D nitrogen-doped graphene (3D-NG) based electrochemical sensor, taking advantage of the superior sensitivity of host-guest interactions. Our 3D-NG was fabricated by a template-directed chemical vapour deposition (CVD) method, and it showed a large specific surface area, a high capacity for biomolecules and a high electron transfer efficiency. Thus, for the first time, we took 3D-NG as an electrode substrate for β-CD to establish a new type of biosensor. Using dopamine (DA) and acetaminophen (APAP) as representative guest molecules, our 3D-NG/β-CD biosensor shows extremely high sensitivities (5468.6 μA mM-1 cm-2 and 2419.2 μA mM-1 cm-2, respectively), which are significantly higher than those reported in most previous studies. The stable adsorption of β-CD on 3D-NG indicates potential applications in clinical detection and medical testing.Host-guest interactions, especially those between cyclodextrins (CDs, including α-, β- and γ-CD) and various guest molecules, exhibit a very high supramolecular recognition ability. Thus, they have received considerable attention in different fields. These specific interactions between host and guest molecules are promising for biosensing and clinical detection. However, there is a lack of an ideal electrode substrate for CDs to increase their performance in electrochemical sensing. Herein, we propose a new 3D nitrogen-doped graphene (3D-NG) based electrochemical sensor, taking advantage of the superior sensitivity of host-guest interactions. Our 3D-NG was fabricated by a template-directed chemical vapour deposition (CVD) method, and it showed a large specific surface area, a high capacity for biomolecules and a high electron transfer efficiency. Thus, for the first time, we took 3D-NG as an electrode substrate for β-CD to establish a new type of biosensor. Using dopamine (DA) and acetaminophen (APAP) as representative guest molecules, our 3D-NG/β-CD biosensor shows extremely high sensitivities (5468.6 μA mM-1 cm-2 and 2419.2 μA mM-1 cm-2, respectively), which are significantly higher than those reported in most previous studies. The stable adsorption of β-CD on 3D-NG indicates potential applications in clinical detection and medical testing. Electronic supplementary information (ESI) available: The procedure for preparing the sensor, wide survey XPS, XRD patterns, the effect of scan rate, more CV data on the stability and selectivity, and a comparison with previous studies. See DOI: 10.1039/c5nr03109e

Intimate partner violence outcomes in women with PTSD and substance use: a secondary analysis of NIDA Clinical Trials Network "Women and Trauma" Multi-site Study.

PubMed

Cohen, Lisa R; Field, Craig; Campbell, Aimee N C; Hien, Denise A

2013-07-01

Studies have shown strong associations between intimate partner violence (IPV) and both posttraumatic stress disorder (PTSD) and substance use disorders (SUD). Despite these linkages, research on the dual diagnosis of PTSD-SUD and its relationship to IPV is in an early stage, and little is known about how PTSD-SUD treatment might influence IPV outcomes. The current study is a secondary analysis of a larger NIDA Clinical Trials Network study exploring the effectiveness of two behavioral interventions for women with comorbid PTSD-SUD. Participants (n=288) were randomly assigned to Seeking Safety (SS), a cognitive-behavioral treatment that focuses on trauma and substance abuse symptoms, or to Women's Health Education, a psychoeducational group. Logistic regressions were used to examine how treatment condition, identified risk factors and their interactions were related to IPV. Results showed that participants who were abstinent at baseline were significantly less likely to experience IPV over the 12-month follow-up period, whereas participants living with someone with an alcohol problem were significantly more likely to experience IPV over follow-up. Findings also showed that at a trend level participants with recent interpersonal trauma at baseline and higher total of lifetime trauma exposures were more likely to report IPV during follow-up. Although there was no main effect for treatment condition, a significant interaction between treatment condition and baseline abstinence was found. Participants who were abstinent at baseline and in the SS condition were significantly less likely to report IPV over follow-up. These findings indicate that an integrated treatment for PTSD and SUD was associated with significantly better IPV outcomes for a subset of individuals. The possibility that women with PTSD-SUD may differentially benefit from SS has important clinical implications. Further research examining the intersection of PTSD, SUD and IPV, and the impact of treatment on a range of outcomes is needed. Copyright © 2013 Elsevier Ltd. All rights reserved.

Factors Affecting Gastrointestinal Absorption of Levothyroxine: A Review.

PubMed

Skelin, Marko; Lucijanić, Tomo; Amidžić Klarić, Daniela; Rešić, Arnes; Bakula, Miro; Liberati-Čizmek, Ana-Marija; Gharib, Hossein; Rahelić, Dario

2017-02-01

Levothyroxine (LT4) is a drug with a narrow therapeutic index, applied in small amounts (micrograms), which makes interactions in the absorption phase clinically significant. The main aim of this article was to review and present the latest information on factors that affect the gastrointestinal absorption of this drug. Relevant data were collected by using the MEDLINE, PubMed, EMBASE, Web of Science, Science Direct, and Scopus databases with the key words levothyroxine and absorption. Searches were not limited to specific publication types, study designs, dates, or languages. The reports were highly variable in the amount of information provided regarding study design and methods. Because of the heterogeneity of studies, no statistical analysis was performed. Many gastrointestinal disorders, such as celiac disease, atrophic gastritis, lactose intolerance, and Helicobacter pylori infection, may impede the absorption of levothyroxine. During treatment of these disorders, it is necessary to monitor serum thyroid-stimulating hormone and free T4 values to reduce the risk of developing iatrogenic hyperthyroidism. Soybeans and coffee have the greatest impact on the reduction of absorption, whereas vitamin C has the ability to increase it. Conversely, the effect of dietary fiber on the absorption of LT4 is not yet fully understood; further research is needed on this topic. A decrease in the absorption of LT4 is established and clinically significant when administered concomitantly with cholestyramine, colesevelam, lanthanum, calcium carbonate, calcium citrate, calcium acetate, iron sulfate, ciprofloxacin, aluminum hydroxide, sevelamer, or proton pump inhibitors. This effect should be taken into consideration when prescribing these drugs concomitantly with LT4. The effects of Giardia lamblia infection and the influence of orlistat, polystyrene sulfonate, raloxifene, and simethicone on absorption of LT4 have been poorly documented. For bariatric surgery, sucralfate and H 2 -antagonist interactions are not well founded or contradictory evidence is available regarding their existence; additional research should be conducted. The majority of the interactions are clinically significant. They are based on the LT4 adsorption on interfering substances in the digestive tract, as well as a consequently reduced amount of the drug available for absorption. These interactions can be avoided by separating the administration of LT4 and the interfering substance. Copyright © 2017 Elsevier HS Journals, Inc. All rights reserved.

Mining association patterns of drug-interactions using post marketing FDA's spontaneous reporting data.

PubMed

Ibrahim, Heba; Saad, Amr; Abdo, Amany; Sharaf Eldin, A

2016-04-01

Pharmacovigilance (PhV) is an important clinical activity with strong implications for population health and clinical research. The main goal of PhV is the timely detection of adverse drug events (ADEs) that are novel in their clinical nature, severity and/or frequency. Drug interactions (DI) pose an important problem in the development of new drugs and post marketing PhV that contribute to 6-30% of all unexpected ADEs. Therefore, the early detection of DI is vital. Spontaneous reporting systems (SRS) have served as the core data collection system for post marketing PhV since the 1960s. The main objective of our study was to particularly identify signals of DI from SRS. In addition, we are presenting an optimized tailored mining algorithm called "hybrid Apriori". The proposed algorithm is based on an optimized and modified association rule mining (ARM) approach. A hybrid Apriori algorithm has been applied to the SRS of the United States Food and Drug Administration's (U.S. FDA) adverse events reporting system (FAERS) in order to extract significant association patterns of drug interaction-adverse event (DIAE). We have assessed the resulting DIAEs qualitatively and quantitatively using two different triage features: a three-element taxonomy and three performance metrics. These features were applied on two random samples of 100 interacting and 100 non-interacting DIAE patterns. Additionally, we have employed logistic regression (LR) statistic method to quantify the magnitude and direction of interactions in order to test for confounding by co-medication in unknown interacting DIAE patterns. Hybrid Apriori extracted 2933 interacting DIAE patterns (including 1256 serious ones) and 530 non-interacting DIAE patterns. Referring to the current knowledge using four different reliable resources of DI, the results showed that the proposed method can extract signals of serious interacting DIAEs. Various association patterns could be identified based on the relationships among the elements which composed a pattern. The average performance of the method showed 85% precision, 80% negative predictive value, 81% sensitivity and 84% specificity. The LR modeling could provide the statistical context to guard against spurious DIAEs. The proposed method could efficiently detect DIAE signals from SRS data as well as, identifying rare adverse drug reactions (ADRs). Copyright © 2016 Elsevier Inc. All rights reserved.

A New Interactive Screening Test for Autism Spectrum Disorders in Toddlers.

PubMed

Choueiri, Roula; Wagner, Sheldon

2015-08-01

To develop a clinically valid interactive level 2 screening assessment for autism spectrum disorders (ASD) in toddlers that is brief, easily administered, and scored by clinicians. We describe the development, training, standardization, and validation of the Rapid Interactive Screening Test for Autism in Toddlers (RITA-T) with ASD-specific diagnostic instruments. The RITA-T can be administered and scored in 10 minutes. We studied the validity of the RITA-T to distinguish between toddlers with ASD from toddlers with developmental delay (DD)/non-ASD in an early childhood clinic. We also evaluated the test's performance in toddlers with no developmental concerns. We identified a cutoff score based on sensitivity, specificity, and positive predictive value of the RITA-T that best differentiates between ASD and DD/non-ASD. A total of 61 toddlers were enrolled. RITA-T scores were correlated with ASD-specific diagnostic tools (r = 0.79; P < .01) and ASD clinical diagnoses (r = 0.77; P < .01). Mean scores were significantly different in subjects with ASD, those with DD/non-ASD, and those with no developmental concerns (20.8 vs 13 vs 10.6, respectively; P < .0001). At a cutoff score of >14 , the RITA-T had a sensitivity of 1.00, specificity of 0.84, and positive predictive value of 0.88 for identifying ASD risk in a high-risk group. The RITA-T is a promising new level 2 interactive screening tool for improving the early identification of ASD in toddlers in general pediatric and early intervention settings and allowing access to treatment. Copyright © 2015 Elsevier Inc. All rights reserved.

Self-transcendence, nurse-patient interaction and the outcome of multidimensional well-being in cognitively intact nursing home patients.

PubMed

Haugan, Gørill; Hanssen, Brith; Moksnes, Unni K

2013-12-01

The aim of this study was to investigate the associations between age, gender, self-transcendence, nurse-patient interaction and multidimensional well-being as the outcome among cognitively intact nursing home patients. Self-transcendence is considered to be a vital resource of well-being in vulnerable populations and at the end of life. Moreover, the quality of care and the nurse-patient interaction is found to influence self-transcendence and well-being in nursing home patients. A cross-sectional design employing the Self-Transcendence Scale, the Nurse-Patient Interaction Scale, the FACT-G Quality of Life and the FACIT-Sp Spiritual Well-Being questionnaires was adopted. A sample of 202 cognitively intact nursing home patients from 44 nursing homes in central Norway was selected. A previous documented two-factor construct of self-transcendence was applied. The statistical analyses were carried out by means of independent sample t-test, correlation and regression analyses. Multiple linear regression analyses revealed significant relationships between interpersonal self-transcendence and social, functional and spiritual well-being, whereas intrapersonal self-transcendence significantly related to emotional, social, functional and spiritual well-being. Nurse-patient interaction related to physical, emotional and functional well-being. Age and gender were not significant predictors for well-being, except for functional and spiritual well-being where women scored higher than men. Nurse-patient interaction and self-transcendence are vital resources for promoting well-being physically, emotionally, functionally, socially and spiritually among cognitively intact nursing home patients. Nurse-patient interaction signifies vital and ultimate nursing qualities promoting self-transcendence and multidimensional well-being. These findings are important for clinical nursing intending to increase patients' well-being. © 2012 The Authors Scandinavian Journal of Caring Sciences © 2012 Nordic College of Caring Science.

Effects of reward and punishment on task performance, mood and autonomic nervous function, and the interaction with personality.

PubMed

Sakuragi, Sokichi; Sugiyama, Yoshiki

2009-06-01

The effects of reward and punishment are different, and there are individual differences in sensitivity to reward and punishment. The purpose of this study was to investigate the effects of reward and punishment on task performance, mood, and autonomic nervous function, along with the interaction with personality. Twenty-one healthy female subjects volunteered for the experiment. The task performance was evaluated by required time and total errors while performing a Wisconsin Card Sorting Test. We assessed their personalities using the Minnesota Multiphasic Personality Inventory (MMPI) questionnaire, and mood states by a profile of mood states. Autonomic nervous function was estimated by a spectral analysis of heart rate variability, baroreflex sensitivity, and blood pressure. Repeated measures analysis of variance (ANOVA) revealed significant interaction of condition x time course on mood and autonomic nervous activity, which would indicate a less stressed state under the rewarding condition, but revealed no significant interaction of condition x time course on the task performance. The interactions with personality were further analyzed by repeated measures ANOVA applying the clinical scales of MMPI as independent variables, and significant interactions of condition x time course x Pt (psychasthenia) on task performance, mood, and blood pressure, were revealed. That is, the high Pt group, whose members tend to be sensitive and prone to worry, showed gradual improvement of task performance under the punishing situation with slight increase in systolic blood pressure, while showed no improvement under the rewarding situation with fatigue sense attenuation. In contrast, the low Pt group, whose members tend to be adaptive and self-confident, showed gradual improvement under the rewarding situation. Therefore, we should carefully choose the strategy of reward or punishment, considering the interaction with personality as well as the context in which it is given.

Large-Scale medical image analytics: Recent methodologies, applications and Future directions.

PubMed

Zhang, Shaoting; Metaxas, Dimitris

2016-10-01

Despite the ever-increasing amount and complexity of annotated medical image data, the development of large-scale medical image analysis algorithms has not kept pace with the need for methods that bridge the semantic gap between images and diagnoses. The goal of this position paper is to discuss and explore innovative and large-scale data science techniques in medical image analytics, which will benefit clinical decision-making and facilitate efficient medical data management. Particularly, we advocate that the scale of image retrieval systems should be significantly increased at which interactive systems can be effective for knowledge discovery in potentially large databases of medical images. For clinical relevance, such systems should return results in real-time, incorporate expert feedback, and be able to cope with the size, quality, and variety of the medical images and their associated metadata for a particular domain. The design, development, and testing of the such framework can significantly impact interactive mining in medical image databases that are growing rapidly in size and complexity and enable novel methods of analysis at much larger scales in an efficient, integrated fashion. Copyright © 2016. Published by Elsevier B.V.

Stress sensitivity interacts with depression history to predict depressive symptoms among youth: Prospective changes following first depression onset

PubMed Central

Technow, Jessica R.; Hazel, Nicholas A.; Abela, John R. Z.; Hankin, Benjamin L.

2015-01-01

Predictors of depressive symptoms may differ before and after the first onset of major depression due to stress sensitization. Dependent stressors, or those to which characteristics of individuals contribute, have been shown to predict depressive symptoms in youth. The current study sought to clarify how stressors’ roles may differ before and after the first depressive episode. Adolescents (N = 382, aged 11 to 15 at baseline) were assessed at baseline and every three months over the course of two years with measures of stressors and depressive symptoms. Semi-structured interviews were conducted every 6 months to assess for clinically significant depressive episodes. Hierarchical linear modeling showed a significant interaction between history of depression and idiographic fluctuations in dependent stressors to predict prospective elevations of symptoms, such that dependent stressors were more predictive of depressive symptoms after onset of disorder. Independent stressors predicted symptoms, but the strength of the association did not vary by depression history. These results suggest a synthesis of stress sensitization and generation processes that might maintain inter-episode depressive symptoms among youth with a history of clinical depression. PMID:25123081

Drug interactions between common illicit drugs and prescription therapies.

PubMed

Lindsey, Wesley T; Stewart, David; Childress, Darrell

2012-07-01

The aim was to summarize the clinical literature on interactions between common illicit drugs and prescription therapies. Medline, Iowa Drug Information Service, International Pharmaceutical Abstracts, EBSCO Academic Search Premier, and Google Scholar were searched from date of origin of database to March 2011. Search terms were cocaine, marijuana, cannabis, methamphetamine, amphetamine, ecstasy, N-methyl-3,4-methylenedioxymethamphetamine, methylenedioxymethamphetamine, heroin, gamma-hydroxybutyrate, sodium oxybate, and combined with interactions, drug interactions, and drug-drug interactions. This review focuses on established clinical evidence. All applicable full-text English language articles and abstracts found were evaluated and included in the review as appropriate. The interactions of illicit drugs with prescription therapies have the ability to potentiate or attenuate the effects of both the illicit agent and/or the prescription therapeutic agent, which can lead to toxic effects or a reduction in the prescription agent's therapeutic activity. Most texts and databases focus on theoretical or probable interactions due to the kinetic properties of the drugs and do not fully explore the pharmacodynamic and clinical implications of these interactions. Clinical trials with coadministration of illicit drugs and prescription drugs are discussed along with case reports that demonstrate a potential interaction between agents. The illicit drugs discussed are cocaine, marijuana, amphetamines, methylenedioxymethamphetamine, heroin, and sodium oxybate. Although the use of illicit drugs is widespread, there are little experimental or clinical data regarding the effects of these agents on common prescription therapies. Potential drug interactions between illicit drugs and prescription drugs are described and evaluated on the Drug Interaction Probability Scale by Horn and Hansten.

An Integrated Process and Outcome Evaluation of a Web-Based Communication Tool for Patients With Malignant Lymphoma: Randomized Controlled Trial.

PubMed

van Bruinessen, Inge Renske; van Weel-Baumgarten, Evelyn M; Gouw, Hans; Zijlstra, Josée M; van Dulmen, Sandra

2016-07-29

The complex nature of the medical dialogue and the often emotional context in cancer care present challenges to health care professionals (HCPs) and patients. Patients are increasingly expected to be informed participants and to be able to make conscious decisions, which they often find very difficult. In an attempt to support patients with malignant lymphoma in clinical communication, we developed a stand-alone, Web-based intervention called "PatientTIME." The development of PatientTIME was based on a participatory intervention mapping framework. Its primary aim is to boost patients' self-efficacy in patient-professional communication (ie, their confidence when interacting with their HCP). Patients can use this intervention before their hospital visit to prepare for their clinical consultation. PatientTIME is fully automated and use is patient-initiated. The aim of this study was to evaluate if and in what way patients benefit from PatientTIME and if it enhances their confidence in clinical communication. The intervention was evaluated in a closed randomized controlled trial with continuous recruitment (using online and offline methods to reach potential participants) and data collection. In accordance with the Medical Research Council guidance, we started with a process evaluation. Subsequently, an outcome evaluation was performed focusing on the patients' perceived confidence in communication with their HCP, measured with the validated PEPPI questionnaire at baseline and at 3 months after participation. Process and outcome data were obtained through Web-based questionnaires, log files (automatically generated files mapping the interactions between program and users), and a logbook (comprising a record of actions and interactions kept by the researchers). Participants were not blinded. A total of 146 patients registered online, of whom 97 gave their informed consent and were assigned at random to the control group (N=34) or 1 of the 2 intervention groups (N=63). Ultimately 87/97 (90%) of these patients actually participated in the study, producing 87 datasets for analysis. More than half of the intervention group patients reported that the intervention helped them prepare for a clinical consultation; it created awareness about the importance of communication and reinforced their existing communication skills. In the postvisit test, the control group showed a small, nonsignificant improvement in perceived communication efficacy. The intervention group showed a significant improvement in perceived efficacy. However, the interaction effect was not significant, indicating that the improvement solely as a result of the intervention may not be significant. A considerable number of patients reported that PatientTIME did provide support. We found a trend indicating that in the long run, patients with access to PatientTIME scored better on the perceived efficacy scale than patients without access. However, at this stage we cannot conclude that PatientTIME improves patients' confidence when interacting with HCPs. Netherlands National Trial Register (NTR): 3779; http://www.trialregister.nl/trialreg/admin/rctview.asp?TC=3779 (archived by WebCite at http://www.webcitation.org/6iztxJ5Nt).

Reconciling the professional and student identities of clinical psychology trainees.

PubMed

McKenzie, Karen; Cossar, Jill A; Fawns, Tim; Murray, Aja L

2013-10-01

The study explored the ways in which qualified and trainee clinical psychologists perceived professional behaviour, as illustrated in a series of short vignettes, in student and clinical practice contexts. Comparisons were made to identify the extent to which ideas of professionalism differed across different learning contexts and between qualified and unqualified staff, with the aim of adding to the literature on which factors influence the development of professional identity in health professionals. An online questionnaire depicting a range of potentially unprofessional behaviours was completed by 265 clinical psychology trainees and 106 qualified clinical psychologists. The data were analysed using a general linear model with simultaneous entry in which rater (trainee vs qualified clinical psychologist), setting (student vs placement) and their interaction predicted acceptability ratings. We found that, in general, trainees and qualified staff agreed on those behaviours that were potentially unprofessional, although where significant differences were found, these were due to trainees rating the same behaviours as more professionally acceptable than qualified clinical psychologists. Despite trainees identifying a range of behaviours as professionally unacceptable, some percentage reported having engaged in a similar behaviour in the past. Irrespective of the status of the rater, the same behaviours tended to be viewed as more professionally unacceptable when in a placement (clinical) setting than in a student (university) setting. Generally, no support was found for a rater by setting interaction. The study suggests that trainee clinical psychologists are generally successful at identifying professional norms, although they do not always act in accordance with these. Conflicting student and professional norms may result in trainees viewing some potentially unprofessional behaviour as less severe than qualified staff. Health professional educators should be aware of this fact and take steps to shape trainee norms to be consistent with that of the professional group.

Histologic effects of resurfacing lasers.

PubMed

Freedman, Joshua R; Greene, Ryan M; Green, Jeremy B

2014-02-01

By utilizing resurfacing lasers, physicians can significantly improve the appearance of sun-damaged skin, scars, and more. The carbon dioxide and erbium:yttrium-aluminum-garnet lasers were the first ablative resurfacing lasers to offer impressive results although these earlier treatments were associated with significant downtime. Later, nonablative resurfacing lasers such as the neodymium:yttrium-aluminum-garnet laser proved effective, after a series of treatments with less downtime, but with more modest results. The theory of fractional photothermolysis has revolutionized resurfacing laser technology by increasing the safety profile of the devices while delivering clinical efficacy. A review of the histologic and molecular consequences of the resurfacing laser-tissue interaction allows for a better understanding of the devices and their clinical effects. Thieme Medical Publishers 333 Seventh Avenue, New York, NY 10001, USA.

Age of dementia diagnosis in community dwelling bilingual and monolingual Hispanic Americans

PubMed Central

Lawton, Deborah M.; Gasquoine, Philip G.; Weimer, Amy A.

2015-01-01

Bilingualism has been reported to delay the age of retrospective report of first symptom in dementia. This study determined if the age of clinically diagnosed Alzheimer's disease and vascular dementia occurred later for bilingual than monolingual, immigrant and U.S. born, Hispanic Americans. It involved a secondary analysis of the subset of 81 bi/monolingual dementia cases identified at yearly follow-up (1998 through 2008) using neuropsychological test results and objective diagnostic criteria from the Sacramento Area Latino Study on Aging that involved a random sampling of community dwelling Hispanic Americans (N = 1789). Age of dementia diagnosis was analyzed in a 2 × 2 (bi/monolingualism × immigrant/U.S. born) ANOVA that space revealed both main effects and the interaction were non-significant. Mean age of dementia diagnosis was descriptively (but not significantly) higher in the monolingual (M = 81.10 years) than the bilingual (M = 79.31) group. Overall, bilingual dementia cases were significantly better educated than monolinguals, but U.S. born bilinguals and monolinguals did not differ significantly in education. Delays in dementia symptomatology pertaining to bilingualism are less likely to be found in studies: (a) that use age of clinical diagnosis vs. retrospective report of first dementia symptom as the dependent variable; and (b) involve clinical cases derived from community samples rather than referrals to specialist memory clinics. PMID:25598395

When Trust Is Not Enough: A Serial Mediation Model Explaining the Effect of Race Identity, eHealth Information Efficacy, and Information Behavior on Intention to Participate in Clinical Research.

PubMed

Strekalova, Yulia A

2018-02-01

Black participants remain significantly underrepresented in clinical research. Mistrust in medical researchers has been named a key barrier to the successful enrollment of minority study participants. However, trust is a social-interactional construct, and its effects on behavior are complex. This study hypothesized that intention to participate in clinical research is mediated by trust in medical researchers, eHealth literacy, and information seeking behavior. The data were collected through an online survey ( N = 340) and analyzed to identify serial mediation. The model showed insignificant direct effect of race identity on behavioral intention, c' = -0.19, t(335) = -1.22, p = .22, but a significant total effect, c = -0.44, t(335) = -2.59, p < .01. The indirect effect of race identity on behavioral intention was also significant. The positive effect of trust in medical researchers on decisions to participate in clinical research can be amplified by stronger eHealth literacy and active information seeking, which can be supported through focused strategic health education and communication interventions. A focus on the development of information literacy that could provide prospective minority research volunteers with skills for informed decision making should be explored as an option for increasing mindful, informed participation in clinical research among currently underrepresented racial and ethnic groups.

Social defeat interacts with Disc1 mutations in the mouse to affect behavior.

PubMed

Haque, F Nipa; Lipina, Tatiana V; Roder, John C; Wong, Albert H C

2012-08-01

DISC1 (Disrupted-in-schizophrenia 1) is a strong candidate susceptibility gene for psychiatric disease that was originally discovered in a family with a chromosomal translocation severing this gene. Although the family members with the translocation had an identical genetic mutation, their clinical diagnosis and presentation varied significantly. Gene-environment interactions have been proposed as a mechanism underlying the complex heritability and variable phenotype of psychiatric disorders such as major depressive disorder and schizophrenia. We hypothesized that gene-environment interactions would affect behavior in a mutant Disc1 mouse model. We examined the effect of chronic social defeat (CSD) as an environmental stressor in two lines of mice carrying different Disc1 point mutations, on behaviors relevant to psychiatric illness: locomotion in a novel open field (OF), pre-pulse inhibition (PPI) of the acoustic startle response, latent inhibition (LI), elevated plus maze (EPM), forced swim test (FST), sucrose consumption (SC), and the social interaction task for sociability and social novelty (SSN). We found that Disc1-L100P +/- and wild-type mice have similar anxiety responses to CSD, while Q31L +/- mice had a very different response. We also found evidence of significant gene-environment interactions in the OF, EPM and SSN. Copyright © 2012 Elsevier B.V. All rights reserved.

Synergistic effect of the interaction between naproxen and citral on inflammation in rats.

PubMed

Ortiz, Mario I; González-García, Martha P; Ponce-Monter, Héctor A; Castañeda-Hernández, Gilberto; Aguilar-Robles, Paulina

2010-12-15

The combination of non-steroidal anti-inflammatory drugs with herbs having analgesic effects can increase their antinociceptive activity and limit their side effects. The aim of the present study was to examine the effects on inflammation and gastric injury in rats resulting from the interaction between naproxen and citral. Naproxen, citral, or fixed-dose naproxen-citral combinations were administered orally and their anti-inflammation (carrageenan-induced paw edema) and gastric damage were assessed in rats. The pharmacological interaction type was evaluated by the isobolographic analysis. Naproxen, citral, or combinations of naproxen and citral produced anti-inflammatory effects. The sole administration of naproxen produced significant gastric damage, but this effect was not obtained with either citral or combinations. ED(30) values were estimated for the individual drugs, and isobolograms were constructed. The derived theoretical ED(30) for the anti-inflammatory effect was 504.4 mg/kg; this was significantly higher than the observed experimental value (190.6 mg/kg). These results indicate that a synergistic interaction underlies the anti-inflammatory effect. The data suggests that the naproxen-citral combination can interact and to produce minor gastric damage and may have therapeutic advantages for the clinical treatment of inflammation. Copyright © 2010 Elsevier GmbH. All rights reserved.

Hyperhomocysteinaemia is an independent risk factor of abdominal aortic aneurysm in a Chinese Han population

PubMed Central

Liu, Jie; Wei Zuo, Shang; Li, Yue; Jia, Xin; Jia, Sen Hao; Zhang, Tao; Xiang Song, Yu; Qi Wei, Ying; Xiong, Jiang; Hua Hu, Yong; Guo, Wei

2016-01-01

The associations between hyperhomocysteinaemia (HHcy), methylenetetrahydrofolate reductase (MTHFR) C677T polymorphism, and abdominal aortic aneurysm (AAA) remain controversial, with only few studies focused on these associations within the Chinese population. We performed subgroup and interaction analyses in a Chinese Han population to investigate these associations. In all, 155 AAA patients and 310 control subjects were evaluated for serum total homocysteine levels and MTHFR C677T polymorphisms. Multiple logistic regression models were used to evaluate the aforementioned associations. Interaction and stratified analyses were conducted according to age, sex, smoking status, drinking status, and chronic disease histories. The multiple logistic analyses showed a significant association between HHcy and AAA but no significant association between MTHFR C677T polymorphism and AAA. The interaction analysis showed that age and peripheral arterial disease played an interactive role in the association between HHcy and AAA, while drinking status played an interactive role in the association between MTHFR C677T polymorphism and AAA. In conclusion, HHcy is an independent risk factor of AAA in a Chinese Han population, especially in the elderly and peripheral arterial disease subgroups. Longitudinal studies and clinical trials aimed to reduce homocysteine levels are warranted to assess the causal nature of these relationships PMID:26865327

Tuberculosis detection and the challenges of integrated care in rural China: A cross-sectional standardized patient study.

