Baseline Characteristics of Patients Predicting Suitability for Rapid Naltrexone Induction

PubMed Central

Mogali, Shanthi; Khan, Nabil A.; Drill, Esther S.; Pavlicova, Martina; Sullivan, Maria A.; Nunes, Edward; Bisaga, Adam

2015-01-01

Background and Objectives Extended-release (XR) injection naltrexone has proved promising in the treatment of opioid dependence. Induction onto naltrexone is often accomplished with a procedure known as rapid naltrexone induction. The purpose of this study was to evaluate pre-treatment patient characteristics as predictors of successful completion of a rapid naltrexone induction procedure prior to XR naltrexone treatment. Methods A chart review of 150 consecutive research participants (N = 84 completers and N = 66 non-completers) undergoing a rapid naltrexone induction with the buprenorphone-clonidine procedure were compared on a number of baseline demographic, clinical and psychosocial factors. Logistic regression was used to identify client characteristics that may predict successful initiation of naltrexone after a rapid induction-detoxification. Results Patients who failed to successfully initiate naltrexone were younger (AOR: 1.040, CI: 1.006, 1.075), and using 10 or more bags of heroin (or equivalent) per day (AOR: 0.881, CI: 0.820, 0.946). Drug use other than opioids was also predictive of failure to initiate naltrexone in simple bivariate analyses, but was no longer significant when controlling for age and opioid use level. Conclusions Younger age, and indicators of greater substance dependence severity (more current opioid use, other substance use) predict difficulty completing a rapid naltrexone induction procedure. Such patients might require a longer period of stabilization and/or more gradual detoxification prior to initiating naltrexone. Scientific Significance Our study findings identify specific characteristics of patients who responded positively to rapid naltrexone induction. PMID:25907815

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

Deibler, Lisa Anne; Brown, Arthur; Puskar, Joseph D.

Drawn 304L stainless steel tubing was subjected to 42 different annealing heat treatments with the goal of initializing a microstructural model to select a heat treatment to soften the tubing from a hardness of 305 Knoop to 225–275 Knoop. The amount of recrystallization and grain size caused by 18 heat treatments were analyzed via optical microscopy and image analysis, revealing the full range of recrystallization from 0 to 100%. The formation of carbides during the longer duration and higher-temperature heat treatments was monitored via transmission electron microscope evaluation. The experimental results informed a model which includes recovery, recrystallization, and grainmore » growth to predict microstructure and hardness. After initialization of the model, it was able to predict hardness with a R 2 value of 0.95 and recrystallization with an R 2 value of 0.99. As a result, the model was then utilized in the design and testing of a heat treatment to soften the tubing.« less

Personality and mental health treatment: Traits as predictors of presentation, usage, and outcome.

PubMed

Thalmayer, Amber Gayle

2018-03-08

Self-report scores on personality inventories predict important life outcomes, including health and longevity, marital outcomes, career success, and mental health problems, but the ways they predict mental health treatment have not been widely explored. Psychotherapy is sought for diverse problems, but about half of those who begin therapy drop out, and only about half who complete therapy experience lasting improvements. Several authors have argued that understanding how personality traits relate to treatment could lead to better targeted, more successful services. Here self-report scores on Big Five and Big Six personality dimensions are explored as predictors of therapy presentation, usage, and outcomes in a sample of community clinic clients (N = 306). Participants received evidence-based treatments in the context of individual-, couples-, or family-therapy sessions. One measure of initial functioning and three indicators of outcome were used. All personality trait scores except Openness associated with initial psychological functioning. Higher Conscientiousness scores predicted more sessions attended for family therapy but fewer for couples-therapy clients. Higher Honesty-Propriety and Extraversion scores predicted fewer sessions attended for family-therapy clients. Better termination outcome was predicted by higher Conscientiousness scores for family- and higher Extraversion scores for individual-therapy clients. Higher Honesty-Propriety and Neuroticism scores predicted more improvement in psychological functioning in terms of successive Outcome Questionnaire-45 administrations. Taken together, the results provide some support for the role of personality traits in predicting treatment usage and outcome and for the utility of a 6-factor model in this context. (PsycINFO Database Record (c) 2018 APA, all rights reserved).

The role of motivation in family-based guided self-help treatment for pediatric obesity.

PubMed

Accurso, Erin C; Norman, Gregory J; Crow, Scott J; Rock, Cheryl L; Boutelle, Kerri N

2014-10-01

Identifying factors associated with effective treatment for childhood obesity is important to improving weight loss outcomes. The current study investigated whether child or parent motivation throughout the course of treatment predicted reductions in BMI. Fifty 8- to 12-year-old children with overweight and obesity (BMI percentiles 85-98%) and their parents participated in a guided self-help weight loss program, which included 12 brief sessions across 5 months. Parents and interventionists reported on child and parent motivation level at each session. Multilevel slopes-as-outcome models were used to examine growth trajectories for both child and parent BMI across sessions. Greater interventionist-rated child motivation predicted greater reductions in child BMI; parent motivation did not. However, interventionist-rated parent motivation predicted greater reductions in parent BMI, and its impact on BMI became more pronounced over the course of treatment, such that sustained motivation was more important than initial motivation. Children who were older, Latino, or who had lower initial BMIs had slower reductions in BMI. This study suggests that motivation may be an important predictor of reduced BMI in child obesity treatment, with sustained motivation being more important than initial motivation. In particular, interventionist-rated, but not parent-rated, motivation is a robust predictor of child and parent BMI outcomes. Future research may evaluate whether motivational interventions can enhance outcome, with particular attention to improving outcomes for Latino children.

Exposure–response model for sibutramine and placebo: suggestion for application to long-term weight-control drug development

PubMed Central

Han, Seunghoon; Jeon, Sangil; Hong, Taegon; Lee, Jongtae; Bae, Soo Hyeon; Park, Wan-su; Park, Gab-jin; Youn, Sunil; Jang, Doo Yeon; Kim, Kyung-Soo; Yim, Dong-Seok

2015-01-01

No wholly successful weight-control drugs have been developed to date, despite the tremendous demand. We present an exposure–response model of sibutramine mesylate that can be applied during clinical development of other weight-control drugs. Additionally, we provide a model-based evaluation of sibutramine efficacy. Data from a double-blind, randomized, placebo-controlled, multicenter study were used (N=120). Subjects in the treatment arm were initially given 8.37 mg sibutramine base daily, and those who lost <2 kg after 4 weeks’ treatment were escalated to 12.55 mg. The duration of treatment was 24 weeks. Drug concentration and body weight were measured predose and at 4 weeks, 8 weeks, and 24 weeks after treatment initiation. Exposure and response to sibutramine, including the placebo effect, were modeled using NONMEM 7.2. An asymptotic model approaching the final body weight was chosen to describe the time course of weight loss. Extent of weight loss was described successfully using a sigmoidal exposure–response relationship of the drug with a constant placebo effect in each individual. The placebo effect was influenced by subjects’ sex and baseline body mass index. Maximal weight loss was predicted to occur around 1 year after treatment initiation. The difference in mean weight loss between the sibutramine (daily 12.55 mg) and placebo groups was predicted to be 4.5% in a simulation of 1 year of treatment, with considerable overlap of prediction intervals. Our exposure–response model, which included the placebo effect, is the first example of a quantitative model that can be used to predict the efficacy of weight-control drugs. Similar approaches can help decision-making during clinical development of novel weight-loss drugs. PMID:26392753

Exposure-response model for sibutramine and placebo: suggestion for application to long-term weight-control drug development.

PubMed

Han, Seunghoon; Jeon, Sangil; Hong, Taegon; Lee, Jongtae; Bae, Soo Hyeon; Park, Wan-su; Park, Gab-jin; Youn, Sunil; Jang, Doo Yeon; Kim, Kyung-Soo; Yim, Dong-Seok

2015-01-01

No wholly successful weight-control drugs have been developed to date, despite the tremendous demand. We present an exposure-response model of sibutramine mesylate that can be applied during clinical development of other weight-control drugs. Additionally, we provide a model-based evaluation of sibutramine efficacy. Data from a double-blind, randomized, placebo-controlled, multicenter study were used (N=120). Subjects in the treatment arm were initially given 8.37 mg sibutramine base daily, and those who lost <2 kg after 4 weeks' treatment were escalated to 12.55 mg. The duration of treatment was 24 weeks. Drug concentration and body weight were measured predose and at 4 weeks, 8 weeks, and 24 weeks after treatment initiation. Exposure and response to sibutramine, including the placebo effect, were modeled using NONMEM 7.2. An asymptotic model approaching the final body weight was chosen to describe the time course of weight loss. Extent of weight loss was described successfully using a sigmoidal exposure-response relationship of the drug with a constant placebo effect in each individual. The placebo effect was influenced by subjects' sex and baseline body mass index. Maximal weight loss was predicted to occur around 1 year after treatment initiation. The difference in mean weight loss between the sibutramine (daily 12.55 mg) and placebo groups was predicted to be 4.5% in a simulation of 1 year of treatment, with considerable overlap of prediction intervals. Our exposure-response model, which included the placebo effect, is the first example of a quantitative model that can be used to predict the efficacy of weight-control drugs. Similar approaches can help decision-making during clinical development of novel weight-loss drugs.

[Usefulness of sputum Gram staining in community-acquired pneumonia].

PubMed

Sato, Tadashi; Aoshima, Masahiro; Ohmagari, Norio; Tada, Hiroshi; Chohnabayashi, Naohiko

2002-07-01

To evaluate the usefulness of sputum gram staining in community-acquired pneumonia (CAP), we reviewed 144 cases requiring hospitalization in the last 4 years. The sensitivity was 75.5%, specificity 68.2%, positive predictive value 74.1%, negative predictive value 69.8%, positive likelihood ratio 2.37, negative likelihood ratio 0.36 and accuracy 72.2% in 97 cases. Both sputum gram staining and culture were performed. Concerning bacterial pneumonia (65 cases), we compared the Gram staining group (n = 33), which received initial antibiotic treatment, based on sputum gram staining with the Empiric group (n = 32) that received antibiotics empirically. The success rates of the initial antibiotic treatment were 87.9% vs. 78.1% (P = 0.473); mean hospitalization periods were 9.67 vs. 11.75 days (P = 0.053); and periods of intravenous therapy were 6.73 vs. 7.91 days (P = 0.044), respectively. As for initial treatment, penicillins were used in the Gram staining group more frequently (P < 0.01). We conclude that sputum gram staining is useful for the shortening of the treatment period and the appropriate selection of initial antibiotics in bacterial pneumonia. We believe, therefore, that sputum gram staining is indispensable as a diagnostic tool CAP.

Healthcare costs among adults with type 2 diabetes initiating saxagliptin or linagliptin: a US-based claims analysis.

PubMed

Kong, Amanda M; Farahbakhshian, Sepehr; Pendergraft, Trudy; Brouillette, Matthew A; Mukherjee, Biswarup; Smith, David M; Sheehan, John J

2017-10-01

To compare healthcare costs of adults with type 2 diabetes (T2D) after initiation of saxagliptin or linagliptin, two antidiabetic medications in the dipeptidyl peptidase-4 inhibitor medication class. Patients with T2D who were at least 18 years old and initiated saxagliptin or linagliptin (index date) between 1 June 2011 and 30 June 2014 were identified in the MarketScan Commercial and Medicare Supplemental Databases. All-cause healthcare costs and diabetes-related costs (T2D diagnosis on a medical claim and/or an antidiabetic medication claim) were measured in the 1 year follow-up period. Saxagliptin and linagliptin initiators were matched using propensity score methods. Cost ratios (CRs) and predicted costs were estimated from generalized linear models and recycled predictions. There were 34,560 saxagliptin initiators and 18,175 linagliptin initiators identified (mean ages 57 and 59; 55% and 56% male, respectively). Before matching, saxagliptin initiators had significantly lower all-cause total healthcare costs than linagliptin initiators (mean = $15,335 [SD $28,923] vs. mean = $20,069 [SD $48,541], p < .001) and significantly lower diabetes-related total healthcare costs (mean = $6109 [SD $13,851] vs. mean = $7393 [SD $26,041], p < .001). In matched analyses (n = 16,069 per cohort), saxagliptin initiators had lower all-cause follow-up costs than linagliptin initiators (CR = 0.953, 95% CI = 0.932-0.974, p < .001; predicted costs = $17,211 vs. $18,068). There was no significant difference in diabetes-related total costs after matching; however, diabetes-related medical costs were significantly lower for saxagliptin initiators (CR = 0.959, 95% CI = 0.927-0.993, p = 0.017; predicted costs = $3989 vs. $4159). Adult patients with T2D initiating treatment with saxagliptin had lower total all-cause healthcare costs and diabetes-related medical costs over 1 year compared with patients initiating treatment with linagliptin.

Do patterns of change during treatment for panic disorder predict future panic symptoms?

PubMed Central

Steinman, Shari A.; Hunter, Michael D.; Teachman, Bethany A.

2012-01-01

Background and Objectives Cognitive-behavioral therapies are currently the gold standard for panic disorder treatment, with well-documented treatment response. However, following interventions, some individuals continue to improve, while others experience a return of symptoms. The field lacks reliable ways to predict follow-up symptomology. In the current study, a cluster analysis with a repeated measures design was conducted to examine change patterns over 12 weeks of cognitive behavioral group therapy for panic disorder. The central aim of the study was to evaluate if change patterns predict level of panic symptom severity at a six month follow-up in this sample. Methods Individuals with panic disorder (N = 36) completed a measure of panic symptoms (Panic Disorder Severity Scale) at the outset of every therapy session and at a six month follow-up. Results Results revealed three patterns of change in this specific trial, which significantly predicted level of panic symptoms six months post-treatment, beyond initial or final level of panic symptoms, and beyond total symptom change. Limitations Given the relatively small, lab-based sample, replications in other settings and samples will be important. Conclusions Overall, results provide initial evidence that change patterns are meaningful predictors of panic symptom severity well after the final session of treatment. PMID:23187115

Predicting outcomes of group cognitive behavior therapy for patients with affective and neurotic disorders.

PubMed

Hooke, Geoffrey R; Page, Andrew C

2002-10-01

An attempt was made to predict outcomes following group Cognitive Behavior Therapy (CBT) for patients with affective and neurotic disorders. A group of 348 patients at a private psychiatric clinic, treated in a group CBT program, completed the Depression, Anxiety, and Stress Scale (DASS) before and after treatment. Prior to treatment, data from the Locus of Control of Behavior (LCB), a Global Assessment of Function (GAF), the Health of the Nation Outcome Scales (HoNOS), and the Rosenberg Self Esteem Scale (RSE) were also collected. Results indicated that posttreatment stress scores of all patients were predicted by pretreatment stress and self-esteem. Among patients with neurotic disorders, posttreatment anxiety was predicted by initial anxiety and self-esteem whereas among patients with affective disorders, posttreatment anxiety scores were predicted by initial anxiety and GAF. For patients with neurotic disorders, self-esteem did not predict variance in posttreatment depression in addition to that explained by pretreatment depression. In contrast, for patients with affective disorders, pretreatment depression and Locus of Control predicted posttreatment depression.

Treatment retention in a prison-based residential sex offender treatment program.

PubMed

Pelissier, Bernadette

2007-12-01

This study assessed the role of static factors, a dynamic factor (motivation to change sexually deviant behavior), and an administrative factor in predicting treatment retention within a prison-based sex offender treatment program. The analyses also included assessing differences in initial levels of motivation and differences in beginning-versus end-of-treatment motivation scores for various types of program discharges. The sample consisted of 251 individuals who were admitted to a residential prison-based sex offender treatment program where 46% completed the program. Paired comparison t-tests showed higher motivation scores at the end of treatment only among treatment completers. Multivariate analyses showed that treatment retention was associated with higher initial motivation scores, higher levels of education and admission to treatment within 3 months of initial commitment to prison. Implications for motivational enhancement programming as well as for changes in admission criteria are discussed.

Predictors of posttreatment drinking outcomes in patients with alcohol dependence.

PubMed

Flórez, Gerardo; Saiz, Pilar A; García-Portilla, Paz; De Cos, Francisco J; Dapía, Sonia; Alvarez, Sandra; Nogueiras, Luis; Bobes, Julio

2015-01-01

This cohort study examined how predictors of alcohol dependence treatment outcomes work together over time by comparing pretreatment and posttreatment predictors. A sample of 274 alcohol-dependent patients was recruited and assessed at baseline, 6 months after treatment initiation (end of the active intervention phase), and 18 months after treatment initiation (end of the 12-month research follow-up phase). At each assessment point, the participants completed a battery of standardized tests [European Addiction Severity Index (EuropASI), Obsessive Compulsive Drinking Scale (OCDS), Alcohol Timeline Followback (TLFB), Fagerström, and International Personality Disorder Examination (IPDE)] that measured symptom severity and consequences; biological markers of alcohol consumption were also tested at each assessment point. A sequential strategy with univariate and multivariate analyses was used to identify how pretreatment and posttreatment predictors influence outcomes up to 1 year after treatment. Pretreatment variables had less predictive power than posttreatment ones. OCDS scores and biological markers of alcohol consumption were the most significant variables for the prediction of posttreatment outcomes. Prior pharmacotherapy treatment and relapse prevention interventions were also associated with posttreatment outcomes. The findings highlight the positive impact of pharmacotherapy during the first 6 months after treatment initiation and of relapse prevention during the first year after treatment and how posttreatment predictors are more important than pretreatment predictors.

Predicting Treatment Response of Colorectal Cancer Liver Metastases to Conventional Lipiodol-Based Transarterial Chemoembolization Using Diffusion-Weighted MR Imaging: Value of Pretreatment Apparent Diffusion Coefficients (ADC) and ADC Changes Under Therapy

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

Lahrsow, Maximilian, E-mail: mlahrsow@gmail.com; Albrecht, Moritz H.; Bickford, Matthew W.

PurposeTo use absolute pretreatment apparent diffusion coefficients (ADC) derived from diffusion-weighted MR imaging (DWI) to predict response to repetitive cTACE for unresectable liver metastases of colorectal carcinoma (CRLM) at 1 and 3 months after start of treatment.Materials and MethodsFifty-five metastases in 34 patients were examined with DWI prior to treatment and 1 month after initial cTACE. Treatment was performed in 4-week intervals. Response was evaluated at 1 and 3 months after start of therapy. Metastases showing a decrease of ≥30% in axial diameter were classified as responding lesions.ResultsOne month after initial cTACE, seven lesions showed early response. There was no significant differencemore » in absolute pretreatment ADC values between responding and non-responding lesions (p = 0.94). Three months after initial cTACE, 17 metastases showed response. There was a significant difference (p = 0.021) between absolute pretreatment ADC values of lesions showing response (median 1.08 × 10{sup −3} mm{sup 2}/s) and no response (median 1.30 × 10{sup −3} mm{sup 2}/s). Pretreatment ADC showed fair diagnostic value to predict response (AUC 0.7). Lesions showing response at 3 months also revealed a significant increase in ADC between measurements before treatment and at one month after initial cTACE (p < 0.001). Applying an increase in ADC of 12.17%, response at 3 months after initial cTACE could be predicted with a sensitivity and specificity of 77 and 74%, respectively (AUC 0.817). Furthermore, there was a strong and significant correlation (r = 0.651, p < 0.001) between percentage change in size after third cTACE and percentage change in ADC.ConclusionIn patients with CRLM, ADC measurements are potential biomarkers for assessing response to cTACE.« less

Verification of Pharmacogenetics-Based Warfarin Dosing Algorithms in Han-Chinese Patients Undertaking Mechanic Heart Valve Replacement

PubMed Central

Zhao, Li; Chen, Chunxia; Li, Bei; Dong, Li; Guo, Yingqiang; Xiao, Xijun; Zhang, Eryong; Qin, Li

2014-01-01

Objective To study the performance of pharmacogenetics-based warfarin dosing algorithms in the initial and the stable warfarin treatment phases in a cohort of Han-Chinese patients undertaking mechanic heart valve replacement. Methods We searched PubMed, Chinese National Knowledge Infrastructure and Wanfang databases for selecting pharmacogenetics-based warfarin dosing models. Patients with mechanic heart valve replacement were consecutively recruited between March 2012 and July 2012. The predicted warfarin dose of each patient was calculated and compared with the observed initial and stable warfarin doses. The percentage of patients whose predicted dose fell within 20% of their actual therapeutic dose (percentage within 20%), and the mean absolute error (MAE) were utilized to evaluate the predictive accuracy of all the selected algorithms. Results A total of 8 algorithms including Du, Huang, Miao, Wei, Zhang, Lou, Gage, and International Warfarin Pharmacogenetics Consortium (IWPC) model, were tested in 181 patients. The MAE of the Gage, IWPC and 6 Han-Chinese pharmacogenetics-based warfarin dosing algorithms was less than 0.6 mg/day in accuracy and the percentage within 20% exceeded 45% in all of the selected models in both the initial and the stable treatment stages. When patients were stratified according to the warfarin dose range, all of the equations demonstrated better performance in the ideal-dose range (1.88–4.38 mg/day) than the low-dose range (<1.88 mg/day). Among the 8 algorithms compared, the algorithms of Wei, Huang, and Miao showed a lower MAE and higher percentage within 20% in both the initial and the stable warfarin dose prediction and in the low-dose and the ideal-dose ranges. Conclusions All of the selected pharmacogenetics-based warfarin dosing regimens performed similarly in our cohort. However, the algorithms of Wei, Huang, and Miao showed a better potential for warfarin prediction in the initial and the stable treatment phases in Han-Chinese patients undertaking mechanic heart valve replacement. PMID:24728385

Verification of pharmacogenetics-based warfarin dosing algorithms in Han-Chinese patients undertaking mechanic heart valve replacement.

PubMed

Zhao, Li; Chen, Chunxia; Li, Bei; Dong, Li; Guo, Yingqiang; Xiao, Xijun; Zhang, Eryong; Qin, Li

2014-01-01

To study the performance of pharmacogenetics-based warfarin dosing algorithms in the initial and the stable warfarin treatment phases in a cohort of Han-Chinese patients undertaking mechanic heart valve replacement. We searched PubMed, Chinese National Knowledge Infrastructure and Wanfang databases for selecting pharmacogenetics-based warfarin dosing models. Patients with mechanic heart valve replacement were consecutively recruited between March 2012 and July 2012. The predicted warfarin dose of each patient was calculated and compared with the observed initial and stable warfarin doses. The percentage of patients whose predicted dose fell within 20% of their actual therapeutic dose (percentage within 20%), and the mean absolute error (MAE) were utilized to evaluate the predictive accuracy of all the selected algorithms. A total of 8 algorithms including Du, Huang, Miao, Wei, Zhang, Lou, Gage, and International Warfarin Pharmacogenetics Consortium (IWPC) model, were tested in 181 patients. The MAE of the Gage, IWPC and 6 Han-Chinese pharmacogenetics-based warfarin dosing algorithms was less than 0.6 mg/day in accuracy and the percentage within 20% exceeded 45% in all of the selected models in both the initial and the stable treatment stages. When patients were stratified according to the warfarin dose range, all of the equations demonstrated better performance in the ideal-dose range (1.88-4.38 mg/day) than the low-dose range (<1.88 mg/day). Among the 8 algorithms compared, the algorithms of Wei, Huang, and Miao showed a lower MAE and higher percentage within 20% in both the initial and the stable warfarin dose prediction and in the low-dose and the ideal-dose ranges. All of the selected pharmacogenetics-based warfarin dosing regimens performed similarly in our cohort. However, the algorithms of Wei, Huang, and Miao showed a better potential for warfarin prediction in the initial and the stable treatment phases in Han-Chinese patients undertaking mechanic heart valve replacement.

Comparison of the Performance of the Warfarin Pharmacogenetics Algorithms in Patients with Surgery of Heart Valve Replacement and Heart Valvuloplasty.

PubMed

Xu, Hang; Su, Shi; Tang, Wuji; Wei, Meng; Wang, Tao; Wang, Dongjin; Ge, Weihong

2015-09-01

A large number of warfarin pharmacogenetics algorithms have been published. Our research was aimed to evaluate the performance of the selected pharmacogenetic algorithms in patients with surgery of heart valve replacement and heart valvuloplasty during the phase of initial and stable anticoagulation treatment. 10 pharmacogenetic algorithms were selected by searching PubMed. We compared the performance of the selected algorithms in a cohort of 193 patients during the phase of initial and stable anticoagulation therapy. Predicted dose was compared to therapeutic dose by using a predicted dose percentage that falls within 20% threshold of the actual dose (percentage within 20%) and mean absolute error (MAE). The average warfarin dose for patients was 3.05±1.23mg/day for initial treatment and 3.45±1.18mg/day for stable treatment. The percentages of the predicted dose within 20% of the therapeutic dose were 44.0±8.8% and 44.6±9.7% for the initial and stable phases, respectively. The MAEs of the selected algorithms were 0.85±0.18mg/day and 0.93±0.19mg/day, respectively. All algorithms had better performance in the ideal group than in the low dose and high dose groups. The only exception is the Wadelius et al. algorithm, which had better performance in the high dose group. The algorithms had similar performance except for the Wadelius et al. and Miao et al. algorithms, which had poor accuracy in our study cohort. The Gage et al. algorithm had better performance in both phases of initial and stable treatment. Algorithms had relatively higher accuracy in the >50years group of patients on the stable phase. Copyright © 2015 Elsevier Ltd. All rights reserved.

Biomarkers from distinct biological pathways improve early risk stratification in medical emergency patients: the multinational, prospective, observational TRIAGE study.

PubMed

Schuetz, Philipp; Hausfater, Pierre; Amin, Devendra; Amin, Adina; Haubitz, Sebastian; Faessler, Lukas; Kutz, Alexander; Conca, Antoinette; Reutlinger, Barbara; Canavaggio, Pauline; Sauvin, Gabrielle; Bernard, Maguy; Huber, Andreas; Mueller, Beat

2015-10-29

Early risk stratification in the emergency department (ED) is vital to reduce time to effective treatment in high-risk patients and to improve patient flow. Yet, there is a lack of investigations evaluating the incremental usefulness of multiple biomarkers measured upon admission from distinct biological pathways for predicting fatal outcome and high initial treatment urgency in unselected ED patients in a multicenter and multinational setting. We included consecutive, adult, medical patients seeking ED care into this observational, cohort study in Switzerland, France and the USA. We recorded initial clinical parameters and batch-measured prognostic biomarkers of inflammation (pro-adrenomedullin [ProADM]), stress (copeptin) and infection (procalcitonin). During a 30-day follow-up, 331 of 7132 (4.6 %) participants reached the primary endpoint of death within 30 days. In logistic regression models adjusted for conventional risk factors available at ED admission, all three biomarkers strongly predicted the risk of death (AUC 0.83, 0.78 and 0.75), ICU admission (AUC 0.67, 0.69 and 0.62) and high initial triage priority (0.67, 0.66 and 0.58). For the prediction of death, ProADM significantly improved regression models including (a) clinical information available at ED admission (AUC increase from 0.79 to 0.84), (b) full clinical information at ED discharge (AUC increase from 0.85 to 0.88), and (c) triage information (AUC increase from 0.67 to 0.83) (p <0.01 for each comparison). Similarly, ProADM also improved clinical models for prediction of ICU admission and high initial treatment urgency. Results were robust in regard to predefined patient subgroups by center, main diagnosis, presenting symptoms, age and gender. Combination of clinical information with results of blood biomarkers measured upon ED admission allows early and more adequate risk stratification in individual unselected medical ED patients. A randomized trial is needed to answer the question whether biomarker-guided initial patient triage reduces time to initial treatment of high-risk patients in the ED and thereby improves patient flow and clinical outcomes. ClinicalTrials.gov NCT01768494 . Registered January 9, 2013.

Watchful waiting and factors predictive of secondary treatment of localized prostate cancer.

PubMed

Wu, Hongyan; Sun, Leon; Moul, Judd W; Wu, Hong Yu; McLeod, David G; Amling, Christopher; Lance, Raymond; Kusuda, Leo; Donahue, Timothy; Foley, John; Chung, Andrew; Sexton, Wade; Soderdahl, Douglas

2004-03-01

Watchful waiting remains an important treatment option for some patients with localized prostate cancer. We defined the demographic, clinical and outcome features of men selecting watchful waiting as an initial treatment strategy, and determined factors predictive of eventual progression to secondary treatment. Of 8390 patients diagnosed with prostate cancer from 1990 to 2001 in the Department of Defense Center for Prostate Disease Research Database, 1158 patients chose watchful waiting as initial treatment. The demographic and clinical differences between patients on watchful waiting and those choosing other initial treatments were compared using the chi-square test. Secondary treatment-free survival according to various prognostic factors was plotted using the Kaplan-Meier method and differences were tested using the log rank test. A multivariate Cox proportional hazards regression analysis was performed to determine which factors were independent predictors of secondary treatment. Compared to other patients, those selecting watchful waiting were older, had lower prostate specific antigen (PSA) at diagnosis, and were more likely to have lower stage (cT1) and lower grade (Gleason sum 7 or less) cancers. Age, PSA and clinical stage were all significant and independent predictors of secondary treatment. The relative risk of secondary treatment can be expressed as EXP (-0.034 x age at diagnosis + 0.284 x LOG (diagnostic PSA) + 0.271 x clinical stage T2 + 0.264 x clinical stage T3). Men who elect watchful waiting as initial management for prostate cancer are older with lower Gleason sums and serum PSA. In these men, age at diagnosis, serum PSA and clinical stage are the most significant predictors of requiring or selecting secondary treatment.

Clinical Prediction Making: Examining Influential Factors Related to Clinician Predictions of Recidivism among Juvenile Offenders

ERIC Educational Resources Information Center

Calley, Nancy G.; Richardson, Emily M.

2011-01-01

This study examined factors influencing clinician predictions of recidivism for juvenile offenders, including youth age at initial juvenile justice system involvement, youth age at discharge, program completion status, clinician perception of strength of the therapeutic relationship, and clinician perception of youth commitment to treatment.…

Traumatic Stress, Perceived Global Stress, and Life Events: Prospectively Predicting Quality of Life in Breast Cancer Patients

PubMed Central

Golden-Kreutz, Deanna M.; Thornton, Lisa M.; Gregorio, Sharla Wells-Di; Frierson, Georita M.; Jim, Heather S.; Carpenter, Kristen M.; Shelby, Rebecca A.; Andersen, Barbara L.

2007-01-01

The authors investigated the relationship between stress at initial cancer diagnosis and treatment and subsequent quality of life (QoL). Women (n = 112) randomized to the assessment-only arm of a clinical trial were initially assessed after breast cancer diagnosis and surgery and then reassessed at 4 months (during adjuvant treatment) and 12 months (postadjuvant treatment). There were 3 types of stress measured: number of stressful life events (K. A. Matthews et al., 1997), cancer-related traumatic stress symptoms (M. J. Horowitz, N. Wilner, & W. Alvarez, 1979), and perceived global stress (S. Cohen, T. Kamarck, & R. Mermelstein, 1983). Using hierarchical multiple regressions, the authors found that stress predicted both psychological and physical QoL (J. E. Ware, K. K. Snow, & M. Kosinski, 2000) at the follow-ups (all ps < .03). These findings substantiate the relationship between initial stress and later QoL and underscore the need for timely psychological intervention. PMID:15898865

Predictors of treatment response in Canadian combat and peacekeeping veterans with military-related posttraumatic stress disorder.

PubMed

Richardson, J Don; Elhai, Jon D; Sarreen, Jitender

2011-09-01

Military-related posttraumatic stress disorder (PTSD) is a significant psychiatric condition associated with severe psychosocial dysfunction. This study examined the predictors of treatment outcome in a group of veterans with military-related PTSD. Participants were 102 Canadian combat and peacekeeping veterans who received treatment at a specialized outpatient clinic for veterans with psychiatric disorders resulting from military operation. Analysis demonstrated a significant decrease in PTSD severity during the 1-year period (Yuan-Bentler χ [86, N = 99] = 282.45, p < 0.001). We did not find chronicity, alcohol use, and anxiety or depression severity as significant predictors for PTSD symptom decline. However, initial depression significantly predicted anxiety symptom decline, and initial anxiety predicted depression symptom decline. This study demonstrated that, despite considerable comorbidity, significant treatment gains, including remission of PTSD, can be achieved in an outpatient setting in veterans with chronic military-related PTSD.

The Role of Motivation in Family-Based Guided Self-Help Treatment for Pediatric Obesity

PubMed Central

Norman, Gregory J.; Crow, Scott J.; Rock, Cheryl L.; Boutelle, Kerri N.

2014-01-01

Abstract Background: Identifying factors associated with effective treatment for childhood obesity is important to improving weight loss outcomes. The current study investigated whether child or parent motivation throughout the course of treatment predicted reductions in BMI. Methods: Fifty 8- to 12-year-old children with overweight and obesity (BMI percentiles 85–98%) and their parents participated in a guided self-help weight loss program, which included 12 brief sessions across 5 months. Parents and interventionists reported on child and parent motivation level at each session. Multilevel slopes-as-outcome models were used to examine growth trajectories for both child and parent BMI across sessions. Results: Greater interventionist-rated child motivation predicted greater reductions in child BMI; parent motivation did not. However, interventionist-rated parent motivation predicted greater reductions in parent BMI, and its impact on BMI became more pronounced over the course of treatment, such that sustained motivation was more important than initial motivation. Children who were older, Latino, or who had lower initial BMIs had slower reductions in BMI. Conclusions: This study suggests that motivation may be an important predictor of reduced BMI in child obesity treatment, with sustained motivation being more important than initial motivation. In particular, interventionist-rated, but not parent-rated, motivation is a robust predictor of child and parent BMI outcomes. Future research may evaluate whether motivational interventions can enhance outcome, with particular attention to improving outcomes for Latino children. PMID:25181608

Anti-E1E2 antibodies status prior therapy favors direct-acting antiviral treatment efficacy.

PubMed

Virlogeux, Victor; Berthillon, Pascale; Bordes, Isabelle; Larrat, Sylvie; Crouy, Stéphanie; Scholtès, Caroline; Pradat, Pierre; Maynard, Marianne; Zoulim, Fabien; Leroy, Vincent; Chemin, Isabelle; Trépo, Christian; Petit, Marie-Anne

2018-03-15

Presence of anti-E1E2 antibodies was previously associated with spontaneous cure of hepatitis C virus (HCV) and predictive before treatment of a sustained virological response (SVR) to bi- or tri-therapy in naïve or experienced patients, regardless of HCV genotype. We investigated the impact of anti-E1E2 seroprevalence at baseline on treatment response in patients receiving direct-acting antiviral (DAA) therapy. We screened anti-E1E2 antibodies by ELISA in serum samples collected at treatment initiation for two groups of patients: 59 with SVR at the end of DAA treatment and 44 relapsers after DAA treatment. Nineteen patients received a combination of ribavirin (RBV) or PEG-interferon/ribavirin with sofosbuvir or daclatasvir and others received interferon-free treatment with DAA±RBV. HCV viral load was measured at different time points during treatment in a subgroup of patients. A significant association was observed between presence of anti-E1E2 and HCV viral load<6log10 prior treatment. Among patients with anti-E1E2 at baseline, 70% achieved SVR whereas among patients without anti-E1E2, only 45% achieved SVR. Conversely, 66% of patients experiencing DAA-failure were anti-E1E2 negative at baseline. In the multivariate analysis, presence of anti-E1E2 was significantly associated with SVR after adjustment on potential cofounders such as age, sex, fibrosis stage, prior HCV treatment and alanine aminotransferase (ALT) level. The presence of anti-E1E2 at treatment initiation is a predictive factor of SVR among patients treated with DAA and more likely among patients with low initial HCV viral load (<6log10). Absence of anti-E1E2 at baseline could predict DAA-treatment failure. Copyright © 2018 Elsevier Masson SAS. All rights reserved.

Development of equations to predict the influence of floor space on average daily gain, average daily feed intake and gain : feed ratio of finishing pigs.

PubMed

Flohr, J R; Dritz, S S; Tokach, M D; Woodworth, J C; DeRouchey, J M; Goodband, R D

2018-05-01

Floor space allowance for pigs has substantial effects on pig growth and welfare. Data from 30 papers examining the influence of floor space allowance on the growth of finishing pigs was used in a meta-analysis to develop alternative prediction equations for average daily gain (ADG), average daily feed intake (ADFI) and gain : feed ratio (G : F). Treatment means were compiled in a database that contained 30 papers for ADG and 28 papers for ADFI and G : F. The predictor variables evaluated were floor space (m2/pig), k (floor space/final BW0.67), Initial BW, Final BW, feed space (pigs per feeder hole), water space (pigs per waterer), group size (pigs per pen), gender, floor type and study length (d). Multivariable general linear mixed model regression equations were used. Floor space treatments within each experiment were the observational and experimental unit. The optimum equations to predict ADG, ADFI and G : F were: ADG, g=337.57+(16 468×k)-(237 350×k 2)-(3.1209×initial BW (kg))+(2.569×final BW (kg))+(71.6918×k×initial BW (kg)); ADFI, g=833.41+(24 785×k)-(388 998×k 2)-(3.0027×initial BW (kg))+(11.246×final BW (kg))+(187.61×k×initial BW (kg)); G : F=predicted ADG/predicted ADFI. Overall, the meta-analysis indicates that BW is an important predictor of ADG and ADFI even after computing the constant coefficient k, which utilizes final BW in its calculation. This suggests including initial and final BW improves the prediction over using k as a predictor alone. In addition, the analysis also indicated that G : F of finishing pigs is influenced by floor space allowance, whereas individual studies have concluded variable results.

Anger and guilt in treatment for chronic posttraumatic stress disorder.

PubMed

Clifton, Erin G; Feeny, Norah C; Zoellner, Lori A

2017-03-01

Feelings of anger and guilt are important to consider when treating PTSD as they are related to higher PTSD severity and may be related to avoidance during treatment. Avoidance may impede emotional engagement, the process of connecting with distressing, fear-related emotions during imaginal exposure, which is considered an important mechanism for successful PTSD treatment in prolonged exposure (PE). Yet, little research has examined possible complications in achieving emotional engagement, such as anger and guilt. The present study utilized data from 116 individuals with PTSD who received PE to investigate whether anger and guilt were associated with poorer emotional engagement, as captured by pre, peak, post, and mean subjective units of distress (SUDs), during the initial imaginal exposure, and whether anger and guilt predicted worse treatment outcome generally and as a result of lessened emotional engagement. Neither initial anger nor guilt hindered engagement nor predicted worse outcome. Contrary to hypotheses, higher guilt was predictive of greater anticipatory distress and slightly better PTSD outcome. The relationship between pre-treatment guilt cognitions and post-treatment PTSD severity was not mediated by engagement. This study used a trauma-specific measure of guilt and general measure for anger, however both are commonly used. In addition, this study examined emotional engagement during imaginal exposure to the exclusion of engagement with other therapy components, such as in vivo exposure. These findings help dispel concerns that those with higher anger and guilt will avoid emotionally engaging during the initial imaginal exposure due to feeling distressed by intense negative emotionality. Copyright © 2016 Elsevier Ltd. All rights reserved.

Motivation Change in Therapeutic Community Residential Treatment

ERIC Educational Resources Information Center

Morgen, Keith; Kressel, David

2010-01-01

Latent growth curve analysis was used to assess motivation change across 3 time points for 120 therapeutic community residents. Models included the time-invariant predictor of readiness for treatment, which significantly predicted initial treatment motivation but not the rate of motivation change over time. (Contains 1 figure and 2 tables.)

Experiments and modeling to characterize microstructure and hardness in 304L

DOE PAGES

Deibler, Lisa Anne; Brown, Arthur; Puskar, Joseph D.

2017-01-12

Drawn 304L stainless steel tubing was subjected to 42 different annealing heat treatments with the goal of initializing a microstructural model to select a heat treatment to soften the tubing from a hardness of 305 Knoop to 225–275 Knoop. The amount of recrystallization and grain size caused by 18 heat treatments were analyzed via optical microscopy and image analysis, revealing the full range of recrystallization from 0 to 100%. The formation of carbides during the longer duration and higher-temperature heat treatments was monitored via transmission electron microscope evaluation. The experimental results informed a model which includes recovery, recrystallization, and grainmore » growth to predict microstructure and hardness. After initialization of the model, it was able to predict hardness with a R 2 value of 0.95 and recrystallization with an R 2 value of 0.99. As a result, the model was then utilized in the design and testing of a heat treatment to soften the tubing.« less

Predictive factors for the methotrexate treatment outcome in ectopic pregnancy: A comparative study of 400 cases.

PubMed

Bonin, Lucie; Pedreiro, Cécile; Moret, Stéphanie; Chene, Gautier; Gaucherand, Pascal; Lamblin, Géry

2017-01-01

We sought to evaluate the global success rate of intramuscular methotrexate for the treatment of ectopic pregnancy, identify factors predictive of treatment success or failure, and study methotrexate tolerability in a large patient cohort. For this single-center retrospective observational study, we retrieved the records of all women who had a clinically or echographically confirmed ectopic pregnancy with a Fernandez score <13 and who were treated according to a 1mg/kg intramuscular single-dose methotrexate protocol. Medical treatment failure was defined by an obligation to proceed to laparoscopy. Needing a second injection was not considered to be medical treatment failure. Between February 2008 and November 2013 (69 months), 400 women received methotrexate for ectopic pregnancy. The medical treatment protocol was effective for 314 patients, i.e., an overall success rate of 78.5%. A single methotrexate dose was sufficient for 63.5% of the women and a second dose was successful for 73.2% of the remaining women. The medical treatment success rate fell as initial hCG levels climbed. The main factors associated with methotrexate failure included day (D) 0, D4 and D7 hCG levels, pretherapeutic blood progesterone, hematosalpinx at D0 and pain at D7. Early favorable kinetics of hCG levels was predictive of success. Methotrexate treatment was successful in 90% of women who had D0 hCG <1000IU/l. Methotrexate tolerability was good, with only 9% of the women reporting non-severe adverse effects. The fertility rate with delivery after medical treatment for ectopic pregnancy was 80.7%. In this study, we showed that an initial hCG value <1000IU/l and favorable early HCG kinetics were predictive factors for the successful medical treatment of ectopic pregnancy by methotrexate, and hematosalpinx and pretherapeutic blood progesterone >5ng/ml at diagnosis were predictive of its failure. We also confirmed good tolerability for single-dose methotrexate protocols. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

Factors influencing soft tissue profile changes following orthodontic treatment in patients with Class II Division 1 malocclusion.

PubMed

Maetevorakul, Suhatcha; Viteporn, Smorntree

2016-01-01

Several studies have shown soft tissue profile changes after orthodontic treatment in Class II Division 1 patients. However, a few studies have described factors influencing the soft tissue changes. The purpose of this study was to investigate the factors influencing the soft tissue profile changes following orthodontic treatment in Class II Division 1 patients. The subjects comprised 104 Thai patients age 8-16 years who presented Class II Division 1 malocclusions and were treated with different orthodontic modalities comprising cervical headgear, Class II traction and extraction of the four first premolars. The profile changes were evaluated from the lateral cephalograms before and after treatment by means of the X-Y coordinate system. Significant soft tissue profile changes were evaluated by paired t test at a 0.05 significance level. The correlations among significant soft tissue changes and independent variables comprising treatment modality, age, sex, pretreatment skeletal, dental and soft tissue morphology were evaluated by stepwise multiple regression analysis at a 0.05 significance level. The multiple regression analysis indicated that different treatment modalities, age, sex, pretreatment skeletal, dental and soft tissue morphology were related to the profile changes. The predictive power of these variables on the soft tissue profile changes ranged from 9.9 to 40.3%. Prediction of the soft tissue profile changes following treatment of Class II Division 1 malocclusion from initial patient morphology, age, sex and types of treatment was complicated and required several variables to explain their variations. Upper lip change in horizontal direction could be found only at the stomion superius and was less predictable than those of the lower lip. Variations in upper lip retraction at the stomion superius were explained by types of treatment (R(2) = 0.099), whereas protrusion of the lower lip at the labrale inferius was correlated with initial inclination of the lower incisor (L1 to NB), jaw relation (ANB angle), lower lip thickness and sex (R(2) = 0.403). Prediction of chin protrusion at the soft tissue pogonion was also low predictable (R(2) = 0.190) depending upon sex, age and initial mandibular plane angle (SN-GoGn). Additionally, age and sex also had mainly effect on change of the soft tissue profile in the vertical direction.

Fuel treatment longevity in a Sierra Nevada mixed conifer forest

Treesearch

Scott. L. Stephens; Brandon M. Collins; Gary. Roller

2012-01-01

Understanding the longevity of fuel treatments in terms of their ability to maintain fire behavior and effects within a desired range is an important question. The objective of this study was to determine how fuels, forest structure, and predicted fire behavior changed 7-years after initial treatments. Three different treatments: mechanical only, mechanical plus fire,...

Predictive model of third molar eruption after second molar extraction.

PubMed

De-la-Rosa-Gay, Cristina; Valmaseda-Castellón, Eduard; Gay-Escoda, Cosme

2010-03-01

Extraction of second permanent molars is an option for providing space in orthodontic treatment. Although many articles have described its impact on the outcome, there are few data on the prognosis of the eruption of the adjacent third molars. The aims of this investigation were to provide predictive models of eruption of third molars after second permanent molar extraction and to validate them. A total of 48 patients (ages, 11-23 years) who had 128 second permanent molars (54 maxillary, 74 mandibular) extracted during orthodontic treatment were followed until eruption of the third molars was complete. A lineal regression model predicted the final angle of the third molars with the permanent first molar by using the variables of initial angle, jaw, and the developmental stage of the third molar. A logistic regression model predicted the probability of correct eruption by using the variables of initial angle, jaw, sex, age, and the developmental stage of the third molar. 2010 American Association of Orthodontists. Published by Mosby, Inc. All rights reserved.

Newly Diagnosed Meniere's Disease: Clinical Course With Initiation of Noninvasive Treatment Including an Accounting of Vestibular Migraine.

PubMed

Sbeih, Firas; Christov, Florian; Gluth, Michael B

2018-05-01

To describe the course of Meniere's disease with noninvasive treatment during the first few years after initial diagnosis. A retrospective review of consecutive patients with newly diagnosed definite Meniere's disease between 2013 and 2016 and a minimum follow-up of 1 year. Patients received a written plan for low sodium, water therapy, and treatment with a diuretic and/or betahistine. Subjects were screened and treated for vestibular migraine as needed. Vertigo control and hearing status at most recent follow-up were assessed. Forty-four subjects had an average follow up of 24.3 months. Thirty-four percent had Meniere's disease and vestibular migraine, and 84% had unilateral Meniere's disease. Seventy-five percent had vertigo well controlled at most recent follow-up, with only noninvasive treatments. Age, gender, body mass index, presence of vestibular migraine, bilateral disease, and duration of follow-up did not predict noninvasive treatment failure. Worse hearing threshold at 250 Hz and lower pure tone average (PTA) at the time of diagnosis did predict failure. Fifty-two percent of ears had improved PTA at most recent visit, 20% had no change, and 28% were worse Conclusions: Encountering excellent vertigo control and stable hearing after a new diagnosis of Meniere's disease is possible with noninvasive treatments. Worse hearing status at diagnosis predicted treatment failure.

Usefulness of induced sputum eosinophil count to assess severity and treatment outcome in asthma patients

PubMed Central

Bandyopadhyay, Ankan; Roy, Partha P.; Saha, Kaushik; Chakraborty, Semanti; Jash, Debraj; Saha, Debabrata

2013-01-01

Context: Currently treatment decisions in asthma are governed by clinical assessment and spirometry. Sputum eosinophil, being a marker of airway inflammation, can serve as a tool for assessing severity and response to treatment in asthma patients. Aims: To establish correlation between change in sputum eosinophil count and forced expiratory volume in one second (FEV1)% predicted value of asthma patients in response to treatment. In this study, we also predicted prognosis and treatment outcome of asthma patients from baseline sputum eosinophil count. Settings and Design: A longitudinal study was conducted to determine the treatment outcome among newly diagnosed asthma patients who were classified into A (n = 80) and B (n = 80) groups on the basis of initial sputum eosinophil count (A ≥ 3% and B < 3%). Materials and Methods: After starting treatment according to Global Initiative for Asthma Guideline, both A and B groups were evaluated every 15 days interval for the 1st month and monthly thereafter for a total duration of 12 months. In each follow-up visit detailed history, induced sputum eosinophil count and spirometry were done to evaluate severity and treatment outcome. Results: FEV1% predicted of group A asthma patients gradually increased and sputum eosinophil count gradually decreased on treatment. Longer time was required to achieve satisfactory improvement (FEV1% predicted) in asthma patients with sputum eosinophil count ≥3%. There was statistically significant negative correlation between FEV1% predicted and sputum eosinophil count (%) in of group A patients in each follow-up visit, with most significant negative correlation found in 8th visit (r = −0.9237 and P = < 0.001). Change in mean FEV1% (predicted) from baseline showed strong positive correlation (r = 0.976) with change in reduction of mean sputum eosinophil count at each follow-up visits in group A patients. Conclusions: Sputum eosinophil count, being an excellent biomarker of airway inflammation, can serve as a useful marker to assess disease severity, treatment outcome, and prognosis in asthma patients. PMID:23741092

Duration of untreated psychosis: Impact of the definition of treatment onset on its predictive value over three years of treatment.

PubMed

Golay, Philippe; Alameda, Luis; Baumann, Philipp; Elowe, Julien; Progin, Pierre; Polari, Andrea; Conus, Philippe

2016-06-01

While reduction of DUP (Duration of Untreated Psychosis) is a key goal in early intervention strategies, the predictive value of DUP on outcome has been questioned. We planned this study in order to explore the impact of three different definition of "treatment initiation" on the predictive value of DUP on outcome in an early psychosis sample. 221 early psychosis patients aged 18-35 were followed-up prospectively over 36 months. DUP was measured using three definitions for treatment onset: Initiation of antipsychotic medication (DUP1); engagement in a specialized programme (DUP2) and combination of engagement in a specialized programme and adherence to medication (DUP3). 10% of patients never reached criteria for DUP3 and therefore were never adequately treated over the 36-month period of care. While DUP1 and DUP2 had a limited predictive value on outcome, DUP3, based on a more restrictive definition for treatment onset, was a better predictor of positive and negative symptoms, as well as functional outcome at 12, 24 and 36 months. Globally, DUP3 explained 2 to 5 times more of the variance than DUP1 and DUP2, with effect sizes falling in the medium range according to Cohen. The limited predictive value of DUP on outcome in previous studies may be linked to problems of definitions that do not take adherence to treatment into account. While they need replication, our results suggest effort to reduce DUP should continue and aim both at early detection and development of engagement strategies. Copyright © 2016 Elsevier Ltd. All rights reserved.

Prediction of hearing outcomes by multiple regression analysis in patients with idiopathic sudden sensorineural hearing loss.

PubMed

Suzuki, Hideaki; Tabata, Takahisa; Koizumi, Hiroki; Hohchi, Nobusuke; Takeuchi, Shoko; Kitamura, Takuro; Fujino, Yoshihisa; Ohbuchi, Toyoaki

2014-12-01

This study aimed to create a multiple regression model for predicting hearing outcomes of idiopathic sudden sensorineural hearing loss (ISSNHL). The participants were 205 consecutive patients (205 ears) with ISSNHL (hearing level ≥ 40 dB, interval between onset and treatment ≤ 30 days). They received systemic steroid administration combined with intratympanic steroid injection. Data were examined by simple and multiple regression analyses. Three hearing indices (percentage hearing improvement, hearing gain, and posttreatment hearing level [HLpost]) and 7 prognostic factors (age, days from onset to treatment, initial hearing level, initial hearing level at low frequencies, initial hearing level at high frequencies, presence of vertigo, and contralateral hearing level) were included in the multiple regression analysis as dependent and explanatory variables, respectively. In the simple regression analysis, the percentage hearing improvement, hearing gain, and HLpost showed significant correlation with 2, 5, and 6 of the 7 prognostic factors, respectively. The multiple correlation coefficients were 0.396, 0.503, and 0.714 for the percentage hearing improvement, hearing gain, and HLpost, respectively. Predicted values of HLpost calculated by the multiple regression equation were reliable with 70% probability with a 40-dB-width prediction interval. Prediction of HLpost by the multiple regression model may be useful to estimate the hearing prognosis of ISSNHL. © The Author(s) 2014.

Quality of life before hyperhidrosis treatment as a predictive factor for oxybutynin treatment outcomes in palmar and axillary hyperhidrosis.

PubMed

Wolosker, Nelson; Krutman, Mariana; Teivelis, Marcelo P; Campbell, Taiz P D A; Kauffman, Paulo; de Campos, José Ribas M; Puech-Leão, Pedro

2014-05-01

Studies have suggested that quality of life (QOL) evaluation before video-assisted thoracoscopic sympathectomy for patients with hyperhidrosis may serve as a predictive factor for positive postoperative outcomes. Our study aims to analyze if this tendency is also observed in patients treated with oxybutynin for palmar and axillary hyperhidrosis. Five hundred sixty-five patients who submitted to a protocol treatment with oxybutynin were retrospectively analyzed between January 2007 and January 2012 and were divided into 2 groups according to QOL assessment before treatment. The groups consisted of 176 patients with "poor" and 389 patients with "very poor" QOL evaluation before oxybutynin treatment. Outcomes involving improvements in QOL and clinical progression of hyperhidrosis were evaluated using a validated clinical questionnaire that was specifically designed to assess satisfaction in patients with excessive sweating. Improvements in hyperhidrosis after oxybutynin were observed in 65.5% of patients with very poor pretreatment QOL scores and in 75% of patients with poor pretreatment QOL scores, and the only adverse event associated with oxybutynin treatment was dry mouth, which was observed with greater intensity in patients with very poor initial QOL evaluation. Improvements in hyperhidrosis after oxybutynin treatment were similar in both groups, suggesting that QOL before treatment is not a predictive factor for clinical outcomes, contrasting with surgical results that disclose significantly better results in patients with initially poorer QOL analysis. Copyright © 2014 Elsevier Inc. All rights reserved.

Treatment dynamics of newly marketed drugs and implications for comparative effectiveness research.

PubMed

Gagne, Joshua J; Bykov, Katsiaryna; Willke, Richard J; Kahler, Kristijan H; Subedi, Prasun; Schneeweiss, Sebastian

2013-01-01

Clinicians and payers require rapid comparative effectiveness (CE) evidence generation to inform decisions for new drugs. We empirically assessed treatment dynamics of newly marked drugs and their implications for conducting CE research. We used claims data to evaluate five drug-outcome pairs: 1) raloxifene (vs. alendronate) and fracture; 2) risedronate (vs. alendronate) and fracture; 3) simvastatin plus ezetimibe fixed-dose combination (simvastatin + ezetimibe) (vs. simvastatin alone) and cardiovascular events; 4) rofecoxib (vs. nonselective nonsteroidal anti-inflammatory drugs [ns-NSAIDs]) and myocardial infarction; and 5) rofecoxib (vs. ns-NSAIDS) and gastrointestinal bleed. We examined utilization dynamics in the early marketing period, including evolving utilization patterns, outcome risk among those treated with new versus established drugs, and prior treatment patterns that may indicate treatment resistance or intolerance. We addressed these challenges by replicating active CE monitoring with sequential matched cohort analysis. Patients initiating new drugs were more likely to have used other drugs for the same indication in the past, but the majority of patients in all new drug cohorts were treatment naive (82.0% overall). Patients initiating rofecoxib had higher predicted baseline risk of gastrointestinal bleed than did patients initiating ns-NSAIDs. Patients initiating risedronate and alendronate had similar predicted baseline risks of fracture, while those initiating raloxifene and simvastatin + ezetimibe had lower risks of outcomes of interest relative to their comparators. Prospective monitoring yielded results consistent with expectation for each example. Many challenges to assessing the CE of new drugs are borne out in empirical data. Attention to these challenges can yield valid CE results. Copyright © 2013, International Society for Pharmacoeconomics and Outcomes Research (ISPOR). Published by Elsevier Inc.

Preclinical Assessment of a Strategy to Minimize the Abuse Liability of Opiate Medications for Pain

DTIC Science & Technology

2016-09-01

This type of CPP design assumes that if an animal subject initially prefers one environment, then it will have a preference for that environment...regardless of the drug treatment. In other words, the initial pre- test is presumed to be predictive of the eventual post - treatment test , where animals...are given a choice of environments and if they spend more time in the drug-paired environment on the test day, they are thought to be drug seeking

Prediction of remission of depression with clinical variables, neuropsychological performance, and serotonergic/dopaminergic gene polymorphisms.

PubMed

Gudayol-Ferré, Esteve; Herrera-Guzmán, Ixchel; Camarena, Beatriz; Cortés-Penagos, Carlos; Herrera-Abarca, Jorge E; Martínez-Medina, Patricia; Asbun-Bojalil, Juan; Lira-Islas, Yuridia; Reyes-Ponce, Celia; Guàrdia-Olmos, Joan

2012-11-01

The aim of our work is to study the possible role of clinical variables, neuropsychological performance, and the 5HTTLPR, rs25531, and val108/58Met COMT polymorphisms on the prediction of depression remission after 12 weeks' treatment with fluoxetine. These variables have been studied as potential predictors of depression remission, but they present poor prognostic sensitivity and specificity by themselves. Seventy-two depressed patients were genotyped according to the aforementioned polymorphisms and were clinically and neuropsychologically assessed before a 12-week fluxetine treatment. Only the La allele of rs25531 polymorphism and the GG and AA forms of the val 108/158 Met polymorphism predict major depressive disorder remission after 12 weeks' treatment with fluoxetine. None of the clinical and neuropsychological variables studied predicted remission. Our results suggest that clinical and neuropsychological variables can initially predict early response to fluoxetine and mask the predictive role of genetic variables; but in remission, where clinical and neuropsychological symptoms associated with depression tend to disappear thanks to the treatment administered, the polymorphisms studied are the only variables in our model capable of predicting remission. However, placebo effects that are difficult to control require cautious interpretation of the results.

[Effect of Continuous Positive Airway Pressure Treatment on Depression, Anxiety and Perceived Stress Levels in Patients with Obstructive Sleep Apnea Syndrome].