PubMed

Sylvia, Sean; Xue, Hao; Zhou, Chengchao; Shi, Yaojiang; Yi, Hongmei; Zhou, Huan; Rozelle, Scott; Pai, Madhukar; Das, Jishnu

2017-10-01

Despite recent reductions in prevalence, China still faces a substantial tuberculosis (TB) burden, with future progress dependent on the ability of rural providers to appropriately detect and refer TB patients for further care. This study (a) provides a baseline assessment of the ability of rural providers to correctly manage presumptive TB cases; (b) measures the gap between provider knowledge and practice and; (c) evaluates how ongoing reforms of China's health system-characterized by a movement toward "integrated care" and promotion of initial contact with grassroots providers-will affect the care of TB patients. Unannounced standardized patients (SPs) presenting with classic pulmonary TB symptoms were deployed in 3 provinces of China in July 2015. The SPs successfully completed 274 interactions across all 3 tiers of China's rural health system, interacting with providers in 46 village clinics, 207 township health centers, and 21 county hospitals. Interactions between providers and standardized patients were assessed against international and national standards of TB care. Using a lenient definition of correct management as at least a referral, chest X-ray or sputum test, 41% (111 of 274) SPs were correctly managed. Although there were no cases of empirical anti-TB treatment, antibiotics unrelated to the treatment of TB were prescribed in 168 of 274 interactions or 61.3% (95% CI: 55%-67%). Correct management proportions significantly higher at county hospitals compared to township health centers (OR 0.06, 95% CI: 0.01-0.25, p < 0.001) and village clinics (OR 0.02, 95% CI: 0.0-0.17, p < 0.001). Correct management in tests of knowledge administered to the same 274 physicians for the same case was 45 percentage points (95% CI: 37%-53%) higher with 24 percentage points (95% CI: -33% to -15%) fewer antibiotic prescriptions. Relative to the current system, where patients can choose to bypass any level of care, simulations suggest that a system of managed referral with gatekeeping at the level of village clinics would reduce proportions of correct management from 41% to 16%, while gatekeeping at the level of the township hospital would retain correct management close to current levels at 37%. The main limitations of the study are 2-fold. First, we evaluate the management of a one-time new patient presenting with presumptive TB, which may not reflect how providers manage repeat patients or more complicated TB presentations. Second, simulations under alternate policies require behavioral and statistical assumptions that should be addressed in future applications of this method. There were significant quality deficits among village clinics and township health centers in the management of a classic case of presumptive TB, with higher proportions of correct case management in county hospitals. Poor clinical performance does not arise only from a lack of knowledge, a phenomenon known as the "know-do" gap. Given significant deficits in quality of care, reforms encouraging first contact with lower tiers of the health system can improve efficiency only with concomitant improvements in appropriate management of presumptive TB patients in village clinics and township health centers.

Drug interactions with neuromuscular blockers.

PubMed

Feldman, S; Karalliedde, L

1996-10-01

Drugs administered to patients undergoing anaesthesia may complicate the use of the neuromuscular blockers that are given to provide good surgical conditions. The various sites of interaction include actions on motor nerve conduction and spinal reflexes, acetylcholine (ACh) synthesis, mobilisation and release, sensitivity of the motor end plate to ACh and the ease of propagation of the motor action potential. In addition, many drugs affect the pharmacokinetics of neuromuscular blockers, especially as most drugs depend to a greater or lesser extent upon renal excretion. The clinically significant interaction between nondepolarisers and depolarisers may be due to blockade of the pre-synaptic nicotinic receptors by the depolarisers, leading to decreased ACh mobilisation and release. Synergism between nondepolarisers probably results from post-synaptic receptor mechanisms. Volatile anaesthetic agents affect the sensitivity of the motor end-plate (post-synaptic receptor blockade) in addition to having effects on pre-synaptic nicotinic function. The effects of nondepolarisers are likely to be potentiated and their action prolonged by large doses of local anaesthetics due to depression of nerve conduction, depression of ACh formation, mobilisation and release, decreases in post-synaptic receptor channel opening times and reductions in muscular contraction. Most antibacterials have effects on pre-synaptic mechanisms. Procainamide and quinidine principally block nicotinic receptor channels. Magnesium has a marked inhibitory effect on ACh release. Calcium antagonists could theoretically interfere with neurotransmitter release and muscle contractility. Phenytoin and lithium decrease ACh release, whilst corticosteroids and furosemide (frusemide) tend to increase the release of the transmitter. Ecothiopate, tacrine, organophosphates, propanidid, metoclopramide and bambuterol depress cholinesterase activity and prolong the duration of the neuromuscular block. The probability of clinically significant interactions increases in patients receiving several drugs with possible effects on neuromuscular transmission and muscle contraction.

An examination of psychopathology and daily impairment in adolescents with social anxiety disorder.

PubMed

Mesa, Franklin; Beidel, Deborah C; Bunnell, Brian E

2014-01-01

Although social anxiety disorder (SAD) is most often diagnosed during adolescence, few investigations have examined the clinical presentation and daily functional impairment of this disorder exclusively in adolescents. Prior studies have demonstrated that some clinical features of SAD in adolescents are unique relative to younger children with the condition. Furthermore, quality of sleep, a robust predictor of anxiety problems and daily stress, has not been examined in socially anxious adolescents. In this investigation, social behavior and sleep were closely examined in adolescents with SAD (n = 16) and normal control adolescents (NC; n = 14). Participants completed a self-report measure and an actigraphy assessment of sleep. Social functioning was assessed via a brief speech and a social interaction task, during which heart rate and skin conductance were measured. Additionally, participants completed a daily social activity journal for 1 week. No differences were observed in objective or subjective quality of sleep. Adolescents with SAD reported greater distress during the analogue social tasks relative to NC adolescents. During the speech task, adolescents with SAD exhibited a trend toward greater speech latency and spoke significantly less than NC adolescents. Additionally, SAD participants manifested greater skin conductance during the speech task. During the social interaction, adolescents with SAD required significantly more confederate prompts to stimulate interaction. Finally, adolescents with SAD reported more frequent anxiety-provoking situations in their daily lives, including answering questions in class, assertive communication, and interacting with a group. The findings suggest that, although adolescents with SAD may not exhibit daily impaired sleep, the group does experience specific behavioral and physiological difficulties in social contexts regularly. Social skills training may be a critical component in therapeutic approaches for this group.

Serum Chloride and Sodium Interplay in Patients With Acute Myocardial Infarction and Heart Failure With Reduced Ejection Fraction: An Analysis From the High-Risk Myocardial Infarction Database Initiative.

PubMed

Ferreira, João Pedro; Girerd, Nicolas; Duarte, Kevin; Coiro, Stefano; McMurray, John J V; Dargie, Henry J; Pitt, Bertram; Dickstein, Kenneth; Testani, Jeffrey M; Zannad, Faiez; Rossignol, Patrick

2017-02-01

Serum chloride levels were recently found to be independently associated with mortality in heart failure (HF). We investigated the relationship between serum chloride and clinical outcomes in 7195 subjects with acute myocardial infarction complicated by reduced left ventricular function and HF. The studied outcomes were all-cause mortality, cardiovascular mortality, and hospitalization for HF. Both chloride and sodium had a nonlinear association with the studied outcomes (P<0.05 for linearity). Patients in the lowest chloride tertile (chloride ≤100) were older, had more comorbidities, and had lower sodium levels (P<0.05 for all). Serum chloride showed a significant interaction with sodium with regard to all studied outcomes (P for interaction <0.05 for all). The lowest chloride tertile (≤100 mmol/L) was associated with increased mortality rates in the context of lower sodium (≤138 mmol/L; adjusted hazard ratio [95% confidence interval] for all-cause mortality=1.42 (1.14-1.77); P=0.002), whereas in the context of higher sodium levels (>141 mmol/L), the association with mortality was lost. Spline-transformed chloride and its interaction with sodium did not add significant prognostic information on top of other well-established prognostic variables (P>0.05 for all outcomes). In post-myocardial infarction with systolic dysfunction and HF, low serum chloride was associated with mortality (but not hospitalization for HF) in the setting of lower sodium. Overall, chloride and its interaction with sodium did not add clinically relevant prognostic information on top of other well-established prognostic variables. Taken together, these data support an integrated and critical consideration of chloride and sodium interplay. © 2017 American Heart Association, Inc.

East Asian perspective on the interaction between proton pump inhibitors and clopidogrel.

PubMed

Zou, Duowu; Goh, Khean-Lee

2017-06-01

Both proton pump inhibitors (PPIs) and clopidogrel are widely prescribed in the Asia-Pacific population. PPIs are the mainstay therapeutic agents for prophylaxis against aspirin gastropathy and for acid-related disorders including gastroesophageal reflux disease. They are also co-prescribed with oral anticoagulant agents and with dual-antiplatelet therapy for the treatment and prevention of gastrointestinal bleeding. Clopidogrel belongs to the drug class of thienopyridines and is currently the most widely prescribed oral anticoagulant agent either alone or in combination with aspirin. Platelet inhibition by clopidogrel is prone to significant inter-individual variability and is believed to be affected by several factors such as genetics and drug-drug interactions. Since it was first reported in 2009, the potential for drug-drug interactions between PPIs and clopidogrel has remained headline news, and its significance in clinical practice is the subject of an ongoing debate. For East Asian patients in particular, the clinical relevance of the interaction between PPIs and clopidogrel remains unclear because of conflicting data, as well as underrepresentation of East Asian subjects in landmark trials. Increased CYP2C19 genetic polymorphisms in individuals from Asia-Pacific countries only fuel the confusion. Recent studies in East Asian cohorts suggests that the potential of PPIs to attenuate the efficacy of clopidogrel could be minimized by the use of newer PPIs with weaker affinity for the CYP2C19 isoenzyme, namely, pantoprazole, dexlansoprazole, and rabeprazole. This review aims to help clinicians choose the most appropriate PPI for co-prescription with clopidogrel in patients from Asia-Pacific countries. © 2016 Journal of Gastroenterology and Hepatology Foundation and John Wiley & Sons Australia, Ltd.

The balance of power in therapeutic interactions with individuals who have intellectual disabilities.

PubMed

Jahoda, Andrew; Selkirk, Mhairi; Trower, Peter; Pert, Carol; Stenfert Kroese, Biza; Dagnan, Dave; Burford, Bronwen

2009-03-01

Establishing a collaborative relationship is a cornerstone of cognitive behavioural therapy (CBT). Increasingly CBT is being offered to people with intellectual disabilities who may have problems with receptive and expressive communication, and a history of disadvantage or discrimination in their relationships with those in positions of power. Consequently, they may have difficulty establishing a collaborative interaction with their therapist. This paper uses a novel method of interactional analysis to examine if collaboration increases as therapy progresses. Fifteen participants with borderline to mild intellectual disabilities and significant problems of depression, anxiety and anger were recruited from specialist clinical services to participate in this study. Verbatim transcripts of therapy sessions 4 and 9 were coded using an initiative-response method of analysing power distribution in dialogue, to investigate collaboration at the level of therapeutic interaction. The initiative-response scores indicated that power was relatively equally distributed between clients and therapists. On this measure there was no significant increase in collaboration as therapy progressed, as the dialogues were relatively equal from session 4. Analyses of the pattern of interaction showed that whilst the therapists asked most questions, the clients contributed to the flow of the analysis and played an active part in dialogues. The implications of these findings are discussed, along with the possible uses of such interactional analyses in identifying barriers to communication and ways of establishing effective therapeutic dialogue.

Linking electronic health records with community-level data to understand childhood obesity risk.

PubMed

Tomayko, E J; Flood, T L; Tandias, A; Hanrahan, L P

2015-12-01

Environmental and socioeconomic factors should be considered along with individual characteristics when determining risk for childhood obesity. To assess relationships and interactions among the economic hardship index (EHI) and race/ethnicity, age and sex in regard to childhood obesity rates in Wisconsin children using an electronic health record dataset. Data were collected using the University of Wisconsin (UW) Public Health Information Exchange database, which links electronic health records with census-derived community-level data. Records from 53,775 children seen at UW clinics from 2007 to 2012 were included. Mixed-effects modelling was used to determine obesity rates and the interaction of EHI with covariates (race/ethnicity, age, sex). When significant interactions were determined, linear regression analyses were performed for each subgroup (e.g. by age groups). The overall obesity rate was 11.7% and significant racial/ethnic disparities were detected. Childhood obesity was significantly associated with EHI at the community level (r = 0.62, P < 0.0001). A significant interaction was determined between EHI and both race/ethnicity and age on obesity rates. Reducing economic disparities and improving environmental conditions may influence childhood obesity risk in some, but not all, races and ethnicities. Furthermore, the impact of EHI on obesity may be compounded over time. Our findings demonstrate the utility of linking electronic health information with census data to rapidly identify community-specific risk factors in a cost-effective manner. © 2014 World Obesity.

Effect of GH/IGF-1 on Bone Metabolism and Osteoporsosis

PubMed Central

Locatelli, Vittorio; Bianchi, Vittorio E.

2014-01-01

Background. Growth hormone (GH) and insulin-like growth factor (IGF-1) are fundamental in skeletal growth during puberty and bone health throughout life. GH increases tissue formation by acting directly and indirectly on target cells; IGF-1 is a critical mediator of bone growth. Clinical studies reporting the use of GH and IGF-1 in osteoporosis and fracture healing are outlined. Methods. A Pubmed search revealed 39 clinical studies reporting the effects of GH and IGF-1 administration on bone metabolism in osteopenic and osteoporotic human subjects and on bone healing in operated patients with normal GH secretion. Eighteen clinical studies considered the effect with GH treatment, fourteen studies reported the clinical effects with IGF-1 administration, and seven related to the GH/IGF-1 effect on bone healing. Results. Both GH and IGF-1 administration significantly increased bone resorption and bone formation in the most studies. GH/IGF-1 administration in patients with hip or tibial fractures resulted in increased bone healing, rapid clinical improvements. Some conflicting results were evidenced. Conclusions. GH and IGF-1 therapy has a significant anabolic effect. GH administration for the treatment of osteoporosis and bone fractures may greatly improve clinical outcome. GH interacts with sex steroids in the anabolic process. GH resistance process is considered. PMID:25147565

Transportability of imagery-enhanced CBT for social anxiety disorder.

PubMed

McEvoy, Peter M; Erceg-Hurn, David M; Barber, Kevin C; Dupasquier, Jessica R; Moscovitch, David A

2018-07-01

Pilot and open trials suggest that imagery-enhanced group cognitive behaviour therapy (CBT) is highly effective for social anxiety disorder (SAD). However, before being considered reliable and generalisable, the effects of the intervention need to be replicated by clinicians in a setting that is independent of the protocol developers. The current study compared outcomes from clients with a principal diagnosis of SAD at the Australian clinic where the protocol was developed (n = 123) to those from an independent Canadian clinic (n = 46) to investigate whether the large effects would generalise. Trainee clinicians from the independent clinic ran the groups using the treatment protocol without any input from its developers. The treatment involved 12 2-h group sessions plus a one-month follow-up. Treatment retention was comparable across both clinics (74% vs. 78%, ≥9/12 sessions) and the between-site effect size was very small and non-significant on the primary outcome (social interaction anxiety, d = 0.09, p = .752). Within-group effect sizes were very large in both settings (ds = 2.05 vs. 2.19), and a substantial minority (41%-44%) achieved clinically significant improvement at follow-up. Replication of treatment effects within an independent clinic and with trainee clinicians increases confidence that outcomes are generalisable. Copyright © 2018 Elsevier Ltd. All rights reserved.

Do Resting Plasma β-Endorphin Levels Predict Responses to Opioid Analgesics?

PubMed

Bruehl, Stephen; Burns, John W; Gupta, Rajnish; Buvanendran, Asokumar; Chont, Melissa; Orlowska, Daria; Schuster, Erik; France, Christopher R

2017-01-01

Clinically feasible predictors of opioid analgesic responses for use in precision pain medicine protocols are needed. This study evaluated whether resting plasma β-endorphin (BE) levels predicted responses to an opioid analgesic, and whether chronic pain status or sex moderated these effects. Participants included 73 individuals with chronic low back pain (CLBP) and 88 pain-free controls, all using no daily opioid analgesics. Participants attended 2 identical laboratory sessions during which they received either intravenous morphine (0.08 mg/kg) or saline placebo, with blood samples obtained before drug administration to assay resting plasma BE levels. Once peak drug activity was achieved in each session, participants engaged in an ischemic forearm pain task (ISC) and a heat pain task. Morphine analgesic effects were derived reflecting the difference in pain outcomes between placebo and morphine conditions. In hierarchical regressions, significant Type (CLBP vs. control)×BE interactions (Ps<0.05) were noted for morphine effects on ISC tolerance, ISC intratask pain ratings, and thermal VAS unpleasantness ratings. These interactions derived primarily from associations between higher BE levels and smaller morphine effects restricted to the CLBP subgroup. All other BE-related effects, including sex interactions, for predicting morphine analgesia failed to reach statistical significance. BE was a predictor of morphine analgesia for only 3 out of 9 outcomes examined, with these effects moderated by chronic pain status but not sex. On the whole, results do not suggest that resting plasma BE levels are likely to be a clinically useful predictor of opioid analgesic responses.

Evaluation of the Potential Pharmacokinetic Interaction between Atomoxetine and Fluvoxamine in Healthy Volunteers.

PubMed

Todor, Ioana; Popa, Adina; Neag, Maria; Muntean, Dana; Bocsan, Corina; Buzoianu, Anca; Vlase, Laurian; Gheldiu, Ana-Maria; Briciu, Corina

2017-01-01

Attention deficit hyperactivity disorder (ADHD) is frequently associated with other psychiatric pathologies. Therefore, the present study investigated a possible pharmacokinetic interaction between atomoxetine (ATX), a treatment option for ADHD, and an antidepressant, namely, fluvoxamine (FVX). Designed as an open-label, non-randomized clinical trial, the study included 2 periods. In period 1 (reference), each subject received ATX 25 mg (single-dose), whereas in period 2 (test), all subjects were given a combination of ATX 25 mg + FVX 100 mg, following a 6-day pretreatment regimen with the enzymatic inhibitor. Non-compartmental methods were employed to determine the pharmacokinetic parameters of ATX and its main active metabolite (glucuronidated form), 4-hydroxyatomoxetine-O-glucuronide. The results revealed significant differences between the study periods for Cmax, AUC0-t and AUC0-∞ values corresponding to ATX and its metabolite. Small, but statistically significant increases in AUC values were reported for both parent drug (1,583.05 ± 1,040.29 vs. 2,111.55 ± 1,411.59 ng*h/ml) and 4-hydroxyatomoxetine-O-glucuronide (5,754.71 ± 1,235.5 vs. 6,293.17 ± 1,219.34 ng*h/ml) after combined treatment of ATX and the enzymatic inhibitor. FVX had a modest effect on the pharmacokinetics of ATX and 4-hydroxyatomoxetine-O-glucuronide. The presence or absence of any clinical consequences associated with this pharmacokinetic drug-drug interaction needs to be established in future studies. © 2016 S. Karger AG, Basel.

A review on therapeutic drug monitoring of immunosuppressant drugs.

PubMed

Mohammadpour, Niloufar; Elyasi, Sepideh; Vahdati, Naser; Mohammadpour, Amir Hooshang; Shamsara, Jamal

2011-11-01

: Immunosuppressants require therapeutic drug monitoring because of their narrow therapeutic index and significant inter-individual variability in blood concentrations. This variability can be because of factors like drug-nutrient interactions, drug-disease interactions, renal-insufficiency, inflammation and infection, gender, age, polymorphism and liver mass. Drug monitoring is widely practiced especially for cyclosporine, tacrolimus, sirolimus and mycophenolic acid. CYCLOSPORINE: Therapeutic monitoring of immunosuppressive therapy with cyclosporine is a critical requirement because of intra- and inter-patient variability of drug absorption, narrow therapeutic window and drug induced nephrotoxicity. MYCOPHENOLIC ACID MPA: Some reasons for therapeutic drug monitoring of MPA during post-transplant period include: relationship between MPA pharmacokinetic parameters and clinical outcomes, Inter-patient pharmacokinetic variability for MPA despite fixed MMF doses, alternations of MPA pharmacokinetics during the first months after transplantation, drug- drug interaction and influence of kidney function on MPA pharmacokinetic. SIROLIMUS: A recent review of the pharmacokinetics of sirolimus suggested a therapeutic range of 5 to 10 μg l(-1) in whole blood. However, the only consensus guidelines published on the therapeutic monitoring of sirolimus concluded that there was not enough information available about the clinical use of the drug to make recommendations. TACROLIMUS: Sudies have shown, in kidney and liver transplant patients, significant associations of low tacrolimus concentrations with rejection and of high concentrations with nephrotoxicity. Although the feasibility of a limited sampling scheme to predict AUC has been demonstrated, as yet, trough, or pre-dose, whole blood concentration monitoring is still the method of choice.

HIV-malaria interactions in North-East India: A prospective cohort study

PubMed Central

Mohapatra, Pradhyumn K.; Pachuau, Elsa; Kumar, Chandra; Borkakoty, Biswajit; Zomawia, Eric; Singh, Achouba; Walia, Kamini; Arora, Rashmi; Mahanta, Jagdish; Subbarao, Sarala K.

2017-01-01

Background & objectives: The interactions between HIV and malaria co-infection have been shown to influence each other in their clinical outcomes in Sub-Saharan Africa. This study was carried out in the two States of north east India endemic for both HIV and malaria infections, to study the interactions between the two diseases in the HIV-infected population. Methods: In this prospective study, a total of 333 HIV-infected individuals were followed up for a period of 6-18 months in Mizoram and Manipur during 2010-2011. The study assessed the changes in viral load and also the therapeutic efficacy of artesunate plus sulphadoxine-pyrimethamine (AS+SP) combination therapy in HIV-infected and HIV-uninfected individuals with Plasmodium falciparum malaria. Results: Viral load in HIV-infected malaria patients on day zero (D0) ranged from 1110 to 147,000 copies/ml. The log transformation of the geometric means of HIV viral loads revealed no significant difference on different days of follow up. There was 100 per cent adequate clinical and parasitological response (ACPR) after treating with artemisinin based combination therapy (ACT) both in HIV-infected and HIV-uninfected P. falciparum-positive individuals. Similarly, chloroquine showed 100 per cent ACPR in P. vivax HIV-infected individuals. Interpretation & conclusion: The study showed no significant increase in HIV viral load in malaria cases. All HIV-infected and HIV-uninfected P. falciparum malaria-positive cases responded to the treatment with 100 per cent ACPR. PMID:28749403

Pharmacokinetic Drug Interactions of Apatinib With Rifampin and Itraconazole.

PubMed

Liu, Xiaoyun; Zhang, Yifan; Chen, Qian; Zhan, Yan; Wang, Quanren; Hu, Chaoying; Yu, Chen; Guo, Zitao; Chen, Xiaoyan; Zhong, Dafang

2017-10-02

Apatinib is a small-molecule tyrosine kinase inhibitor that has been approved for the treatment of patients with advanced-stage gastric cancer or gastroesophageal junction cancer who have progressed or recurred after at least 2 kinds of systemic chemotherapy. In vitro data indicate that cytochrome P450 (CYP) 3A4 is the primary CYP isoenzyme involved in the metabolism of apatinib. Pharmacokinetic drug-drug interactions of apatinib and (1) a CYP3A4 inducer (rifampin) or (2) a CYP3A inhibitor (itraconazole) were clinically evaluated in healthy volunteers. Compared with the single administration of apatinib, its coadministration with rifampin resulted in a 5.6-fold plasma clearance (CL/F) and 83% decrease in plasma AUC 0-t of apatinib. By contrast, coadministration with itraconazole reduced the CL/F of apatinib by 40% and increased its AUC 0-t by 75%. In summary, a strong CYP3A4 inducer (rifampin) had a strong effect (>5-fold) on the clinical pharmacokinetics of apatinib, whereas a strong CYP3A inhibitor (itraconazole 100 mg once a day) had a weak effect (1.25- to 2-fold). Whether these effects are of clinical significance needs further research and information about the exposure-safety and exposure-efficacy relationship of apatinib. © 2017, The American College of Clinical Pharmacology.

Predoctoral Dental Students' Perceptions of Dental Implant Training: Effect of Preclinical Simulation and Clinical Experience.

PubMed

Prasad, Soni; Bansal, Naveen

2017-04-01

The aims of this study were to assess 1) differences in perceptions of dental implant training between dental students who received didactic training alone (control group) and those who received didactic plus simulation training (test group); 2) differences in response between students with and without clinical experience in implant dentistry; and 3) the interaction effect of simulation training and clinical experience on students' satisfaction. A survey was distributed to the control group in 2014 and to the test group in 2015; both groups were at the same U.S. dental school. Data were collected on confidence levels with various implant restorative procedures along with overall satisfaction and number of implant restorations performed by each student. The response rate was 78.7% in the control group and 81.3% in the test group. In the control group, 85.7% of students reported being satisfied with implant training compared to 90.8% of students in the test group. The interaction effect of simulation training and clinical experience on overall student satisfaction was OR=1.5 at 95% CI: 0.8, 3.0. The students who had clinical experience with implant restorative procedures had significantly greater satisfaction than those who did not (OR=4.8, 95% CI: 2.1, 11.1, p<0.01). This study found that both the simulation and clinical experience affected these students' confidence and satisfaction levels with implant education: they were almost five times more satisfied with implant training when clinical experience in implant restorative procedures was a part of their implant education.

Design and Evaluation of a Cochlear Implant Strategy Based on a “Phantom” Channel

PubMed Central

Nogueira, Waldo; Litvak, Leonid M.; Saoji, Aniket A.; Büchner, Andreas

2015-01-01

Unbalanced bipolar stimulation, delivered using charge balanced pulses, was used to produce “Phantom stimulation”, stimulation beyond the most apical contact of a cochlear implant’s electrode array. The Phantom channel was allocated audio frequencies below 300Hz in a speech coding strategy, conveying energy some two octaves lower than the clinical strategy and hence delivering the fundamental frequency of speech and of many musical tones. A group of 12 Advanced Bionics cochlear implant recipients took part in a chronic study investigating the fitting of the Phantom strategy and speech and music perception when using Phantom. The evaluation of speech in noise was performed immediately after fitting Phantom for the first time (Session 1) and after one month of take-home experience (Session 2). A repeated measures of analysis of variance (ANOVA) within factors strategy (Clinical, Phantom) and interaction time (Session 1, Session 2) revealed a significant effect for the interaction time and strategy. Phantom obtained a significant improvement in speech intelligibility after one month of use. Furthermore, a trend towards a better performance with Phantom (48%) with respect to F120 (37%) after 1 month of use failed to reach significance after type 1 error correction. Questionnaire results show a preference for Phantom when listening to music, likely driven by an improved balance between high and low frequencies. PMID:25806818

Pharmacokinetic Interaction Study of Ranitidine and Daijokito in Healthy Volunteers

PubMed Central

Endo, Yusuke; Ishihara, Yoshitaka; Tsuno, Satoshi; Matsuda, Akiko; Qian, Weibin; Miura, Norimasa; Hasegawa, Junichi

2016-01-01

Background Ranitidine is a histamine 2 receptor antagonist, and daijokito is a Kampo (Chinese herbal medicine as practiced in Japan) formula, which is traditionally used for treating constipation and digestive trouble. Previous study demonstrated that daijokito significantly affected the pharmacokinetics of ranitidine in rats; however, the doses of ranitidine and daijokito in that study were higher than in clinical practice. Therefore, we examined the pharmacokinetic interaction between ranitidine and daijokito in clinical practice doses in healthy volunteers. Methods This was a randomized, open label, two-period crossover study in healthy volunteers (n = 7). Volunteers received administrations of either a single dose of ranitidine 300 mg, or ranitidine 300 mg in combination with daijokito extract granules 2.5 g. Plasma concentrations of ranitidine were measured over 12 h by LC/MS/MS method. Results Plasma concentrations of ranitidine were lower with co-administration of daijokito compared with ranitidine alone. Co-administration of daijokito significantly decreased ranitidine area under the plasma concentration-time curve from 0 to 12 h (AUC0–12) and maximum plasma concentration (Cmax) with geometric mean (GM) ratio [90% confidence interval (CI)] for AUC0–12 of 0.609 (0.449, 0.826) and Cmax of 0.515 (0.345, 0.771). Conclusion Co-administration of ranitidine with daijokito resulted in a significant decrease in plasma level of ranitidine in healthy volunteers. PMID:27493481

Interaction Between Low-Dose Methotrexate and Nonsteroidal Anti-inflammatory Drugs, Penicillins, and Proton Pump Inhibitors.

PubMed

Hall, Jill J; Bolina, Monika; Chatterley, Trish; Jamali, Fakhreddin

2017-02-01

To review the potential drug interactions between low-dose methotrexate (LD-MTX) and nonsteroidal anti-inflammatory drugs (NSAIDs), penicillins, and proton-pump inhibitors (PPIs) given the disparity between interactions reported for high-dose and low-dose MTX to help guide clinicians. A literature search was performed in MEDLINE (1946 to September 2016), EMBASE (1974 to September 2016), and International Pharmaceutical Abstracts (1970 to January 2015) to identify reports describing potential drug interactions between LD-MTX and NSAIDS, penicillins, or PPIs. Reference lists of included articles were reviewed to find additional eligible articles. All English-language observational, randomized, and pharmacokinetic (PK) studies assessing LD-MTX interactions in humans were analyzed to determine clinical relevance in making recommendations to clinicians. Clinical case reports were assigned a Drug Interaction Probability Scale score. A total of 32 articles were included (28 with NSAIDs, 3 with penicillins, and 2 with PPIs [1 including both PPI and NSAID]). Although there are some PK data to describe increased LD-MTX concentrations when NSAIDs are used concomitantly, the clinical relevance remains unclear. Based on the limited data on LD-MTX with penicillins and PPIs, no clinically meaningful interaction was identified. Given the available evidence, the clinical importance of the interaction between LD-MTX and NSAIDs, penicillins, and PPIs cannot be substantiated. Health care providers should assess the benefit and risk of LD-MTX regardless of concomitant drug use, including factors known to predispose patients to MTX toxicity, and continue to monitor clinical and laboratory parameters per guideline recommendations.

A proteomic approach to identifying new drug targets (potentiating topoisomerase II poisons).