PubMed

Çelik, Mustafa; Sarıkaya, Yasin; Acar, Mustafa; Kalenderoğlu, Aysun; Doğan, Sedat; Kaskalan, Emin; Karataş, Mehmet

2016-01-01

The aim of this study is to determine the effects of continuous positive airway pressure (CPAP) treatment on depression, anxiety, and perceived stress levels and to identify factors predictive of treatment efficacy in patients with obstructive sleep apnea syndrome (OSAS). This study included 51 patients admitted to the Adiyaman University Medical School Otorhinolaryngology Department or Eskisehir Yunus Emre State Hospital between January and September 2014 with one or more complaints including snoring, excessive daytime sleepiness, or apnea witnessed by the partner. Diagnosis of OSAS was made by polysomnography and CPAP treatment was initiated. Depression levels were assessed in all study subjects using the Hospital Anxiety and Depression Scale (HADS) at the start of treatment and at 3 months. Anxiety levels were assessed using both the HADS and the State and Trait Anxiety Inventory (STAI), and perceived stress level was assessed using the Perceived Stress Questionnaire (PSQ). After CPAP treatment, we observed significant decreases in both the Depression and Anxiety Subscales of the HADS, in the Trait Anxiety subscale of the STAI, and in the PSQ. An evaluation of the initial parameters that predict improvements in these scales revealed that snoring time predicted decreases in all scale scores. In OSAS patients CPAP treatment has positive effects on psychological parameters like depression, anxiety, and perceived stress. We suggest that possible psychogenic benefits should be considered when deciding to start CPAP treatment, particularly in patients with pronounced and extended snoring who may also have social problems.

Increasing time to treatment initiation for head and neck cancer: an analysis of the National Cancer Database.

PubMed

Murphy, Colin T; Galloway, Thomas J; Handorf, Elizabeth A; Wang, Lora; Mehra, Ranee; Flieder, Douglas B; Ridge, John A

2015-04-15

The objective of this study was to identify trends and predictors of the time to treatment initiation (TTI) for patients with head and neck squamous cell carcinoma (HNSCC). The National Cancer Database (NCDB) was reviewed for the following head and neck cancer sites: oral tongue, oropharynx, larynx, and hypopharynx. TTI was defined as the number of days from diagnosis to the initiation of definitive treatment and was measured according to covariates. Significant differences in the median TTI across each covariate were measured using the Kruskal-Wallis test, and the Spearman test was used to measure trends within covariates. For multivariate analysis, a zero-inflated, negative, binomial regression model was used to estimate the expected TTI, which was expressed in the predicted number of days; and the Vuong test was used to identify the predictors of TTI. In total, 274,630 patients were included. Between 1998 and 2011, the median TTI for all patients was 26 days, and it increased from 19 days to 30 days (P < .0001). Treatment with chemoradiation (CRT) (P < .0001), treatment at academic facilities (P < .0001), and stage IV disease (P < .0001) were associated with increased TTI. TTI significantly increased for each disease stage (P < .0001), treatment modality (P < .0001), and facility type (P < .0001) over time. In addition, patients became more likely to transition care between facilities after diagnosis for treatment initiation (P < .0001) over time. On multivariate analysis, treatment at academic facilities (33 days), transitioning care (37 days), and receipt of CRT (39 days) predicted for a longer TTI. TTI is rising for patients with HNSCC. Those who have advanced-stage disease, receive treatment with CRT, are treated at academic facilities, and who have a transition in care realized the greatest increases in TTI. © 2014 American Cancer Society.

Combat Wound Initiative program.

PubMed

Stojadinovic, Alexander; Elster, Eric; Potter, Benjamin K; Davis, Thomas A; Tadaki, Doug K; Brown, Trevor S; Ahlers, Stephen; Attinger, Christopher E; Andersen, Romney C; Burris, David; Centeno, Jose; Champion, Hunter; Crumbley, David R; Denobile, John; Duga, Michael; Dunne, James R; Eberhardt, John; Ennis, William J; Forsberg, Jonathan A; Hawksworth, Jason; Helling, Thomas S; Lazarus, Gerald S; Milner, Stephen M; Mullick, Florabel G; Owner, Christopher R; Pasquina, Paul F; Patel, Chirag R; Peoples, George E; Nissan, Aviram; Ring, Michael; Sandberg, Glenn D; Schaden, Wolfgang; Schultz, Gregory S; Scofield, Tom; Shawen, Scott B; Sheppard, Forest R; Stannard, James P; Weina, Peter J; Zenilman, Jonathan M

2010-07-01

The Combat Wound Initiative (CWI) program is a collaborative, multidisciplinary, and interservice public-private partnership that provides personalized, state-of-the-art, and complex wound care via targeted clinical and translational research. The CWI uses a bench-to-bedside approach to translational research, including the rapid development of a human extracorporeal shock wave therapy (ESWT) study in complex wounds after establishing the potential efficacy, biologic mechanisms, and safety of this treatment modality in a murine model. Additional clinical trials include the prospective use of clinical data, serum and wound biomarkers, and wound gene expression profiles to predict wound healing/failure and additional clinical patient outcomes following combat-related trauma. These clinical research data are analyzed using machine-based learning algorithms to develop predictive treatment models to guide clinical decision-making. Future CWI directions include additional clinical trials and study centers and the refinement and deployment of our genetically driven, personalized medicine initiative to provide patient-specific care across multiple medical disciplines, with an emphasis on combat casualty care.

Predictors of treatment efficacy in a clinical trial of three psychosocial treatments for adolescent depression.

PubMed

Brent, D A; Kolko, D J; Birmaher, B; Baugher, M; Bridge, J; Roth, C; Holder, D

1998-09-01

To assess the predictors of treatment outcome across treatments, as well as those associated with differential treatment response. One hundred seven adolescent outpatients, aged 13 to 18 years, with DSM-III-R major depression were randomly assigned to one of three manual-based, brief (12 to 16 sessions) psychosocial treatments: cognitive-behavioral therapy (CBT), systemic-behavioral family therapy, or nondirective supportive therapy. Those with good and poor outcomes were compared. Continued depression was predicted by clinical referral (versus via advertisement) and was in part mediated by hopelessness. Other predictors of depression were comorbid anxiety disorder and higher levels of cognitive distortion and hopelessness at intake. Achievement of clinical remission was predicted by a higher level of self-reported depression. Poorer functional status was predicted by a higher level of initial interviewer-rated depression. Comorbid anxiety and maternal depressive symptoms predicted differential treatment efficacy. CBT's performance continued to be robust with respect to nondirective supportive therapy, even in the presence of the above-noted adverse predictors. Predictors of poor outcome may give clues as to how to boost treatment response. Subjects who come to treatment for clinical trials via advertisement (versus clinical referral) may show more favorable treatment responses. CBT is likely to be a robust intervention even in more complex and difficult-to-treat patients.

Development and validation of a Client Problem Profile and Index for drug treatment.

PubMed

Joe, George W; Simpson, D Dwayne; Greener, Jack M; Rowan-Szal, Grace A

2004-08-01

The development of the Client Problem Profile and Index are described, and initial concurrent and predictive validity data are presented for a sample of 547 patients in outpatient methadone treatment. Derived from the TCU Brief Intake for drug treatment admissions, the profile covers 14 problem areas related to drug use (particularly cocaine, heroin/opiate, marijuana, other illegal drugs, and multiple drug use), HIV risks, psychosocial-functioning, health, employment, and criminality. Analyses of predictive validity show the profile and its index (number of problem areas) were significantly related to therapeutic engagement, during-treatment performance, and posttreatment follow-up outcomes. Low moderate to high moderate effect sizes were observed in analyses of the index's discrimination.

Baseline psychophysiological and cortisol reactivity as a predictor of PTSD treatment outcome in virtual reality exposure therapy

PubMed Central

Norrholm, Seth Davin; Jovanovic, Tanja; Gerardi, Maryrose; Breazeale, Kathryn G.; Price, Matthew; Davis, Michael; Duncan, Erica; Ressler, Kerry J.; Bradley, Bekh; Rizzo, Albert; Tuerk, Peter W.; Rothbaum, Barbara O.

2017-01-01

Baseline cue-dependent physiological reactivity may serve as an objective measure of posttraumatic stress disorder (PTSD) symptoms. Additionally, prior animal model and psychological studies would suggest that subjects with greatest symptoms at baseline may have the greatest violation of expectancy to danger when undergoing exposure based psychotherapy; thus treatment approaches which enhanced the learning under these conditions would be optimal for those with maximal baseline cue-dependent reactivity. However methods to study this hypothesis objectively are lacking. Virtual reality (VR) methodologies have been successfully employed as an enhanced form of imaginal prolonged exposure therapy for the treatment of PTSD. Our goal was to examine the predictive nature of initial psychophysiological (e.g., startle, skin conductance, heart rate) and stress hormone responses (e.g., cortisol) during presentation of VR-based combat-related stimuli on PTSD treatment outcome. Combat veterans with PTSD underwent 6 weeks of VR exposure therapy combined with either D-cycloserine (DCS), alprazolam (ALP), or placebo (PBO). In the DCS group, startle response to VR scenes prior to initiation of treatment accounted for 76% of the variance in CAPS change scores, p < 0.001, in that higher responses predicted greater changes in symptom severity over time. Additionally, baseline cortisol reactivity was inversely associated with treatment response in the ALP group, p = 0.04. We propose that baseline cue-activated physiological measures will be sensitive to predicting patients’ level of response to exposure therapy, in particular in the presence of enhancement (e.g., DCS). PMID:27183343

Cost trend analysis of initial cancer treatment in Taiwan.

PubMed

Li, Tsai-Yun; Hsieh, Jan-Sing; Lee, King-Teh; Hou, Ming-Feng; Wu, Chia-Ling; Kao, Hao-Yun; Shi, Hon-Yi

2014-01-01

Despite the high cost of initial cancer care, that is, care in the first year after diagnosis, limited information is available for specific categories of cancer-related costs, especially costs for specific services. This study purposed to identify causes of change in cancer treatment costs over time and to perform trend analyses of the percentage of cancer patients who had received a specific treatment type and the mean cost of care for patients who had received that treatment. The analysis of trends in initial treatment costs focused on cancer-related surgery, chemotherapy, radiation therapy, and treatments other than active treatments. For each cancer-specific trend, slopes were calculated for regression models with 95% confidence intervals. Analyses of patients diagnosed in 2007 showed that the National Health Insurance (NHI) system paid, on average, $10,780 for initial care of a gastric cancer patient and $10,681 for initial care of a lung cancer patient, which were inflation-adjusted increases of $6,234 and $5,522, respectively, over the 1996 care costs. During the same interval, the mean NHI payment for initial care for the five specific cancers increased significantly (p<0.05). Hospitalization costs comprised the largest portion of payments for all cancers. During 1996-2007, the use of chemotherapy and radiation therapy significantly increased in all cancer types (p<0.05). In 2007, NHI payments for initial care for these five cancers exceeded $12 billion, and gastric and lung cancers accounted for the largest share. In addition to the growing number of NHI beneficiaries with cancer, treatment costs and the percentage of patients who undergo treatment are growing. Therefore, the NHI must accurately predict the economic burden of new chemotherapy agents and radiation therapies and may need to develop programs for stratifying patients according to their potential benefit from these expensive treatments.

Prediction of inspiratory flow shapes during sleep with a mathematic model of upper airway forces.

PubMed

Aittokallio, Tero; Gyllenberg, Mats; Saaresranta, Tarja; Polo, Olli

2003-11-01

To predict the airflow dynamics during sleep using a mathematic model that incorporates a number of static and dynamic upper airway forces, and to compare the numerical results to clinical flow data recorded from patients with sleep-disordered breathing on and off various treatment options. Upper airway performance was modeled in virtual subjects characterized by parameter settings that describe common combinations of risk factors predisposing to upper airway collapse during sleep. The treatments effect were induced by relevant changes of the initial parameter values. Computer simulations at our website (http://www.utu.fi/ml/sovmat/bio/). Risk factors considered in the simulation settings were sex, obesity, pharyngeal collapsibility, and decreased phasic activity of pharyngeal muscles. The effects of weight loss, pharyngeal surgery, nasal continuous positive airway pressure, and respiratory stimulation on the inspiratory flow characteristics were tested with the model. Numerical predictions were investigated by means of 3 measurable inspiratory airflow characteristics: initial slope, total volume, and flow shape. The model was able to reproduce the inspiratory flow shape characteristics that have previously been described in the literature. Simulation results also supported the observations that a multitude of factors underlie the pharyngeal collapse and, therefore, certain medical therapies that are effective in some conditions may prove ineffective in others. A mathematic model integrating the current knowledge of upper airway physiology is able to predict individual treatment responses. The model provides a framework for designing novel and potentially feasible treatment alternatives for sleep-disordered breathing.

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.

Initial treatment seeking from professional health care providers for eating disorders: A review and synthesis of potential barriers to and facilitators of "first contact".

PubMed

Regan, Pamela; Cachelin, Fary M; Minnick, Alyssa M

2017-03-01

The objective of this study is to provide a comprehensive review of empirical research exploring barriers to and facilitators of initial treatment seeking ("first contact") from professional health care providers by adults and young adults with eating disorders (EDs). A search of databases PsycINFO and MEDLINE using the terms "treatment" and "eating disorder*" yielded 9,468 peer-reviewed articles published from January 1945 to June 2016. Screening identified 31 articles meeting the following criteria: (1) participants were 16 or older and presented with a self-reported or clinically diagnosed ED; (2) studies focused on (a) initial treatment seeking (b) for an ED (c) from professional health care providers; (3) articles were empirical, and (4) peer reviewed. Quantitative studies revealed few consistent correlates of treatment seeking, perhaps because most variables were examined in only one or two investigations. Variables with some degree of predictive utility (i.e., produced significant results in multiple studies) were age (older), ethnicity (nonethnic minority), ED type (anorexia, purging BN), specific ED-related behaviors (i.e., purging), and time spent on a treatment waitlist following referral (less). Although BMI was one of the most investigated variables, it did not predict treatment seeking. Qualitative studies revealed the following perceived barriers: (1) personal feelings of shame/fear, (2) ED-related beliefs/perceptions, (3) lack of access/availability, and (4) aspects of the treatment process. Perceived facilitators included (1) health-related concerns, (2) emotional distress, and (3) social support. Implications for clinical practice and areas for further research are discussed. Results highlight the need for shared definitions and methodologies across studies of treatment seeking. © 2017 Wiley Periodicals, Inc.

Utility of the PET-CT in the evaluation of early response to treatment in the diffuse large B-cell lymphoma. Preliminary results.

PubMed

Cortés Romera, M; Gámez Cenzano, C; Caresia Aróztegui, A P; Martín-Comín, J; González-Barca, E; Ricart Brulles, Y; Palacios Abufón, A; Robles Barba, J; Rodríguez-Bel, L; Rossi Seoane, S; Fernández de Sevilla, A

2012-01-01

To assess the role of FDG-PET/CT performed after the first cycles of chemotherapy in the prediction of response to treatment in patients with diffuse large B-cell lymphoma. Twenty patients (mean age: 48 years) were included, 16 initial staging and 4 relapse. All patients underwent PET/CT at 3 times: 1) Baseline, 2) After 1-3 cycles of chemotherapy (early response assessment), and 3) End of treatment (evaluation of final response). Early PET/CT findings were correlated to the end-treatment PET/CT and follow-up. The evaluation of the response was established according to the decrease in uptake of the lesions (SUVmax). In the early assessment, a good response indicator (GRI) was obtained when the lesion disappeared or had more than 50% reduction in SUVmax. At the end of the treatment, a complete metabolic response (CMR) was determined in negative PET scans. Follow-up was superior to 19 months and final outcome was established as progression/relapse or no evidence of disease (NED). At the early treatment evaluation, 16/16 patients of initial staging (100%) and 2/4 of relapse (50%) achieved GRI. At the end of treatment evaluation, 14/16 patients of initial staging with GRI achieved CMR and 1/16 PMR: 14 were alive with NED in the follow-up while 1 relapsed. In the second group, 2/2 patients with GRI achieved CMR (100%): 1 continued with NED in the follow-up and another relapsed. FDG-PET/CT after the first cycles of chemotherapy is useful to monitor treatment due to its high negative predictive value (87.5%), using it to modify treatment early in the non-responders. Copyright © 2011 Elsevier España, S.L. y SEMNIM. All rights reserved.

Analysis of correlation between initial alveolar bone density and apical root resorption after 12 months of orthodontic treatment without extraction

PubMed Central

Scheibel, Paula Cabrini; Ramos, Adilson Luiz; Iwaki, Lilian Cristina Vessoni; Micheletti, Kelly Regina

2014-01-01

OBJECTIVE: The aim of the present study was to investigate the correlation between initial alveolar bone density of upper central incisors (ABD-UI) and external apical root resorption (EARR) after 12 months of orthodontic movement in cases without extraction. METHODS: A total of 47 orthodontic patients 11 years old or older were submitted to periapical radiography of upper incisors prior to treatment (T1) and after 12 months of treatment (T2). ABD-UI and EARR were measured by means of densitometry. RESULTS: No statistically significant correlation was found between initial ABD-UI and EARR at T2 (r = 0.149; p = 0.157). CONCLUSION: Based on the present findings, alveolar density assessed through periapical radiography is not predictive of root resorption after 12 months of orthodontic treatment in cases without extraction. PMID:25715722

Post-treatment control of HIV infection

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

Conway, Jessica M.; Perelson, Alan S.

Antiretroviral therapy (ART) for HIV is not a cure. However, recent studies suggest that ART, initiated early during primary infection, may induce post-treatment control (PTC) of HIV infection with HIV RNA maintained at <50 copies per mL. We investigate the hypothesis that ART initiated early during primary infection permits PTC by limiting the size of the latent reservoir, which, if small enough at treatment termination, may allow the adaptive immune response to prevent viral rebound (VR) and control infection. We use a mathematical model of within host HIV dynamics to capture interactions among target cells, productively infected cells, latently infectedmore » cells, virus, and cytotoxic T lymphocytes (CTLs). Analysis of our model reveals a range in CTL response strengths where a patient may show either VR or PTC, depending on the size of the latent reservoir at treatment termination. Below this range, patients will always rebound, whereas above this range, patients are predicted to behave like elite controllers. As a result, using data on latent reservoir sizes in patients treated during primary infection, we also predict population-level VR times for non-controllers consistent with observations.« less

Post-treatment control of HIV infection

DOE PAGES

Conway, Jessica M.; Perelson, Alan S.

2015-04-13

Antiretroviral therapy (ART) for HIV is not a cure. However, recent studies suggest that ART, initiated early during primary infection, may induce post-treatment control (PTC) of HIV infection with HIV RNA maintained at <50 copies per mL. We investigate the hypothesis that ART initiated early during primary infection permits PTC by limiting the size of the latent reservoir, which, if small enough at treatment termination, may allow the adaptive immune response to prevent viral rebound (VR) and control infection. We use a mathematical model of within host HIV dynamics to capture interactions among target cells, productively infected cells, latently infectedmore » cells, virus, and cytotoxic T lymphocytes (CTLs). Analysis of our model reveals a range in CTL response strengths where a patient may show either VR or PTC, depending on the size of the latent reservoir at treatment termination. Below this range, patients will always rebound, whereas above this range, patients are predicted to behave like elite controllers. As a result, using data on latent reservoir sizes in patients treated during primary infection, we also predict population-level VR times for non-controllers consistent with observations.« less

Neuropsychological impairments predict the clinical course in schizophrenia.

PubMed

Wölwer, Wolfgang; Brinkmeyer, Jürgen; Riesbeck, Mathias; Freimüller, Lena; Klimke, Ansgar; Wagner, Michael; Möller, Hans-Jürgen; Klingberg, Stefan; Gaebel, Wolfgang

2008-11-01

To add to the open question whether cognitive impairments predict clinical outcome in schizophrenia, a sample of 125 first episode patients was assessed at the onset and over one year of controlled long-term treatment within a study of the German Research Network on Schizophrenia. No relapse according to predefined criteria occurred within the first year, but a total of 29 patients fulfilled post-hoc criteria of "clinical deterioration". Impairments in cognitive functioning assessed by the Trail-Making Test B at the onset of long-term treatment differentiated between patients with vs. without later clinical deterioration and proved to be a significant predictor of the clinical course in a regression analysis outperforming initial clinical status as predictor. However, low sensitivity (72%) and specificity (51%) limit possibilities of a transfer to individual predictions. As a linear combination of neuropsychological and psychopathological variables obtained highest predictive validity, such a combination may improve the prediction of the course of schizophrenic disorders and may ultimately lead to a more efficient and comprehensive treatment planning.

Inability to access addiction treatment predicts injection initiation among street-involved youth in a Canadian setting.

PubMed

DeBeck, Kora; Kerr, Thomas; Nolan, Seonaid; Dong, Huiru; Montaner, Julio; Wood, Evan

2016-01-06

Preventing injection drug use among vulnerable youth is critical for reducing serious drug-related harms. Addiction treatment is one evidence-based intervention to decrease problematic substance use; however, youth frequently report being unable to access treatment services and the impact of this on drug use trajectories remains largely unexplored. This study examines the relationship between being unable to access addiction treatment and injection initiation among street-involved youth. Data were derived from the At-Risk Youth Study (ARYS), a prospective cohort of street-involved youth aged 14-26 who use illicit drugs, from September 2005 to May 2014. An extended Cox model with time-dependent variables was used to identify factors independently associated with injection initiation. Among 462 participants who were injection naïve at baseline, 97 (21 %) initiated injection drug use over study follow-up and 129 (28 %) reported trying but being unable to access addiction treatment in the previous 6 months at some point during the study period. The most frequently reported reason for being unable to access treatment was being put on a wait list. In a multivariable Cox regression analysis, being unable to access addiction treatment remained independently associated with a more rapid rate of injection initiation (Adjusted Hazard Ratio =2.02; 95 % Confidence Interval: 1.12-3.62), after adjusting for potential confounders. Inability to access addiction treatment was common among our sample and associated with injection initiation. Findings highlight the need for easily accessible, evidence-based addiction treatment for high-risk youth as a means to prevent injection initiation and subsequent serious drug-related harms.

Decay model for biocide treatment of unballasted vessels: application for the Laurentian Great Lakes.

PubMed

Sano, Larissa L; Bartell, Steven M; Landrum, Peter F

2005-10-01

A biocide decay model was developed to assess the potential efficacy and environmental impacts associated with using glutaraldehyde to treat unballasted overseas vessels trading on the Laurentian Great Lakes. The results of Monte Carlo simulations indicate that effective glutaraldehyde concentrations can be maintained for the duration of a vessel's oceanic transit (approximately 9-12 days): During this transit, glutaraldehyde concentrations were predicted to decrease by approximately 10% from initial treatment levels (e.g., 500 mgL(-1)). In terms of environmental impacts, mean glutaraldehyde concentrations released at Duluth-Superior Harbor, MN were predicted to be 100-fold lower than initial treatment concentrations, and ranged from 3.2 mgL(-1) (2 SD: 2.74) in April to 0.7 mgL(-1) (2 SD: 1.28) in August. Sensitivity analyses indicated that the re-ballasting dilution factor was the major variable governing final glutaraldehyde concentrations; however, lake surface temperatures became increasingly important during the warmer summer months.

WE-AB-202-11: Radiobiological Modeling of Tumor Response During Radiotherapy Based On Pre-Treatment Dynamic PET Imaging Data

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

Crispin-Ortuzar, M; Grkovski, M; Beattie, B

Purpose: To evaluate the ability of a multiscale radiobiological model of tumor response to predict mid-treatment hypoxia images, based on pretreatment imaging of perfusion and hypoxia with [18-F]FMISO dynamic PET and glucose metabolism with [18-F]FDG PET. Methods: A mechanistic tumor control probability (TCP) radiobiological model describing the interplay between tumor cell proliferation and hypoxia (Jeong et al., PMB 2013) was extended to account for intra-tumor nutrient heterogeneity, dynamic cell migration due to nutrient gradients, and stromal cells. This extended model was tested on 10 head and neck cancer patients treated with chemoradiotherapy, randomly drawn from a larger MSKCC protocol involvingmore » baseline and mid-therapy dynamic PET scans. For each voxel, initial fractions of proliferative and hypoxic tumor cells were obtained by finding an approximate solution to a system of linear equations relating cell fractions to voxel-level FDG uptake, perfusion (FMISO K{sub 1}) and hypoxia (FMISO k{sub 3}). The TCP model then predicted their evolution over time up until the mid treatment scan. Finally, the linear model was reapplied to predict each lesion’s median hypoxia level (k{sub 3}[med,sim]) which in turn was compared to the FMISO k{sub 3}[med] measured at mid-therapy. Results: The average k3[med] of the tumors in pre-treatment scans was 0.0035 min{sup −1}, with an inter-tumor standard deviation of σ[pre]=0.0034 min{sup −1}. The initial simulated k{sub 3}[med,sim] of each tumor agreed with the corresponding measurements within 0.1σ[pre]. In 7 out of 10 lesions, the mid-treatment k{sub 3}[med,sim] prediction agreed with the data within 0.3σ[pre]. The remaining cases corresponded to the most extreme relative changes in k{sub 3}[med]. Conclusion: This work presents a method to personalize the prediction of a TCP model using pre-treatment kinetic imaging data, and validates the modeling of radiotherapy response by predicting changes in median hypoxia values during treatment. Variations from predicted response may be a useful biomarker, which should be further explored. Partially supported by NIH grant #1 R01 CA157770-01A1 and a grant from Varian Corporation.« less

Reductions in pulmonary function detected in patients with lymphangioleiomyomatosis: An analysis of the Japanese National Research Project on Intractable Diseases database.

PubMed

Hayashida, Mie; Yasuo, Masanori; Hanaoka, Masayuki; Seyama, Kuniaki; Inoue, Yoshikazu; Tatsumi, Koichiro; Mishima, Michiaki

2016-05-01

In lymphangioleiomyomatosis (LAM), predicting lung disease progression is essential for treatment planning. However, no previous Japanese studies have attempted to predict the reductions in pulmonary function that occur in LAM patients. The data for 89 LAM patients who had undergone ≥3 spirometry tests and whose data had been registered in the Japanese National Research Project on Intractable Diseases database between October 2009 and March 2014 were analyzed after excluding patients who had undergone (1) a lung transplant; (2) mTOR inhibitor treatment; or (3) thoracic drainage, pleurodesis, surgery, or thoracic duct ligation during the study period. The rates of change (slope) in pulmonary parameters were calculated, and their associations with clinical background factors were investigated. Among the whole study population, the median (quartiles) slope of forced expiratory volume in one second (FEV1) was -46.7 (-95.2; -15.0)mL per year. Episodes of conservatively treated pneumothorax during the study period were found to be associated with rapid reductions in FEV1 (% predicted). Pregnancy during the study period was associated with a reduction in FEV1 (% predicted). When the patients were divided into those who exhibited initial FEV1 (% predicted) values of >70% (Group A) and ≤70% (Group B), Group B displayed significantly faster reductions in FEV1 (% predicted) than Group A. LAM patients whose initial FEV1 (% predicted) values are ≤70% subsequently exhibit rapid reductions in their FEV1 values, and hence, require treatment. However, the FEV1 reduction rate varies markedly among individuals and should be monitored in all cases. Copyright © 2015 The Japanese Respiratory Society. Published by Elsevier B.V. All rights reserved.

Aspirin for acute stroke of unknown etiology in resource-limited settings: a decision analysis.

PubMed

Berkowitz, Aaron L; Westover, M Brandon; Bianchi, Matt T; Chou, Sherry H-Y

2014-08-26

To analyze the potential impact of aspirin on outcome at hospital discharge after acute stroke in resource-limited settings without access to neuroimaging to distinguish ischemic stroke from intracerebral hemorrhage (ICH). A decision analysis was conducted to evaluate aspirin use in all patients with acute stroke of unknown type for the duration of initial hospitalization. Data were obtained from the International Stroke Trial and Chinese Acute Stroke Trial. Predicted in-hospital mortality and stroke recurrence risk were determined across the worldwide reported range of the proportion of strokes caused by ICH. Sensitivity analyses were performed on aspirin-associated relative risks in patients with ICH. At the highest reported proportion of strokes due to ICH from a large epidemiologic study (34% in sub-Saharan Africa), aspirin initiation after acute stroke of undetermined etiology is predicted to reduce in-hospital mortality (from 85/1,000 without treatment to 81/1,000 with treatment), in-hospital stroke recurrence (58/1,000 to 50/1,000), and combined risk of in-hospital mortality or stroke recurrence (127/1,000 to 114/1,000). Benefits of aspirin therapy remained in sensitivity analyses across a range of plausible parameter estimates for relative risks associated with aspirin initiation after ICH. Aspirin treatment for the period of initial hospitalization after acute stroke of undetermined etiology is predicted to decrease acute stroke-related mortality and in-hospital stroke recurrence even at the highest reported proportion of acute strokes due to ICH. In the absence of clinical trials to test this approach empirically, clinical decisions require patient-specific evaluation of risks and benefits of aspirin in this context. © 2014 American Academy of Neurology.

Time-to-treatment of mental disorders in a community sample of Dutch adolescents. A TRAILS study.

PubMed

Raven, D; Jörg, F; Visser, E; Oldehinkel, A J; Schoevers, R A

2017-04-01

Timely recognition and treatment of mental disorders with an onset in childhood and adolescence is paramount, as these are characterized by greater severity and longer persistence than disorders with an onset in adulthood. Studies examining time-to-treatment, also referred to as treatment delay, duration of untreated illness or latency to treatment, and defined as the time between disorder onset and initial treatment contact, are sparse and all based on adult samples. The aim of this study was to describe time-to-treatment and its correlates for any health care professional (any care) and secondary mental health care (secondary care), for a broad range of mental disorders, in adolescents. Data from the Dutch community-based cohort study TRacking Adolescents' Individual Lives Survey (TRAILS; N = 2230) were used. The Composite International Diagnostic Interview (CIDI) was administered to assess DSM-IV disorders, the age of onset, and the age of initial treatment contact with any health care professional in 1584 adolescents of 18-20 years old. In total 43% of the adolescents (n = 675) were diagnosed with a lifetime DSM-IV disorder. The age of initial treatment contact with secondary care was based on administrative records from 321 adolescents without a disorder onset before the age of 10. Descriptive statistics, cumulative lifetime probability plots, and Cox regression analyses were used analyze time-to-treatment. The proportion of adolescents who reported lifetime treatment contact with any care varied from 15% for alcohol dependence to 82% for dysthymia. Regarding secondary care, proportions of lifetime treatment contact were lower for mood disorders and higher for substance dependence. Time-to-treatment for any care varied considerably between and within diagnostic classes. The probability of lifetime treatment contact for mood disorders was above 90%, whereas for other mental disorders this was substantially lower. An earlier age of onset predicted a longer, and the presence of a co-morbid mood disorder predicted a shorter time-to-treatment in general. Disorder severity predicted a shorter time-to-treatment for any care, but not for secondary care. Time-to-treatment for secondary care was shorter for adolescents from low and middle socioeconomic background than for adolescents from a high socioeconomic background. Although the time-to-treatment was shorter for adolescents than for adults, it was still substantial, and the overall patterns were remarkably similar to those found in adults. Efforts to reduce time-to-treatment should therefore be aimed at children and adolescents. Future research should address mechanisms underlying time-to-treatment and its consequences for early-onset disorders in particular.

Assessment of induced rat mammary tumour response to chemotherapy using the apparent diffusion coefficient of tissue water as determined by diffusion-weighted 1H-NMR spectroscopy in vivo.

PubMed

Lemaire, L; Howe, F A; Rodrigues, L M; Griffiths, J R

1999-03-01

Chemosensitivity of N-methyl-N-nitrosourea-induced rat mammary tumours treated with 5-fluorouracil at a dose of 100 mg kg(-1) i.p. was assessed by using diffusion-weighted 1H-MRS to measure the average diffusion coefficient (ADC) of water in the tumour tissue. ADC measurements prior to any therapy correlated positively with necrotic fraction. Tumours with low initial ADC (< 0.95 x 10(9) m2 s(-1)) showed an increase in ADC 7 days after treatment, whereas tumours with a high initial ADC (> 1.2 x 10(9) m2 s(-1)) showed a decrease. All tumours decreased significantly in volume (P < 0.05) 2, 5 and 7 days after treatment. At day 7 post-treatment, tumours with a high pre-treatment ADC started to regrow. The initial ADC value, as well as changes after treatment predict tumour chemosensitivity, which could be clinically relevant.

Testing the predictive value of peripheral gene expression for nonremission following citalopram treatment for major depression.

PubMed

Guilloux, Jean-Philippe; Bassi, Sabrina; Ding, Ying; Walsh, Chris; Turecki, Gustavo; Tseng, George; Cyranowski, Jill M; Sibille, Etienne

2015-02-01

Major depressive disorder (MDD) in general, and anxious-depression in particular, are characterized by poor rates of remission with first-line treatments, contributing to the chronic illness burden suffered by many patients. Prospective research is needed to identify the biomarkers predicting nonremission prior to treatment initiation. We collected blood samples from a discovery cohort of 34 adult MDD patients with co-occurring anxiety and 33 matched, nondepressed controls at baseline and after 12 weeks (of citalopram plus psychotherapy treatment for the depressed cohort). Samples were processed on gene arrays and group differences in gene expression were investigated. Exploratory analyses suggest that at pretreatment baseline, nonremitting patients differ from controls with gene function and transcription factor analyses potentially related to elevated inflammation and immune activation. In a second phase, we applied an unbiased machine learning prediction model and corrected for model-selection bias. Results show that baseline gene expression predicted nonremission with 79.4% corrected accuracy with a 13-gene model. The same gene-only model predicted nonremission after 8 weeks of citalopram treatment with 76% corrected accuracy in an independent validation cohort of 63 MDD patients treated with citalopram at another institution. Together, these results demonstrate the potential, but also the limitations, of baseline peripheral blood-based gene expression to predict nonremission after citalopram treatment. These results not only support their use in future prediction tools but also suggest that increased accuracy may be obtained with the inclusion of additional predictors (eg, genetics and clinical scales).

Psychological distress and in vitro fertilization outcome

PubMed Central

Pasch, Lauri A.; Gregorich, Steven E.; Katz, Patricia K.; Millstein, Susan G.; Nachtigall, Robert D.; Bleil, Maria E.; Adler, Nancy E.

2016-01-01

Objective To examine whether psychological distress predicts IVF treatment outcome as well as whether IVF treatment outcome predicts subsequent psychological distress. Design Prospective cohort study over an 18-month period. Setting Five community and academic fertility practices. Patients Two hundred and two women who initiated their first IVF cycle. Interventions Women completed interviews and questionnaires at baseline and at 4, 10, and 18 months follow-up. Main Outcome Measures IVF cycle outcome and psychological distress. Results Using a binary logistic model including covariates (woman’s age, ethnicity, income, education, parity, duration of infertility, and time interval), pre-treatment depression and anxiety were not significant predictors of the outcome of the first IVF cycle. Using linear regression models including covariates (woman’s age, income, education, parity, duration of infertility, assessment point, time since last treatment cycle, and pre-IVF depression or anxiety), experiencing failed IVF was associated with higher post-IVF depression and anxiety. Conclusions IVF failure predicts subsequent psychological distress, but pre-IVF psychological distress does not predict IVF failure. Instead of focusing efforts on psychological interventions specifically aimed at improving the chance of pregnancy, these findings suggest that attention be paid to helping patients prepare for and cope with treatment and treatment failure. PMID:22698636

Predicting therapy outcome in patients with early and late obsessive-compulsive disorder (EOCD and LOCD).

PubMed

Langner, Judith; Laws, Manuela; Röper, Gisela; Zaudig, Michael; Hauke, Walter; Piesbergen, Christoph

2009-10-01

Increasing attention has been given to subtyping OCD with respect to different clinical profiles, response to drug treatments, comorbidity and age of onset. There are a number of studies looking at predictors of treatment outcome in OCD, but so far not for OCD subtypes. Prediction of outcome after cognitive-behavioural therapy was evaluated in 63 inpatients with early obsessive-compulsive disorder (EOCD < or = 12 years of age) and 191 patients with late obsessive-compulsive disorder (LOCD > 15 years of age). For EOCD patients factors predicting a good outcome included high motivation and high initial Y-BOCS scores. Factors associated with a bad outcome were higher age at assessment, a longer duration of psychiatric inpatient treatment before assessment and a low level of social functioning (BSS). For LOCD patients living in a stable relationship, high motivation and completing treatment predicted a favourable therapy outcome, while a low level of psychological functioning (BSS) and a longer duration of inpatient psychiatric treatment before assessment were associated with an undesirable therapy outcome. Subtyping OCD patients according to age of onset seems to be a promising avenue towards improving and developing more specified treatment programs.

Barriers to access to treatment for mothers with postpartum depression in primary health care centers: a predictive model1

PubMed Central

Martínez, Pablo; Vöhringer, Paul A.; Rojas, Graciela

2016-01-01

Objective to develop a predictive model to evaluate the factors that modify the access to treatment for Postpartum Depression (PPD). Methods prospective study with mothers who participated in the monitoring of child health in primary care centers. For the initial assessment and during 3 months, it was considered: sociodemographic data, gyneco-obstetric data, data on the services provided, depressive symptoms according to the Edinburgh Postpartum Depression Scale (EPDS) and quality of life according to the Short Form-36 Health Status Questionnaire (SF-36). The diagnosis of depression was made based on MINI. Mothers diagnosed with PPD in the initial evaluation, were followed-up. Results a statistical model was constructed to determine the factors that prevented access to treatment, which consisted of: item 2 of EPDS (OR 0.43, 95%CI: 0.20-0.93) and item 5 (OR 0.48, 95%CI: 0.21-1.09), and previous history of depression treatment (OR 0.26, 95%CI: 0.61-1.06). Area under the ROC curve for the model=0.79; p-value for the Hosmer-Lemershow=0.73. Conclusion it was elaborated a simple, well standardized and accurate profile, which advises that nurses should pay attention to those mothers diagnosed with PPD, presenting low/no anhedonia (item 2 of EPDS), scarce/no panic/fear (item 5 of EPDS), and no history of depression, as it is likely that these women do not initiate treatment. PMID:27027674

Dynamic value assessments in oncology supported by the PACE Continuous Innovation Indicators.

PubMed

Paddock, Silvia; Goodman, Clifford; Shortenhaus, Scott; Grainger, David; Zummo, Jacqueline; Thomas, Samuel

2017-10-01

Several recently developed frameworks aim to assess the value of cancer treatments, but the most appropriate metrics remain uncertain. We use data from the Patient Access to Cancer care Excellence Continuous Innovation Indicators to examine the relationship between hazard ratios (HRs) from clinical trials and dynamic therapeutic value accumulating over time. Our analysis shows that HRs from initial clinical trials poorly predict the eventual therapeutic value of cancer treatments. Relying strongly on HRs from registration trials to predict the long-term success of treatments leaves a lot of the variance unexplained. The Continuous Innovation Indicators offer a complementing, dynamic method to track the therapeutic value of cancer treatments and continuously update value assessments as additional evidence accumulates.

Presenting hydrothorax predicts failure of needle aspiration in primary spontaneous pneumothorax.

PubMed

Wu, Kwok Kei; Lui, Chun Tat; Ho, Chik Leung; Tsui, Kwok Leung; Fung, Hin Tat

2016-06-01

The objective was to evaluate if existence of hydrothorax in initial chest radiograph predicts treatment outcome in patients with primary spontaneous pneumothorax who received needle thoracostomy. This is a retrospective cohort study carried out from January 2011 to August 2014 in 1 public hospital in Hong Kong. All consecutive adult patients aged 18years or above who attended the emergency department with the diagnosis of primary spontaneous pneumothorax with needle aspiration performed as primary treatment were included. Age, smoking status, size of pneumothorax, previous history of pneumothorax, aspirated gas volume and presence of hydropneumothorax in initial radiograph were included in the analysis. The outcome was success or failure of the needle aspiration. Logistic regression was used to identify the predicting factors of failure of needle aspiration. There were a total of 127 patients included. Seventy-three patients (57.5%) were successfully treated with no recurrence upon discharge. Among 54 failure cases, 13 patients (10.2%) failed immediately after procedure as evident by chest radiograph and required second treatment. Forty-one patients (32.3%) failed upon subsequent chest radiographs. Multivariate logistic regression showed factors independently associated with the failure of needle aspiration, which included hydropneumothorax in the initial radiograph (odds ratio [OR]=4.47 [1.56i12.83], P=.005), previous history of pneumothorax (OR=3.92 [1.57-9.79], P=.003), and large size of pneumothorax defined as apex-to-cupola distance ≥5cm (OR=2.75 [1.21-6.26], P=.016). Hydropneumothorax, previous history of pneumothorax, and large size were independent predictors of failure of needle aspiration in treatment of primary spontaneous pneumothorax. Copyright © 2016 Elsevier Inc. All rights reserved.

Thinning guidelines from crown area relationships for young hardwood plantations

Treesearch

Jeffrey W. Stringer; Luke Cecil

2010-01-01

Crown closure in hardwood plantations signals the first opportunity to apply density control treatments such as thinning or release. The proper timing of these treatments is a function of stocking levels and is generally scheduled within several years after initial crown closure. Predicting crown closure for a plantation provides practitioners with the ability to plan...

Circulating endothelial cells and their progenitors in acute myeloid leukemia

PubMed Central

Zahran, Asmaa Mohammed; Aly, Sanaa Shaker; Altayeb, Hanan Ahmed; Ali, Arwa Mohammed

2016-01-01

Acute myeloid leukemia (AML) is an aggressive hematological malignancy characterized by the accumulation of immature myeloid progenitor cells in the bone marrow. Studies are required to investigate the prognostic and predictive value of surrogate biomarkers. Given the importance of angiogenesis in oncology in terms of pathogenesis as well as being a target for treatment, circulating endothelial cells (CECs) and endothelial progenitor cells (EPCs) are promising candidates to serve as such markers. The aim of the present study was to quantify CECs and EPCs in patients with AML at initial diagnosis and following induction chemotherapy, and to correlate these findings with the response to treatment in AML patients. The present study included 40 patients with de novo AML and 20 age- and gender-matched healthy controls. CECs and EPCs were evaluated by flow cytometry at initial diagnosis and after induction chemotherapy (3+7 protocol for AML other than M3 and all-trans-retinoic acid plus anthracycline for M3 disease). CECs and EPCs were significantly higher in AML patients at diagnosis and after induction chemotherapy than in controls. After induction chemotherapy, CECs and EPCs were significantly decreased compared with the levels at initial diagnosis. Patients who achieved complete response (n=28) had lower initial CEC and EPC levels compared with patients who did not respond to treatment. These results suggest that CEC levels are higher in AML patients and may correlate with disease status and treatment response. Further investigations are required to better determine the predictive value and implication of these cells in AML management. PMID:27602121

Physical examination variables predict response to conservative treatment of non-chronic plantar fasciitis: Secondary analysis of a randomized placebo controlled footwear study

PubMed Central

Matzkin-Bridger, Jonathon; Fascione, Jeanna; Crews, Ryan; Bruning, Nicholas; Jarrett, Beth

2016-01-01

Background Plantar fasciitis is a common disabling condition and the prognosis of conservative treatment is difficult to predict. Objective To determine whether initial clinical findings could help predict patient response to conservative treatment primarily consisting of supportive footwear and stretching. Setting Patients were recruited and seen at two outpatient podiatric clinics in the Chicago, Illinois metropolitan area. Patients Seventy-seven patients with non-chronic plantar fasciitis were recruited. Patients were excluded if they had a heel injection in the previous six months or were currently utilizing custom foot orthoses at the time of screening. Sixty-nine patients completed the final follow-up visit three months after receiving the footwear intervention. Methods Treatment failure was considered a <50% reduction in heel pain at three month follow23 Logistic regression models evaluated the possible association between over thirty clinical and physical exam findings prospectively assessed at enrollment, and treatment response. Results Inability to dorsiflex the ankle past −5° (OR 27 3.9, p=.024), non-severe (≤ 7 on ordinal scale) first-step pain (OR 3.8, p=.021), and heel valgus in relaxed stance (OR 4.0, p=.014) each predicted treatment failure in multivariable analysis (Receiver operating characteristic area under the curve=.769). Limited ankle dorsiflexion also correlated with higher heel pain severity at initial presentation (r = −.312, p =.006). Conclusions Patients with severe ankle equinus were nearly four times more likely to experience a favorable response to treatment centered on home Achilles tendon stretching and supportive therapy. Thus earlier use of more advanced therapies may be most appropriate in those presenting without severe ankle equinus or without severe first step pain. The findings from our study may not be clinically intuitive as patients with less severe equinus and less severe pain at presentation did worse with conservative care. PMID:26409199

Physical Examination Variables Predict Response to Conservative Treatment of Nonchronic Plantar Fasciitis: Secondary Analysis of a Randomized, Placebo-Controlled Footwear Study.

PubMed

Wrobel, James S; Fleischer, Adam E; Matzkin-Bridger, Jonathon; Fascione, Jeanna; Crews, Ryan T; Bruning, Nicholas; Jarrett, Beth

2016-05-01

Plantar fasciitis is a common, disabling condition, and the prognosis of conservative treatment is difficult to predict. To determine whether initial clinical findings could help predict patient response to conservative treatment that primarily consisted of supportive footwear and stretching. Patients were recruited and seen at 2 outpatient podiatric clinics in the Chicago, Illinois, metropolitan area. Seventy-seven patients with nonchronic plantar fasciitis were recruited. Patients were excluded if they had a heel injection in the previous 6 months or were currently using custom foot orthoses at the time of screening. Sixty-nine patients completed the final follow-up visit 3 months after receiving the footwear intervention. Treatment failure was considered a <50% reduction in heel pain at 3 month follow-up. Logistic regression models evaluated the possible association between more than 30 clinical and physical examination findings prospectively assessed at enrollment, and treatment response. Inability to dorsiflex the ankle past -5° (odds ratio [OR] 3.9, P = .024), nonsevere (≤7 on ordinal scale) first-step pain (OR 3.8, P = .021), and heel valgus in relaxed stance (OR 4.0, P = .014) each predicted treatment failure in multivariable analysis (receiver operating characteristic area under the curve = .769). Limited ankle dorsiflexion also correlated with greater heel pain severity at initial presentation (r = - 0.312, P = .006). Patients with severe ankle equinus were nearly 4 times more likely to experience a favorable response to treatment centered on home Achilles tendon stretching and supportive therapy. Thus, earlier use of more advanced therapies may be most appropriate in those presenting without severe ankle equinus or without severe first step pain. The findings from our study may not be clinically intuitive because patients with less severe equinus and less severe pain at presentation did worse with conservative care. Copyright © 2016 American Academy of Physical Medicine and Rehabilitation. Published by Elsevier Inc. All rights reserved.

Baseline psychophysiological and cortisol reactivity as a predictor of PTSD treatment outcome in virtual reality exposure therapy.

PubMed

Norrholm, Seth Davin; Jovanovic, Tanja; Gerardi, Maryrose; Breazeale, Kathryn G; Price, Matthew; Davis, Michael; Duncan, Erica; Ressler, Kerry J; Bradley, Bekh; Rizzo, Albert; Tuerk, Peter W; Rothbaum, Barbara O

2016-07-01

Baseline cue-dependent physiological reactivity may serve as an objective measure of posttraumatic stress disorder (PTSD) symptoms. Additionally, prior animal model and psychological studies would suggest that subjects with greatest symptoms at baseline may have the greatest violation of expectancy to danger when undergoing exposure based psychotherapy; thus treatment approaches which enhanced the learning under these conditions would be optimal for those with maximal baseline cue-dependent reactivity. However methods to study this hypothesis objectively are lacking. Virtual reality (VR) methodologies have been successfully employed as an enhanced form of imaginal prolonged exposure therapy for the treatment of PTSD. Our goal was to examine the predictive nature of initial psychophysiological (e.g., startle, skin conductance, heart rate) and stress hormone responses (e.g., cortisol) during presentation of VR-based combat-related stimuli on PTSD treatment outcome. Combat veterans with PTSD underwent 6 weeks of VR exposure therapy combined with either d-cycloserine (DCS), alprazolam (ALP), or placebo (PBO). In the DCS group, startle response to VR scenes prior to initiation of treatment accounted for 76% of the variance in CAPS change scores, p < 0.001, in that higher responses predicted greater changes in symptom severity over time. Additionally, baseline cortisol reactivity was inversely associated with treatment response in the ALP group, p = 0.04. We propose that baseline cue-activated physiological measures will be sensitive to predicting patients' level of response to exposure therapy, in particular in the presence of enhancement (e.g., DCS). Published by Elsevier Ltd.

Performance of Remotely Controlled Mandibular Protrusion Sleep Studies for Prediction of Oral Appliance Treatment Response

PubMed Central

Sutherland, Kate; Ngiam, Joachim; Cistulli, Peter A.

2017-01-01

Study Objectives: Mandibular protrusion during sleep monitoring has been proposed as a method to predict oral appliance treatment outcome. A commercial remotely controlled mandibular protrusion (RCMP) device has become available for this purpose with predictive accuracy demonstrated in an initial study. Our aim was to validate this RCMP method for oral appliance treatment outcome prediction in a clinical sleep laboratory setting. Methods: Forty-two obstructive sleep apnea (OSA) patients (apnea-hypopnea index [AHI] > 10 events/h) were recruited to undergo a RCMP sleep study before commencing oral appliance treatment. The RCMP study was used to make a prediction of treatment “Success” or “Failure” based on a rule of ≤ 1 respiratory event per 5 min supine rapid eye movement sleep. Oral appliance treatment response was verified by polysomonography and defined as treatment AHI < 10 events/h with 50% reduction. Results: Participants were on average middle-aged (57.1 ± 11.6 y) and overweight (29.6 ± 4.5 kg/m2) with baseline AHI 31.5 ± 20.5 events/h, 39% severe OSA (AHI > 30 events/h). Two participants (5%) were not able to tolerate the RCMP study. Oral appliance treatment outcome was verified in 33 participants (RCMP results: “Success” n = 10, “Failure” n = 15, “Inconclusive” n = 8). In those with a treatment outcome prediction (n = 25) the diagnostic characteristics of the RCMP test were sensitivity 81.8%, specificity 92.9%, positive predictive value 90%, and negative predictive value 86.7% (n = 3 misclassified). Conclusions: The RCMP device was well tolerated by patients and successfully used to perform mandibular protrusion sleep studies in our sleep laboratory. The RCMP sleep study showed good accuracy as a prediction technique for oral appliance treatment outcome, although there was a high rate of inconclusive tests. Citation: Sutherland K, Ngiam J, Cistulli PA. Performance of remotely controlled mandibular protrusion sleep studies for prediction of oral appliance treatment response. J Clin Sleep Med. 2017;13(3):411–417. PMID:27923436

Predicting Treatment Response in Social Anxiety Disorder From Functional Magnetic Resonance Imaging

PubMed Central

Doehrmann, Oliver; Ghosh, Satrajit S.; Polli, Frida E.; Reynolds, Gretchen O.; Horn, Franziska; Keshavan, Anisha; Triantafyllou, Christina; Saygin, Zeynep M.; Whitfield-Gabrieli, Susan; Hofmann, Stefan G.; Pollack, Mark; Gabrieli, John D.

2013-01-01

Context Current behavioral measures poorly predict treatment outcome in social anxiety disorder (SAD). To our knowledge, this is the first study to examine neuroimaging-based treatment prediction in SAD. Objective To measure brain activation in patients with SAD as a biomarker to predict subsequent response to cognitive behavioral therapy (CBT). Design Functional magnetic resonance imaging (fMRI) data were collected prior to CBT intervention. Changes in clinical status were regressed on brain responses and tested for selectivity for social stimuli. Setting Patients were treated with protocol-based CBT at anxiety disorder programs at Boston University or Massachusetts General Hospital and underwent neuroimaging data collection at Massachusetts Institute of Technology. Patients Thirty-nine medication-free patients meeting DSM-IV criteria for the generalized subtype of SAD. Interventions Brain responses to angry vs neutral faces or emotional vs neutral scenes were examined with fMRI prior to initiation of CBT. Main Outcome Measures Whole-brain regression analyses with differential fMRI responses for angry vs neutral faces and changes in Liebowitz Social Anxiety Scale score as the treatment outcome measure. Results Pretreatment responses significantly predicted subsequent treatment outcome of patients selectively for social stimuli and particularly in regions of higher-order visual cortex. Combining the brain measures with information on clinical severity accounted for more than 40% of the variance in treatment response and substantially exceeded predictions based on clinical measures at baseline. Prediction success was unaffected by testing for potential confounding factors such as depression severity at baseline. Conclusions The results suggest that brain imaging can provide biomarkers that substantially improve predictions for the success of cognitive behavioral interventions and more generally suggest that such biomarkers may offer evidence-based, personalized medicine approaches for optimally selecting among treatment options for a patient. PMID:22945462

Vulnerabilities in Older Patients when Cancer Treatment is Initiated: Does a Cognitive Impairment Impact the Two-Year Survival?

PubMed Central

Borghgraef, Cindy; Etienne, Anne-Marie; Merckaert, Isabelle; Paesmans, Marianne; Reynaert, Christine; Roos, Myriam; Slachmuylder, Jean-Louis; Vandenbossche, Sandrine; Bron, Dominique; Razavi, Darius

2016-01-01

Introduction Dementia is a known predictor of shorter survival times in older cancer patients. However, no empirical evidence is available to determine how much a cognitive impairment shortens survival in older patients when cancer treatment is initiated. Purpose To longitudinally investigate how much a cognitive impairment detected at the initiation of cancer treatment influences survival of older patients during a two-year follow-up duration and to compare the predictive value of a cognitive impairment on patients survival with the predictive value of other vulnerabilities associated with older age. Methods Three hundred and fifty-seven consecutive patients (≥65 years old) admitted for breast, prostate, or colorectal cancer surgeries were prospectively recruited. A cognitive impairment was assessed with the Montreal Cognitive Assessment (MoCA<26). Socio-demographic, disease-related, and geriatric vulnerabilities were assessed using validated tools. Univariate and subsequent multivariate Cox proportional hazards models stratified for diagnosis (breast/prostate cancer versus colorectal cancer) and disease status (metastatic versus non-metastatic) were used. Results A cognitive impairment was detected in 46% (n = 163) of patients. Survival was significantly influenced by a cognitive impairment (HR = 6.13; 95% confidence interval [CI] = 2.07–18.09; p = 0.001), a loss in instrumental autonomy (IADL ≤7) (HR = 3.06; 95% CI = 1.31–7.11; p = 0.009) and fatigue (Mob-T<5) (HR = 5.98; 95% CI = 2.47–14.44; p <0.001). Conclusions During the two years following cancer treatment initiation, older patients with a cognitive impairment were up to six times more likely to die than patients without. Older patients should be screened for cognitive impairments at cancer treatment initiation to enable interventions to reduce morbidity and mortality. Further studies should address processes underlying the relationship between cognitive impairments and an increased risk of dying in older cancer patients. PMID:27479248

Predictive factors for rebleeding and death in alcoholic cirrhotic patients with acute variceal bleeding: a multivariate analysis.

PubMed

Krige, Jake E J; Kotze, Urda K; Distiller, Greg; Shaw, John M; Bornman, Philippus C

2009-10-01

Bleeding from esophageal varices is a leading cause of death in alcoholic cirrhotic patients. The aim of the present single-center study was to identify risk factors predictive of variceal rebleeding and death within 6 weeks of initial treatment. Univariate and multivariate analyses were performed on 310 prospectively documented alcoholic cirrhotic patients with acute variceal hemorrhage (AVH) who underwent 786 endoscopic variceal injection treatments between January 1984 and December 2006. All injections were administered during the first 6 weeks after the patients were treated for their first variceal bleed. Seventy-five (24.2%) patients experienced a rebleed, 38 within 5 days of the initial treatment and 37 within 6 weeks of their initial treatment. Of the 15 variables studied and included in a multivariate analysis using a logistic regression model, a bilirubin level >51 mmol/l and transfusion of >6 units of blood during the initial hospital admission were predictors of variceal rebleeding within the first 6 weeks. Seventy-seven (24.8%) patients died, 29 (9.3%) within 5 days and 48 (15.4%) between 6 and 42 days after the initial treatment. Stepwise multivariate logistic regression analysis showed that six variables were predictors of death within the first 6 weeks: encephalopathy, ascites, bilirubin level >51 mmol/l, international normalized ratio (INR) >2.3, albumin <25 g/l, and the need for balloon tube tamponade. Survival was influenced by the severity of liver failure, with most deaths occurring in Child-Pugh grade C patients. Patients with AVH and encephalopathy, ascites, bilirubin levels >51 mmol/l, INR >2.3, albumin <25 g/l and who require balloon tube tamponade are at increased risk of dying within the first 6 weeks. Bilirubin levels >51 mmol/l and transfusion of >6 units of blood were predictors of variceal rebleeding.

Influence of timing and dose of thyroid hormone replacement on mental, psychomotor, and behavioral development in children with congenital hypothyroidism.

PubMed

Bongers-Schokking, Jacoba J; de Muinck Keizer-Schrama, Sabine M P F

2005-12-01

To evaluate the influence of initial and postinitial treatment factors on cognitive, psychomotor, and psychological outcome in schoolchildren with congenital hypothyroidism (CH). We studied 45 patients (19 with severe CH and 26 with mild CH) and 37 control children by correlating initial and postinitial treatment factors (free thyroxine and thyroid-stimulating hormone [TSH] concentrations, and the percentage of overtreatment and undertreatment periods) with the results of neuropsychological tests and behavior (as reported on the Teacher Report Form [TRF]). The global IQ of the children with CH was comparable to that of the controls; visuomotor and verbal scores were lower, and total TRF scores were higher. Ethnic group, previous development, and overtreatment predicted IQ and verbal scores, with higher scores seen for the overtreated patients than for the control children and those patients who had not been overtreated. As initial treatment was less satisfactory, total TRF scores were higher. Our study suggests that initial and postinitial suboptimal treatment of CH leads to abnormalities in IQ and specific fields. Overtreatment may advance cognitive development in 5-1/2- to 7-year-olds. Suboptimal initial treatment may lead to behavioral problems. We recommend that TSH concentrations be maintained within the normal range in patients with CH.

The value of initial cavitation to predict re-treatment with pulmonary tuberculosis.

PubMed

Huang, Qiusheng; Yin, Yongmei; Kuai, Shougang; Yan, Yan; Liu, Jun; Zhang, YingYing; Shan, Zhongbao; Gu, Lan; Pei, Hao; Wang, Jun

2016-05-06

Pulmonary cavitation is the classic hallmark of pulmonary tuberculosis (PTB) and is the site of very high mycobacterial burden associated with antimycobacterial drug resistance and treatment failure. The objective of this study was to investigate the relationship between re-treatment PTB and initial pulmonary cavitation coordinated with other clinical factors. We conducted a case-control study of 291 newly diagnosed cases of pulmonary TB in The Infectious Hospital of Wuxi from Dec 2009 to Dec 2011 with complete follow-up information until December 31st of 2014. 68 patients were followed-up with PTB re-treatment; the rest of the PTB patients (n = 223) had completed anti-TB treatment, and cured without re-treatment were selected as controls. The univariate analysis [hazard ratio (HR) 1.885, 95 % CI 1.170-3.035, P = 0.009] and the multivariable analysis (HR 2.242, 95 % CI 1.294-3.882, P = 0.004) demonstrated that the initial pulmonary cavitation was a prognostic predictor for TB re-treatment. Additionally, the re-treatment rates in PTB patients with cavitation and no-cavitation were 27.1 and 15.5 %, respectively, with significant difference (log-rank test; P = 0.010). Other factors, age of ≥60 and history of smoking, were also prognostic variables. Initial pulmonary cavitation of chest X-ray was a significant predictor for PTB re-treatment.

Predicting dropout in adolescents receiving therapy for depression.

PubMed

O'Keeffe, Sally; Martin, Peter; Goodyer, Ian M; Wilkinson, Paul; Consortium, Impact; Midgley, Nick

2017-10-30

Therapy dropout is a common occurrence, especially in adolescence. This study investigated whether dropout could be predicted from a range of child, family, and treatment factors in a sample of adolescents receiving therapy for depression. This study draws on data from 406 participants of the IMPACT study, a randomized controlled trial, investigating three types of therapy in the treatment of adolescent depression. Logistic regression was used to estimate the effects of predictors on the odds of dropout. Few pre-treatment predictors of dropout were found, with the only significant predictors being older age, antisocial behaviour, and lower scores of verbal intelligence. Missed sessions and poorer therapeutic alliance early in treatment also predicted dropout. Most child and family factors investigated were not significantly associated with dropout. There may be little about depressed adolescents' presentation prior to therapy starting that indicates their risk of dropout. However, within-treatment factors indicated that warning signs of dropout may be identifiable during the initial phase of therapy. Identifying and targeting early treatment indicators of dropout may provide possibilities for improving engagement. Clinical and methodological significance of this article: In the literature, a great deal of attention has been paid to child and family factors that predict therapy dropout, yet in this study, few pre-treatment characteristics were predictive of dropout. However, findings revealed possible warning signs of dropout in the early part of treatment, as poor therapeutic alliance and missed sessions were both found to be predictive of dropout. These findings call for therapists to be aware of such warning signs and clinical guidelines for managing cases at risk of dropout are warranted.

Predicting factors of fistula healing and clinical remission after infliximab-based combined therapy for perianal fistulizing Crohn's disease.

PubMed

Tougeron, David; Savoye, Guillaume; Savoye-Collet, Céline; Koning, Edith; Michot, Francis; Lerebours, Eric

2009-08-01

Perianal fistulizing Crohn's disease (PFCD) treatment is based on fistula drainage, antibiotics, immunosuppressant (IS) drugs, and infliximab. Our aim was to study the effectiveness of combination therapy on PFCD and to search for clinical or imaging features associated with the initial complete clinical response and its stability overtime. All patients with PFCD treated in our tertiary center between 2000 and 2005 by infliximab in combination with seton placement and/or IS and evaluated by MRI before treatment were included in the study. Basal clinical and MRI characteristics were recorded. Response to treatment was evaluated after the infliximab induction regiment and at the end of the follow-up. Twenty-six patients were included and followed-up for an average 4.9 years. A complex fistula was present in 69% (18/26 patients) of cases and eight (8/26 patients) had an ano-vaginal fistula. After infliximab induction therapy, 13 patients (50%) achieved a complete clinical response. The initial clinical response was significantly associated with the absence of both, active intestinal disease (54% vs. 8%, P = 0.03) and active proctitis (77% vs. 23%, P = 0.01). No initial MRI characteristics were linked to the initial response. In multivariate analysis, only the presence of active proctitis was associated with the lack of response (P = 0.047). At the end of the follow-up, 42% of the patients remained in clinical remission. No clinical characteristics were associated to sustained response when among long-standing responders two exhibited a normal post-treatment MRI. An initial complete response of PFCD was observed in half of the patients after combined therapy including infliximab that decreased to 42% later on. Complete healing of fistulas on MRI was possible but unusual. The initial response seemed related to the absence of active intestinal disease, especially in the rectum, when the long-term response could not be predicted by the basal characteristics of patients.

Governing Laws of Complex System Predictability under Co-evolving Uncertainty Sources: Theory and Nonlinear Geophysical Applications

NASA Astrophysics Data System (ADS)

Perdigão, R. A. P.

2017-12-01

Predictability assessments are traditionally made on a case-by-case basis, often by running the particular model of interest with randomly perturbed initial/boundary conditions and parameters, producing computationally expensive ensembles. These approaches provide a lumped statistical view of uncertainty evolution, without eliciting the fundamental processes and interactions at play in the uncertainty dynamics. In order to address these limitations, we introduce a systematic dynamical framework for predictability assessment and forecast, by analytically deriving governing equations of predictability in terms of the fundamental architecture of dynamical systems, independent of any particular problem under consideration. The framework further relates multiple uncertainty sources along with their coevolutionary interplay, enabling a comprehensive and explicit treatment of uncertainty dynamics along time, without requiring the actual model to be run. In doing so, computational resources are freed and a quick and effective a-priori systematic dynamic evaluation is made of predictability evolution and its challenges, including aspects in the model architecture and intervening variables that may require optimization ahead of initiating any model runs. It further brings out universal dynamic features in the error dynamics elusive to any case specific treatment, ultimately shedding fundamental light on the challenging issue of predictability. The formulated approach, framed with broad mathematical physics generality in mind, is then implemented in dynamic models of nonlinear geophysical systems with various degrees of complexity, in order to evaluate their limitations and provide informed assistance on how to optimize their design and improve their predictability in fundamental dynamical terms.

Interrelated effects of substance use diagnosis, race, and smoking severity on abstinence initiation in dually dependent male smokers: results of a retrospective chart review.

PubMed

Heffner, Jaimee L; Blom, Thomas J; Camerota, Elaine; Sansone, Linda E; Bodie, Linda; Smith, Joshua; Lin, Show; Drake, J Michael; Meyer, Corey; Anthenelli, Robert M

2007-12-01

: Study goals were 2-fold: 1) to examine differences in demographic and clinical characteristics of smokers who fell into 3 diagnostic groups: alcohol abuse/dependence only (ALC), cocaine abuse/dependence only (COC), and mixed alcohol and cocaine abuse/dependence (ALC + COC); and 2) to determine the degree to which diagnostic grouping predicted short-term abstinence from smoking. : Retrospective chart reviews were conducted by using the treatment records of male veterans (N = 175) who participated in a voluntary smoking cessation program during their stay in residential substance dependence treatment. : The ALC group smoked more heavily, had higher levels of nicotine dependence, and reported more emotional problems than the other 2 groups. Short-term abstinence rates were high across the 3 groups (38%, 58%, and 57% for the ALC, COC, and ALC + COC groups, respectively). Lighter smoking at treatment entry, non-white race, and a diagnosis of cocaine abuse/dependence (with or without alcohol abuse/dependence) predicted short-term abstinence in the program. : Substance misusers motivated to quit smoking can initiate smoking abstinence at relatively high rates with the aid of combined pharmacotherapy and intensive group counseling. White subjects who smoke more heavily and have a diagnosis of alcohol abuse/dependence only have lower success rates for abstinence initiation.

Clinical and Genetic Determinants of Warfarin Pharmacokinetics and Pharmacodynamics during Treatment Initiation

PubMed Central

Gong, Inna Y.; Schwarz, Ute I.; Crown, Natalie; Dresser, George K.; Lazo-Langner, Alejandro; Zou, GuangYong; Roden, Dan M.; Stein, C. Michael; Rodger, Marc; Wells, Philip S.; Kim, Richard B.; Tirona, Rommel G.

2011-01-01

Variable warfarin response during treatment initiation poses a significant challenge to providing optimal anticoagulation therapy. We investigated the determinants of initial warfarin response in a cohort of 167 patients. During the first nine days of treatment with pharmacogenetics-guided dosing, S-warfarin plasma levels and international normalized ratio were obtained to serve as inputs to a pharmacokinetic-pharmacodynamic (PK-PD) model. Individual PK (S-warfarin clearance) and PD (Imax) parameter values were estimated. Regression analysis demonstrated that CYP2C9 genotype, kidney function, and gender were independent determinants of S-warfarin clearance. The values for Imax were dependent on VKORC1 and CYP4F2 genotypes, vitamin K status (as measured by plasma concentrations of proteins induced by vitamin K absence, PIVKA-II) and weight. Importantly, indication for warfarin was a major independent determinant of Imax during initiation, where PD sensitivity was greater in atrial fibrillation than venous thromboembolism. To demonstrate the utility of the global PK-PD model, we compared the predicted initial anticoagulation responses with previously established warfarin dosing algorithms. These insights and modeling approaches have application to personalized warfarin therapy. PMID:22114699

Psychological distress and in vitro fertilization outcome.

PubMed

Pasch, Lauri A; Gregorich, Steven E; Katz, Patricia K; Millstein, Susan G; Nachtigall, Robert D; Bleil, Maria E; Adler, Nancy E

2012-08-01

To examine whether psychological distress predicts IVF treatment outcome as well as whether IVF treatment outcome predicts subsequent psychological distress. Prospective cohort study over an 18-month period. Five community and academic fertility practices. Two hundred two women who initiated their first IVF cycle. Women completed interviews and questionnaires at baseline and at 4, 10, and 18 months' follow-up. IVF cycle outcome and psychological distress. In a binary logistic model including covariates (woman's age, ethnicity, income, education, parity, duration of infertility, and time interval), pretreatment depression and anxiety were not significant predictors of the outcome of the first IVF cycle. In linear regression models including covariates (woman's age, income, education, parity, duration of infertility, assessment point, time since last treatment cycle, and pre-IVF depression or anxiety), experiencing failed IVF was associated with higher post-IVF depression and anxiety. IVF failure predicts subsequent psychological distress, but pre-IVF psychological distress does not predict IVF failure. Instead of focusing efforts on psychological interventions specifically aimed at improving the chance of pregnancy, these findings suggest that attention be paid to helping patients prepare for and cope with treatment and treatment failure. Copyright © 2012 American Society for Reproductive Medicine. Published by Elsevier Inc. All rights reserved.

Effect of initial pH on anaerobic co-digestion of kitchen waste and cow manure.

PubMed

Zhai, Ningning; Zhang, Tong; Yin, Dongxue; Yang, Gaihe; Wang, Xiaojiao; Ren, Guangxin; Feng, Yongzhong

2015-04-01

This study investigated the effects of different initial pH (6.0, 6.5, 7.0, 7.5 and 8.0) and uncontrolled initial pH (CK) on the lab-scale anaerobic co-digestion of kitchen waste (KW) with cow manure (CM). The variations of pH, alkalinity, volatile fatty acids (VFAs) and total ammonia nitrogen (NH4(+)-N) were analyzed. The modified Gompertz equation was used for selecting the optimal initial pH through comprehensive evaluation of methane production potential, degradation of volatile solids (VS), and lag-phase time. The results showed that CK and the fermentation with initial pH of 6.0 failed. The pH values of the rest treatments reached 7.7-7.9 with significantly increased methane production. The predicted lag-phase times of treatments with initial pH of 6.5 and 7.5 were 21 and 22 days, which were 10 days shorter than the treatments with initial pH of 7.0 and 8.0, respectively. The maximum methane production potential (8579 mL) and VS degradation rate (179.8 mL/g VS) were obtained when the initial pH was 7.5, which is recommended for co-digestion of KW and CM. Copyright © 2015 Elsevier Ltd. All rights reserved.

Sex differences in the relation of weight loss self-efficacy, binge eating, and depressive symptoms to weight loss success in a residential obesity treatment program.

PubMed

Presnell, Katherine; Pells, Jennifer; Stout, Anna; Musante, Gerard

2008-04-01

The aim of the current study was to examine whether weight loss self-efficacy, binge eating, and depressive symptoms predicted weight loss during treatment, and whether gender moderates these associations with prospective data from 297 participants (223 women and 74 men) enrolled in a residential obesity treatment program. Men reported higher initial levels of self-efficacy than women, whereas women reported greater pre-treatment levels of binge eating and depressive symptoms. Higher pre-treatment levels of weight control self-efficacy, binge eating, and depressive symptoms predicted greater weight loss in men, but not in women. Results suggest that certain psychological and behavioral factors should be considered when implementing weight loss interventions, and indicate a need to consider gender differences in predictors of weight loss treatment. Future research should seek to identify predictors of weight loss among women.

False Positive Positron Emission Tomography / Computed Tomography Scans in Treated Head and Neck Cancers

PubMed Central

Cheung, Michael K; Ong, Shawn Y; Goyal, Uma; Wertheim, Betsy C; Hsu, Charles C

2017-01-01

Objective Positron emission tomography/computed tomography (PET/CT) imaging for head and neck cancers (HNC) is commonly utilized for post-treatment assessment. Though PET/CT in this setting has been reported to have high negative predictive values (> 90%), positive predictive values have been reported at approximately 50%, leading to high rates of false positivity (FP) and troubling management decisions for both patient and practitioner. The objective of this study was to identify patient, disease, treatment and imaging factors that might be associated with a higher likelihood of FP on initial post-treatment PET/CT imaging for patients treated for HNC.  Materials and methods A retrospective chart review was performed on 84 patients treated for HNC who received radiation therapy (RT) as part of their overall management from October 2005 to August 2013. Of the patients screened, 19 were found to have mucosally based squamous cell carcinoma (SCC) with positive initial post-treatment PET/CT studies (23%). Fisher’s exact test was used to analyze the association between categorical variables and FP, including patient's gender, disease laterality, primary tumor site and stage, nodal and overall stage, high dose RT fraction size, number of RT fractions completed, total RT dose, biologically effective dose and timing of PET/CT acquisition. Wilcoxon rank-sum test was used to analyze the association between continuous variables and FP, including patient age, total elapsed days of RT, an amount of infused fluorodeoxyglucose 18F-FDG, pre-PET/CT serum glucose levels, and maximum standardized uptake value SUVmax. Statistically significant findings were those that were deemed p <0.05. Results Among patients with positive initial post-treatment PET/CT scans for treated HNC, there was a lower proportion of higher primary disease stage associated with FP versus true positivity (T-stage 3-4: 20 vs 78%, respectively, p=0.023). We also discovered that 50% of patients that underwent confirmation for FP findings suffered serious complications as a direct consequence of invasive exploratory procedures. Conclusions Although PET/CT is known for its exceptional negative predictive value (> 90%) in the post-treatment setting for HNC, high rates of FP remains a clinical challenge. Our study suggests that tumor stage (T-stage) may impact FP rates in positive initial post-treatment PET/CT scans. We recommend careful multidisciplinary discussion regarding positive PET/CT studies in the post-treatment setting for HNC, particularly if invasive intervention is considered. PMID:28497009

A Randomized Clinical Trial of Methadone Maintenance for Prisoners: Prediction of Treatment Entry and Completion in Prison

ERIC Educational Resources Information Center

Gordon, Michael S.; Kinlock, Timothy W.; Couvillion, Kathryn A.; Schwartz, Robert P.; O'Grady, Kevin

2012-01-01

The present report is an intent-to-treat analysis involving secondary data drawn from the first randomized clinical trial of prison-initiated methadone in the United States. This study examined predictors of treatment entry and completion in prison. A sample of 211 adult male prerelease inmates with preincarceration heroin dependence were randomly…

CSF tau and tau/Aβ42 predict cognitive decline in Parkinson's disease.

PubMed

Liu, Changqin; Cholerton, Brenna; Shi, Min; Ginghina, Carmen; Cain, Kevin C; Auinger, Peggy; Zhang, Jing

2015-03-01

A substantial proportion of patients with Parkinson's disease (PD) have concomitant cognitive dysfunction. Identification of biomarker profiles that predict which PD patients have a greater likelihood for progression of cognitive symptoms is pressingly needed for future treatment and prevention approaches. Subjects were drawn from the Deprenyl and Tocopherol Antioxidative Therapy of Parkinsonism (DATATOP) study, a large clinical trial that enrolled initially untreated PD patients. For the current study, Phase One encompassed trial baseline until just prior to levodopa administration (n = 403), and Phase Two spanned the initiation of levodopa treatment until the end of cognitive follow-up (n = 305). Correlations and linear mixed models were performed to determine cross-sectional and longitudinal associations between baseline amyloid β1-42 (Aβ42), total tau (t-tau), and phosphorylated tau (p-tau) in cerebrospinal fluid (CSF) and measures of memory and executive function. Analyses also considered APOE genotype and tremor- vs. rigidity-dominant phenotype. No association was found between baseline CSF biomarkers and cognitive test performance during Phase One. However, once levodopa treatment was initiated, higher p-tau and p-tau/Aβ42 predicted subsequent decline on cognitive tasks involving both memory and executive functions. The interactions between biomarkers and cognition decline did not appear to be influenced by levodopa dosage, APOE genotype or motor phenotype. The current study has, for the first time, demonstrated the possible involvement of tau species, whose gene (MAPT) has been consistently linked to the risk of PD by genome-wide association studies, in the progression of cognitive symptoms in PD. Copyright © 2015 Elsevier Ltd. All rights reserved.

Promoting Homework Adherence in Cognitive-Behavioral Therapy for Adolescent Depression

PubMed Central

Jungbluth, Nathaniel J.; Shirk, Stephen R.

2012-01-01

Objective This study used prospective, observational methods to evaluate six features of therapist behavior as predictors of homework adherence in cognitive-behavioral therapy (CBT) for adolescent depression, with the goal of identifying therapist strategies with the potential to improve adolescent adherence. Therapist behaviors were expected to interact with initial levels of client resistance or adherence to predict subsequent homework completion. Method Participants were 50 referred adolescents (33 females, 54% ethnic minority) ages 14–18 (M=15.9) meeting diagnostic criteria for a depressive disorder, and without co-morbid psychotic disorder, bipolar disorder, autism spectrum disorder, intellectual disability, or concurrent treatments. Therapist homework-related behaviors were coded from audiotapes of Sessions 1 and 2 and used to predict adolescents’ homework adherence, coded from audiotapes of Sessions 2 and 3. Results Several therapist behaviors were predictive of subsequent homework adherence, particularly for initially resistant or non-adherent adolescents. Stronger homework rationale and greater time allocated to explaining homework in Session 1 predicted greater adherence at Session 2, particularly for initially resistant adolescents. Stronger rationale and eliciting reactions/troubleshooting obstacles in Session 2 predicted greater adherence at Session 3, particularly for adolescents who were less adherent to prior homework. Conclusions Strategies such as providing a strong rationale, allocating more time to assigning homework, and eliciting reactions/troubleshooting obstacles may be effective ways to bolster homework adherence among initially less engaged, depressed teens. PMID:23237021

Promoting homework adherence in cognitive-behavioral therapy for adolescent depression.

PubMed

Jungbluth, Nathaniel J; Shirk, Stephen R

2013-01-01

This study used prospective, observational methods to evaluate six features of therapist behavior as predictors of homework adherence in cognitive-behavioral therapy for adolescent depression, with the goal of identifying therapist strategies with the potential to improve adolescent adherence. Therapist behaviors were expected to interact with initial levels of client resistance or adherence to predict subsequent homework completion. Participants were 50 referred adolescents (33 female, 54% ethnic minority) ages 14 to 18 (M = 15.9) meeting diagnostic criteria for a depressive disorder, and without comorbid psychotic disorder, bipolar disorder, autism spectrum disorder, intellectual disability, or concurrent treatments. Therapist homework-related behaviors were coded from audiotapes of Sessions 1 and 2 and used to predict adolescents' homework adherence, coded from audiotapes of Sessions 2 and 3. Several therapist behaviors were predictive of subsequent homework adherence, particularly for initially resistant or nonadherent adolescents. Stronger homework rationale and greater time allocated to explaining homework in Session 1 predicted greater adherence at Session 2, particularly for initially resistant adolescents. Stronger rationale and eliciting reactions/troubleshooting obstacles in Session 2 predicted greater adherence at Session 3, particularly for adolescents who were less adherent to prior homework. Strategies such as providing a strong rationale, allocating more time to assigning homework, and eliciting reactions/troubleshooting obstacles may be effective ways to bolster homework adherence among initially less engaged, depressed teens.

Do personality traits predict outcome of psychodynamically oriented psychosomatic inpatient treatment beyond initial symptoms?

PubMed

Steinert, Christiane; Klein, Susanne; Leweke, Frank; Leichsenring, Falk

2015-03-01

Whether personality characteristics have an impact on treatment outcome is an important question in psychotherapy research. One of the most common approaches for the description of personality is the five-factor model of personality. Only few studies investigated whether patient personality as measured with the NEO-Five-Factor Inventory (NEO-FFI, Costa & McCrae [1992b]. Revised NEO-PI-R and NEO-FFI. Professional manual. Odessa, FL: Psychological Assessment Recources) predicts outcome. Results were inconsistent. Studies reporting personality to be predictive of outcome did not control for baseline symptoms, while studies controlling initial symptoms could not support these findings. We hypothesized that after taking into account baseline symptoms, the NEO-FFI would not predict outcome and tested this in a large sample of inpatients at a psychosomatic clinic. Naturalistic, non-controlled study using patients' data for multiple regression analysis to identify predictors of outcome. Data of 254 inpatients suffering primarily from depressive, anxiety, stress, and somatoform disorders were analysed. Personality was assessed at the beginning of therapy. For psychotherapy outcome, changes in anxiety and depression (Hospital Anxiety and Depression Scale; HADS), overall psychopathology (Symptom Checklist-90-R Global Severity Index [GSI]), and interpersonal problems (Inventory of Interpersonal Problems; IIP) were measured. The treatment resulted in significant decreases on all outcome measures corresponding to moderate to large effect sizes (HADS: d = 1.03; GSI: d = 0.90; IIP: d = 0.38). Consistent with our hypothesis, none of the personality domains predicted outcome when baseline symptoms were controlled for. Personality assessment at baseline does not seem to have an added value in the prediction of inpatient psychotherapy outcome beyond initial symptoms. Clinical implications Personality dimensions overlap with symptomatic distress. Rather than serve as predictors of outcome, the domains tapped by the NEO-FFI reflect current psychological symptomatology in inpatients with depressive, anxiety, stress or somatoform disorders. From a clinician's point of view monitoring individual progress by using actuarial measures is more valuable than trying to predict who will benefit from treatment using personality assessments. Limitations of the study Diagnostic assessment was solely based on clinical evaluation rather than structured interviews. Twenty-five per cent of the original sample had to be excluded due to missing data. There was a focus on only one set of client characteristics (i.e., five-factor model personality traits). Assessment of personality domains in the acute phase of a mental disorder may be problematic and could have influenced findings. © 2014 The British Psychological Society.

Changes in Gene Expression Predicting Local Control in Cervical Cancer: Results from Radiation Therapy Oncology Group 0128

PubMed Central

Weidhaas, Joanne B.; Li, Shu-Xia; Winter, Kathryn; Ryu, Janice; Jhingran, Anuja; Miller, Bridgette; Dicker, Adam P.; Gaffney, David

2009-01-01

Purpose To evaluate the potential of gene expression signatures to predict response to treatment in locally advanced cervical cancer treated with definitive chemotherapy and radiation. Experimental Design Tissue biopsies were collected from patients participating in Radiation Therapy Oncology Group (RTOG) 0128, a phase II trial evaluating the benefit of celecoxib in addition to cisplatin chemotherapy and radiation for locally advanced cervical cancer. Gene expression profiling was done and signatures of pretreatment, mid-treatment (before the first implant), and “changed” gene expression patterns between pre- and mid-treatment samples were determined. The ability of the gene signatures to predict local control versus local failure was evaluated. Two-group t test was done to identify the initial gene set separating these end points. Supervised classification methods were used to enrich the gene sets. The results were further validated by leave-one-out and 2-fold cross-validation. Results Twenty-two patients had suitable material from pretreatment samples for analysis, and 13 paired pre- and mid-treatment samples were obtained. The changed gene expression signatures between the pre- and mid-treatment biopsies predicted response to treatment, separating patients with local failures from those who achieved local control with a seven-gene signature. The in-sample prediction rate, leave-one-out prediction rate, and 2-fold prediction rate are 100% for this seven-gene signature. This signature was enriched for cell cycle genes. Conclusions Changed gene expression signatures during therapy in cervical cancer can predict outcome as measured by local control. After further validation, such findings could be applied to direct additional therapy for cervical cancer patients treated with chemotherapy and radiation. PMID:19509178

Prealbumin, platelet factor 4 and S100A12 combination at baseline predicts good response to TNF alpha inhibitors in Rheumatoid Arthritis.

PubMed

Nguyen, Minh Vu Chuong; Baillet, Athan; Romand, Xavier; Trocmé, Candice; Courtier, Anaïs; Marotte, Hubert; Thomas, Thierry; Soubrier, Martin; Miossec, Pierre; Tébib, Jacques; Grange, Laurent; Toussaint, Bertrand; Lequerré, Thierry; Vittecoq, Olivier; Gaudin, Philippe

2018-06-06

Tumour necrosis factor-alpha inhibitors (TNFi) are effective treatments for Rheumatoid Arthritis (RA). Responses to treatment are barely predictable. As these treatments are costly and may induce a number of side effects, we aimed at identifying a panel of protein biomarkers that could be used to predict clinical response to TNFi for RA patients. Baseline blood levels of C-reactive protein, platelet factor 4, apolipoprotein A1, prealbumin, α1-antitrypsin, haptoglobin, S100A8/A9 and S100A12 proteins in bDMARD naive patients at the time of TNFi treatment initiation were assessed in a multicentric prospective French cohort. Patients fulfilling good EULAR response at 6 months were considered as responders. Logistic regression was used to determine best biomarker set that could predict good clinical response to TNFi. A combination of biomarkers (prealbumin, platelet factor 4 and S100A12) was identified and could predict response to TNFi in RA with sensitivity of 78%, specificity of 77%, positive predictive values (PPV) of 72%, negative predictive values (NPV) of 82%, positive likelihood ratio (LR+) of 3.35 and negative likelihood ratio (LR-) of 0.28. Lower levels of prealbumin and S100A12 and higher level of platelet factor 4 than the determined cutoff at baseline in RA patients are good predictors for response to TNFi treatment globally as well as to Infliximab, Etanercept and Adalimumab individually. A multivariate model combining 3 biomarkers (prealbumin, platelet factor 4 and S100A12) accurately predicted response of RA patients to TNFi and has potential in a daily practice personalized treatment. Copyright © 2018. Published by Elsevier Masson SAS.

Factors predicting survival following noninvasive ventilation in amyotrophic lateral sclerosis.

PubMed

Peysson, S; Vandenberghe, N; Philit, F; Vial, C; Petitjean, T; Bouhour, F; Bayle, J Y; Broussolle, E

2008-01-01

The involvement of respiratory muscles is a major predicting factor for survival in amyotrophic lateral sclerosis (ALS). Recent studies show that noninvasive ventilation (NIV) can relieve symptoms of alveolar hypoventilation. However, factors predicting survival in ALS patients when treated with NIV need to be clarified. We conducted a retrospective study of 33 consecutive ALS patients receiving NIV. Ten patients had bulbar onset. We determined the median survivals from onset, diagnosis and initiation of NIV and factors predicting survival. Statistical analysis was performed using the Kaplan-Meier test and Cox proportional hazard models. The median initial and maximal total uses of NIV were 10 and 14 h/24h. The overall median survival from ALS onset was 34.2 months and worsened with increasing age and bulbar onset of the disease. The median survival from initiation of NIV was 8.4 months and was significantly poorer in patients with advanced age or with airway mucus accumulation. Survival from initiation of NIV was not influenced by respiratory parameters or bulbar symptoms. Advanced age at diagnosis and airway mucus accumulation represent poorer prognostic factors of ALS patients treated with NIV. NIV is a helpful treatment of sleep-disordered breathing, including patients with bulbar involvement. Copyright 2008 S. Karger AG, Basel.

Can a quality-of-life assessment assist in identifying women at risk of prematurely discontinuing IVF treatment? A prospective cohort study utilizing the FertiQoL questionnaire.

PubMed

Neumann, Kay; Kayser, Janna; Depenbusch, Marion; Schultze-Mosgau, Askan; Griesinger, Georg

2018-07-01

This study aimed at assessing quality of life (QoL) by means of a validated measurement tool (FertiQoL) in German infertile patients before a first IVF/ICSI cycle with ancillary assessment of changes in FertiQoL scores after a failed first cycle and the predictive capacity of FertiQoL scores for treatment discontinuation. The validated FertiQoL tool consisting of 24 questions regarding fertility-specific aspects of QoL was used for this prospective cohort study conducted at a university affiliated IVF center in Germany. Female patients (n = 119) filled out the FertiQoL form and questionnaire on sociodemographic variables on initiation of a first- and second-cycle IVF/ICSI treatment, respectively. On initiation of a first IVF/ICSI cycle, the mean scores (± standard deviation) for subscales emotional, mind-body, relational, and social items were 62 (± 19), 75 (± 17), 82 (± 13), and 78 (± 14), respectively; the total FertiQoL score was 73 (± 12). The mean total FertiQoL score at initiation of a first treatment cycle did not differ between patients who continued vs. discontinued treatment in case of no pregnancy achievement in the first cycle (73) (± 10) vs. 74 (± 14), p = 0.46). Furthermore, the mean total FertiQoL score did not change after an unsuccessful first IVF cycle (74 vs. 76, p = 0.46). There was no statistical difference in a small sample size for FertiQoL scores between all groups. In this study, FertiQoL scores were, therefore, not usable to predict withdrawal from infertility treatment.

Utility of MRCP in clinical decision making of suspected choledocholithiasis: An institutional analysis and literature review.

PubMed

Badger, Wesley R; Borgert, Andrew J; Kallies, Kara J; Kothari, Shanu N

2017-08-01

The ideal treatment algorithm for suspected choledocholithiasis is not yet well defined. Imaging options include magnetic resonance cholangiopancreatography (MRCP), endoscopic retrograde cholangiopancreatography (ERCP), and intraoperative cholangiogram (IOC). MRCP is diagnostic, while the other two modalities can also be therapeutic. Each of these modalities for diagnosis and treatment carries its own set of risks, benefits, and institutional costs. We hypothesized that there would be a significant difference between the biochemical profiles and characteristics of patients who undergo ERCP vs. MRCP vs. operative intervention as the initial choice of treatment/imaging modality. We performed a retrospective review of the electronic medical records for all patients with a coded diagnosis of choledocholithiasis from 2011 to 2014. The initial diagnostic modality was assessed for each hospital encounter. The statistical characteristics of MRCP as compared to fluoroscopic imaging of the biliary tree (ERCP, IOC) were analyzed. Overall, 527 hospital encounters were identified. Initial intervention included ERCP in 63%, MRCP in 12%, and cholecystectomy in 25% of patients. Patients undergoing cholecystectomy first, compared to MRCP or ERCP, tended to have lower values for alkaline phosphatase (P < 0.001) and AST (P = 0.002) as well as be of younger age (P < 0.0001). Of the patients that underwent MRCP as their initial procedure, 82% subsequently underwent either ERCP or laparoscopic cholecystectomy. In patients who underwent an initial MRCP followed by either ERCP or IOC, the predictive performance of MRCP was as follows: sensitivity = 0.90, specificity = 0.86, positive predictive value = 0.97, negative predictive value = 0.60, agreement (Cohen's Kappa) = 0.64. There is a significant difference in the laboratory evaluation and demographics of patients undergoing ERCP, MRCP, and laparoscopic cholecystectomy. MRCP was followed with a more invasive test a majority of the time. Since MRCP did not change the management of patients with suspected choledocholithiasis, its utility in this patient population should be questioned. Further research is needed to better define the pretest characteristics which would predict which patients do not need further intervention after MRCP as well as defining the most cost-effective strategy. Copyright © 2016 Elsevier Inc. All rights reserved.

RNA sequencing to predict response to TNF-α inhibitors reveals possible mechanism for nonresponse in smokers.

PubMed

Cuppen, Bart V J; Rossato, Marzia; Fritsch-Stork, Ruth D E; Concepcion, Arno N; Linn-Rasker, Suzanne P; Bijlsma, Johannes W J; van Laar, Jacob M; Lafeber, Floris P J G; Radstake, Timothy R

2018-06-06

Several studies have employed microarray-based profiling to predict response to tumor necrosis factor-alpha inhibitors (TNFi) in rheumatoid arthritis (RA); yet efforts to validate these targets have failed to show predictive abilities acceptable for clinical practice. The eighty most extreme responders and nonresponders to TNFi therapy were selected from the observational BiOCURA cohort. RNA sequencing was performed on mRNA from peripheral blood mononuclear cells (PBMCs) collected before initiation of treatment. The expression of pathways as well as individual gene transcripts between responders and nonresponders was investigated. Promising targets were technically replicated and validated in n = 40 new patients using qPCR assays. Before therapy initiation, nonresponders had lower expression of pathways related to interferon and cytokine signaling, while also showing higher levels of two genes, GPR15 and SEMA6B (p = 0.02). The two targets could be validated, however, additional analyses revealed that GPR15 and SEMA6B did not independently predict response, but were rather dose-dependent markers of smoking (p < 0.0001). The study did not identify new transcripts ready to use in clinical practice, yet GPR15 and SEMA6B were recognized as candidate explanatory markers for the reduced treatment success in RA smokers.

Collagenase injections for treatment of Dupuytren disease.

PubMed

Hentz, Vincent R

2014-02-01

Palmodigital fasciectomy remains the gold standard. The initial outcome is, in my experience, far more predictable than either NA or enzyme fasciotomy (EF). It is also a more durable treatment. NA and EF can be conceptualized as similar procedures--one uses a needle and the other an enzyme to weaken a cord sufficient to be able to rupture it and thus straighten a contracted joint. Both are less invasive and the hand is quick to recover. Both procedures are equally initially effective. CHH seems to offer greater durability. Today’s patients are often better educated and seek a specific type of treatment, in particular, effective nonoperative treatment. Pharmaceutical companies now market directly and effectively to patients, and this strategy and Internet use have already resulted in an increase in the number of patients searching for practitioners willing to administer and capable of administering collagenase treatment. Copyright © 2014 Elsevier Inc. All rights reserved.

Motivation for Treatment and Motivation for Change in Substance-Dependent Patients with Co-Occurring Psychiatric Disorders.

PubMed

de Weert-van Oene, Gerdien H; Gongora, Vanesa; von Sternberg, Kirk; de Jong, Cor A J

2015-01-01

The aims of this study were to examine the relationship between motivation for treatment and for change, and to explore their role in the prediction of treatment completion. The sample was composed of 560 predominantly polydrug-using inpatients with co-occurring psychiatric disorders. Motivation for treatment was assessed with the Motivation for Treatment Scales, and motivation for change was measured with the Readiness to Change Questionnaire. Patients indicated strong motivation to change illegal drug and alcohol use. In initial factor analysis, motivation for treatment and for change did not load on the same factors, confirming that these are distinct domains. Four categories were discerned with respect to readiness for treatment and for change, with low agreement between the two. In performing survival analysis, we found that being in readiness category 4 (RT↑RC↑) was associated with a greater chance of remaining in treatment for a period of 105 days without premature attrition (Log Rank chi-sq=5.000; p=0.02). To a limited extent, intake measures of motivation can be used to predict attrition from treatment. Clinicians can use motivation assessment both for clinical purposes and in the prediction of those who need extra monitoring due to increased risk of premature attrition.

Measuring Motivation: Change Talk and Counter-Change Talk in Cognitive Behavioral Therapy for Generalized Anxiety

PubMed Central

Lombardi, Diana R.; Button, Melissa

2013-01-01

How clients talk about change early in treatment has been found to be a potent predictor of their subsequent treatment success. Studies examining such client motivational language (arguments for and against change) have typically been conducted in the context of motivational interviewing for addictions. The present study examined the capacity of client motivational language to predict treatment outcomes in the context of cognitive behavioral therapy (CBT) for generalized anxiety. Client early in-session statements against change (counter-change talk) were found to be robust predictors of post-treatment worry scores and differentiated treatment responders from nonresponders. Moreover, client motivational language predicted outcomes beyond initial symptom severity and self-report measures of motivation. These results strongly support the relevance of client motivational language outcomes in CBT and provide a foundation for advancing research on motivation for change in a CBT context. PMID:24134594

Measuring motivation: change talk and counter-change talk in cognitive behavioral therapy for generalized anxiety.

PubMed

Lombardi, Diana R; Button, Melissa L; Westra, Henny A

2014-01-01

How clients talk about change early in treatment has been found to be a potent predictor of their subsequent treatment success. Studies examining such client motivational language (arguments for and against change) have typically been conducted in the context of motivational interviewing for addictions. This study examined the capacity of client motivational language to predict treatment outcomes in the context of cognitive behavioral therapy (CBT) for generalized anxiety. Client early in-session statements against change (counter-change talk) were found to be robust predictors of post-treatment worry scores and differentiated treatment responders from nonresponders. Moreover, client motivational language predicted outcomes beyond initial symptom severity and self-report measures of motivation. These results strongly support the relevance of client motivational language outcomes in CBT and provide a foundation for advancing research on motivation for change in a CBT context.

An evaluation of rational-emotive imagery as a component of rational-emotive therapy in the treatment of test anxiety.

PubMed

Hymen, S P; Warren, R

1978-06-01

This study evaluated the efficacy of rational-emotive imagery as a component of rational-emotive therapy in reduction of college students' test anxiety. 11 volunteers met for 6 1-hr. group treatment sessions over a 3-wk. period. After 2 initial treatment sessions subjects were randomly assigned to groups given either rational-emotive therapy with rational-emotive imagery or rational-emotive therapy without imagery. Contrary to predictions, improvement between groups on self-report and performance measures was nonsignificant. Failure to obtain differences was attributed to similarities in content of treatment sessions and short treatment time. Combined groups reported significant improvement on all dependent measures. Although the study did not yield the predicted benefits of the imagery, results lend further support to the efficacy of rational-emotive therapy procedures in the reduction of test anxiety.

Predicting post-traumatic stress disorder treatment response in refugees: Multilevel analysis.

PubMed

Haagen, Joris F G; Ter Heide, F Jackie June; Mooren, Trudy M; Knipscheer, Jeroen W; Kleber, Rolf J

2017-03-01

Given the recent peak in refugee numbers and refugees' high odds of developing post-traumatic stress disorder (PTSD), finding ways to alleviate PTSD in refugees is of vital importance. However, there are major differences in PTSD treatment response between refugees, the determinants of which are largely unknown. This study aimed at improving PTSD treatment for adult refugees by identifying PTSD treatment response predictors. A prospective longitudinal multilevel modelling design was used to predict PTSD severity scores over time. We analysed data from a randomized controlled trial with pre-, post-, and follow-up measurements of the safety and efficacy of eye movement desensitization and reprocessing and stabilization in asylum seekers and refugees suffering from PTSD. Lack of refugee status, comorbid depression, demographic, trauma-related and treatment-related variables were analysed as potential predictors of PTSD treatment outcome. Treatment outcome data from 72 participants were used. The presence (B = 6.5, p = .03) and severity (B = 6.3, p < .01) of a pre-treatment depressive disorder predicted poor treatment response and explained 39% of the variance between individuals. Refugee patients who suffer from PTSD and severe comorbid depression benefit less from treatment aimed at alleviating PTSD. Results highlight the need for treatment adaptations for PTSD and comorbid severe depression in traumatized refugees, including testing whether initial targeting of severe depressive symptoms increases PTSD treatment effectiveness. There are differences in post-traumatic stress disorder (PTSD) treatment response between traumatized refugees. Comorbid depressive disorder and depression severity predict poor PTSD response. Refugees with PTSD and severe depression may not benefit from PTSD treatment. Targeting comorbid severe depression before PTSD treatment is warranted. This study did not correct for multiple hypothesis testing. Comorbid depression may differentially impact alternative PTSD treatments. © 2016 The British Psychological Society.

Inactivation of Alicyclobacillus acidoterrestris ATCC 49025 spores in apple juice by pulsed light. Influence of initial contamination and required reduction levels.

PubMed

Ferrario, Mariana I; Guerrero, Sandra N

The purpose of this study was to analyze the response of different initial contamination levels of Alicyclobacillus acidoterrestris ATCC 49025 spores in apple juice as affected by pulsed light treatment (PL, batch mode, xenon lamp, 3pulses/s, 0-71.6J/cm 2 ). Biphasic and Weibull frequency distribution models were used to characterize the relationship between inoculum size and treatment time with the reductions achieved after PL exposure. Additionally, a second order polynomial model was computed to relate required PL processing time to inoculum size and requested log reductions. PL treatment caused up to 3.0-3.5 log reductions, depending on the initial inoculum size. Inactivation curves corresponding to PL-treated samples were adequately characterized by both Weibull and biphasic models (R adj 2 94-96%), and revealed that lower initial inoculum sizes were associated with higher inactivation rates. According to the polynomial model, the predicted time for PL treatment increased exponentially with inoculum size. Copyright © 2017 Asociación Argentina de Microbiología. Publicado por Elsevier España, S.L.U. All rights reserved.

Analysing the accuracy of machine learning techniques to develop an integrated influent time series model: case study of a sewage treatment plant, Malaysia.

PubMed

Ansari, Mozafar; Othman, Faridah; Abunama, Taher; El-Shafie, Ahmed

2018-04-01

The function of a sewage treatment plant is to treat the sewage to acceptable standards before being discharged into the receiving waters. To design and operate such plants, it is necessary to measure and predict the influent flow rate. In this research, the influent flow rate of a sewage treatment plant (STP) was modelled and predicted by autoregressive integrated moving average (ARIMA), nonlinear autoregressive network (NAR) and support vector machine (SVM) regression time series algorithms. To evaluate the models' accuracy, the root mean square error (RMSE) and coefficient of determination (R 2 ) were calculated as initial assessment measures, while relative error (RE), peak flow criterion (PFC) and low flow criterion (LFC) were calculated as final evaluation measures to demonstrate the detailed accuracy of the selected models. An integrated model was developed based on the individual models' prediction ability for low, average and peak flow. An initial assessment of the results showed that the ARIMA model was the least accurate and the NAR model was the most accurate. The RE results also prove that the SVM model's frequency of errors above 10% or below - 10% was greater than the NAR model's. The influent was also forecasted up to 44 weeks ahead by both models. The graphical results indicate that the NAR model made better predictions than the SVM model. The final evaluation of NAR and SVM demonstrated that SVM made better predictions at peak flow and NAR fit well for low and average inflow ranges. The integrated model developed includes the NAR model for low and average influent and the SVM model for peak inflow.

Predictors of unstructured antiretroviral treatment interruption and resumption among HIV-positive individuals in Canada.

PubMed

Samji, H; Taha, T E; Moore, D; Burchell, A N; Cescon, A; Cooper, C; Raboud, J M; Klein, M B; Loutfy, M R; Machouf, N; Tsoukas, C M; Montaner, J S G; Hogg, R S

2015-02-01

Sustained optimal use of combination antiretroviral therapy (cART) has been shown to decrease morbidity, mortality and HIV transmission. However, incomplete adherence and treatment interruption (TI) remain challenges to the full realization of the promise of cART. We estimated trends and predictors of treatment interruption and resumption among individuals in the Canadian Observational Cohort (CANOC) collaboration. cART-naïve individuals ≥ 18 years of age who initiated cART between 2000 and 2011 were included in the study. We defined TIs as ≥ 90 consecutive days off cART. We used descriptive analyses to study TI trends over time and Cox regression to identify factors predicting time to first TI and time to treatment resumption after a first TI. A total of 7633 participants were eligible for inclusion in the study, of whom 1860 (24.5%) experienced a TI. The prevalence of TI in the first calendar year of cART decreased by half over the study period. Our analyses highlighted a higher risk of TI among women [adjusted hazard ratio (aHR) 1.59; 95% confidence interval (CI) 1.33-1.92], younger individuals (aHR 1.27; 95% CI 1.15-1.37 per decade increase), earlier treatment initiators (CD4 count ≥ 350 vs. <200 cells/μL: aHR 1.46; 95% CI 1.17-1.81), Aboriginal participants (aHR 1.67; 95% CI 1.27-2.20), injecting drug users (aHR 1.43; 95% CI 1.09-1.89) and users of zidovudine vs. tenofovir in the initial cART regimen (aHR 2.47; 95% CI 1.92-3.20). Conversely, factors predicting treatment resumption were male sex, older age, and a CD4 cell count <200 cells/μL at cART initiation. Despite significant improvements in cART since its advent, our results demonstrate that TIs remain relatively prevalent. Strategies to support continuous HIV treatment are needed to maximize the benefits of cART. © 2014 British HIV Association.

Fourier and non-Fourier bio-heat transfer models to predict ex vivo temperature response to focused ultrasound heating

NASA Astrophysics Data System (ADS)

Li, Chenghai; Miao, Jiaming; Yang, Kexin; Guo, Xiasheng; Tu, Juan; Huang, Pintong; Zhang, Dong

2018-05-01

Although predicting temperature variation is important for designing treatment plans for thermal therapies, research in this area is yet to investigate the applicability of prevalent thermal conduction models, such as the Pennes equation, the thermal wave model of bio-heat transfer, and the dual phase lag (DPL) model. To address this shortcoming, we heated a tissue phantom and ex vivo bovine liver tissues with focused ultrasound (FU), measured the temperature response, and compared the results with those predicted by these models. The findings show that, for a homogeneous-tissue phantom, the initial temperature increase is accurately predicted by the Pennes equation at the onset of FU irradiation, although the prediction deviates from the measured temperature with increasing FU irradiation time. For heterogeneous liver tissues, the predicted response is closer to the measured temperature for the non-Fourier models, especially the DPL model. Furthermore, the DPL model accurately predicts the temperature response in biological tissues because it increases the phase lag, which characterizes microstructural thermal interactions. These findings should help to establish more precise clinical treatment plans for thermal therapies.

Microstructure Modeling of 3rd Generation Disk Alloy

NASA Technical Reports Server (NTRS)

Jou, Herng-Jeng

2008-01-01

The objective of this initiative, funded by NASA's Aviation Safety Program, is to model, validate, and predict, with high fidelity, the microstructural evolution of third-generation high-refractory Ni-based disc superalloys during heat treating and service conditions. This initiative is a natural extension of the DARPA-AIM (Accelerated Insertion of Materials) initiative with GE/Pratt-Whitney and with other process simulation tools. Strong collaboration with the NASA Glenn Research Center (GRC) is a key component of this initiative and the focus of this program is on industrially relevant disk alloys and heat treatment processes identified by GRC. Employing QuesTek s Computational Materials Dynamics technology and PrecipiCalc precipitation simulator, physics-based models are being used to achieve high predictive accuracy and precision. Combining these models with experimental data and probabilistic analysis, "virtual alloy design" can be performed. The predicted microstructures can be optimized to promote desirable features and concurrently eliminate nondesirable phases that can limit the reliability and durability of the alloys. The well-calibrated and well-integrated software tools that are being applied under the proposed program will help gas turbine disk alloy manufacturers, processing facilities, and NASA, to efficiently and effectively improve the performance of current and future disk materials.

Predicting long-term outcome of Internet-delivered cognitive behavior therapy for social anxiety disorder using fMRI and support vector machine learning.

PubMed

Månsson, K N T; Frick, A; Boraxbekk, C-J; Marquand, A F; Williams, S C R; Carlbring, P; Andersson, G; Furmark, T

2015-03-17

Cognitive behavior therapy (CBT) is an effective treatment for social anxiety disorder (SAD), but many patients do not respond sufficiently and a substantial proportion relapse after treatment has ended. Predicting an individual's long-term clinical response therefore remains an important challenge. This study aimed at assessing neural predictors of long-term treatment outcome in participants with SAD 1 year after completion of Internet-delivered CBT (iCBT). Twenty-six participants diagnosed with SAD underwent iCBT including attention bias modification for a total of 13 weeks. Support vector machines (SVMs), a supervised pattern recognition method allowing predictions at the individual level, were trained to separate long-term treatment responders from nonresponders based on blood oxygen level-dependent (BOLD) responses to self-referential criticism. The Clinical Global Impression-Improvement scale was the main instrument to determine treatment response at the 1-year follow-up. Results showed that the proportion of long-term responders was 52% (12/23). From multivariate BOLD responses in the dorsal anterior cingulate cortex (dACC) together with the amygdala, we were able to predict long-term response rate of iCBT with an accuracy of 92% (confidence interval 95% 73.2-97.6). This activation pattern was, however, not predictive of improvement in the continuous Liebowitz Social Anxiety Scale-Self-report version. Follow-up psychophysiological interaction analyses revealed that lower dACC-amygdala coupling was associated with better long-term treatment response. Thus, BOLD response patterns in the fear-expressing dACC-amygdala regions were highly predictive of long-term treatment outcome of iCBT, and the initial coupling between these regions differentiated long-term responders from nonresponders. The SVM-neuroimaging approach could be of particular clinical value as it allows for accurate prediction of treatment outcome at the level of the individual.

Prediction of chemo-response in serous ovarian cancer.

PubMed

Gonzalez Bosquet, Jesus; Newtson, Andreea M; Chung, Rebecca K; Thiel, Kristina W; Ginader, Timothy; Goodheart, Michael J; Leslie, Kimberly K; Smith, Brian J

2016-10-19

Nearly one-third of serous ovarian cancer (OVCA) patients will not respond to initial treatment with surgery and chemotherapy and die within one year of diagnosis. If patients who are unlikely to respond to current standard therapy can be identified up front, enhanced tumor analyses and treatment regimens could potentially be offered. Using the Cancer Genome Atlas (TCGA) serous OVCA database, we previously identified a robust molecular signature of 422-genes associated with chemo-response. Our objective was to test whether this signature is an accurate and sensitive predictor of chemo-response in serous OVCA. We first constructed prediction models to predict chemo-response using our previously described 422-gene signature that was associated with response to treatment in serous OVCA. Performance of all prediction models were measured with area under the curves (AUCs, a measure of the model's accuracy) and their respective confidence intervals (CIs). To optimize the prediction process, we determined which elements of the signature most contributed to chemo-response prediction. All prediction models were replicated and validated using six publicly available independent gene expression datasets. The 422-gene signature prediction models predicted chemo-response with AUCs of ~70 %. Optimization of prediction models identified the 34 most important genes in chemo-response prediction. These 34-gene models had improved performance, with AUCs approaching 80 %. Both 422-gene and 34-gene prediction models were replicated and validated in six independent datasets. These prediction models serve as the foundation for the future development and implementation of a diagnostic tool to predict response to chemotherapy for serous OVCA patients.

Sci-Thur AM: YIS – 05: Prediction of lung tumor motion using a generalized neural network optimized from the average prediction outcome of a group of patients

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

Teo, Troy; Alayoubi, Nadia; Bruce, Neil

Purpose: In image-guided adaptive radiotherapy systems, prediction of tumor motion is required to compensate for system latencies. However, due to the non-stationary nature of respiration, it is a challenge to predict the associated tumor motions. In this work, a systematic design of the neural network (NN) using a mixture of online data acquired during the initial period of the tumor trajectory, coupled with a generalized model optimized using a group of patient data (obtained offline) is presented. Methods: The average error surface obtained from seven patients was used to determine the input data size and number of hidden neurons formore » the generalized NN. To reduce training time, instead of using random weights to initialize learning (method 1), weights inherited from previous training batches (method 2) were used to predict tumor position for each sliding window. Results: The generalized network was established with 35 input data (∼4.66s) and 20 hidden nodes. For a prediction horizon of 650 ms, mean absolute errors of 0.73 mm and 0.59 mm were obtained for method 1 and 2 respectively. An average initial learning period of 8.82 s is obtained. Conclusions: A network with a relatively short initial learning time was achieved. Its accuracy is comparable to previous studies. This network could be used as a plug-and play predictor in which (a) tumor positions can be predicted as soon as treatment begins and (b) the need for pretreatment data and optimization for individual patients can be avoided.« less

The role of clinical variables, neuropsychological performance and SLC6A4 and COMT gene polymorphisms on the prediction of early response to fluoxetine in major depressive disorder.

PubMed

Gudayol-Ferré, Esteve; Herrera-Guzmán, Ixchel; Camarena, Beatriz; Cortés-Penagos, Carlos; Herrera-Abarca, Jorge E; Martínez-Medina, Patricia; Cruz, David; Hernández, Sandra; Genis, Alma; Carrillo-Guerrero, Mariana Y; Avilés Reyes, Rubén; Guàrdia-Olmos, Joan

2010-12-01

Major depressive disorder (MDD) is treated with antidepressants, but only between 50% and 70% of the patients respond to the initial treatment. Several authors suggested different factors that could predict antidepressant response, including clinical, psychophysiological, neuropsychological, neuroimaging, and genetic variables. However, these different predictors present poor prognostic sensitivity and specificity by themselves. The aim of our work is to study the possible role of clinical variables, neuropsychological performance, and the 5HTTLPR, rs25531, and val108/58Met COMT polymorphisms in the prediction of the response to fluoxetine after 4weeks of treatment in a sample of patient with MDD. 64 patients with MDD were genotyped according to the above-mentioned polymorphisms, and were clinically and neuropsychologically assessed before a 4-week fluoxetine treatment. Fluoxetine response was assessed by using the Hamilton Depression Rating Scale. We carried out a binary logistic regression model for the potential predictive variables. Out of the clinical variables studied, only the number of anxiety disorders comorbid with MDD have predicted a poor response to the treatment. A combination of a good performance in variables of attention and low performance in planning could predict a good response to fluoxetine in patients with MDD. None of the genetic variables studied had predictive value in our model. The possible placebo effect has not been controlled. Our study is focused on response prediction but not in remission prediction. Our work suggests that the combination of the number of comorbid anxiety disorders, an attentional variable, and two planning variables makes it possible to correctly classify 82% of the depressed patients who responded to the treatment with fluoxetine, and 74% of the patients who did not respond to that treatment. Copyright © 2010 Elsevier B.V. All rights reserved.

The Use of Physiotherapy among Patients with Subacromial Impingement Syndrome: Impact of Sex, Socio-Demographic and Clinical Factors

PubMed Central

Christiansen, David Høyrup; Frost, Poul; Frich, Lars Henrik; Falla, Deborah; Svendsen, Susanne Wulff

2016-01-01

Background Physiotherapy with exercises is generally recommended in the treatment of patients with subacromial impingement syndrome (SIS). Objective We aimed to investigate the use of physiotherapy in patients with SIS in Danish hospital settings as part of initial non-surgical treatment and after SIS-related surgery and to evaluate to which extent sex, socio-demographic and clinical factors predict the use of physiotherapy. Methods Using national health registers, we identified 57,311 patients who had a first hospital contact with a diagnosis of ICD-10, groups M75.1–75.9, 1 July 2007 to 30 June 2011. Records of physiotherapy were extracted within 52 weeks after first contact (or until surgery), and for surgically treated patients within 26 weeks after surgery. Predictors of the use of physiotherapy after first contact and after surgery were analysed as time-to-event. Results Within 52 weeks after first contact, 43% of the patients had physiotherapy and 30% underwent surgery. Within 26 weeks after surgery, 80% had a record of physiotherapy. After first contact and after surgery, exercise was part of physiotherapy in 65% and 84% of the patients, respectively. A public hospital contact, physiotherapy before hospital contact, administrative region, female sex, a diagnosis of other or unspecified disorders (M75.8-M75.9), and surgical procedure predicted higher use of physiotherapy. Low education level predicted slightly lower use of physiotherapy after first contact, but not after surgery. Conclusion In patients with SIS in Danish hospital settings, physiotherapy was more often used after surgery than as part of initial non-surgical treatment. The use of physiotherapy was less common among men than women, whereas unequal use of physiotherapy in relation to education level was not noticeable. The use of physiotherapy with exercises in initial non-surgical treatment was relatively limited. PMID:26954692

A prospective observational study to evaluate the effect of social and personality factors on continuous positive airway pressure (CPAP) compliance in obstructive sleep apnoea syndrome.

PubMed

Gulati, Atul; Ali, Masood; Davies, Mike; Quinnell, Tim; Smith, Ian

2017-03-22

Compliance with CPAP treatment for OSAS is not reliably predicted by the severity of symptoms or physiological variables. We examined a range of factors which could be measured before CPAP initiation to look for predictors of compliance. This was a prospective cohort-study of CPAP treatment for OSAS, recording; socio-economic status, education, type D personality and clinician's prediction of compliance. We recruited 265 subjects, of whom 221 were still using CPAP at 6 months; median age 53 years, M: F, 3.4:1, ESS 15 and pre-treatment ODI 21/h. Median compliance at 6 months was 5.6 (3.4- 7.1) hours/night with 73.3% of subjects using CPAP ≥4 h/night. No association was found between compliance and different socio-economic classes for people in work, type D personality, education level, sex, age, baseline ESS or ODI. The clinician's initial impression could separate groups of good and poor compliers but had little predictive value for individual patients. Compared to subjects who were working, those who were long term unemployed had a lower CPAP usage and were more likely to use CPAP < 4 h a night (OR 4.6; p value 0.011). A high Beck Depression Index and self-reported anxiety also predicted poor compliance. In our practice there is no significant association between CPAP compliance with socio-economic status, education or personality type. Long term unemployed or depressed individuals may need more intensive support to gain the optimal benefit from CPAP.

Acute graft-versus-host disease biomarkers measured during therapy can predict treatment outcomes: a Blood and Marrow Transplant Clinical Trials Network study

PubMed Central

Logan, Brent R.; Wu, Juan; Alousi, Amin M.; Bolaños-Meade, Javier; Ferrara, James L. M.; Ho, Vincent T.; Weisdorf, Daniel J.

2012-01-01

Acute graft-versus-host disease (GVHD) is the primary limitation of allogeneic hematopoietic cell transplantation, and once it develops, there are no reliable diagnostic tests to predict treatment outcomes. We hypothesized that 6 previously validated diagnostic biomarkers of GVHD (IL-2 receptor-α; tumor necrosis factor receptor-1; hepatocyte growth factor; IL-8; elafin, a skin-specific marker; and regenerating islet–derived 3-α, a gastrointestinal tract–specific marker) could discriminate between therapy responsive and nonresponsive patients and predict survival in patients receiving GVHD therapy. We measured GVHD biomarker concentrations from samples prospectively obtained at the initiation of treatment, day 14, and day 28, on a multicenter, randomized, 4-arm phase 2 clinical trial for newly diagnosed acute GVHD. We found that at each of 3 time points, GVHD onset, 2 weeks into treatment, and 4 weeks into treatment, a 6-protein biomarker panel predicted for the important clinical outcomes of day 28 posttherapy nonresponse and mortality at day 180 from onset. GVHD biomarker panels can be used for early identification of patients at high or low risk for treatment nonresponsiveness or death, and they may provide opportunities for early intervention and improved survival after hematopoietic cell transplantation. The study was registered in clinicaltrials.gov as NCT00224874. PMID:22383800

Self-reported dietary intake and appetite predict early treatment outcome among low-BMI adults initiating HIV treatment in sub-Saharan Africa.