PubMed

Jenkins, J R

2008-10-01

Topoisomerase II poisons are an established part of best clinical practice for the treatment of a number of solid tumours and haematological malignancies. However, toxicity and resistance to chemotherapeutic drugs often complicate the treatment. Furthermore, topoisomerase II poisons can also induce sister chromatid exchange, chromosomal recombination and chromosome aberrations and are associated with a significant risk of secondary leukaemia. It would therefore be of great clinical benefit if the efficacy of topoisomerase II inhibitors could be enhanced without the increased toxic side effects. It is proposed that clinical agents targeting topoisomerase II can be enhanced by inhibiting proteins that modulate topoisomerase II. The aim is to identify proteins, that by the nature of their interaction with topoisomerase II, represent putative drug targets.

[Development of Diagrammatic Recording System for Choledochoscope and Its Clinical Application].

PubMed

Xue, Zhao; Hu, Liangshuo; Tang, Bo; Zhang, Xiaogang; Lyu, Yi

2017-11-30

To develop a diagrammatic recording system for choledochoscopy and evaluate the system with clinical application. To match the real-time image and procedure illustration during choledochoscopy examination, we combined video-image capture and speech recognition technology to quickly generate personalized choledochoscopy images and texts records. The new system could be used in sharing territorial electronic medical records, telecommuting, scientific research and education, et al. In the clinical application of 32 patients, the choledochoscopy diagrammatic recording system could significantly improve the surgeons' working efficiency and patients' satisfaction. It could also meet the design requirement of remote information interaction. The choledochoscopy diagrammatic recording system which is recommended could elevate the quality of medical service and promote academic exchange and training.

Getting seamless care right from the beginning - integrating computers into the human interaction.

PubMed

Pearce, Christopher; Kumarpeli, Pushpa; de Lusignan, Simon

2010-01-01

The digital age is coming to the health space, behind many other fields of society. In part this is because health remains heavily reliant on human interaction. The doctor-patient relationship remains a significant factor in determining patient outcomes. Whilst there are many benefits to E-Health, there are also significant risks if computers are not adequately integrated into this interaction and accurate data are consequently not available on the patient's journey through the health system. Video analysis of routine clinical consultations in Australian and UK primary care. We analyzed 308 consultations (141+167 respectively) from these systems, with an emphasis on how the consultation starts. Australian consultations have a mean duration of 12.7 mins, UK 11.8 mins. In both countries around 7% of consultations are computer initiated. Where doctors engaged with computer use the patient observed the computer screen much more and better records were produced. However, there was suboptimal engagement and poor records and no coding in around 20% of consultations. How the computer is used at the start of the consultation can set the scene for an effective interaction or reflect disengagement from technology and creation of poor records.

Effect of Playing Interactive Computer Game on Distress of Insulin Injection Among Type 1 Diabetic Children

PubMed Central

Ebrahimpour, Fatemeh; Sadeghi, Narges; Najafi, Mostafa; Iraj, Bijan; Shahrokhi, Akram

2015-01-01

Background: Diabetic children and their families experience high level stress because of daily insulin injection. Objectives: This study was conducted to investigate the impact of an interactive computer game on behavioral distress due to insulin injection among diabetic children. Patients and Methods: In this clinical trial, thirty children (3-12 years) with type 1 diabetes who needed daily insulin injection were recruited and allocated randomly into two groups. Children in intervention groups received an interactive computer game and asked to play at home for a week. No special intervention was done for control group. The behavioral distress of groups was assessed before, during and after the intervention by Observational Scale of Behavioral Distress–Revised (OSBD-R). Results: Repeated measure ANOVA test showed no significantly difference of OSBD-R over time for control group (P = 0.08), but this changes is signification in the study group (P = 0.001). Comparison mean score of distress were significantly different between two groups (P = 0.03). Conclusions: According to the findings, playing interactive computer game can decrease behavioral distress induced by insulin injection in type 1 diabetic children. It seems this game can be beneficial to be used alongside other interventions. PMID:26199708

Acculturative stress and experiential avoidance: relations to depression, suicide, and anxiety symptoms among minority college students.

PubMed

Zvolensky, Michael J; Jardin, Charles; Garey, Lorra; Robles, Zuzuky; Sharp, Carla

2016-11-01

Although college campuses represent strategic locations to address mental health disparity among minorities in the US, there has been strikingly little empirical work on risk processes for anxiety/depression among this population. The present investigation examined the interactive effects of acculturative stress and experiential avoidance in relation to anxiety and depressive symptoms among minority college students (n = 1,095; 78.1% female; Mage = 21.92, SD = 4.23; 15.1% African-American (non-Hispanic), 45.3% Hispanic, 32.5% Asian, and 7.1% other races/ethnicities. Results provided empirical evidence of an interaction between acculturative stress and experiential avoidance for suicidal, social anxiety, and anxious arousal symptoms among the studied sample. Inspection of the significant interactions revealed that acculturative stress was related to greater levels of suicidal symptoms, social anxiety, and anxious arousal among minority college students with higher, but not lower, levels of experiential avoidance. However, in contrast to prediction, there was no significant interaction for depressive symptoms. Together, these data provide novel empirical evidence for the clinically-relevant interplay between acculturative stress and experiential avoidance in regard to a relatively wide array of negative emotional states among minority college students.

Social consequences of subclinical negative symptoms: An EMG study of facial expressions within a social interaction.

PubMed

Riehle, Marcel; Lincoln, Tania M

2017-06-01

The negative symptoms of schizophrenia are related to lower social functioning even in non-clinical samples, but little is known about the distinct social consequences of motivational and expressive negative symptoms. In this study we focused on expressive negative symptoms and examined how these symptoms and varying degrees of pro-social facial expressiveness (smiling and mimicry of smiling) relate to the social evaluations by face-to-face interaction partners and to social support. We examined 30 dyadic interactions within a sample of non-clinical participants (N = 60) who were rated on motivational and expressive negative symptoms with the Clinical Assessment Interview for Negative Symptoms (CAINS). We collected data on both interaction partners' smiling-muscle (zygomaticus major) activation simultaneously with electromyography and assessed the general amount of smiling and the synchrony of smiling muscle activations between interaction partners (mimicry of smiling). Interaction partners rated their willingness for future interactions with each other after the interactions. Interaction partners of participants scoring higher on expressive negative symptoms expressed less willingness for future interactions with these participants (r = -0.37; p = 0.01). Smiling behavior was negatively related to expressive negative symptoms but also explained by motivational negative symptoms. Mimicry of smiling and both negative symptom domains were also associated with participants' satisfaction with their social support network. Non-clinical sample with (relatively) low levels of symptoms. Expressive negative symptoms have tangible negative interpersonal consequences and directly relate to diminished pro-social behavior and social support, even in non-clinical samples. Copyright © 2017 Elsevier Ltd. All rights reserved.

Clinically relevant pharmacokinetic herb-drug interactions in antiretroviral therapy

USDA-ARS?s Scientific Manuscript database

For healthcare professionals, the volume of literature available on herb-drug interactions often makes it difficult to separate experimental/potential interactions from those deemed clinically relevant. There is a need for concise and conclusive information to guide pharmacotherapy in HIV/AIDS. In t...

Using Interactive Web-Based Screening, Brief Intervention and Referral to Treatment in an Urban, Safety-Net HIV Clinic

PubMed Central

Rose, Carol Dawson; Cuca, Yvette P.; Kamitani, Emiko; Eng, Shannon; Zepf, Roland; Draughon, Jessica; Lum, Paula

2015-01-01

Substance use among PLHIV is high, and screening, brief intervention, and referral to treatment (SBIRT) is an evidence-based approach to addressing the issue. We examined the acceptability of a technology-based SBIRT program in an urban HIV clinic. An SBIRT intervention was programmed into the clinic’s electronic personal health record. We examined: demographic, health, HIV, and substance use characteristics of participants who completed the web-based intervention compared to those who did not. Fewer than half of the 96 participants assigned to the web-based SBIRT completed it (n=39; 41%). Severity of tobacco and amphetamine use differed significantly between participants who did and did not complete the intervention (p=.03, .04 respectively). Participants with higher severity of tobacco and amphetamines were significantly more likely to utilize the web-based SBIRT. It is important for technology-based approaches to behavioral interventions in clinic take into consideration feasibility, client knowledge, and comfort using technology. PMID:25963770

Interactions between angiotensin AT1 receptor antagonists and second-generation antiepileptic drugs in the test of maximal electroshock.

PubMed

Łukawski, Krzysztof; Janowska, Agnieszka; Jakubus, Tomasz; Czuczwar, Stanisław J

2014-06-01

The anticonvulsant activity of angiotensin AT1 receptor antagonists, losartan (2-n-butyl-4-chloro-5-hydroxymethyl-1-[(2'(1H-tetrazol-5-yl)-biphenil-4-yl)methyl]imidazole) and telmisartan (49-[(1,49-dimethyl-29-propyl[2,69-bi-1H-benzimidazo]-19-yl)methyl]-[1,19-biphenyl]-2-carboxylic acid), has been reported recently. It is suggested that AT1 receptor antagonists may affect the protective action of antiepileptic drugs. The aim of this study was to determine the influence of losartan and telmisartan on the anticonvulsant activity of some second-generation antiepileptics (lamotrigine - LTG, oxcarbazepine - OXC, and topiramate - TPM). For this purpose, the maximal electroshock seizure (MES) test in mice was used. Additionally, the drug combinations were checked for adverse effects in the passive avoidance and chimney tests. In the MES test, losartan at the doses of 30 and 50 mg/kg, administered intraperitoneally (i.p.), potentiated the protective action of LTG (P < 0.01). This interaction was not accompanied by a significant change of LTG level either in plasma or in the brain. Telmisartan at the dose of 30 mg/kg i.p. enhanced the anticonvulsant action of TPM (P < 0.01). However, this interaction was pharmacokinetic in nature, as telmisartan significantly increased plasma and total brain concentrations of TPM (P < 0.001). The combinations of AT1 receptor antagonists with antiepileptic drugs did not affect retention in the passive avoidance test or motor coordination in the chimney test. The potentiation of the anticonvulsant action of LTG by losartan probably on account of pharmacodynamic interactions, make this combination important for further experimental and clinical studies. The combination of telmisartan and TPM is less beneficial due to pharmacokinetic interactions. © 2013 The Authors Fundamental and Clinical Pharmacology © 2013 Société Française de Pharmacologie et de Thérapeutique.

Population-based analysis of Alzheimer's disease risk alleles implicates genetic interactions.

PubMed

Ebbert, Mark T W; Ridge, Perry G; Wilson, Andrew R; Sharp, Aaron R; Bailey, Matthew; Norton, Maria C; Tschanz, JoAnn T; Munger, Ronald G; Corcoran, Christopher D; Kauwe, John S K

2014-05-01

Reported odds ratios and population attributable fractions (PAF) for late-onset Alzheimer's disease (LOAD) risk loci (BIN1, ABCA7, CR1, MS4A4E, CD2AP, PICALM, MS4A6A, CD33, and CLU) come from clinically ascertained samples. Little is known about the combined PAF for these LOAD risk alleles and the utility of these combined markers for case-control prediction. Here we evaluate these loci in a large population-based sample to estimate PAF and explore the effects of additive and nonadditive interactions on LOAD status prediction performance. 2419 samples from the Cache County Memory Study were genotyped for APOE and nine LOAD risk loci from AlzGene.org. We used logistic regression and receiver operator characteristic analysis to assess the LOAD status prediction performance of these loci using additive and nonadditive models and compared odds ratios and PAFs between AlzGene.org and Cache County. Odds ratios were comparable between Cache County and AlzGene.org when identical single nucleotide polymorphisms were genotyped. PAFs from AlzGene.org ranged from 2.25% to 37%; those from Cache County ranged from .05% to 20%. Including non-APOE alleles significantly improved LOAD status prediction performance (area under the curve = .80) over APOE alone (area under the curve = .78) when not constrained to an additive relationship (p < .03). We identified potential allelic interactions (p values uncorrected): CD33-MS4A4E (synergy factor = 5.31; p < .003) and CLU-MS4A4E (synergy factor = 3.81; p < .016). Although nonadditive interactions between loci significantly improve diagnostic ability, the improvement does not reach the desired sensitivity or specificity for clinical use. Nevertheless, these results suggest that understanding gene-gene interactions may be important in resolving Alzheimer's disease etiology. Copyright © 2014 Society of Biological Psychiatry. Published by Elsevier Inc. All rights reserved.

Effects of Video Feedback on Early Coercive Parent–Child Interactions: The Intervening Role of Caregivers’ Relational Schemas

PubMed Central

Smith, Justin D.; Dishion, Thomas J.; Moore, Kevin J.; Shaw, Daniel S.; Wilson, Melvin N.

2013-01-01

Objective We examined the effect of adding a video feedback intervention component to the assessment feedback session of the Family Check-Up intervention (FCU; Dishion & Stormshak, 2007). We hypothesized that the addition of video feedback procedures during the FCU feedback at child age 2 would have a positive effect on caregivers’ negative relational schemas of their child, which in turn would mediate reductions in observed coercive caregiver-child interactions assessed at age 5. Method We observed the caregiver-child interaction videotapes of 79 high-risk families with toddlers exhibiting clinically significant problem behaviors. A quasi-random sample of families were provided with direct feedback on their interactions during the feedback session of the FCU protocol. Results Path analysis indicated that reviewing and engaging in feedback about videotaped age-2 assessment predicted reduced caregivers’ negative relational schemas of the child at age 3, which acted as an intervening variable on the reduction of observed parent–child coercive interactions recorded at age 5. Video feedback predicted improved family functioning over and above level of engagement in the FCU in subsequent years, indicating the important incremental contribution of using video feedback procedures in early family-based preventive interventions for problem behaviors. Conclusions Supportive video feedback on coercive family dynamics is an important strategy for promoting caregiver motivation to reduce negative attributions toward the child, which fuel coercive interactions. Our study also contributes to the clinical and research literature concerning coercion theory and effective intervention strategies by identifying a potential mechanism of change. PMID:23534831

Transcriptome profiling identified differentially expressed genes and pathways associated with tamoxifen resistance in human breast cancer

PubMed Central

Men, Xin; Ma, Jun; Wu, Tong; Pu, Junyi; Wen, Shaojia; Shen, Jianfeng; Wang, Xun; Wang, Yamin; Chen, Chao; Dai, Penggao

2018-01-01

Tamoxifen (TAM) resistance is an important clinical problem in the treatment of breast cancer. In order to identify the mechanism of TAM resistance for estrogen receptor (ER)-positive breast cancer, we screened the transcriptome using RNA-seq and compared the gene expression profiles between the MCF-7 mamma carcinoma cell line and the TAM-resistant cell line TAMR/MCF-7, 52 significant differential expression genes (DEGs) were identified including SLIT2, ROBO, LHX, KLF, VEGFC, BAMBI, LAMA1, FLT4, PNMT, DHRS2, MAOA and ALDH. The DEGs were annotated in the GO, COG and KEGG databases. Annotation of the function of the DEGs in the KEGG database revealed the top three pathways enriched with the most DEGs, including pathways in cancer, the PI3K-AKT pathway, and focal adhesion. Then we compared the gene expression profiles between the Clinical progressive disease (PD) and the complete response (CR) from the cancer genome altas (TCGA). 10 common DEGs were identified through combining the clinical and cellular analysis results. Protein-protein interaction network was applied to analyze the association of ER signal pathway with the 10 DEGs. 3 significant genes (GFRA3, NPY1R and PTPRN2) were closely related to ER related pathway. These significant DEGs regulated many biological activities such as cell proliferation and survival, motility and migration, and tumor cell invasion. The interactions between these DEGs and drug resistance phenomenon need to be further elucidated at a functional level in further studies. Based on our findings, we believed that these DEGs could be therapeutic targets, which can be explored to develop new treatment options. PMID:29423105

Statin therapy for acute respiratory distress syndrome: an individual patient data meta-analysis of randomised clinical trials.

PubMed

Nagendran, Myura; McAuley, Daniel F; Kruger, Peter S; Papazian, Laurent; Truwit, Jonathon D; Laffey, John G; Thompson, B Taylor; Clarke, Mike; Gordon, Anthony C

2017-05-01

We performed an individual patient data meta-analysis to assess the possible benefits and harms of statin therapy in adults with acute respiratory distress syndrome (ARDS) and to investigate effects in specific ARDS subgroups. We identified randomised clinical trials up to 31 October 2016 that had investigated statin therapy versus placebo in patients with ARDS. Individual patient data from each trial were compiled. Conventional two-stage meta-analyses were performed for primary and secondary outcomes, and one-stage regression models with single treatment-covariate interactions for subgroup analyses. Risk of bias was assessed using the Cochrane Risk of Bias Tool. Six trials with a total of 1755 patients were included. For the primary outcomes, there was no significant effect of statin therapy on 28-day mortality [relative risk (RR) 1.03, 95% CI 0.86-1.23], ventilator-free days (mean difference 0.34 days, 95% CI -0.68 to 1.36) or serious adverse events (RR 1.14, 95% CI 0.84-1.53). There was a significantly increased incidence of raised serum creatine kinase or transaminase levels with statin therapy (106/879; 12.1%) versus control (78/876; 8.9%) (RR 1.40, 95% CI 1.07-1.83, p = 0.015). There were no significant treatment-covariate interactions in the predefined subgroups investigated. We found no clinical benefit from initiation of statin therapy in adult patients with ARDS, either overall or in predefined subgroups. While there was an increased incidence of raised serum creatine kinase and transaminase levels, there was no difference in serious adverse events among groups. Therefore, we do not recommend initiation of statin therapy for the treatment of ARDS.

Harnessing interactive technologies to improve health outcomes in juvenile idiopathic arthritis.

PubMed

Coda, Andrea; Sculley, Dean; Santos, Derek; Girones, Xavier; Brosseau, Lucie; Smith, Derek R; Burns, Joshua; Rome, Keith; Munro, Jane; Singh-Grewal, Davinder

2017-05-16

Children and adolescents with Juvenile Idiopathic Arthritis (JIA) typically have reduced physical activity level and impaired aerobic and anaerobic exercise capacity when compared to their non-JIA counterparts. Low intensity exercise regimens appear to be safe in children with JIA and may results in improvements in overall physical function. Poor adherence to paediatric rheumatology treatment may lead to negative clinical outcomes and possibly increased disease activity. This includes symptoms such as pain, fatigue, quality of life, longer term outcomes including joint damage, as well as increase of healthcare associated costs. Low adherence to medications such as methotrexate and biological-drugs remains a significant issue for paediatric rheumatologists, with alarming reports that less than half of the children with JIA are compliant to drug-therapy. The recent advances in interactive technology resulting in a variety of wearable user-friendly smart devices may become a key solution to address important questions in JIA clinical management. Fully understanding the impact that arthritis and treatment complications have upon individual children and their families has long been a challenge for clinicians. Modern interactive technologies can be customised and accessed directly in the hands or wrists of children with JIA. These secured networks could be accessible 'live' at anytime and anywhere by the child, parents and clinicians. Multidisciplinary teams in paediatric rheumatology may benefit from adopting these technologies to better understand domains such as patient biological parameters, symptoms progression, adherence to drug-therapy, quality of life, and participation in physical activities. Most importantly the use of smart devices technologies may also facilitate more timely clinical decisions, improve self-management and parents awareness in the progression of their child's disease. Paediatric rheumatology research could also benefit from the use of these smart devices, as they would allow real-time access to meaningful data to thoroughly understand the disease-patterns of JIA, such as pain and physical activity outcomes. Data collection that typically occurs once every 1 or 3 months in the clinical setting could instead be gathered every week, day, minute or virtually live online. Arguably, few limitations in wearing such interactive technologies still exist and require further developments. Finally, by embracing and adapting these new and now highly accessible interactive technologies, clinical management and research in paediatric rheumatology may be greatly advanced.

Patient perceptions and expectations of an anticoagulation service: a quantitative comparison study of clinic-based testers and patient self-testers.

PubMed

Money, Arthur G; Barnett, Julie; Kuljis, Jasna; Duffin, Debbie

2015-12-01

Government initiatives see the provision of technology-assisted self-care as one of the key areas in which there is capacity for improving quality of care whilst reducing costs. However, levels of patient engagement in self-testing and management (STM) remain low. Little emphasis has been placed on understanding the patients' perspectives of the reasons for this limited engagement. Typically, patient engagement in STM is achieved via the provision of patient education programmes, which aim to enable patients to make the changes necessary to become competent self-carers. However, placing the onus to change on the individual patient is unrealistic. If levels of patient engagement are to be improved, patient needs and expectations of clinical services must be better understood and service provision must be adapted accordingly. Explore patient perceptions and expectations of clinical service provision and their views of having and making choices about care. Participants [N = 191, 103 patient self-tester managers (PSTMs) and 87 clinic-based testers (CBTs)] completed the SERVQUAL and ChQ instruments to capture perspectives on service quality and choice, respectively. A comparative statistical analysis explored the similarities and differences between PSTMs' and CBTs' responses. Clinic-based testers' perceptions of service quality were significantly more positive than PSTMs', as were their expectations of the 'tangible' aspects of service delivery. PSTMs' expectations of service quality were significantly higher than their perceptions. PSTMs attributed significantly more value to making choices compared with CBTs. To close the gap between PSTMs expectations and perceptions of service quality and better cater for their choice preferences, service providers may benefit from taking into account the following practice considerations: maintain frequent, timely, personalised and direct interactions with PSTMs; prioritise investment in resources to facilitate patient/practitioner interaction over tangible facilities; ensure that PSTMs are given the opportunity to make choices about their care. © 2015 The Authors. Scandinavian Journal of Caring Sciences published by John Wiley & Sons Ltd on behalf of Nordic College of Caring Science.

Effects of septum and pericardium on heart-lung interactions in a cardiopulmonary simulation model.

PubMed

Karamolegkos, Nikolaos; Albanese, Antonio; Chbat, Nicolas W

2017-07-01

Mechanical heart-lung interactions are often overlooked in clinical settings. However, their impact on cardiac function can be quite significant. Mechanistic physiology-based models can provide invaluable insights into such cardiorespiratory interactions, which occur not only under external mechanical ventilatory support but in normal physiology as well. In this work, we focus on the cardiac component of a previously developed mathematical model of the human cardiopulmonary system, aiming to improve the model's response to the intrathoracic pressure variations that are associated with the respiratory cycle. Interventricular septum and pericardial membrane are integrated into the existing model. Their effect on the overall cardiac response is explained by means of comparison against simulation results from the original model as well as experimental data from literature.

Effects of Age and Sex on Clinical Outcomes After Percutaneous Coronary Intervention Relative to Coronary Artery Bypass Grafting in Patients With Triple-Vessel Coronary Artery Disease.

PubMed

Yamaji, Kyohei; Shiomi, Hiroki; Morimoto, Takeshi; Nakatsuma, Kenji; Toyota, Toshiaki; Ono, Koh; Furukawa, Yutaka; Nakagawa, Yoshihisa; Kadota, Kazushige; Ando, Kenji; Shirai, Shinichi; Onodera, Tomoya; Watanabe, Hirotoshi; Natsuaki, Masahiro; Sakata, Ryuzo; Hanyu, Michiya; Nishiwaki, Noboru; Komiya, Tatsuhiko; Kimura, Takeshi

2016-05-10

Age and sex are important considerations in the choice between percutaneous coronary intervention (PCI) and coronary artery bypass grafting (CABG) in daily clinical practice. Of 25 816 patients enrolled in the multicenter Coronary Revascularization Demonstrating Outcome Study in Kyoto (CREDO-Kyoto; Cohort-1, n=9877; Cohort-2, n=15 939), the present study population consisted of 5651 patients (men, n=3998; women, n=1653) with triple-vessel coronary artery disease who were considered to be pertinent in comparisons of PCI with CABG (PCI, n=3165; CABG, n=2486). Patients were divided into 3 groups according to the tertiles of age: ≤65 years (n=1972), 66 to 73 years (n=1820), and ≥74 years (n=1859). The excess adjusted mortality risk of PCI relative to CABG was significant in patients ≥74 years of age (hazard ratio [HR], 1.40; 95% confidence interval [CI], 1.10-1.79; P=0.006), whereas the risks were neutral in patients ≤65 years of age (HR, 1.05; 95% CI, 0.73-1.53; P=0.78) and in patients 66 to 73 years of age (HR, 1.03; 95% CI, 0.78-1.36; P=0.85; interaction P=0.003). The excess mortality risk of PCI relative to CABG was significant in men (HR, 1.24; 95% CI, 1.03-1.50; P=0.02) and trended to be significant in women (HR, 1.34; 95% CI, 0.98-1.84; P=0.07) without significant interaction between sex and the mortality risk of PCI relative to CABG (interaction P=0.40). There was a significant association between age and the mortality risk of PCI relative to CABG with excess risk in patients ≥74 years of age and neutral risk in younger patients. There was no significant sex-related difference in the mortality risk of PCI relative to CABG. © 2016 American Heart Association, Inc.

Patient educational technologies and their use by patients diagnosed with localized prostate cancer.

PubMed

Baverstock, Richard J; Crump, R Trafford; Carlson, Kevin V

2015-09-29

Two urology practices in Calgary, Canada use patient educational technology (PET) as a core component of their clinical practice. The purpose of this study was to determine how patients interact with PET designed to inform them about their treatment options for clinically localized prostate cancer. A PET library was developed with 15 unique prostate-related educational modules relating to diagnosis, treatment options, and potential side effects. The PET collected data regarding its use, and those data were used to conduct a retrospective analysis. Descriptive analyses were conducted and comparisons made between patients' utilization of the PET library during first and subsequent access; Pearson's Chi-Square was used to test for statistical significance, where appropriate. Every patient (n = 394) diagnosed with localized prostate cancer was given access to the PET library using a unique identifier. Of those, 123 logged into the library and viewed at least one module and 94 patients logged into the library more than once. The average patient initially viewed modules pertaining to their diagnosis. Viewing behavior significantly changed in subsequent logins, moving towards modules pertaining to treatment options, decision making, and post-surgical information. As observed through the longitudinal utilization of the PET library, information technology offers clinicians an opportunity to provide an interactive platform to meet patients' dynamic educational needs. Understanding these needs will help inform the development of more useful PETs. The informational needs of patients diagnosed with clinically localized prostate cancer changed throughout the course of their diagnosis and treatment.

Music therapy in the assessment and treatment of autistic spectrum disorder: clinical application and research evidence.

PubMed

Wigram, T; Gold, C

2006-09-01

Children and adolescents with autistic spectrum disorder (ASD) presenting with significant limitations in conventional forms of verbal and non-verbal communication are found to respond positively to music therapy intervention involving both active, improvizational methods and receptive music therapy approaches. Improvizational musical activity with therapeutic objectives and outcomes has been found to facilitate motivation, communication skills and social interaction, as well as sustaining and developing attention. The structure and predictability found in music assist in reciprocal interaction, from which tolerance, flexibility and social engagement to build relationships emerge, relying on a systematic approach to promote appropriate and meaningful interpersonal responses. Published reports of the value and effectiveness of music therapy as an intervention for children with ASD range from controlled studies to clinical case reports. Further documentation has emphasized the role music therapy plays in diagnostic and clinical assessment. Music therapy assessment can identify limitations and weaknesses in children, as well as strengths and potentials. Research evidence from a systematic review found two randomized controlled trials that examined short-term effects of structured music therapy intervention. Significant effects were found in these studies even with extremely small samples, and the findings are important because they demonstrate the potential of the medium of music for autistic children. Case series studies were identified that examined the effects of improvizational music therapy where communicative behaviour, language development, emotional responsiveness, attention span and behavioural control improved over the course of an intervention of improvizational music therapy.

Evaluation of an interactive case simulation system in dermatology and venereology for medical students

PubMed Central

Wahlgren, Carl-Fredrik; Edelbring, Samuel; Fors, Uno; Hindbeck, Hans; Ståhle, Mona

2006-01-01

Background Most of the many computer resources used in clinical teaching of dermatology and venereology for medical undergraduates are information-oriented and focus mostly on finding a "correct" multiple-choice alternative or free-text answer. We wanted to create an interactive computer program, which facilitates not only factual recall but also clinical reasoning. Methods Through continuous interaction with students, a new computerised interactive case simulation system, NUDOV, was developed. It is based on authentic cases and contains images of real patients, actors and healthcare providers. The student selects a patient and proposes questions for medical history, examines the skin, and suggests investigations, diagnosis, differential diagnoses and further management. Feedback is given by comparing the user's own suggestions with those of a specialist. In addition, a log file of the student's actions is recorded. The program includes a large number of images, video clips and Internet links. It was evaluated with a student questionnaire and by randomising medical students to conventional teaching (n = 85) or conventional teaching plus NUDOV (n = 31) and comparing the results of the two groups in a final written examination. Results The questionnaire showed that 90% of the NUDOV students stated that the program facilitated their learning to a large/very large extent, and 71% reported that extensive working with authentic computerised cases made it easier to understand and learn about diseases and their management. The layout, user-friendliness and feedback concept were judged as good/very good by 87%, 97%, and 100%, respectively. Log files revealed that the students, in general, worked with each case for 60–90 min. However, the intervention group did not score significantly better than the control group in the written examination. Conclusion We created a computerised case simulation program allowing students to manage patients in a non-linear format supporting the clinical reasoning process. The student gets feedback through comparison with a specialist, eliminating the need for external scoring or correction. The model also permits discussion of case processing, since all transactions are stored in a log file. The program was highly appreciated by the students, but did not significantly improve their performance in the written final examination. PMID:16907972

Does patient-perceived handicap correspond to the modified clinical test for the sensory interaction on balance?

PubMed

Loughran, Sean; Gatehouse, Stuart; Kishore, Ameet; Swan, Iain R C

2006-01-01

To determine whether patient self-reported handicap correlates with scores obtained from the modified Clinical Test for the Sensory Interaction on Balance as assessed by the Neurocom VSR Balance Master platform. Prospective observational. Balance clinic in tertiary referral center. Patients referred with dizziness or imbalance as their primary complaint. The modified Clinical Test for the Sensory Interaction on Balance scores as assessed by the Neurocom VSR Balance Master platform, the Dizziness Handicap Inventory, and the Health Utilities Index Marks 2 and 3. One hundred fifty-nine patients were entered into the study. The mean age of participants was 54.5 years, with a female-to-male ratio of 2.1:1. The scores for the Dizziness Handicap Inventory and Health Utilities Index are similar between sexes, and although the Dizziness Handicap Inventory score did not correlate with age, Health Utilities Index 2 and 3 scores did show a negative correlation with increasing age. There are weak, positive correlations between the Dizziness Handicap Inventory and the firm surface conditions of the modified Clinical Test for the Sensory Interaction on Balance but no useful correlation with the foam conditions. Similar weak negative correlations were found between the Health Utilities Index 2 and 3 and the modified Clinical Test for the Sensory Interaction on Balance scores. Patient-perceived handicap of imbalance appears to correlate poorly with assessment of postural stability using the modified Clinical Test for the Sensory Interaction on Balance.

SeqReporter: automating next-generation sequencing result interpretation and reporting workflow in a clinical laboratory.

PubMed

Roy, Somak; Durso, Mary Beth; Wald, Abigail; Nikiforov, Yuri E; Nikiforova, Marina N

2014-01-01

A wide repertoire of bioinformatics applications exist for next-generation sequencing data analysis; however, certain requirements of the clinical molecular laboratory limit their use: i) comprehensive report generation, ii) compatibility with existing laboratory information systems and computer operating system, iii) knowledgebase development, iv) quality management, and v) data security. SeqReporter is a web-based application developed using ASP.NET framework version 4.0. The client-side was designed using HTML5, CSS3, and Javascript. The server-side processing (VB.NET) relied on interaction with a customized SQL server 2008 R2 database. Overall, 104 cases (1062 variant calls) were analyzed by SeqReporter. Each variant call was classified into one of five report levels: i) known clinical significance, ii) uncertain clinical significance, iii) pending pathologists' review, iv) synonymous and deep intronic, and v) platform and panel-specific sequence errors. SeqReporter correctly annotated and classified 99.9% (859 of 860) of sequence variants, including 68.7% synonymous single-nucleotide variants, 28.3% nonsynonymous single-nucleotide variants, 1.7% insertions, and 1.3% deletions. One variant of potential clinical significance was re-classified after pathologist review. Laboratory information system-compatible clinical reports were generated automatically. SeqReporter also facilitated quality management activities. SeqReporter is an example of a customized and well-designed informatics solution to optimize and automate the downstream analysis of clinical next-generation sequencing data. We propose it as a model that may envisage the development of a comprehensive clinical informatics solution. Copyright © 2014 American Society for Investigative Pathology and the Association for Molecular Pathology. Published by Elsevier Inc. All rights reserved.

Interaction of Antibiotics with Innate Host Defense Factors against Salmonella enterica Serotype Newport

PubMed Central

Kumaraswamy, Monika; Kousha, Armin; Nizet, Victor

2017-01-01

ABSTRACT This study examines the pharmacodynamics of antimicrobials that are used to treat Salmonella with each other and with key components of the innate immune system. Antimicrobial synergy was assessed using time-kill and checkerboard assays. Antimicrobial interactions with innate immunity were studied by employing cathelicidin LL-37, whole-blood, and neutrophil killing assays. Ceftriaxone and ciprofloxacin were found to be synergistic in vitro against Salmonella enterica serotype Newport. Ceftriaxone, ciprofloxacin, and azithromycin each demonstrated synergy with the human cathelicidin defense peptide LL-37 in killing Salmonella. Exposure of Salmonella to sub-MICs of ceftriaxone resulted in enhanced susceptibility to LL-37, whole blood, and neutrophil killing. The activity of antibiotics in vivo against Salmonella may be underestimated in bacteriologic media lacking components of innate immunity. The pharmacodynamic interactions of antibiotics used to treat Salmonella with each other and with components of innate immunity warrant further study in light of recent findings showing in vivo selection of antimicrobial resistance by single agents in this pathogen. IMPORTANCE It is becoming increasingly understood that the current paradigms of in vitro antimicrobial susceptibility testing may have significant shortcomings in predicting activity in vivo. This study evaluated the activity of several antibiotics alone and in combination against clinical isolates of Salmonella enterica serotype Newport (meningitis case) utilizing both conventional and physiological media. In addition, the interactions of these antibiotics with components of the innate immune system were evaluated. Azithromycin, which has performed quite well clinically despite high MICs in conventional media, was shown to be more active in physiological media and to enhance innate immune system killing. Alternatively, chloramphenicol did not show enhanced immune system killing, paralleling its inferior clinical performance to other antibiotics that have been used to treat Salmonella meningitis. These findings are important additions to the building understanding of current in vitro antimicrobial assay limitations that hopefully will amount to future improvements in these assays to better predict clinical efficacy and activity in vivo. PMID:29242830

Association of unconscious race and social class bias with vignette-based clinical assessments by medical students.

PubMed

Haider, Adil H; Sexton, Janel; Sriram, N; Cooper, Lisa A; Efron, David T; Swoboda, Sandra; Villegas, Cassandra V; Haut, Elliott R; Bonds, Morgan; Pronovost, Peter J; Lipsett, Pamela A; Freischlag, Julie A; Cornwell, Edward E

2011-09-07

Studies involving physicians suggest that unconscious bias may be related to clinical decision making and may predict poor patient-physician interaction. The presence of unconscious race and social class bias and its association with clinical assessments or decision making among medical students is unknown. To estimate unconscious race and social class bias among first-year medical students and investigate its relationship with assessments made during clinical vignettes. A secure Web-based survey was administered to 211 medical students entering classes at Johns Hopkins School of Medicine, Baltimore, Maryland, in August 2009 and August 2010. The survey included the Implicit Association Test (IAT) to assess unconscious preferences, direct questions regarding students' explicit race and social class preferences, and 8 clinical assessment vignettes focused on pain assessment, informed consent, patient reliability, and patient trust. Adjusting for student demographics, multiple logistic regression was used to determine whether responses to the vignettes were associated with unconscious race or social class preferences. Association of scores on an established IAT for race and a novel IAT for social class with vignette responses. Among the 202 students who completed the survey, IAT responses were consistent with an implicit preference toward white persons among 140 students (69%, 95% CI, 61%-75%). Responses were consistent with a preference toward those in the upper class among 174 students (86%, 95% CI, 80%-90%). Assessments generally did not vary by patient race or occupation, and multivariable analyses for all vignettes found no significant relationship between implicit biases and clinical assessments. Regression coefficient for the association between pain assessment and race IAT scores was -0.49 (95% CI, -1.00 to 0.03) and for social class, the coefficient was -0.04 (95% CI, -0.50 to 0.41). Adjusted odds ratios for other vignettes ranged from 0.69 to 3.03 per unit change in IAT score, but none were statistically significant. Analysis stratified by vignette patient race or class status yielded similarly negative results. Tests for interactions between patient race or class status and student IAT D scores in predicting clinical assessments were not statistically significant. The majority of first-year medical students at a single school had IAT scores consistent with implicit preference for white persons and possibly for those in the upper class. However, overall vignette-based clinical assessments were not associated with patient race or occupation, and no association existed between implicit preferences and the assessments.

Association of Unconscious Race and Social Class Bias With Vignette-Based Clinical Assessments by Medical Students

PubMed Central

Haider, Adil H.; Sexton, Janel; Sriram, N.; Cooper, Lisa A.; Efron, David T.; Swoboda, Sandra; Villegas, Cassandra V.; Haut, Elliott R.; Bonds, Morgan; Pronovost, Peter J.; Lipsett, Pamela A.; Freischlag, Julie A.; Cornwell, Edward E.

2012-01-01

Context Studies involving physicians suggest that unconscious bias may be related to clinical decision making and may predict poor patient-physician interaction. The presence of unconscious race and social class bias and its association with clinical assessments or decision making among medical students is unknown. Objective To estimate unconscious race and social class bias among first-year medical students and investigate its relationship with assessments made during clinical vignettes. Design, Setting, and Participants A secure Web-based survey was administered to 211 medical students entering classes at Johns Hopkins School of Medicine, Baltimore, Maryland, in August 2009 and August 2010. The survey included the Implicit Association Test (IAT) to assess unconscious preferences, direct questions regarding students’ explicit race and social class preferences, and 8 clinical assessment vignettes focused on pain assessment, informed consent, patient reliability, and patient trust. Adjusting for student demographics, multiple logistic regression was used to determine whether responses to the vignettes were associated with unconscious race or social class preferences. Main Outcome Measures Association of scores on an established IAT for race and a novel IAT for social class with vignette responses. Results Among the 202 students who completed the survey, IAT responses were consistent with an implicit preference toward white persons among 140 students (69%, 95% CI, 61%–75%). Responses were consistent with a preference toward those in the upper class among 174 students (86%, 95% CI, 80%–90%). Assessments generally did not vary by patient race or occupation, and multivariable analyses for all vignettes found no significant relationship between implicit biases and clinical assessments. Regression coefficient for the association between pain assessment and race IAT scores was −0.49 (95% CI, −1.00 to 0.03) and for social class, the coefficient was −0.04 (95% CI, −0.50 to 0.41). Adjusted odds ratios for other vignettes ranged from 0.69 to 3.03 per unit change in IAT score, but none were statistically significant. Analysis stratified by vignette patient race or class status yielded similarly negative results. Tests for interactions between patient race or class status and student IAT D scores in predicting clinical assessments were not statistically significant. Conclusions The majority of first-year medical students at a single school had IAT scores consistent with implicit preference for white persons and possibly for those in the upper class. However, overall vignette-based clinical assessments were not associated with patient race or occupation, and no association existed between implicit preferences and the assessments. PMID:21900134

Improving the learning of clinical reasoning through computer-based cognitive representation.

PubMed

Wu, Bian; Wang, Minhong; Johnson, Janice M; Grotzer, Tina A

2014-01-01

Objective Clinical reasoning is usually taught using a problem-solving approach, which is widely adopted in medical education. However, learning through problem solving is difficult as a result of the contextualization and dynamic aspects of actual problems. Moreover, knowledge acquired from problem-solving practice tends to be inert and fragmented. This study proposed a computer-based cognitive representation approach that externalizes and facilitates the complex processes in learning clinical reasoning. The approach is operationalized in a computer-based cognitive representation tool that involves argument mapping to externalize the problem-solving process and concept mapping to reveal the knowledge constructed from the problems. Methods Twenty-nine Year 3 or higher students from a medical school in east China participated in the study. Participants used the proposed approach implemented in an e-learning system to complete four learning cases in 4 weeks on an individual basis. For each case, students interacted with the problem to capture critical data, generate and justify hypotheses, make a diagnosis, recall relevant knowledge, and update their conceptual understanding of the problem domain. Meanwhile, students used the computer-based cognitive representation tool to articulate and represent the key elements and their interactions in the learning process. Results A significant improvement was found in students' learning products from the beginning to the end of the study, consistent with students' report of close-to-moderate progress in developing problem-solving and knowledge-construction abilities. No significant differences were found between the pretest and posttest scores with the 4-week period. The cognitive representation approach was found to provide more formative assessment. Conclusions The computer-based cognitive representation approach improved the learning of clinical reasoning in both problem solving and knowledge construction.

Improving the learning of clinical reasoning through computer-based cognitive representation

PubMed Central

Wu, Bian; Wang, Minhong; Johnson, Janice M.; Grotzer, Tina A.

2014-01-01

Objective Clinical reasoning is usually taught using a problem-solving approach, which is widely adopted in medical education. However, learning through problem solving is difficult as a result of the contextualization and dynamic aspects of actual problems. Moreover, knowledge acquired from problem-solving practice tends to be inert and fragmented. This study proposed a computer-based cognitive representation approach that externalizes and facilitates the complex processes in learning clinical reasoning. The approach is operationalized in a computer-based cognitive representation tool that involves argument mapping to externalize the problem-solving process and concept mapping to reveal the knowledge constructed from the problems. Methods Twenty-nine Year 3 or higher students from a medical school in east China participated in the study. Participants used the proposed approach implemented in an e-learning system to complete four learning cases in 4 weeks on an individual basis. For each case, students interacted with the problem to capture critical data, generate and justify hypotheses, make a diagnosis, recall relevant knowledge, and update their conceptual understanding of the problem domain. Meanwhile, students used the computer-based cognitive representation tool to articulate and represent the key elements and their interactions in the learning process. Results A significant improvement was found in students’ learning products from the beginning to the end of the study, consistent with students’ report of close-to-moderate progress in developing problem-solving and knowledge-construction abilities. No significant differences were found between the pretest and posttest scores with the 4-week period. The cognitive representation approach was found to provide more formative assessment. Conclusions The computer-based cognitive representation approach improved the learning of clinical reasoning in both problem solving and knowledge construction. PMID:25518871

Improving the learning of clinical reasoning through computer-based cognitive representation.

PubMed

Wu, Bian; Wang, Minhong; Johnson, Janice M; Grotzer, Tina A

2014-01-01

Clinical reasoning is usually taught using a problem-solving approach, which is widely adopted in medical education. However, learning through problem solving is difficult as a result of the contextualization and dynamic aspects of actual problems. Moreover, knowledge acquired from problem-solving practice tends to be inert and fragmented. This study proposed a computer-based cognitive representation approach that externalizes and facilitates the complex processes in learning clinical reasoning. The approach is operationalized in a computer-based cognitive representation tool that involves argument mapping to externalize the problem-solving process and concept mapping to reveal the knowledge constructed from the problems. Twenty-nine Year 3 or higher students from a medical school in east China participated in the study. Participants used the proposed approach implemented in an e-learning system to complete four learning cases in 4 weeks on an individual basis. For each case, students interacted with the problem to capture critical data, generate and justify hypotheses, make a diagnosis, recall relevant knowledge, and update their conceptual understanding of the problem domain. Meanwhile, students used the computer-based cognitive representation tool to articulate and represent the key elements and their interactions in the learning process. A significant improvement was found in students' learning products from the beginning to the end of the study, consistent with students' report of close-to-moderate progress in developing problem-solving and knowledge-construction abilities. No significant differences were found between the pretest and posttest scores with the 4-week period. The cognitive representation approach was found to provide more formative assessment. The computer-based cognitive representation approach improved the learning of clinical reasoning in both problem solving and knowledge construction.

In Vitro CYP2D Inhibitory Effect and Influence on Pharmacokinetics and Pharmacodynamic Parameters of Metoprolol Succinate by Terminalia arjuna in Rats.

PubMed

Varghese, Alice; Savai, Jay; Mistry, Shruti; Khandare, Preeti; Barve, Kalyani; Pandita, Nancy; Gaud, Ram

2016-01-01

Terminalia arjuna Wight & Arn. (Combretaceae) is a tree having an extensive medicinal potential in cardiovascular disorders. T. arjuna bark extract has been reported to play a significant role as a cardiac stimulant for its beneficial effects in angina. Herb - drug interactions (HDI) are one of the most important clinical concerns in the concomitant consumption of herbs and prescription drugs. Our study was to investigate the in vitro CYP2D inhibition potential of Terminalia arjuna (T. arjuna) extracts in rat liver microsomes and to study the influence of aqueous bark extract of T. arjuna on the oral pharmacokinetics and pharmacodynamics of metoprolol succinate in rats. The CYP2D inhibition potential of herbal extracts of T. arjuna was investigated in rat liver microsomes. Pharmacokinetic-pharmacodynamic interaction of aqueous extract of T. arjuna with metoprolol succinate was investigated in rats. The ethyl acetate, alcoholic & aqueous bark extracts of T. arjuna showed potent reversible non-competitive inhibition CYP2D enzyme in rat liver microsomes with IC50 values less than 40 μg/mL. Arjunic acid, arjunetin and arjungenin did not show significant inhibition of CYP2D enzyme in rat liver microsomes. Pharmacokinetic studies showed that aqueous bark extract of T. arjuna led to a significant reduction (P < 0.05) in AUC0-24h and Cmax of metoprolol succinate in rats, when co-administered. Pharmacodynamic studies reveal a significant reduction in therapeutic activity of metoprolol succinate on co-administration with aqueous bark extract of T. arjuna. Based on our in vitro and in vivo findings and until further clinical drug interaction experiments are conducted, the co-administration of drugs, especially those primarily cleared via CYP2D catalyzed metabolism, with T. arjuna extracts should be done with caution.

Rh blood phenotyping (D, E, e, C, c) microarrays using multichannel surface plasmon resonance imaging.

PubMed

Pipatpanukul, Chinnawut; Takeya, Sasaki; Baba, Akira; Amarit, Ratthasart; Somboonkaew, Armote; Sutapun, Boonsong; Kitpoka, Pimpun; Kunakorn, Mongkol; Srikhirin, Toemsak

2018-04-15

The application of Surface Plasmon Resonance Imaging (SPRi) for the detection of transmembrane antigen of the Rhesus (Rh) blood group system is demonstrated. Clinically significant Rh blood group system antigens, including D, C, E, c, and e, can be simultaneously identified via solid phase immobilization assay, which offers significant time savings and assay simplification. Red blood cells (RBCs) flowed through the micro-channel, where a suitable condition for Rh blood group detection was an RBC dilution of 1:10 with a stop-flow condition. Stop flow showed an improvement in specific binding compared to continuous flow. Rh antigens required a longer incubation time to react with the immobilized antibody than A and B antigens due to the difference in antigen type and their location on the RBC. The interaction between the immobilized antibodies and their specific antigenic counterpart on the RBC showed a significant difference in RBC removal behavior using shear flow, measured from the decay of the SPR signal. The strength of the interaction between the immobilized antibody and RBC antigen was determined from the minimum wall shear stress required to start the decay process in the SPR signal. For a given range of immobilized antibody surface densities, the Rh antigen possesses a stronger interaction than A, B, and AB antigens. Identification of 82 samples of ABO and Rh blood groups using SPRi showed good agreement with the standard micro-column agglutination technique. A wider coverage of antigenic recognition for RBC when using the solid phase immobilization assay was demonstrated for the RBC with the antigenic site located on the transmembrane protein of the clinically significant Rh antigen. Given the level of accuracy and precision, the technique showed potential for the detection of the Rh minor blood group system. Copyright © 2017 Elsevier B.V. All rights reserved.

Case Series Analysis of New Zealand Reports of Rapid Intense Potentiation of Warfarin by Roxithromycin.

PubMed

Savage, Ruth L; Tatley, Michael V

2018-05-01

We undertook an analysis of all the reports to the New Zealand Centre for Adverse Reactions Monitoring of a roxithromycin/warfarin interaction after two recent reports described intense rapid warfarin potentiation. The interaction was first published in 1995. Cytochrome P450 3A4 inhibition has been the proposed mechanism but has limited biologic plausibility. There are suggestions that the clinical significance of the interaction may be increased by severe illness, polypharmacy, renal dysfunction, older age and increased warfarin sensitivity. To investigate the potentiating effect of warfarin on roxithromycin in this New Zealand case series, the reports were reviewed to identify patients at risk, compare the reporting pattern with published Australian data and evaluate the appropriateness of current prescribing advice. Thirty patient reports were identified. The age range was 23-88 years, mean 66.8, median 73.0 (standard deviation 17.7) and the international normalised ratios after roxithromycin commencement ranged from 3.6 to 16.7 (mean 7.6, median 7.6, standard deviation 3.6). For eight patients with measurements on day 3, international normalised ratios were 4.3-16.7 (mean 10.4, median 8.8, standard deviation 4.4). Four patients had serious haemorrhage. Indications for roxithromycin were a range of respiratory tract infections. Anticoagulation was stable for most patients prior to acute infection. Serious infection occurred in 54.5% (12 of 22 patients with information). Polypharmacy (five or more medicines daily) was used by 36.7% of patients long term, increasing acutely to 83.3%, including additional potentially interacting medicines. Warfarin daily dose (1.5-13.0 mg, mean 4.4, median 4.0, standard deviation 2.2) was moderate to low. Pre-roxithromycin international normalised ratio values ranged from 1.4 to 3.7, mean and median 2.5, standard deviation 0.5. A high proportion of interactions were observed between warfarin and roxithromycin compared with other macrolides and compared with cytochrome P450 3A4-related macrolide interactions. The pattern was similar to published Australian data. In this case series, the high prevalence of acute polypharmacy, including potentially interacting medicines, and serious infection suggests that they may have contributed to warfarin potentiation and increased the clinical significance of a roxithromycin/warfarin interaction.

Polymicrobial airway bacterial communities in adult bronchiectasis patients

PubMed Central

2014-01-01

Background Chronic airway infection contributes to the underlying pathogenesis of non-cystic fibrosis bronchiectasis (NCFBr). In contrast to other chronic airway infections, associated with COPD and CF bronchiectasis, where polymicrobial communities have been implicated in lung damage due to the vicious circle of recurrent bacterial infections and inflammation, there is sparse information on the composition of bacterial communities in NCFBr. Seventy consecutive patients were recruited from an outpatient adult NCFBr clinic. Bacterial communities in sputum samples were analysed by culture and pyrosequencing approaches. Bacterial sequences were analysed using partial least square discrimination analyses to investigate trends in community composition and identify those taxa that contribute most to community variation. Results The lower airway in NCFBr is dominated by three bacterial taxa Pasteurellaceae, Streptococcaceae and Pseudomonadaceae. Moreover, the bacterial community is much more diverse than indicated by culture and contains significant numbers of other genera including anaerobic Prevotellaceae, Veillonellaceae and Actinomycetaceae. We found particular taxa are correlated with different clinical states, 27 taxa were associated with acute exacerbations, whereas 11 taxa correlated with stable clinical states. We were unable to demonstrate a significant effect of antibiotic therapy, gender, or lung function on the diversity of the bacterial community. However, presence of clinically significant culturable taxa; particularly Pseudomonas aeruginosa and Haemophilus influenzae correlated with a significant change in the diversity of the bacterial community in the lung. Conclusions We have demonstrated that acute exacerbations, the frequency of exacerbation and episodes of clinical stability are correlated, in some patients, with a significantly different bacterial community structure, that are associated with a presence of particular taxa in the NCFBr lung. Moreover, there appears to be an inverse relationship between the abundance of P. aeruginosa and that of of H. influenzae within the NCFBr lung bacterial community. This interaction requires further exploration. PMID:24886473

Borderline Symptoms and Suicidality/Self-injury in Late Adolescence: Prospectively Observed Relationship Correlates in Infancy and Childhood

PubMed Central

Lyons-Ruth, Karlen; Bureau, Jean-Francois; Holmes, Bjarne; Easterbrooks, Ann; Brooks, Nancy Hall

2012-01-01

The primary objective was to assess whether prospectively observed quality of parent-child interaction in infancy and middle childhood contributed to the prediction of borderline symptoms and recurrent suicidality/self-injury in late adolescence. Adolescents (mean 19.9 years) from 56 families participating in a longitudinal study since infancy (retention rate 74%) were assessed on the SCID-II for symptoms of borderline personality disorder, including suicidality/self-injury. Early clinical risk was indexed by clinical referral to parent-infant services. Attachment security and parent-child interaction were assessed from videotape at 18 months and 8 years. Severity of childhood abuse was rated from interview and self-report measures. Maternal withdrawal in infancy was a significant predictor of both borderline symptoms and suicidality/self-injury in late adolescence. Disorganizedcontrolling child behavior at age 8 contributed independently to the prediction of borderline symptoms. The effect of maternal withdrawal was independent of, and additive to, variability explained by severity of childhood abuse. Borderline symptoms and suicidality/self-injury may be preceded developmentally by disturbed interactions as early as 18 months of age. A parent-child transactional model is proposed to account for the findings. PMID:23123044

Bioinformatics and variability in drug response: a protein structural perspective

PubMed Central

Lahti, Jennifer L.; Tang, Grace W.; Capriotti, Emidio; Liu, Tianyun; Altman, Russ B.

2012-01-01

Marketed drugs frequently perform worse in clinical practice than in the clinical trials on which their approval is based. Many therapeutic compounds are ineffective for a large subpopulation of patients to whom they are prescribed; worse, a significant fraction of patients experience adverse effects more severe than anticipated. The unacceptable risk–benefit profile for many drugs mandates a paradigm shift towards personalized medicine. However, prior to adoption of patient-specific approaches, it is useful to understand the molecular details underlying variable drug response among diverse patient populations. Over the past decade, progress in structural genomics led to an explosion of available three-dimensional structures of drug target proteins while efforts in pharmacogenetics offered insights into polymorphisms correlated with differential therapeutic outcomes. Together these advances provide the opportunity to examine how altered protein structures arising from genetic differences affect protein–drug interactions and, ultimately, drug response. In this review, we first summarize structural characteristics of protein targets and common mechanisms of drug interactions. Next, we describe the impact of coding mutations on protein structures and drug response. Finally, we highlight tools for analysing protein structures and protein–drug interactions and discuss their application for understanding altered drug responses associated with protein structural variants. PMID:22552919

Developing the IVIG biomimetic, Hexa-Fc, for drug and vaccine applications

PubMed Central

Czajkowsky, Daniel M.; Andersen, Jan Terje; Fuchs, Anja; Wilson, Timothy J.; Mekhaiel, David; Colonna, Marco; He, Jianfeng; Shao, Zhifeng; Mitchell, Daniel A.; Wu, Gang; Dell, Anne; Haslam, Stuart; Lloyd, Katy A.; Moore, Shona C.; Sandlie, Inger; Blundell, Patricia A.; Pleass, Richard J.

2015-01-01

The remarkable clinical success of Fc-fusion proteins has driven intense investigation for even more potent replacements. Using quality-by-design (QbD) approaches, we generated hexameric-Fc (hexa-Fc), a ~20 nm oligomeric Fc-based scaffold that we here show binds low-affinity inhibitory receptors (FcRL5, FcγRIIb, and DC-SIGN) with high avidity and specificity, whilst eliminating significant clinical limitations of monomeric Fc-fusions for vaccine and/or cancer therapies, in particular their poor ability to activate complement. Mass spectroscopy of hexa-Fc reveals high-mannose, low-sialic acid content, suggesting that interactions with these receptors are influenced by the mannose-containing Fc. Molecular dynamics (MD) simulations provides insight into the mechanisms of hexa-Fc interaction with these receptors and reveals an unexpected orientation of high-mannose glycans on the human Fc that provides greater accessibility to potential binding partners. Finally, we show that this biosynthetic nanoparticle can be engineered to enhance interactions with the human neonatal Fc receptor (FcRn) without loss of the oligomeric structure, a crucial modification for these molecules in therapy and/or vaccine strategies where a long plasma half-life is critical. PMID:25912958

Associations between intrusive thoughts, reality discrimination and hallucination-proneness in healthy young adults.

PubMed

Smailes, David; Meins, Elizabeth; Fernyhough, Charles

2015-01-01

People who experience intrusive thoughts are at increased risk of developing hallucinatory experiences, as are people who have weak reality discrimination skills. No study has yet examined whether these two factors interact to make a person especially prone to hallucinatory experiences. The present study examined this question in a non-clinical sample. Participants were 160 students, who completed a reality discrimination task, as well as self-report measures of cannabis use, negative affect, intrusive thoughts and auditory hallucination-proneness. The possibility of an interaction between reality discrimination performance and level of intrusive thoughts was assessed using multiple regression. The number of reality discrimination errors and level of intrusive thoughts were independent predictors of hallucination-proneness. The reality discrimination errors × intrusive thoughts interaction term was significant, with participants who made many reality discrimination errors and reported high levels of intrusive thoughts being especially prone to hallucinatory experiences. Hallucinatory experiences are more likely to occur in people who report high levels of intrusive thoughts and have weak reality discrimination skills. If applicable to clinical samples, these findings suggest that improving patients' reality discrimination skills and reducing the number of intrusive thoughts they experience may reduce the frequency of hallucinatory experiences.

Comprehensive mitigation framework for concurrent application of multiple clinical practice guidelines.

PubMed

Wilk, Szymon; Michalowski, Martin; Michalowski, Wojtek; Rosu, Daniela; Carrier, Marc; Kezadri-Hamiaz, Mounira

2017-02-01

In this work we propose a comprehensive framework based on first-order logic (FOL) for mitigating (identifying and addressing) interactions between multiple clinical practice guidelines (CPGs) applied to a multi-morbid patient while also considering patient preferences related to the prescribed treatment. With this framework we respond to two fundamental challenges associated with clinical decision support: (1) concurrent application of multiple CPGs and (2) incorporation of patient preferences into the decision making process. We significantly expand our earlier research by (1) proposing a revised and improved mitigation-oriented representation of CPGs and secondary medical knowledge for addressing adverse interactions and incorporating patient preferences and (2) introducing a new mitigation algorithm. Specifically, actionable graphs representing CPGs allow for parallel and temporal activities (decisions and actions). Revision operators representing secondary medical knowledge support temporal interactions and complex revisions across multiple actionable graphs. The mitigation algorithm uses the actionable graphs, revision operators and available (and possibly incomplete) patient information represented in FOL. It relies on a depth-first search strategy to find a valid sequence of revisions and uses theorem proving and model finding techniques to identify applicable revision operators and to establish a management scenario for a given patient if one exists. The management scenario defines a safe (interaction-free) and preferred set of activities together with possible patient states. We illustrate the use of our framework with a clinical case study describing two patients who suffer from chronic kidney disease, hypertension, and atrial fibrillation, and who are managed according to CPGs for these diseases. While in this paper we are primarily concerned with the methodological aspects of mitigation, we also briefly discuss a high-level proof of concept implementation of the proposed framework in the form of a clinical decision support system (CDSS). The proposed mitigation CDSS "insulates" clinicians from the complexities of the FOL representations and provides semantically meaningful summaries of mitigation results. Ultimately we plan to implement the mitigation CDSS within our MET (Mobile Emergency Triage) decision support environment. Copyright © 2016 Elsevier Inc. All rights reserved.