PubMed

Koethe, John R; Blevins, Meridith; Bosire, Claire; Nyirenda, Christopher; Kabagambe, Edmond K; Mwango, Albert; Kasongo, Webster; Zulu, Isaac; Shepherd, Bryan E; Heimburger, Douglas C

2013-03-01

Low BMI is a major risk factor for early mortality among HIV-infected persons starting antiretrovial therapy (ART) in sub-Saharan Africa and the common patient belief that antiretroviral medications produce distressing levels of hunger is a barrier to treatment adherence. We assessed relationships between appetite, dietary intake and treatment outcome 12 weeks after ART initiation among HIV-infected adults with advanced malnutrition and immunosuppression. A prospective, observational cohort study. Dietary intake was assessed using a 24 h recall survey. The relationships of appetite, intake and treatment outcome were analysed using time-varying Cox models. A public-sector HIV clinic in Lusaka, Zambia. One hundred and forty-two HIV-infected adults starting ART with BMI <16 kg/m2 and/or CD4+ lymphocyte count <50 cells/μl. Median age, BMI and CD4+ lymphocyte count were 32 years, 16 kg/m2 and 34 cells/μl, respectively. Twenty-five participants (18%) died before 12 weeks and another thirty-three (23%) were lost to care. A 500 kJ/d higher energy intake at any time after ART initiation was associated with an approximate 16% reduction in the hazard of death (adjusted hazard ratio = 0.84; P = 0.01), but the relative contribution of carbohydrate, protein or fat to total energy was not a significant predictor of outcome. Appetite normalized gradually among survivors and hunger was rarely reported. Poor early ART outcomes were strikingly high in a cohort of HIV-infected adults with advanced malnutrition and mortality was predicted by lower dietary intake. Intervention trials to promote post-ART intake in this population may benefit survival and are warranted.

Self-reported Dietary Intake and Appetite Predict Early Treatment Outcome among Low Body Mass Index Adults Initiating HIV Treatment in sub-Saharan Africa

PubMed Central

Koethe, John R.; Blevins, Meridith; Bosire, Claire; Nyirenda, Christopher; Kabagambe, Edmond K.; Mwango, Albert; Kasongo, Webster; Zulu, Isaac; Shepherd, Bryan E.; Heimburger, Douglas C.

2013-01-01

Objective Low body mass index (BMI) is a major risk factor for early mortality among HIV infected persons starting antiretrovial therapy (ART) in sub-Saharan Africa, and the common patient belief that antiretroviral medications produce distressing levels of hunger is a barrier to treatment adherence. We assessed relationships between appetite, dietary intake, and treatment outcome 12 weeks after ART initiation among HIV infected adults with advanced malnutrition and immunosuppression. Design A prospective, observational cohort study. Dietary intake was assessed using a 24-hour recall survey. The relationships of appetite, intake, and treatment outcome were analyzed using time-varying Cox models. Setting A public-sector HIV clinic in Lusaka, Zambia. Subjects 142 HIV-infected adults starting ART with BMI <16 kg/m2 and/or CD4+ lymphocyte count <50 cells/µl. Results Median age, BMI, and CD4+ lymphocyte count were 32 years, 16 kg/m2, and 34 cells/µL, respectively. Twenty-five participants (18%) died before 12 weeks, and another 33 (23%) were lost to care. A 500 kJ/day higher energy intake at any time after ART initiation was associated with an approximate 16% reduction in the hazard of death (AHR 0.84; p=0.01), but the relative contribution of carbohydrate, protein, and fat to total energy was not a significant predictor of outcome. Appetite normalized gradually among survivors, and hunger was rarely reported. Conclusions Poor early ART outcomes were strikingly high in a cohort of HIV-infected adults with advanced malnutrition, and mortality was predicted by lower dietary intake. Intervention trials to promote post-ART intake in this population may benefit survival and are warranted. PMID:22691872

Role of 2-month sputum smears in predicting culture conversion in pulmonary tuberculosis.

PubMed

Su, W-J; Feng, J-Y; Chiu, Y-C; Huang, S-F; Lee, Y-C

2011-02-01

Sputum smears and culture conversion are frequently used to evaluate treatment response in pulmonary tuberculosis patients. Limited data are available on the evaluation of the correlation between under-treatment sputum smear results and culture conversion. This prospective study included sputum culture-proven pulmonary tuberculosis patients at six hospitals in Taiwan. At least two sets of sputum were collected at the completion of 8 weeks of TB treatment. The sensitivities and specificities of 2-month sputum smears were estimated based on culture conversion status. A total of 371 patients were enrolled for analysis. Factors associated with culture conversion included having a smear positive before treatment, presence of a cavity on radiography, rifampicin resistance and usage of the DOTS (directly observed therapy, short course) strategy. The sensitivities of 2-month sputum smears for culture conversion among all patients, initially smear-positive patients and initially smear-negative patients were 64.3, 71.4 and 38%, respectively, and the specificities were 81.6, 69.9 and 92.8%, respectively. In patients who were 2-month sputum smear-positive, the 2-month culture conversion rate was 80% if the patients were under DOTS and without cavitary lesions in radiograms. The predictive value of 2-month sputum smears in culture conversion was limited and highly influenced by clinical factors in pulmonary tuberculosis patients.

Hierarchical Interactions Model for Predicting Mild Cognitive Impairment (MCI) to Alzheimer's Disease (AD) Conversion

PubMed Central

Li, Han; Liu, Yashu; Gong, Pinghua; Zhang, Changshui; Ye, Jieping

2014-01-01

Identifying patients with Mild Cognitive Impairment (MCI) who are likely to convert to dementia has recently attracted increasing attention in Alzheimer's disease (AD) research. An accurate prediction of conversion from MCI to AD can aid clinicians to initiate treatments at early stage and monitor their effectiveness. However, existing prediction systems based on the original biosignatures are not satisfactory. In this paper, we propose to fit the prediction models using pairwise biosignature interactions, thus capturing higher-order relationship among biosignatures. Specifically, we employ hierarchical constraints and sparsity regularization to prune the high-dimensional input features. Based on the significant biosignatures and underlying interactions identified, we build classifiers to predict the conversion probability based on the selected features. We further analyze the underlying interaction effects of different biosignatures based on the so-called stable expectation scores. We have used 293 MCI subjects from Alzheimer's Disease Neuroimaging Initiative (ADNI) database that have MRI measurements at the baseline to evaluate the effectiveness of the proposed method. Our proposed method achieves better classification performance than state-of-the-art methods. Moreover, we discover several significant interactions predictive of MCI-to-AD conversion. These results shed light on improving the prediction performance using interaction features. PMID:24416143

Do 12-step meeting attendance trajectories over 9 years predict abstinence?

PubMed Central

Witbrodt, Jane; Mertens, Jennifer; Kaskutas, Lee Ann; Bond, Jason; Chi, Felicia; Weisner, Constance

2011-01-01

This study grouped treatment-seeking individuals (n=1825) by common patterns of 12-step attendance using 5 waves of data (75% interviewed year-9) to isolate unique characteristics and use-related outcomes distinguishing each class profile. The high class reported the highest attendance and abstention. The descending class reported high baseline alcohol severity, long treatment episodes, and high initial attendance and abstinence; but by year-5 their attendance and abstinence dropped. The early-drop class, which started with high attendance and abstinence but with low problem severity, reported no attendance after year 1. The rising class, with fairly high alcohol and psychiatric severity throughout, reported initially low attendance, followed by increasing attendance paralleling their abstention. Last, the low and no classes, which reported low problem-severity and very low/no attendance, had the lowest abstention. Female gender and high alcohol severity predicted attendance all years. Consistent with a sustained benefit for 12-step exposure, abstinence patterns aligned much like attendance profiles. PMID:22206631

Beliefs and behavioural intentions towards pharmacotherapy for stuttering: A survey of adults who stutter.

PubMed

McGroarty, Allan; McCartan, Rebecca

Although considerable efforts have been made to investigate the effectiveness of pharmacological treatments for stuttering, little is known about how the stuttering community perceives these treatments. This study aimed to assess and quantify beliefs regarding pharmacotherapy for adults who stutter and to establish whether behavioural intentions to undertake treatment were related to these beliefs. An adapted version of the Beliefs about Medicine Questionnaire was completed by adults who stutter. Participants also reported perceptions of their stuttering including its overall impact, ratings of previous speech therapy, and behavioural intentions to initiate pharmacotherapy and speech therapy in future. Necessity and concern beliefs were distributed widely across the sample and in a pattern indicating a relatively balanced perception of the benefits and costs of medication prescribed specifically for stuttering. Of the study's measures, the necessity-concerns differential most strongly predicted the behavioural intention to initiate pharmacotherapy. The overall impact of stuttering predicted intentions to seek both pharmacotherapy and speech therapy. Participants reported the likelihood of pursuing pharmacotherapy and speech therapy in equal measure. The theoretical model of medication representations appears to be a useful framework for understanding the beliefs of adults who stutter towards the medical treatment of their disorder. The findings of this study may be of interest to clinicians and researchers working in the field of stuttering treatment and to people who stutter considering pharmacotherapy. Copyright © 2018 Elsevier Inc. All rights reserved.

Upper digestive bleeding in cirrhosis. Post-therapeutic outcome and prognostic indicators.

PubMed

D'Amico, Gennaro; De Franchis, Roberto

2003-09-01

Several treatments have been proven to be effective for variceal bleeding in patients with cirrhosis. The aim of this multicenter, prospective, cohort study was to assess how these treatments are used in clinical practice and what are the posttherapeutic prognosis and prognostic indicators of upper digestive bleeding in patients with cirrhosis. A training set of 291 and a test set of 174 bleeding cirrhotic patients were included. Treatment was according to the preferences of each center and the follow-up period was 6 weeks. Predictive rules for 5-day failure (uncontrolled bleeding, rebleeding, or death) and 6-week mortality were developed by the logistic model in the training set and validated in the test set. Initial treatment controlled bleeding in 90% of patients, including vasoactive drugs in 27%, endoscopic therapy in 10%, combined (endoscopic and vasoactive) in 45%, balloon tamponade alone in 1%, and none in 17%. The 5-day failure rate was 13%, 6-week rebleeding was 17%, and mortality was 20%. Corresponding findings for variceal versus nonvariceal bleeding were 15% versus 7% (P =.034), 19% versus 10% (P =.019), and 20% versus 15% (P =.22). Active bleeding on endoscopy, hematocrit levels, aminotransferase levels, Child-Pugh class, and portal vein thrombosis were significant predictors of 5-day failure; alcohol-induced etiology, bilirubin, albumin, encephalopathy, and hepatocarcinoma were predictors of 6-week mortality. Prognostic reassessment including blood transfusions improved the predictive accuracy. All the developed prognostic models were superior to the Child-Pugh score. In conclusion, prognosis of digestive bleeding in cirrhosis has much improved over the past 2 decades. Initial treatment stops bleeding in 90% of patients. Accurate predictive rules are provided for early recognition of high-risk patients.

Predictors of HbA1c levels in patients initiating metformin.

PubMed

Martono, Doti P; Hak, Eelko; Lambers Heerspink, Hiddo; Wilffert, Bob; Denig, Petra

2016-12-01

The aim was to assess demographic and clinical factors as predictors of short (6 months) and long term (18 months) HbA1c levels in diabetes patients initiating metformin treatment. We conducted a cohort study including type 2 diabetes patients who received their first metformin prescription between 2007 and 2013 in the Groningen Initiative to Analyze Type 2 Diabetes Treatment (GIANTT) database. The primary outcome was HbA1c level at follow-up adjusted for baseline HbA1c; the secondary outcome was failing to achieve the target HbA1c level of 53 mmol/mol. Associations were analyzed by linear and logistic regression. Multiple imputation was used for missing data. Additional analyses stratified by dose and adherence level were conducted. The cohort included 6050 patients initiating metformin. Baseline HbA1c at target consistently predicted better HbA1c outcomes. Longer diabetes duration and lower total cholesterol level at baseline were predictors for higher HbA1c levels at 6 months. At 18 months, cholesterol level was not a predictor. Longer diabetes duration was also associated with not achieving the target HbA1c at follow-up. The association for longer diabetes duration was especially seen in patients starting on low dose treatment. No consistent associations were found for comorbidity and comedication. Diabetes duration was a relevant predictor of HbA1c levels after 6 and 18 months of follow-up in patients initiating metformin treatment. Given the study design, no causal inference can be made. Our study suggests that prompt treatment intensification may be needed in patients who have a longer diabetes duration at treatment initiation.

Prediction of treatment outcomes to exercise in patients with nonremitted major depressive disorder.

PubMed

Rethorst, Chad D; South, Charles C; Rush, A John; Greer, Tracy L; Trivedi, Madhukar H

2017-12-01

Only one-third of patients with major depressive disorder (MDD) achieve remission with initial treatment. Consequently, current clinical practice relies on a "trial-and-error" approach to identify an effective treatment for each patient. The purpose of this report was to determine whether we could identify a set of clinical and biological parameters with potential clinical utility for prescription of exercise for treatment of MDD in a secondary analysis of the Treatment with Exercise Augmentation in Depression (TREAD) trial. Participants with nonremitted MDD were randomized to one of two exercise doses for 12 weeks. Participants were categorized as "remitters" (≤12 on the IDS-C), nonresponders (<30% drop in IDS-C), or neither. The least absolute shrinkage and selection operator (LASSO) and random forests were used to evaluate 30 variables as predictors of both remission and nonresponse. Predictors were used to model treatment outcomes using logistic regression. Of the 122 participants, 36 were categorized as remitters (29.5%), 56 as nonresponders (45.9%), and 30 as neither (24.6%). Predictors of remission were higher levels of brain-derived neurotrophic factor (BDNF) and IL-1B, greater depressive symptom severity, and higher postexercise positive affect. Predictors of treatment nonresponse were low cardiorespiratory fitness, lower levels of IL-6 and BDNF, and lower postexercise positive affect. Models including these predictors resulted in predictive values greater than 70% (true predicted remitters/all predicted remitters) with specificities greater than 25% (true predicted remitters/all remitters). Results indicate feasibility in identifying patients who will either remit or not respond to exercise as a treatment for MDD utilizing a clinical decision model that incorporates multiple patient characteristics. © 2017 Wiley Periodicals, Inc.

Superselective Wada test for ruptured spontaneous fusiform middle cerebral artery aneurysm: a technical case report.

PubMed

Rajpal, Sharad; Moftakhar, Roham; Bauer, Andrew M; Turk, Aquilla S; Niemann, David B

2011-09-01

Spontaneous fusiform aneurysms of the middle cerebral artery (sfaMCA) are quite uncommon and tend to occur in young adults. The use of superselective angiography for ruptured and unruptured aneurysms can help delineate vital angioarchitecture and assist with perioperative planning and treatment modality. The use of superselective Wada testing (SWT) for treatment of a ruptured sfaMCA involving the dominant hemisphere, however, has never been described in the English literature. We report a case of a ruptured sfaMCA involving the dominant hemisphere where superselective angiography and SWT were utilized to predict the ability to occlude a major vessel without adverse neurological sequelae. A healthy young patient presented with subarachnoid hemorrhage. Initial CT-angiogram of the head identified a left-sided fusiform MCA aneurysm measuring 1.3 cm by 0.5 cm in maximum dimensions. Diagnostic angiography evaluation demonstrated an irregular, fusiform aneurysm involving the central (Rolandic) trunk of the left MCA. An SWT was then performed through an SL 10 microcatheter with injection of sodium amytal. Verbal, motor and cognitive testing were performed twice and revealed no neurological defects. The patient underwent subsequent coil embolization of the aneurysm. Formal post-procedure evaluation revealed no speech, language or cognitive deficits. She was eventually discharged home and remained without neurological deficits at her follow-up appointment 12 months after her initial presentation. Intraoperative SWT can be performed as part of the initial evaluation for patients with sfaMCA of the dominant cerebral hemisphere to help choose the appropriate treatment algorithm and predict post-treatment neurological deficits.

Early detection of response to radiation therapy in patients with brain malignancies using conventional and high b-value diffusion-weighted magnetic resonance imaging.

PubMed

Mardor, Yael; Pfeffer, Raphael; Spiegelmann, Roberto; Roth, Yiftach; Maier, Stephan E; Nissim, Ouzi; Berger, Raanan; Glicksman, Ami; Baram, Jacob; Orenstein, Arie; Cohen, Jack S; Tichler, Thomas

2003-03-15

To study the feasibility of using diffusion-weighted magnetic resonance imaging (DWMRI), which is sensitive to the diffusion of water molecules in tissues, for detection of early tumor response to radiation therapy; and to evaluate the additional information obtained from high DWMRI, which is more sensitive to low-mobility water molecules (such as intracellular or bound water), in increasing the sensitivity to response. Standard MRI and DWMRI were acquired before and at regular intervals after initiating radiation therapy for 10 malignant brain lesions in eight patients. One week posttherapy, three of six responding lesions showed an increase in the conventional DWMRI parameters. Another three responding lesions showed no change. Four nonresponding lesions showed a decrease or no change. The early change in the diffusion parameters was enhanced by using high DWMRI. When high DWMRI was used, all responding lesions showed increase in the diffusion parameter and all nonresponding lesions showed no change or decrease. Response was determined by standard MRI 7 weeks posttherapy. The changes in the diffusion parameters measured 1 week after initiating treatment were correlated with later tumor response or no response (P <.006). This correlation was increased to P <.0006 when high DWMRI was used. The significant correlation between changes in diffusion parameters 1 week after initiating treatment and later tumor response or no response suggests the feasibility of using DWMRI for early, noninvasive prediction of tumor response. The ability to predict response may enable early termination of treatment in nonresponding patients, prevent additional toxicity, and allow for early changes in treatment.

Predictors of early versus late smoking abstinence within a 24-month disease management program.

PubMed

Cox, Lisa Sanderson; Wick, Jo A; Nazir, Niaman; Cupertino, A Paula; Mussulman, Laura M; Ahluwalia, Jasjit S; Ellerbeck, Edward F

2011-03-01

Standard smoking cessation treatment studies have been limited to 6- to 12-month follow-up, and examination of predictors of abstinence has been restricted to this timeframe. The KanQuit study enrolled 750 rural smokers across all stages of readiness to stop smoking and provided pharmacotherapy management and/or disease management, including motivational interviewing (MI) counseling every 6 months over 2 years. This paper examines differences in predictors of abstinence following initial (6-month) and extended (24-month) intervention. Baseline variables were analyzed as potential predictors of self-reported smoking abstinence at Month 6 and at Month 24. Chi-square tests, 2-sample t tests, and multiple logistic regression analyses were used to identify predictors of abstinence among 592 participants who completed assessment at baseline and Months 6 and 24. Controlling for treatment group, the final regression models showed that male gender and lower baseline cigarettes per day predicted abstinence at both 6 and 24 months. While remaining significant, the relative advantage of being male decreased over time. Global motivation to stop smoking, controlled motivation, and self-efficacy predicted abstinence at 6 months but did not predict abstinence at Month 24. In contrast, stage of change was strongly predictive of 24-month smoking status. While the importance of some predictors of successful smoking cessation appeared to diminish over time, initial lack of interest in cessation and number of cigarettes per day strongly predicted continued smoking following a 2-year program.

Risky decision-making predicts short-term outcome of community but not residential treatment for opiate addiction. Implications for case management.

PubMed

Passetti, F; Clark, L; Davis, P; Mehta, M A; White, S; Checinski, K; King, M; Abou-Saleh, M

2011-10-01

Opiate addiction is associated with decision-making deficits and we previously showed that the extent of these impairments predicts aspects of treatment outcome. Here we aimed to establish whether measures of decision-making performance might be used to inform placement matching. Two groups of opiate dependent individuals, one receiving treatment in a community setting (n=48) and one in a residential setting (n=32) were administered computerised tests of decision-making, impulsivity and planning shortly after the beginning of treatment, to be followed up three months into each programme. In the community sample, performance on the decision-making tasks at initial assessment predicted abstinence from illicit drugs at follow-up. In contrast, in the residential sample there was no relationship between decision-making and clinical outcome. Intact decision-making processes appear to be necessary for upholding a resolve to avoid taking drugs in a community setting, but the importance of these mechanisms may be attenuated in a residential treatment setting. The results support the placement matching hypothesis, suggesting that individuals with more prominent decision-making deficits may particularly benefit from treatment in a residential setting and from the inclusion of aspects of cognitive rehabilitation in their treatment programme. Copyright © 2011 Elsevier Ireland Ltd. All rights reserved.

A retrospective chart review of pirfenidone-treated patients in Sweden: the REPRIS study.

PubMed

Sköld, Carl Magnus; Janson, Christer; Elf, Åsa Klackenberg; Fiaschi, Marie; Wiklund, Kerstin; Persson, Hans Lennart

2016-01-01

Idiopathic pulmonary fibrosis (IPF) is a chronic, progressive lung disease that usually results in respiratory failure and death. Pirfenidone was approved as the first licensed therapy for IPF in Europe based on phase III trials where patients with a forced vital capacity (FVC) >50% of predicted were included. The aim of this study was to characterise patients treated with pirfenidone in Swedish clinical practice and to describe the adherence to the reimbursement restriction since reimbursement was only applied for patients with FVC below 80% of predicted. This was a retrospective, observational chart review of IPF patients treated with pirfenidone from three Swedish university clinics. Patients initiated on treatment during the period 28 June 2012 to 20 November 2014 were included. Data on patient characteristics, basis of diagnosis, treatment duration, quality of life, and adverse drug reactions (ADRs) were collected from medical charts. Forty-four patients were screened and 33 were included in the study. The mean treatment duration from start of pirfenidone until discontinuation or end of study was 38 weeks. At the initiation of pirfenidone treatment, FVC was 62.7% (12.1) [mean (SD)], diffusion capacity (DLco) was 45.1% (13.8) of predicted, and the ratio of forced expiratory volume on 1 sec (FEV1) to FVC was 0.78 (0.1). The percentage of patients with an FVC between 50 and 80% was 87%. Ten of the patients had ADRs including gastrointestinal and skin-related events, cough and signs of impaired hepatic function, but this led to treatment discontinuation in only two patients. Data from this chart review showed that adherence to the Swedish reimbursement restriction was followed in the majority of patients during the study period. At the start of pirfenidone treatment, lung function, measured as FVC, was lower in the present cohort of Swedish IPF patients compared with other registry and real-life data. About a third of the patients had ADRs, but discontinuation of the treatment because of ADRs was relatively uncommon.

Predicting the future prevalence of cigarette smoking in Italy over the next three decades.

PubMed

Carreras, Giulia; Gorini, Giuseppe; Gallus, Silvano; Iannucci, Laura; Levy, David T

2012-10-01

Smoking prevalence in Italy decreased by 37% from 1980 to now. This is due to changes in smoking initiation and cessation rates and is in part attributable to the development of tobacco control policies. This work aims to estimate the age- and sex-specific smoking initiation and cessation probabilities for different time periods and to predict the future smoking prevalence in Italy, assuming different scenarios. A dynamic model describing the evolution of current, former and never smokers was developed. Cessation and relapse rates were estimated by fitting the model with smoking prevalence in Italy, 1986-2009. The estimated parameters were used to predict prevalence, according to scenarios: (1) 2000-09 initiation/cessation; (2) half initiation; (3) double cessation; (4) Scenarios 2+3; (5) triple cessation; and (6) Scenarios 2+5. Maintaining the 2000-09 initiation/cessation, the 10% goal will not be achieved within next three decades: prevalence will stabilize at 12.1% for women and 20.3% for men. The goal could be rapidly achieved for women by halving initiation and tripling cessation (9.9%, 2016), or tripling cessation only (10.4%, 2017); for men halving initiation and tripling cessation (10.8%, 2024), or doubling cessation and halving initiation (10.5%, 2033), or tripling cessation only (10.8%, 2033). The 10% goal will be achieved within the next few decades, mainly by increasing smoking cessation. Policies to reach this goal would include increasing cigarette taxes, introducing total reimbursement of smoking cessation treatment, with a further development of quitlines and smoking cessation services. These measures are not yet fully implemented in Italy.

Cognitive predictors and moderators of winter depression treatment outcomes in cognitive-behavioral therapy vs. light therapy.

PubMed

Sitnikov, Lilya; Rohan, Kelly J; Evans, Maggie; Mahon, Jennifer N; Nillni, Yael I

2013-12-01

There is no empirical basis for determining which seasonal affective disorder (SAD) patients are best suited for what type of treatment. Using data from a parent clinical trial comparing light therapy (LT), cognitive-behavioral therapy (CBT), and their combination (CBT + LT) for SAD, we constructed hierarchical linear regression models to explore baseline cognitive vulnerability constructs (i.e., dysfunctional attitudes, negative automatic thoughts, response styles) as prognostic and prescriptive factors of acute and next winter depression outcomes. Cognitive constructs did not predict or moderate acute treatment outcomes. Baseline dysfunctional attitudes and negative automatic thoughts were prescriptive of next winter treatment outcomes. Participants with higher baseline levels of dysfunctional attitudes and negative automatic thoughts had less severe depression the next winter if treated with CBT than if treated with LT. In addition, participants randomized to solo LT who scored at or above the sample mean on these cognitive measures at baseline had more severe depressive symptoms the next winter relative to those who scored below the mean. Baseline dysfunctional attitudes and negative automatic thoughts did not predict treatment outcomes in participants assigned to solo CBT or CBT + LT. Therefore, SAD patients with extremely rigid cognitions did not fare as well in the subsequent winter if treated initially with solo LT. Such patients may be better suited for initial treatment with CBT, which directly targets cognitive vulnerability processes. Copyright © 2013 Elsevier Ltd. All rights reserved.

Does universal active MRSA surveillance influence anti-MRSA antibiotic use? A retrospective analysis of the treatment of patients admitted with suspicion of infection at Veterans Affairs Medical Centers between 2005 and 2010

PubMed Central

Jones, Makoto; Huttner, Benedikt; Leecaster, Molly; Huttner, Angela; Damal, Kavitha; Tanner, Windy; Nielson, Christopher; Rubin, Michael A.; Goetz, Matthew Bidwell; Madaras-Kelly, Karl; Samore, Matthew H.

2014-01-01

Objectives After the implementation of an active surveillance programme for MRSA in US Veterans Affairs (VA) Medical Centers, there was an increase in vancomycin use. We investigated whether positive MRSA admission surveillance tests were associated with MRSA-positive clinical admission cultures and whether the availability of surveillance tests influenced prescribers' ability to match initial anti-MRSA antibiotic use with anticipated MRSA results from clinical admission cultures. Methods Analyses were based on barcode medication administration data, microbiology data and laboratory data from 129 hospitals between January 2005 and September 2010. Hospitalized patient admissions were included if clinical cultures were obtained and antibiotics started within 2 days of admission. Mixed-effects logistic regression was used to examine associations between positive MRSA admission cultures and (i) admission MRSA surveillance test results and (ii) initial anti-MRSA therapy. Results Among 569 815 included admissions, positive MRSA surveillance tests were strong predictors of MRSA-positive admission cultures (OR 8.5; 95% CI 8.2–8.8). The negative predictive value of MRSA surveillance tests was 97.6% (95% CI 97.5%–97.6%). The diagnostic OR between initial anti-MRSA antibiotics and MRSA-positive admission cultures was 3.2 (95% CI 3.1–3.4) for patients without surveillance tests and was not significantly different for admissions with surveillance tests. Conclusions The availability of nasal MRSA surveillance tests in VA hospitals did not seem to improve the ability of prescribers to predict the necessity of initial anti-MRSA treatment despite the high negative predictive value of MRSA surveillance tests. Prospective trials are needed to establish the safety and effectiveness of using MRSA surveillance tests to guide antibiotic therapy. PMID:25103488

[Value of MRI in the treatment of Grave's disease orbital myopathy].

PubMed

Oğuz, V; Yolar, M; Yetik, H; Cakirer, D; Uysal, O; Pazarli, H

2001-10-01

In order to evaluate the predictability of the results in the treatment of myopathy in cases with the clinical signs of muscle involvement, 177 extraocular muscles of 27 cases whose oedematous status was detected by MRI and who were given antiinflammatory treatment according to the data of this method, were studied. The nature of involvement was detected in respect with the signal intensity and thickness of each rectus muscle prior to the treatment and at the end of the sixth month following a three months' application of combined treatment of steroids and irradiation of 2000 rads. When the initial and final results were compared, the signal intensities of four involved recti showed significant decrease at the end of the treatment, as they were evaluated separately or together. Besides the thicknesses of these groups of involved recti which were evaluated separately showed significant decrease. The evaluation of the signal intensities by MRI is a way that enables noninvasive detection of the edema and prediction of the anti-inflammatory treatment's results of dysthyroid myopathy. Therefore a systematic follow up by MRI is recommended for the treatment choice in dysthyroid myopathy.

Effect of pathologic revision and Ki67 and ERG immunohistochemistry on predicting radical prostatectomy outcome in men initially on active surveillance.

PubMed

Bokhorst, Leonard P; Roobol, Monique J; Bangma, Chris H; van Leenders, Geert J

2017-07-01

To investigate if pathologic biopsy reevaluation and implementation of immunohistochemical biomarkers could improve prediction of radical prostatectomy outcome in men initially on active surveillance. Biopsy specimens from diagnosis until switching to radical prostatectomy in men initially on active surveillance in the Dutch part of the Prostate cancer Research International Active Surveillance (PRIAS) study were collected and revised by a single pathologist. Original and revised biopsy Gleason score were compared and correlated with radical prostatectomy Gleason score. Biopsy specimens were immunohistochemically stained for Ki67 and ERG. Predictive ability of clinical characteristics and biomarkers on Gleason ≥7 or ≥pT3 on radical prostatectomy was tested using logistic regression and ROC curve analysis. A total of 150 biopsies in 95 men were revised. In 13% of diagnostic or second-to-last biopsies and 20% of the last biopsies on active surveillance revision of Gleason score resulted in change of recommendation (ie, active treatment or active surveillance). Concordance with Gleason score on radical prostatectomy was however similar for both the revised and original Gleason on biopsy. Ki67 and ERG were not statistically significant predictors of Gleason ≥7 or ≥pT3 on radical prostatectomy. Although interobserver differences in pathology reporting on biopsy could result in a change of management strategy in approximately 13-20% of men on active surveillance, both pathological revision and tested biomarkers (Ki67 and ERG) did not improve prediction of outcome on radical prostatectomy. Undersampling of most aggressive tumor remains the main focus in order to increase accurate grading at time of treatment decision making. © 2017 Wiley Periodicals, Inc.

Numerical Modeling of STARx for Ex Situ Soil Remediation

NASA Astrophysics Data System (ADS)

Gerhard, J.; Solinger, R. L.; Grant, G.; Scholes, G.

2016-12-01

Growing stockpiles of contaminated soils contaminated with petroleum hydrocarbons are an outstanding problem worldwide. Self-sustaining Treatment for Active Remediation (STAR) is an emerging technology based on smouldering combustion that has been successfully deployed for in situ remediation. STAR has also been developed for ex situ applications (STARx). This work used a two-dimensional numerical model to systematically explore the sensitivity of ex situ remedial performance to key design and operational parameters. First the model was calibrated and validated against pilot scale experiments, providing confidence that the rate and extent of treatment were correctly predicted. Simulations then investigated sensitivity of remedial performance to injected air flux, contaminant saturation, system configuration, heterogeneity of intrinsic permeability, heterogeneity of contaminant saturation, and system scale. Remedial performance was predicted to be most sensitive to the injected air flux, with higher air fluxes achieving higher treatment rates and remediating larger fractions of the initial contaminant mass. The uniformity of the advancing smouldering front was predicted to be highly dependent on effective permeability contrasts between treated and untreated sections of the contaminant pack. As a result, increased heterogeneity (of intrinsic permeability in particular) is predicted to lower remedial performance. Full-scale systems were predicted to achieve treatment rates an order of magnitude higher than the pilot scale for similar contaminant saturation and injected air flux. This work contributed to the large scale STARx treatment system that is being tested at a field site in Fall 2016.

Surgical Versus Nonsurgical Management of Rotator Cuff Tears: Predictors of Treatment Allocation.

PubMed

Kweon, Christopher; Gagnier, Joel J; Robbins, Christopher B; Bedi, Asheesh; Carpenter, James E; Miller, Bruce S

2015-10-01

Rotator cuff tears are a common shoulder disorder resulting in significant disability to patients and financial burden on the health care system. While both surgical and nonsurgical management are accepted treatment options, there is a paucity of data to support a treatment algorithm for care providers. Defining variables to guide treatment allocation may be important for patient education and counseling, as well as to deliver the most efficient care plan at the time of presentation. To identify independent variables at the time of initial clinical presentation that are associated with preferred allocation to surgical versus nonsurgical management for patients with known full-thickness rotator cuff tears. Case control study; Level of evidence, 3. A total of 196 consecutive adult patients with known full-thickness rotator cuff tears were enrolled into a prospective cohort study. Robust data were collected for each subject at baseline, including age, sex, body mass index (BMI), shoulder activity score, smoking status, size of cuff tear, duration of symptoms, functional comorbidity index, the American Shoulder and Elbow Surgeons (ASES) score, the Western Ontario Rotator Cuff index (WORC), and the Veterans Rand 12-Item Health Survey (VR-12). Logistic regression was performed to identify variables associated with treatment allocation, and the corresponding odds ratios were calculated. Of the 196 patients enrolled, 112 underwent surgical intervention and 84 nonoperative management. With covariates controlled for, significant baseline patient characteristics predictive of eventual allocation to surgical treatment included younger age, lower BMI, and durations of symptoms less than 1 year. Increasing age, higher BMI, and duration of symptoms longer than 1 year were predictive of nonsurgical treatment. Factors that were not associated with treatment allocation included sex, tear size, functional comorbidity score, or any of the patient-derived outcome scores at presentation (ASES, WORC, VR-12, shoulder activity score). Patient demographics at the time of initial presentation for a symptomatic rotator cuff tear are more predictive of treatment allocation to a surgical or nonoperative approach than the patient-derived outcome scores for activity level and shoulder disability. Further study is warranted to help define appropriate indications for treatment allocation in patients with rotator cuff tears. © 2015 The Author(s).

Predictors of dropout from care among HIV-infected patients initiating antiretroviral therapy at a public sector HIV treatment clinic in sub-Saharan Africa.

PubMed

Asiimwe, Stephen B; Kanyesigye, Michael; Bwana, Bosco; Okello, Samson; Muyindike, Winnie

2016-02-01

In sub-Saharan Africa (SSA), antiretroviral therapy (ART) can prolong life for HIV-infected patients. However, patients initiating ART, especially in routine treatment programs, commonly dropout from care either due to death or loss to follow-up. In a cohort of HIV-infected patients initiating ART at a public sector clinic in Uganda, we assessed predictors of dropout from care (a composite outcome combining death and loss to follow-up). From a large set of socio-demographic, clinical, and laboratory variables routinely collected at ART initiation, we selected those predicting dropout at P <0.1 in unadjusted analyses for inclusion into a multivariable proportional hazards regression model. We then used a stepwise backward selection procedure to identify variables which independently predicted dropout at P <0.05. Data from 5,057 patients were analyzed. The median age was 33 years (IQR 28 to 40) and 27.4% had CD4+ T-cell counts <100 cells/μL at ART initiation. The median duration of follow-up was 24 months (IQR = 14 to 42, maximum follow-up = 64 months). Overall dropout was 26.9% (established cumulative mortality = 2.3%, loss to follow-up = 24.6%), 5.6% were transferred to other service providers, and 67.5% were retained in care. A diagnosis of Kaposi's sarcoma (hazard ratio (HR) = 3.3, 95% CI 2.5 to 4.5); HIV-associated dementia (HR = 2.6, 95% CI 1.5 to 4.6); history of cryptococcosis (HR = 2.2, 95% CI 1.4 to 3.3); and reduced hemoglobin concentration (<11 g/dl versus ≥13.8 g/dl (HR = 1.9, 95% CI 1.6 to 2.2) were strong predictors of dropout. Other independent predictors of dropout were: year of ART initiation; weight loss ≥10%; reduced total lymphocyte count; chronic diarrhea; male sex; young age (≤28 years); and marital status. Among HIV-infected patients initiating ART at a public sector clinic in SSA, biological factors that usually predict death were especially predictive of dropout. As most of the dropouts were lost to follow-up, this observation suggests that many losses to follow-up may have died. Future studies are needed to identify appropriate interventions that may improve both individual-level patient outcomes and outcome ascertainment among HIV-infected ART initiators in this setting.

Treatment intensification using long-acting insulin -predictors of future basal insulin supported oral therapy in the DIVE registry.

PubMed

Danne, Thomas; Bluhmki, Tobias; Seufert, Jochen; Kaltheuner, Matthias; Rathmann, Wolfgang; Beyersmann, Jan; Bramlage, Peter

2015-10-07

In patients with type-2 diabetes receiving oral antidiabetic drugs (OADs), the addition of insulin is frequently required to achieve sufficient control over blood glucose levels. It is, however, difficult to predict if, when and in which patients insulin therapy will be needed. We aimed to identify patient related variables associated with the addition of basal insulin to oral therapy resulting in a basal supported oral therapy (BOT). DIVE (DIabetes Versorgungs-Evaluation) is a prospective, observational, multi-centre diabetes registry established in Germany in 2011. For the present explorative analysis, 31,008 patients with type-2 diabetes prescribed at least one OAD were included. Patients who had previously received insulin and those over 90 years old were excluded. The event of interest was defined as the initiation of BOT during the observational period. Cause-specific Cox proportional hazards models based on a competing risk framework were applied for risk quantification. Multivariable adjusted hazard ratios demonstrated that longer diabetes duration, higher BMI, poorer glycaemic control, documentation of any micro- or macrovascular comorbidity, the presence of concomitant non-antidiabetic pharmacotherapies, and greater numbers of prescribed OADs increased the likelihood of BOT initiation. On the other hand BOT initiation was less likely in patients with older age and female gender. Analysing the likelihood of OAD termination without initiation of BOT provided supportive evidence for the variables predictive of BOT initiation. Analysis of the DIVE registry has resulted in the identification of a number of factors that may be predictive for the initiation of BOT for type-2 diabetes patients initially prescribed one or more OADs. Poor glycaemic control, the presence of vascular comorbidities and concomitant medications, and a greater number of OADs were all detected to increase the risk of a switch to BOT. Female gender and younger age showed protective properties. The close monitoring of patients displaying these characteristics may help to identify individuals who might benefit from early addition of insulin therapy to their oral treatment regimen.

A Biomathematical Model of Pneumococcal Lung Infection and Antibiotic Treatment in Mice.

PubMed

Schirm, Sibylle; Ahnert, Peter; Wienhold, Sandra; Mueller-Redetzky, Holger; Nouailles-Kursar, Geraldine; Loeffler, Markus; Witzenrath, Martin; Scholz, Markus

2016-01-01

Pneumonia is considered to be one of the leading causes of death worldwide. The outcome depends on both, proper antibiotic treatment and the effectivity of the immune response of the host. However, due to the complexity of the immunologic cascade initiated during infection, the latter cannot be predicted easily. We construct a biomathematical model of the murine immune response during infection with pneumococcus aiming at predicting the outcome of antibiotic treatment. The model consists of a number of non-linear ordinary differential equations describing dynamics of pneumococcal population, the inflammatory cytokine IL-6, neutrophils and macrophages fighting the infection and destruction of alveolar tissue due to pneumococcus. Equations were derived by translating known biological mechanisms and assuming certain response kinetics. Antibiotic therapy is modelled by a transient depletion of bacteria. Unknown model parameters were determined by fitting the predictions of the model to data sets derived from mice experiments of pneumococcal lung infection with and without antibiotic treatment. Time series of pneumococcal population, debris, neutrophils, activated epithelial cells, macrophages, monocytes and IL-6 serum concentrations were available for this purpose. The antibiotics Ampicillin and Moxifloxacin were considered. Parameter fittings resulted in a good agreement of model and data for all experimental scenarios. Identifiability of parameters is also estimated. The model can be used to predict the performance of alternative schedules of antibiotic treatment. We conclude that we established a biomathematical model of pneumococcal lung infection in mice allowing predictions regarding the outcome of different schedules of antibiotic treatment. We aim at translating the model to the human situation in the near future.

Patients with RA in remission on TNF blockers: when and in whom can TNF blocker therapy be stopped?

PubMed

Saleem, Benazir; Keen, Helen; Goeb, Vincent; Parmar, Rekha; Nizam, Sharmin; Hensor, Elizabeth M A; Churchman, Sarah M; Quinn, Mark; Wakefield, Richard; Conaghan, Philip G; Ponchel, Frederique; Emery, Paul

2010-09-01

Combination therapy with methotrexate (MTX) and tumour necrosis factor (TNF) blockade has increased remission rates in patients with rheumatoid arthritis. However, there are no guidelines regarding cessation of therapy. There is a need for markers predictive of sustained remission following cessation of TNF blocker therapy. Patients in remission (DAS28 <2.6) treated with a TNF blocker and MTX as initial or delayed therapy were recruited. Joints were assessed for grey scale synovitis and power Doppler (PD) activity. Immunological assessment involved advanced six-colour flow cytometry. Of the 47 patients recruited, 27 had received initial treatment and 20 delayed treatment with TNF blocking drugs. Two years after stopping TNF blocker therapy, the main predictor of successful cessation was timing of treatment; 59% of patients in the initial treatment group sustained remission compared with 15% in the delayed treatment group (p=0.003). Within the initial treatment group, secondary analysis showed that the only clinical predictor of successful cessation of treatment was shorter symptom duration before receiving treatment (median 5.5 months vs 9 months; p=0.008). No other clinical features were associated with successful cessation of therapy. Thirty-five per cent of patients had low PD activity but levels were not informative. Several immunological parameters were significantly associated with sustained remission including abnormal differentiation subset of T cells and regulatory T cells. Similar non-significant trends were observed in the delayed treatment group. In patients in remission with low levels of imaging synovitis receiving combination treatment with a TNF blocker and MTX, immunological parameters and short duration of untreated symptoms were associated with successful cessation of TNF blocker therapy.

Prevalence and patterns of antidepressant switching amongst primary care patients in the UK.

PubMed

Mars, Becky; Heron, Jon; Gunnell, David; Martin, Richard M; Thomas, Kyla H; Kessler, David

2017-05-01

Non-response to antidepressant treatment is a substantial problem in primary care, and many patients with depression require additional second-line treatments. This study aimed to examine the prevalence and patterns of antidepressant switching in the UK, and identify associated demographic and clinical factors. Cohort analysis of antidepressant prescribing data from the Clinical Practice Research Datalink, a large, anonymised UK primary care database. The sample included 262,844 patients who initiated antidepressant therapy between 1 January 2005 and 31 June 2011. 9.3% of patients switched to a different antidepressant product, with most switches (60%) occurring within 8 weeks of the index date. The proportion switching was similar for selective serotonin reuptake inhibitors (SSRIs), tricyclic antidepressants and other antidepressants (9.3%, 9.8% and 9.2%, respectively). Most switches were to an SSRI (64.5%), and this was the preferred option regardless of initial antidepressant class. Factors predictive of switching included male gender, age, and history of self-harm and psychiatric illness. Over one in every 11 patients who initiates antidepressant therapy will switch medication, suggesting that initial antidepressant treatment has been unsatisfactory. Evidence to guide choice of second-line treatment for individual patients is currently limited. Additional research comparing different pharmacological and psychological second-line treatment strategies is required in order to inform guidelines and improve patient outcomes.

How I treat acute graft-versus-host disease of the gastrointestinal tract and the liver.

PubMed

McDonald, George B

2016-03-24

Treatment of acute graft-versus-host disease (GVHD) has evolved from a one-size-fits-all approach to a more nuanced strategy based on predicted outcomes. Lower and time-limited doses of immune suppression for patients predicted to have low-risk GVHD are safe and effective. In more severe GVHD, prolonged exposure to immunosuppressive therapies, failure to achieve tolerance, and inadequate clinical responses are the proximate causes of GVHD-related deaths. This article presents acute GVHD-related scenarios representing, respectively, certainty of diagnosis, multiple causes of symptoms, jaundice, an initial therapy algorithm, secondary therapy, and defining futility of treatment. © 2016 by The American Society of Hematology.

Changes in the retreatment radiation tolerance of the spinal cord with time after the initial treatment.

PubMed

Woolley, Thomas E; Belmonte-Beitia, Juan; Calvo, Gabriel F; Hopewell, John W; Gaffney, Eamonn A; Jones, Bleddyn

2018-06-01

To estimate, from experimental data, the retreatment radiation 'tolerances' of the spinal cord at different times after initial treatment. A model was developed to show the relationship between the biological effective doses (BEDs) for two separate courses of treatment with the BED of each course being expressed as a percentage of the designated 'retreatment tolerance' BED value, denoted [Formula: see text] and [Formula: see text]. The primate data of Ang et al. ( 2001 ) were used to determine the fitted parameters. However, based on rodent data, recovery was assumed to commence 70 days after the first course was complete, and with a non-linear relationship to the magnitude of the initial BED (BED init ). The model, taking into account the above processes, provides estimates of the retreatment tolerance dose after different times. Extrapolations from the experimental data can provide conservative estimates for the clinic, with a lower acceptable myelopathy incidence. Care must be taken to convert the predicted [Formula: see text] value into a formal BED value and then a practical dose fractionation schedule. Used with caution, the proposed model allows estimations of retreatment doses with elapsed times ranging from 70 days up to three years after the initial course of treatment.

Communication and patient participation influencing patient recall of treatment discussions.

PubMed

Richard, Claude; Glaser, Emma; Lussier, Marie-Thérèse

2017-08-01

Patient recall of treatment information is a key variable towards chronic disease (CD) management. It is unclear what communication and patient participation characteristics predict recall. To assess what aspects of doctor-patient communication predict patient recall of medication information. To describe lifestyle treatment recall, in CD primary care patients. Observational study within a RCT. Community-based primary care (PC) practices. Family physicians (n=18): practicing >5 years, with a CD patient caseload. Patients (n=159): >40 years old, English speaking, computer literate, off-target hypertension, type II diabetes and/or dyslipidaemia. Patient characteristics: age, education, number of CDs. Information characteristics: length of encounter, medication status, medication class. Communication variables: socio-emotional utterances, physician dominance and communication control scores and PACE (ask, check and express) utterances, measured by RIAS. Number of medication themes, dialogue and initiative measured by MEDICODE. Recall of CD, lifestyle treatment and medication information. Frequency of lifestyle discussions varied by topic. Patients recalled 43% (alcohol), 52% (diet) to 70% (exercise) of discussions. Two and a half of six possible medication themes were broached per medication discussion. Less than one was recalled. Discussing more themes, greater dialogue and patient initiative were significant predictors of improved medication information recall. Critical treatment information is infrequently exchanged. Active patient engagement and explicit conversations about medications are associated with improved treatment information recall in off-target CD patients followed in PC. Providers cannot take for granted that long-term off-target CD patients recall information. They need to encourage patient participation to improve recall of treatment information. © 2016 The Authors. Health Expectations Published by John Wiley & Sons Ltd.

Baseline Brain Activity Predicts Response to Neuromodulatory Pain Treatment

PubMed Central

Jensen, Mark P.; Sherlin, Leslie H.; Fregni, Felipe; Gianas, Ann; Howe, Jon D.; Hakimian, Shahin

2015-01-01

Objectives The objective of this study was to examine the associations between baseline electroencephalogram (EEG)-assessed brain oscillations and subsequent response to four neuromodulatory treatments. Based on available research, we hypothesized that baseline theta oscillations would prospectively predict response to hypnotic analgesia. Analyses involving other oscillations and the other treatments (meditation, neurofeedback, and both active and sham transcranial direct current stimulation) were viewed as exploratory, given the lack of previous research examining brain oscillations as predictors of response to these other treatments. Design Randomized controlled study of single sessions of four neuromodulatory pain treatments and a control procedure. Methods Thirty individuals with spinal cord injury and chronic pain had their EEG recorded before each session of four active treatments (hypnosis, meditation, EEG biofeedback, transcranial direct current stimulation) and a control procedure (sham transcranial direct stimulation). Results As hypothesized, more presession theta power was associated with greater response to hypnotic analgesia. In exploratory analyses, we found that less baseline alpha power predicted pain reduction with meditation. Conclusions The findings support the idea that different patients respond to different pain treatments and that between-person treatment response differences are related to brain states as measured by EEG. The results have implications for the possibility of enhancing pain treatment response by either 1) better patient/treatment matching or 2) influencing brain activity before treatment is initiated in order to prepare patients to respond. Research is needed to replicate and confirm the findings in additional samples of individuals with chronic pain. PMID:25287554

Stand changes in the first 10 years after seedbed preparation for paper birch

Treesearch

John C. Bjorkbom; John C. Bjorkbom

1972-01-01

Changes may take place rapidly in young forest stands. Stands that appear good may deteriorate unexpectedly: stands that hold little promise initially may suddenly show great potential. The ability to understand and predict such changes increases our ability to prescribe effective silvicultural treatments.

78 FR 45538 - The Patient Preference Initiative: Incorporating Patient Preference Information Into the Medical...

Federal Register 2010, 2011, 2012, 2013, 2014

2013-07-29

... decision making. It also aims to advance the science of measuring treatment preferences of patients...: Incorporating Patient Preference Information into the Medical Device Regulatory Processes.'' The purpose of the... predictability, consistency, and transparency of the premarket review process. In 2012, CDRH published the...

Accelerating recovery after trauma with free flaps.

PubMed

Harris, G D; Nagle, D J; Lewis, V L; Bauer, B S

1987-08-01

Free flap versatility and dependability make the final result of microvascular reconstruction highly predictable. Free tissue transplantation should be considered as a primary treatment after trauma. The early use of free tissue transfer will result in fewer operations and a shortened duration of hospitalization in the initial post-trauma period.

Predicting sex offender treatment entry among individuals convicted of sexual offense crimes.

PubMed

Jones, Nicole; Pelissier, Bernadette; Klein-Saffran, Jody

2006-01-01

This study examined what factors were predictive of who volunteers for sex offender treatment (self-selection) as well as who enters treatment after volunteering (administration selection). Research participants included 404 treatment volunteers and 387 nonvolunteers to treatment who were convicted of a sexual offense involving minors within the federal prison system. Maximum likelihood probit estimation procedures indicated that when compared with nonvolunteers, treatment volunteers were more likely to be recommended by a judge to receive treatment at the time of sentencing, had received prior treatment for sexually deviant behavior, reported higher levels of motivation to change their sexually deviant behavior, and had lower rates of a substance use disorder in the year prior to incarceration. Of those persons who initially volunteered, 62% were accepted and entered treatment, 16% were denied entry to treatment by program staff, and 22% refused treatment after being accepted to the waiting list. When compared with those who were accepted and entered treatment, motivation was the only predictor of being denied admission into treatment by program staff and for refusal of treatment once accepted. The findings emphasize the need to control for selection bias in treatment outcome studies and the importance of examining the role of motivation in treatment volunteerism and treatment entry for sexual offenders.

What Good are Positive Emotions for Treatment? Trait Positive Emotionality Predicts Response to Cognitive Behavioral Therapy for Anxiety

PubMed Central

Taylor, Charles T.; Knapp, Sarah E.; Bomyea, Jessica A.; Ramsawh, Holly J.; Paulus, Martin P.; Stein, Murray B.

2017-01-01

Objective Cognitive behavioral therapy (CBT) is empirically supported for the treatment of anxiety disorders; however, not all individuals achieve recovery following CBT. Positive emotions serve a number of functions that theoretically should facilitate response to CBT – they promote flexible patterns of information processing and assimilation of new information, encourage approach-oriented behavior, and speed physiological recovery from negative emotions. We conducted a secondary analysis of an existing clinical trial dataset to test the a priori hypothesis that individual differences in trait positive emotions would predict CBT response for anxiety. Method Participants meeting diagnostic criteria for panic disorder (n=28) or generalized anxiety disorder (n=31) completed 10 weekly individual CBT sessions. Trait positive emotionality was assessed at pre-treatment, and severity of anxiety symptoms and associated impairment was assessed throughout treatment. Results Participants who reported a greater propensity to experience positive emotions at pre-treatment displayed the largest reduction in anxiety symptoms as well as fewer symptoms following treatment. Positive emotions remained a robust predictor of change in symptoms when controlling for baseline depression severity. Conclusions Initial evidence supports the predictive value of trait positive emotions as a prognostic indicator for CBT outcome in a GAD and PD sample. PMID:28342947

What good are positive emotions for treatment? Trait positive emotionality predicts response to Cognitive Behavioral Therapy for anxiety.

PubMed

Taylor, Charles T; Knapp, Sarah E; Bomyea, Jessica A; Ramsawh, Holly J; Paulus, Martin P; Stein, Murray B

2017-06-01

Cognitive behavioral therapy (CBT) is empirically supported for the treatment of anxiety disorders; however, not all individuals achieve recovery following CBT. Positive emotions serve a number of functions that theoretically should facilitate response to CBT - they promote flexible patterns of information processing and assimilation of new information, encourage approach-oriented behavior, and speed physiological recovery from negative emotions. We conducted a secondary analysis of an existing clinical trial dataset to test the a priori hypothesis that individual differences in trait positive emotions would predict CBT response for anxiety. Participants meeting diagnostic criteria for panic disorder (n = 28) or generalized anxiety disorder (n = 31) completed 10 weekly individual CBT sessions. Trait positive emotionality was assessed at pre-treatment, and severity of anxiety symptoms and associated impairment was assessed throughout treatment. Participants who reported a greater propensity to experience positive emotions at pre-treatment displayed the largest reduction in anxiety symptoms as well as fewer symptoms following treatment. Positive emotions remained a robust predictor of change in symptoms when controlling for baseline depression severity. Initial evidence supports the predictive value of trait positive emotions as a prognostic indicator for CBT outcome in a GAD and PD sample. Copyright © 2017 Elsevier Ltd. All rights reserved.

Do treatment quality indicators predict cardiovascular outcomes in patients with diabetes?

PubMed

Sidorenkov, Grigory; Voorham, Jaco; de Zeeuw, Dick; Haaijer-Ruskamp, Flora M; Denig, Petra

2013-01-01

Landmark clinical trials have led to optimal treatment recommendations for patients with diabetes. Whether optimal treatment is actually delivered in practice is even more important than the efficacy of the drugs tested in trials. To this end, treatment quality indicators have been developed and tested against intermediate outcomes. No studies have tested whether these treatment quality indicators also predict hard patient outcomes. A cohort study was conducted using data collected from >10.000 diabetes patients in the Groningen Initiative to Analyze Type 2 Treatment (GIANTT) database and Dutch Hospital Data register. Included quality indicators measured glucose-, lipid-, blood pressure- and albuminuria-lowering treatment status and treatment intensification. Hard patient outcome was the composite of cardiovascular events and all-cause death. Associations were tested using Cox regression adjusting for confounding, reporting hazard ratios (HR) with 95% confidence intervals. Lipid and albuminuria treatment status, but not blood pressure lowering treatment status, were associated with the composite outcome (HR = 0.77, 0.67-0.88; HR = 0.75, 0.59-0.94). Glucose lowering treatment status was associated with the composite outcome only in patients with an elevated HbA1c level (HR = 0.72, 0.56-0.93). Treatment intensification with glucose-lowering but not with lipid-, blood pressure- and albuminuria-lowering drugs was associated with the outcome (HR = 0.73, 0.60-0.89). Treatment quality indicators measuring lipid- and albuminuria-lowering treatment status are valid quality measures, since they predict a lower risk of cardiovascular events and mortality in patients with diabetes. The quality indicators for glucose-lowering treatment should only be used for restricted populations with elevated HbA1c levels. Intriguingly, the tested indicators for blood pressure-lowering treatment did not predict patient outcomes. These results question whether all treatment indicators are valid measures to judge quality of health care and its economics.

Can machine-learning improve cardiovascular risk prediction using routine clinical data?

PubMed Central

Kai, Joe; Garibaldi, Jonathan M.; Qureshi, Nadeem

2017-01-01

Background Current approaches to predict cardiovascular risk fail to identify many people who would benefit from preventive treatment, while others receive unnecessary intervention. Machine-learning offers opportunity to improve accuracy by exploiting complex interactions between risk factors. We assessed whether machine-learning can improve cardiovascular risk prediction. Methods Prospective cohort study using routine clinical data of 378,256 patients from UK family practices, free from cardiovascular disease at outset. Four machine-learning algorithms (random forest, logistic regression, gradient boosting machines, neural networks) were compared to an established algorithm (American College of Cardiology guidelines) to predict first cardiovascular event over 10-years. Predictive accuracy was assessed by area under the ‘receiver operating curve’ (AUC); and sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV) to predict 7.5% cardiovascular risk (threshold for initiating statins). Findings 24,970 incident cardiovascular events (6.6%) occurred. Compared to the established risk prediction algorithm (AUC 0.728, 95% CI 0.723–0.735), machine-learning algorithms improved prediction: random forest +1.7% (AUC 0.745, 95% CI 0.739–0.750), logistic regression +3.2% (AUC 0.760, 95% CI 0.755–0.766), gradient boosting +3.3% (AUC 0.761, 95% CI 0.755–0.766), neural networks +3.6% (AUC 0.764, 95% CI 0.759–0.769). The highest achieving (neural networks) algorithm predicted 4,998/7,404 cases (sensitivity 67.5%, PPV 18.4%) and 53,458/75,585 non-cases (specificity 70.7%, NPV 95.7%), correctly predicting 355 (+7.6%) more patients who developed cardiovascular disease compared to the established algorithm. Conclusions Machine-learning significantly improves accuracy of cardiovascular risk prediction, increasing the number of patients identified who could benefit from preventive treatment, while avoiding unnecessary treatment of others. PMID:28376093

Can machine-learning improve cardiovascular risk prediction using routine clinical data?