Interactive Anatomical and Surgical Live Stream Lectures Improve Students' Academic Performance in Applied Clinical Anatomy

ERIC Educational Resources Information Center

Shiozawa, Thomas; Butz, Benjamin; Herlan, Stephan; Kramer, Andreas; Hirt, Bernhard

2017-01-01

Tuebingen's "Sectio Chirurgica" (TSC) is an innovative, interactive, multimedia, and transdisciplinary teaching method designed to complement dissection courses. The Tuebingen's "Sectio Chirurgica" (TSC) allows clinical anatomy to be taught via interactive live stream surgeries moderated by an anatomist. This method aims to…

Development and initial evaluation of a treatment decision dashboard

PubMed Central

2013-01-01

Background For many healthcare decisions, multiple alternatives are available with different combinations of advantages and disadvantages across several important dimensions. The complexity of current healthcare decisions thus presents a significant barrier to informed decision making, a key element of patient-centered care. Interactive decision dashboards were developed to facilitate decision making in Management, a field marked by similarly complicated choices. These dashboards utilize data visualization techniques to reduce the cognitive effort needed to evaluate decision alternatives and a non-linear flow of information that enables users to review information in a self-directed fashion. Theoretically, both of these features should facilitate informed decision making by increasing user engagement with and understanding of the decision at hand. We sought to determine if the interactive decision dashboard format can be successfully adapted to create a clinically realistic prototype patient decision aid suitable for further evaluation and refinement. Methods We created a computerized, interactive clinical decision dashboard and performed a pilot test of its clinical feasibility and acceptability using a multi-method analysis. The dashboard summarized information about the effectiveness, risks of side effects and drug-drug interactions, out-of-pocket costs, and ease of use of nine analgesic treatment options for knee osteoarthritis. Outcome evaluations included observations of how study participants utilized the dashboard, questionnaires to assess usability, acceptability, and decisional conflict, and an open-ended qualitative analysis. Results The study sample consisted of 25 volunteers - 7 men and 18 women - with an average age of 51 years. The mean time spent interacting with the dashboard was 4.6 minutes. Mean evaluation scores on scales ranging from 1 (low) to 7 (high) were: mechanical ease of use 6.1, cognitive ease of use 6.2, emotional difficulty 2.7, decision-aiding effectiveness 5.9, clarification of values 6.5, reduction in decisional uncertainty 6.1, and provision of decision-related information 6.0. Qualitative findings were similarly positive. Conclusions Interactive decision dashboards can be adapted for clinical use and have the potential to foster informed decision making. Additional research is warranted to more rigorously test the effectiveness and efficiency of patient decision dashboards for supporting informed decision making and other aspects of patient-centered care, including shared decision making. PMID:23601912

The challenge of cardiac modeling--interaction and integration.

PubMed

Sideman, Samuel

2006-10-01

The goal of clinical cardiology is to obtain an integrated picture of the interacting parameters of muscle and vessel mechanics, blood circulation and myocardial perfusion, oxygen consumption and energy metabolism, and electrical activation and heart rate, thus relating to the true physiological and pathophysiological characteristics of the heart. Scientific insight into the cardiac physiology and performance is achieved by utilizing life sciences, for example, molecular biology, genetics and related intra- and intercellular phenomena, as well as the exact sciences, for example, mathematics, computer science, and related imaging and visualization techniques. The tools to achieve these goals are based on the intimate interactions between engineering science and medicine and the developments of modern, medically oriented technology. Most significant is the beneficiary effect of the globalization of science, the Internet, and the unprecedented international interaction and scientific cooperation in facing difficult multidisciplined challenges. This meeting aims to explore some important interactions in the cardiac system and relate to the integration of spatial and temporal interacting system parameters, so as to gain better insight into the structure and function of the cardiac system, thus leading to better therapeutic modalities.

Behavioural and Developmental Interventions for Autism Spectrum Disorder: A Clinical Systematic Review

PubMed Central

Ospina, Maria B.; Krebs Seida, Jennifer; Clark, Brenda; Karkhaneh, Mohammad; Hartling, Lisa; Tjosvold, Lisa; Vandermeer, Ben; Smith, Veronica

2008-01-01

Background Much controversy exists regarding the clinical efficacy of behavioural and developmental interventions for improving the core symptoms of autism spectrum disorders (ASD). We conducted a systematic review to summarize the evidence on the effectiveness of behavioural and developmental interventions for ASD. Methods and Findings Comprehensive searches were conducted in 22 electronic databases through May 2007. Further information was obtained through hand searching journals, searching reference lists, databases of theses and dissertations, and contacting experts in the field. Experimental and observational analytic studies were included if they were written in English and reported the efficacy of any behavioural or developmental intervention for individuals with ASD. Two independent reviewers made the final study selection, extracted data, and reached consensus on study quality. Results were summarized descriptively and, where possible, meta-analyses of the study results were conducted. One-hundred-and-one studies at predominantly high risk of bias that reported inconsistent results across various interventions were included in the review. Meta-analyses of three controlled clinical trials showed that Lovaas treatment was superior to special education on measures of adaptive behaviour, communication and interaction, comprehensive language, daily living skills, expressive language, overall intellectual functioning and socialization. High-intensity Lovaas was superior to low-intensity Lovaas on measures of intellectual functioning in two retrospective cohort studies. Pooling the results of two randomized controlled trials favoured developmental approaches based on initiative interaction compared to contingency interaction in the amount of time spent in stereotyped behaviours and distal social behaviour, but the effect sizes were not clinically significant. No statistically significant differences were found for: Lovaas versus special education for non-verbal intellectual functioning; Lovaas versus Developmental Individual-difference relationship-based intervention for communication skills; computer assisted instruction versus no treatment for facial expression recognition; and TEACCH versus standard care for imitation skills and eye-hand integration. Conclusions While this review suggests that Lovaas may improve some core symptoms of ASD compared to special education, these findings are based on pooling of a few, methodologically weak studies with few participants and relatively short-term follow-up. As no definitive behavioural or developmental intervention improves all symptoms for all individuals with ASD, it is recommended that clinical management be guided by individual needs and availability of resources. PMID:19015734

[Drug-food interactions in internal medicine: What physicians should know?].

PubMed

Mouly, S; Morgand, M; Lopes, A; Lloret-Linares, C; Bergmann, J-F

2015-08-01

Orally administered medications may interact with various fruits, vegetables, herbal medicines, functional foods or dietary supplements. Drug-food interactions, which are mostly unknown from prescribers, including internists, may be responsible for changes in drug plasma concentrations, which may decrease efficacy or led to sometimes life-threatening toxicity. Aging, concomitant medications, transplant recipients, patients with cancer, malnutrition, HIV infection and those receiving enteral or parenteral feeding are at increased risk of drug-food interactions. This review focused on the most clinically relevant drug-food interactions, including those with grapefruit juice, Saint-John's Wort, enteral or parenteral nutrition, their respective consequences in the clinical setting in order to provide thoughtful information for internists in their routine clinical practice. Specific clinical settings are also detailed, such as the Ramadan or multiple medications especially in elderly patients. Drug-food interactions are also presented with respect to the main therapeutic families, including the non-steroidal anti-inflammatory drugs, analgesics, cardiovascular medications, warfarin as well as new oral anticoagulants, anticancer drugs and immunosuppressant medications. Considerable effort has been achieved to a better understanding of food-drug interactions and increase clinicians' ability to anticipate their occurrence and consequences in clinical practice. Describing the frequency of relevant food-drug interactions in internal medicine is paramount in order to optimize patient care and drug dosing on an individual basis as well as to increase patients and doctors information. Copyright © 2015 Société nationale française de médecine interne (SNFMI). Published by Elsevier SAS. All rights reserved.

Busulfan and metronidazole: an often forgotten but significant drug interaction.

PubMed

Gulbis, Alison M; Culotta, Kirk S; Jones, Roy B; Andersson, Borje S

2011-07-01

To report the case of a clinically significant drug interaction between intravenous busulfan and oral metronidazole observed through busulfan therapeutic drug monitoring (TDM). A 7-year-old boy with a history of myelodysplasia that progressed to acute myeloid leukemia received busulfan with therapeutic drug monitoring (TDM), clofarabine, and thiotepa as a pretransplant conditioning regimen for a cord blood transplant. The patient received metronidazole the day after a busulfan test dose of 0.5 mg/kg was administered. On the day of the first busulfan therapeutic dose, TDM was performed and the clearance of busulfan was significantly decreased by 46%. After 2 doses of busulfan therapy, the course area under the curve was exceeded, requiring discontinuation of busulfan. Metronidazole is not known to affect glutathione or the glutathione S-transferase A1 (GSTA1) enzyme system or cytochrome P450 (CYP) 3A4. Busulfan is a bifunctional alkylating agent widely used in pretransplant conditioning regimens in patients undergoing stem cell transplantation for hematologic malignancies. Busulfan metabolism is best described by hepatic conjugation to glutathione by GSTA1, although some CYP-dependent pathways have been described. Currently there is 1 publication describing the drug interaction between oral busulfan and oral metronidazole, in which concomitant use of metronidazole resulted in higher busulfan trough concentrations and higher risk of veno-occlusive disease. Our case represents a possible drug interaction based on the Horn Drug Interaction Probability Scale. Though the mechanistic basis for this interaction is unknown, the risks and benefits of using metronidazole during and in close proximity to busulfan should be carefully considered and therapeutic alternatives to metronidazole should be used when appropriate.

Magnesium for treatment of acute lacunar stroke syndromes: further analysis of the IMAGES trial.

PubMed

Aslanyan, Stella; Weir, Christopher J; Muir, Keith W; Lees, Kennedy R

2007-04-01

A prespecified interaction analysis of the neutral Intravenous Magnesium Efficacy in Stroke (IMAGES) trial revealed significant benefit from magnesium (Mg) in patients with noncortical stroke. Post hoc analysis indicated that this effect was seen in lacunar clinical syndromes (LACS), interaction P=0.005. We have now examined whether this interaction could be explained by confounding baseline factors. LACS was defined on the basis of neurological signs and did not include imaging. We investigated the interaction between baseline variables and Mg treatment on global outcome. We used logistic-regression models to test whether the Mg-LACS interaction remained significant after adjusting for stratification variables, sex, a novel stroke severity score, and baseline variables that had an interaction with treatment (P<0.1). The Mg (n=383) and placebo (n=382) groups of LACS patients were well matched on baseline factors. In addition to LACS, we found an interaction between beneficial Mg treatment effect and younger age (P=0.003), higher baseline diastolic blood pressure (P=0.02), higher mean blood pressure (P=0.02), and absence of ischemic heart disease (P=0.07). Even so, the adjusted Mg-LACS interaction remained significant (odds ratio [OR] 0.57; 95% CI, 0.39 to 0.83; P=0.003). In the LACS subgroup, Mg improved Barthel Index <95 (OR 0.73; 95% CI, 0.55 to 0.98), modified Rankin Scale >1 (OR 0.67; 95% CI, 0.50 to 0.91), and global outcome (OR 0.70; 95% CI, 0.53 to 0.92) but not Barthel Index <60 or mortality. The positive treatment effect of Mg in LACS cannot be ascribed to general issues of severity, time to treatment, blood pressure, or other baseline factors; equally, this finding may be due to chance. A large trial of Mg treatment in LACS appears justified.

Radiotherapy and "new" drugs-new side effects?

PubMed Central

2011-01-01

Background and purpose Targeted drugs have augmented the cancer treatment armamentarium. Based on the molecular specificity, it was initially believed that these drugs had significantly less side effects. However, currently it is accepted that all of these agents have their specific side effects. Based on the given multimodal approach, special emphasis has to be placed on putative interactions of conventional cytostatic drugs, targeted agents and other modalities. The interaction of targeted drugs with radiation harbours special risks, since the awareness for interactions and even synergistic toxicities is lacking. At present, only limited is data available regarding combinations of targeted drugs and radiotherapy. This review gives an overview on the current knowledge on such combined treatments. Materials and methods Using the following MESH headings and combinations of these terms pubmed database was searched: Radiotherapy AND cetuximab/trastuzumab/panitumumab/nimotuzumab, bevacizumab, sunitinib/sorafenib/lapatinib/gefitinib/erlotinib/sirolimus, thalidomide/lenalidomide as well as erythropoietin. For citation crosscheck the ISI web of science database was used employing the same search terms. Results Several classes of targeted substances may be distinguished: Small molecules including kinase inhibitors and specific inhibitors, antibodies, and anti-angiogenic agents. Combination of these agents with radiotherapy may lead to specific toxicities or negatively influence the efficacy of RT. Though there is only little information on the interaction of molecular targeted radiation and radiotherapy in clinical settings, several critical incidents are reported. Conclusions The addition of molecular targeted drugs to conventional radiotherapy outside of approved regimens or clinical trials warrants a careful consideration especially when used in conjunction in hypo-fractionated regimens. Clinical trials are urgently needed in order to address the open question in regard to efficacy, early and late toxicity. PMID:22188921

Quantitative Assessment of Combination Antimicrobial Therapy against Multidrug-Resistant Acinetobacter baumannii▿

PubMed Central

Lim, Tze-Peng; Ledesma, Kimberly R.; Chang, Kai-Tai; Hou, Jing-Guo; Kwa, Andrea L.; Nikolaou, Michael; Quinn, John P.; Prince, Randall A.; Tam, Vincent H.

2008-01-01

Treatment of multidrug-resistant bacterial infections poses a therapeutic challenge to clinicians; combination therapy is often the only viable option for multidrug-resistant infections. A quantitative method was developed to assess the combined killing abilities of antimicrobial agents. Time-kill studies (TKS) were performed using a multidrug-resistant clinical isolate of Acinetobacter baumannii with escalating concentrations of cefepime (0 to 512 mg/liter), amikacin (0 to 256 mg/liter), and levofloxacin (0 to 64 mg/liter). The bacterial burden data in single and combined (two of the three agents with clinically achievable concentrations in serum) TKS at 24 h were mathematically modeled to provide an objective basis for comparing various antimicrobial agent combinations. Synergy and antagonism were defined as interaction indices of <1 and >1, respectively. A hollow-fiber infection model (HFIM) simulating various clinical (fluctuating concentrations over time) dosing exposures was used to selectively validate our quantitative assessment of the combined killing effect. Model fits in all single-agent TKS were satisfactory (r2 > 0.97). An enhanced combined overall killing effect was seen in the cefepime-amikacin combination (interactive index, 0.698; 95% confidence interval [CI], 0.675 to 0.722) and the cefepime-levofloxacin combination (interactive index, 0.929; 95% CI, 0.903 to 0.956), but no significant difference in the combined overall killing effect for the levofloxacin-amikacin combination was observed (interactive index, 0.994; 95% CI, 0.982 to 1.005). These assessments were consistent with observations in HFIM validation studies. Our method could be used to objectively rank the combined killing activities of two antimicrobial agents when used together against a multidrug-resistant A. baumannii isolate. It may offer better insights into the effectiveness of various antimicrobial combinations and warrants further investigations. PMID:18505848

Potential Drug-Drug Interactions in a Cohort of Elderly, Polymedicated Primary Care Patients on Antithrombotic Treatment.

PubMed

Schneider, Katharina Luise; Kastenmüller, Kathrin; Weckbecker, Klaus; Bleckwenn, Markus; Böhme, Miriam; Stingl, Julia Carolin

2018-06-01

Drug-drug interactions (DDIs) are an important risk factor for adverse drug reactions. Older, polymedicated patients are particularly affected. Although antithrombotics have been detected as high-risk drugs for DDIs, data on older patients exposed to them are scarce. Baseline data of 365 IDrug study outpatients (≥ 60 years, use of an antithrombotic and one or more additional long-term drug) were analyzed regarding potential drug-drug interactions (pDDIs) with a clinical decision support system. Data included prescription and self-medication drugs. The prevalence of having one or more pDDI was 85.2%. The median number of alerts per patient was three (range 0-17). For 58.4% of the patients, potential severe/contraindicated interactions were detected. Antiplatelets and non-steroidal anti-inflammatory drugs (NSAIDs) showed the highest number of average pDDI alert involvements per use (2.9 and 2.2, respectively). For NSAIDs, also the highest average number of severe/contraindicated alert involvements per use (1.2) was observed. 91.8% of all pDDI involvements concerned the 25 most frequently used drug classes. 97.5% of the severe/contraindicated pDDIs were attributed to only nine different potential clinical manifestations. The most common management recommendation for severe/contraindicated pDDIs was to intensify monitoring. Number of drugs was the only detected factor significantly associated with increased number of pDDIs (p < 0.001). The findings indicate a high risk for pDDIs in older, polymedicated patients on antithrombotics. As a consequence of patients' frequently similar drug regimens, the variety of potential clinical manifestations was small. Awareness of these pDDI symptoms and the triggering drugs as well as patients' self-medication use may contribute to increased patient safety.

Predictors of mortality in patients with lacunar stroke in the secondary prevention of small subcortical strokes trial.

PubMed

Sharma, Mukul; Pearce, Lesly A; Benavente, Oscar R; Anderson, David C; Connolly, Stuart J; Palacio, Santiago; Coffey, Christopher S; Hart, Robert G

2014-10-01

The Secondary Prevention of Small Subcortical Stroke trial (SPS3) recruited participants meeting clinical and radiological criteria for symptomatic lacunes. Individuals randomized to dual antiplatelet therapy with clopidogrel and aspirin had an unanticipated increase in all-cause mortality compared with those assigned to aspirin. We investigated the factors associated with mortality in this well-characterized population. We identified independent predictors of mortality among baseline demographic and clinical factors by Cox regression analysis in participants of the SPS3 trial. Separately, we examined the effect on mortality of nonfatal bleeding during the trial. During a mean follow-up of 3.6 years, the mortality rate was 1.78% per year for the 3020 participants (mean age, 63 years). Significant independent predictors of mortality at study entry were age, diabetes mellitus, history of hypertension, systolic blood pressure (hazard ratio [HR], 1.3 per 20 mm Hg increase), serum hemoglobin<13 g/dL (HR, 1.6), renal function (HR, 1.3 per estimated glomerular filtration rate decrease of 20 mL/min), and body mass index (HR, 1.8 per 10 kg/m2 decrease). Participants with ischemic heart disease (P=0.01 for interaction) and normotensive/prehypertensive participants (P=0.03 for interaction) were at increased risk if assigned to dual antiplatelet therapy. Nonfatal major hemorrhage increased mortality in both treatment arms (HR, 4.5; 95% confidence interval, 3.1-6.6; P<0.001). Unexpected interactions between assigned antiplatelet therapy and each of ischemic heart disease and normal/prehypertensive status accounted for increased mortality among patients with recent lacunar stroke given dual antiplatelet therapy. Despite extensive exploratory analyses, the mechanisms underlying these interactions are uncertain. http://www.SPS3ClinicalTrials.gov. Unique identifier: NCT00059306. © 2014 American Heart Association, Inc.

Report on Provider-Client Interaction From 68 Methadone Maintenance Clinics in China.

PubMed

Li, Li; Comulada, W Scott; Lin, Chunqing; Lan, Chiao-Wen; Cao, Xiaobin; Wu, Zunyou

2017-11-01

Provider-client interaction is an integral of clinical practice and central to the delivery of high-quality medical care. This article examines factors related to the provider-client interaction in the context of methadone maintenance treatment (MMT). Data were collected from 68 MMT clinics in China. In total, 418 service providers participated in the survey. Linear mixed effects regression models were performed to identify factors associated with provider-client interaction. It was observed that negative attitude toward drug users was associated with lower level of provider-client interaction and less time spent with each client. Other factors associated with lower level of interaction included being female, being younger, being a nurse, and fewer years in medical field. Higher provider-client interaction was associated with provider reported job satisfaction. The findings of this study call for a need to address provider negative attitudes that can impact provider-client interaction and the effectiveness of MMT. Future intervention efforts targeting MMT providers should be tailored by gender, provider type, and medical experiences.

Semiautomated segmentation of head and neck cancers in 18F-FDG PET scans: A just-enough-interaction approach

PubMed Central

Beichel, Reinhard R.; Van Tol, Markus; Ulrich, Ethan J.; Bauer, Christian; Chang, Tangel; Plichta, Kristin A.; Smith, Brian J.; Sunderland, John J.; Graham, Michael M.; Sonka, Milan; Buatti, John M.

2016-01-01

Purpose: The purpose of this work was to develop, validate, and compare a highly computer-aided method for the segmentation of hot lesions in head and neck 18F-FDG PET scans. Methods: A semiautomated segmentation method was developed, which transforms the segmentation problem into a graph-based optimization problem. For this purpose, a graph structure around a user-provided approximate lesion centerpoint is constructed and a suitable cost function is derived based on local image statistics. To handle frequently occurring situations that are ambiguous (e.g., lesions adjacent to each other versus lesion with inhomogeneous uptake), several segmentation modes are introduced that adapt the behavior of the base algorithm accordingly. In addition, the authors present approaches for the efficient interactive local and global refinement of initial segmentations that are based on the “just-enough-interaction” principle. For method validation, 60 PET/CT scans from 59 different subjects with 230 head and neck lesions were utilized. All patients had squamous cell carcinoma of the head and neck. A detailed comparison with the current clinically relevant standard manual segmentation approach was performed based on 2760 segmentations produced by three experts. Results: Segmentation accuracy measured by the Dice coefficient of the proposed semiautomated and standard manual segmentation approach was 0.766 and 0.764, respectively. This difference was not statistically significant (p = 0.2145). However, the intra- and interoperator standard deviations were significantly lower for the semiautomated method. In addition, the proposed method was found to be significantly faster and resulted in significantly higher intra- and interoperator segmentation agreement when compared to the manual segmentation approach. Conclusions: Lack of consistency in tumor definition is a critical barrier for radiation treatment targeting as well as for response assessment in clinical trials and in clinical oncology decision-making. The properties of the authors approach make it well suited for applications in image-guided radiation oncology, response assessment, or treatment outcome prediction. PMID:27277044

Semiautomated segmentation of head and neck cancers in 18F-FDG PET scans: A just-enough-interaction approach

DOE Office of Scientific and Technical Information (OSTI.GOV)

Beichel, Reinhard R., E-mail: reinhard-beichel@uiowa.edu; Iowa Institute for Biomedical Imaging, University of Iowa, Iowa City, Iowa 52242; Department of Internal Medicine, University of Iowa, Iowa City, Iowa 52242

Purpose: The purpose of this work was to develop, validate, and compare a highly computer-aided method for the segmentation of hot lesions in head and neck 18F-FDG PET scans. Methods: A semiautomated segmentation method was developed, which transforms the segmentation problem into a graph-based optimization problem. For this purpose, a graph structure around a user-provided approximate lesion centerpoint is constructed and a suitable cost function is derived based on local image statistics. To handle frequently occurring situations that are ambiguous (e.g., lesions adjacent to each other versus lesion with inhomogeneous uptake), several segmentation modes are introduced that adapt the behaviormore » of the base algorithm accordingly. In addition, the authors present approaches for the efficient interactive local and global refinement of initial segmentations that are based on the “just-enough-interaction” principle. For method validation, 60 PET/CT scans from 59 different subjects with 230 head and neck lesions were utilized. All patients had squamous cell carcinoma of the head and neck. A detailed comparison with the current clinically relevant standard manual segmentation approach was performed based on 2760 segmentations produced by three experts. Results: Segmentation accuracy measured by the Dice coefficient of the proposed semiautomated and standard manual segmentation approach was 0.766 and 0.764, respectively. This difference was not statistically significant (p = 0.2145). However, the intra- and interoperator standard deviations were significantly lower for the semiautomated method. In addition, the proposed method was found to be significantly faster and resulted in significantly higher intra- and interoperator segmentation agreement when compared to the manual segmentation approach. Conclusions: Lack of consistency in tumor definition is a critical barrier for radiation treatment targeting as well as for response assessment in clinical trials and in clinical oncology decision-making. The properties of the authors approach make it well suited for applications in image-guided radiation oncology, response assessment, or treatment outcome prediction.« less

3D Slicer as a tool for interactive brain tumor segmentation.

PubMed

Kikinis, Ron; Pieper, Steve

2011-01-01

User interaction is required for reliable segmentation of brain tumors in clinical practice and in clinical research. By incorporating current research tools, 3D Slicer provides a set of interactive, easy to use tools that can be efficiently used for this purpose. One of the modules of 3D Slicer is an interactive editor tool, which contains a variety of interactive segmentation effects. Use of these effects for fast and reproducible segmentation of a single glioblastoma from magnetic resonance imaging data is demonstrated. The innovation in this work lies not in the algorithm, but in the accessibility of the algorithm because of its integration into a software platform that is practical for research in a clinical setting.

Information Retention and Overload in First-Time Hearing Aid Users: An Interactive Multimedia Educational Solution.

PubMed

Ferguson, Melanie; Brandreth, Marian; Brassington, William; Wharrad, Heather

2015-09-01

An educational intervention to improve knowledge of hearing aids and communication in first-time hearing aid users was assessed. This intervention was based on the concept of reusable learning objects (RLOs). A randomized controlled trial was conducted. One group received the educational intervention, and the other acted as a control group. RLOs were delivered online and through DVD for television and personal computer. Knowledge of both practical and psychosocial aspects of hearing aids and communication was assessed using a free-recall method 6 weeks postfitting. Knowledge of both practical and psychosocial issues was significantly higher in the group that received the RLOs than in the control group. Moderate to large effect sizes indicated that these differences were clinically significant. An educational intervention that supplements clinical practice results in improved knowledge in first-time hearing aid users.

Comprehensive oral-health assessment of individuals with acquired brain-injury in neuro-rehabilitation setting.

PubMed

Kothari, Mohit; Spin-Neto, Rubens; Nielsen, Jørgen Feldbæk

2016-01-01

To perform a detailed clinical oral health assessment and oral-health-related social and behavioural aspect assessment in individuals with acquired brain injury (ABI). Prospective observational study. Thirteen individuals with ABI were recruited. Individual's social and behavioural history, bed-side oral examination score (BOE), tooth condition and periodontal status (bleeding, plaque and clinical attachment loss) were thoroughly examined. The entire examination took up to 60 minutes, using proper dental armamentarium. All evaluated individuals were diagnosed with chronic generalized periodontitis. A relationship between active periodontal disease and severe BOE score was observed (p = 0.01). Significant interaction between severe BOE scores (≥ 15 or ≥ 14) and periodontal disease severity of ≥ 2 mm (p = 0.01) was observed. The same interaction was seen between severe BOE scores and the combination of 75% extent and 2 mm severity (p = 0.01). Severity and activity of periodontitis showed dependence on individual brushing frequency (p = 0.03 and p = 0.05, respectively). Individuals with ABI had a poor status across a range of oral-, dental- and periodontal-related parameters. Further structured studies are required to define evidence-based assessment approaches for such clinical reality.

The stories we tell: how age, gender, and forgiveness affect the emotional content of autobiographical narratives.

PubMed

Robertson, Sarah M C; Swickert, Rhonda J

2018-04-01

Researchers have been attempting to understand the variables that predict differences in autobiographical narratives, given that these differences often reveal important information about the psychological characteristics of the person providing the narrative. A sample of young adults (n = 80) and older adults (n = 80) completed a battery of self-report measures in addition to an autobiographical narrative task in which they described a negative emotional experience. These narratives were transcribed and entered into a text analysis program. Results indicated a significant three-way interaction (age × gender × forgiveness) for negative emotion words. Results also indicated two significant two-way interactions (age × forgiveness and gender × forgiveness) and one significant main effect for anger words. There were no significant findings related to anxiety or sad words. Results are discussed in the context of Socioemotional Selectivity Theory, which asserts that social and emotional goals shift throughout the lifespan such that older adults are more motivated to regulate their emotions than young adults. Clinical applications and future directions are discussed.

Factor solutions of the Social Phobia Scale (SPS) and the Social Interaction Anxiety Scale (SIAS) in a Swedish population.

PubMed

Mörtberg, Ewa; Reuterskiöld, Lena; Tillfors, Maria; Furmark, Tomas; Öst, Lars-Göran

2017-06-01

Culturally validated rating scales for social anxiety disorder (SAD) are of significant importance when screening for the disorder, as well as for evaluating treatment efficacy. This study examined construct validity and additional psychometric properties of two commonly used scales, the Social Phobia Scale and the Social Interaction Anxiety Scale, in a clinical SAD population (n = 180) and in a normal population (n = 614) in Sweden. Confirmatory factor analyses of previously reported factor solutions were tested but did not reveal acceptable fit. Exploratory factor analyses (EFA) of the joint structure of the scales in the total population yielded a two-factor model (performance anxiety and social interaction anxiety), whereas EFA in the clinical sample revealed a three-factor solution, a social interaction anxiety factor and two performance anxiety factors. The SPS and SIAS showed good to excellent internal consistency, and discriminated well between patients with SAD and a normal population sample. Both scales showed good convergent validity with an established measure of SAD, whereas the discriminant validity of symptoms of social anxiety and depression could not be confirmed. The optimal cut-off score for SPS and SIAS were 18 and 22 points, respectively. It is concluded that the factor structure and the additional psychometric properties of SPS and SIAS support the use of the scales for assessment in a Swedish population.

Beyond immune checkpoint blockade: new approaches to targeting host-tumor interactions in prostate cancer: report from the 2014 Coffey-Holden prostate cancer academy meeting.

PubMed

Miyahira, Andrea K; Kissick, Haydn T; Bishop, Jennifer L; Takeda, David Y; Barbieri, Christopher E; Simons, Jonathan W; Pienta, Kenneth J; Soule, Howard R

2015-03-01

The 2014 Coffey-Holden Prostate Cancer Academy Meeting, held in La Jolla, CA from June 26 to 29, 2014, was themed: "Beyond Immune Checkpoint Blockade: New Approaches to Targeting Host-Tumor Interactions in Prostate Cancer." Sponsored by the Prostate Cancer Foundation (PCF), this annual, invitation-only meeting is structured as an action-tank, and brought together 72 investigators with diverse academic backgrounds to discuss the most relevant topics in the fields of prostate cancer immunotherapy and the tumor microenvironment. The questions addressed at the meeting included: mechanisms underlying the successes and failures of prostate cancer immunotherapies, how to trigger an effective immune response against prostate cancer, the tumor microenvironment and its role in therapy resistance and tumor metastasis, clinically relevant prostate cancer mouse models, how host-tumor interactions affect current therapies and tumor phenotypes, application of principles of precision medicine to prostate cancer immunotherapy, optimizing immunotherapy clinical trial design, and complex multi-system interactions that affect prostate cancer and immune responses including the effects of obesity and the potential role of the host microbiome. This article highlights the most significant recent progress and unmet needs that were discussed at the meeting toward the goal of speeding the development of optimal immunotherapies for the treatment of prostate cancer. © 2014 Wiley Periodicals, Inc.