PubMed

Weng, Stephen F; Reps, Jenna; Kai, Joe; Garibaldi, Jonathan M; Qureshi, Nadeem

2017-01-01

Current approaches to predict cardiovascular risk fail to identify many people who would benefit from preventive treatment, while others receive unnecessary intervention. Machine-learning offers opportunity to improve accuracy by exploiting complex interactions between risk factors. We assessed whether machine-learning can improve cardiovascular risk prediction. Prospective cohort study using routine clinical data of 378,256 patients from UK family practices, free from cardiovascular disease at outset. Four machine-learning algorithms (random forest, logistic regression, gradient boosting machines, neural networks) were compared to an established algorithm (American College of Cardiology guidelines) to predict first cardiovascular event over 10-years. Predictive accuracy was assessed by area under the 'receiver operating curve' (AUC); and sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV) to predict 7.5% cardiovascular risk (threshold for initiating statins). 24,970 incident cardiovascular events (6.6%) occurred. Compared to the established risk prediction algorithm (AUC 0.728, 95% CI 0.723-0.735), machine-learning algorithms improved prediction: random forest +1.7% (AUC 0.745, 95% CI 0.739-0.750), logistic regression +3.2% (AUC 0.760, 95% CI 0.755-0.766), gradient boosting +3.3% (AUC 0.761, 95% CI 0.755-0.766), neural networks +3.6% (AUC 0.764, 95% CI 0.759-0.769). The highest achieving (neural networks) algorithm predicted 4,998/7,404 cases (sensitivity 67.5%, PPV 18.4%) and 53,458/75,585 non-cases (specificity 70.7%, NPV 95.7%), correctly predicting 355 (+7.6%) more patients who developed cardiovascular disease compared to the established algorithm. Machine-learning significantly improves accuracy of cardiovascular risk prediction, increasing the number of patients identified who could benefit from preventive treatment, while avoiding unnecessary treatment of others.

Preclinical Assessment of a Strategy to Minimize the Abuse Liability of Opiate Medications for Pain

DTIC Science & Technology

2015-07-01

Animal subjects typically undergo handling by the experimenter prior to a pre- test phase, where their initial preference for one of the environments is...other words, the initial pre- test is presumed to be predictive 6 of the eventual post -treatment test , where animals are given a choice of...environments and if they spend more time in the drug-paired environment on the test day, they are thought to be drug seeking or craving. However, in the

Initiation, adherence, and retention in a randomized controlled trial of directly administered antiretroviral therapy.

PubMed

Maru, Duncan Smith-Rohrberg; Bruce, R Douglas; Walton, Mary; Mezger, Jo Anne; Springer, Sandra A; Shield, David; Altice, Frederick L

2008-03-01

Directly administered antiretroviral therapy (DAART) can improve health outcomes among HIV-infected drug users. An understanding of the utilization of DAART-initiation, adherence, and retention-is critical to successful program design. Here, we use the Behavioral Model to assess the enabling, predisposing, and need factors impacting adherence in our randomized, controlled trial of DAART versus self-administered therapy (SAT) among 141 HIV-infected drug users. Of 88 participants randomized to DAART, 74 (84%) initiated treatment, and 51 (69%) of those who initiated were retained in the program throughout the entire six-month period. Mean adherence to directly observed visits was 73%, and the mean overall composite adherence score was 77%. These results were seen despite the finding that 75% of participants indicated that they would prefer to take their own medications. Major causes of DAART discontinuation included hospitalization, incarceration, and entry into drug-treatment programs. The presence of depression and the lack of willingness to travel greater than four blocks to receive DAART predicted time-to-discontinuation.

Initiation, Adherence, and Retention in a Randomized Controlled Trial of Directly Administered Antiretroviral Therapy

PubMed Central

Maru, Duncan Smith-Rohrberg; Bruce, R. Douglas; Walton, Mary; Mezger, Jo Anne; Springer, Sandra A.; Shield, David

2009-01-01

Directly administered antiretroviral therapy (DAART) can improve health outcomes among HIV-infected drug users. An understanding of the utilization of DAART—initiation, adherence, and retention—is critical to successful program design. Here, we use the Behavioral Model to assess the enabling, predisposing, and need factors impacting adherence in our randomized, controlled trial of DAART versus self-administered therapy (SAT) among 141 HIV-infected drug users. Of 88 participants randomized to DAART, 74 (84%) initiated treatment, and 51 (69%) of those who initiated were retained in the program throughout the entire six-month period. Mean adherence to directly observed visits was 73%, and the mean overall composite adherence score was 77%. These results were seen despite the finding that 75% of participants indicated that they would prefer to take their own medications. Major causes of DAART discontinuation included hospitalization, incarceration, and entry into drug-treatment programs. The presence of depression and the lack of willingness to travel greater than four blocks to receive DAART predicted time-to-discontinuation. PMID:18085432

Long-term medical costs and life expectancy of acute myeloid leukemia: a probabilistic decision model.

PubMed

Wang, Han-I; Aas, Eline; Howell, Debra; Roman, Eve; Patmore, Russell; Jack, Andrew; Smith, Alexandra

2014-03-01

Acute myeloid leukemia (AML) can be diagnosed at any age and treatment, which can be given with supportive and/or curative intent, is considered expensive compared with that for other cancers. Despite this, no long-term predictive models have been developed for AML, mainly because of the complexities associated with this disease. The objective of the current study was to develop a model (based on a UK cohort) to predict cost and life expectancy at a population level. The model developed in this study combined a decision tree with several Markov models to reflect the complexity of the prognostic factors and treatments of AML. The model was simulated with a cycle length of 1 month for a time period of 5 years and further simulated until age 100 years or death. Results were compared for two age groups and five different initial treatment intents and responses. Transition probabilities, life expectancies, and costs were derived from a UK population-based specialist registry-the Haematological Malignancy Research Network (www.hmrn.org). Overall, expected 5-year medical costs and life expectancy ranged from £8,170 to £81,636 and 3.03 to 34.74 months, respectively. The economic and health outcomes varied with initial treatment intent, age at diagnosis, trial participation, and study time horizon. The model was validated by using face, internal, and external validation methods. The results show that the model captured more than 90% of the empirical costs, and it demonstrated good fit with the empirical overall survival. Costs and life expectancy of AML varied with patient characteristics and initial treatment intent. The robust AML model developed in this study could be used to evaluate new diagnostic tools/treatments, as well as enable policy makers to make informed decisions. Copyright © 2014 International Society for Pharmacoeconomics and Outcomes Research (ISPOR). Published by Elsevier Inc. All rights reserved.

Predictors of short-term treatment outcomes among California's Proposition 36 participants.

PubMed

Hser, Yih-Ing; Evans, Elizabeth; Teruya, Cheryl; Huang, David; Anglin, M Douglas

2007-05-01

California's voter-initiated Proposition 36 offers non-violent drug offenders community-based treatment as an alternative to incarceration or probation without treatment. This article reports short-term treatment outcomes subsequent to this major shift in drug policy. Data are from 1104 individuals randomly selected from all Proposition 36 participants assessed for treatment in five California counties during 2004. The overall study sample was 30% female, 51% white, 18% Black, 24% Hispanic, and 7% other racial/ethnic groups. The mean+/-SD age was 37+/-10 years. Counties varied considerably in participant characteristics, treatment service intensity, treatment duration, urine testing, and employment and recidivism outcomes, but not in drug use at 3-month follow-up. Controlling for county, logistic regression analysis showed that drug abstinence was predicted by gender (female), employment at baseline (full or part-time), residential (vs. outpatient) stay, low psychiatric severity, frequent urine testing by treatment facility, and more days in treatment. Recidivism was predicted only by shorter treatment duration. Employment predictors included age (younger), gender (male), baseline employment, and lower psychiatric severity. The study findings support drug testing to monitor abstinence and highlight the need to address employment and psychiatric problems among Proposition 36 participants.

Dronedarone (Sanofi-Synthélabo).

PubMed

Le Grand, B

2001-05-01

Sanofi-Synthelabo (formerly Sanofi) is developing the class III antiarrhythmic agent, dronedarone, for the potential treatment of atrial fibrillation and ventricular tachycardia [157842]. Phase III trials for the treatment of arrhythmia are planned for 2001 [399945]. By December 1998, phase IIb trials for the treatment of cardiac arrhythmia had been initiated [295681,320585], and the compound was shown to have the same efficacy as, and better tolerability than amiodarone [330073]. By 1997, the compound had entered phase IIa trials in Europe [219077,295681]. In November 1997, Sanofi expected to file for marketing in 2001/2 [270242]. ABN Amro predicted sales of FFR 50 million in 2001, rising to FFR 150 million in 2002 [317536]. Lehman Brothers predicted a 20% chance of the compound reaching market, with a launch anticipated in 2003 and potential peak sales of $200 million in 2011 [346267].

Endovascular Treatment of Malignant Superior Vena Cava Syndrome: Results and Predictive Factors of Clinical Efficacy

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

Fagedet, Dorothee, E-mail: DFagedet@chu-grenoble.fr; Thony, Frederic, E-mail: FThony@chu-grenoble.fr; Timsit, Jean-Francois, E-mail: JFTimsit@chu-grenoble.fr

To demonstrate the effectiveness of endovascular treatment (EVT) with self-expandable bare stents for malignant superior vena cava syndrome (SVCS) and to analyze predictive factors of EVT efficacy. Retrospective review of the 164 patients with malignant SVCS treated with EVT in our hospital from August 1992 to December 2007 and followed until February 2009. Endovascular treatment includes angioplasty before and after stent placement. We used self-expandable bare stents. We studied results of this treatment and looked for predictive factors of clinical efficacy, recurrence, and complications by statistical analysis. Endovascular treatment was clinically successful in 95% of cases, with an acceptable ratemore » of early mortality (2.4%). Thrombosis of the superior vena cava was the only independent factor for EVT failure. The use of stents over 16 mm in diameter was a predictive factor for complications (P = 0.008). Twenty-one complications (12.8%) occurred during the follow-up period. Relapse occurred in 36 patients (21.9%), with effective restenting in 75% of cases. Recurrence of SVCS was significantly increased in cases of occlusion (P = 0.01), initial associated thrombosis (P = 0.006), or use of steel stents (P = 0.004). Long-term anticoagulant therapy did not influence the risk of recurrence or complications. In malignancy, EVT with self-expandable bare stents is an effective SVCS therapy. These results prompt us to propose treatment with stents earlier in the clinical course of patients with SVCS and to avoid dilatation greater than 16 mm.« less

Factors predicting survival in amyotrophic lateral sclerosis patients on non-invasive ventilation.

PubMed

Gonzalez Calzada, Nuria; Prats Soro, Enric; Mateu Gomez, Lluis; Giro Bulta, Esther; Cordoba Izquierdo, Ana; Povedano Panades, Monica; Dorca Sargatal, Jordi; Farrero Muñoz, Eva

2016-01-01

Non invasive ventilation (NIV) improves quality of life and extends survival in amyotrophic lateral sclerosis (ALS) patients. However, few data exist about the factors related to survival. We intended to assess the predictive factors that influence survival in patients after NIV initiation. Patients who started NIV from 2000 to 2014 and were tolerant (compliance ≥ 4 hours) were included; demographic, disease related and respiratory variables at NIV initiation were analysed. Statistical analysis was performed using the Kaplan-Meier test and Cox proportional hazard models. 213 patients were included with median survival from NIV initiation of 13.5 months. In univariate analysis, the identified risk factors for mortality were severity of bulbar involvement (HR 2), Forced Vital Capacity (FVC) % (HR 0.99) and ALSFRS-R (HR 0.97). Multivariate analysis showed that bulbar involvement (HR 1.92) and ALSFRS-R (HR 0.97) were independent predictive factors of survival in patients on NIV. In our study, the two prognostic factors in ALS patients following NIV were the severity of bulbar involvement and ALSFRS-R at the time on NIV initiation. A better assessment of bulbar involvement, including evaluation of the upper airway, and a careful titration on NIV are necessary to optimize treatment efficacy.

Effects of a GABA-ergic medication combination and initial alcohol withdrawal severity on cue-elicited brain activation among treatment-seeking alcoholics.

PubMed

Schacht, Joseph P; Anton, Raymond F; Randall, Patrick K; Li, Xingbao; Henderson, Scott; Myrick, Hugh

2013-06-01

Many studies have reported medication effects on alcohol cue-elicited brain activation or associations between such activation and subsequent drinking. However, few have combined the methodological rigor of a randomized clinical trial (RCT) with follow-up assessments to determine whether cue-elicited activation predicts relapse during treatment, the crux of alcoholism. This study analyzed functional magnetic resonance imaging (fMRI) data from 48 alcohol-dependent subjects enrolled in a 6-week RCT of an investigational pharmacotherapy. Subjects were randomized, based on their level of alcohol withdrawal (AW) at study entry, to receive either a combination of gabapentin (GBP; up to 1,200 mg for 39 days) and flumazenil (FMZ) infusions (2 days) or two placebos. Midway through the RCT, subjects were administered an fMRI alcohol cue reactivity task. There were no main effects of medication or initial AW status on cue-elicited activation, but these factors interacted, such that the GBP/FMZ/higher AW and placebo/lower AW groups, which had previously been shown to have relatively reduced drinking, demonstrated greater dorsal anterior cingulate cortex (dACC) activation to alcohol cues. Further analysis suggested that this finding represented differences in task-related deactivation and was associated with greater control over alcohol-related thoughts. Among study completers, regardless of medication or AW status, greater left dorsolateral prefrontal cortex (DLPFC) activation predicted more post-scan heavy drinking. These data suggest that alterations in task-related deactivation of dACC, a component of the default mode network, may predict better alcohol treatment response, while activation of DLPFC, an area associated with selective attention, may predict relapse drinking.

Trajectories of drinking urges and the initiation of abstinence during cognitive-behavioral alcohol treatment.

PubMed

Hallgren, Kevin A; McCrady, Barbara S; Epstein, Elizabeth E

2016-05-01

Drinking urges during treatment for alcohol use disorders (AUDs) are common, can cause distress and predict relapse. Clients may have little awareness of how their drinking urges might be expected to change during AUD treatment in general and in response to initiating abstinence. The aim of the present study was to test whether drinking urges change on a daily level during treatment and after initiating abstinence. Secondary data analysis was performed using daily drinking urge ratings from two randomized clinical trials. Women (n = 98) and men (n = 79) with AUDs in separate clinical trials of out-patient AUD-focused cognitive-behavioral therapy. Daily dichotomous indicators of any drinking urges or acute escalations in urges (i.e. at least two more urges compared with the previous day) were examined using generalized linear mixed growth-curve modeling. Participants who initiated abstinence reported reductions in urges immediately thereafter (log odds ratios: women B = -0.701, P < 0.001; men B = -0.628, P = 0.018), followed by additional, gradual reductions over time (women B = -0.118, P < 0.001; men B = -0.141, P < 0.001). Participants who entered treatment abstaining from alcohol also reported significant reductions in urges over time (women B = -0.147, P < 0.001; men B = -0.142, P < 0.001). Participants who drank throughout treatment had smaller (women B = -0.042, P = 0.012) or no reductions in urges (men B = 0.015, P = 0.545). There was no evidence that urges increased systematically in response to initiating abstinence. Drinking urges during out-patient behavioral treatment for alcohol use disorders may be maintained in part by alcohol consumption. Initiating abstinence is associated with reductions in drinking urges immediately and then more gradually over time. © 2015 Society for the Study of Addiction.

Impact of Gram stain results on initial treatment selection in patients with ventilator-associated pneumonia: a retrospective analysis of two treatment algorithms.

PubMed

Yoshimura, Jumpei; Kinoshita, Takahiro; Yamakawa, Kazuma; Matsushima, Asako; Nakamoto, Naoki; Hamasaki, Toshimitsu; Fujimi, Satoshi

2017-06-19

Ventilator-associated pneumonia (VAP) is a common and serious problem in intensive care units (ICUs). Several studies have suggested that the Gram stain of endotracheal aspirates is a useful method for accurately diagnosing VAP. However, the usefulness of the Gram stain in predicting which microorganisms cause VAP has not been established. The purpose of this study was to evaluate whether a Gram stain of endotracheal aspirates could be used to determine appropriate initial antimicrobial therapy for VAP. Data on consecutive episodes of microbiologically confirmed VAP were collected from February 2013 to February 2016 in the ICU of a tertiary care hospital in Japan. We constructed two hypothetical empirical antimicrobial treatment algorithms for VAP: a guidelines-based algorithm (GLBA) based on the recommendations of the American Thoracic Society-Infectious Diseases Society of America (ATS-IDSA) guidelines and a Gram stain-based algorithm (GSBA) which limited the choice of initial antimicrobials according to the results of bedside Gram stains. The GLBA and the GSBA were retrospectively reviewed for each VAP episode. The initial coverage rates and the selection of broad-spectrum antimicrobial agents were compared between the two algorithms. During the study period, 219 suspected VAP episodes were observed and 131 episodes were assessed for analysis. Appropriate antimicrobial coverage rates were not significantly different between the two algorithms (GLBA 95.4% versus GSBA 92.4%; p = 0.134). The number of episodes for which antimethicillin-resistant Staphylococcus aureus agents were selected as an initial treatment was larger in the GLBA than in the GSBA (71.0% versus 31.3%; p < 0.001), as were the number of episodes for which antipseudomonal agents were recommended as an initial treatment (70.2% versus 51.9%; p < 0.001). Antimicrobial treatment based on Gram stain results may restrict the administration of broad-spectrum antimicrobial agents without increasing the risk of treatment failure. UMIN-CTR, UMIN000026457 . Registered 8 March 2017 (retrospectively registered).

Country, Sex, EDSS Change and Therapy Choice Independently Predict Treatment Discontinuation in Multiple Sclerosis and Clinically Isolated Syndrome

PubMed Central

Jokubaitis, Vilija G.; Trojano, Maria; Izquierdo, Guillermo; Grand’Maison, François; Oreja-Guevara, Celia; Boz, Cavit; Lugaresi, Alessandra; Girard, Marc; Grammond, Pierre; Iuliano, Gerardo; Fiol, Marcela; Cabrera-Gomez, Jose Antonio; Fernandez-Bolanos, Ricardo; Giuliani, Giorgio; Lechner-Scott, Jeannette; Cristiano, Edgardo; Herbert, Joseph; Petkovska-Boskova, Tatjana; Bergamaschi, Roberto; van Pesch, Vincent; Moore, Fraser; Vella, Norbert; Slee, Mark; Santiago, Vetere; Barnett, Michael; Havrdova, Eva; Young, Carolyn; Sirbu, Carmen-Adella; Tanner, Mary; Rutherford, Michelle; Butzkueven, Helmut

2012-01-01

Objectives We conducted a prospective study, MSBASIS, to assess factors leading to first treatment discontinuation in patients with a clinically isolated syndrome (CIS) and early relapsing-remitting multiple sclerosis (RRMS). Methods The MSBASIS Study, conducted by MSBase Study Group members, enrols patients seen from CIS onset, reporting baseline demographics, cerebral magnetic resonance imaging (MRI) features and Expanded Disability Status Scale (EDSS) scores. Follow-up visits report relapses, EDSS scores, and the start and end dates of MS-specific therapies. We performed a multivariable survival analysis to determine factors within this dataset that predict first treatment discontinuation. Results A total of 2314 CIS patients from 44 centres were followed for a median of 2.7 years, during which time 1247 commenced immunomodulatory drug (IMD) treatment. Ninety percent initiated IMD after a diagnosis of MS was confirmed, and 10% while still in CIS status. Over 40% of these patients stopped their first IMD during the observation period. Females were more likely to cease medication than males (HR 1.36, p = 0.003). Patients treated in Australia were twice as likely to cease their first IMD than patients treated in Spain (HR 1.98, p = 0.001). Increasing EDSS was associated with higher rate of IMD cessation (HR 1.21 per EDSS unit, p<0.001), and intramuscular interferon-β-1a (HR 1.38, p = 0.028) and subcutaneous interferon-β-1a (HR 1.45, p = 0.012) had higher rates of discontinuation than glatiramer acetate, although this varied widely in different countries. Onset cerebral MRI features, age, time to treatment initiation or relapse on treatment were not associated with IMD cessation. Conclusion In this multivariable survival analysis, female sex, country of residence, EDSS change and IMD choice independently predicted time to first IMD cessation. PMID:22768046

Clinical prediction of Gardnerella vaginalis in general practice

PubMed Central

O'Dowd, T.C.; West, R.R.

1987-01-01

In a study of 162 women with vaginal symptoms the clinical features of increased discharge, yellow discharge, 'high cheese' odour and pH greater than 5 were statistically strongly associated with the presence of Gardnerella vaginalis, confirmed by microbiological culture. The sensitivities and specificities of these clinical tests, although not as high as those of previously described sideroom tests using the amine test and microscopy for 'clue cells' nevertheless allow the clinician to predict G. vaginalis reliably and initiate treatment at first consultation. PMID:3499508

SU-E-T-512: Evaluation of Treatment Planning Dose Calculation Accuracy at the Interface of Prosthetic Devices.

PubMed

Paulu, D; Alaei, P

2012-06-01

To evaluate the ability of treatment planning algorithm to accurately predict dose delivered at the interface of high density implanted devices. A high density (7.6 g/cc) Cobalt-Chromium-Molybdenum hip prosthesis was molded into an epoxy-based cylindrical leg phantom. The phantom was designed to be separated in half to access the prosthesis and to place the TLDs. Using MVCT to image the apparatus, a simple treatment plan was developed using the Philips Pinnacle treatment planning system. Wires were placed in the molded epoxy to allow for accurate definition of measurement sites (TLD positions) along the surface of the prosthesis. Micro-cube TLDs (1 mm 3 ) were placed at six measurement locations for which the dose had been calculated by the treatment planning system. An Elekta Synergy linear accelerator was used to deliver a 400 cGy plan to the phantom with 6 MV photons in a single fraction. A total of four 10 cm × 21 cm fields were used at 0, 90, 180, and 270 degree gantry rotations. Initial results indicate that the measured dose is 7-17% lower than the dose calculated by the treatment planning system. Further study using high energy beams are also in progress. Initial results indicate that the treatment planning system does predict the dose near a high density prosthetic device within 10-15% but underestimates the dose. The results of this study could help in designing treatment plans which would reduce the uncertainty of the dose delivered in the vicinity of prosthetic hip implants and similar devices. © 2012 American Association of Physicists in Medicine.

Esophageal stasis in achalasia patients without symptoms after treatment does not predict symptom recurrence.

PubMed

van Hoeij, F B; Smout, A J P M; Bredenoord, A J

2017-08-01

After achalasia treatment, a subset of patients has poor esophageal emptying without having symptoms. There is no consensus on whether to pre-emptively treat these patients. We hypothesized that, if left untreated, these patients will experience earlier symptom recurrence than patients without stasis. 99 treated achalasia patients who were in clinical remission (Eckardt ≤3) at 3 months after treatment were divided into two groups, based on presence or absence of esophageal stasis on a timed barium esophagogram performed after 3 months. Two years after initial treatment, patients with stasis after treatment still had a wider esophagus (3 cm; IQR: 2.2-3.8) and more stasis (3.5 cm; IQR: 1.9-5.6) than patients without stasis (1.8 cm wide and 0 cm stasis; both P<.001). In patients with stasis, the esophageal diameter had increased from 2.5 to 3.0 cm within 2 years of follow-up. The symptoms, need for and time to retreatment were comparable between the two groups. Quality of life and reflux symptoms were also comparable between the two groups. Although patients with stasis initially had a wider esophagus and 2 years after treatment also had a higher degree of stasis and a more dilated esophagus, compared to patients without stasis, they did not have a higher chance of requiring retreatment. We conclude that stasis in symptom-free achalasia patients after treatment does not predict treatment failure within 2 years and can therefore not serve as a sole reason for retreatment. © 2017 John Wiley & Sons Ltd.

White Matter Integrity and Treatment-Based Change in Speech Performance in Minimally Verbal Children with Autism Spectrum Disorder.

PubMed

Chenausky, Karen; Kernbach, Julius; Norton, Andrea; Schlaug, Gottfried

2017-01-01

We investigated the relationship between imaging variables for two language/speech-motor tracts and speech fluency variables in 10 minimally verbal (MV) children with autism. Specifically, we tested whether measures of white matter integrity-fractional anisotropy (FA) of the arcuate fasciculus (AF) and frontal aslant tract (FAT)-were related to change in percent syllable-initial consonants correct, percent items responded to, and percent syllable insertion errors (from best baseline to post 25 treatment sessions). Twenty-three MV children with autism spectrum disorder (ASD) received Auditory-Motor Mapping Training (AMMT), an intonation-based treatment to improve fluency in spoken output, and we report on seven who received a matched control treatment. Ten of the AMMT participants were able to undergo a magnetic resonance imaging study at baseline; their performance on baseline speech production measures is compared to that of the other two groups. No baseline differences were found between groups. A canonical correlation analysis (CCA) relating FA values for left- and right-hemisphere AF and FAT to speech production measures showed that FA of the left AF and right FAT were the largest contributors to the synthetic independent imaging-related variable. Change in percent syllable-initial consonants correct and percent syllable-insertion errors were the largest contributors to the synthetic dependent fluency-related variable. Regression analyses showed that FA values in left AF significantly predicted change in percent syllable-initial consonants correct, no FA variables significantly predicted change in percent items responded to, and FA of right FAT significantly predicted change in percent syllable-insertion errors. Results are consistent with previously identified roles for the AF in mediating bidirectional mapping between articulation and acoustics, and the FAT in its relationship to speech initiation and fluency. They further suggest a division of labor between the hemispheres, implicating the left hemisphere in accuracy of speech production and the right hemisphere in fluency in this population. Changes in response rate are interpreted as stemming from factors other than the integrity of these two fiber tracts. This study is the first to document the existence of a subgroup of MV children who experience increases in syllable- insertion errors as their speech develops in response to therapy.

Marital stability and repartnering: infertility-related stress trajectories of unsuccessful fertility treatment.

PubMed

Martins, Mariana V; Costa, Patrício; Peterson, Brennan D; Costa, Maria E; Schmidt, Lone

2014-12-01

To compare the trajectories of infertility-related stress between patients who remain in the same relationship and patients who repartner. Longitudinal cohort study using latent growth modeling. Fertility centers. Childless men and women evaluated before starting a new cycle of fertility treatment and observed for a 5-year period of unsuccessful treatments. None. Marital stability and infertility-related stress. The majority of patients (86%) remained with their initial partner, but 14% of participants separated and repartnered while pursuing fertility treatments. Marital stability significantly predicted the initial status of infertility stress and infertility stress growth levels. Specifically, patients who repartnered had higher infertility stress levels at all time points compared with those who remained in the same relationship, regardless of the partner they were with at assessment. Furthermore, results showed an increasing stress trajectory over time for those who repartnered, compared with those who remained in a stable relationship. Men and women in fertility treatment who form a second union have higher initial levels of stress in their original relationship and higher changes in stress levels over the course of treatments. These findings suggest that high infertility-related stress levels before entering fertility treatment can negatively affect the stability of marital relationships and lead to repartnering. Copyright © 2014 American Society for Reproductive Medicine. Published by Elsevier Inc. All rights reserved.

Predictors of remission in depression to individual and combined treatments (PReDICT): study protocol for a randomized controlled trial

PubMed Central

2012-01-01

Background Limited controlled data exist to guide treatment choices for clinicians caring for patients with major depressive disorder (MDD). Although many putative predictors of treatment response have been reported, most were identified through retrospective analyses of existing datasets and very few have been replicated in a manner that can impact clinical practice. One major confound in previous studies examining predictors of treatment response is the patient’s treatment history, which may affect both the predictor of interest and treatment outcomes. Moreover, prior treatment history provides an important source of selection bias, thereby limiting generalizability. Consequently, we initiated a randomized clinical trial designed to identify factors that moderate response to three treatments for MDD among patients never treated previously for the condition. Methods/design Treatment-naïve adults aged 18 to 65 years with moderate-to-severe, non-psychotic MDD are randomized equally to one of three 12-week treatment arms: (1) cognitive behavior therapy (CBT, 16 sessions); (2) duloxetine (30–60 mg/d); or (3) escitalopram (10–20 mg/d). Prior to randomization, patients undergo multiple assessments, including resting state functional magnetic resonance imaging (fMRI), immune markers, DNA and gene expression products, and dexamethasone-corticotropin-releasing hormone (Dex/CRH) testing. Prior to or shortly after randomization, patients also complete a comprehensive personality assessment. Repeat assessment of the biological measures (fMRI, immune markers, and gene expression products) occurs at an early time-point in treatment, and upon completion of 12-week treatment, when a second Dex/CRH test is also conducted. Patients remitting by the end of this acute treatment phase are then eligible to enter a 21-month follow-up phase, with quarterly visits to monitor for recurrence. Non-remitters are offered augmentation treatment for a second 12-week course of treatment, during which they receive a combination of CBT and antidepressant medication. Predictors of the primary outcome, remission, will be identified for overall and treatment-specific effects, and a statistical model incorporating multiple predictors will be developed to predict outcomes. Discussion The PReDICT study’s evaluation of biological, psychological, and clinical factors that may differentially impact treatment outcomes represents a sizeable step toward developing personalized treatments for MDD. Identified predictors should help guide the selection of initial treatments, and identify those patients most vulnerable to recurrence, who thus warrant maintenance or combination treatments to achieve and maintain wellness. Trial registration Clinicaltrials.gov Identifier: NCT00360399. Registered 02 AUG 2006. First patient randomized 09 FEB 2007. PMID:22776534

Modelling Predictors of Molecular Response to Frontline Imatinib for Patients with Chronic Myeloid Leukaemia

PubMed Central

Brown, Fred; Adelson, David; White, Deborah; Hughes, Timothy; Chaudhri, Naeem

2017-01-01

Background Treatment of patients with chronic myeloid leukaemia (CML) has become increasingly difficult in recent years due to the variety of treatment options available and challenge deciding on the most appropriate treatment strategy for an individual patient. To facilitate the treatment strategy decision, disease assessment should involve molecular response to initial treatment for an individual patient. Patients predicted not to achieve major molecular response (MMR) at 24 months to frontline imatinib may be better treated with alternative frontline therapies, such as nilotinib or dasatinib. The aims of this study were to i) understand the clinical prediction ‘rules’ for predicting MMR at 24 months for CML patients treated with imatinib using clinical, molecular, and cell count observations (predictive factors collected at diagnosis and categorised based on available knowledge) and ii) develop a predictive model for CML treatment management. This predictive model was developed, based on CML patients undergoing imatinib therapy enrolled in the TIDEL II clinical trial with an experimentally identified achieving MMR group and non-achieving MMR group, by addressing the challenge as a machine learning problem. The recommended model was validated externally using an independent data set from King Faisal Specialist Hospital and Research Centre, Saudi Arabia. Principle Findings The common prognostic scores yielded similar sensitivity performance in testing and validation datasets and are therefore good predictors of the positive group. The G-mean and F-score values in our models outperformed the common prognostic scores in testing and validation datasets and are therefore good predictors for both the positive and negative groups. Furthermore, a high PPV above 65% indicated that our models are appropriate for making decisions at diagnosis and pre-therapy. Study limitations include that prior knowledge may change based on varying expert opinions; hence, representing the category boundaries of each predictive factor could dramatically change performance of the models. PMID:28045960

Risk and the physics of clinical prediction.

PubMed

McEvoy, John W; Diamond, George A; Detrano, Robert C; Kaul, Sanjay; Blaha, Michael J; Blumenthal, Roger S; Jones, Steven R

2014-04-15

The current paradigm of primary prevention in cardiology uses traditional risk factors to estimate future cardiovascular risk. These risk estimates are based on prediction models derived from prospective cohort studies and are incorporated into guideline-based initiation algorithms for commonly used preventive pharmacologic treatments, such as aspirin and statins. However, risk estimates are more accurate for populations of similar patients than they are for any individual patient. It may be hazardous to presume that the point estimate of risk derived from a population model represents the most accurate estimate for a given patient. In this review, we exploit principles derived from physics as a metaphor for the distinction between predictions regarding populations versus patients. We identify the following: (1) predictions of risk are accurate at the level of populations but do not translate directly to patients, (2) perfect accuracy of individual risk estimation is unobtainable even with the addition of multiple novel risk factors, and (3) direct measurement of subclinical disease (screening) affords far greater certainty regarding the personalized treatment of patients, whereas risk estimates often remain uncertain for patients. In conclusion, shifting our focus from prediction of events to detection of disease could improve personalized decision-making and outcomes. We also discuss innovative future strategies for risk estimation and treatment allocation in preventive cardiology. Copyright © 2014 Elsevier Inc. All rights reserved.

Objectives and Design of BLEEDS: A Cohort Study to Identify New Risk Factors and Predictors for Major Bleeding during Treatment with Vitamin K Antagonists.

PubMed

van Rein, Nienke; Lijfering, Willem M; Bos, Mettine H A; Herruer, Martien H; Vermaas, Helga W; van der Meer, Felix J M; Reitsma, Pieter H

2016-01-01

Risk scores for patients who are at high risk for major bleeding complications during treatment with vitamin K antagonists (VKAs) do not perform that well. BLEEDS was initiated to search for new biomarkers that predict bleeding in these patients. To describe the outline and objectives of BLEEDS and to examine whether the study population is generalizable to other VKA treated populations. A cohort was created consisting of all patients starting VKA treatment at three Dutch anticoagulation clinics between January-2012 and July-2014. We stored leftover plasma and DNA following analysis of the INR. Of 16,706 eligible patients, 16,570 (99%) were included in BLEEDS and plasma was stored from 13,779 patients (83%). Patients had a mean age of 70 years (SD 14), 8713 were male (53%). The most common VKA indications were atrial fibrillation (10,876 patients, 66%) and venous thrombosis (3920 patients, 24%). 326 Major bleeds occurred during 17,613 years of follow-up (incidence rate 1.85/100 person years, 95%CI 1.66-2.06). The risk for major bleeding was highest in the initial three months of VKA treatment and increased when the international normalized ratio increased. These results and characteristics are in concordance with results from other VKA treated populations. BLEEDS is generalizable to other VKA treated populations and will permit innovative and unbiased research of biomarkers that may predict major bleeding during VKA treatment.

Severe pulmonary hypertension as the initial manifestation of systemic lupus erythematosus: a case report and review of the literature.

PubMed

Prete, M; Fatone, M C; Vacca, A; Racanelli, V; Perosa, F

2014-01-01

Severe pulmonary arterial hypertension (PAH) is rarely observed as the initial manifestation of systemic lupus erythematosus (SLE), and the diagnosis is often delayed. Here we present the case of a 32-year-old woman with severe PAH as the initial manifestation of SLE, who was successfully treated with mycophenolate mofetil and cyclosporine. This case offered the opportunity to critically review the epidemiology data, predictive markers, and pathogenic pathways of SLE-associated PAH (SLE-PAH) in relation to the currently available therapeutic options and to the main clinical trials of the last 10 years focused on the treatment of SLE-PAH. Mycophenolate mofetil and cyclosporine - currently used in the maintenance phase of the disease in certain clinical settings - should be considered, as an alternative to cyclophosphamide, in future clinical trials aimed at evaluating the most effective treatment of SLE-PAH at presentation.

A numerical simulation of tooth movement by wire bending.

PubMed

Kojima, Yukio; Fukui, Hisao

2006-10-01

In orthodontic treatment, wires are bent and attached to teeth to move them via elastic recovery. To predict how a tooth will move, the initial force system produced from the wire is calculated. However, the initial force system changes as the tooth moves and may not be used to predict the final tooth position. The purpose of this study was to develop a comprehensive mechanical, 3-dimensional, numerical model for predicting tooth movement. Tooth movements produced by wire bending were simulated numerically. The teeth moved as a result of bone remodeling, which occurs in proportion to stress in the periodontal ligament. With an off-center bend, a tooth near the bending position was subjected to a large moment and tipped more noticeably than the other teeth. Also, a tooth far from the bending position moved slightly in the mesial or the distal direction. With the center V-bend, when the second molar was added as an anchor tooth, the tipping angle and the intrusion of the canine increased, and movement of the first molar was prevented. When a wire with an inverse curve of Spee was placed in the mandibular arch, the calculated tendency of vertical tooth movements was the same as the measured result. In these tooth movements, the initial force system changed as the teeth moved. Tooth movement was influenced by the size of the root surface area. Tooth movements produced by wire bending could be estimated. It was difficult to predict final tooth positions from the initial force system.

Patterns of osteoporosis treatment change and treatment discontinuation among commercial and Medicare Advantage Prescription Drug members in a national health plan.

PubMed

Xu, Yihua; Viswanathan, Hema N; Ward, Melea A; Clay, Brad; Adams, John L; Stolshek, Bradley S; Kallich, Joel D; Fine, Shari; Saag, Kenneth G

2013-02-01

Multiple treatments are available for osteoporosis; however, little is known about treatment change patterns and associated factors. Osteoporosis treatment change patterns, discontinuation and factors associated with treatment change in members of a large national health plan were examined. A retrospective cohort study was conducted in 7315 commercial and 34 146 Medicare Advantage Prescription Drug (MAPD) members newly initiated on an osteoporosis medication between 2006 and 2008. Osteoporosis treatment change, discontinuation and re-initiation patterns were assessed. Multivariate logistic regression was used to examine factors associated with treatment change. Commercial and MAPD members were assessed separately because of differences in demographics and insurance benefits. Approximately 12% of members had a change in index therapy within 12 months. Almost 60% of members discontinued the index medication at least once, based on a 90-day refill gap. Over 40% of members discontinued all osteoporosis medications by the end of 12 months post-index. Among MAPD and commercial members, women and those with risedronate, ibandronate or calcitonin at index, index therapy in 2008 and an osteoporosis diagnosis were more likely to have a treatment change while members with health plans other than health maintenance organizations and generic alendronate at index were less likely to have a treatment change. Osteoporosis treatment change occurred in approximately 12% of members, while a greater proportion of members discontinued treatment completely within 12 months. Member characteristics may be used to predict therapy change for evaluation and quality initiatives within a health plan. © 2011 Blackwell Publishing Ltd.

Machine-Learning-Based Prediction of a Missed Scheduled Clinical Appointment by Patients With Diabetes.

PubMed

Kurasawa, Hisashi; Hayashi, Katsuyoshi; Fujino, Akinori; Takasugi, Koichi; Haga, Tsuneyuki; Waki, Kayo; Noguchi, Takashi; Ohe, Kazuhiko

2016-05-01

About 10% of patients with diabetes discontinue treatment, resulting in the progression of diabetes-related complications and reduced quality of life. The objective was to predict a missed clinical appointment (MA), which can lead to discontinued treatment for diabetes patients. A machine-learning algorithm was used to build a logistic regression model for MA predictions, with L2-norm regularization used to avoid over-fitting and 10-fold cross validation used to evaluate prediction performance. Data associated with patient MAs were extracted from electronic medical records and classified into two groups: one related to patients' clinical condition (X1) and the other related to previous findings (X2). The records used were those of the University of Tokyo Hospital, and they included the history of 16 026 clinical appointments scheduled by 879 patients whose initial clinical visit had been made after January 1, 2004, who had diagnostic codes indicating diabetes, and whose HbA1c had been tested within 3 months after their initial visit. Records between April 1, 2011, and June 30, 2014, were inspected for a history of MAs. The best predictor of MAs proved to be X1 + X2 (AUC = 0.958); precision and recall rates were, respectively, 0.757 and 0.659. Among all the appointment data, the day of the week when an appointment was made was most strongly associated with MA predictions (weight = 2.22). Our findings may provide information to help clinicians make timely interventions to avoid MAs. © 2015 Diabetes Technology Society.

Machine-Learning-Based Prediction of a Missed Scheduled Clinical Appointment by Patients With Diabetes

PubMed Central

Kurasawa, Hisashi; Hayashi, Katsuyoshi; Fujino, Akinori; Takasugi, Koichi; Haga, Tsuneyuki; Waki, Kayo; Noguchi, Takashi; Ohe, Kazuhiko

2015-01-01

Background: About 10% of patients with diabetes discontinue treatment, resulting in the progression of diabetes-related complications and reduced quality of life. Objective: The objective was to predict a missed clinical appointment (MA), which can lead to discontinued treatment for diabetes patients. Methods: A machine-learning algorithm was used to build a logistic regression model for MA predictions, with L2-norm regularization used to avoid over-fitting and 10-fold cross validation used to evaluate prediction performance. Data associated with patient MAs were extracted from electronic medical records and classified into two groups: one related to patients’ clinical condition (X1) and the other related to previous findings (X2). The records used were those of the University of Tokyo Hospital, and they included the history of 16 026 clinical appointments scheduled by 879 patients whose initial clinical visit had been made after January 1, 2004, who had diagnostic codes indicating diabetes, and whose HbA1c had been tested within 3 months after their initial visit. Records between April 1, 2011, and June 30, 2014, were inspected for a history of MAs. Results: The best predictor of MAs proved to be X1 + X2 (AUC = 0.958); precision and recall rates were, respectively, 0.757 and 0.659. Among all the appointment data, the day of the week when an appointment was made was most strongly associated with MA predictions (weight = 2.22). Conclusions: Our findings may provide information to help clinicians make timely interventions to avoid MAs. PMID:26555782

Surgical prediction of skeletal and soft tissue changes in treatment of Class II.

PubMed

de Lira, Ana de Lourdes Sá; de Moura, Walter Leal; Artese, Flávia; Bittencourt, Marcos Alan Vieira; Nojima, Lincoln Issamu

2013-04-01

The purpose of this study was to study the treatment outcomes and the accuracy of digital prediction and the actual postoperative outcome with Dolphin program on subjects presenting Class II malocclusions. Forty patients underwent surgical mandibular advancement (Group 1) and 40 underwent combined surgery of mandibular advancement and maxillary impaction (Group 2). The available pre surgical (t₁) and a minimum of 12 months post surgical (t₂) cephalometric radiographs were digitized. Predictive cephalograms (t₃) for both groups were traced. At all times evaluated, Group 1 displayed a shorter mandibular length and Group 2 had a longer lower face. In both groups the surgical interventions (t₂) were greater than initially predicted. There was no significant difference between groups with regards to overjet, overbite and soft tissue measurements. In both groups surgeries were more extensive than planned. Facial convexity and the distance of the lips to cranial base presented similar values between t₂ (post surgical) and t₃ (predicted). Copyright © 2012 European Association for Cranio-Maxillo-Facial Surgery. Published by Elsevier Ltd. All rights reserved.

Growth hormone treatment of early growth failure in toddlers with Turner syndrome: a randomized, controlled, multicenter trial.

PubMed

Davenport, Marsha L; Crowe, Brenda J; Travers, Sharon H; Rubin, Karen; Ross, Judith L; Fechner, Patricia Y; Gunther, Daniel F; Liu, Chunhua; Geffner, Mitchell E; Thrailkill, Kathryn; Huseman, Carol; Zagar, Anthony J; Quigley, Charmian A

2007-09-01

Typically, growth failure in Turner syndrome (TS) begins prenatally, and height sd score (SDS) declines progressively from birth. This study aimed to determine whether GH treatment initiated before 4 yr of age in girls with TS could prevent subsequent growth failure. Secondary objectives were to identify factors associated with treatment response, to determine whether outcome could be predicted by a regression model using these factors, and to assess the safety of GH treatment in this young cohort. This study was a prospective, randomized, controlled, open-label, multicenter clinical trial (Toddler Turner Study, August 1999 to August 2003). The study was conducted at 11 U.S. pediatric endocrine centers. Eighty-eight girls with TS, aged 9 months to 4 yr, were enrolled. Interventions comprised recombinant GH (50 mug/kg.d; n = 45) or no treatment (n = 43) for 2 yr. The main outcome measure was baseline-to-2-yr change in height SDS. Short stature was evident at baseline (mean length/height SDS = -1.6 +/- 1.0 at mean age 24.0 +/- 12.1 months). Mean height SDS increased in the GH group from -1.4 +/- 1.0 to -0.3 +/- 1.1 (1.1 SDS gain), whereas it decreased in the control group from -1.8 +/- 1.1 to -2.2 +/- 1.2 (0.5 SDS decline), resulting in a 2-yr between-group difference of 1.6 +/- 0.6 SDS (P < 0.0001). The baseline variable that correlated most strongly with 2-yr height gain was the difference between mid-parental height SDS and subjects' height SDS (r = 0.32; P = 0.04). Although attained height SDS at 2 yr could be predicted with good accuracy using baseline variables alone (R(2) = 0.81; P < 0.0001), prediction of 2-yr change in height SDS required inclusion of initial treatment response data (4-month or 1-yr height velocity) in the model (R(2) = 0.54; P < 0.0001). No new or unexpected safety signals associated with GH treatment were detected. Early GH treatment can correct growth failure and normalize height in infants and toddlers with TS.

How Does Decommissioning Forest Roads Effect Hydrologic and Geomorphic Risk?

NASA Astrophysics Data System (ADS)

Black, T.; Luce, C.; Cissel, R. M.; Nelson, N.; Staab, B.

2010-12-01

The US Forest Service is investigating road decommissioning projects to understand how treatments change hydrologic and geomorphic risks. Road treatment effect was measured using a before after control impact design (BACI), using the Geomorphic Road Analysis and Inventory Package (http://www.fs.fed.us/GRAIP). This suite of inventory and analysis tools evaluates: road-stream hydrologic connectivity, fine sediment production and delivery, shallow landslide risk, gully initiation risk, and risks associated with stream crossing failures. The Skokomish River study site is steep and wet and received a high intensity treatment including the removal of stream crossing pipes and fills, all ditch relief pipes and a full hillslope recontouring. Road to stream hydrologic connectivity was reduced by 70%. The treatments reduced fine sediment delivery by 21.8 tons or 81%. The removal of the stream crossing culverts and large associated road fills eliminated the risk of pipe plugging related failures and the eventual erosion of over 4,000 m3 of fill. The slope stability risk was assessed using a modified version of SINMAP (Pack et al, 2005). Risk below drain point locations on the original road was reduced as water was redistributed across the hillslope to waterbars and diffuse drainage. It is unclear; however, if landslide risk was reduced across the entire treated road length because treatments slightly increased risk in some areas where new concentrated drainage features were added above steep slopes. Similarly, values of a gully index ESI (Istanbulluoglu et al, 2003), were reduced at many of the original drainage points, however some new drainage was added. ESI values still exceed a predicted conservative initiation thresholds at some sites, therefore it is uncertain if gully risk will be changed. Mann Creek occupies a moderately steep mid-elevation site in Southern Idaho. The high intensity treatments removed all constructed road drainage features including stream crossing pipes and fills, and recontoured the hillslope. The length of road that was hydrologically connected to streams was reduced by 2,923 m, or 97%. The model predicts that fine sediment delivery was reduced by 98%, to 1.0 ton annually. The risk presented by stream crossings becoming plugged was eliminated. The potential for streamflow diversion onto roads and hillslopes was precluded. The slope stability risk below drain point locations on the original road was reduced as water was no longer concentrated and discharged through a single drainage feature. Treatments are predicted to return slope stability to near undisturbed levels. Gully initiation risks, already low prior to treatment, may be reduced to negligible values. Results from these two case studies suggest that high intensity road decommissioning can be effective at reducing the risk of road sediment delivery, hydrologic connectivity and failures associated with stream crossings. Post storm monitoring will help validate these predictions and reduce uncertainty around the hydrology of decommissioned roads. If decommissioned roads continue to concentrate water and discharge it onto steep slopes, landslides and gully risk may remain elevated.

Factors predicting Behavior Management Problems during Initial Dental Examination in Children Aged 2 to 8 Years

PubMed Central

Kumar, Dipanshu; Anand, Ashish; Mittal, Vipula; Singh, Aparna; Aggarwal, Nidhi

2017-01-01

Aim The aim of the present study was to identify the various background variables and its influence on behavior management problems (BMP) in children. Materials and methods The study included 165 children aged 2 to 8 years. During the initial dental visit, an experienced operator obtained each child’s background variables from accompanying guardians using a standardized questionnaire. Children’s dental behavior was rated by Frankel behavior rating scale. The behavior was then analyzed in relation to the answers of the questionnaire, and a logistic regression model was used to determine the power of the variables, separately or combined, to predict BMP. Results The logistic regression analysis considering differences in background variables between children with negative or positive behavior. Four variables turned out to be as predictors: Age, the guardian’s expectation of the child’s behavior at the dental examination, the child’s anxiety when meeting unfamiliar people, and the presence and absence of toothache. Conclusion The present study concluded that by means of simple questionnaire BMP in children may be expected if one of these attributes is found. Clinical significance Information on the origin of dental fear and uncooperative behavior in a child patient prior to treatment process may help the pediatric dentist plan appropriate behavior management and treatment strategy. How to cite this article Sharma A, Kumar D, Anand A, Mittal V, Singh A, Aggarwal N. Factors predicting Behavior Management Problems during Initial Dental Examination in Children Aged 2 to 8 Years. Int J Clin Pediatr Dent 2017;10(1):5-9. PMID:28377646

The Juvenile Addiction Risk Rating: Development and Initial Psychometrics

ERIC Educational Resources Information Center

Powell, Michael; Newgent, Rebecca A.

2016-01-01

This article describes the development and psychometrics of the Juvenile Addiction Risk Rating. The Juvenile Addiction Risk Rating is a brief screening of addiction potential based on 10 risk factors predictive of youth alcohol and drug-related problems that assists examiners in more accurate treatment planning when self-report information is…

Long Sick Leave after Orthopaedic Inpatient Rehabilitation: Treatment Failure or Relapse?

ERIC Educational Resources Information Center

Mangels, Marija; Schwarz, Susanne; Worringen, Ulrike; Holme, Martin; Rief, Winfried

2011-01-01

We investigated whether short-term versus long-term sick leave after orthopaedic inpatient rehabilitation can be predicted by initial assessment information, the clinical status at discharge, or whether the follow-up interval is crucial for later sick leave. We examined 214 patients from an orthopaedic rehabilitation hospital at admission,…

Dual purpose recovered coagulant from drinking water treatment residuals for adjustment of initial pH and coagulation aid in electrocoagulation process.

PubMed

Jung, Kyung-Won; Ahn, Kyu-Hong

2016-01-01

The present study is focused on the application of recovered coagulant (RC) by acidification from drinking water treatment residuals for both adjusting the initial pH and aiding coagulant in electrocoagulation. To do this, real cotton textile wastewater was used as a target pollutant, and decolorization and chemical oxygen demand (COD) removal efficiency were monitored. A preliminary test indicated that a stainless steel electrode combined with RC significantly accelerated decolorization and COD removal efficiencies, by about 52% and 56%, respectively, even at an operating time of 5 min. A single electrocoagulation system meanwhile requires at least 40 min to attain the similar removal performances. Subsequently, the interactive effect of three independent variables (applied voltage, initial pH, and reaction time) on the response variables (decolorization and COD removal) was evaluated, and these parameters were statistically optimized using the response surface methodology. Analysis of variance showed a high coefficient of determination values (decolorization, R(2) = 0.9925 and COD removal, R(2) = 0.9973) and satisfactory prediction second-order polynomial quadratic regression models. Average decolorization and COD removal of 89.52% and 94.14%, respectively, were achieved, corresponding to 97.8% and 98.1% of the predicted values under statistically optimized conditions. The results suggest that the RC effectively played a dual role of both adjusting the initial pH and aiding coagulant in the electrocoagulation process.

Predictors of outcome after treatment of mild traumatic brain injury: a pilot study.

PubMed

Leininger, Shelley; Strong, Carrie-Ann H; Donders, Jacobus

2014-01-01

To determine factors affecting outcome of comprehensive outpatient rehabilitation of individuals who sustained a mild traumatic brain injury. From a 4-year series of referrals, 49 nonconsecutive participants met criteria for mild traumatic brain injury (ie, loss of consciousness <30 minutes, Glasgow Coma Scale score >12). Outpatient, community-based postconcussion clinic at a rehabilitation hospital. Participants and therapy staff completed the Mayo-Portland Adaptability Inventory-Fourth Edition (MPAI-4) at the initiation and conclusion of treatment. Participants were also administered the Trail Making Test at the start of treatment. Participants generally gave poorer adaptability ratings than staff at the beginning and discharge of treatment. Regression analyses revealed that after controlling for baseline ratings, psychiatric history was associated with worse participant-rated MPAI-4 Adjustment scores at treatment discharge, whereas better Trail Making Test Part B performance at initiation of treatment predicted better participant-rated MPAI-4 Ability at treatment discharge. Premorbid demographic and baseline neurocognitive factors should be taken into account prior to comprehensive treatment of mild traumatic brain injury, as they can influence long-term outcomes. Adaptability ratings from both staff and participants can be useful in gaining different perspectives and assessing factors affecting recovery.

Pharmacogenetics-based area-under-curve model can predict efficacy and adverse events from axitinib in individual patients with advanced renal cell carcinoma.

PubMed

Yamamoto, Yoshiaki; Tsunedomi, Ryouichi; Fujita, Yusuke; Otori, Toru; Ohba, Mitsuyoshi; Kawai, Yoshihisa; Hirata, Hiroshi; Matsumoto, Hiroaki; Haginaka, Jun; Suzuki, Shigeo; Dahiya, Rajvir; Hamamoto, Yoshihiko; Matsuyama, Kenji; Hazama, Shoichi; Nagano, Hiroaki; Matsuyama, Hideyasu

2018-03-30

We investigated the relationship between axitinib pharmacogenetics and clinical efficacy/adverse events in advanced renal cell carcinoma (RCC) and established a model to predict clinical efficacy and adverse events using pharmacokinetic and gene polymorphisms related to drug metabolism and efflux in a phase II trial. We prospectively evaluated the area under the plasma concentration-time curve (AUC) of axitinib, objective response rate, and adverse events in 44 consecutive advanced RCC patients treated with axitinib. To establish a model for predicting clinical efficacy and adverse events, polymorphisms in genes including ABC transporters ( ABCB1 and ABCG2 ), UGT1A , and OR2B11 were analyzed by whole-exome sequencing, Sanger sequencing, and DNA microarray. To validate this prediction model, calculated AUC by 6 gene polymorphisms was compared with actual AUC in 16 additional consecutive patients prospectively. Actual AUC significantly correlated with the objective response rate ( P = 0.0002) and adverse events (hand-foot syndrome, P = 0.0055; and hypothyroidism, P = 0.0381). Calculated AUC significantly correlated with actual AUC ( P < 0.0001), and correctly predicted objective response rate ( P = 0.0044) as well as adverse events ( P = 0.0191 and 0.0082, respectively). In the validation study, calculated AUC prior to axitinib treatment precisely predicted actual AUC after axitinib treatment ( P = 0.0066). Our pharmacogenetics-based AUC prediction model may determine the optimal initial dose of axitinib, and thus facilitate better treatment of patients with advanced RCC.

Pharmacogenetics-based area-under-curve model can predict efficacy and adverse events from axitinib in individual patients with advanced renal cell carcinoma

PubMed Central

Yamamoto, Yoshiaki; Tsunedomi, Ryouichi; Fujita, Yusuke; Otori, Toru; Ohba, Mitsuyoshi; Kawai, Yoshihisa; Hirata, Hiroshi; Matsumoto, Hiroaki; Haginaka, Jun; Suzuki, Shigeo; Dahiya, Rajvir; Hamamoto, Yoshihiko; Matsuyama, Kenji; Hazama, Shoichi; Nagano, Hiroaki; Matsuyama, Hideyasu

2018-01-01

We investigated the relationship between axitinib pharmacogenetics and clinical efficacy/adverse events in advanced renal cell carcinoma (RCC) and established a model to predict clinical efficacy and adverse events using pharmacokinetic and gene polymorphisms related to drug metabolism and efflux in a phase II trial. We prospectively evaluated the area under the plasma concentration–time curve (AUC) of axitinib, objective response rate, and adverse events in 44 consecutive advanced RCC patients treated with axitinib. To establish a model for predicting clinical efficacy and adverse events, polymorphisms in genes including ABC transporters (ABCB1 and ABCG2), UGT1A, and OR2B11 were analyzed by whole-exome sequencing, Sanger sequencing, and DNA microarray. To validate this prediction model, calculated AUC by 6 gene polymorphisms was compared with actual AUC in 16 additional consecutive patients prospectively. Actual AUC significantly correlated with the objective response rate (P = 0.0002) and adverse events (hand-foot syndrome, P = 0.0055; and hypothyroidism, P = 0.0381). Calculated AUC significantly correlated with actual AUC (P < 0.0001), and correctly predicted objective response rate (P = 0.0044) as well as adverse events (P = 0.0191 and 0.0082, respectively). In the validation study, calculated AUC prior to axitinib treatment precisely predicted actual AUC after axitinib treatment (P = 0.0066). Our pharmacogenetics-based AUC prediction model may determine the optimal initial dose of axitinib, and thus facilitate better treatment of patients with advanced RCC. PMID:29682213

MicroRNAs and Glucocorticoid-Induced Apoptosis in Lymphoid Malignancies

PubMed Central

Sionov, Ronit Vogt

2013-01-01

The initial response of lymphoid malignancies to glucocorticoids (GCs) is a critical parameter predicting successful treatment. Although being known as a strong inducer of apoptosis in lymphoid cells for almost a century, the signaling pathways regulating the susceptibility of the cells to GCs are only partly revealed. There is still a need to develop clinical tests that can predict the outcome of GC therapy. In this paper, I discuss important parameters modulating the pro-apoptotic effects of GCs, with a specific emphasis on the microRNA world comprised of small players with big impacts. The journey through the multifaceted complexity of GC-induced apoptosis brings forth explanations for the differential treatment response and raises potential strategies for overcoming drug resistance. PMID:23431463

Prioritizing CD4 Count Monitoring in Response to ART in Resource-Constrained Settings: A Retrospective Application of Prediction-Based Classification

PubMed Central

Liu, Yan; Li, Xiaohong; Johnson, Margaret; Smith, Collette; Kamarulzaman, Adeeba bte; Montaner, Julio; Mounzer, Karam; Saag, Michael; Cahn, Pedro; Cesar, Carina; Krolewiecki, Alejandro; Sanne, Ian; Montaner, Luis J.

2012-01-01

Background Global programs of anti-HIV treatment depend on sustained laboratory capacity to assess treatment initiation thresholds and treatment response over time. Currently, there is no valid alternative to CD4 count testing for monitoring immunologic responses to treatment, but laboratory cost and capacity limit access to CD4 testing in resource-constrained settings. Thus, methods to prioritize patients for CD4 count testing could improve treatment monitoring by optimizing resource allocation. Methods and Findings Using a prospective cohort of HIV-infected patients (n = 1,956) monitored upon antiretroviral therapy initiation in seven clinical sites with distinct geographical and socio-economic settings, we retrospectively apply a novel prediction-based classification (PBC) modeling method. The model uses repeatedly measured biomarkers (white blood cell count and lymphocyte percent) to predict CD4+ T cell outcome through first-stage modeling and subsequent classification based on clinically relevant thresholds (CD4+ T cell count of 200 or 350 cells/µl). The algorithm correctly classified 90% (cross-validation estimate = 91.5%, standard deviation [SD] = 4.5%) of CD4 count measurements <200 cells/µl in the first year of follow-up; if laboratory testing is applied only to patients predicted to be below the 200-cells/µl threshold, we estimate a potential savings of 54.3% (SD = 4.2%) in CD4 testing capacity. A capacity savings of 34% (SD = 3.9%) is predicted using a CD4 threshold of 350 cells/µl. Similar results were obtained over the 3 y of follow-up available (n = 619). Limitations include a need for future economic healthcare outcome analysis, a need for assessment of extensibility beyond the 3-y observation time, and the need to assign a false positive threshold. Conclusions Our results support the use of PBC modeling as a triage point at the laboratory, lessening the need for laboratory-based CD4+ T cell count testing; implementation of this tool could help optimize the use of laboratory resources, directing CD4 testing towards higher-risk patients. However, further prospective studies and economic analyses are needed to demonstrate that the PBC model can be effectively applied in clinical settings. Please see later in the article for the Editors' Summary PMID:22529752

The current use of estrogens for growth-suppressant therapy in adolescent girls.

PubMed

Barnard, Neal D; Scialli, Anthony R; Bobela, Suzanne

2002-02-01

To assess the current prevalence of growth-suppressant therapy using oral estrogens for tall adolescent girls among U.S. pediatric endocrinologists. A questionnaire was mailed to pediatric endocrinologists practicing in the United States, asking how many patients each clinician had recently treated for tall stature using oral estrogens, whether he/she continued to offer such treatment, reasons for offering or declining to offer it, criteria for initiating and terminating treatment, choice of estrogen, and typical doses, durations, and effects. Of 411 respondents, 92 (22%) reported having treated 1-5 girls for tall stature during the preceding five years. Only 4 (1%) had treated more than 5 cases during this period. Growth-suppression treatment was currently offered by 137 respondents (33.3%). Reasons for doing so included parents' and patients' concerns about stature and the adverse social effects of unusually tall stature. Reasons for not offering such treatments were that its long-term risks are unknown, that tall stature is not a disease, and a lack of referrals. Few clinicians initiated treatment if predicted mature height was below 183 cm. Treatment was typically terminated based on evidence of epiphyseal fusion, usually within less than two years, although extended treatments were common. Frequently reported adverse effects included weight gain, nausea/vomiting, areolar or nipple pigmentation, headache, and irregular menses. Although treatment is less commonly initiated than in the past, many pediatric endocrinologists continue to offer oral estrogens to suppress growth for tall adolescent girls.

Post-infectious bronchiolitis obliterans in children: CT features that predict responsiveness to pulse methylprednisolone.

PubMed

Yoon, H M; Lee, J S; Hwang, J-Y; Cho, Y A; Yoon, H-K; Yu, J; Hong, S-J; Yoon, C H

2015-05-01

Intravenous pulse methylprednisolone therapy (IPMT) is an important treatment option for post-infectious obliterative bronchiolitis (OB), although it must be used carefully and only in selected patients because of its drawbacks. This study evaluated whether CT and clinical features of children with post-infectious OB can predict their responsiveness to IPMT. We searched the medical records for patients (less than 18 years of age) who were diagnosed with post-infectious OB between January 2000 and December 2011. 17 children who received IPMT were included in this study. All underwent chest CT before and after IPMT. The radiological features seen on pre-treatment CT were recorded. The air-trapping area percentages on pre- and post-treatment CT images were determined. The nine patients who exhibited decreased air trapping on post-treatment CT scans relative to pre-treatment scans were classed as responders. The patient ages and time from initial pneumonia to IPMT were recorded. All responders and only four non-responders had thickened bronchial walls before treatment (p = 0.029). The two groups did not differ significantly in terms of bronchiolitis, bronchiectasis or the extent of air trapping, although the responders had a significantly shorter median interval between initial pneumonia and IPMT (4 vs 50 months; p = 0.005) and were significantly younger (median, 2.0 vs 7.5 years; p = 0.048). Immediate IPMT may improve the degree of air trapping in children with post-infectious OB if they show a thickened bronchial wall on CT. Children with post-infectious OB may respond favourably to IPMT when pre-treatment CT indicates bronchial-wall thickening.

Predictive factors for successful clinical outcome 1 year after an intensive combined physical and psychological programme for chronic low back pain.

PubMed

van Hooff, Miranda L; Spruit, Maarten; O'Dowd, John K; van Lankveld, Wim; Fairbank, Jeremy C T; van Limbeek, Jacques

2014-01-01

The aim of this longitudinal study is to determine the factors which predict a successful 1-year outcome from an intensive combined physical and psychological (CPP) programme in chronic low back pain (CLBP) patients. A prospective cohort of 524 selected consecutive CLBP patients was followed. Potential predictive factors included demographic characteristics, disability, pain and cognitive behavioural factors as measured at pre-treatment assessment. The primary outcome measure was the oswestry disability index (ODI). A successful 1-year follow-up outcome was defined as a functional status equivalent to 'normal' and healthy populations (ODI ≤22). The 2-week residential programme fulfills the recommendations in international guidelines. For statistical analysis we divided the database into two equal samples. A random sample was used to develop a prediction model with multivariate logistic regression. The remaining cases were used to validate this model. The final predictive model suggested being 'in employment' at pre-treatment [OR 3.61 (95 % CI 1.80-7.26)] and an initial 'disability score' [OR 0.94 (95 % CI 0.92-0.97)] as significant predictive factors for a successful 1-year outcome (R (2) = 22 %; 67 % correctly classified). There was no predictive value from measures of psychological distress. CLBP patients who are in work and mild to moderately disabled at the start of a CPP programme are most likely to benefit from it and to have a successful treatment outcome. In these patients, the disability score falls to values seen in healthy populations. This small set of factors is easily identified, allowing selection for programme entry and triage to alternative treatment regimes.

A review of temporal effects and outcome predictors in substance abuse treatment studies with long-term follow-ups. Preliminary results and methodological issues.

PubMed

McKay, J R; Weiss, R V

2001-04-01

This article is an initial report from a review of alcohol and drug treatment studies with follow-ups of 2 years or more. The goals of the review are to examine the stability of substance use outcomes and the factors that moderate or mediate these outcomes. Results from 12 studies that generated multiple research reports are presented, and methodological problems encountered in the review are discussed. Substance use outcomes at the group level were generally stable, although moderate within-subject variation in substance use status over time was observed. Of factors assessed at baseline, psychiatric severity was a significant predictor of outcome in the highest percentage of reports, although the nature of the relationship varied. Stronger motivation and coping at baseline also consistently predicted better drinking outcomes. Better progress while in treatment, and the performance of pro-recovery behaviors and low problem severity in associated areas following treatment, consistently predicted better substance use outcomes.

Revascularization of smokers with claudication is not predicted to limit quality of life despite a higher risk of late failure.

PubMed

Mixson, Joshua D; Brothers, Thomas E

2017-01-01

Tobacco smoking after lower extremity revascularization for claudication has repeatedly been shown to increase the risk of adverse events, such that many vascular specialists consider that refusal to abstain from smoking constitutes a major contraindication to open surgical bypass or endovascular intervention. A Markov decision analysis (DA) model was used to compare the options of direct revascularization vs medical therapy only in smokers with claudication. The primary outcome was calculated quality of life (cQoL), determined for each patient at follow-up based on the outcomes of the treatment received. Markov DA software was used to predict the QoL for each treatment option preoperatively based on smoking status. Among patients referred during a recent 64-month period with vasculogenic claudication, 94 were actively smoking compared with 217 who were not. The DA model predicted that if the patients who smoked were to discontinue smoking, the best therapy would be bypass surgery for 77% and endovascular intervention for 17%. However, despite at least doubling the risks with intervention in the patients who continue to smoke, the DA model still predicted that 78% and 9% would fare better with open surgical or endovascular intervention, respectively. Among actively smoking patients, open surgical (3%) or endovascular (4%) therapies were initially performed in few patients, whereas 93% were offered only medical therapy. Among initial nonsmokers, revascularization was performed by open (27%) or endovascular (42%) means. At 3 years, the median (interquartile range [IQR]) cQoL was lower in initial smokers than in nonsmokers (0.73 [IQR, 0.73-0.77] vs 0.82 [IQR, 0.75-0.86]; P < .0001), primarily because of a lack of revascularization for smokers. Among initial smokers who did undergo revascularization initially, because of progression of symptoms, or after smoking cessation, cQoL was similar to initial nonsmokers (0.77 [IQR, 0.73-0.84] vs 0.73 [IQR, 0.73-0.73]; P = .37). Although 26% of initial smokers had stopped by the time of their last follow-up, 10% of initially nonsmoking patients were smoking at follow-up. However, among all patients undergoing intervention, the cQoL of patients smoking at the time of last their follow-up was similar to nonsmokers (0.82 [IQR, 0.82-0.86] vs 0.83 [IQR, 0.73-0.86]; P = .99). Patients with claudication who smoke may be denied the symptom improvement associated with revascularization, yet recidivism for smoking also occurs among patients who have stopped smoking in order to receive revascularization. The strategy not to directly revascularize patients with claudication who continue to smoke does not appear to maximize patient midterm QoL. Published by Elsevier Inc.

Isolating the Role of Psychological Dysfunction in Smoking Cessation Failure: Relations of Personality and Psychopathology to Attaining Smoking Cessation Milestones

PubMed Central

Leventhal, Adam M.; Japuntich, Sandra J.; Piper, Megan E.; Jorenby, Douglas E.; Schlam, Tanya R.; Baker, Timothy B.

2012-01-01

Research exploring psychological dysfunction as a predictor of smoking cessation success may be limited by nonoptimal predictor variables (i.e., categorical psychodiagnostic measures vs. continuous personality-based manifestations of dysfunction) and imprecise outcomes (i.e., summative point prevalence abstinence vs. constituent cessation milestone measures). Accordingly, this study evaluated the unique and overlapping relations of broad-spectrum personality traits (positive emotionality, negative emotionality, and constraint) and past-year psychopathology (anxiety, mood, and substance use disorder) to point prevalence abstinence and three smoking cessation milestones: (1) initiating abstinence; (2) first lapse; and (3) transition from lapse to relapse. Participants were daily smokers (N=1365) enrolled in a smoking cessation treatment study. In single predictor regression models, each manifestation of internalizing dysfunction (lower positive emotionality, higher negative emotionality, and anxiety and mood disorder) predicted failure at one or more cessation milestone. In simultaneous predictor models, lower positive and higher negative emotionality significantly predicted failure to achieve milestones after controlling for psychopathology. Psychopathology did not predict any outcome when controlling for personality. Negative emotionality showed the most robust and consistent effects, significantly predicting failure to initiate abstinence, earlier lapse, and lower point prevalence abstinence rates. Substance use disorder and constraint did not predict cessation outcomes, and no single variable predicted lapse-to-relapse transition. These findings suggest that personality-related manifestations of internalizing dysfunction are more accurate markers of affective sources of relapse risk than mood and anxiety disorders. Further, individuals with high trait negative emotionality may require intensive intervention to promote the initiation and early maintenance of abstinence. PMID:22642858

Early vedolizumab trough levels predict mucosal healing in inflammatory bowel disease: a multicentre prospective observational study.

PubMed

Yacoub, W; Williet, N; Pouillon, L; Di-Bernado, T; De Carvalho Bittencourt, M; Nancey, S; Lopez, A; Paul, S; Zallot, C; Roblin, X; Peyrin-Biroulet, L

2018-04-01

The correlation between vedolizumab trough levels during induction therapy and mucosal healing remains unknown. To compare early vedolizumab trough levels in patients with and without mucosal healing within the first year after treatment initiation. We prospectively collected vedolizumab trough levels in all inflammatory bowel disease patients at weeks 2, 6 and 14 of vedolizumab treatment in three French referral centres between 1 June 2014 and 31 March 2017. Results of every patient that underwent mucosal assessment by magnetic resonance imaging and/or endoscopy in the first year after treatment initiation were analysed. Median vedolizumab trough levels in the overall population (n = 82) were 27 μg/mL (interquartile range, IQR 21.2-33.8 μg/mL) at week 2, 23 μg/mL (IQR 15-34.5 μg/mL) at week 6 and 10.7 μg/mL (IQR 4.6-20.4 μg/mL) at week 14. Only median vedolizumab trough levels at week 6 differed between patients with and without mucosal healing within the first year after treatment initiation (26.8 vs 15.1 μg/mL, P = 0.035). A cut-off trough level of 18 μg/mL at week 6 predicted mucosal healing within the first year after the start of vedolizumab with an area under the receiver operating curve of 0.735 (95% confidence interval 0.531-0.939). A vedolizumab trough level above 18 μg/mL at week 6 was the only independent variable associated with mucosal healing within the first year of treatment (odds ratio 15.7, 95% confidence interval 2.4-173.0, P = 0.01). Early therapeutic drug monitoring might improve timely detection of vedolizumab-treated patients in need for an intensified dosing regimen. © 2018 John Wiley & Sons Ltd.

Population Pharmacokinetic Analysis and Model-Based Simulations of Aripiprazole for a 1-Day Initiation Regimen for the Long-Acting Antipsychotic Aripiprazole Lauroxil.

PubMed

Hard, Marjie L; Wehr, Angela Y; Sadler, Brian M; Mills, Richard J; von Moltke, Lisa

2018-06-11

BACKGROUND AND OBJECTIVES: Aripiprazole lauroxil (AL), a long-acting injectable antipsychotic for the treatment of schizophrenia, requires 21 days of oral aripiprazole supplementation upon initiation (21-day initiation regimen). An alternative 1-day initiation regimen utilizing a nano-crystalline milled dispersion of AL (AL NCD ) plus a single 30 mg oral aripiprazole dose achieved aripiprazole concentrations associated with therapeutic doses of aripiprazole in the same time frame as the 21-day initiation regimen when starting AL (441 or 882 mg). A population pharmacokinetic (PopPK) model was developed to describe aripiprazole pharmacokinetics following administration of AL NCD , AL and oral aripiprazole, and evaluate dosing scenarios likely to be encountered in clinical practice. In total, 12,768 plasma aripiprazole concentrations from 343 patients (from 4 clinical studies) were included in the PopPK analysis and used to construct the model. Concomitant administration of the 1-day initiation regimen with all approved AL dosing regimens (441, 662, or 882 mg monthly, 882 mg every 6 weeks, or 1064 mg every 2 months) is predicted to achieve aripiprazole concentrations associated with therapeutic doses of AL using the 21-day initiation regimen within 4 days, maintaining these concentrations until the next AL dose. Administration of the first AL injection 10 days after the 1-day initiation regimen resulted in median aripiprazole concentrations just before the second dose of AL ≥ 77% of that when coadministered on the same day. Coadministration of AL with a single AL NCD injection was predicted to be effective in rapidly re-establishing concentrations associated with therapeutic doses of AL following dose delay. Model-based simulations demonstrate that the 1-day initiation regimen is suitable for starting treatment with all AL doses, allowing a window of ≤ 10 days between initiation and AL administration. AL NCD may also be used to re-establish concentrations associated with therapeutic doses of AL in conjunction with a delayed AL dose.

Early physiological response to intensive care as a clinically relevant approach to predicting the outcome in severe acute pancreatitis.

PubMed

Flint, Richard; Windsor, John A

2004-04-01

The physiological response to treatment is a better predictor of outcome in acute pancreatitis than are traditional static measures. Retrospective diagnostic test study. The criterion standard was Organ Failure Score (OFS) and Acute Physiology and Chronic Health Evaluation II (APACHE II) score at the time of hospital admission. Intensive care unit of a tertiary referral center, Auckland City Hospital, Auckland, New Zealand. Consecutive sample of 92 patients (60 male, 32 female; median age, 61 years; range, 24-79 years) with severe acute pancreatitis. Twenty patients were not included because of incomplete data. The cause of pancreatitis was gallstones (42%), alcohol use (27%), or other (31%). At hospital admission, the mean +/- SD OFS was 8.1 +/- 6.1, and the mean +/- SD APACHE II score was 19.9 +/- 8.2. All cases were managed according to a standardized protocol. There was no randomization or testing of any individual interventions. Survival and death. There were 32 deaths (pretest probability of dying was 35%). The physiological response to treatment was more accurate in predicting the outcome than was OFS or APACHE II score at hospital admission. For example, 17 patients had an initial OFS of 7-8 (posttest probability of dying was 58%); after 48 hours, 7 had responded to treatment (posttest probability of dying was 28%), and 10 did not respond (posttest probability of dying was 82%). The effect of the change in OFS and APACHE II score was graphically depicted by using a series of logistic regression equations. The resultant sigmoid curve suggests that there is a midrange of scores (the steep portion of the graph) within which the probability of death is most affected by the response to intensive care treatment. Measuring the initial severity of pancreatitis combined with the physiological response to intensive care treatment is a practical and clinically relevant approach to predicting death in patients with severe acute pancreatitis.

Can multivariate models based on MOAKS predict OA knee pain? Data from the Osteoarthritis Initiative

NASA Astrophysics Data System (ADS)

Luna-Gómez, Carlos D.; Zanella-Calzada, Laura A.; Galván-Tejada, Jorge I.; Galván-Tejada, Carlos E.; Celaya-Padilla, José M.

2017-03-01

Osteoarthritis is the most common rheumatic disease in the world. Knee pain is the most disabling symptom in the disease, the prediction of pain is one of the targets in preventive medicine, this can be applied to new therapies or treatments. Using the magnetic resonance imaging and the grading scales, a multivariate model based on genetic algorithms is presented. Using a predictive model can be useful to associate minor structure changes in the joint with the future knee pain. Results suggest that multivariate models can be predictive with future knee chronic pain. All models; T0, T1 and T2, were statistically significant, all p values were < 0.05 and all AUC > 0.60.

Risk Score to Predict Need for Intensive Care in Initially Hemodynamically Stable Adults With Non-ST-Segment-Elevation Myocardial Infarction.

PubMed

Fanaroff, Alexander C; Chen, Anita Y; Thomas, Laine E; Pieper, Karen S; Garratt, Kirk N; Peterson, Eric D; Newby, L Kristin; de Lemos, James A; Kosiborod, Mikhail N; Amsterdam, Ezra A; Wang, Tracy Y

2018-05-25

Intensive care unit (ICU) use for initially stable patients presenting with non-ST-segment-elevation myocardial infarction (NSTEMI) varies widely across hospitals and minimally correlates with severity of illness. We aimed to develop a bedside risk score to assist in identifying high-risk patients with NSTEMI for ICU admission. Using the Acute Coronary Treatment and Intervention Outcomes Network (ACTION) Registry linked to Medicare data, we identified patients with NSTEMI aged ≥65 years without cardiogenic shock or cardiac arrest on presentation. Complications requiring ICU care were defined as subsequent development of cardiac arrest, shock, high-grade atrioventricular block, respiratory failure, stroke, or death during the index hospitalization. We developed and validated a model and integer risk score (Acute Coronary Treatment and Intervention Outcomes Network (ACTION) ICU risk score) that uses variables present at hospital admission to predict requirement for ICU care. Of 29 973 patients with NSTEMI, 4282 (14%) developed a complication requiring ICU-level care, yet 12 879 (43%) received care in an ICU. Signs or symptoms of heart failure, initial heart rate, initial systolic blood pressure, initial troponin, initial serum creatinine, prior revascularization, chronic lung disease, ST-segment depression, and age had statistically significant associations with requirement for ICU care after adjusting for other risk factors. The ACTION ICU risk score had a C-statistic of 0.72. It identified 11% of patients as having very high risk (>30%) of developing complications requiring ICU care and 49% as having low likelihood (<10%) of requiring an ICU. The ACTION ICU risk score quantifies the risk of initially stable patients with NSTEMI developing a complication requiring ICU care, and could be used to more effectively allocate limited ICU resources. © 2018 The Authors. Published on behalf of the American Heart Association, Inc., by Wiley.

The effect of lesion characteristic on remineralization and model sensitivity.

PubMed

Schäfer, F; Raven, S J; Parr, T A

1992-04-01

A major criterion for assessing the value of any experimental model in scientific research is the degree of correspondence between its results and data from the real-life process it is designed to model. Intra-oral models aimed at predicting the anti-caries efficacy of toothpastes or other topical treatments should therefore be calibrated against treatments proven to be effective in a caries clinical trial. For this to be achieved, it is necessary that a model with high sensitivity be designed, while at the same time retaining relevance to the process to be modeled. This means that the effects of the various experimental conditions and parameters of the model on its performance must be understood. The purpose of this paper was to assess the influence of two specific factors on the performance of an in situ enamel remineralization model, which is based on human enamel slabs attached to partial dentures. The two factors are initial lesion severity and origin of enamel sample. The results indicated that initial lesion size affected whether net remineralization or net demineralization occurred during in situ treatment. Samples with an initial range of from 1500 to 2500 (delta Z) tended more toward demineralization than did samples with delta Z greater than 3500. This means that treatment groups must be well-balanced with respect to initial lesion size. Differences in initial demineralization severity between different tooth locations must also be considered so that systematic treatment bias can be avoided. The solution used in the model discussed here is based on a balanced experimental design, which allows this effect to be taken into account in the data analysis.

Experimental test of an eco-evolutionary dynamic feedback loop between evolution and population density in the green peach aphid.

PubMed

Turcotte, Martin M; Reznick, David N; Daniel Hare, J

2013-05-01

An eco-evolutionary feedback loop is defined as the reciprocal impacts of ecology on evolutionary dynamics and evolution on ecological dynamics on contemporary timescales. We experimentally tested for an eco-evolutionary feedback loop in the green peach aphid, Myzus persicae, by manipulating initial densities and evolution. We found strong evidence that initial aphid density alters the rate and direction of evolution, as measured by changes in genotype frequencies through time. We also found that evolution of aphids within only 16 days, or approximately three generations, alters the rate of population growth and predicts density compared to nonevolving controls. The impact of evolution on population dynamics also depended on density. In one evolution treatment, evolution accelerated population growth by up to 10.3% at high initial density or reduced it by up to 6.4% at low initial density. The impact of evolution on population growth was as strong as or stronger than that caused by a threefold change in intraspecific density. We found that, taken together, ecological condition, here intraspecific density, alters evolutionary dynamics, which in turn alter concurrent population growth rate (ecological dynamics) in an eco-evolutionary feedback loop. Our results suggest that ignoring evolution in studies predicting population dynamics might lead us to over- or underestimate population density and that we cannot predict the evolutionary outcome within aphid populations without considering population size.

Management of fibular hemimelia using the Ilizarov method at Siriraj Hospital in Thailand.

PubMed

Unprasert, Prangthong; Kaewpornsawan, Kamolporn; Chotigavanichaya, Chatupon; Eamsobhana, Perajit

2014-09-01

Fibular hemimelia is one of the most common congenital longitudinal bone deficiencies. Previous treatment protocols called for amputation of the deficient limb; while others made attempts to save the limb. The objective of treatment is to restore function and achieve patient satisfaction. The authors evaluated the outcomes of the Ilizarov technique for the treatment of leg-length discrepancy and bone associated deformities in patients with fibular hemimelia. The present study also evaluated and assessed complications, knee and ankle function, and patient satisfaction with the treatment. Nine patients with fibular hemimelia who underwent tibial lengthening using the Ilizarov method were reviewed in the present study. Initial condition data, including age, gender type offibular hemimelia, initial limb-length discrepancy, predicted limb-length discrepancy, and the data were collected and analyzed. Activity level, patient satisfaction, complications, and residual leg-length discrepancy were assessed at the end of treatment. According to Achterman and Kalamchi classification, there were 4 patients with Type IA, 3 patients with Type IB, and 2 patients with Type II. In Type IA, the affected leg-length discrepancy and mean age at the initial treatment were 3.25 cm and 7.75 years, respectively. In type IB, the affected leg-length discrepancy and mean age at the initial treatment were 5.83 cm and 4.3 years, respectively. In Type II, the affected leg-length discrepancy and mean age at the initial treatment were 5.5 cm and 5 years, respectively. The mean follow-up was 5 years (range: 7-10). The mean lengthening was 7.52 cm (range: 4-13). The lengthening index was 1.28 mo/cm. The mean residual leg-length discrepancy was 0.94 cm. There was ankle joint stiffness and mild equinous foot in type II cases, but patients could walk well without gait aid. No patients were experiencing pain by the end of treatment. All patients expressed satisfaction with this technique. The Ilizarov technique for bone lengthening of the tibia has shown satisfactory results in the treatment of all types of congenital fibular hemimelia and should be considered an attractive alternative to amputation, as measureable functional improvement can be expected.

Comorbid insomnia symptoms predict lower 6-month adherence to CPAP in US veterans with obstructive sleep apnea.

PubMed

Wallace, Douglas M; Sawyer, A M; Shafazand, S

2018-03-01

There is limited information on the association between pre-treatment insomnia symptoms and dysfunctional sleep beliefs with continuous positive airway pressure (CPAP) adherence in veterans with obstructive sleep apnea (OSA). Our aims were to describe demographic and sleep characteristics of veterans with and without comorbid insomnia and determine whether pre-treatment insomnia symptoms and dysfunctional sleep beliefs predict CPAP use after 6 months of therapy. Hispanic veterans attending the Miami VA sleep clinic were recruited and completed the insomnia severity index, the dysfunctional sleep belief and attitude scale (DBAS), and other questionnaires. Participants were asked to return after 7 days and 1 and 6 months to repeat questionnaires and for objective CPAP adherence download. Hierarchical regression models were performed to determine adjusted associations of pre-treatment insomnia symptoms and DBAS sub-scores on 6-month mean daily CPAP use. Fifty-three participants completed the 6-month follow-up visit with a mean CPAP use of 3.4 ± 1.9 h. Veterans with comorbid insomnia had lower mean daily CPAP use (168 ± 125 vs 237 ± 108 min, p = 0.04) and lower percent daily CPAP use ≥ 4 h (32 ± 32 vs 51 ± 32%, p = 0.05) compared to participants without insomnia. In adjusted analyses, pre-treatment insomnia symptoms (early, late, and aggregated nocturnal symptoms) and sleep dissatisfaction were predictive of lower CPAP use at 6 months. Pre-treatment dysfunctional sleep beliefs were not associated with CPAP adherence. Pre-treatment nocturnal insomnia symptoms and sleep dissatisfaction predicted poorer 6- month CPAP use. Insomnia treatment preceding or concurrent with CPAP initiation may eliminate a barrier to regular use.

A Two-Year Follow-up on Systematic Desensitization with Data Pertaining to the External Validity of Laboratory Fear Assessment

ERIC Educational Resources Information Center

Rosen, Gerald M.; And Others

1977-01-01

A 2-year follow-up questionnaire was sent to subjects originally tested by Rosen, Glasgow, and Barrera. Initial treatment gains for self- and therapist-directed desensitization subjects were maintained. Posttest behavior approach scores were not predictive of real-life behavioral change as reported at follow-up. (Author)

Emergencies in Child Psychiatry: A Definition and Comparison of Two Groups.

ERIC Educational Resources Information Center

Morrison, Gilbert C.; Smith, Wiley R.

The two groups of children and adolescents seen for emergency psychiatric treatment were studied in an attempt to determine what constitutes an emergency in child psychiatry, whose anxiety initiates consultation, what the precipitating factors are and how they can be predicted, and to ascertain who is crucial to the management of these problems.…

Validation of the Predictive Value of Modeled Human Chorionic Gonadotrophin Residual Production in Low-Risk Gestational Trophoblastic Neoplasia Patients Treated in NRG Oncology/Gynecologic Oncology Group-174 Phase III Trial.

PubMed

You, Benoit; Deng, Wei; Hénin, Emilie; Oza, Amit; Osborne, Raymond

2016-01-01

In low-risk gestational trophoblastic neoplasia, chemotherapy effect is monitored and adjusted with serum human chorionic gonadotrophin (hCG) levels. Mathematical modeling of hCG kinetics may allow prediction of methotrexate (MTX) resistance, with production parameter "hCGres." This approach was evaluated using the GOG-174 (NRG Oncology/Gynecologic Oncology Group-174) trial database, in which weekly MTX (arm 1) was compared with dactinomycin (arm 2). Database (210 patients, including 78 with resistance) was split into 2 sets. A 126-patient training set was initially used to estimate model parameters. Patient hCG kinetics from days 7 to 45 were fit to: [hCG(time)] = hCG7 * exp(-k * time) + hCGres, where hCGres is residual hCG tumor production, hCG7 is the initial hCG level, and k is the elimination rate constant. Receiver operating characteristic (ROC) analyses defined putative hCGRes predictor of resistance. An 84-patient test set was used to assess prediction validity. The hCGres was predictive of outcome in both arms, with no impact of treatment arm on unexplained variability of kinetic parameter estimates. The best hCGres cutoffs to discriminate resistant versus sensitive patients were 7.7 and 74.0 IU/L in arms 1 and 2, respectively. By combining them, 2 predictive groups were defined (ROC area under the curve, 0.82; sensitivity, 93.8%; specificity, 70.5%). The predictive value of hCGres-based groups regarding resistance was reproducible in test set (ROC area under the curve, 0.81; sensitivity, 88.9%; specificity, 73.1%). Both hCGres and treatment arm were associated with resistance by logistic regression analysis. The early predictive value of the modeled kinetic parameter hCGres regarding resistance seems promising in the GOG-174 study. This is the second positive evaluation of this approach. Prospective validation is warranted.

Objectives and Design of BLEEDS: A Cohort Study to Identify New Risk Factors and Predictors for Major Bleeding during Treatment with Vitamin K Antagonists

PubMed Central

van Rein, Nienke; Lijfering, Willem M.; Bos, Mettine H. A.; Herruer, Martien H.; Vermaas, Helga W.; van der Meer, Felix J. M.; Reitsma, Pieter H.

2016-01-01

Background Risk scores for patients who are at high risk for major bleeding complications during treatment with vitamin K antagonists (VKAs) do not perform that well. BLEEDS was initiated to search for new biomarkers that predict bleeding in these patients. Objectives To describe the outline and objectives of BLEEDS and to examine whether the study population is generalizable to other VKA treated populations. Methods A cohort was created consisting of all patients starting VKA treatment at three Dutch anticoagulation clinics between January-2012 and July-2014. We stored leftover plasma and DNA following analysis of the INR. Results Of 16,706 eligible patients, 16,570 (99%) were included in BLEEDS and plasma was stored from 13,779 patients (83%). Patients had a mean age of 70 years (SD 14), 8713 were male (53%). The most common VKA indications were atrial fibrillation (10,876 patients, 66%) and venous thrombosis (3920 patients, 24%). 326 Major bleeds occurred during 17,613 years of follow-up (incidence rate 1.85/100 person years, 95%CI 1.66–2.06). The risk for major bleeding was highest in the initial three months of VKA treatment and increased when the international normalized ratio increased. These results and characteristics are in concordance with results from other VKA treated populations. Conclusion BLEEDS is generalizable to other VKA treated populations and will permit innovative and unbiased research of biomarkers that may predict major bleeding during VKA treatment. PMID:27935941

The two faces of enhancing utilization of health-care services: determinants of patient initiation and retention in rural Burkina Faso.

PubMed Central

Mugisha, Frederick; Bocar, Kouyate; Dong, Hengjin; Chepng'eno, Gloria; Sauerborn, Rainer

2004-01-01

OBJECTIVE: To explore the factors that determine whether a patient will initiate treatment within a system of health-care services, and the factors that determine whether the patient will be retained in the chosen system, in Nouna, rural Burkina Faso. METHODS: The data used were pooled from four rounds of a household survey conducted in Nouna, rural Burkina Faso. The ongoing demographic surveillance system provided a sampling framework for this survey in which 800 households were sampled using a two-stage cluster sampling procedure. More than one treatment episode was observed for a single episode of illness per patient. The multinomial logit model was used to explore the determinants of patient initiation to systems of modern, traditional and home treatment, and a binary logit model was used to explore the determinants of patient retention within the chosen health-care provider system. FINDINGS: The results suggest that the determinants of patient initiation and their subsequent retention are different. Household income, education, urban residence and expected competency of the provider are positive predictors of initiation, but not of retention, for modern health-care services. Only perceived quality of care positively predicted retention in modern health-care services. CONCLUSION: Interventions focusing on patient initiation and patient retention are likely to be different. Policies directed at enhancing initiation for modern health-care services would primarily focus on reducing financial barriers, while those directed at increasing retention would primarily focus on attributes that improve the perceived quality of care. PMID:15375446

Treatment, alcoholics anonymous, and 16-year changes in impulsivity and legal problems among men and women with alcohol use disorders.

PubMed

Blonigen, Daniel M; Timko, Christine; Moos, Bernice S; Moos, Rudolf H

2009-09-01

The link between impulsive personality traits and alcohol use disorders (AUDs) is well established. No studies, however, have investigated whether receipt of help for AUDs predicts change in impulsivity or whether such change is associated with relevant outcomes such as legal problems. The present study examined predictive associations between the duration of help for AUDs (Alcoholics Anonymous [AA], professional treatment) and impulsivity and legal problems over 16 years in men and women with AUDs. Participants who were initially untreated for their AUDs (n(men) = 332, n(women) = 296) completed follow-up telephone interviews at 1 and 16 years after their baseline assessment. Impulsivity and legal problems declined between baseline and the 1-year and 16-year follow-ups among both women and men. A longer duration of participation in AA predicted a decline in impulsivity at both follow-up assessments, and, in turn, a decline in impulsivity predicted a decline in legal problems at Years 1 and 16. In addition, a longer duration of participation in AA predicted fewer legal problems at Year 1, and this association was moderated by gender (significant in men) and impulsivity (significant for individuals with higher baseline scores). The results highlight the potential for AA and professional treatment to reduce the expression of impulsivity and related disinhibitory traits and legal problems in individuals with AUDs.

In Silico Identification of Bioremediation Potential: Carbamazepine and Other Recalcitrant Personal Care Products.

PubMed

Aukema, Kelly G; Escalante, Diego E; Maltby, Meghan M; Bera, Asim K; Aksan, Alptekin; Wackett, Lawrence P

2017-01-17

Emerging contaminants are principally personal care products not readily removed by conventional wastewater treatment and, with an increasing reliance on water recycling, become disseminated in drinking water supplies. Carbamazepine, a widely used neuroactive pharmaceutical, increasingly escapes wastewater treatment and is found in potable water. In this study, a mechanism is proposed by which carbamazepine resists biodegradation, and a previously unknown microbial biodegradation was predicted computationally. The prediction identified biphenyl dioxygenase from Paraburkholderia xenovorans LB400 as the best candidate enzyme for metabolizing carbamazepine. The rate of degradation described here is 40 times greater than the best reported rates. The metabolites cis-10,11-dihydroxy-10,11-dihydrocarbamazepine and cis-2,3-dihydroxy-2,3-dihydrocarbamazepine were demonstrated with the native organism and a recombinant host. The metabolites are considered nonharmful and mitigate the generation of carcinogenic acridine products known to form when advanced oxidation methods are used in water treatment. Other recalcitrant personal care products were subjected to prediction by the Pathway Prediction System and tested experimentally with P. xenovorans LB400. It was shown to biodegrade structurally diverse compounds. Predictions indicated hydrolase or oxygenase enzymes catalyzed the initial reactions. This study highlights the potential for using the growing body of enzyme-structural and genomic information with computational methods to rapidly identify enzymes and microorganisms that biodegrade emerging contaminants.

Do patients׳ illness beliefs predict depression measures at six months in primary care; a longitudinal study.

PubMed

Lynch, Jeannette; Moore, Michael; Moss-Morris, Rona; Kendrick, Tony

2015-03-15

Depressive disorders are prevalent and costly but there is a lack of evidence on how best to select treatments for mild to moderate depression in primary care. Illness beliefs have been shown to affect the outcome from physical illness, but there is limited information on the beliefs of patients who are depressed. To measure patients׳ beliefs about depression at baseline and determine whether these relate to depression severity at six months. Primary care patients with a recently diagnosed episode of depression completed the Beliefs about Depression Questionnaire and depression severity scores at baseline. The primary outcome was the change in depression severity score on the Hospital Anxiety and Depression Scale after six months. 227/292 (78%) participants completed follow-up questionnaires. Initial severity of depression at baseline, and particular beliefs about the causes, consequences and timeline of depression predicted poorer outcomes, whereas a belief in using exercise or keeping busy to treat depression predicted improved outcomes. Prescription of antidepressants did not appear to mediate these relationships. This was an initial study using a new validated questionnaire and it cannot be predicted whether these results are representative or would be reproduced in other populations. Although participants were primary care patients whose GP (General Practitioner) had coded as having a new incident episode of depression in the preceding six months, 43% of participants stated they had been depressed for more than a year. Sufficient participants were recruited to ensure the study was adequately powered but participation rate was 30%, raising the possibility of response bias. Illness beliefs may help to predict outcomes in depression and therefore assessing and addressing patients׳ beliefs about their depression may enhance treatment. Crown Copyright © 2015. Published by Elsevier B.V. All rights reserved.

Persistence of thyrotropin (TSH) receptor antibodies in children and adolescents with Graves' disease treated using antithyroid medication.

PubMed

Smith, Jessica; Brown, Rosalind S

2007-11-01

To determine the course of thyrotropin (thyroid-stimulating hormone [TSH]) receptor antibodies (TRAbs) in children and adolescents with Graves' disease treated using antithyroid drugs (ATDs). Retrospective, cross-sectional study of 86 children and adolescents with Graves' disease treated medically for >3 years. Patients with Hashimoto's thyroiditis and idiopathic short stature (n = 30) served as controls. A second-generation enzyme-linked immunosorbent assay (ELISA) for TRAbs was used. Twenty-two out of 23 (95.7%) patients with newly diagnosed Graves' disease, but 0/30 controls, had detectable TRAbs (22.0 +/- 13.5 U/L [mean +/- SD] vs. 0.9 +/- 0.9 U/L, p < 0.0001). Mean TRAb levels decreased with duration of therapy, but even after 13-24 months, TRAbs had normalized in only 3/16 (18.8%) patients. The initial TRAb titer correlated significantly with severity of the initial hyperthyroidism, but did not predict the response to therapy as indicated by the dosage of ATD required to control the hyperthyroidism at 6 and 12 months. Unlike adults, most children and adolescents with Graves' disease require >2 years of ATD treatment before TRAbs are normalized. Although initial TRAb activity reflects disease severity, it does not predict the response to medical therapy. Recommendations as to treatment duration developed for adult patients should not be applied to the young.

Predicting Early Death Among Elderly Dialysis Patients: Development and Validation of a Risk Score to Assist Shared Decision Making for Dialysis Initiation.

PubMed

Thamer, Mae; Kaufman, James S; Zhang, Yi; Zhang, Qian; Cotter, Dennis J; Bang, Heejung

2015-12-01

A shared decision-making tool could help elderly patients with advanced chronic kidney disease decide about initiating dialysis therapy. Because mortality may be high in the first few months after initiating dialysis therapy, incorporating early mortality predictors in such a tool would be important for an informed decision. Our objective is to derive and validate a predictive risk score for early mortality after initiating dialysis therapy. Retrospective observational cohort, with development and validation cohorts. US Renal Data System and claims data from the Centers for Medicare & Medicaid Services for 69,441 (aged ≥67 years) patients with end-stage renal disease with a previous 2-year Medicare history who initiated dialysis therapy from January 1, 2009, to December 31, 2010. Demographics, predialysis care, laboratory data, functional limitations, and medical history. All-cause mortality in the first 3 and 6 months. Predicted mortality by logistic regression. The simple risk score (total score, 0-9) included age (0-3 points), low albumin level, assistance with daily living, nursing home residence, cancer, heart failure, and hospitalization (1 point each), and showed area under the receiver operating characteristic curve (AUROC)=0.69 in the validation sample. A comprehensive risk score with additional predictors was also developed (with AUROC=0.72, high concordance between predicted vs observed risk). Mortality probabilities were estimated from these models, with the median score of 3 indicating 12% risk in 3 months and 20% in 6 months, and the highest scores (≥8) indicating 39% risk in 3 months and 55% in 6 months. Patients who did not choose dialysis therapy and did not have a 2-year Medicare history were excluded. Routinely available information can be used by patients with chronic kidney disease, families, and their nephrologists to estimate the risk of early mortality after dialysis therapy initiation, which may facilitate informed decision making regarding treatment options. Copyright © 2015 National Kidney Foundation, Inc. All rights reserved.

Does universal active MRSA surveillance influence anti-MRSA antibiotic use? A retrospective analysis of the treatment of patients admitted with suspicion of infection at Veterans Affairs Medical Centers between 2005 and 2010.

PubMed

Jones, Makoto; Huttner, Benedikt; Leecaster, Molly; Huttner, Angela; Damal, Kavitha; Tanner, Windy; Nielson, Christopher; Rubin, Michael A; Goetz, Matthew Bidwell; Madaras-Kelly, Karl; Samore, Matthew H

2014-12-01

After the implementation of an active surveillance programme for MRSA in US Veterans Affairs (VA) Medical Centers, there was an increase in vancomycin use. We investigated whether positive MRSA admission surveillance tests were associated with MRSA-positive clinical admission cultures and whether the availability of surveillance tests influenced prescribers' ability to match initial anti-MRSA antibiotic use with anticipated MRSA results from clinical admission cultures. Analyses were based on barcode medication administration data, microbiology data and laboratory data from 129 hospitals between January 2005 and September 2010. Hospitalized patient admissions were included if clinical cultures were obtained and antibiotics started within 2 days of admission. Mixed-effects logistic regression was used to examine associations between positive MRSA admission cultures and (i) admission MRSA surveillance test results and (ii) initial anti-MRSA therapy. Among 569,815 included admissions, positive MRSA surveillance tests were strong predictors of MRSA-positive admission cultures (OR 8.5; 95% CI 8.2-8.8). The negative predictive value of MRSA surveillance tests was 97.6% (95% CI 97.5%-97.6%). The diagnostic OR between initial anti-MRSA antibiotics and MRSA-positive admission cultures was 3.2 (95% CI 3.1-3.4) for patients without surveillance tests and was not significantly different for admissions with surveillance tests. The availability of nasal MRSA surveillance tests in VA hospitals did not seem to improve the ability of prescribers to predict the necessity of initial anti-MRSA treatment despite the high negative predictive value of MRSA surveillance tests. Prospective trials are needed to establish the safety and effectiveness of using MRSA surveillance tests to guide antibiotic therapy. Published by Oxford University Press on behalf of the British Society for Antimicrobial Chemotherapy 2014. This work is written by (a) US Government employee(s) and is in the public domain in the US.

Methicillin-Resistant Staphylococcus aureus in Foot Osteomyelitis.

PubMed

Ashong, Chester N; Raheem, Shazia A; Hunter, Andrew S; Mindru, Cezarina; Barshes, Neal R

Conflicting studies exist regarding the impact of methicillin-resistant Staphylococcus aureus (MRSA) on increased time to wound healing, future need for surgical procedures, and likelihood of treatment failure in patients with diabetic foot osteomyelitis. The purpose of this study is to determine the overall significance of MRSA in predicting treatment failure in bone infections of the foot and to determine an appropriate pre-operative and empiric post-operative antibiotic regimen. Patients presenting with an initial episode of "probable" or "definite" foot osteomyelitis were included for review and analysis if the following criteria were met: (1) Osteomyelitis occurred in the foot (i.e., distal to the malleoli of the ankle); episodes occurring above the ankle were excluded. (2) Patients received either no antibiotics or only oral antibiotics for long-term treatment; episodes managed with long-term parenteral antibiotics were excluded. (3) The infection was managed initially with medical therapy or conservative surgical therapy; episodes managed with major (above-ankle) amputation as the initial treatment were excluded. The primary objective of this study was to assess whether episodes of foot osteomyelitis associated with MRSA resulted in treatment failure more frequently than not. Of 178 episodes included in the study, 50 (28.1%) episodes had treatment failure. Median time-to-treatment failure was 60 days (range 7-598 days). In 28.1% (9/32 episodes) in which treatment failure occurred and 39.0% (41/105) episodes in which no treatment failure occurred, MRSA was present. The presence of MRSA was not significantly associated with treatment failure (p = 0.99). The presence of MRSA in bone culture and whether antibiotic use had anti-MRSA activity was not associated with increased treatment failure of diabetic foot osteomyelitis in our institution. Empiric antibiotic coverage of MRSA may not be necessary for many patients presenting with foot osteomyelitis.

A Randomized Clinical Trial of Methadone Maintenance for Prisoners: Prediction of Treatment Entry and Completion in Prison

PubMed Central

GORDON, MICHAEL S.; KINLOCK, TIMOTHY W.; COUVILLION, KATHRYN A.; SCHWARTZ, ROBERT P.; O’GRADY, KEVIN

2014-01-01

The present report is an intent-to-treat analysis involving secondary data drawn from the first randomized clinical trial of prison-initiated methadone in the United States. This study examined predictors of treatment entry and completion in prison. A sample of 211 adult male prerelease inmates with preincarceration heroin dependence were randomly assigned to one of three treatment conditions: counseling only (counseling in prison; n= 70); counseling plus transfer (counseling in prison with transfer to methadone maintenance treatment upon release; n= 70); and counseling plus methadone (methadone maintenance in prison, continued in a community-based methadone maintenance program upon release; n= 71). Entered prison treatment (p <. 01), and completed prison treatment (p< .001) were significantly predicted by the set of 10 explanatory variables and favored the treatment conditions receiving methadone. The present results indicate that individuals who are older in age and have longer prison sentences may have better outcomes than younger individuals with shorter sentences, meaning they are more likely to enter and complete prison-based treatment. Furthermore, implications for the treatment of prisoners with prior heroin dependence and for conducting clinical trials may indicate the importance of examining individual characteristics and the possibility of the examination of patient preference. PMID:25392605

Military sexual assault, gender, and PTSD treatment outcomes of U.S. Veterans.

PubMed

Tiet, Quyen Q; Leyva, Yani E; Blau, Kathy; Turchik, Jessica A; Rosen, Craig S

2015-04-01

This study examined whether gender and military sexual assault (MSA) were associated with psychiatric severity differences at initiation of treatment for posttraumatic stress disorder (PTSD) and whether MSA and gender predicted psychiatric treatment outcomes. Male (n = 726) and female (n = 111) patients were recruited from 7 U.S. Department of Veterans Affairs (VA) PTSD specialty intensive treatment programs and completed an intake survey; 69% (n = 574) of the participants completed a 4-month postdischarge follow-up survey. Measures included current PTSD and depressive symptoms, aggressive/violent behaviors, alcohol and drug use severity, and quality of life. Multilevel multivariate regression analyses were conducted to examine the main and interaction effects of gender and MSA on psychiatric treatment outcomes at 4-month follow-up, including demographics, baseline severity, hostile fire, and treatment length of stay. Baseline PTSD severity did not differ by gender or MSA status, but women had more severe depressive symptoms (d = 0.40) and less aggressive/violent symptoms (d = -0.46) than men. Gender, MSA status, and the interaction between gender and MSA did not predict treatment outcomes as hypothesized. Male and female veterans with and without MSA responded equally well to treatment in VA PTSD intensive treatment programs. Published 2015. This article is a U.S. Government work and is in the public domain in the USA.

A Randomized Clinical Trial of Methadone Maintenance for Prisoners: Prediction of Treatment Entry and Completion in Prison.

PubMed

Gordon, Michael S; Kinlock, Timothy W; Couvillion, Kathryn A; Schwartz, Robert P; O'Grady, Kevin

2012-05-01

The present report is an intent-to-treat analysis involving secondary data drawn from the first randomized clinical trial of prison-initiated methadone in the United States. This study examined predictors of treatment entry and completion in prison. A sample of 211 adult male prerelease inmates with preincarceration heroin dependence were randomly assigned to one of three treatment conditions: counseling only (counseling in prison; n= 70); counseling plus transfer (counseling in prison with transfer to methadone maintenance treatment upon release; n= 70); and counseling plus methadone (methadone maintenance in prison, continued in a community-based methadone maintenance program upon release; n= 71). Entered prison treatment (p <. 01), and completed prison treatment (p< .001) were significantly predicted by the set of 10 explanatory variables and favored the treatment conditions receiving methadone. The present results indicate that individuals who are older in age and have longer prison sentences may have better outcomes than younger individuals with shorter sentences, meaning they are more likely to enter and complete prison-based treatment. Furthermore, implications for the treatment of prisoners with prior heroin dependence and for conducting clinical trials may indicate the importance of examining individual characteristics and the possibility of the examination of patient preference.

Artificial neural network predictions of lengths of stay on a post-coronary care unit.

PubMed

Mobley, B A; Leasure, R; Davidson, L

1995-01-01

To create and validate a model that predicts length of hospital unit stay. Ex post facto. Seventy-four independent admission variables in 15 general categories were utilized to predict possible stays of 1 to 20 days. Laboratory. Records of patients discharged from a post-coronary care unit in early 1993. An artificial neural network was trained on 629 records and tested on an additional 127 records of patients. The absolute disparity between the actual lengths of stays in the test records and the predictions of the network averaged 1.4 days per record, and the actual length of stay was predicted within 1 day 72% of the time. The artificial neural network demonstrated the capacity to utilize common patient admission characteristics to predict lengths of stay. This technology shows promise in aiding timely initiation of treatment and effective resource planning and cost control.

Treatment Concerns and Functional Impairment in Pediatric Anxiety.

PubMed

Wu, Monica S; Salloum, Alison; Lewin, Adam B; Selles, Robert R; McBride, Nicole M; Crawford, Erika A; Storch, Eric A

2016-08-01

Although there are efficacious, evidence-based treatments for anxiety disorders, youth often experience delays in seeking therapy. Myriad reasons may contribute to this lag in treatment initiation, with some youth possessing concerns about therapy. Treatment concerns are broadly characterized by worries/ambivalence about seeking treatment, including concerns about the negative reactions, consequences, and inconvenience of treatment. As no studies exist for youth with anxiety disorders, this study examined the phenomenology of treatment concerns in 119 treatment-seeking, anxious youth and utilized a structural equation model to examine the relationship between child anxiety, depressive symptoms, treatment concerns, and anxiety-related functional impairment. Over 90 % of the children positively endorsed some type of treatment-related fear, with the most frequently expressed concern being that therapy would take too much time (50.4 %). Based on the model, both child anxiety and depressive symptoms predicted functional impairment, and treatment concerns mediated the relationship between child anxiety and functional impairment.

Scanning laser Doppler imaging may predict disease progression of localized scleroderma in children and young adults.

PubMed

Shaw, L J; Shipley, J; Newell, E L; Harris, N; Clinch, J G; Lovell, C R

2013-07-01

Localized scleroderma is a rare but potentially disfiguring and disabling condition. Systemic treatment should be started early in those with active disease in key functional and cosmetic sites, but disease activity is difficult to determine clinically. Superficial blood flow has been shown to correlate with disease activity in localized scleroderma. To examine whether superficial blood flow measured by laser Doppler imaging (LDI) has the potential to predict disease progression and therefore select patients for early systemic treatment. A group of 20 individuals had clinical assessment and scanning LDI blood-flow measurements of 32 affected body sites. After a mean follow-up of 8.7 months their clinical outcome was compared with the results of the initial LDI assessment. Eleven out of 15 patients with an assessment of active LDI had progressed clinically, and 16 out of the 17 scans with inactive LDI assessment had not progressed, giving a positive predictive value of 73% and a negative predictive value of 94%. We believe that LDI can be a useful tool in predicting disease progression in localized scleroderma, and it may help clinicians to decide which patients to treat early. © 2013 The Authors BJD © 2013 British Association of Dermatologists.

Vascular plant abundance and diversity in an alpine heath under observed and simulated global change

PubMed Central

Alatalo, Juha M.; Little, Chelsea J.; Jägerbrand, Annika K.; Molau, Ulf

2015-01-01

Global change is predicted to cause shifts in species distributions and biodiversity in arctic tundra. We applied factorial warming and nutrient manipulation to a nutrient and species poor alpine/arctic heath community for seven years. Vascular plant abundance in control plots increased by 31%. There were also notable changes in cover in the nutrient and combined nutrient and warming treatments, with deciduous and evergreen shrubs declining, grasses overgrowing these plots. Sedge abundance initially increased significantly with nutrient amendment and then declined, going below initial values in the combined nutrient and warming treatment. Nutrient addition resulted in a change in dominance hierarchy from deciduous shrubs to grasses. We found significant declines in vascular plant diversity and evenness in the warming treatment and a decline in diversity in the combined warming and nutrient addition treatment, while nutrient addition caused a decline in species richness. The results give some experimental support that species poor plant communities with low diversity may be more vulnerable to loss of species diversity than communities with higher initial diversity. The projected increase in nutrient deposition and warming may therefore have negative impacts on ecosystem processes, functioning and services due to loss of species diversity in an already impoverished environment. PMID:25950370

Predictors of hospitalization of tuberculosis patients in Montreal, Canada: a retrospective cohort study.

PubMed

Ronald, Lisa A; FitzGerald, J Mark; Benedetti, Andrea; Boivin, Jean-François; Schwartzman, Kevin; Bartlett-Esquilant, Gillian; Menzies, Dick

2016-11-15

Hospitalization is the most costly health system component of tuberculosis (TB) control programs. Our objectives were to identify how frequently patients are hospitalized, and the factors associated with hospitalizations and length-of-stay (LOS) of TB patients in a large Canadian city. We extracted data from the Montreal TB Resource database, a retrospective cohort of all active TB cases reported to the Montreal Public Health Department between January 1996 and May 2007. Data included patient demographics, clinical characteristics, and dates of treatment and hospitalization. Predictors of hospitalization and LOS were estimated using logistic regression and Cox proportional hazards regression, respectively. There were 1852 active TB patients. Of these, 51% were hospitalized initially during the period of diagnosis and/or treatment initiation (median LOS 17.5 days), and 9.0% hospitalized later during treatment (median LOS 13 days). In adjusted models, patients were more likely to be hospitalized initially if they were children, had co-morbidities, smear-positive symptomatic pulmonary TB, cavitary or miliary TB, and multi- or poly-TB drug resistance. Factors predictive of longer initial LOS included having HIV, renal disease, symptomatic pulmonary smear-positive TB, multi- or poly-TB drug resistance, and being in a teaching hospital. We found a high hospitalization rate during diagnosis and treatment of patients with TB. Diagnostic delay due to low index of suspicion may result in patients presenting with more severe disease at the time of diagnosis. Earlier identification and treatment, through interventions to increase TB awareness and more targeted prevention programs, might reduce costly TB-related hospital use.

5-years APAP adherence in OSA patients--do first impressions matter?

PubMed

van Zeller, Mafalda; Severo, Milton; Santos, Ana Cristina; Drummond, Marta

2013-12-01

Although continuous positive airway pressure (CPAP) is effective in treating obstructive sleep apnoea (OSA), inadequate adherence remains a major cause of treatment failure. This study aimed to determine long term adherence to auto adjusting-CPAP (APAP) and its influencing factors including the role of initial compliance. Eighty-eight male patients with newly diagnosed moderate/severe OSA were included. After initiation of APAP treatment, patients had periodic follow-up appointments at 2 weeks, 6 months and then annually for at least 5 years. Patient's compliance to therapy was assessed in each appointment and predictors to treatment abandonment and poor compliance were evaluated. The studied population had a mean age of 53.8 years and mean apnoea-hypopnoea index of 52.71/h. The mean time of follow-up was 5.2 (± 1.6) years, during that time 22 (25%) patients abandoned APAP, those who maintained treatment had good compliance to it since 94% of them used it more than 4 h/day for at least 70% of days. A significant negative association was found between age, % of days and mean time of APAP use on 12th day and 6th month and the risk of abandoning. APAP use lower than 33% and 57% of days at 12th day and 6th month, respectively had high specificity (≈ 100%) to detect treatment abandonment. the majority of patients adheres to long term APAP treatment and has good compliance after 5-years of follow-up. Age and initial compliance (% days of use and mean hour/day) have the ability to predict future adherence, as soon as 12 days and 6 months after initiation. Copyright © 2013 Elsevier Ltd. All rights reserved.

Dependency and Self-Criticism in Treatments for Depression

PubMed Central

Chui, Harold; Zilcha-Mano, Sigal; Dinger, Ulrike; Barrett, Marna S.; Barber, Jacques P.

2016-01-01

Dependency and self-criticism are vulnerability factors for depression. How these personality factors change with treatment for depression, and how they relate to symptom change across different types of treatment require further research. In addition, cultural differences that interact with the dependency/self-criticism-depression relation remain under-investigated. One hundred and forty-nine adults with major depression were randomly assigned to receive active medication (MED; n = 50), supportive-expressive therapy (SET; n = 49), or placebo pill (PBO; n = 50). Participants completed the Depressive Experiences Questionnaire (DEQ; Blatt, D'Afflitti, & Quinlan, 1976) before and after treatment, and were administered the Hamilton Rating Scale for Depression (Hamilton, 1967) throughout the course of treatment. Self-criticism as measured on the DEQ decreased with treatment similarly across conditions. DEQ Dependency decreased in MED but remained unchanged in SET and PBO. Higher initial dependency, but not higher initial self-criticism, predicted poor treatment response across conditions. Greater reduction in self-criticism was associated with greater reduction in depressive symptoms, but the effect was weaker for racial minorities (vs. White). Increase in connectedness, an adaptive form of dependency, was associated with symptom improvement in SET but not MED. Hence, different pathways of change seem to be implicated in the treatment of depression depending on culture and type of intervention. Implications for future research are discussed. PMID:26866638

Inpatient Hospitalization in Addiction Treatment for Patients with a History of Suicide Attempt: A Case of Support for Treatment Performance Measures†

PubMed Central

Glass, Joseph E.; Ilgen, Mark A.; Winters, Jamie J.; Murray, Regan L.; Perron, Brian E.; Chermack, Stephen T.