The combination of naproxen and citral reduces nociception and gastric damage in rats.

PubMed

Ortiz, Mario I; Ramírez-Montiel, Martha L; González-García, Martha P; Ponce-Monter, Héctor A; Castañeda-Hernández, Gilberto; Cariño-Cortés, Raquel

2010-10-01

It has been shown that the association of non-steroidal anti-inflammatory drugs with plant extracts can increase their antinociceptive activity, allowing the use of lower doses and, thus, limiting side effects. Therefore, the aim of this study was to examine the effects of the interaction between naproxen and citral on nociception and gastric injury in rats. Naproxen, citral, or combinations of naproxen and citral produced an antinociceptive effect. The administration of naproxen produced significant gastric damage, but this effect was not obtained with either citral or the naproxen-citral combination. The ED(50) value was estimated for the individual drugs and an isobologram was constructed. The derived theoretical ED(50) for the antinociceptive effect (423.8 mg/kg) was not significantly different from the observed experimental value (359.0 mg/kg); hence, the interaction between naproxen and citral mediating the antinociceptive effect is additive. These data suggest that the naproxen-citral combination interacts at the systemic level, produces minor gastric damage, and potentially has therapeutic advantages for the clinical treatment of inflammatory pain.

The Organophosphate Paraoxon and Its Antidote Obidoxime Inhibit Thrombin Activity and Affect Coagulation In Vitro

PubMed Central

Golderman, Valery; Shavit-Stein, Efrat; Tamarin, Ilia; Rosman, Yossi; Shrot, Shai; Rosenberg, Nurit

2016-01-01

Organophosphates (OPs) are potentially able to affect serine proteases by reacting with their active site. The potential effects of OPs on coagulation factors such as thrombin and on coagulation tests have been only partially characterized and potential interactions with OPs antidotes such as oximes and muscarinic blockers have not been addressed. In the current study, we investigated the in vitro interactions between coagulation, thrombin, the OP paraoxon, and its antidotes obidoxime and atropine. The effects of these substances on thrombin activity were measured in a fluorescent substrate and on coagulation by standard tests. Both paraoxon and obidoxime but not atropine significantly inhibited thrombin activity, and prolonged prothrombin time, thrombin time, and partial thromboplastin time. When paraoxon and obidoxime were combined, a significant synergistic effect was found on both thrombin activity and coagulation tests. In conclusion, paraoxon and obidoxime affect thrombin activity and consequently alter the function of the coagulation system. Similar interactions may be clinically relevant for coagulation pathways in the blood and possibly in the brain. PMID:27689805

Interactive associations of depression and sleep apnea with adverse clinical outcomes after acute myocardial infarction

PubMed Central

Hayano, Junichiro; Carney, Robert M.; Watanabe, Eiichi; Kawai, Kiyohiro; Kodama, Itsuo; Stein, Phyllis K.; Watkins, Lana L.; Freedland, Kenneth E.; Blumenthal, James A.

2012-01-01

Objective Depression and sleep apnea (SA) are common among patients after acute myocardial infarction (AMI), and both are associated with increased risk for adverse outcomes. We tested the hypothesis that there is an interaction between depression and SA in relation to prognosis in post-AMI patients. Methods Participants were 337 depressed and 379 nondepressed post-AMI patients who participated in a substudy of the Enhancing Recovery in Coronary Heart Disease (ENRICHD) clinical trial. SA was identified from Holter ECG at the entry by an algorithm that detects cyclic variation of heart rate. Results During a median follow-up of 25 months, 43 (6.0%) of patients died and 83 (11.6%) either died or experienced a recurrent AMI. Among 94 patients with both depression and SA, these endpoints occurred in 20 (21.3%) and 25 (26.6%), the prevalence that was 6.9 and 3.9 times higher than predicted probabilities by ENRICHD clinical risk scores (P <.001 for both). In the patients with depression alone, SA alone, or neither, the frequencies did not differ significantly from the predicted probability. Although both depression and SA predicted death and the combined endpoint, we observed depression by SA interactions (P = .03 and .02). SA independently predicted these endpoints in depressed (P <.001 and P = .001), but not in nondepressed patients (P = .73 and .84). Similarly, depression independently predicted these endpoints in SA (P <.001 for both), but not in non-SA patients (P = .61 and .12). Conclusion The combination of depression and SA estimated by CVHR is associated with long-term adverse clinical outcomes after AMI. PMID:23023681

Workflow oriented software support for image guided radiofrequency ablation of focal liver malignancies

NASA Astrophysics Data System (ADS)

Weihusen, Andreas; Ritter, Felix; Kröger, Tim; Preusser, Tobias; Zidowitz, Stephan; Peitgen, Heinz-Otto

2007-03-01

Image guided radiofrequency (RF) ablation has taken a significant part in the clinical routine as a minimally invasive method for the treatment of focal liver malignancies. Medical imaging is used in all parts of the clinical workflow of an RF ablation, incorporating treatment planning, interventional targeting and result assessment. This paper describes a software application, which has been designed to support the RF ablation workflow under consideration of the requirements of clinical routine, such as easy user interaction and a high degree of robust and fast automatic procedures, in order to keep the physician from spending too much time at the computer. The application therefore provides a collection of specialized image processing and visualization methods for treatment planning and result assessment. The algorithms are adapted to CT as well as to MR imaging. The planning support contains semi-automatic methods for the segmentation of liver tumors and the surrounding vascular system as well as an interactive virtual positioning of RF applicators and a concluding numerical estimation of the achievable heat distribution. The assessment of the ablation result is supported by the segmentation of the coagulative necrosis and an interactive registration of pre- and post-interventional image data for the comparison of tumor and necrosis segmentation masks. An automatic quantification of surface distances is performed to verify the embedding of the tumor area into the thermal lesion area. The visualization methods support representations in the commonly used orthogonal 2D view as well as in 3D scenes.

Interactive contour delineation of organs at risk in radiotherapy: Clinical evaluation on NSCLC patients.

PubMed

Dolz, J; Kirişli, H A; Fechter, T; Karnitzki, S; Oehlke, O; Nestle, U; Vermandel, M; Massoptier, L

2016-05-01

Accurate delineation of organs at risk (OARs) on computed tomography (CT) image is required for radiation treatment planning (RTP). Manual delineation of OARs being time consuming and prone to high interobserver variability, many (semi-) automatic methods have been proposed. However, most of them are specific to a particular OAR. Here, an interactive computer-assisted system able to segment various OARs required for thoracic radiation therapy is introduced. Segmentation information (foreground and background seeds) is interactively added by the user in any of the three main orthogonal views of the CT volume and is subsequently propagated within the whole volume. The proposed method is based on the combination of watershed transformation and graph-cuts algorithm, which is used as a powerful optimization technique to minimize the energy function. The OARs considered for thoracic radiation therapy are the lungs, spinal cord, trachea, proximal bronchus tree, heart, and esophagus. The method was evaluated on multivendor CT datasets of 30 patients. Two radiation oncologists participated in the study and manual delineations from the original RTP were used as ground truth for evaluation. Delineation of the OARs obtained with the minimally interactive approach was approved to be usable for RTP in nearly 90% of the cases, excluding the esophagus, which segmentation was mostly rejected, thus leading to a gain of time ranging from 50% to 80% in RTP. Considering exclusively accepted cases, overall OARs, a Dice similarity coefficient higher than 0.7 and a Hausdorff distance below 10 mm with respect to the ground truth were achieved. In addition, the interobserver analysis did not highlight any statistically significant difference, at the exception of the segmentation of the heart, in terms of Hausdorff distance and volume difference. An interactive, accurate, fast, and easy-to-use computer-assisted system able to segment various OARs required for thoracic radiation therapy has been presented and clinically evaluated. The introduction of the proposed system in clinical routine may offer valuable new option to radiation oncologists in performing RTP.

A Picture is Worth a Thousand Words

PubMed Central

Pinsky, Linda E; Wipf, Joyce E

2000-01-01

Videotapes, through vividly displayed clinical images and teaching interactions, are valuable tools for both learners and teachers. Visual images in combination with verbal instruction have been shown to significantly increase recall and retention. Many clinicians and medical teachers are aware of videotape resources, but have not had a chance to develop their use in medical education. In this paper, we discuss creative applications of videotapes in three major categories: presenting information, triggering discussion, and as a tool for direct self-observation and feedback. Videotapes may be valuable for presenting information in settings of didactic instruction; for triggering discussion during teaching workshops; and for self-observation of patient-doctor interactions and learner-teacher encounters. The article presents learner-centered approaches to review a videotaped clinical encounter in order to enhance value and comfort for the learner and teacher. Sources of tapes include on-site videotaping, published educational tapes and commercial tapes shown in accordance with fair use guidelines, examples of which are referenced. Videotapes add another dimension to traditional sources of physician education. PMID:11119173

Effective Information Extraction Framework for Heterogeneous Clinical Reports Using Online Machine Learning and Controlled Vocabularies

PubMed Central

Zheng, Shuai; Ghasemzadeh, Nima; Hayek, Salim S; Quyyumi, Arshed A

2017-01-01

Background Extracting structured data from narrated medical reports is challenged by the complexity of heterogeneous structures and vocabularies and often requires significant manual effort. Traditional machine-based approaches lack the capability to take user feedbacks for improving the extraction algorithm in real time. Objective Our goal was to provide a generic information extraction framework that can support diverse clinical reports and enables a dynamic interaction between a human and a machine that produces highly accurate results. Methods A clinical information extraction system IDEAL-X has been built on top of online machine learning. It processes one document at a time, and user interactions are recorded as feedbacks to update the learning model in real time. The updated model is used to predict values for extraction in subsequent documents. Once prediction accuracy reaches a user-acceptable threshold, the remaining documents may be batch processed. A customizable controlled vocabulary may be used to support extraction. Results Three datasets were used for experiments based on report styles: 100 cardiac catheterization procedure reports, 100 coronary angiographic reports, and 100 integrated reports—each combines history and physical report, discharge summary, outpatient clinic notes, outpatient clinic letter, and inpatient discharge medication report. Data extraction was performed by 3 methods: online machine learning, controlled vocabularies, and a combination of these. The system delivers results with F1 scores greater than 95%. Conclusions IDEAL-X adopts a unique online machine learning–based approach combined with controlled vocabularies to support data extraction for clinical reports. The system can quickly learn and improve, thus it is highly adaptable. PMID:28487265

New technologies, human-microbe interactions, and the search for previously unrecognized pathogens.

PubMed

Relman, David A

2002-12-01

Evidence suggests that a significant number of clinically important microbial pathogens remain unrecognized. Observations from the natural world, from patterns of disease in human populations, from the bedside, and from the clinical laboratory all contribute to this body of evidence. A variety of acute and chronic neurologic syndromes illustrate this point; despite features of infection, most cases of aseptic meningitis, encephalitis, and cerebral vasculitis cannot be assigned a microbiologic diagnosis. The development and clinical application of molecular methods have led to the discovery of novel members of the endogenous normal flora as well as putative disease agents. Current challenges include the establishment of criteria for disease causation and further characterization of the human microbiome during states of health. These challenges and the goal of understanding microbial contributions to inflammatory disease may be addressed effectively through the thoughtful integration of modern technologies and clinical insight.

Vestibular Assessments in Children With Global Developmental Delay: An Exploratory Study.

PubMed

Dannenbaum, Elizabeth; Horne, Victoria; Malik, Farwa; Villeneuve, Myriam; Salvo, Lora; Chilingaryan, Gevorg; Lamontagne, Anouk

2016-01-01

To compare results of 3 clinical vestibular tests between children with global developmental delay (GDD) and children with typical development (TD) and investigate the test-retest reliability. Twenty children with GDD (aged 4.1-12.1 years) and 11 age-matched controls with TD participated. Participants with GDD underwent 2 sessions of testing. Each session consisted of the Clinical Test of Sensory Interaction and Balance (CTSIB), Dynamic Visual Acuity (DVA) test, and the modified Emory Clinical Vestibular Chair Test (m-ECVCT). Up to 33% of the children with GDD had abnormal DVA scores. m-ECVCT results of children with GDD demonstrated larger variance than children with TD. The CTSIB score was significantly reduced in the group with GDD. The test-retest reliability varied, with good reliability for the m-ECVCT and CTSIB, and fair reliability for the DVA. Findings suggest vestibular involvement in children in GDD. The clinical tests demonstrated moderate test-retest reliability.

Interprofessional education in a primary care teaching clinic: findings from a study involving pharmacy and medical students.

PubMed

Sicat, Brigitte Luong; Huynh, Christine; Willett, Rita; Polich, Susan; Mayer, Sallie

2014-01-01

Interprofessional education (IPE) can be hindered by the lack of infrastructure required to support it. We developed a clinical IPE experience for medical and pharmacy students built upon an existing infrastructure. We created tools to orient students to IPE and had students participate in pharmacist-led and physician-led IPE clinics. Results from the surveys indicated that after participating in the IPE experience, there were no significant changes in attitudes toward interprofessional teamwork or attitudes toward different members of the healthcare team. Students found less value in tools outlining roles and responsibilities of team members, on-line modules about the other profession, and IPE group discussion. They placed more value on the actual clinical experience. Themes derived from analysis of open-ended survey questions reflected the value that students placed on interprofessional interaction in the setting of direct patient care.

High fidelity simulation effectiveness in nursing students' transfer of learning.

PubMed

Kirkman, Tera R

2013-07-13

Members of nursing faculty are utilizing interactive teaching tools to improve nursing student's clinical judgment; one method that has been found to be potentially effective is high fidelity simulation (HFS). The purpose of this time series design study was to determine whether undergraduate nursing students were able to transfer knowledge and skills learned from classroom lecture and a HFS clinical to the traditional clinical setting. Students (n=42) were observed and rated on their ability to perform a respiratory assessment. The observations and ratings took place at the bedside, prior to a respiratory lecture, following the respiratory lecture, and following simulation clinical. The findings indicated that there was a significant difference (p=0.000) in transfer of learning demonstrated over time. Transfer of learning was demonstrated and the use of HFS was found to be an effective learning and teaching method. Implications of results are discussed.

Age of dementia diagnosis in community dwelling bilingual and monolingual Hispanic Americans.

PubMed

Lawton, Deborah M; Gasquoine, Philip G; Weimer, Amy A

2015-05-01

Bilingualism has been reported to delay the age of retrospective report of first symptom in dementia. This study determined if the age of clinically diagnosed Alzheimer's disease and vascular dementia occurred later for bilingual than monolingual, immigrant and U.S. born, Hispanic Americans. It involved a secondary analysis of the subset of 81 bi/monolingual dementia cases identified at yearly follow-up (1998 through 2008) using neuropsychological test results and objective diagnostic criteria from the Sacramento Area Latino Study on Aging that involved a random sampling of community dwelling Hispanic Americans (N = 1789). Age of dementia diagnosis was analyzed in a 2 × 2 (bi/monolingualism × immigrant/U.S. born) ANOVA that space revealed both main effects and the interaction were non-significant. Mean age of dementia diagnosis was descriptively (but not significantly) higher in the monolingual (M = 81.10 years) than the bilingual (M = 79.31) group. Overall, bilingual dementia cases were significantly better educated than monolinguals, but U.S. born bilinguals and monolinguals did not differ significantly in education. Delays in dementia symptomatology pertaining to bilingualism are less likely to be found in studies: (a) that use age of clinical diagnosis vs. retrospective report of first dementia symptom as the dependent variable; and (b) involve clinical cases derived from community samples rather than referrals to specialist memory clinics. Copyright © 2014 Elsevier Ltd. All rights reserved.

Randomized clinical trials as reflexive-interpretative process in patients with rheumatoid arthritis: a qualitative study.

PubMed

de Jorge, Mercedes; Parra, Sonia; de la Torre-Aboki, Jenny; Herrero-Beaumont, Gabriel

2015-08-01

Patients in randomized clinical trials have to adapt themselves to a restricted language to capture the necessary information to determine the safety and efficacy of a new treatment. The aim of this study was to explore the experience of patients with rheumatoid arthritis after completing their participation in a biologic therapy randomized clinical trial for a period of 3 years. A qualitative approach was used. The information was collected using 15 semi-structured interviews of patients with rheumatoid arthritis. Data collection was guided by the emergent analysis until no more relevant variations in the categories were found. The data were analysed using the grounded theory method. The objective of the patients when entering the study was to improve their quality of life by initiating the treatment. However, the experience changed the significance of the illness as they acquired skills and practical knowledge related to the management of their disease. The category "Interactional Empowerment" emerged as core category, as it represented the participative experience in a clinical trial. The process integrates the follow categories: "weight of systematisation", "working together", and the significance of the experience: "the duties". Simultaneously these categories evolved. The clinical trial monitoring activities enabled patients to engage in a reflexive-interpretative mechanism that transformed the emotional and symbolic significance of their disease and improved the empowerment of the patient. A better communicative strategy with the health professionals, the relatives of the patients, and the community was also achieved.

Early exposure to probiotics in a canine model of atopic dermatitis has long-term clinical and immunological effects.

PubMed

Marsella, Rosanna; Santoro, Domenico; Ahrens, Kim

2012-04-15

Probiotics modulate the immune response and may have protective effects against atopic dermatitis (AD). Clinical trials using dogs with spontaneous disease are limited by confounding factors such as different diets, environments and sensitizations while a more controlled evaluation is possible using experimental models. A validated model of canine AD showed that early exposure to Lactobacillus rhamnosus GG (LGG) significantly decreases allergen-specific IgE and partially prevents AD in the first 6 months of life. This study is a follow-up three years after discontinuation of LGG. Clinical signs were evaluated after allergen challenge with ragweed, timothy, Dermatophagoides farinae. Allergen-specific IgE, IL-10 and TGF-β were measured on the 1st day of challenge, before allergen exposure. Normal dogs were included as controls. Analyses included seven dogs in the non-probiotic and nine in the probiotic litter. For clinical scores, a 2-Group × 9-Time Analysis of Variance showed significant effects of group (p=0.0003, probiotic

Standardized patient assessment of medical student empathy: ethnicity and gender effects in a multi-institutional study.

PubMed

Berg, Katherine; Blatt, Benjamin; Lopreiato, Joseph; Jung, Julianna; Schaeffer, Arielle; Heil, Daniel; Owens, Tamara; Carter-Nolan, Pamela L; Berg, Dale; Veloski, Jon; Darby, Elizabeth; Hojat, Mohammadreza

2015-01-01

To examine, primarily, the effects of ethnicity and gender, which could introduce bias into scoring, on standardized patient (SP) assessments of medical students and, secondarily, to examine medical students' self-reported empathy for ethnicity and gender effects so as to compare self-perception with the perceptions of SPs. Participants were 577 students from four medical schools in 2012: 373 (65%) were white, 79 (14%) black/African American, and 125 (22%) Asian/Pacific Islander. These students were assessed by 84 SPs: 62 (74%) were white and 22 (26%) were black/African American. SPs completed the Jefferson Scale of Patient Perceptions of Physician Empathy (JSPPPE) and the Global Ratings of Empathy tool. Students completed the Jefferson Scale of Empathy and two Interpersonal Reactivity Index subscales. The investigators used 2,882 student-SP encounters in their analyses. Analyses of SPs' assessments of students' empathy indicated significant interaction effects of gender and ethnicity. Female students, regardless of ethnicity, obtained significantly higher mean JSPPPE scores than men. Female black/African American, female white, and female Asian/Pacific Islander students scored significantly higher on the JSPPPE than their respective male counterparts. Male black/African American students obtained the lowest SP assessment scores of empathy regardless of SP ethnicity. Black/African American students obtained the highest mean scores on self-reported empathy. The significant interaction effects of ethnicity and gender in clinical encounters, plus the inconsistencies observed between SPs' assessments of students' empathy and students' self-reported empathy, raise questions about possible ethnicity and gender biases in the SPs' assessments of medical students' clinical skills.

Cross-kingdom interactions: Candida albicans and bacteria.

PubMed

Shirtliff, Mark E; Peters, Brian M; Jabra-Rizk, Mary Ann

2009-10-01

Bacteria and fungi are found together in a myriad of environments and particularly in a biofilm, where adherent species interact through diverse signaling mechanisms. Yet, despite billions of years of coexistence, the area of research exploring fungal-bacterial interactions, particularly within the context of polymicrobial infections, is still in its infancy. However, reports describing a multitude of wide-ranging interactions between the fungal pathogen Candida albicans and various bacterial pathogens are on the rise. An example of a mutually beneficial interaction is coaggregation, a phenomenon that takes place in oral biofilms where the adhesion of C. albicans to oral bacteria is considered crucial for its colonization of the oral cavity. In contrast, the interaction between C. albicans and Pseudomonas aeruginosa is described as being competitive and antagonistic in nature. Another intriguing interaction is that occurring between Staphylococcus aureus and C. albicans, which although not yet fully characterized, appears to be initially synergistic. These complex interactions between such diverse and important pathogens would have significant clinical implications if they occurred in an immunocompromised host. Therefore, understanding the mechanisms of adhesion and signaling involved in fungal-bacterial interactions may lead to the development of novel therapeutic strategies for impeding microbial colonization and development of polymicrobial disease. © 2009 Federation of European Microbiological Societies. Published by Blackwell Publishing Ltd. All rights reserved.

Use of Clinical Anatomy Resources by Musculoskeletal Outpatient Physiotherapists in Australian Public Hospitals: A Cross-Sectional Study

PubMed Central

Davies, Tilman M.; Cornwall, Jon

2015-01-01

ABSTRACT Purpose: To investigate how musculoskeletal outpatient physiotherapists in public hospitals interact with and perceive clinical anatomy resources in the workplace. Method: This cross-sectional study used a postal survey sent to musculoskeletal outpatient physiotherapists in 64 Australian public hospitals. Survey questions examined demographics, qualifications, experience, types of resources used, whether resources meet requirements, and what improvements could be made to current resources. Results: A total of 193 physiotherapists responded (75% response rate; 60% female), of whom 49% were age 35 years or younger; 67% had only an undergraduate qualification, and 37% had practised for 5 years or less. More experienced physiotherapists used resources significantly less frequently ([odds ratio]=1.35; 95% CI, 1.17–1.57), and we found no significant associations between preference for online versus printed resources and age, sex, qualifications, or experience. Trends included less experienced physiotherapists identifying the absence of online access as a barrier to resource use and provision of improved online facilities as necessary to improve access to clinical anatomy resources. Conclusion: Results indicate distinct trends in physiotherapists' use of clinical anatomy resources, including a desire for improved online resource access on the part of less experienced physiotherapists. The findings are relevant to hospital outpatient clinics, particularly those that employ less experienced physiotherapists. PMID:26839457

Grapefruit and drug interactions.

PubMed

2012-12-01

Since the late 1980s, grapefruit juice has been known to affect the metabolism of certain drugs. Several serious adverse effects involving drug interactions with grapefruit juice have been published in detail. The components of grapefruit juice vary considerably depending on the variety, maturity and origin of the fruit, local climatic conditions, and the manufacturing process. No single component accounts for all observed interactions. Other grapefruit products are also occasionally implicated, including preserves, lyophylised grapefruit juice, powdered whole grapefruit, grapefruit seed extract, and zest. Clinical reports of drug interactions with grapefruit juice are supported by pharmacokinetic studies, each usually involving about 10 healthy volunteers, in which the probable clinical consequences were extrapolated from the observed plasma concentrations. Grapefruit juice inhibits CYP3A4, the cytochrome P450 isoenzyme most often involved in drug metabolism. This increases plasma concentrations of the drugs concerned, creating a risk of overdose and dose-dependent adverse effects. Grapefruit juice also inhibits several other cytochrome P450 isoenzymes, but they are less frequently implicated in interactions with clinical consequences. Drugs interacting with grapefruit and inducing serious clinical consequences (confirmed or very probable) include: immunosuppressants, some statins, benzodiazepines, most calcium channel blockers, indinavir and carbamazepine. There are large inter-individual differences in enzyme efficiency. Along with the variable composition of grapefruit juice, this makes it difficult to predict the magnitude and clinical consequences of drug interactions with grapefruit juice in a given patient. There is increasing evidence that transporter proteins such as organic anion transporters and P-glycoprotein are involved in interactions between drugs and grapefruit juice. In practice, numerous drugs interact with grapefruit juice. Although only a few reports involving severe clinical consequences have been published, they suggest that grapefruit juice should be avoided during drug therapy, especially when the drug has a narrow therapeutic margin or carries a risk of serious dose-dependent adverse effects. Patients should be informed of this risk whenever a drug is prescribed or dispensed.

The effect of an automated clinical reminder on weight loss in primary care.

PubMed

O'Grady, Jason S; Thacher, Tom D; Chaudhry, Rajeev

2013-01-01

Overweight and obese individuals have increased health risks. Clinical reminders positively affect health outcomes in diabetes and osteoporosis, but the effect of automated prompts on weight loss in obesity has not been studied. Our objective was to determine whether an automatic prompt for the clinician to recommend lifestyle changes to patients with a body mass index (BMI) >25 kg/m(2) led to greater weight loss over a 3- to 6-month interval compared with the absence of a clinical reminder. We conducted a retrospective analysis of electronic medical records of obese adult patients with a BMI >25 kg/m(2) who were seen in 2009 and 2010, before and after implementation of an automated printed clinical reminder, respectively. We evaluated 1600 patients in each of the control and intervention groups. The primary outcome was the mean change in BMI between the control and intervention groups. Multiple linear regression was used to assess the effect of the clinical reminder on the change in BMI while adjusting for baseline BMI and potential confounding factors. The reduction in BMI (mean ± standard deviation) in the group with the clinical reminder (-0.084 ± 1.56 kg/m(2)) was not significantly greater than the control group (-0.053 ± 1.49 kg/m(2); P = .56). A regression model incorporating the clinical reminder, age, baseline BMI, obesity diagnosis, diabetes, and hyperlipidemia found that baseline BMI (P < .001), obesity diagnosis (P < .001), age (P = .001), and hyperlipidemia diagnosis (P = .02) were significant predictors of weight loss, but the clinical reminder was not (P = .78). There was a significant interaction between the clinical reminder and baseline BMI (P = .005), as the prompt increased weight loss more in those with lower baseline BMI. Automated clinical reminders alone do not improve weight loss in overweight and obese patients. Physician diagnoses of obesity or hyperlipidemia were associated with weight loss, suggesting that formally noting these diagnoses contributes to successful weight loss.

Pharmacokinetic Drug Interactions with Panax ginseng.

PubMed

Ramanathan, Meenakshi R; Penzak, Scott R

2017-08-01

Panax ginseng is widely used as an adaptogen throughout the world. The major active constituents of P. ginseng are ginsenosides. Most naturally occurring ginsenosides are deglycosylated by colonic bacteria to intestinal metabolites. Ginsenosides along with these metabolites are widely accepted as being responsible for the pharmacologic activity and drug interaction potential of ginseng. Numerous preclinical studies have assessed the influence of various ginseng components on cytochrome P450 (CYP), glucuronidation, and drug transport activity. Results from these investigations have been largely inconclusive due to the use of different ginseng products and variations in methodology between studies. Drug interaction studies in humans have been conflicting and have largely yielded negative results or results that suggest only a weak interaction. One study using a midazolam probe found weak CYP3A induction and another using a fexofenadine probe found weak P-gp inhibition. Despite several case reports indicating a drug interaction between warfarin and P. ginseng, pharmacokinetic studies involving these agents in combination have failed to find significant pharmacokinetic or pharmacodynamic interactions. To this end, drug interactions involving P. ginseng appear to be rare; however, close clinical monitoring is still suggested for patients taking warfarin or CYP3A or P-gp substrates with narrow therapeutic indices.

PTEN Loss as Determined by Clinical-grade Immunohistochemistry Assay Is Associated with Worse Recurrence-free Survival in Prostate Cancer.

PubMed

Lotan, Tamara L; Wei, Wei; Morais, Carlos L; Hawley, Sarah T; Fazli, Ladan; Hurtado-Coll, Antonio; Troyer, Dean; McKenney, Jesse K; Simko, Jeffrey; Carroll, Peter R; Gleave, Martin; Lance, Raymond; Lin, Daniel W; Nelson, Peter S; Thompson, Ian M; True, Lawrence D; Feng, Ziding; Brooks, James D

2016-06-01

PTEN is the most commonly deleted tumor suppressor gene in primary prostate cancer (PCa) and its loss is associated with poor clinical outcomes and ERG gene rearrangement. We tested whether PTEN loss is associated with shorter recurrence-free survival (RFS) in surgically treated PCa patients with known ERG status. A genetically validated, automated PTEN immunohistochemistry (IHC) protocol was used for 1275 primary prostate tumors from the Canary Foundation retrospective PCa tissue microarray cohort to assess homogeneous (in all tumor tissue sampled) or heterogeneous (in a subset of tumor tissue sampled) PTEN loss. ERG status as determined by a genetically validated IHC assay was available for a subset of 938 tumors. Associations between PTEN and ERG status were assessed using Fisher's exact test. Kaplan-Meier and multivariate weighted Cox proportional models for RFS were constructed. When compared to intact PTEN, homogeneous (hazard ratio [HR] 1.66, p = 0.001) but not heterogeneous (HR 1.24, p = 0.14) PTEN loss was significantly associated with shorter RFS in multivariate models. Among ERG-positive tumors, homogeneous (HR 3.07, p < 0.0001) but not heterogeneous (HR 1.46, p = 0.10) PTEN loss was significantly associated with shorter RFS. Among ERG-negative tumors, PTEN did not reach significance for inclusion in the final multivariate models. The interaction term for PTEN and ERG status with respect to RFS did not reach statistical significance ( p = 0.11) for the current sample size. These data suggest that PTEN is a useful prognostic biomarker and that there is no statistically significant interaction between PTEN and ERG status for RFS. We found that loss of the PTEN tumor suppressor gene in prostate tumors as assessed by tissue staining is correlated with shorter time to prostate cancer recurrence after radical prostatectomy.