2010-01-01

This study attempts to validate substance use disorder (SUD) treatment performance measures (PM) in a naturalistic treatment setting. Despite its significance in healthcare systems and in SUD populations, suicidality is one patient characteristic that remains unexplored in the context of SUD PMs. The current study focused on the extent to which the care processes encouraged by SUD PMs were associated with improved outcomes in patients with a prior suicide attempt as compared to those without. We abstracted Addiction Severity Index and health services data from the VA medical record for 381 veterans who initiated outpatient SUD treatment and completed baseline intake measures at a Midwestern VA hospital. Cox proportional hazard regressions examined how baseline characteristics, prior suicide attempts, and PM status predicted the time until hospitalization for psychiatric or substance use problems. Prior suicide attempts significantly interacted with treatment engagement, and hospitalization risk was significantly higher among individuals with a prior suicide attempt who did not meet PMs. This study provides initial observational evidence that past suicide attempts may be a factor that should be considered when defining performance standards that influence the processes of SUD treatment. Future research on PMs should take into account the differences on indicators of high risk and poor treatment outcomes. PMID:21053754

Alzheimer’s Prevention Initiative: a proposal to evaluate presymptomatic treatments as quickly as possible

PubMed Central

Reiman, Eric M; Langbaum, Jessica BS; Tariot, Pierre N

2010-01-01

Now is the time to launch the era of Alzheimer’s disease (AD) prevention research, establish the methods and infrastructure to rapidly evaluate presymptomatic AD treatments and evaluate them rigorously and rapidly in randomized clinical trials. This article is a call to arms. It contends that the evaluation of presymptomatic AD treatments must become an urgent priority, it identifies what is holding us back and proposes new public policies and scientific strategies to overcome these roadblocks. It defines the term ‘presymptomatic AD treatment,’ notes the best established biomarkers of AD progression and pathology and suggests how they could be used to rapidly evaluate presymptomatic AD treatments in the people at risk. It introduces an approach to evaluate presymptomatic AD treatments in asymptomatic people at the highest risk of imminent clinical onset and determines the extent to which the treatment’s biomarker predicts a clinical outcome. We propose an Alzheimer’s Prevention Initiative, which is now being reviewed and refined in partnership with leading academic and industry investigators. It is intended to evaluate the most promising presymptomatic AD treatments, help develop a regulatory pathway for their accelerated approval using reasonably likely surrogate end points and find demonstrably effective presymptomatic AD treatments as quickly as possible. PMID:20383319

Current strategies for the diagnosis and management of chronic lymphocytic leukemia (CLL), with a focus on poor-risk CLL: A review.

PubMed

Clanahan, Fabienne Mc; Dreger, Peter

2011-06-05

Despite substantial advancement in the understanding and treatment of chronic lymphocytic leukemia (CLL), a standard curative approach does not exist. The choice of treatment is generally based on the existence of biological and genetic factors associated with the prediction of prognosis, individual response to therapy, and duration of remission. About 20% of patients that require treatment have an aggressive disease course and die within a few years, despite early initiation of intensive therapy (poor-risk CLL). Poor-risk CLL can be predicted by the presence of genomic markers, and the quality and duration of response to purine-analogue-based treatment. Within this patient subgroup alternative treatment approaches such as alemtuzumab or new substances such as flavopiridol or IMiDs® should be considered. To date, the only treatment bearing curative potential is allogeneic stem cell transplantation; in contrast to conventional immunochemotherapy, it can provide long-term disease control, even in patients with del 17p or other unfavorable biological and clinical risk factors. The aim of this review was to outline the current strategies for the diagnosis and management of CLL, with a focus on high-risk CLL.

Usefulness of 3'-[F-18]fluoro-3'-deoxythymidine with positron emission tomography in predicting breast cancer response to therapy.

PubMed

Pio, Betty S; Park, Cecilia K; Pietras, Richard; Hsueh, Wei-Ann; Satyamurthy, Nagichettiar; Pegram, Mark D; Czernin, Johannes; Phelps, Michael E; Silverman, Daniel H S

2006-01-01

The usefulness of 2-deoxy-2-[F-18]fluoro-D-glucose (FDG)-positron emission tomography (PET) in monitoring breast cancer response to chemotherapy has previously been reported. Elevated uptake of FDG by treated tumors can persist however, particularly in the early period after treatment is initiated. 3'-[F-18]Fluoro-3'-deoxythymidine (FLT) has been developed as a marker for cellular proliferation and, in principle, could be a more accurate predictor of the long-term effect of chemotherapy on tumor viability. We examined side-by-side FDG and FLT imaging for monitoring and predicting tumor response to chemotherapy. Fourteen patients with newly diagnosed primary or metastatic breast cancer, who were about to commence a new pharmacologic treatment regimen, were prospectively studied. Dynamic 3-D PET imaging of uptake into a field of view centered over tumor began immediately after administration of FDG or FLT (150 MBq). After 45 minutes of dynamic acquisition, a clinically standard whole-body PET scan was acquired. Patients were scanned with both tracers on two separate days within one week of each other (1) before beginning treatment, (2) two weeks following the end of the first cycle of the new regimen, and (3) following the final cycle of that regimen, or one year after the initial PET scans, whichever came first. (Median and mean times of early scans were 5.0 and 6.6 weeks after treatment initiation; median and mean times for late scans were 26.0 and 30.6 weeks after treatment initiation.) Scan data were analyzed on both tumor-by-tumor and patient-by-patient bases, and compared to each patient's clinical course. Mean change in FLT uptake in primary and metastatic tumors after the first course of chemotherapy showed a significant correlation with late (av. interval 5.8 months) changes in CA27.29 tumor marker levels (r = 0.79, P = 0.001). When comparing changes in tracer uptake after one chemotherapy course versus late changes in tumor size as measured by CT scans, FLT was again a good predictor of eventual tumor response (r = 0.74, P = 0.01). Tumor uptake of FLT was near-maximal by 10 minutes after injection. The time frame five to 10 minutes postinjection of FLT produced standardized uptake value (SUV) values highly correlated with SUV values obtained after 45-minute uptake (r = 0.83, P < 0.0001), and changes in these early SUVs after the first course of chemotherapy correlated with late changes in CA27.29 (r = 0.93, P = 0.003). A 10-minute FLT-PET scan acquired two weeks after the end of the first course of chemotherapy is useful for predicting longer-term efficacy of chemotherapy regimens for women with breast cancer.

An exploratory study of adolescent response to fluoxetine using psychological and biological predictors.

PubMed

Zohar, Ada H; Eilat, Tamar; Amitai, Maya; Taler, Michal; Bari, Romi; Chen, Alon; Apter, Alan; Weizman, Avraham; Fennig, Silvana

2018-01-01

Not enough is known about predicting therapeutic response to serotonin-specific reuptake inhibitors, and specifically to fluoxetine. This exploratory study used psychological and biological markers for (retrospective) prediction of treatment-response to fluoxetine in depressed and/or anxious adolescents. Forty-one consecutive adolescent outpatients with a primary diagnosis of severe affective and/or anxiety disorders were assessed and treated with an open-label 8-week trial of fluoxetine. Type D personality was assessed with the 14-item questionnaire, the DS14. In addition, TNFα, IL-6, and IL-1b were measured pre- and post-treatment. There was an elevation of Type D personality in patients, compared to the adolescent population rate. Post-treatment, 44% of patients were classified as non-responders; the relative risk of non-response for Type D personality patients was 2.8. Binary logistic regression predicting response vs. non-response showed a contribution of initial TNFα levels as well as Type D personality to non-response. In this exploratory study, the most significant contributor to non-response was Type D personality. However, the measurement of Type D was not prospective, and thus may be confounded with psychiatric morbidity. The measurement of personality in psychiatric settings may contribute to the understanding of treatment response and have clinical utility.

An investigation of client mood in the initial and final sessions of cognitive-behavioral therapy and psychodynamic-interpersonal therapy.

PubMed

Mcclintock, Andrew S; Stiles, William B; Himawan, Lina; Anderson, Timothy; Barkham, Michael; Hardy, Gillian E

2016-01-01

Our aim was to examine client mood in the initial and final sessions of cognitive-behavioral therapy (CBT) and psychodynamic-interpersonal therapy (PIT) and to determine how client mood is related to therapy outcomes. Hierarchical linear modeling was applied to data from a clinical trial comparing CBT with PIT. In this trial, client mood was assessed before and after sessions with the Session Evaluation Questionnaire-Positivity Subscale (SEQ-P). In the initial sessions, CBT clients had higher pre-session and post-session SEQ-P ratings and greater pre-to-post session mood change than did clients in PIT. In the final sessions, these pre, post, and change scores were generally equivalent across CBT and PIT. CBT outcome was predicted by pre- and post-session SEQ-P ratings from both the initial sessions and the final sessions of CBT. However, PIT outcome was predicted by pre- and post-session SEQ-P ratings from the final sessions only. Pre-to-post session mood change was unrelated to outcome in both treatments. These results suggest different change processes are at work in CBT and PIT.

Metabolic and anthropometric parameters contribute to ART-mediated CD4+ T cell recovery in HIV-1-infected individuals: an observational study.

PubMed

Azzoni, Livio; Foulkes, Andrea S; Firnhaber, Cynthia; Yin, Xiangfan; Crowther, Nigel J; Glencross, Deborah; Lawrie, Denise; Stevens, Wendy; Papasavvas, Emmanouil; Sanne, Ian; Montaner, Luis J

2011-07-29

The degree of immune reconstitution achieved in response to suppressive ART is associated with baseline individual characteristics, such as pre-treatment CD4 count, levels of viral replication, cellular activation, choice of treatment regimen and gender. However, the combined effect of these variables on long-term CD4 recovery remains elusive, and no single variable predicts treatment response. We sought to determine if adiposity and molecules associated with lipid metabolism may affect the response to ART and the degree of subsequent immune reconstitution, and to assess their ability to predict CD4 recovery. We studied a cohort of 69 (48 females and 21 males) HIV-infected, treatment-naïve South African subjects initiating antiretroviral treatment (d4T, 3Tc and lopinavir/ritonavir). We collected information at baseline and six months after viral suppression, assessing anthropometric parameters, dual energy X-ray absorptiometry and magnetic resonance imaging scans, serum-based clinical laboratory tests and whole blood-based flow cytometry, and determined their role in predicting the increase in CD4 count in response to ART. We present evidence that baseline CD4+ T cell count, viral load, CD8+ T cell activation (CD95 expression) and metabolic and anthropometric parameters linked to adiposity (LDL/HDL cholesterol ratio and waist/hip ratio) significantly contribute to variability in the extent of CD4 reconstitution (ΔCD4) after six months of continuous ART. Our final model accounts for 44% of the variability in CD4+ T cell recovery in virally suppressed individuals, representing a workable predictive model of immune reconstitution.

Theoretical Treatment of Ion Transfers in Two Polarizable Interface Systems When the Analyte Has Access to Both Interfaces.

PubMed

Olmos, José Manuel; Molina, Ángela; Laborda, Eduardo; Millán-Barrios, Enrique; Ortuño, Joaquín Ángel

2018-02-06

A new theory is presented to tackle the study of transfer processes of hydrophilic ions in two polarizable interface systems when the analyte is initially present in both aqueous phases. The treatment is applied to macrointerfaces (linear diffusion) and microholes (highly convergent diffusion), obtaining analytical equations for the current response in any voltammetric technique. The novel equations predict two signals in the current-potential curves that are symmetric when the compositions of the aqueous phases are identical while asymmetries appear otherwise. The theoretical results show good agreement with the experimental behavior of the "double transfer voltammograms" reported by Dryfe et al. in cyclic voltammetry (CV) ( Anal. Chem. 2014 , 86 , 435 - 442 ) as well as with cyclic square wave voltammetry (cSWV) experiments performed in the current work. The theoretical treatment is also extended to the situation where the target ion is lipophilic and initially present in the organic phase. The theory predicts an opposite effect of the lipophilicity of the ion on the shape of the voltammograms, which is validated experimentally via both CV and cSWV. For the above two cases, simple and manageable expressions and diagnosis criteria are derived for the qualitative and quantitative study of ion lipophilicity. The ion-transfer potentials can be easily quantified from the separation between the two signals making use of explicit analytical equations.

Pharmacogenetically driven treatments for alcoholism: are we there yet?

PubMed

Arias, Albert J; Sewell, R Andrew

2012-06-01

Pharmacogenetic analyses of treatments for alcohol dependence attempt to predict treatment response and side-effect risk for specific medications. We review the literature on pharmacogenetics relevant to alcohol dependence treatment, and describe state-of-the-art methods of pharmacogenetic research in this area. Two main pharmacogenetic study designs predominate: challenge studies and treatment-trial analyses. Medications studied include US FDA-approved naltrexone and acamprosate, both indicated for treating alcohol dependence, as well as several investigational (and off-label) treatments such as sertraline, olanzapine and ondansetron. The best-studied functional genetic variant relevant to alcoholism treatment is rs1799971, a single-nucleotide polymorphism in exon 1 of the OPRM1 gene that encodes the μ-opioid receptor. Evidence from clinical trials suggests that the presence of the variant G allele of rs1799971 may predict better treatment response to opioid receptor antagonists such as naltrexone. Evidence from clinical trials also suggests that several medications interact pharmacogenetically with variation in genes that encode proteins involved in dopaminergic and serotonergic neurotransmission. Variation in the DRD4 gene, which encodes the dopamine D(4) receptor, may predict better response to naltrexone and olanzapine. A polymorphism in the serotonin transporter gene SLC6A4 promoter region appears related to differential treatment response to sertraline depending on the subject's age of onset of alcoholism. Genetic variation in SLC6A4 may also be associated with better treatment response to ondansetron. Initial pharmacogenetic efforts in alcohol research have identified functional variants with potential clinical utility, but more research is needed to further elucidate the mechanism of these pharmacogenetic interactions and their moderators in order to translate them into clinical practice.

Gratitude, hope, mindfulness and personal-growth initiative: buffers or risk factors for problem gambling?

PubMed

Loo, Jasmine M Y; Tsai, Jung-Shun; Raylu, Namrata; Oei, Tian P S

2014-01-01

The majority of prevention and intervention research in problem gambling (PG) has focused on identifying negative risk factors. However, not all at-risk individuals go on to develop anticipated disorders and many thrive in spite of them. In healthcare settings, PG and other disorders are typically conceptualized from the biomedical perspective that frame disorders as something negative residing within the individual and reduction in negativity is seen as success. Indeed, this problem-focused conceptualization may be adequate in many cases as reducing PG behaviour is undoubtedly an important outcome, but the focus on negativity alone is too narrow to capture the complexity of human behaviour. Hence, this study attempts to bridge the gap in literature by providing an evaluation of the predictive ability of the positive dispositions on problem gambling severity, gambling-related cognitions, and gambling urges. The positive psychological dispositions examined were curiosity, gratitude, hope, personal growth initiative, and mindfulness. Participants consisted of 801 Taiwanese Chinese students and community individuals (Mean age = 25.36 years). Higher levels of gratitude and hope have been found to predict lower PG, gambling-related cognitions, or gambling urges. Meanwhile, higher mindfulness predicted lower PG, but only among Chinese males. However, lower personal growth initiative predicted lower PG, gambling-related cognitions, and gambling urges. These analyses have small to medium effect sizes with significant predictions. Findings of this study have essential implications in understanding and treating Chinese problem gamblers. These positive dispositions should be addressed by mental health professionals in preventative and treatment programs among Chinese individuals. Further implications and suggestions for future research are discussed.

Modeling tree-level fuel connectivity to evaluate the effectiveness of thinning treatments for reducing crown fire potential

Treesearch

Marco A. Contreras; Russell A. Parsons; Woodam Chung

2012-01-01

Land managers have been using fire behavior and simulation models to assist in several fire management tasks. These widely-used models use average attributes to make stand-level predictions without considering spatial variability of fuels within a stand. Consequently, as the existing models have limitations in adequately modeling crown fire initiation and propagation,...

Rumen degradable protein supply affects microbial efficiency in continuous culture and growth in steers.

PubMed

Brooks, M A; Harvey, R M; Johnson, N F; Kerley, M S

2012-12-01

We hypothesized that microbial efficiency and output from fermentation in the rumen would be optimized when peptide supply was balanced with peptide requirement of ruminal microflora. This study was conducted to measure response of varying rumen degradable peptide (RDPep) supply on ruminal fermentation characteristics and steer growth. A continuous culture experiment was conducted with diets formulated to achieve a predicted RDPep balance (RDPep supplied above RDPep required) of -0.30 to 1.45% CP with rumen degradable N (RDN) balance (RDN supplied above RDN required) above dietary ammonia-N requirement of microbes. Two additional treatments had RDPep balances of -0.30 and 0.78% CP with insufficient ammonia-N supply to meet microbial requirements. Single-flow fermenters (N = 24; n = 6) were inoculated with rumen fluid and maintained anaerobically at 39°C with a 0.06 h(-1) dilution rate. Inadequate RDN decreased OM digestion and microbial N flow, and increased rumen undegradable N (P < 0.01). Microbial efficiency decreased in RDN-deficient diets and was greatest when RDPep balance did not excessively exceed microbial requirement of RDPep predicted (P < 0.01). A growth study was conducted with 49 yearling, crossbred, Angus steers (initial BW 370 ± 34 kg). Animals were assigned to 1 of 4 treatment groups by BW and further divided into 3 pens with 4 steers per pen to achieve similar initial pen weights. Treatments consisted of 4 isonitrogenous diets balanced for RDN but varying in predicted RDPep balance (0.55%, -0.02%, -0.25%, and -0.65% CP). Animals were maintained on treatment for 70 d with individual BW taken on d 0, 1, 21, 42, 70, and 71. Final BW decreased linearly with decreasing RDPep (P = 0.05). Average daily gain and G:F displayed a quadratic effect with greater ADG and G:F at greater and lesser RDPep levels (P = 0.02). We concluded that balancing RDPep supply to predicted requirement improved fermentation efficiency and microbial output, which in turn improved animal performance.

Prediction of the containment of HIV infection by antiretroviral therapy - a variable structure control approach.

PubMed

Anelone, Anet J N; Spurgeon, Sarah K

2017-02-01

It is demonstrated that the reachability paradigm from variable structure control theory is a suitable framework to monitor and predict the progression of the human immunodeficiency virus (HIV) infection following initiation of antiretroviral therapy (ART). A manifold is selected which characterises the infection-free steady-state. A model of HIV infection together with an associated reachability analysis is used to formulate a dynamical condition for the containment of HIV infection on the manifold. This condition is tested using data from two different HIV clinical trials which contain measurements of the CD4+ T cell count and HIV load in the peripheral blood collected from HIV infected individuals for the six month period following initiation of ART. The biological rates of the model are estimated using the multi-point identification method and data points collected in the initial period of the trial. Using the parameter estimates and the numerical solutions of the model, the predictions of the reachability analysis are shown to be consistent with the clinical diagnosis at the conclusion of the trial. The methodology captures the dynamical characteristics of eventual successful, failed and marginal outcomes. The findings evidence that the reachability analysis is an appropriate tool to monitor and develop personalised antiretroviral treatment.

Increased pathologic upstaging with rising time to treatment initiation for head and neck cancer: A mechanism for increased mortality.

PubMed

Xiao, Roy; Ward, Matthew C; Yang, Kailin; Adelstein, David J; Koyfman, Shlomo A; Prendes, Brandon L; Burkey, Brian B

2018-04-01

Time to treatment initiation (TTI) is increasing and is associated with worsening survival. In the current study, the authors sought to identify a mechanism for this relationship by assessing the effect of TTI on clinical-to-pathologic upstaging in patients with head and neck squamous cell carcinoma (HNSCC). Using the National Cancer Data Base, the authors analyzed patients receiving definitive surgery for SCC of the oral cavity, oropharynx, larynx, and hypopharynx from 2005 through 2014. The primary outcome was T, N, or stage group upstaging, defined as higher pathologic stage than clinical stage. TTI was defined as the time between diagnosis and surgery. Multivariable logistic and Cox proportional hazards regression modeled upstaging and survival, respectively. Cohorts of 60,194 patients, 51,380 patients, and 52,980 patients, respectively, with complete T, N, and stage group data were included. N upstaging was most common (18.6%), followed by stage group (17.4%) and T (12.1%) upstaging; all types were predicted by TTI. Compared with a TTI of 1 to 6 days, TTIs as short as 7 to 13 days (odds ratio, 1.20; P = .038) or ≥ 70 days (odds ratio, 2.04; P < .001) were found to predict T upstaging, a finding that is consistent for N and stage group upstaging. Using restricted cubic splines, relative odds of T and stage group upstaging escalated to 2.25 and 1.93, respectively, at a TTI of 365 days. In survival analyses, T (hazard ratio [HR], 1.53), N (HR, 1.88), and stage group (HR, 1.69) upstaging all predicted mortality (P < .001), whereas TTI only predicted mortality after 70 days (HR, 1.11; P = .023). Tumor progression, measured by clinical-to-pathologic upstaging, increases mortality for patients with HNSCC experiencing treatment delays. Cancer 2018;124:1400-14. © 2018 American Cancer Society. © 2018 American Cancer Society.

Enrolment and programmatic trends and predictors of antiretroviral therapy initiation from president's emergency plan for AIDS Relief (PEPFAR)-supported public HIV care and treatment sites in rural Mozambique.

PubMed

Moon, T D; Burlison, J R; Blevins, M; Shepherd, B E; Baptista, A; Sidat, M; Vergara, A E; Vermund, S H

2011-11-01

Many countries in sub-Saharan Africa have made antiretroviral therapy (ART) available in urban settings, but the progress of treatment expansion into rural Africa has been slower. We analysed routine data for patients enrolled in a rural HIV treatment programme in Zambézia Province, Mozambique (1 June 2006 through 30 March 2009). There were 12,218 patients who were ≥15 years old enrolled (69% women). Median age was 25 years for women and 31 years for men. Older age and higher level of education were strongly predictive of ART initiation (P < 0.001). Patients with a CD4+ count of 350 cells/μL versus 50 cells/μL were less likely to begin ART (odds ratio [OR]: 0.19, 95% confidence interval [CI]: 0.16-0.23). In rural sub-Saharan Africa, HIV testing, linkage to care, logistics for ART initiation and fears among some patients to take ART require specialized planning to maximize successes. Sustainability will require improved health manpower, infrastructure, stable funding, continuous drug supplies, patient record systems and, most importantly, community engagement.

Sequential nitric oxide measurements during the emergency department treatment of acute vasoocclusive sickle cell crisis.

PubMed

Lopez, B L; Davis-Moon, L; Ballas, S K; Ma, X L

2000-05-01

This prospective study was designed to examine the relationship between serial serum nitric oxide (NO) levels and pain during the emergency department (ED) treatment of acute vasoocclusive sickle cell crisis (SCC). 102 patient visits, age > or =18 years of age, presenting to the ED with uncomplicated, typical SCC pain had serum NO levels obtained at 2-hr intervals during treatment of pain and were measured using an NO-specific chemiluminesence technique. Pain was measured prior to each NO measurement using a 10 cm visual analog scale (VAS), and subjects were divided into a persistent pain group and an improved pain group. Patients with persistent pain had significantly low initial NO levels (11.51 microM +/- 2.8, P < 0.05) while those with pain improvement had higher initial NO levels (18.1 microM +/- 3.08, P < 0.05). There was no significant correlation between changes in NO and changes in pain scores. These results suggest that the initial NO level may serve as a marker for the severity of tissue ischemia. Sequential NO levels do not appear useful in predicting the course of SCC.

Change Factors in the Process of Cognitive-Behavioural Therapy for Obsessive-Compulsive Disorder.

PubMed

Schwartz, C; Hilbert, S; Schubert, C; Schlegl, S; Freyer, T; Löwe, B; Osen, B; Voderholzer, U

2017-05-01

While there is a plethora of evidence for the efficacy of cognitive-behavioural therapy (CBT) in obsessive-compulsive disorder (OCD), studies on change factors of the therapeutic process that account for this success are scarce. In the present study, 155 participants with primary OCD were investigated during CBT inpatient treatment. The Yale-Brown Obsessive-Compulsive Scale-SR served as a measure of symptom severity. In addition, the following process change factors were measured: therapeutic relationship, experience of self-esteem during therapy, experience of mastery, problem actualization and clarification. All variables were assessed on a weekly basis for seven weeks. Linear mixed growth curve analyses were conducted to model the decrease of symptoms over time and to analyse whether the change factors predicted symptom reduction. The analyses revealed a linear decrease of symptoms with high inter-individual variation. Results further showed that increase in self-esteem and mastery experiences as well as the initial score on mastery experience and clarification predicted decrease on the Y-BOCS. We conclude that CBT therapists should focus on clarification in the very first sessions, and try to boost self-esteem and self-efficacy, which is related to mastery, throughout the treatment of OCD. Copyright © 2016 John Wiley & Sons, Ltd. Increase in mastery and self-esteem experiences are associated with symptom decrease in obsessive-compulsive disorder (OCD) during cognitive-behavioural therapy (CBT). Initial score of mastery experiences and problem clarification predict symptom decrease in OCD during CBT. CBT therapists should focus on problem clarification in the very first sessions and try to boost self-esteem and self-efficacy throughout the treatment of OCD. Copyright © 2016 John Wiley & Sons, Ltd.

High-pitched breath sounds indicate airflow limitation in asymptomatic asthmatic children.

PubMed

Habukawa, Chizu; Nagasaka, Yukio; Murakami, Katsumi; Takemura, Tsukasa

2009-04-01

Asthmatic children may have airway dysfunction even when asymptomatic, indicating that their long-term treatment is less than optimal. Although airway dysfunction can be identified on lung function testing, performing these tests can be difficult in infants. We studied whether breath sounds reflect subtle airway dysfunction in asthmatic children. The highest frequency of inspiratory breaths sounds (HFI) and the highest frequency of expiratory breath sounds (HFE) were measured in 131 asthmatic children while asymptomatic and with no wheezes for more than 2 weeks. No child was being treated with inhaled corticosteroids (ICS). Breath sounds were recorded and analysed by sound spectrography and compared with spirometric parameters. After initial evaluation, cases with more than step 2 (mild persistent) asthma were treated using inhaled fluticasone (100-200 microg/day) for 1 month, and then breath sound analysis and pulmonary function testing were repeated. On initial evaluation, HFI correlated with the percentage of predicted FEF(50) (%FEF(50)), (r = -0.45, P < 0.001), the percentage of predicted FEF(75) (%FEF(75)) (r = -0.456, P < 0.001), and FEV(1) as a percentage of FVC (FEV(1)/FVC (%)) (r = -0.32, P < 0.001). HFI did not correlate with the percentage of predicted PEF (%PEF). The 69 children with lower than normal %FEF(50) were then treated with ICS. The %FEF(50) and %FEF(75) improved after ICS treatment, and increases in %FEF(50) (P < 0.005) correlated with decreases in HFI (P < 0.001). Higher HFI in asymptomatic asthmatic children may indicate small airway obstruction. Additional ICS treatment may improve the pulmonary function indices representing small airway function with simultaneous HFI decreases in such patients.

Extreme Attributions Predict the Course of Bipolar Depression: Results from the STEP-BD Randomized Controlled Trial of Psychosocial Treatment

PubMed Central

Stange, Jonathan P.; Sylvia, Louisa G.; da Silva Magalhães, Pedro Vieira; Miklowitz, David J.; Otto, Michael W.; Frank, Ellen; Berk, Michael; Nierenberg, Andrew A.; Deckersbach, Thilo

2013-01-01

Objective Little is known about predictors of recovery from bipolar depression or moderators of treatment response. In the present study we investigated attributional style (a cognitive pattern of explaining the causes of life events) as a predictor of recovery from episodes of bipolar depression and as a moderator of response to psychotherapy for bipolar depression. Method 106 depressed outpatients with DSM-IV bipolar I or II disorder enrolled in the Systematic Treatment Enhancement Program for Bipolar Disorder (STEP-BD) were randomized to intensive psychotherapy for depression (n=62), or collaborative care (n=44), a minimal psychoeducational intervention. The primary outcome was recovery status at each study visit as measured by the Clinical Monitoring Form. Attributional style was measured at baseline using the Attributional Style Questionnaire. Data were collected between 1998 and 2005. Results All analyses were by intention to treat. Extreme attributions predicted a lower likelihood of recovery (p=.01, OR=0.93, 95% CI=.88-.98) and longer time until recovery (p<.01, OR=0.96, 95% CI=.93-.99), independent of the effects of initial depression severity. Among individuals with more pessimistic attributional styles, initial depression severity predicted a lower likelihood of recovery (p=.01, OR=0.64, 95% CI=.45-.91) and longer time until recovery (p<.001, OR=0.76, 95% CI=.66-.88). There was no difference in recovery rates between intensive psychotherapy and collaborative care (OR=0.90, 95% CI=0.40-2.01) in the full sample. Conclusions These results suggest that extreme, rigid attributions may be associated with a more severe course of depression, and that evaluating attributional style may help clinicians to identify patients who are at risk for experiencing a more severe course of depression. PMID:23561230

C-reactive protein, fibrinogen, and cardiovascular disease prediction.

PubMed

Kaptoge, Stephen; Di Angelantonio, Emanuele; Pennells, Lisa; Wood, Angela M; White, Ian R; Gao, Pei; Walker, Matthew; Thompson, Alexander; Sarwar, Nadeem; Caslake, Muriel; Butterworth, Adam S; Amouyel, Philippe; Assmann, Gerd; Bakker, Stephan J L; Barr, Elizabeth L M; Barrett-Connor, Elizabeth; Benjamin, Emelia J; Björkelund, Cecilia; Brenner, Hermann; Brunner, Eric; Clarke, Robert; Cooper, Jackie A; Cremer, Peter; Cushman, Mary; Dagenais, Gilles R; D'Agostino, Ralph B; Dankner, Rachel; Davey-Smith, George; Deeg, Dorly; Dekker, Jacqueline M; Engström, Gunnar; Folsom, Aaron R; Fowkes, F Gerry R; Gallacher, John; Gaziano, J Michael; Giampaoli, Simona; Gillum, Richard F; Hofman, Albert; Howard, Barbara V; Ingelsson, Erik; Iso, Hiroyasu; Jørgensen, Torben; Kiechl, Stefan; Kitamura, Akihiko; Kiyohara, Yutaka; Koenig, Wolfgang; Kromhout, Daan; Kuller, Lewis H; Lawlor, Debbie A; Meade, Tom W; Nissinen, Aulikki; Nordestgaard, Børge G; Onat, Altan; Panagiotakos, Demosthenes B; Psaty, Bruce M; Rodriguez, Beatriz; Rosengren, Annika; Salomaa, Veikko; Kauhanen, Jussi; Salonen, Jukka T; Shaffer, Jonathan A; Shea, Steven; Ford, Ian; Stehouwer, Coen D A; Strandberg, Timo E; Tipping, Robert W; Tosetto, Alberto; Wassertheil-Smoller, Sylvia; Wennberg, Patrik; Westendorp, Rudi G; Whincup, Peter H; Wilhelmsen, Lars; Woodward, Mark; Lowe, Gordon D O; Wareham, Nicholas J; Khaw, Kay-Tee; Sattar, Naveed; Packard, Chris J; Gudnason, Vilmundur; Ridker, Paul M; Pepys, Mark B; Thompson, Simon G; Danesh, John

2012-10-04

There is debate about the value of assessing levels of C-reactive protein (CRP) and other biomarkers of inflammation for the prediction of first cardiovascular events. We analyzed data from 52 prospective studies that included 246,669 participants without a history of cardiovascular disease to investigate the value of adding CRP or fibrinogen levels to conventional risk factors for the prediction of cardiovascular risk. We calculated measures of discrimination and reclassification during follow-up and modeled the clinical implications of initiation of statin therapy after the assessment of CRP or fibrinogen. The addition of information on high-density lipoprotein cholesterol to a prognostic model for cardiovascular disease that included age, sex, smoking status, blood pressure, history of diabetes, and total cholesterol level increased the C-index, a measure of risk discrimination, by 0.0050. The further addition to this model of information on CRP or fibrinogen increased the C-index by 0.0039 and 0.0027, respectively (P<0.001), and yielded a net reclassification improvement of 1.52% and 0.83%, respectively, for the predicted 10-year risk categories of "low" (<10%), "intermediate" (10% to <20%), and "high" (≥20%) (P<0.02 for both comparisons). We estimated that among 100,000 adults 40 years of age or older, 15,025 persons would initially be classified as being at intermediate risk for a cardiovascular event if conventional risk factors alone were used to calculate risk. Assuming that statin therapy would be initiated in accordance with Adult Treatment Panel III guidelines (i.e., for persons with a predicted risk of ≥20% and for those with certain other risk factors, such as diabetes, irrespective of their 10-year predicted risk), additional targeted assessment of CRP or fibrinogen levels in the 13,199 remaining participants at intermediate risk could help prevent approximately 30 additional cardiovascular events over the course of 10 years. In a study of people without known cardiovascular disease, we estimated that under current treatment guidelines, assessment of the CRP or fibrinogen level in people at intermediate risk for a cardiovascular event could help prevent one additional event over a period of 10 years for every 400 to 500 people screened. (Funded by the British Heart Foundation and others.).

Quantum-mechanical treatment of an electron undergoing synchrotron radiation.

NASA Technical Reports Server (NTRS)

White, D.

1972-01-01

The problem of an electron moving perpendicular to an intense magnetic field is approached from the framework of quantum mechanics. A numerical solution to the related rate equations describing the probabilities of occupation of the electron's energy states is put forth along with the expected errors involved. The quantum-mechanical approach is found to predict a significant amount of energy broadening with time for an initially monoenergetic electron beam entering a region of an intense magnetic field as long as the product of initial energy and magnetic field is of order 50 MG BeV or larger.

Can heart rate predict blood pressure response to anti-hypertensive drug therapy?

PubMed

Owens, P E; Lyons, S; O'Brien, E

1998-04-01

The use of heart rate in clinical practice is limited by its variability under measurement situations. The mean heart rate on ambulatory monitoring provides a more robust statistic for clinical use. We examined the relationship between mean heart rate on initial referral ambulatory blood pressure monitoring (ABPM) to the BP-lowering efficacy of the four main groups of anti-hypertensive medications, in a referral hypertensive population. Patients were retrospectively identified by review of the BP database, and data collected from the initial referral BP monitor off medication, and the subsequent ABPM after treatment with either beta-blockers, diuretics, calcium antagonists or angiotensin-converting enzyme (ACE) inhibitors. The change in mean arterial BP from the initial to the subsequent ABPM (ie, as a result of treatment) was correlated with the mean heart rate on the initial ABPM. A moderate association was found for initial daytime heart rate and BP response to beta-blockers (r = 0.24, P = 0.02), and ACE inhibitors (r = 0.14, P = 0.05). No such association was found for calcium antagonists or diuretics. When the groups were divided into those with a mean daytime heart rate <75 and > or =75 beats per min, BP reduction from beta-blocker and ACE inhibitor therapy was significantly greater in those patients with a higher daytime heart rate. We conclude that average daytime heart rate on pre-treatment ABPM can be useful as a predictor of BP response to beta-blockade or ACE inhibition.

Quality of life and sexuality issues in aging women.

PubMed

Birkhäuser, M H

2009-01-01

Quality of life may decrease after menopause. Hormone replacement therapy remains the first-line and most effective treatment for menopausal symptoms and improvement of low quality of life due to estrogen deficiency. The decrease of health-related quality of life in women suffering from cardiovascular disease may be superimposed on the decrease of quality of life induced by menopause itself. Postmenopausal women with acute cardiovascular disease have a significantly higher probability of death than men of the same age. Quality of life predicts long-term mortality. A myocardial infarction does not automatically interdict sexual activity. The Princeton guidelines classify patients suffering from cardiovascular diseases in three categories. Most patients belong to the low-risk category. In general, these patients can be safely encouraged to initiate or resume sexual activity or to receive treatment for sexual dysfunction. Patients at intermediate (or indeterminate) levels of risk should further receive cardiologic evaluation to be classified into either the low- or high-risk group. Patients in the high-risk category have to be stabilized by specific treatment for their cardiac condition before resumption of sexual activity, or initiation of treatment for sexual dysfunction.

SfDronc, an initiator caspase involved in apoptosis in the fall armyworm Spodoptera frugiperda

PubMed Central

Huang, Ning; Civciristov, Srgjan; Hawkins, Christine J.; Clem, Rollie J.

2013-01-01

Initiator caspases are the first caspases that are activated following an apoptotic stimulus, and are responsible for cleaving and activating downstream effector caspases, which directly cause apoptosis. We have cloned a cDNA encoding an ortholog of the initiator caspase Dronc in the lepidopteran insect Spodoptera frugiperda. The SfDronc cDNA encodes a predicted protein of 447 amino acids with a molecular weight of 51 kDa. Overexpression of SfDronc induced apoptosis in Sf9 cells, while partial silencing of SfDronc expression in Sf9 cells reduced apoptosis induced by baculovirus infection or by treatment with UV or actinomycin D. Recombinant SfDronc exhibited several expected biochemical characteristics of an apoptotic initiator caspase: 1) SfDronc efficiently cleaved synthetic initiator caspase substrates, but had very little activity against effector caspase substrates; 2) mutation of a predicted cleavage site at position D340 blocked autoprocessing of recombinant SfDronc and reduced enzyme activity by approximately 10-fold; 3) SfDronc cleaved the effector caspase Sf-caspase-1 at the expected cleavage site, resulting in Sf-caspase-1 activation; and 4) SfDronc was strongly inhibited by the baculovirus caspase inhibitor SpliP49, but not by the related protein AcP35. These results indicate that SfDronc is an initiator caspase involved in caspase-dependent apoptosis in S. frugiperda, and as such is likely to be responsible for the initiator caspase activity in S. frugiperda cells known as Sf-caspase-X. PMID:23474489

Smoker Characteristics and Smoking-Cessation Milestones

PubMed Central

Japuntich, Sandra J.; Leventhal, Adam M.; Piper, Megan E.; Bolt, Daniel M.; Roberts, Linda J.; Fiore, Michael C.; Baker, Timothy B.

2011-01-01

Background Contextual variables often predict long-term abstinence, but little is known about how these variables exert their effects. These variables could influence abstinence by affecting the ability to quit at all, or by altering risk of lapsing, or progressing from a lapse to relapse. Purpose To examine the effect of common predictors of smoking-cessation failure on smoking-cessation processes. Methods The current study (N = 1504, 58% female, 84% Caucasian; recruited from January 2005 to June 2007; data analyzed in 2009) uses the approach advocated by Shiffman et al., (2006), which measures cessation outcomes on three different cessation milestones (achieving initial abstinence, lapse risk, and the lapse-relapse transition) to examine relationships of smoker characteristics (dependence, contextual and demographic factors) with smoking-cessation process. Results High nicotine dependence strongly predicted all milestones: not achieving initial abstinence, and a higher risk of both lapse and transitioning from lapse to complete relapse. Numerous contextual and demographic variables were associated with higher initial cessation rates and/or decreased lapse risk at 6 months post-quit (e.g., ethnicity, gender, marital status, education, smoking in the workplace, number of smokers in the social network, and number of supportive others). However, aside from nicotine dependence, only gender significantly predicted the risk of transition from lapse to relapse. Conclusions These findings demonstrate that: (1) higher nicotine dependence predicted worse outcomes across every cessation milestone; (2) demographic and contextual variables are generally associated with initial abstinence rates and lapse risk and not the lapse-relapse transition. These results identify groups who are at risk for failure at specific stages of the smoking-cessation process, and this may have implications for treatment. PMID:21335259

Intravaginal metronidazole gel versus metronidazole plus nystatin ovules for bacterial vaginosis: a randomized controlled trial.

PubMed

Sanchez, Sixto; Garcia, Patricia J; Thomas, Katherine K; Catlin, Mary; Holmes, King K

2004-12-01

We compared metronidazole 0.75% gel (containing 37.5 mg metronidazole per dose) with ovules containing metronidazole 500 mg and nystatin 100,000 U, for intravaginal treatment of bacterial vaginosis (BV). In a single-blinded trial, symptomatic women with BV by both Amsel and Nugent criteria were randomly assigned to gel or ovules, once nightly for 5 nights, and asked to return 3 times after treatment. Analyses were intent-to-treat. Of 151 women with BV by both criteria at enrollment, 138 (91%) returned at least once. Product limit estimates for persistence or recurrence of BV at 14, 42, and 104 days were 20% (95% CI 10%-29%), 38% (95% CI 25%-48%), and 52% (95% CI 37%-63%) after gel treatment, and 4% (95% CI 0%-9%), 17% (95% CI 7%-26%), and 33% (95% CI 21%-46%) after ovule treatment ( P = .01). Among women without BV at first follow-up, subsequent intercourse without condoms independently predicted subsequent recurrence ( P

Surgical treatment of secondary peritonitis : A continuing problem.

PubMed

van Ruler, O; Boermeester, M A

2017-01-01

Secondary peritonitis remains associated with high mortality and morbidity rates. Treatment of secondary peritonitis is challenging even in modern medicine. Surgical intervention for source control remains the cornerstone of treatment, beside adequate antimicrobial therapy and resuscitation. A randomized clinical trial showed that relaparotomy on demand (ROD) after initial emergency surgery is the preferred treatment strategy, irrespective of the severity and extent of peritonitis. The effective and safe use of ROD requires intensive monitoring of the patient in a setting where diagnostic tests and decision making about relaparotomy are guaranteed round the clock. The lack of knowledge on timely and adequate patient selection, together with the lack of use of easy but reliable monitoring tools, seems to hamper full implementation of ROD. The accuracy of the relap decision tool is reasonable for prediction of ongoing peritonitis and selection for computer tomography (CT). The value of CT in an early postoperative phase is unclear. Future research and innovative technologies should focus on the additive value of CT in cases of operated secondary peritonitis and on the further optimization of bedside prediction tools to enhance adequate patient selection for intervention in a multidisciplinary setting.

Predictive value of initial FDG-PET features for treatment response and survival in esophageal cancer patients treated with chemo-radiation therapy using a random forest classifier.

PubMed

Desbordes, Paul; Ruan, Su; Modzelewski, Romain; Pineau, Pascal; Vauclin, Sébastien; Gouel, Pierrick; Michel, Pierre; Di Fiore, Frédéric; Vera, Pierre; Gardin, Isabelle

2017-01-01

In oncology, texture features extracted from positron emission tomography with 18-fluorodeoxyglucose images (FDG-PET) are of increasing interest for predictive and prognostic studies, leading to several tens of features per tumor. To select the best features, the use of a random forest (RF) classifier was investigated. Sixty-five patients with an esophageal cancer treated with a combined chemo-radiation therapy were retrospectively included. All patients underwent a pretreatment whole-body FDG-PET. The patients were followed for 3 years after the end of the treatment. The response assessment was performed 1 month after the end of the therapy. Patients were classified as complete responders and non-complete responders. Sixty-one features were extracted from medical records and PET images. First, Spearman's analysis was performed to eliminate correlated features. Then, the best predictive and prognostic subsets of features were selected using a RF algorithm. These results were compared to those obtained by a Mann-Whitney U test (predictive study) and a univariate Kaplan-Meier analysis (prognostic study). Among the 61 initial features, 28 were not correlated. From these 28 features, the best subset of complementary features found using the RF classifier to predict response was composed of 2 features: metabolic tumor volume (MTV) and homogeneity from the co-occurrence matrix. The corresponding predictive value (AUC = 0.836 ± 0.105, Se = 82 ± 9%, Sp = 91 ± 12%) was higher than the best predictive results found using the Mann-Whitney test: busyness from the gray level difference matrix (P < 0.0001, AUC = 0.810, Se = 66%, Sp = 88%). The best prognostic subset found using RF was composed of 3 features: MTV and 2 clinical features (WHO status and nutritional risk index) (AUC = 0.822 ± 0.059, Se = 79 ± 9%, Sp = 95 ± 6%), while no feature was significantly prognostic according to the Kaplan-Meier analysis. The RF classifier can improve predictive and prognostic values compared to the Mann-Whitney U test and the univariate Kaplan-Meier survival analysis when applied to several tens of features in a limited patient database.

The MTA at 8 Years: Prospective Follow-Up of Children Treated for Combined Type ADHD in a Multisite Study

PubMed Central

Molina, Brooke S.G.; Hinshaw, Stephen P.; Swanson, James M.; Arnold, L. Eugene; Vitiello, Benedetto; Jensen, Peter S.; Epstein, Jeffery N.; Hoza, Betsy; Hechtman, Lily; Abikoff, Howard B.; Elliott, Glen R.; Greenhill, Laurence L.; Newcorn, Jeffrey H.; Wells, Karen C.; Wigal, Timothy; Gibbons, Robert D.; Hur, Kwan; Houck, Patricia R.

2011-01-01

Objectives To determine any long-term effects, 6 and 8 years after childhood enrollment, of the randomly assigned 14-month treatments in the Multimodal Treatment Study of Children with ADHD (MTA; N=436); to test whether Attention-Deficit/Hyperactivity Disorder (ADHD) symptom trajectory through 3-years predicts outcome in subsequent years; to examine functioning level of the MTA adolescents relative to their non-ADHD peers (Local Normative Comparison Group or LNCG; N=261). Method Mixed effects regression models with planned contrasts at 6- and 8-years tested a wide range of symptom and impairment variables assessed by parent, teacher, and youth report. Results In nearly every analysis, the originally randomized treatment groups did not differ significantly on repeated measures or newly-analyzed variables (e.g., grades earned in school, arrests, psychiatric hospitalizations, or other clinically relevant outcomes). Medication use decreased by 62% after the 14-month controlled trial, but adjusting for this did not change the results. ADHD symptom trajectory in the first 3 years predicted 55% of the outcomes. MTA participants fared worse than LNCG on 91% of the variables tested. Conclusions Type or intensity of 14 months of treatment for ADHD in childhood (at age 7.0–9.9 years old) does not predict functioning six-to-eight years later. Rather, early ADHD symptom trajectory regardless of treatment type is prognostic. This finding implies that children with behavioral and sociodemographic advantage, with the best response to any treatment, will have the best longterm prognosis. As a group, however, despite initial symptom improvement during treatment that is largely maintained post-treatment, children with Combined-Type ADHD exhibit significant impairment in adolescence. Innovative treatment approaches targeting specific areas of adolescent impairment are needed. PMID:19318991

Positioning the principles of precision medicine in care pathways for allergic rhinitis and chronic rhinosinusitis - A EUFOREA-ARIA-EPOS-AIRWAYS ICP statement.

PubMed

Hellings, P W; Fokkens, W J; Bachert, C; Akdis, C A; Bieber, T; Agache, I; Bernal-Sprekelsen, M; Canonica, G W; Gevaert, P; Joos, G; Lund, V; Muraro, A; Onerci, M; Zuberbier, T; Pugin, B; Seys, S F; Bousquet, J

2017-09-01

Precision medicine (PM) is increasingly recognized as the way forward for optimizing patient care. Introduced in the field of oncology, it is now considered of major interest in other medical domains like allergy and chronic airway diseases, which face an urgent need to improve the level of disease control, enhance patient satisfaction and increase effectiveness of preventive interventions. The combination of personalized care, prediction of treatment success, prevention of disease and patient participation in the elaboration of the treatment plan is expected to substantially improve the therapeutic approach for individuals suffering from chronic disabling conditions. Given the emerging data on the impact of patient stratification on treatment outcomes, European and American regulatory bodies support the principles of PM and its potential advantage over current treatment strategies. The aim of the current document was to propose a consensus on the position and gradual implementation of the principles of PM within existing adult treatment algorithms for allergic rhinitis (AR) and chronic rhinosinusitis (CRS). At the time of diagnosis, prediction of success of the initiated treatment and patient participation in the decision of the treatment plan can be implemented. The second-level approach ideally involves strategies to prevent progression of disease, in addition to prediction of success of therapy, and patient participation in the long-term therapeutic strategy. Endotype-driven treatment is part of a personalized approach and should be positioned at the tertiary level of care, given the efforts needed for its implementation and the high cost of molecular diagnosis and biological treatment. © 2017 EAACI and John Wiley and Sons A/S. Published by John Wiley and Sons Ltd.

NATURAL COURSE OF PATIENTS DISCONTINUING TREATMENT FOR AGE-RELATED MACULAR DEGENERATION AND FACTORS ASSOCIATED WITH VISUAL PROGNOSIS.

PubMed

Kim, Jae Hui; Chang, Young Suk; Kim, Jong Woo

2017-12-01

To evaluate the 24-month natural course of visual changes in patients discontinuing treatment despite persistent or recurrent fluid and factors predictive of visual prognosis. This retrospective, observational study included 35 patients (35 eyes) who initially received anti-vascular endothelial growth factor treatment for neovascular age-related macular degeneration (AMD), but discontinued treatment despite persistent or recurrent fluid. The best-corrected visual acuity (BCVA) at treatment discontinuation was determined and compared with the 24-month BCVA, which was then compared between polypoidal choroidal vasculopathy and other neovascular age-related macular degeneration subtypes. Baseline characteristics predictive of visual outcome and the degree of visual change were also analyzed. The mean number of anti-vascular endothelial growth factor injections before treatment discontinuation was 4.0 ± 1.6. The mean logarithm of minimal angle of resolution of BCVA at treatment discontinuation and that at 24 months were 1.02 ± 0.20 (Snellen equivalents = 20/209) and 1.60 ± 0.56 (20/796), respectively (P < 0.001). The 24-month BCVA was not different between polypoidal choroidal vasculopathy and other neovascular age-related macular degeneration subtypes (P = 0.803). The type of fluid (intraretinal fluid vs. no intraretinal fluid) was predictive of 24-month BCVA (P = 0.004) and the degree of changes in BCVA (P = 0.043). Marked deterioration in visual acuity was noted in patients discontinuing treatment, regardless of neovascular age-related macular degeneration subtypes. The presence of intraretinal fluid was associated with worse visual prognosis, suggesting that patients with intraretinal fluid should be strongly warned about their poor prognosis before they decide to discontinue treatment.

Concerns about dose and underutilization of twelve-step programs: models, scales, and theory that inform treatment planning.

PubMed

Cloud, Richard N; Kingree, J B

2008-01-01

Researchers have observed that a majority of addicted persons who are encouraged and facilitated by treatment providers to attend twelve-step (TS) programs either drop out or sporadically use twelve-step programs following treatment. This is troubling given considerable evidence of TS program benefits associated with regular weekly attendance and ubiquitous reliance by treatment professionals on these programs to provide important support services. This chapter reviews and advances theory of TS utilization and dose that is supported by prior research, multivariate models, and scales that predict risk of TS meeting underutilization. Advancing theory should organize and clarify the process of initial utilization, guide intervention development, and improve adherence of TS program referrals, all of which should lead to improved treatment planning and better outcomes. Three theories are integrated to explain processes that may influence TS program dose: the health belief model, self-determination theory (motivational theory), and a person-in-organization cultural fit theory. Four multidimensional scales developed specifically to predict participation are described. Implications for practice and future research are considered in a final discussion. Information contained in this chapter raises awareness of the need for TS-focused treatments to focus on achieving weekly attendance during and after treatment.

Clinical Factors Predicting Detection of T790M Mutation in Rebiopsy for EGFR-Mutant Non-small-cell Lung Cancer.

PubMed

Kawamura, Takahisa; Kenmotsu, Hirotsugu; Omori, Shota; Nakashima, Kazuhisa; Wakuda, Kazushige; Ono, Akira; Naito, Tateaki; Murakami, Haruyasu; Omae, Katsuhiro; Mori, Keita; Tanigawara, Yusuke; Nakajima, Takashi; Ohde, Yasuhisa; Endo, Masahiro; Takahashi, Toshiaki

2018-03-01

T790M, a secondary epidermal growth factor receptor (EGFR) mutation, accounts for approximately 50% of acquired resistance to EGFR-tyrosine kinase inhibitors (TKIs). To facilitate the use of third-generation EGFR-TKIs to potentially overcome T790M-mediated resistance, we evaluated the clinical factors influencing the incidence of T790M mutation. We retrospectively screened patients with non-small-cell lung cancer harboring EGFR mutations with progressive disease who were rebiopsied between January 2013 and December 2016. Factors influencing T790M status were evaluated by univariate and multivariate analysis. Among 131 rebiopsied patients for whom EGFR mutation status was available, 58 (44%) had T790M mutations. Patient characteristics at rebiopsy were not significantly different between T790M-positive and -negative groups, except for surgical history (postsurgery recurrence). Total duration of EGFR-TKI treatment before rebiopsy, TKI-free interval, EGFR-TKI treatment history immediately before rebiopsy, continuation of initial EGFR-TKI beyond progressive disease, progression-free survival after initial TKI treatment, and rebiopsy site (other than fluid samples) significantly influenced T790M status. The incidence of T790M mutation was shown by multivariate analysis to be significantly higher in patients with postsurgery recurrence and total duration of EGFR-TKI treatment ≥ 1 year before rebiopsy (odds ratio, 4.2; 95% confidence interval, 1.3-15.7 and odds ratio, 4.4; 95% confidence interval, 1.1-19.8, respectively). Postsurgery recurrence and longer total duration of EGFR-TKI treatment before rebiopsy may represent useful predictive markers for T790M detection. In patients with these clinical factors, rebiopsies are more recommended to detect T790M mutation. Copyright © 2017 Elsevier Inc. All rights reserved.

Predictive value and cost-effectiveness analysis of a rapid polymerase chain reaction for preoperative detection of nasal carriage of Staphylococcus aureus.

PubMed

Shrestha, Nabin K; Shermock, Kenneth M; Gordon, Steven M; Tuohy, Marion J; Wilson, Deborah A; Cwynar, Roberta E; Banbury, Michael K; Longworth, David L; Isada, Carlos M; Mawhorter, Steven D; Procop, Gary W

2003-05-01

To determine the accuracy and cost-effectiveness of a polymerase chain reaction (PCR) for detecting nasal carriage of Staphylococcus aureus directly from clinical specimens. CROSS-SECTIONAL STUDY: This occurred in a tertiary-care hospital in Cleveland, Ohio, and included 239 consecutive patients who were scheduled for a cardiothoracic surgical procedure. Conventional cultures and a PCR for S. aureus from nasal swabs were used as measurements. COST-EFFECTIVENESS ANALYSIS: Data sources were market prices and Bureau of Labor Statistics. The time horizon was the maximum period for availability of culture results (3 days). Interventions included universal mupirocin therapy without testing; initial therapy, with termination if PCR negative (treat-PCR); initial therapy, with termination if culture negative (treat-culture); treat PCR-positive carriers (PCR-guided treatment); and treat culture-positive carriers (culture-guided treatment). The perspective was institutional and costs and the length of time to treatment were outcome measures. Sixty-seven (28%) of the 239 swabs grew S. aureus. Rapid PCR was 97.0% sensitive and 97.1% specific for the detection of S. aureus. For populations with prevalences of nasal S. aureus carriage of up to 50%, the PCR assay had negative predictive values of greater than 97%. PCR-guided treatment had the lowest incremental cost-effectiveness ratio (1.93 dollars per additional day compared with the culture strategy). Among immediate treatment strategies, treat-PCR was most cost-effective. The universal therapy strategy cost 38.19 dollars more per additional day gained with carrier identification compared with the PCR strategy. Rapid real-time PCR is an accurate, rapid, and cost-effective method for identifying S. aureus carriers for preoperative intervention.

SU-E-T-106: Development of a Collision Prediction Algorithm for Determining Problematic Geometry for SBRT Treatments Using a Stereotactic Body Frame

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

Wagar, M; Friesen, S; Mannarino, E

2014-06-01

Purpose: Collision between the gantry and the couch or patient during Radiotherapy is not a common concern for conventional RT (static fields or arc). With the increase in the application of stereotactic planning techniques to the body, collisions have become a greater concern. Non-coplanar beam geometry is desirable in stereotatic treatments in order to achieve sharp gradients and a high conformality. Non-coplanar geometry is less intuitive in the body and often requires an iterative process of planning and dry runs to guarantee deliverability. Methods: Purpose written software was developed in order to predict the likelihood of collision between the headmore » of the gantry and the couch, patient or stereotatic body frame. Using the DICOM plan and structures set, exported by the treatment planning system, this software is able to predict the possibility of a collision. Given the plan's isocenter, treatment geometry and exterior contours, the software is able to determine if a particular beam/arc is clinically deliverable or if collision is imminent. Results: The software was tested on real world treatment plans with untreatable beam geometry. Both static non-coplanar and VMAT plans were tested. Of these, the collision prediction software could identify all as having potentially problematic geometry. Re-plans of the same cases were also tested and validated as deliverable. Conclusion: This software is capable of giving good initial indication of deliverability for treatment plans that utilize complex geometry (SBRT) or have lateral isocenters. This software is not intended to replace the standard pre-treatment QA dry run. The effectiveness is limited to those portions of the patient and immobilization devices that have been included in the simulation CT and contoured in the planning system. It will however aid the planner in reducing the iterations required to create complex treatment geometries necessary to achieve ideal conformality and organ sparing.« less

The utility of MMPI-2-RF substantive scales in prediction of negative treatment outcomes in a community mental health center.

PubMed

Anestis, Joye C; Gottfried, Emily D; Joiner, Thomas E

2015-02-01

This study examined the utility of the Minnesota Multiphasic Personality Inventory-2-Restructured Form (MMPI-2-RF) substantive scales in the prediction of premature termination and therapy no-shows while controlling for other relevant predictors in a university-based community mental health center, a sample at high risk of both premature termination and no-show appointments. Participants included 457 individuals seeking services from a university-based psychology clinic. Results indicated that Juvenile Conduct Problems (JCP) predicted premature termination and Behavioral/Externalizing Dysfunction and JCP predicted number of no-shows, when accounting for initial severity of illness, personality disorder diagnosis, therapist experience, and other related MMPI-2-RF scales. The MMPI-2-RF Aesthetic-Literary Interests scale also predicted number of no-shows. Recommendations for applying these findings in clinical practice are discussed. © The Author(s) 2014.

Utilizing electronic health records to predict acute kidney injury risk and outcomes: workgroup statements from the 15(th) ADQI Consensus Conference.

PubMed

Sutherland, Scott M; Chawla, Lakhmir S; Kane-Gill, Sandra L; Hsu, Raymond K; Kramer, Andrew A; Goldstein, Stuart L; Kellum, John A; Ronco, Claudio; Bagshaw, Sean M

2016-01-01

The data contained within the electronic health record (EHR) is "big" from the standpoint of volume, velocity, and variety. These circumstances and the pervasive trend towards EHR adoption have sparked interest in applying big data predictive analytic techniques to EHR data. Acute kidney injury (AKI) is a condition well suited to prediction and risk forecasting; not only does the consensus definition for AKI allow temporal anchoring of events, but no treatments exist once AKI develops, underscoring the importance of early identification and prevention. The Acute Dialysis Quality Initiative (ADQI) convened a group of key opinion leaders and stakeholders to consider how best to approach AKI research and care in the "Big Data" era. This manuscript addresses the core elements of AKI risk prediction and outlines potential pathways and processes. We describe AKI prediction targets, feature selection, model development, and data display.