Population Genetics Study of Isoniazid Resistance Mutations and Evolution of Multidrug-Resistant Mycobacterium tuberculosis†

PubMed Central

Hazbón, Manzour Hernando; Brimacombe, Michael; Bobadilla del Valle, Miriam; Cavatore, Magali; Guerrero, Marta Inírida; Varma-Basil, Mandira; Billman-Jacobe, Helen; Lavender, Caroline; Fyfe, Janet; García-García, Lourdes; León, Clara Inés; Bose, Mridula; Chaves, Fernando; Murray, Megan; Eisenach, Kathleen D.; Sifuentes-Osornio, José; Cave, M. Donald; Ponce de León, Alfredo; Alland, David

2006-01-01

The molecular basis for isoniazid resistance in Mycobacterium tuberculosis is complex. Putative isoniazid resistance mutations have been identified in katG, ahpC, inhA, kasA, and ndh. However, small sample sizes and related potential biases in sample selection have precluded the development of statistically valid and significant population genetic analyses of clinical isoniazid resistance. We present the first large-scale analysis of 240 alleles previously associated with isoniazid resistance in a diverse set of 608 isoniazid-susceptible and 403 isoniazid-resistant clinical M. tuberculosis isolates. We detected 12 mutant alleles in isoniazid-susceptible isolates, suggesting that these alleles are not involved in isoniazid resistance. However, mutations in katG, ahpC, and inhA were strongly associated with isoniazid resistance, while kasA mutations were associated with isoniazid susceptibility. Remarkably, the distribution of isoniazid resistance-associated mutations was different in isoniazid-monoresistant isolates from that in multidrug-resistant isolates, with significantly fewer isoniazid resistance mutations in the isoniazid-monoresistant group. Mutations in katG315 were significantly more common in the multidrug-resistant isolates. Conversely, mutations in the inhA promoter were significantly more common in isoniazid-monoresistant isolates. We tested for interactions among mutations and resistance to different drugs. Mutations in katG, ahpC, and inhA were associated with rifampin resistance, but only katG315 mutations were associated with ethambutol resistance. There was also a significant inverse association between katG315 mutations and mutations in ahpC or inhA and between mutations in kasA and mutations in ahpC. Our results suggest that isoniazid resistance and the evolution of multidrug-resistant strains are complex dynamic processes that may be influenced by interactions between genes and drug-resistant phenotypes. PMID:16870753

Does ethnicity, gender or age of physiotherapy students affect performance in the final clinical placements? An exploratory study.

PubMed

Naylor, Sandra; Norris, Meriel; Williams, Annabel

2014-03-01

To explore demographic differences in awarded marks of the final clinical placement in a physiotherapy undergraduate programme. Retrospective analysis of clinical placement assessment marks. A London university offering clinical placements throughout South East England. 333 physiotherapy students entering physiotherapy training between 2005 to 2009. Marks awarded following assessment using a clinical placement assessment form. The mean mark (SD) for age were standard entry 71 (7.4) vs. mature entry 72 (7.99) (ns); for gender male 72 (8.45) vs. female 71 (7.21) (ns); and ethnicity White British 72 (7.71) vs. ethnic minority 70 (7.01) (p=0.023). No interaction effects were observed between the independent variables and only ethnicity demonstrated a statistically significant effect (mean difference (MD) 2.4% 95%CI 0.5 to 4.3, F=5.24, p=0.023). This difference was maintained in most subcategories. Significant differences were observed for the interpersonal section (MD 2.21% 95%CI 0.14 to 4.28, F=4.409, p=0.03), the clinical reasoning section (MD 2.39% 95%CI 0.53 to 4.25, F=6.37, p=0.012) and the treatment section (MD 2.93 95%CI 1.10 to 4.83, F=9.198, p=0.003). Physiotherapy students from minority ethnic backgrounds were awarded a significantly lower mark than their white majority peers in final clinical placements, although the difference was small. Potential reasons are considered, with the strongest recommendation being for further enquiry into the potential relationship between ethnicity and success in undergraduate physiotherapy education. Copyright © 2013 Chartered Society of Physiotherapy. Published by Elsevier Ltd. All rights reserved.

The Paradox of Pelvic Exenteration: The Interaction of Clinical and Psychological Variables.

PubMed

Arnaboldi, Paola; Santoro, Luigi; Mazzocco, Ketti; Oliveri, Serena; Maggioni, Angelo; Pravettoni, Gabriella

2015-10-01

To text the feasibility of a psychological intervention package administered to 49 pelvic exenteration candidates, aimed at evaluating the preoperative prevalence of psychological distress and assessing the presence of any correlation between preoperative psychological distress and clinical variables such as pain and hospitalization length. Patients were referred to the psychology unit from the very beginning of their clinical pathway and were administered the Psychological Distress Inventory (PDI) and the Mini-Mental Adjustment to Cancer (Mini-MAC) questionnaire at prehospital admission. Patients presenting with a significant level of distress received nonstandardized psychological support. Statistical analyses were performed to detect the presence of any correlation between psychological variables at prehospital admission and clinical outcomes. The 40% of patients had significant levels of distress at prehospital admission (PDI ≥ 30). As regards Mini-MAC, the mean value of fighting spirit attitude and fatalism was higher in our sample than in the normative sample of the Mini-MAC validation study in the Italian cancer population. Their anxious preoccupation attitude was lower. There were no correlations between clinical and psychological variables: level of postsurgery pain was higher (3.7) in the subgroup of patients with presurgery PDI < 30 compared with those with PDI ≥ 30 (3.5). However, this difference was not statistically significant (P = 1.00). Considering hospitalization length, the above described trend was similar. Although highly distressed, pelvic exenteration candidates show an adaptive range of coping mechanisms. This calls for a greater effort in studying the complexity of their psychoemotional status to provide them with the best multidisciplinary care. Extensive study of the real effectiveness of psychological intervention is warranted: randomized clinical trials could help in detecting the presence of any correlation between clinical and psychological variables in a multidisciplinary approach.

Treatment of Binge Eating Disorder in Racially and Ethnically Diverse Obese Patients in Primary Care: Randomized Placebo-Controlled Clinical Trial of Self-Help and Medication

PubMed Central

Grilo, Carlos M.; Masheb, Robin M.; White, Marney A.; Gueorguieva, Ralitza; Barnes, Rachel D.; Walsh, B. Timothy; McKenzie, Katherine C.; Genao, Inginia; Garcia, Rina

2014-01-01

Objective The objective was to determine whether treatments with demonstrated efficacy for binge eating disorder (BED) in specialist treatment centers can be delivered effectively in primary care settings to racially/ethnically diverse obese patients with BED. This study compared the effectiveness of self-help cognitive-behavioral therapy (shCBT) and an anti-obesity medication (sibutramine), alone and in combination, and it is only the second placebo-controlled trial of any medication for BED to evaluate longer-term effects after treatment discontinuation. Method 104 obese patients with BED (73% female, 55% non-white) were randomly assigned to one of four 16-week treatments (balanced 2-by-2 factorial design): sibutramine (N=26), placebo (N=27), shCBT+sibutramine (N=26), or shCBT+placebo (N=25). Medications were administered in double-blind fashion. Independent assessments were performed monthly throughout treatment, post-treatment, and at 6- and 12-month follow-ups (16 months after randomization). Results Mixed-models analyses revealed significant time and medication-by-time interaction effects for percent weight loss, with sibutramine but not placebo associated with significant change over time. Percent weight loss differed significantly between sibutramine and placebo by the third month of treatment and at post-treatment. After the medication was discontinued at post-treatment, weight re-gain occurred in sibutramine groups and percent weight loss no longer differed among the four treatments at 6- and 12-month follow-ups. For binge-eating, mixed-models revealed significant time and shCBT-by-time interaction effects: shCBT had significantly lower binge-eating frequency at 6-month follow-up but the treatments did not differ significantly at any other time point. Demographic factors did not significantly predict or moderate clinical outcomes. Discussion Our findings suggest that pure self-help CBT and sibutramine did not show long-term effectiveness relative to placebo for treating BED in racially/ethnically diverse obese patients in primary care. Overall, the treatments differed little with respect to binge-eating and associated outcomes. Sibutramine was associated with significantly greater acute weight loss than placebo and the observed weight-regain following discontinuation of medication suggests that anti-obesity medications need to be continued for weight loss maintenance. Demographic factors did not predict/moderate clinical outcomes in this diverse patient group. PMID:24857821

Effectiveness of computer-assisted interactive videodisc instruction in teaching rheumatology to physical and occupational therapy students.

PubMed

Sanford, M K; Hazelwood, S E; Bridges, A J; Cutts, J H; Mitchell, J A; Reid, J C; Sharp, G

1996-01-01

A computer-assisted interactive videodisc instructional program, HP-RHEUM was designed to teach clinical findings in arthritis to occupational and physical therapy students. Using the Rheumatology Image Library videodisc produced by the National Library of Medicine, HP-RHEUM consists of instructional modules which employ advance organizers, examples/nonexamples, summaries, and immediate feedback. To see if HP-RHEUM would be as effective as traditional classroom instruction, control data were collected in 1991 from 52 OT and PT students. Treatment data were collected from 61 students in 1992 when HP-RHEUM entirely replaced lectures. Identical pre- and post-tests consisted of 70 multiple choice questions, with 24 matched to slides. On the slide questions the HP-RHEUM group had significantly higher scores. Otherwise, there was no significant difference in performance between groups. HP-RHEUM provided an independent learning method and enhanced visual comprehension of rheumatologic disease concepts.

The effects of acupuncture on rates of clinical pregnancy among women undergoing in vitro fertilization: a systematic review and meta-analysis

PubMed Central

Manheimer, Eric; van der Windt, Daniëlle; Cheng, Ke; Stafford, Kristen; Liu, Jianping; Tierney, Jayne; Lao, Lixing; Berman, Brian M.; Langenberg, Patricia; Bouter, Lex M.

2013-01-01

BACKGROUND Recent systematic reviews of adjuvant acupuncture for IVF have pooled heterogeneous trials, without examining variables that might explain the heterogeneity. The aims of our meta-analysis were to quantify the overall pooled effects of adjuvant acupuncture on IVF clinical pregnancy success rates, and evaluate whether study design-, treatment- and population-related factors influence effect estimates. METHODS We included randomized controlled trials that compared needle acupuncture administered within 1 day of embryo transfer, versus sham acupuncture or no adjuvant treatment. Our primary outcome was clinical pregnancy rates. We obtained from all investigators additional methodological details and outcome data not included in their original publications. We analysed sham-controlled and no adjuvant treatment-controlled trials separately, but since there were no large or significant differences between these two subsets, we pooled all trials for subgroup analyses. We prespecified 11 subgroup variables (5 clinical and 6 methodological) to investigate sources of heterogeneity, using single covariate meta-regressions. RESULTS Sixteen trials (4021 participants) were included in the meta-analyses. There was no statistically significant difference between acupuncture and controls when combining all trials [risk ratio (RR) 1.12, 95% confidence interval (CI), 0.96–1.31; I2 = 68%; 16 trials; 4021 participants], or when restricting to sham-controlled (RR 1.02, 0.83–1.26; I2 = 66%; 7 trials; 2044 participants) or no adjuvant treatment-controlled trials (RR 1.22, 0.97–1.52; I2 = 67%; 9 trials; 1977 participants). The type of control used did not significantly explain the statistical heterogeneity (interaction P = 0.27). Baseline pregnancy rate, measured as the observed rate of clinical pregnancy in the control group of each trial, was a statistically significant effect modifier (interaction P < 0.001), and this covariate explained most of the heterogeneity of the effects of adjuvant acupuncture across all trials (adjusted R2 = 93%; I2 residual = 9%). Trials with lower control group rates of clinical pregnancy showed larger effects of adjuvant acupuncture (RR 1.53, 1.28–1.84; 7 trials; 1732 participants) than trials with higher control group rates of clinical pregnancy (RR 0.90, 0.80–1.01; 9 trials; 2289 participants). The asymmetric funnel plot showed a tendency for the intervention effects to be more beneficial in smaller trials. CONCLUSIONS We found no pooled benefit of adjuvant acupuncture for IVF. The subgroup finding of a benefit in trials with lower, but not higher, baseline pregnancy rates (the only statistically significant subgroup finding in our earlier review) has been confirmed in this update, and was not explained by any confounding variables evaluated. However, this baseline pregnancy rate subgroup finding among published trials requires further confirmation and exploration in additional studies because of the multiple subgroup tests conducted, the risk of unidentified confounders, the multiple different factors that determine baseline rates, and the possibility of publication bias. PMID:23814102

An Assessment of the Science and Technology Predictions in the Army’s STAR21 Report

DTIC Science & Technology

2008-07-01

electronics, optics, and photonics; aeromechanics; molecular genetics ; clinical medicine ; atmospheric sciences; and terrain sciences. Both the Navy and the...for medical diagnostics, functional materials, and manufacturing at the nano-scale. There were a few serious misses, such as significant developments...overstatement. The predictions for vaccines and medicines are right. The study did not mention the key interactions between biomolecules and their

Providing Competency Training to Clinical Supervisors through an Interactional Supervision Approach

ERIC Educational Resources Information Center

Tebes, Jacob Kraemer; Matlin, Samantha L.; Migdole, Scott J.; Farkas, Melanie S.; Money, Roy W.; Shulman, Lawrence; Hoge, Michael A.

2011-01-01

Training in supervisory competencies is essential to effective clinical practice and helps address the current national crisis in the behavioral health workforce. Interactional supervision, the approach used in the current study, is well established in clinical social work and focuses the task of the supervisee on the interpersonal exchanges…

A comparison of the cooperative learning and traditional learning methods in theory classes on nursing students' communication skill with patients at clinical settings.

PubMed

Baghcheghi, Nayereh; Koohestani, Hamid Reza; Rezaei, Koresh

2011-11-01

The purpose of this study was to compare the effect of traditional learning and cooperative learning methods on nursing students' communication skill with patients. This was an experimental study in which 34 nursing students in their 2nd semester of program participated. They were divided randomly into two groups, a control group who were taught their medical/surgical nursing course by traditional learning method and an experimental group, who were taught the same material using cooperative learning method. Before and after the teaching intervention, the students' communication skills with patients at clinical settings were examined. The results showed that no significant difference between the two groups in students' communication skills scores before the teaching intervention, but did show a significant difference between the two groups in the interaction skills and problem follow up sub-scales scores after the teaching intervention. This study provides evidence that cooperative learning is an effective method for improving and increasing communication skills of nursing students especially in interactive skills and follow up the problems sub-scale, thereby it is recommended to increase nursing students' participation in arguments by applying active teaching methods which can provide the opportunity for increased communication skills. Copyright © 2011 Elsevier Ltd. All rights reserved.

Child Directed Interaction Training for Young Children in Kinship Care: A Pilot Study

PubMed Central

N’zi, Amanda M.; Stevens, Monica L.; Eyberg, Sheila M.

2016-01-01

This pilot study used a randomized controlled trial design to examine the feasibility and explore initial outcomes of a twice weekly, 8-session Child Directed Interaction Training (CDIT) program for children living in kinship care. Participants included 14 grandmothers and great-grandmothers with their 2- to 7-year-old children randomized either to CDIT or a waitlist control condition. Training was delivered at a local, community library with high fidelity to the training protocol. There was no attrition in either condition. After training, kinship caregivers in the CDIT condition demonstrated more positive relationships with their children during behavioral observation. The caregivers in the CDIT condition also reported clinically and statistically significant decreases in parenting stress and caregiver depression, as well as fewer externalizing child behavior problems than waitlist controls. Parent daily report measures indicated significant changes in disciplining that included greater use of limit-setting and less use of critical verbal force. Results appeared stable at 3-month follow-up. Changes in child internalizing behaviors and caregiver use of non-critical verbal force were not seen until 3-month follow-up. Results of this pilot study suggest both the feasibility of conducting full scale randomized clinical trials of CDIT in the community and the promise of this approach for providing effective parent training for kinship caregivers. PMID:27012997

Proteomic Identification of the Galectin-1-Involved Molecular Pathways in Urinary Bladder Urothelial Carcinoma.

PubMed

Li, Chien-Feng; Shen, Kun-Hung; Chien, Lan-Hsiang; Huang, Cheng-Hao; Wu, Ting-Feng; He, Hong-Lin

2018-04-19

Among various heterogeneous types of bladder tumors, urothelial carcinoma is the most prevalent lesion. Some of the urinary bladder urothelial carcinomas (UBUCs) develop local recurrence and may cause distal invasion. Galectin-1 de-regulation significantly affects cell transformation, cell proliferation, angiogenesis, and cell invasiveness. In continuation of our previous investigation on the role of galectin-1 in UBUC tumorigenesis, in this study, proteomics strategies were implemented in order to find more galectin-1-associated signaling pathways. The results of this study showed that galectin-1 knockdown could induce 15 down-regulated proteins and two up-regulated proteins in T24 cells. These de-regulated proteins might participate in lipid/amino acid/energy metabolism, cytoskeleton, cell proliferation, cell-cell interaction, cell apoptosis, metastasis, and protein degradation. The aforementioned dys-regulated proteins were confirmed by western immunoblotting. Proteomics results were further translated to prognostic markers by analyses of biopsy samples. Results of cohort studies demonstrated that over-expressions of glutamine synthetase, alcohol dehydrogenase (NADP⁺), fatty acid binding protein 4, and toll interacting protein in clinical specimens were all significantly associated with galectin-1 up-regulation. Univariate analyses showed that de-regulations of glutamine synthetase and fatty acid binding protein 4 in clinical samples were respectively linked to disease-specific survival and metastasis-free survival.

Peer mentorship in student-run free clinics: the impact on preclinical education.

PubMed

Choudhury, Noura; Khanwalkar, Ashoke; Kraninger, Jennifer; Vohra, Adam; Jones, Kohar; Reddy, Shalini

2014-03-01

Our study examines the perceptions of first-year medical students (MS1s) toward fourth-year colleagues (MS4s) in student-run free clinics to investigate the impact of peer mentorship on augmenting the clinical education received by MS1s in a primary care setting. To our knowledge, this is the first study examining the impact of MS4 mentorship in free clinics. A 55-item online questionnaire was administered to MS1s 9 months after matriculation in April 2012. Questions focused on MS1 perceptions of MS4 impact on comfort with patients, self-reported improvement in clinical skills, and overall satisfaction with mentorship in free clinics. The MS4s referenced in the questionnaire were enrolled in a longitudinal service-learning elective. Results were analyzed using one-sample Wilcoxon sign-ranked median test and ordered logistic regression with STATA software. Fifty-five of 77 (71.4%) eligible students began the online survey, with 48 (62.3%) completing it. Responses reflected experiences at four student-run free clinics. Overall, MS4 presence improved MS1 comfort with patients and enhanced interactions with attendings. MS1s were satisfied with the level of MS4 mentorship and agreed that MS4s had a distinct mentoring role from attendings. Ordered logistic regression showed that presence of MS4s was significantly associated with self-reported improvements to physical exam skills at one clinic. At each clinic, MS1s reported improved comfort with patients and satisfaction with mentorship received from MS4s. MS4s did not merely duplicate the role of attending physicians but enhanced interactions between MS1s and physicians. This suggests that the consistent presence of MS4s is a valuable adjunct to the educational experience of free clinics volunteering for MS1s.

Silybin and the liver: From basic research to clinical practice

PubMed Central

Loguercio, Carmela; Festi, Davide

2011-01-01

Herbal products are increasingly used, mainly in chronic liver disease. Extracts of milk thistle, Silymarin and silybin, are the most prescribed natural compounds, with different indications, but with no definitive results in terms of clinical efficacy. This review analyzes the available studies on the effects of the purified product silybin, both as a free and a conjugated molecule, on liver cells or on experimentally induced liver damage, and in patients with liver disease. We searched PUBMED for articles pertaining to the in vitro and in vivo effects of silybin, its antifibrotic, anti-inflammatory, and antioxidant properties, as well as its metabolic effects, combined with the authors’ own knowledge of the literature. Results indicate that the bioavailability of silybin phytosome is higher than that of silymarin and is less influenced by liver damage; silybin does not show significant interactions with other drugs and at doses < 10 g/d has no significant side effects. Experimental studies have clearly demonstrated the antifibrotic, antioxidant and metabolic effects of silybin; previous human studies were insufficient for confirming the clinical efficacy in chronic liver disease, while ongoing clinical trials are promising. On the basis of literature data, silybin seems a promising drug for chronic liver disease. PMID:21633595

History of Childhood Abuse, Drinking Motives, Alcohol Use, and Sexual Risk Behavior Among STD Clinic Patients in St. Petersburg, Russia: A Cross-Sectional Study.

PubMed

Abdala, Nadia; Li, Fangyong; Shaboltas, Alla V; Skochilov, Roman V; Krasnoselskikh, Tatiana V

2016-03-01

The relationship between level of childhood abuse (physical and emotional) and sexual risk behavior of sexually transmitted disease clinic patients in St. Petersburg, Russia was examined through path analyses. Mediating variables investigated were: Alcohol Use Disorder Identification Test (AUDIT), drinking motives (for social interaction, to enhance mood, to facilitate sexual encounters), intimate partner violence (IPV), anxiety, and depression symptoms. Results showed a significant indirect effect of childhood abuse on women's sexual risk behavior: higher level of childhood abuse was associated with a greater likelihood of IPV, motivations to drink, leading to higher AUDIT scores and correlated to higher likelihood of having multiple, new or casual sexual partner(s). No significant effect was identified in paths to condom use. Among men, childhood abuse had no significant effect on sexual risk behavior. Reduction in alcohol-related sexual risk behavior may be achieved by addressing the effects of childhood abuse among female participants.

History of Childhood Abuse, Drinking Motives, Alcohol Use, and Sexual Risk Behavior among STD clinic patients in St. Petersburg, Russia: a cross-sectional study

PubMed Central

Abdala, Nadia; Li, Fangyong; Shaboltas, Alla V.; Skochilov, Roman V.; Krasnoselskikh, Tatiana V.

2015-01-01

The relationship between level of childhood abuse (physical and emotional) and sexual risk behavior of sexually transmitted disease (STD) clinic patients in St. Petersburg, Russia was examined through path analyses. Mediating variables investigated were: Alcohol Use Disorder Identification Test (AUDIT), drinking motives (for social interaction, to enhance mood, to facilitate sexual encounters), intimate partner violence (IPV), anxiety, and depression symptoms. Results showed a significant indirect effect of childhood abuse on women’s sexual risk behavior: higher level of childhood abuse was associated with a greater likelihood of IPV, motivations to drink, leading to higher AUDIT scores and correlated to higher likelihood of having multiple, new or casual sexual partner(s). No significant effect was identified in paths to condom use. Among men, childhood abuse had no significant effect on sexual risk behavior. Reduction in alcohol-related sexual risk behavior may be achieved by addressing the effects of childhood abuse among female participants. PMID:25801476

Individual differences in posttraumatic distress: problems with the DSM-IV model.

PubMed

Bowman, M L

1999-02-01

To evaluate the evidence concerning the role of threatening life events in accounting for clinically significant posttraumatic stress responses. Research was examined to review the epidemiology, evidence of dose-response relations, and individual difference factors in accounting for variations in conditions, including posttraumatic stress disorder, after exposure to threatening events. The evidence is significantly discrepant from the clinical Diagnostic and Statistical Manual of Mental Disorders (DSM-IV) model. Greater distress arises from individual differences than from event characteristics. Important individual differences that interact with threat exposures include trait negative affectivity (neuroticism); beliefs about emotions, the self, the world, and the sources and consequences of danger; and prevent acts, disorders, and intelligence. Reasons for the discrepancies between the evidence and the current model of posttraumatic distress are proposed. In accounting for responses to threatening life events, the relatively minor contribution of event qualities compared with individual differences has significant treatment implications. Treatment approaches assuming that toxic event exposure creates a posttraumatic disorder fail to consider individual differences that could improve treatment efficacy.

The pharmacokinetics and safety profile of oral ganciclovir in combination with trimethoprim in HIV- and CMV-seropositive patients

PubMed Central

Jung, Donald; AbdelHameed, Magdy H; Hunter, John; Teitelbaum, Philip; Dorr, Albert; Griffy, Kay

1999-01-01

Aims We investigated the pharmacokinetics and safety profile of oral ganciclovir coadministered with trimethoprim in HIV-and CMV-seropositive patients. Methods In an open-label, randomized, 3-way crossover study, 12 adult males received oral ganciclovir 1000 mg every 8h, oral trimethoprim 200 mg once daily, or both drugs concomitantly in a sequence of three 7-day treatment periods. Pharmacokinetic parameters were determined and adverse events recorded for each treatment. Results The presence of trimethoprim significantly decreased CLr (12.9%, P = 0.0068) and increased t1/2 (18.1%, P = 0.0378) of ganciclovir. However, these changes are unlikely to be clinically meaningful. There were no statistically significant changes in trimethoprim pharmacokinetic parameters in the presence of ganciclovir, with the exception of a 12.7% increase in Cmin. Ganciclovir was well tolerated when administered alone or in combination with trimethoprim. Conclusions There was no clinically significant pharmacokinetic interaction between oral ganciclovir and trimethoprim when coadministered. PMID:10215748

Articulating nurse practitioner practice using King's theory of goal attainment.

PubMed

de Leon-Demare, Kathleen; MacDonald, Jane; Gregory, David M; Katz, Alan; Halas, Gayle

2015-11-01

To further understand the interactions between nurse practitioners (NPs) and patients, King's nursing theory of goal attainment was applied as the conceptual framework to describe the interactions between NPs and patients in the primary care setting. Six dyads of NPs and their patients were video- and audio-taped over three consecutive clinic visits. For the purposes of this arm of the study, the audio-taped interactions were transcribed and then coded using King's concepts in her theory of goal attainment. King's theory was applicable to describe NP practice. King's concepts and processes of nurse-patient interactions, such as disturbances, mutual goal setting, and transactions, were observed in NP-patient interactions. Disturbances during clinical encounters were essential in the progression toward goal attainment. Elements, such as social exchange, symptom reporting, role explanation, and information around clinical processes facilitated relationship building. NPs as practitioners need to be reflective of their own practice, embrace disturbances in the clinical encounter, and attend to these as opportunities for mutual goal setting. ©2015 American Association of Nurse Practitioners.

The interaction between a HSP-70 gene variant with dietary calories in determining serum markers of inflammation and cardiovascular risk.

PubMed

Mehramiz, Mehrane; Hassanian, Seyed Mahdi; Mardan-Nik, Maryam; Pasdar, Alireza; Jamialahmadi, Khadijeh; Fiuji, Hamid; Moetamani-Ahmadi, Mehrdad; Parizadeh, Seyed Mohammad Reza; Moohebati, Mohsen; Heidari-Bakavoli, Alireza; Ebrahimi, Mahmoud; Ferns, Gordon A; Ghayour-Mobarhan, Majid; Avan, Amir

2017-10-24

The high prevalence of cardiovascular disease (CVD) globally is attributable to an interaction between environmental and genetic factors. Gene × diet interaction studies aim to explore how a modifiable factor interacts with genetic predispositions. Here we have explored the interaction of a heat shock protein (HSP70) gene polymorphism (+1267A > G) with dietary intake and their possible association with serum C-reactive protein (CRP), an inflammatory marker, that is a major component of CVD risk. HSP70 genotype was determined using a TaqMan real time PCR based method.Dietary intake was assessed using a dietary questionnaire. Serum high sensitivity (Hs) CRP and other cardiovascular risk factors were assessed by routine methods. This included coronary angioplasty to determine the presence of coronary artery stenosis. There were significant differences between serum lipid profile and Hs-CRP across the genotypes for Hsp70. The carriers of G allele had higher serum hs-CRP concentrations, compared with the AA homozygotes, with the wild genotype. Interaction analysis showed the association was modulated by total energy intake; the interaction of high energy intake with GG genotype: RERI = 0.77, AP = 0.26, S = 1.6. We have found a significant association between the +1267A > G variant of the HSP70 gene with cardiovascular risk factors and serum hs-CRP concentrations. It is possible that a low energy diet could ameliorate the unfavorable effects of G allele of HSP70. Copyright © 2017 Elsevier Ltd and European Society for Clinical Nutrition and Metabolism. All rights reserved.

Interactions of donor sources and media influence the histo-morphological quality of full-thickness skin models.

PubMed

Lange, Julia; Weil, Frederik; Riegler, Christoph; Groeber, Florian; Rebhan, Silke; Kurdyn, Szymon; Alb, Miriam; Kneitz, Hermann; Gelbrich, Götz; Walles, Heike; Mielke, Stephan

2016-10-01

Human artificial skin models are increasingly employed as non-animal test platforms for research and medical purposes. However, the overall histopathological quality of such models may vary significantly. Therefore, the effects of manufacturing protocols and donor sources on the quality of skin models built-up from fibroblasts and keratinocytes derived from juvenile foreskins is studied. Histo-morphological parameters such as epidermal thickness, number of epidermal cell layers, dermal thickness, dermo-epidermal adhesion and absence of cellular nuclei in the corneal layer are obtained and scored accordingly. In total, 144 full-thickness skin models derived from 16 different donors, built-up in triplicates using three different culture conditions were successfully generated. In univariate analysis both media and donor age affected the quality of skin models significantly. Both parameters remained statistically significant in multivariate analyses. Performing general linear model analyses we could show that individual medium-donor-interactions influence the quality. These observations suggest that the optimal choice of media may differ from donor to donor and coincides with findings where significant inter-individual variations of growth rates in keratinocytes and fibroblasts have been described. Thus, the consideration of individual medium-donor-interactions may improve the overall quality of human organ models thereby forming a reproducible test platform for sophisticated clinical research. Copyright © 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

The insecure psychotherapy base: Using client and therapist attachment styles to understand the early alliance.

PubMed

Marmarosh, Cheri L; Kivlighan, Dennis M; Bieri, Kathryn; LaFauci Schutt, Jean M; Barone, Carrie; Choi, Jaehwa

2014-09-01

The purpose of this study was to test the notion that complementary attachments are best for achieving a secure base in psychotherapy. Specifically, we predicted third to fifth session alliance from client- and therapist-rated attachment style interactions. Using a combined sample of 46 therapy dyads from a community mental health clinic and university counseling center, the client- and therapist-perceived therapy alliance, attachment anxiety, and attachment avoidance were examined at the beginning of therapy. The results of an Actor-Partner Interdependence Model (APIM; Kenny & Cook, 1999, Partner effects in relationship research: Conceptual issues, analytic difficulties, and illustrations. Personal Relationships, 6, 433-448.) indicated that there was no direct effect of either client or therapist attachment style on therapist or client early ratings of the alliance. One significant interaction emerged and indicated that client-perceived alliance was influenced by therapist and client attachment anxiety. The client-perceived early alliance was higher when more anxious therapists worked with clients with decreasing anxiety. The client early alliance was higher when less anxious therapists worked with clients with increasing anxiety. The findings partially support the notion that different attachment configurations between the therapist and client facilitate greater alliance, but this was the case only when assessing client-perceived early alliance and only with regards to the dimension of attachment anxiety. There were no significant main effects or interactions when exploring therapist-perceived alliance. Implications of the findings are discussed along with recommendations for future study and clinical training. PsycINFO Database Record (c) 2014 APA, all rights reserved.

Clowns Benefit Children Hospitalized for Respiratory Pathologies

PubMed Central

Bertini, Mario; Isola, Elena; Paolone, Giuseppe; Curcio, Giuseppe

2011-01-01

The study aims at evaluating health-generating function of humor therapy in a hospital ward hosting children suffering from respiratory pathologies. The main scope of this study is to investigate possible positive effects of the presence of a clown on both the clinical evolution of the on-going disease, and on some physiological and pain parameters. Forty-three children with respiratory pathologies participated in the study: 21 of them belonged to the experimental group (EG) and 22 children to the control group (CG). During their hospitalization, the children of the EG interacted with two clowns who were experienced in the field of pediatric intervention. All participants were evaluated with respect to clinical progress and to a series of physiological and pain measures both before and after the clown interaction. When compared with the CG, EG children showed an earlier disappearance of the pathological symptoms. Moreover, the interaction of the clown with the children led to a statistically significant lowering of diastolic blood pressure, respiratory frequency and temperature in the EG as compared with the control group. The other two parameters of systolic pressure and heart frequency yielded results in the same direction, without reaching statistical significance. A similar health-inducing effect of clown presence was observed on pain parameters, both by self evaluation and assessment by nurses. Taken together, our data indicate that the presence of clowns in the ward has a possible health-inducing effect. Thus, humor can be seen as an easy-to-use, inexpensive and natural therapeutic modality to be used within different therapeutic settings. PMID:21785637

Comparative Clinical Pharmacokinetics of Midodrine and Its Active Metabolite Desglymidodrine in Cirrhotic Patients with Tense Ascites Versus Healthy Volunteers.

PubMed

Ali, Ahmed; Farid, Samar; Amin, Mona; Kassem, Mohamed; Al-Garem, Nouman; Al-Ghobashy, Medhat

2016-02-01

Midodrine is an α-agonist prodrug of desglymidodrine used for the management of hypotension, and can also be used for hepatorenal syndrome and cirrhotic patients with tense ascites. The objective of the present work was to study the clinical pharmacokinetic parameters of midodrine and its active metabolite desglymidodrine in cirrhotic patients with tense ascites, which may help in dose selection and improve treatment outcome. This was a prospective, open-label, single-dose, parallel-group study. At first, a pilot study was performed on one healthy volunteer by taking serial blood samples at scheduled time intervals to validate the method of analysis and sampling times. The full study was then conducted by selecting 12 cirrhotic patients with tense ascites in one group and taking nine blood samples. We also selected five healthy volunteers as the control group and took 11 blood samples. Statistically significant differences were observed between the healthy volunteer group and the patients group in the area under the concentration versus time curve (AUC0-t) and maximum plasma concentration (Cmax) values of midodrine and desglymidodrine. Based on the results of the pharmacokinetic analysis, the patient group was further subdivided into those receiving the interacting drug ranitidine (five patients) and those not receiving the interacting drug (seven patients). Pharmacokinetic parameters of midodrine can differ significantly in cirrhotic patients with tense ascites from those in healthy individuals. Drug monitoring, dose adjustments, and drug-drug interactions should all be considered during therapy in this vulnerable patient group.

Evaluation of linear classifiers on articles containing pharmacokinetic evidence of drug-drug interactions.

PubMed

Kolchinsky, A; Lourenço, A; Li, L; Rocha, L M

2013-01-01

Drug-drug interaction (DDI) is a major cause of morbidity and mortality. DDI research includes the study of different aspects of drug interactions, from in vitro pharmacology, which deals with drug interaction mechanisms, to pharmaco-epidemiology, which investigates the effects of DDI on drug efficacy and adverse drug reactions. Biomedical literature mining can aid both kinds of approaches by extracting relevant DDI signals from either the published literature or large clinical databases. However, though drug interaction is an ideal area for translational research, the inclusion of literature mining methodologies in DDI workflows is still very preliminary. One area that can benefit from literature mining is the automatic identification of a large number of potential DDIs, whose pharmacological mechanisms and clinical significance can then be studied via in vitro pharmacology and in populo pharmaco-epidemiology. We implemented a set of classifiers for identifying published articles relevant to experimental pharmacokinetic DDI evidence. These documents are important for identifying causal mechanisms behind putative drug-drug interactions, an important step in the extraction of large numbers of potential DDIs. We evaluate performance of several linear classifiers on PubMed abstracts, under different feature transformation and dimensionality reduction methods. In addition, we investigate the performance benefits of including various publicly-available named entity recognition features, as well as a set of internally-developed pharmacokinetic dictionaries. We found that several classifiers performed well in distinguishing relevant and irrelevant abstracts. We found that the combination of unigram and bigram textual features gave better performance than unigram features alone, and also that normalization transforms that adjusted for feature frequency and document length improved classification. For some classifiers, such as linear discriminant analysis (LDA), proper dimensionality reduction had a large impact on performance. Finally, the inclusion of NER features and dictionaries was found not to help classification.

In Vitro Drug Interaction Modeling of Combinations of Azoles with Terbinafine against Clinical Scedosporium prolificans Isolates

PubMed Central

Meletiadis, Joseph; Mouton, Johan W.; Meis, Jacques F. G. M.; Verweij, Paul E.

2003-01-01

The in vitro interaction between terbinafine and the azoles voriconazole, miconazole, and itraconazole against five clinical Scedosporium prolificans isolates after 48 and 72 h of incubation was tested by a microdilution checkerboard (eight-by-twelve) technique. The antifungal effects of the drugs alone and in combination on the fungal biomass as well as on the metabolic activity of fungi were measured using a spectrophotometric method and two colorimetric methods, based on the lowest drug concentrations showed 75 and 50% growth inhibition (MIC-1 and MIC-2, respectively). The nature and the intensity of the interactions were assessed using a nonparametric approach (fractional inhibitory concentration [FIC] index model) and a fully parametric response surface approach (Greco model) of the Loewe additivity (LA) no-interaction theory as well as a nonparametric (Prichard model) and a semiparametric response surface approaches of the Bliss independence (BI) no-interaction theory. Statistically significant synergy was found between each of the three azoles and terbinafine in all cases, although with different intensities. A 27- to 64-fold and 16- to 90-fold reduction of the geometric mean of the azole and terbinafine MICs, respectively, was observed when they were combined, resulting in FIC indices of <1 to 0.02. Using the MIC-1 higher levels of synergy were obtained, , which were more consistent between the two incubation periods than using the MIC-2. The strongest synergy among the azoles was found with miconazole using the BI-based models and with voriconazole using the LA-based models. The synergistic effects both on fungal growth and metabolic activity were more potent after 72 h of incubation. Fully parametric approaches in combination with the modified colorimetric method might prove useful for testing the in vitro interaction of antifungal drugs against filamentous fungi. PMID:12499177

In Vitro and Clinical Evaluations of the Drug-Drug Interaction Potential of a Metabotropic Glutamate 2/3 Receptor Agonist Prodrug with Intestinal Peptide Transporter 1

PubMed Central

Long, Amanda J.; Annes, William F.; Witcher, Jennifer W.; Knadler, Mary Pat; Ayan-Oshodi, Mosun A.; Mitchell, Malcolm I.; Leese, Phillip; Hillgren, Kathleen M.

2017-01-01

Despite peptide transporter 1 (PEPT1) being responsible for the bioavailability for a variety of drugs, there has been little study of its potential involvement in drug-drug interactions. Pomaglumetad methionil, a metabotropic glutamate 2/3 receptor agonist prodrug, utilizes PEPT1 to enhance absorption and bioavailability. In vitro studies were conducted to guide the decision to conduct a clinical drug interaction study and to inform the clinical study design. In vitro investigations determined the prodrug (LY2140023 monohydrate) is a substrate of PEPT1 with Km value of approximately 30 µM, whereas the active moiety (LY404039) is not a PEPT1 substrate. In addition, among the eight known PEPT1 substrates evaluated in vitro, valacyclovir was the most potent inhibitor (IC50 = 0.46 mM) of PEPT1-mediated uptake of the prodrug. Therefore, a clinical drug interaction study was conducted to evaluate the potential interaction between the prodrug and valacyclovir in healthy subjects. No effect of coadministration was observed on the pharmacokinetics of the prodrug, valacyclovir, or either of their active moieties. Although in vitro studies showed potential for the prodrug and valacyclovir interaction via PEPT1, an in vivo study showed no interaction between these two drugs. PEPT1 does not appear to easily saturate because of its high capacity and expression in the intestine. Thus, a clinical interaction at PEPT1 is unlikely even with a compound with high affinity for the transporter. PMID:27895114

Evaluation of Evidence of Statistical Support and Corroboration of Subgroup Claims in Randomized Clinical Trials.

PubMed

Wallach, Joshua D; Sullivan, Patrick G; Trepanowski, John F; Sainani, Kristin L; Steyerberg, Ewout W; Ioannidis, John P A

2017-04-01

Many published randomized clinical trials (RCTs) make claims for subgroup differences. To evaluate how often subgroup claims reported in the abstracts of RCTs are actually supported by statistical evidence (P < .05 from an interaction test) and corroborated by subsequent RCTs and meta-analyses. This meta-epidemiological survey examines data sets of trials with at least 1 subgroup claim, including Subgroup Analysis of Trials Is Rarely Easy (SATIRE) articles and Discontinuation of Randomized Trials (DISCO) articles. We used Scopus (updated July 2016) to search for English-language articles citing each of the eligible index articles with at least 1 subgroup finding in the abstract. Articles with a subgroup claim in the abstract with or without evidence of statistical heterogeneity (P < .05 from an interaction test) in the text and articles attempting to corroborate the subgroup findings. Study characteristics of trials with at least 1 subgroup claim in the abstract were recorded. Two reviewers extracted the data necessary to calculate subgroup-level effect sizes, standard errors, and the P values for interaction. For individual RCTs and meta-analyses that attempted to corroborate the subgroup findings from the index articles, trial characteristics were extracted. Cochran Q test was used to reevaluate heterogeneity with the data from all available trials. The number of subgroup claims in the abstracts of RCTs, the number of subgroup claims in the abstracts of RCTs with statistical support (subgroup findings), and the number of subgroup findings corroborated by subsequent RCTs and meta-analyses. Sixty-four eligible RCTs made a total of 117 subgroup claims in their abstracts. Of these 117 claims, only 46 (39.3%) in 33 articles had evidence of statistically significant heterogeneity from a test for interaction. In addition, out of these 46 subgroup findings, only 16 (34.8%) ensured balance between randomization groups within the subgroups (eg, through stratified randomization), 13 (28.3%) entailed a prespecified subgroup analysis, and 1 (2.2%) was adjusted for multiple testing. Only 5 (10.9%) of the 46 subgroup findings had at least 1 subsequent pure corroboration attempt by a meta-analysis or an RCT. In all 5 cases, the corroboration attempts found no evidence of a statistically significant subgroup effect. In addition, all effect sizes from meta-analyses were attenuated toward the null. A minority of subgroup claims made in the abstracts of RCTs are supported by their own data (ie, a significant interaction effect). For those that have statistical support (P < .05 from an interaction test), most fail to meet other best practices for subgroup tests, including prespecification, stratified randomization, and adjustment for multiple testing. Attempts to corroborate statistically significant subgroup differences are rare; when done, the initially observed subgroup differences are not reproduced.

Evaluation of community pharmacists' knowledge and awareness of food-drug interactions in Palestine.

PubMed

Radwan, Asma; Sweileh, Anwar; Shraim, We'am; Hroub, Amr; Elaraj, Josephean; Shraim, Naser

2018-05-02

Background Food-drug interactions can produce undesirable outcomes during the therapy process. The pharmacist is responsible for providing patients counseling about common food-drug interactions. Knowledge of such interactions is important to avoid their occurrence. Objective This study aimed to assess the knowledge and awareness of community pharmacists about common food-drug interactions. Setting Pharmacists working in community pharmacies across Northern Palestine. Method This is a cross-sectional study, which involved a convenience sample of 259 pharmacists working in community pharmacies in Palestine. A self-administered questionnaire consisted of 29 questions (mainly yes/no questions) was used to assess pharmacists' knowledge towards the most common and clinically significant interactions between food and medicines. Main outcome measure Pharmacists' issues related to the knowledge of food drug interactions were evaluated. Results A total of 320 questionnaires were distributed of which 259 were completed providing a response rate 80.9%. One pharmacist from each community pharmacy was asked to complete the questionnaire. The overall knowledge score of food-drug interactions for the pharmacists was 17.9 (61.7%) out of a possible maximum of 29. The pharmacists surveyed in this study have demonstrated good knowledge of some interactions; but poor knowledge of others. Conclusion Pharmacists' knowledge about common food-drug interactions is inadequate. These findings support the need for training and educational courses for pharmacists regarding food-drug interactions.

Multimodal Pressure Flow Analysis: Application of Hilbert Huang Transform in Cerebral Blood Flow Regulation

PubMed Central

Lo, Men-Tzung; Hu, Kun; Liu, Yanhui; Peng, C.-K.; Novak, Vera

2008-01-01

Quantification of nonlinear interactions between two nonstationary signals presents a computational challenge in different research fields, especially for assessments of physiological systems. Traditional approaches that are based on theories of stationary signals cannot resolve nonstationarity-related issues and, thus, cannot reliably assess nonlinear interactions in physiological systems. In this review we discuss a new technique “Multi-Modal Pressure Flow method (MMPF)” that utilizes Hilbert-Huang transformation to quantify dynamic cerebral autoregulation (CA) by studying interaction between nonstationary cerebral blood flow velocity (BFV) and blood pressure (BP). CA is an important mechanism responsible for controlling cerebral blood flow in responses to fluctuations in systemic BP within a few heart-beats. The influence of CA is traditionally assessed from the relationship between the well-pronounced systemic BP and BFV oscillations induced by clinical tests. Reliable noninvasive assessment of dynamic CA, however, remains a challenge in clinical and diagnostic medicine. In this brief review we: 1) present an overview of transfer function analysis (TFA) that is traditionally used to quantify CA; 2) describe the a MMPF method and its modifications; 3) introduce a newly developed automatic algorithm and engineering aspects of the improved MMPF method; and 4) review clinical applications of MMPF and its sensitivity for detection of CA abnormalities in clinical studies. The MMPF analysis decomposes complex nonstationary BP and BFV signals into multiple empirical modes adaptively so that the fluctuations caused by a specific physiologic process can be represented in a corresponding empirical mode. Using this technique, we recently showed that dynamic CA can be characterized by specific phase delays between the decomposed BP and BFV oscillations, and that the phase shifts are significantly reduced in hypertensive, diabetics and stroke subjects with impaired CA. In addition, the new technique enables reliable assessment of CA using both data collected during clinical test and spontaneous BP/BFV fluctuations during baseline resting conditions. PMID:18725996

Task-technology fit of video telehealth for nurses in an outpatient clinic setting.

PubMed

Cady, Rhonda G; Finkelstein, Stanley M

2014-07-01

Incorporating telehealth into outpatient care delivery supports management of consumer health between clinic visits. Task-technology fit is a framework for understanding how technology helps and/or hinders a person during work processes. Evaluating the task-technology fit of video telehealth for personnel working in a pediatric outpatient clinic and providing care between clinic visits ensures the information provided matches the information needed to support work processes. The workflow of advanced practice registered nurse (APRN) care coordination provided via telephone and video telehealth was described and measured using a mixed-methods workflow analysis protocol that incorporated cognitive ethnography and time-motion study. Qualitative and quantitative results were merged and analyzed within the task-technology fit framework to determine the workflow fit of video telehealth for APRN care coordination. Incorporating video telehealth into APRN care coordination workflow provided visual information unavailable during telephone interactions. Despite additional tasks and interactions needed to obtain the visual information, APRN workflow efficiency, as measured by time, was not significantly changed. Analyzed within the task-technology fit framework, the increased visual information afforded by video telehealth supported the assessment and diagnostic information needs of the APRN. Telehealth must provide the right information to the right clinician at the right time. Evaluating task-technology fit using a mixed-methods protocol ensured rigorous analysis of fit within work processes and identified workflows that benefit most from the technology.

Dentin Biomodification: Strategies, Renewable Resources and Clinical Applications

PubMed Central

Bedran-Russo, Ana K.; Pauli, Guido F.; Chen, Shao-Nong; McAlpine, James; Castellan, Carina S.; Phansalkar, Rasika S; Aguiar, Thaiane R.; Vidal, Cristina M.P.; Napotilano, José; Nam, Joo-Won; Leme, Ariene A.

2014-01-01

Objectives The biomodification of dentin is a biomimetic approach, mediated by bioactive agents, to enhance and reinforce the dentin by locally altering the biochemistry and biomechanical properties. This review provides an overview of key dentin matrix components, targeting effects of biomodification strategies, the chemistry of renewable natural sources, and current research on their potential clinical applications. Methods The PubMed database and collected literature were used as a resource for peer-reviewed articles to highlight the topics of dentin hierarchical structure, biomodification agents, and laboratorial investigations of their clinical applications. In addition, new data is presented on laboratorial methods for the standardization of proanthocyanidin-rich preparations as a renewable source of plant-derived biomodification agents. Results Biomodification agents can be categorized as physical methods and chemical agents. Synthetic and naturally occurring chemical strategies present distinctive mechanism of interaction with the tissue. Initially thought to be driven only by inter- or intra-molecular collagen induced non-enzymatic collagen cross-linking, multiple interactions with other dentin components are fundamental for the long-term biomechanics and biostability of the tissue. Oligomeric proanthocyanidins show promising bioactivity, and their chemical complexity requires systematic evaluation of the active compounds to produce a fully standardized intervention material from renewable resource, prior to their detailed clinical evaluation. Significance Understanding the hierarchical structure of dentin and the targeting effect of the bioactive compounds will establish their use in both dentin-biomaterials interface and caries management. PMID:24309436

Comparative effectiveness of instructional methods: oral and pharyngeal cancer examination.

PubMed

Clark, Nereyda P; Marks, John G; Sandow, Pamela R; Seleski, Christine E; Logan, Henrietta L

2014-04-01

This study compared the effectiveness of different methods of instruction for the oral and pharyngeal cancer examination. A group of thirty sophomore students at the University of Florida College of Dentistry were randomly assigned to three training groups: video instruction, a faculty-led hands-on instruction, or both video and hands-on instruction. The training intervention involved attending two sessions spaced two weeks apart. The first session used a pretest to assess students' baseline didactic knowledge and clinical examination technique. The second session utilized two posttests to assess the comparative effectiveness of the training methods on didactic knowledge and clinical technique. The key findings were that students performed the clinical examination significantly better with the combination of video and faculty-led hands-on instruction (p<0.01). All students improved their clinical exam skills, knowledge, and confidence in performing the oral and pharyngeal cancer examination independent of which training group they were assigned. Utilizing both video and interactive practice promoted greater performance of the clinical technique on the oral and pharyngeal cancer examination.

Distance management of inflammatory bowel disease: Systematic review and meta-analysis

PubMed Central

Huang, Vivian W; Reich, Krista M; Fedorak, Richard N

2014-01-01

AIM: To review the effectiveness of distance management methods in the management of adult inflammatory bowel disease (IBD) patients. METHODS: A systematic review and meta-analysis of randomized controlled trials comparing distance management and standard clinic follow-up in the management of adult IBD patients. Distance management intervention was defined as any remote management method in which there is a patient self-management component whereby the patient interacts remotely via a self-guided management program, electronic interface, or self-directs open access to clinic follow up. The search strategy included electronic databases (Medline, PubMed, CINAHL, The Cochrane Central Register of Controlled Trials, EMBASE, KTPlus, Web of Science, and SCOPUS), conference proceedings, and internet search for web publications. The primary outcome was the mean difference in quality of life, and the secondary outcomes included mean difference in relapse rate, clinic visit rate, and hospital admission rate. Study selection, data extraction, and risk of bias assessment were completed by two independent reviewers. RESULTS: The search strategy identified a total of 4061 articles, but only 6 randomized controlled trials met the inclusion and exclusion criteria for the systematic review and meta-analysis. Three trials involved telemanagement, and three trials involved directed patient self-management and open access clinics. The total sample size was 1463 patients. There was a trend towards improved quality of life in distance management patients with an end IBDQ quality of life score being 7.28 (95%CI: -3.25-17.81) points higher than standard clinic follow-up. There was a significant decrease in the clinic visit rate among distance management patients mean difference -1.08 (95%CI: -1.60--0.55), but no significant change in relapse rate or hospital admission rate. CONCLUSION: Distance management of IBD significantly decreases clinic visit utilization, but does not significantly affect relapse rates or hospital admission rates. PMID:24574756

Food intake attenuates the drug interaction between new quinolones and aluminum.

PubMed

Imaoka, Ayuko; Abiru, Kosuke; Akiyoshi, Takeshi; Ohtani, Hisakazu

2018-01-01

Intestinal absorption of new quinolones is decreased by oral administration of polyvalent metal cations. Some clinical studies have demonstrated this drug - drug interaction is more prominent under fasted condition. However, the effect of food intake on the extent of drug - drug interaction between new quinolones and metal cations remains to be investigated quantitatively and systematically. The aim of this study was to develop an animal model that enables to evaluate the effect of food intake on the extent of drug - drug interaction in the gastrointestinal tract by chelation and to apply the model to evaluate quantitatively the effect of food intake on the drug - drug interaction between two new quinolones, ofloxacin or ciprofloxacin and sucralfate. The rats were orally administered new quinolones (5.3 mg/kg of ofloxacin or 10 mg/kg of ciprofloxacin) with or without 13.3 mg/kg of sucralfate under fasted or fed condition and plasma concentration profiles of new quinolones were monitored. To the fed group, standard breakfast used in human studies was pasted and administered at a dose of 8.8 g/kg. The area under the plasma concentration - time curves (AUC 0-6 ) of ofloxacin and ciprofloxacin under the fasted condition were significantly decreased to 28.8 and 17.1% by co-administration of sucralfate, respectively. On the contrary, sucralfate moderately decreased the AUC 0-6 of ofloxacin and ciprofloxacin to 54.9 and 33.2%, respectively, under fed condition. The effects of sucralfate and food intake on the kinetics of ofloxacin in this study were well consistent with the results of previous clinical trial. The developed animal model quantitatively reproduced the effect of food intake on the drug - drug interaction between ofloxacin and sucralfate. The similar influences were observed for the drug - drug interaction between ciprofloxacin and sucralfate, suggesting that the extent of drug - drug interaction caused by chelation is generally attenuated by food intake.

Identification of two clinical hepatocellular carcinoma patient phenotypes from results of standard screening parameters

PubMed Central

Carr, Brian I.; Giannini, Edoardo G.; Farinati, Fabio; Ciccarese, Francesca; Rapaccini, Gian Ludovico; Marco, Maria Di; Benvegnù, Luisa; Zoli, Marco; Borzio, Franco; Caturelli, Eugenio; Chiaramonte, Maria; Trevisani, Franco

2014-01-01

Background Previous work has shown that 2 general processes contribute to hepatocellular cancer (HCC) prognosis. They are: a. liver damage, monitored by indices such as blood bilirubin, prothrombin time and AST; as well as b. tumor biology, monitored by indices such as tumor size, tumor number, presence of PVT and blood AFP levels. These 2 processes may affect one another, with prognostically significant interactions between multiple tumor and host parameters. These interactions form a context that provide personalization of the prognostic meaning of these factors for every patient. Thus, a given level of bilirubin or tumor diameter might have a different significance in different personal contexts. We previously applied Network Phenotyping Strategy (NPS) to characterize interactions between liver function indices of Asian HCC patients and recognized two clinical phenotypes, S and L, differing in tumor size and tumor nodule numbers. Aims To validate the applicability of the NPS-based HCC S/L classification on an independent European HCC cohort, for which survival information was additionally available. Methods Four sets of peripheral blood parameters, including AFP-platelets, derived from routine blood parameter levels and tumor indices from the ITA.LI.CA database, were analyzed using NPS, a graph-theory based approach, which compares personal patterns of complete relationships between clinical data values to reference patterns with significant association to disease outcomes. Results Without reference to the actual tumor sizes, patients were classified by NPS into 2 subgroups with S and L phenotypes. These two phenotypes were recognized using solely the HCC screening test results, consisting of eight common blood parameters, paired by their significant correlations, including an AFP-Platelets relationship. These trends were combined with patient age, gender and self-reported alcoholism into NPS personal patient profiles. We subsequently validated (using actual scan data) that patients in L phenotype group had 1.5x larger mean tumor masses relative to S, p=6×10−16. Importantly, with the new data, liver test pattern-identified S-phenotype patients had typically 1.7 × longer survival compared to L-phenotype. NPS integrated the liver, tumor and basic demographic factors. Cirrhosis associated thrombocytopenia was typical for smaller S-tumors. In L-tumor phenotype, typical platelet levels increased with the tumor mass. Hepatic inflammation and tumor factors contributed to more aggressive L tumors, with parenchymal destruction and shorter survival. Summary NPS provides integrative interpretation for HCC behavior, identifying two tumor and survival phenotypes by clinical parameter patterns. The NPS classifier is provided as an Excel tool. The NPS system shows the importance of considering each tumor marker and parameter in the total context of all the other parameters of an individual patient. PMID:25023357

Clopidogrel-Proton Pump Inhibitor Drug-Drug Interaction and Risk of Adverse Clinical Outcomes Among PCI-Treated ACS Patients: A Meta-analysis.

PubMed

Serbin, Michael A; Guzauskas, Gregory F; Veenstra, David L

2016-08-01

Uncertainty regarding clopidogrel effectiveness attenuation because of a drug-drug interaction with proton pump inhibitors (PPI) has led to conflicting guidelines on concomitant therapy. In particular, the effect of this interaction in patients who undergo a percutaneous coronary intervention (PCI), a population known to have increased risk of adverse cardiovascular events, has not been systematically evaluated. To synthesize the evidence of the effect of clopidogrel-PPI drug interaction on adverse cardiovascular outcomes in a PCI patient population. We conducted a systematic literature review for studies reporting clinical outcomes in patients who underwent a PCI and were initiated on clopidogrel with or without a PPI. Studies were included in the analysis if they reported at least 1 of the clinical outcomes of interest (major adverse cardiovascular event [MACE], cardiovascular death, all-cause death, myocardial infarction, stroke, stent thrombosis, and bleed events). We excluded studies that were not exclusive to PCI patients or had no PCI subgroup analysis and/or did not report at least a 6-month follow-up. Statistical and clinical heterogeneity were evaluated and HRs and 95% CIs for adverse clinical events were pooled using the DerSimonian and Laird random-effects meta-analysis method. We identified 12 studies comprising 50,277 PCI patients that met our inclusion and exclusion criteria. Our analysis included retrospective analyses of randomized controlled trials (2), health registries (3), claims databases (2), and institutional records (5); no prospective studies of PCI patients were identified. On average, patients were in their mid-60s, male, and had an array of comorbidities, including hyperlipidemia, diabetes, hypertension, and smoking history. Concomitant therapy following PCI resulted in statistically significant increases in composite MACE (HR = 1.28; 95% CI = 1.24-1.32), myocardial infarction (HR = 1.51; 95% CI = 1.40-1.62), and stroke (HR = 1.46; 95% CI = 1.15-1.86). However, concomitant therapy had no statistically significant effect on stent thrombosis, mortality measured by all-cause or cardiovascular death, or major bleeding before or after the grouping of studies that reported a major or minor bleed outcome. Only 1 study reported on gastrointestinal bleed, and pooled analysis could not be conducted. Statistical testing suggested heterogeneity among studies, but subgroup analysis did not reveal a clear source. Based on the results from this meta-analysis of retrospective analyses of randomized controlled trials and observational studies, concomitant clopidogrel-PPI therapy following PCI appears to be significantly associated with adverse cardiovascular events. Further research on the effect of individual PPIs is needed. Serbin, Guzauskas, and Veenstra were supported by the NIH Common Fund and NIA (1U01AG047109-01, Veenstra, PI) via the Personalized Medicine Economics Research (PriMER) project. The authors do not report any conflicting interests. All authors contributed to the study concept and design. Serbin took the lead in data collection; data interpretation was performed primarily by Serbin, with assistance from the other authors. The manuscript was written primarily by Serbin, along with Guzauskas, and revised by Guzauskas and Veenstra, with assistance from Serbin.