Primary gastric mucosa associated lymphoid tissue lymphoma: Clinical data predicted treatment outcome

PubMed Central

Todorovic, Milena; Balint, Bela; Jevtic, Miodrag; Suvajdzic, Nada; Ceric, Amela; Stamatovic, Dragana; Markovic, Olivera; Perunicic, Maja; Marjanovic, Slobodan; Krstic, Miodrag

2008-01-01

AIM: To determine clinical characteristics and treatment outcome of gastric lymphoma after chemotherapy and immuno-chemotherapy. METHODS: Thirty four patients with primary gastric mucosa associated lymphoid tissue (MALT) lymphoma (Ann Arbor stages I to IV) were enrolled. All had upper gastric endoscopy, abdominal ultrasonography, CT and H pylori status assessment (histology and serology). After anti-H pylori treatment and initial chemotherapy, patients were re-examined every 4 mo. RESULTS: Histological regression of the lymphoma was complete in 22/34 (64.7%) and partial in 9 (26.5%) patients. Median follow up time for these 31 responders was 60 mo (range 48-120). No regression was noted in 3 patients. Among the 25 (73.5%) H pylori positive patients, the eradication rate was 100%. CONCLUSION: Using univariate analysis, predictive factors for overall survival were international prognostic index (IPI) score, hemoglobin level, erythrocyte sedimentation rate (ESR), and platelet numbers (P < 0.005). In addition to this, Cox proportion hazard model differentiate IPI score, ESR, and platelets as predictors of survival. PMID:18416467

Children's and Parents' Ability to Tolerate Child Distress: Impact on Cognitive Behavioral Therapy for Pediatric Obsessive Compulsive Disorder.

PubMed

Selles, Robert R; Franklin, Martin; Sapyta, Jeffrey; Compton, Scott N; Tommet, Doug; Jones, Richard N; Garcia, Abbe; Freeman, Jennifer

2018-04-01

The present study explored the concept of tolerance for child distress in 46 children (ages 5-8), along with their mothers and fathers, who received family-based CBT for OCD. The study sought to describe baseline tolerance, changes in tolerance with treatment, and the predictive impact of tolerance on symptom improvement. Tolerance was rated by clinicians on a single item and the CY-BOCS was used to measure OCD severity. Descriptive results suggested that all participants had some difficulty tolerating the child's distress at baseline while paired t tests indicated large improvements were made over treatment (d = 1.2-2.0). Fathers' initial tolerance was significantly related to symptom improvement in a multivariate regression as were fathers' and children's changes in distress tolerance over the course of treatment. Overall, results provide support for examining tolerance of child distress including its predictive impact and potential as a supplemental intervention target.

Cohort study of oncologic emergencies in patients with head and neck cancer.

PubMed

Reyes-Gibby, Cielito C; Melkonian, Stephanie C; Hanna, Ehab Y; Yeung, Sai-Ching J; Lu, Charles; Chambers, Mark S; Banala, Srinivas R; Gunn, Gary B; Shete, Sanjay S

2017-06-01

Treatments for head and neck squamous cell carcinoma (HNSCC) are associated with toxicities that lead to emergency department presentation. We utilized data from an ongoing prospective cohort of newly diagnosed, previously untreated patients (N = 298) with HNSCC to evaluate the association between clinical and epidemiologic factors and risk for and frequency of emergency department presentation. Time to event was calculated from the date of treatment initiation to emergency department presentation, date of death, or current date. Frequency of emergency department presentation was the sum of emergency department visits during the follow-up time. History of hypertension, normal/underweight body mass index (BMI), and probable depression predicted increased risk for emergency department presentation. BMI and severe pain were associated with higher frequency of emergency department presentations. Clinical and epidemiologic factors can help predict patients with HNSCC who will present to the emergency department. Such knowledge may improve treatment-related patient outcomes and quality of life. © 2017 Wiley Periodicals, Inc. Head Neck 39: 1195-1204, 2017. © 2017 Wiley Periodicals, Inc.

Cannabis Withdrawal, Posttreatment Abstinence, and Days to First Cannabis Use Among Emerging Adults in Substance Use Treatment: A Prospective Study

PubMed Central

Davis, Jordan P.; Smith, Douglas C.; Morphew, Jason W.; Lei, Xinrong; Zhang, Saijun

2015-01-01

Very little prospective research investigates how cannabis withdrawal is associated with treatment outcomes, and this work has not used the Diagnostic and Statistical Manual of Mental Disorders (5th ed.; DSM-5) thresholds for cannabis withdrawal. The sample included 110 emerging adults entering outpatient substance use treatment who were heavy cannabis users with no other drug use and limited alcohol use. We used survival analyses to predict days to first use of cannabis and logistic regression to predict whether participants were abstinent and living in the community at 3 months. Those meeting criteria for cannabis withdrawal were more likely to return to use sooner than those not meeting criteria for cannabis withdrawal. However, the presence of cannabis withdrawal was not a significant predictor of 3-month abstinence. Emerging adults with DSM-5 cannabis withdrawal may have difficulty initiating abstinence in the days following their intake assessment, implying the need for strategies to mitigate their more rapid return to cannabis use. PMID:26877548

Preferences for Early Intervention Mental Health Services: A Discrete-Choice Conjoint Experiment.

PubMed

Becker, Mackenzie P E; Christensen, Bruce K; Cunningham, Charles E; Furimsky, Ivana; Rimas, Heather; Wilson, Fiona; Jeffs, Lisa; Bieling, Peter J; Madsen, Victoria; Chen, Yvonne Y S; Mielko, Stephanie; Zipursky, Robert B

2016-02-01

Early intervention services (EISs) for mental illness may improve outcomes, although treatment engagement is often a problem. Incorporating patients' preferences in the design of interventions improves engagement. A discrete-choice conjoint experiment was conducted in Canada to identify EIS attributes that encourage treatment initiation. Sixteen four-level attributes were formalized into a conjoint survey, completed by patients, family members, and mental health professionals (N=562). Participants were asked which EIS option people with mental illness would contact. Latent-class analysis identified respondent classes characterized by shared preferences. Randomized first-choice simulations predicted which hypothetical options, based on attributes, would result in maximum utilization. Participants in the conventional-service class (N=241, 43%) predicted that individuals would contact traditional services (for example, hospital location and staffed by psychologists or psychiatrists). Membership was associated with being a patient or family member and being male. Participants in the convenient-service class (N=321, 57%) predicted that people would contact services promoting easy access (for example, self-referral and access from home). Membership was associated with being a professional. Both classes predicted that people would contact services that included short wait times, direct contact with professionals, patient autonomy, and psychological treatment information. The convenient-service class predicted that people would use an e-health model, whereas the conventional-service class predicted that people would use a primary care or clinic-hospital model. Provision of a range of services may maximize EIS use. Professionals may be more apt to adopt EISs in line with their beliefs regarding patient preferences. Considering several perspectives is important for service design.

Current status of the congenital hypothyroidism neonatal screening program in Adana Province, Turkey.

PubMed

Kor, Yılmaz; Kor, Deniz

2018-06-27

Congenital hypothyroidism (CH) is a common cause of mental retardation; it has a worldwide incidence ranging from 1:3000 to 1:4500 live births. Predictably, an increase in the reported incidence of primary CH occurs when the cut-off levels of thyroid-stimulating hormone are lowered. We aimed to evaluate the results of a congenital hypothyroidism screening program and current status in this study. Analysis results of 1300 infants who were referred to the endocrinology polyclinic because of suspected CH within the scope of the Ministry of Health National Neonatal Screening Program were retrospectively evaluated. The diagnosis of CH and initiation of treatment were both done in 223 (18.5%) and 10 (0.8%) infants as a result of the initial evaluation and follow-up, respectively. The mean capillary and venous thyroid-stimulating hormone (TSH) levels of 223 patients were 40.78 (5.5-100) μIU/mL and 67.26 (10.7-100) μIU/mL, respectively. These patients' mean heel prick time was 8.65 (0-30, median: 7) days. The mean age of the 223 infants whose treatment was initiated as a result of the initial evaluation was 19.87 (4-51, median: 20) days, and the mean age of the infants whose treatment was started at follow-up was 43.71 (29-65) days. The duration between heel prick time and venous TSH time was 11.10 (2-28, median: 11) days and was longer than planned (3-5 days). Although the duration for the diagnosis and initiation of CH treatment were markedly reduced with the implementation of the screening program in Turkey compared to those before the implementation of the screening program, we have not yet achieved the ideal time (≤14 days).

Insights into the management of chronic myeloid leukemia in resource-poor settings: a Mexican perspective.

PubMed

Gomez-de-León, Andrés; Gómez-Almaguer, David; Ruiz-Delgado, Guillermo J; Ruiz-Arguelles, Guillermo J

2017-09-01

The arrival of targeted therapy for chronic myeloid leukemia (CML) was revolutionary. However, due to the high cost of tyrosine kinase inhibitors, access to this highly effective therapy with strict monitoring strategies is limited in low to middle-income countries. In this context, following standard recommendations proposed by experts in developed countries is difficult. Areas covered: This review aims to provide an insight into the management of patients with CML living in a resource-limited setting. It addresses several issues: diagnosis, initial treatment, disease monitoring, and additional treatment alternatives including allogeneic hematopoietic stem cell transplantation. Expert commentary: Imatinib is probably the most cost-effective TKI for initial treatment in developing and underdeveloped countries. Generic imatinib preparations should be evaluated before considering their widespread use. Adherence to treatment should be emphasized. Adequate monitoring can be performed through several methods successfully and is important for predicting outcomes, particularly early in the first year, and if treatment suspension is being considered. Access to further therapeutic alternatives should define our actions after failure or intolerance to imatinib, preferring additional TKIs if possible. Allogeneic transplantation in chronic phase is a viable option in this context.

Anovulation and ovulation induction

PubMed Central

Katsikis, I; Kita, M; Karkanaki, A; Prapas, N; Panidis, D

2006-01-01

Conventional treatment of normogonadotropic anovulatory infertility is ovulation induction using the antiestrogen clomiphene citrate, followed by follicle-stimulating hormone. Multiple follicle development, associated with ovarian hyperstimulation, and multiple pregnancy remain the major complications. Cumulative singleton and multiple pregnancy rate data after different induction treatments are needed. Newer ovulation induction interventions, such as insulin-sensitizing drugs, aromatase inhibitors and laparoscopic ovarian electrocoagulation, should be compared with conventional treatments. Ovulation induction efficiency might improve if patient subgroups with altered chances for success or complications with new or conventional techniques could be identified, using multivariate prediction models based on initial screening characteristics. This would make ovulation induction more cost-effective, safe and convenient, enabling doctors to advise patients on the most effective and patient-tailored treatment strategy. PMID:20351807

The STarT Back Screening Tool and Individual Psychological Measures: Evaluation of Prognostic Capabilities for Low Back Pain Clinical Outcomes in Outpatient Physical Therapy Settings

PubMed Central

Bishop, Mark D.; Fritz, Julie M.; Robinson, Michael E.; Asal, Nabih R.; Nisenzon, Anne N.

2013-01-01

Background Psychologically informed practice emphasizes routine identification of modifiable psychological risk factors being highlighted. Objective The purpose of this study was to test the predictive validity of the STarT Back Screening Tool (SBT) in comparison with single-construct psychological measures for 6-month clinical outcomes. Design This was an observational, prospective cohort study. Methods Patients (n=146) receiving physical therapy for low back pain were administered the SBT and a battery of psychological measures (Fear-Avoidance Beliefs Questionnaire physical activity scale and work scale [FABQ-PA and FABQ-W, respectively], Pain Catastrophizing Scale [PCS], 11-item version of the Tampa Scale of Kinesiophobia [TSK-11], and 9-item Patient Health Questionnaire [PHQ-9]) at initial evaluation and 4 weeks later. Treatment was at the physical therapist's discretion. Clinical outcomes consisted of pain intensity and self-reported disability. Prediction of 6-month clinical outcomes was assessed for intake SBT and psychological measure scores using multiple regression models while controlling for other prognostic variables. In addition, the predictive capabilities of intake to 4-week changes in SBT and psychological measure scores for 6-month clinical outcomes were assessed. Results Intake pain intensity scores (β=.39 to .45) and disability scores (β=.47 to .60) were the strongest predictors in all final regression models, explaining 22% and 24% and 43% and 48% of the variance for the respective clinical outcome at 6 months. Neither SBT nor psychological measure scores improved prediction of 6-month pain intensity. The SBT overall scores (β=.22) and SBT psychosocial scores (β=.25) added to the prediction of disability at 6 months. Four-week changes in TSK-11 scores (β=−.18) were predictive of pain intensity at 6 months. Four-week changes in FABQ-PA scores (β=−.21), TSK-11 scores (β=−.20) and SBT overall scores (β=−.18) were predictive of disability at 6 months. Limitations Physical therapy treatment was not standardized or accounted for in the analysis. Conclusions Prediction of clinical outcomes by psychology-based measures was dependent upon the clinical outcome domain of interest. Similar to studies from the primary care setting, initial screening with the SBT provided additional prognostic information for 6-month disability and changes in SBT overall scores may provide important clinical decision-making information for treatment monitoring. PMID:23125279

Towards personalized therapy for multiple sclerosis: prediction of individual treatment response.

PubMed

Kalincik, Tomas; Manouchehrinia, Ali; Sobisek, Lukas; Jokubaitis, Vilija; Spelman, Tim; Horakova, Dana; Havrdova, Eva; Trojano, Maria; Izquierdo, Guillermo; Lugaresi, Alessandra; Girard, Marc; Prat, Alexandre; Duquette, Pierre; Grammond, Pierre; Sola, Patrizia; Hupperts, Raymond; Grand'Maison, Francois; Pucci, Eugenio; Boz, Cavit; Alroughani, Raed; Van Pesch, Vincent; Lechner-Scott, Jeannette; Terzi, Murat; Bergamaschi, Roberto; Iuliano, Gerardo; Granella, Franco; Spitaleri, Daniele; Shaygannejad, Vahid; Oreja-Guevara, Celia; Slee, Mark; Ampapa, Radek; Verheul, Freek; McCombe, Pamela; Olascoaga, Javier; Amato, Maria Pia; Vucic, Steve; Hodgkinson, Suzanne; Ramo-Tello, Cristina; Flechter, Shlomo; Cristiano, Edgardo; Rozsa, Csilla; Moore, Fraser; Luis Sanchez-Menoyo, Jose; Laura Saladino, Maria; Barnett, Michael; Hillert, Jan; Butzkueven, Helmut

2017-09-01

Timely initiation of effective therapy is crucial for preventing disability in multiple sclerosis; however, treatment response varies greatly among patients. Comprehensive predictive models of individual treatment response are lacking. Our aims were: (i) to develop predictive algorithms for individual treatment response using demographic, clinical and paraclinical predictors in patients with multiple sclerosis; and (ii) to evaluate accuracy, and internal and external validity of these algorithms. This study evaluated 27 demographic, clinical and paraclinical predictors of individual response to seven disease-modifying therapies in MSBase, a large global cohort study. Treatment response was analysed separately for disability progression, disability regression, relapse frequency, conversion to secondary progressive disease, change in the cumulative disease burden, and the probability of treatment discontinuation. Multivariable survival and generalized linear models were used, together with the principal component analysis to reduce model dimensionality and prevent overparameterization. Accuracy of the individual prediction was tested and its internal validity was evaluated in a separate, non-overlapping cohort. External validity was evaluated in a geographically distinct cohort, the Swedish Multiple Sclerosis Registry. In the training cohort (n = 8513), the most prominent modifiers of treatment response comprised age, disease duration, disease course, previous relapse activity, disability, predominant relapse phenotype and previous therapy. Importantly, the magnitude and direction of the associations varied among therapies and disease outcomes. Higher probability of disability progression during treatment with injectable therapies was predominantly associated with a greater disability at treatment start and the previous therapy. For fingolimod, natalizumab or mitoxantrone, it was mainly associated with lower pretreatment relapse activity. The probability of disability regression was predominantly associated with pre-baseline disability, therapy and relapse activity. Relapse incidence was associated with pretreatment relapse activity, age and relapsing disease course, with the strength of these associations varying among therapies. Accuracy and internal validity (n = 1196) of the resulting predictive models was high (>80%) for relapse incidence during the first year and for disability outcomes, moderate for relapse incidence in Years 2-4 and for the change in the cumulative disease burden, and low for conversion to secondary progressive disease and treatment discontinuation. External validation showed similar results, demonstrating high external validity for disability and relapse outcomes, moderate external validity for cumulative disease burden and low external validity for conversion to secondary progressive disease and treatment discontinuation. We conclude that demographic, clinical and paraclinical information helps predict individual response to disease-modifying therapies at the time of their commencement. © The Author (2017). Published by Oxford University Press on behalf of the Guarantors of Brain. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

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

Espinoza, I; Peschke, P; Karger, C

Purpose: In radiotherapy, it is important to predict the response of tumour to irradiation prior to the treatment. Mathematical modelling of tumour control probability (TCP) based on the dose distribution, medical imaging and other biological information may help to improve this prediction and to optimize the treatment plan. The aim of this work is to develop an image based 3D multiscale radiobiological model, which describes the growth and the response to radiotherapy of hypoxic tumors. Methods: The computer model is based on voxels, containing tumour, normal (including capillary) and dead cells. Killing of tumour cells due to irradiation is calculatedmore » by the Linear Quadratic Model (extended for hypoxia), and the proliferation and resorption of cells are modelled by exponential laws. The initial shape of the tumours is taken from CT images and the initial vascular and cell density information from PET and/or MR images. Including the fractionation regime and the physical dose distribution of the radiation treatment, the model simulates the spatial-temporal evolution of the tumor. Additionally, the dose distribution may be biologically optimized. Results: The model describes the appearance of hypoxia during tumour growth and the reoxygenation processes during radiotherapy. Among other parameters, the TCP is calculated for different dose distributions. The results are in accordance with published results. Conclusion: The simulation model may contribute to the understanding of the influence of biological parameters on tumor response during treatment, and specifically on TCP. It may be used to implement dose-painting approaches. Experimental and clinical validation is needed. This study is supported by a grant from the Ministry of Education of Chile, Programa Mece Educacion Superior (2)« less

Long-term changes in neurocognition and behavior following treatment of sleep disordered breathing in school-aged children.

PubMed

Biggs, Sarah N; Vlahandonis, Anna; Anderson, Vicki; Bourke, Robert; Nixon, Gillian M; Davey, Margot J; Horne, Rosemary S C

2014-01-01

Sleep disordered breathing (SDB) in children is associated with detrimental neurocognitive and behavioral consequences. The long term impact of treatment on these outcomes is unknown. This study examined the long-term effect of treatment of SDB on neurocognition, academic ability, and behavior in a cohort of school-aged children. Four-year longitudinal study. Children originally diagnosed with SDB and healthy non-snoring controls underwent repeat polysomnography and age-standardized neurocognitive and behavioral assessment 4y following initial testing. Melbourne Children's Sleep Centre, Melbourne, Australia. Children 12-16 years of age, originally assessed at 7-12 years, were categorized into Treated (N = 12), Untreated (N = 26), and Control (N = 18) groups. Adenotonsillectomy, Tonsillectomy, Nasal Steroids. Decision to treat was independent of this study. Changes in sleep and respiratory parameters over time were assessed. A decrease in obstructive apnea hypopnea index (OAHI) from Time 1 to Time 2 was seen in 63% and 100% of the Untreated and Treated groups, respectively. The predictive relationship between change in OAHI and standardized neurocognitive, academic, and behavioral scores over time was examined. Improvements in OAHI were predictive of improvements in Performance IQ, but not Verbal IQ or academic measures. Initial group differences in behavioral assessment on the Child Behavior Checklist did not change over time. Children with SDB at baseline continued to exhibit significantly poorer behavior than Controls at follow-up, irrespective of treatment. After four years, improvements in SDB are concomitant with improvements in some areas of neurocognition, but not academic ability or behavior in school-aged children.

Health utility and survival after hospital admission with acute cardiogenic pulmonary oedema.

PubMed

Goodacre, Steve; Gray, Alasdair; Newby, David; Dixon, Simon; Masson, Moyra; Sampson, Fiona; Nicholl, Jon; Elliot, Mark; Crane, Steven

2011-06-01

The aim of this study was to measure health utility and survival in patients with acute cardiogenic pulmonary oedema (ACPO), identify predictors of outcome and determine the effect of initial treatment with non-invasive ventilation (NIV) upon outcomes. A randomised controlled trial was conducted at 26 hospitals in the UK. 1069 adults with ACPO were randomised to continuous positive airway pressure (CPAP), non-invasive positive pressure ventilation (NIPPV) or standard oxygen therapy. The main outcome measures were survival to 1-5 years, health utility measured using the EQ-5D survey at 1, 3 and 6 months, and quality-adjusted life years (QALYs). Median survival was 771 days (95% CI 669 to 875), with no difference between the three treatment groups (p = 0.827). Age (HR 1.042, 95% CI 1.031 to 1.052), chronic obstructive pulmonary disease (HR 1.13, 95% CI 1.06 to 1.62), cerebrovascular disease (HR 1.41, 95% CI 1.14 to 1.73) and diabetes mellitus (HR 1.31, 95% CI 1.01 to 1.63) independently predicted mortality. Mean EQ-5D scores were 0.578, 0.576 and 0.582 at 1, 3 and 6 months, respectively, with no significant difference between the treatment groups. Male gender (+0.045 QALYs, 95% CI 0.009 to 0.081) and cerebrovascular disease (-0.080 QALYs, 95% CI -0.131 to -0.029) independently predicted health utility. Patients with ACPO have high mortality and reduced health utility. Initial treatment with CPAP or NIPPV does not alter subsequent survival or health utility.

Accumulating Data to Optimally Predict Obesity Treatment (ADOPT) Core Measures: Behavioral Domain.

PubMed

Lytle, Leslie A; Nicastro, Holly L; Roberts, Susan B; Evans, Mary; Jakicic, John M; Laposky, Aaron D; Loria, Catherine M

2018-04-01

The ability to identify and measure behaviors that are related to weight loss and the prevention of weight regain is crucial to understanding the variability in response to obesity treatment and the development of tailored treatments. The overarching goal of the Accumulating Data to Optimally Predict obesity Treatment (ADOPT) Core Measures Project is to provide obesity researchers with guidance on a set of constructs and measures that are related to weight control and that span and integrate obesity-related behavioral, biological, environmental, and psychosocial domains. This article describes how the behavioral domain subgroup identified the initial list of high-priority constructs and measures to be included, and it describes practical considerations for assessing the following four behavioral areas: eating, activity, sleep, and self-monitoring of weight. Challenges and considerations for advancing the science related to weight loss and maintenance behaviors are also discussed. Assessing a set of core behavioral measures in combination with those from other ADOPT domains is critical to improve our understanding of individual variability in response to adult obesity treatment. The selection of behavioral measures is based on the current science, although there continues to be much work needed in this field. © 2018 The Obesity Society.

Longitudinal Examination of the Influence of Individual Posttraumatic Stress Disorder Symptoms and Clusters of Symptoms on the Initiation of Cigarette Smoking.

PubMed

Seelig, Amber D; Bensley, Kara M; Williams, Emily C; Armenta, Richard F; Rivera, Anna C; Peterson, Arthur V; Jacobson, Isabel G; Littman, Alyson J; Maynard, Charles; Bricker, Jonathan B; Rull, Rudolph P; Boyko, Edward J

2018-06-06

The aim of this study was to determine whether specific individual posttraumatic stress disorder (PTSD) symptoms or symptom clusters predict cigarette smoking initiation. Longitudinal data from the Millennium Cohort Study were used to estimate the relative risk for smoking initiation associated with PTSD symptoms among 2 groups: (1) all individuals who initially indicated they were nonsmokers (n = 44,968, main sample) and (2) a subset of the main sample who screened positive for PTSD (n = 1622). Participants were military service members who completed triennial comprehensive surveys that included assessments of smoking and PTSD symptoms. Complementary log-log models were fit to estimate the relative risk for subsequent smoking initiation associated with each of the 17 symptoms that comprise the PTSD Checklist and 5 symptom clusters. Models were adjusted for demographics, military factors, comorbid conditions, and other PTSD symptoms or clusters. In the main sample, no individual symptoms or clusters predicted smoking initiation. However, in the subset with PTSD, the symptoms "feeling irritable or having angry outbursts" (relative risk [RR] 1.41, 95% confidence interval [CI] 1.13-1.76) and "feeling as though your future will somehow be cut short" (RR 1.19, 95% CI 1.02-1.40) were associated with increased risk for subsequent smoking initiation. Certain PTSD symptoms were associated with higher risk for smoking initiation among current and former service members with PTSD. These results may help identify individuals who might benefit from more intensive smoking prevention efforts included with PTSD treatment.

Treatment expectancy affects the outcome of cognitive-behavioral interventions in chronic pain.

PubMed

Goossens, Mariëlle E J B; Vlaeyen, Johan W S; Hidding, Alita; Kole-Snijders, Ank; Evers, Silvia M A A

2005-01-01

Patients' initial beliefs about the success of a given pain treatment are shown to have an important influence on the final treatment outcome. The aims of the paper are to assess determinants of patients' treatment expectancy and to examine the extent to which treatment expectancy predicts the short-term and long-term outcome of cognitive-behavioral treatment of chronic pain. This study employs the data of 2 pooled randomized clinical trials evaluating the effectiveness of cognitive-behavioral interventions for 171 patients with fibromyalgia and chronic low back pain. Pretreatment and posttreatment expectancy were measured by a short questionnaire, which was based on the procedure by Borkovec and Nau. Four composite outcome variables (pain coping and control, motoric behavior, negative affect, and quality of life) were measured before and after the intervention and at 12 months follow-up. Furthermore, several patient characteristics were taken into account. Patients with higher treatment expectancies significantly received less disability compensation and were less fearful. A regression model of 3 factors (better pain coping and control, active and positive interpretation of pain, and less disability compensation) significantly explained 10% of the variance in pretreatment expectancy. Pretreatment expectancy significantly predicted each of the 4 outcome measures immediately after treatment and at 12 months follow-up. This study corroborates the importance of treatment expectation before entering a cognitive-behavioral intervention in patients with chronic musculoskeletal pain.

Value of gastrografin in adhesive small bowel obstruction after unsuccessful conservative treatment: a prospective evaluation.

PubMed

Choi, Hok-Kwok; Law, Wai-Lun; Ho, Judy-Wai-Chu; Chu, Kin-Wah

2005-06-28

Gastrografin is a hyperosmolar water-soluble contrast medium. Besides its predictive value for the need for operative treatment, a potential therapeutic role of this agent in adhesive small bowel obstruction has been suggested. This study aimed at evaluating the effectiveness of gastrografin in adhesive small bowel obstruction when conservative treatment failed. Patients with adhesive small bowel obstruction were given trial conservative treatment unless there was fear of bowel strangulation. Those responded in the initial 48 h had conservative treatment continued. Patients who showed no improvement in the initial 48 h were given 100 mL of gastrografin through nasogastric tube followed by serial abdominal radiographs. Patients with the contrast appeared in large bowel within 24 h were regarded as having partial obstruction and conservative treatment was continued. Patients in which the contrast failed to reach large bowel within 24 h were considered to have complete obstruction and laparotomy was performed. Two hundred and twelve patients with 245 episodes of adhesive obstruction were included. Fifteen patients were operated on soon after admission due to fear of strangulation. One hundred and eighty-six episodes of obstruction showed improvement in the initial 48 h and conservative treatment was continued. Two patients had subsequent operations because of persistent obstruction. Forty-four episodes of obstruction showed no improvement within 48 h and gastrografin was administered. Seven patients underwent complete obstruction surgery. Partial obstruction was demonstrated in 37 other cases, obstruction resolved subsequently in all of them except one patient who required laparotomy because of persistent obstruction. The overall operative rate in this study was 10%. There was no complication that could be attributed to the use of gastrografin. The use of gastrografin in adhesive small bowel obstruction after unsuccessful conservative treatment is safe and reduces the need for surgical intervention.

Early wound infection identification using the WIRE tool in community health care settings: An audit report.

PubMed

Siaw-Sakyi, Vincent

2017-12-01

Wound infection is proving to be a challenge for health care professionals. The associated complications and cost of wound infection is immense and can lead to death in extreme cases. Current management of wound infection is largely subjective and relies on the knowledge of the health care professional to identify and initiate treatment. In response, we have developed an infection prediction and assessment tool. The Wound Infection Risk-Assessment and Evaluation tool (WIRE) and its management strategy is a tool with the aim to bring objectivity to infection prediction, assessment and management. A local audit carried out indicated a high infection prediction rate. More work is being done to improve its effectiveness.

SU-E-T-287: Robustness Study of Passive-Scattering Proton Therapy in Lung: Is Range and Setup Uncertainty Calculation On the Initial CT Enough to Predict the Plan Robustness?

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

Ding, X; Dormer, J; Kenton, O

Purpose: Plan robustness of the passive-scattering proton therapy treatment of lung tumors has been studied previously using combined uncertainties of 3.5% in CT number and 3 mm geometric shifts. In this study, we investigate whether this method is sufficient to predict proton plan robustness by comparing to plans performed on weekly verification CT scans. Methods: Ten lung cancer patients treated with passive-scattering proton therapy were randomly selected. All plans were prescribed 6660cGy in 37 fractions. Each initial plan was calculated using +/− 3.5% range and +/− 0.3cm setup uncertainty in x, y and z directions in Eclipse TPS(Method-A). Throughout themore » treatment course, patients received weekly verification CT scans to assess the daily treatment variation(Method-B). After contours and imaging registrations are verified by the physician, the initial plan with the same beamline and compensator was mapped into the verification CT. Dose volume histograms (DVH) were evaluated for robustness study. Results: Differences are observed between method A and B in terms of iCTV coverage and lung dose. Method-A shows all the iCTV D95 are within +/− 1% difference, while 20% of cases fall outside +/−1% range in Method-B. In the worst case scenario(WCS), the iCTV D95 is reduced by 2.5%. All lung V5 and V20 are within +/−5% in Method-A while 15% of V5 and 10% of V20 fall outside of +/−5% in Method-B. In the WCS, Lung V5 increased by 15% and V20 increased by 9%. Method A and B show good agreement with regard to cord maximum and Esophagus mean dose. Conclusion: This study suggests that using range and setup uncertainty calculation (+/−3.5% and +/−3mm) may not be sufficient to predict the WCS. In the absence of regular verification scans, expanding the conventional uncertainty parameters(e.g., to +/−3.5% and +/−4mm) may be needed to better reflect plan actual robustness.« less

Understanding Chronically Reported Families

PubMed Central

Jonson-Reid, Melissa; Emery, Clifton R.; Drake, Brett; Stahlschmidt, Mary Jo

2013-01-01

Although a strong literature on child maltreatment re-reporting exists, much of that literature stops at the first re-report. The literature on chronic re-reporting, meaning reports beyond the second report, is scant. The authors follow Loman’s lead in focusing on reports beyond the first two to determine what factors predict these “downstream” report stages. Cross-sector, longitudinal administrative data are used. The authors analyze predictors at each of the first four recurrences (first to second report, second to third report, third to fourth report, and fourth to fifth report). Findings demonstrate that some factors (e.g., tract poverty) which predict initial recurrence lose their predictive value at later stages, whereas others (e.g., aid to families with dependent children history) remain predictive across stages. In-home child welfare services and mental health treatment emerged as consistent predictors of reduced recurrence. PMID:20941889

[Non operative treatment for perforated peptic ulcer: results of a prospective study].

PubMed

Songne, B; Jean, F; Foulatier, O; Khalil, H; Scotté, M

2004-12-01

The conservative management of perforated peptic ulcer has not gained widespread acceptance despite introduction of proton-pomp inhibitors because surgical procedures can achieve immediate closure by eventually using a laparoscopic approach. The aim of this prospective study was to evaluate the results of Taylor's method and to identify predictive factors of failure of medical treatment in patients presenting with perforated peptic ulcer. Between 1990 and 2000, 82 consecutive patients, with diagnosis of perforated peptic ulcer were prospectively included in this study. They were initially treated with non-operative procedure (nasogastric suction and intravenous administration of H2-blockers or proton-pomp inhibitors). No clinical improvement after 24 hours required a surgical treatment. Predictive factors of failure of non-operative treatment were tested in univariate or multivariate analysis. Clinical improvement was obtained with non-operative treatment in 54% of the patients (44/82). The overall mortality rate was 1%. In univariate analysis, significant predictive factors of failure of non-operative treatment were: size of pneumoperitoneum, heart beat >94 bpm, abdominal meteorism, pain at digital rectal exam, and age >59 years. In multivariate analysis, the significant factors were the size of pneumoperitoneum, heart beat, and abdominal meteorism. The association of these criteria: size of pneumoperitoneum >size of the first lumbar vertebra, heart beat >94 bpm, pain at digital rectal exam and age > 59 years , led to surgical treatment in all cases. These results suggest that more than 50% of patients with perforated peptic ulcer respond to conservative treatment without surgery and that the association of few criteria (size of pneumoperitoneum, heart beat, pain at digital rectal exam and age) require emergency surgery.

Sleep-stage sequencing of sleep-onset REM periods in MSLT predicts treatment response in patients with narcolepsy.

PubMed

Drakatos, Panagis; Patel, Kishankumar; Thakrar, Chiraag; Williams, Adrian J; Kent, Brian D; Leschziner, Guy D

2016-04-01

Current treatment recommendations for narcolepsy suggest that modafinil should be used as a first-line treatment ahead of conventional stimulants or sodium oxybate. In this study, performed in a tertiary sleep disorders centre, treatment responses were examined following these recommendations, and the ability of sleep-stage sequencing of sleep-onset rapid eye movement periods in the multiple sleep latency test to predict treatment response. Over a 3.5-year period, 255 patients were retrospectively identified in the authors' database as patients diagnosed with narcolepsy, type 1 (with cataplexy) or type 2 (without) using clinical and polysomnographic criteria. Eligible patients were examined in detail, sleep study data were abstracted and sleep-stage sequencing of sleep-onset rapid eye movement periods were analysed. Response to treatment was graded utilizing an internally developed scale. Seventy-five patients were included (39% males). Forty (53%) were diagnosed with type 1 narcolepsy with a mean follow-up of 2.37 ± 1.35 years. Ninety-seven percent of the patients were initially started on modafinil, and overall 59% reported complete response on the last follow-up. Twenty-nine patients (39%) had the sequence of sleep stage 1 or wake to rapid eye movement in all of their sleep-onset rapid eye movement periods, with most of these diagnosed as narcolepsy type 1 (72%). The presence of this specific sleep-stage sequence in all sleep-onset rapid eye movement periods was associated with worse treatment response (P = 0.0023). Sleep-stage sequence analysis of sleep-onset rapid eye movement periods in the multiple sleep latency test may aid the prediction of treatment response in narcoleptics and provide a useful prognostic tool in clinical practice, above and beyond their classification as narcolepsy type 1 or 2. © 2015 European Sleep Research Society.

“How Will It Help Me?”: Reasons Underlying Treatment Preferences Between Sertraline and Prolonged Exposure in PTSD

PubMed Central

Chen, Jessica A.; Keller, Stephanie M.; Zoellner, Lori A.; Feeny, Norah C.

2014-01-01

Individuals with posttraumatic stress disorder (PTSD) often wait years before seeking treatment. Improving treatment initiation and adherence requires a better understanding patient beliefs that lead to treatment preferences. Using a treatment-seeking sample (N = 200) with chronic PTSD, qualitative reasons underlying treatment preferences for either prolonged exposure (PE) or sertraline (SER) were examined. Reasons for treatment preference primarily focused on how the treatment was perceived to reduce PTSD symptoms rather than practical ones. Patients were more positive about PE than SER. Individual differences did not reliably predict underlying preference reasons, suggesting that what makes a treatment desirable is not strongly determined by current functioning, treatment, or trauma history. Taken together, this information is critical for treatment providers, arguing for enhancing psychoeducation about how treatment works and acknowledging pre-existing biases against pharmacotherapy for PTSD that should be addressed. This knowledge has the potential to optimize and better personalize PTSD patient care. PMID:23896851

SU-D-16A-07: Photobleaching Predicts Necrosis in Interstitial PDT

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

Kim, M; Finlay, J; Liu, B

Purpose: Dosimetry for PDT has proven to be a challenge thus far, and for prediction of PDT outcome, a singlet oxygen model based on fundamental photophysical parameters has been developed. Previously, the photobleaching effect of photosensitizers was taken into account in the singlet oxygen explicit dosimetry model; here we report of direct measurements of photobleaching in the same model to assess the conditions under which implicit dosimetry using photobleaching can serve as an intermediate surrogate for PDT damage. Methods: Fluorescence spectra were measured interstitially in sensitized mouse tumors prior to after irradiation via a cylindrical diffuser. Photobleaching was determined bymore » the relative decrease in fluorescence amplitude from the initial pre-treatment measurement. Spectra were analyzed by singular value decomposition to determine the photosensitizer concentration. Different photosensitizers were used to see the effect of photobleaching on PDT outcome and the impact of fluence on photobleaching. The drugs used were BPD (at two drug-light intervals), HPPH, and Photofrin. PDT outcome was determined by tumor necrosis radii measured upon sectioning and staining of treated tumors. Results: Post-PDT photosentizer concentrations were compared to initial pre-PDT photosensitizer concentrations, and the decrease was greater with a higher fluence measured during treatment. Furthermore, photobleaching and necrosis radius were found to be positively correlated. The relationship between photobleaching and necrosis radius is sensitizer-dependent, however the differences among sensitizers can be understood in terms of their respective photophysical parameters. Conclusions: Photobleaching is predictive of PDT outcome, but a comprehensive singlet oxygen model, has the potential to further improve the prediction of PDT outcome and the understanding of implicit dosimetry.« less

The Prevalence Rate of Tuberculin Skin Test Positive by Contacts Group to Predict the Development of Active Tuberculosis After School Outbreaks.

PubMed

Kim, Hee Jin; Chun, Byung Chul; Kwon, AmyM; Lee, Gyeong-Ho; Ryu, Sungweon; Oh, Soo Yeon; Lee, Jin Beom; Yoo, Se Hwa; Kim, Eui Sook; Kim, Je Hyeong; Shin, Chol; Lee, Seung Heon

2015-10-01

The tuberculin skin test (TST) is the standard tool to diagnose latent tuberculosis infection (LTBI) in mass screening. The aim of this study is to find an optimal cut-off point of the TST+ rate within tuberculosis (TB) contacts to predict the active TB development among adolescents in school TB outbreaks. The Korean National Health Insurance Review and Assessment database was used to identify active TB development in relation to the initial TST (cut-off, 10 mm). The 7,475 contacts in 89 schools were divided into two groups: Incident TB group (43 schools) and no incident TB group (46 schools). LTBI treatment was initiated in 607 of the 1,761 TST+ contacts. The association with active TB progression was examined at different cut-off points of the TST+ rate. The mean duration of follow-up was 3.9±0.9 years. Thirty-three contacts developed active TB during the 4,504 person-years among the TST+ contacts without LTBI treatment (n=1,154). The average TST+ rate for the incident TB group (n=43) and no incident TB group (n=46) were 31.0% and 15.5%, respectively. The TST+ rate per group was related with TB progression (odds ratio [OR], 1.025; 95% confidence interval [CI], 1.001-1.050; p=0.037). Based on the TST+ rate per group, active TB was best predicted at TST+ ≥ 16% (OR, 3.11; 95% CI, 1.29-7.51; area under curve, 0.64). Sixteen percent of the TST+ rate per group within the same grade students can be suggested as an optimal cut-off to predict active TB development in middle and high schools TB outbreaks.

The impact of comorbid body dysmorphic disorder on the response to sequential pharmacological trials for obsessive-compulsive disorder.

PubMed

Diniz, Juliana B; Costa, Daniel Lc; Cassab, Raony Cc; Pereira, Carlos Ab; Miguel, Euripedes C; Shavitt, Roseli G

2014-06-01

Our aim was to investigate the impact of comorbid body dysmorphic disorder (BDD) on the response to sequential pharmacological trials in adult obsessive-compulsive disorder (OCD) patients. The sequential trial initially involved fluoxetine monotherapy followed by one of three randomized, add-on strategies: placebo, clomipramine or quetiapine. We included 138 patients in the initial phase of fluoxetine, up to 80 mg or the maximum tolerated dosage, for 12 weeks. We invited 70 non-responders to participate in the add-on trial; as 54 accepted, we allocated 18 to each treatment group and followed them for an additional 12 weeks. To evaluate the combined effects of sex, age, age at onset, initial severity, type of augmentation and BDD on the response to sequential treatments, we constructed a model using generalized estimating equations (GEE). Of the 39 patients who completed the study (OCD-BDD, n = 13; OCD-non-BDD, n = 26), the OCD-BDD patients were less likely to be classified as responders than the OCD-non-BDD patients (Pearson Chi-Square = 4.4; p = 0.036). In the GEE model, BDD was not significantly associated with a worse response to sequential treatments (z-robust = 1.77; p = 0.07). The predictive potential of BDD regarding sequential treatment strategies for OCD did not survive when the analyses were controlled for other clinical characteristics. © The Author(s) 2013.

Metabolic and anthropometric parameters contribute to ART-mediated CD4+ T cell recovery in HIV-1-infected individuals: an observational study

PubMed Central

2011-01-01

Background The degree of immune reconstitution achieved in response to suppressive ART is associated with baseline individual characteristics, such as pre-treatment CD4 count, levels of viral replication, cellular activation, choice of treatment regimen and gender. However, the combined effect of these variables on long-term CD4 recovery remains elusive, and no single variable predicts treatment response. We sought to determine if adiposity and molecules associated with lipid metabolism may affect the response to ART and the degree of subsequent immune reconstitution, and to assess their ability to predict CD4 recovery. Methods We studied a cohort of 69 (48 females and 21 males) HIV-infected, treatment-naïve South African subjects initiating antiretroviral treatment (d4T, 3Tc and lopinavir/ritonavir). We collected information at baseline and six months after viral suppression, assessing anthropometric parameters, dual energy X-ray absorptiometry and magnetic resonance imaging scans, serum-based clinical laboratory tests and whole blood-based flow cytometry, and determined their role in predicting the increase in CD4 count in response to ART. Results We present evidence that baseline CD4+ T cell count, viral load, CD8+ T cell activation (CD95 expression) and metabolic and anthropometric parameters linked to adiposity (LDL/HDL cholesterol ratio and waist/hip ratio) significantly contribute to variability in the extent of CD4 reconstitution (ΔCD4) after six months of continuous ART. Conclusions Our final model accounts for 44% of the variability in CD4+ T cell recovery in virally suppressed individuals, representing a workable predictive model of immune reconstitution. PMID:21801351

Evaluating Response to High-Dose 13.3 mg/24 h Rivastigmine Patch in Patients with Severe Alzheimer's Disease.

PubMed

Farlow, Martin R; Sadowsky, Carl H; Velting, Drew M; Meng, Xiangyi; Islam, M Zahur

2015-06-01

To identify factors predicting improvement/stabilization on the Alzheimer's Disease Cooperative Study-Clinical Global Impression of Change (ADCS-CGIC) and investigate whether early treatment responses can predict long-term outcomes, during a trial of 13.3 mg/24 h versus 4.6 mg/24 h rivastigmine patch in patients with severe Alzheimer's disease (AD). Logistic regression was used to relate Week 24 ADCS-CGIC score to potential baseline predictors. Additional analyses based on receiver-operating characteristic curves were performed using Week 8/16 ADCS-CGIC scores to predict response (13.3 mg/24 h patch) at Week 24. ADCS-CGIC score of (1) 1-3 = "improvement," (2) 1-4 = "improvement or no change". "Treatment" (13.3 mg/24 h patch) and increased age were significant predictors of "improvement" (P = 0.01 and P = 0.003, respectively), and "treatment" (P = 0.001), increased age (P = 0.002), and prior AD treatment (P = 0.03) for "improvement or no change". At Week 8 and 16, ADCS-CGIC scores of 4 and 5 were optimal thresholds in predicting "improvement," and "improvement or no change," respectively, at Week 24. A significant therapeutic effect of high-dose rivastigmine patch on ADCS-CGIC response was observed. The 13.3 mg/24 h patch was identified as a predictor of "improvement" or "improvement or no change". Patients with minimal worsening/improvement/no change after treatment initiation may be more likely to respond following long-term therapy. © 2015 John Wiley & Sons Ltd.

Graft-versus-Host Disease Treatment: Predictors of Survival

PubMed Central

Levine, John E.; Logan, Brent; Wu, Juan; Alousi, Amin M.; Ho, Vincent; Bolaños-Meade, Javier; Weisdorf, Daniel

2010-01-01

Acute graft-versus-host disease (aGVHD) following allogeneic hematopoietic cell transplant (HCT) is the major reason for non-relapse mortality and thus is a major determinant of long term survival. Clinical trials of new aGVHD treatments are needed in order to identify approaches that will ultimately improve upon HCT survival. At present it is not clear how quickly response to GVHD treatment needs to be established in order to reliably categorize patients at high risk for death or to promptly identify those who might benefit from alternate treatment. Therefore, we analyzed time to response from onset of aGVHD treatment in 180 patients who were enrolled on a national, randomized, phase II aGVHD treatment clinical trial whose initial treatment of GVHD consisted of high dose steroids plus a second immunosuppressive agent. The aim of this analysis was to determine whether time to aGVHD treatment response predicts patient outcomes, especially survival. We used response at 14, 28 and 56 days from initiation of aGVHD treatment to categorize patients for non-relapse mortality and survival. Multivariate analyses and specificity/sensitivity analyses identified that day 28 response (complete or partial response) best categorized patients by non-relapse mortality and survival at 9 months from start of aGVHD treatment. If verified as a reliable predictor of late outcomes following other aGVHD treatment approaches, day 28 response should serve as a standard early endpoint for future trials of aGVHD therapy. PMID:20541024

Recombinant factor VIIa (eptacog alfa): a pharmacoeconomic review of its use in haemophilia in patients with inhibitors to clotting factors VIII or IX.

PubMed

Lyseng-Williamson, Katherine A; Plosker, Greg L

2007-01-01

Recombinant factor VIIa (NovoSeven; also known as recombinant activated factor VII or eptacog alfa) is indicated as an intravenous haemostatic agent in haemophilia patients with inhibitors to clotting factors VIII or IX. In noncomparative trials in haemophilia patients with inhibitors, on-demand home treatment with recombinant factor VIIa was effective in controlling episodes of mild to moderate bleeding and well tolerated, with early treatment being associated with a greater rate of success and the need for fewer doses than delayed treatment. Prophylactic treatment with recombinant factor VIIa was also effective in maintaining haemostasis in patients with this indication undergoing surgery. Relative to prior treatment with plasma-derived agents, treatment with recombinant factor VIIa was associated with improvements in health-related quality of life in a cost-utility study in haemophilia patients with inhibitors in Australia. In well designed decision-model cost analyses conducted from a healthcare payer perspective in several countries, on-demand treatment with recombinant factor VIIa to control mild to moderate bleeding episodes in this patient population was predicted to be cost saving or cost neutral relative to on-demand treatment with intravenous activated prothrombin complex concentrate (aPCC). Although the acquisition cost of recombinant factor VIIa was greater than that of aPCC in some studies, the greater initial efficacy of recombinant factor VIIa than aPCC resulted in lower predicted total medical costs. Results were generally robust to plausible changes in key parameters. Orthopaedic surgery with recombinant factor VIIa to maintain haemostasis in haemophilia patients with inhibitors was generally predicted to be cost saving, relative to not having surgery, over the medium to long term in modelled cost analyses from a healthcare payer perspective in the UK and US. The initial cost of surgery was high, but the difference in costs between patients undergoing or not undergoing surgery was predicted to decline over time, as savings were realised from the decrease in the number of bleeding episodes requiring treatment in patients who underwent surgery. In haemophilia patients with inhibitors, recombinant factor VIIa is clinically effective in controlling mild to moderate bleeds, and in maintaining haemostasis in patients undergoing orthopaedic surgery. Available pharmacoeconomic data from several countries, despite inherent limitations, support the use of recombinant factor VIIa as a treatment option that is at least cost neutral relative to aPCC in treating mild to moderate bleeds in this patient population. In addition, orthopaedic surgery with recombinant factor VIIa to maintain haemostasis in haemophilia patients with inhibitors is generally cost saving relative to not having surgery over the medium to long term, as the acquisition costs of recombinant factor VIIa are offset by cost savings resulting from the decrease in the number of joint-related bleeds.

Dependency and self-criticism in treatments for depression.

PubMed

Chui, Harold; Zilcha-Mano, Sigal; Dinger, Ulrike; Barrett, Marna S; Barber, Jacques P

2016-07-01

Dependency and self-criticism are vulnerability factors for depression. How these personality factors change with treatment for depression and how they relate to symptom change across different types of treatment require further research. In addition, cultural differences that interact with the dependency/self-criticism-depression relation remain underinvestigated. We randomly assigned 149 adults with major depression to receive active medication (MED; n = 50), supportive-expressive therapy (SET; n = 49), or placebo pill (PBO; n = 50). Participants completed the Depressive Experiences Questionnaire (DEQ; Blatt, D'Afflitti, & Quinlan, 1976) before and after treatment and completed the Hamilton Rating Scale for Depression (Hamilton, 1967) throughout the course of treatment. Self-criticism as measured on the DEQ decreased with treatment similarly across conditions. DEQ Dependency decreased in MED but remained unchanged in SET and PBO. Higher initial dependency, but not higher initial self-criticism, predicted poor treatment response across conditions. Greater reduction in self-criticism was associated with greater reduction in depressive symptoms, but the effect was weaker for racial minorities (vs. White). Increase in connectedness, an adaptive form of dependency, was associated with symptom improvement in SET but not MED. Hence, different pathways of change seem to be implicated in the treatment of depression depending on culture and type of intervention. Implications for future research are discussed. (PsycINFO Database Record (c) 2016 APA, all rights reserved).

The influence of patient's motivation on reported pain during orthodontic treatment.

PubMed

Campos, Marcio José da Silva; Vitral, Robert Willer Farinazzo

2013-01-01

Patients usually experience pain during orthodontic treatment. This fact can affect cooperation and the development of treatment. Reporting pain during treatment seems to be influenced by emotional aspects such as the patient's motivation. To assess the relationship between patient's motivation and the intensity of reported pain during two stages of treatment. Twenty males (11-37 years old) answered a questionnaire divided into five categories regarding their motivation towards treatment. The subjects were studied for 14 days (7 days with bonded brackets and 7 days with the initial arch inserted) and the intensity of pain was evaluated on a daily basis. All the issues, including the intensity of pain, were measured through the visual analog scale (VAS). The VAS-associated questionnaire proved to have good temporal reliability and reasonable internal consistency, being that the "perceived severity" domain had the greatest, although not significant (p = 0.196) correlation with pain intensity. Only the question asking the patients if they thought that their teeth were too uneven showed a positive correlation with pain intensity (p = 0.048). The results seem to indicate that the five categories related to treatment motivation cannot be used to predict discomfort during treatment. In addition, patients who think their teeth are too uneven may experience more severe pain due to greater force application after insertion of the initial arch.

Examining Temptation to Drink from an Existential Perspective: Associations among Temptation, Purpose in Life, and Drinking Outcomes

PubMed Central

Roos, Corey R.; Kirouac, Megan; Pearson, Matthew R.; Fink, Brandi C.; Witkiewitz, Katie

2015-01-01

Temptation to drink, defined as the degree to which one feels compelled to drink in the presence of internal or external alcohol-related cues, has been shown to predict alcohol treatment outcomes among individuals with alcohol use disorders (AUDs). Research examining temptation to drink from an existential perspective is lacking and little is known about how existential issues such as purpose in life (PIL) relate to temptation to drink, which is surprising given the role of existential issues in many treatments and mutual help approaches for AUDs. The current study examined the longitudinal associations among temptation to drink, PIL, and drinking outcomes using data from Project MATCH (N = 1726). Parallel process latent growth curve analyses indicated that PIL and temptation to drink were significantly associated across time, such that higher initial levels of PIL and increases in PIL over time were associated with lower initial levels of temptation to drink and decreases in temptation to drink over time. Higher initial levels of temptation to drink, lower initial levels of PIL, increases in temptation to drink, and decreases in PIL were significantly associated with greater intensity and frequency of drinking and greater drinking-related consequences at the 15-month follow-up. Accordingly, temptation to drink and PIL may be important constructs for clinicians to consider throughout the course of treatment. Future studies should examine if and how various kinds of treatments for AUDs are associated with increases in PIL, and whether these increases are related to decreased temptation to drink and reduced drinking. PMID:25730630

Combination growth hormone and gonadotropin releasing hormone analog therapy in 11beta-hydroxylase deficiency.

PubMed

Bajpai, Anurag; Kabra, Madhulika; Menon, P S N

2006-06-01

Diagnosis of 11beta-hydroxylase deficiency was made in a boy at the age of 2 1/2 years on the basis of peripheral precocious puberty, growth acceleration (height standard deviation score +4.4) with advanced skeletal maturation (bone age 8.4 years) and elevated deoxycortisol levels. Glucocorticoid supplementation led to normalization of blood pressure but was associated with progression to central precocious puberty and increase in bone age resulting in decrease in predicted adult height to 133.7 cm (target height 163 cm). The child was started on GnRH analog (triptorelin 3.75 mg every 28 days), which led to improvement in predicted adult height by 3.1 cm over 15 months. Addition of growth hormone (0.1 IU/kg/day) resulted in improvement in predicted adult height (151 cm) and height deficit (12 cm) over the next 3.6 years. Final height (151 cm) exceeded predicted height at the initiation of GnRH analog treatment by 17.3 cm. This report suggests that combination GH and GnRH analog treatment may be useful in improving height outcome in children with 11beta-hydroxylase deficiency and compromised final height.

Smaller hippocampal volumes predict lower antidepressant response/remission rates in depressed patients: A meta-analysis.

PubMed

Colle, Romain; Dupong, Irène; Colliot, Olivier; Deflesselle, Eric; Hardy, Patrick; Falissard, Bruno; Ducreux, Denis; Chupin, Marie; Corruble, Emmanuelle

2016-08-15

Whether hippocampal volume predicts response and/or remission after antidepressant treatment of major depressive episodes (MDE) in major depressive disorder (MDD) remains unclear. We meta-analysed prospective studies comparing baseline hippocampal volume in patients with or without response/remission after antidepressant treatment. Pubmed, Embase and Google Scholar were searched for studies of patients with current MDE in MDD, with hippocampal volume assessments at baseline, initiation of antidepressant drug treatment, and prospective assessment of response/remission after treatment. Six studies (374 patients), of which two were positive and four negative, were meta-analysed. Compared to responders/remitters, patients who failed to achieve response/remission had smaller total hippocampus volumes at baseline (mean volume difference = 260 mm 3 , 95% CI [93; 427], P = 0.002). These results remained significant in patients under 60 years of age (P = 0.02), in those over 60 years old (P = 0.04), and for right (P = 0.006) and left (P = 0.02) hippocampi. The probability of non-response/non-remission was 68.6% for patients with a total hippocampal volume at least 10% lower than the average, and 47.1% for patients with a total hippocampal volume 10% higher than the average. In depressed patients treated with antidepressant drugs, smaller hippocampal volumes predict lower response/remission rates.

Predictors of treatment outcome among Asian pathological gamblers (PGs): clinical, behavioural, demographic, and treatment process factors.

PubMed

Guo, Song; Manning, Victoria; Thane, Kyaw Kyaw Wai; Ng, Andrew; Abdin, Edimansyah; Wong, Kim Eng

2014-03-01

Research on predictors of treatment outcome among pathological gamblers (PGs) is inconclusive and dominated by studies from Western countries. Using a prospective longitudinal design, the current study examined demographic, clinical, behavioural and treatment programme predictors of gambling frequency at 3, 6 and 12-months, among PGs treated at an addiction clinic in Singapore. Measures included the Hospital anxiety and depression scale, gambling symptom assessment scale (GSAS), personal well-being index (PWI), treatment perception questionnaire and gambling readiness to change scale. Treatment response in relation to changes in symptom severity, personal wellbeing and abstinence were also assessed. Abstinence rates were 38.6, 46.0 and 44.4 % at 3, 6 and 12-months respectively. Significant reductions in gambling frequency, GSAS, and improvement in PWI were reported between baseline and subsequent outcome assessments, with the greatest change occurring in the initial three months. No demographic, clinical, behavioural or treatment programme variable consistently predicted outcome at all three assessments, though treatment satisfaction was the most frequent significant predictor. However, being unemployed, having larger than average debts, poor treatment satisfaction and attending fewer sessions at the later stages of treatment were associated with significantly poorer outcomes, up to 1-year after initiating treatment. These findings show promise for the effectiveness of a CBT-based treatment approach for the treatment of predominantly Chinese PGs. Clinical implications and suggestions for future research are discussed. Taken together, the findings suggest early treatment satisfaction is paramount in improving short-term outcomes, with baseline gambling behaviour and treatment intensity playing a more significant role in the longer term.

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

Fuangrod, T; Simpson, J; Greer, P

Purpose: A real-time patient treatment delivery verification system using EPID (Watchdog) has been developed as an advanced patient safety tool. In a pilot study data was acquired for 119 prostate and head and neck (HN) IMRT patient deliveries to generate body-site specific action limits using statistical process control. The purpose of this study is to determine the sensitivity of Watchdog to detect clinically significant errors during treatment delivery. Methods: Watchdog utilizes a physics-based model to generate a series of predicted transit cine EPID images as a reference data set, and compares these in real-time to measured transit cine-EPID images acquiredmore » during treatment using chi comparison (4%, 4mm criteria) after the initial 2s of treatment to allow for dose ramp-up. Four study cases were used; dosimetric (monitor unit) errors in prostate (7 fields) and HN (9 fields) IMRT treatments of (5%, 7%, 10%) and positioning (systematic displacement) errors in the same treatments of (5mm, 7mm, 10mm). These errors were introduced by modifying the patient CT scan and re-calculating the predicted EPID data set. The error embedded predicted EPID data sets were compared to the measured EPID data acquired during patient treatment. The treatment delivery percentage (measured from 2s) where Watchdog detected the error was determined. Results: Watchdog detected all simulated errors for all fields during delivery. The dosimetric errors were detected at average treatment delivery percentage of (4%, 0%, 0%) and (7%, 0%, 0%) for prostate and HN respectively. For patient positional errors, the average treatment delivery percentage was (52%, 43%, 25%) and (39%, 16%, 6%). Conclusion: These results suggest that Watchdog can detect significant dosimetric and positioning errors in prostate and HN IMRT treatments in real-time allowing for treatment interruption. Displacements of the patient require longer to detect however incorrect body site or very large geographic misses will be detected rapidly.« less

Estimation of treatment effects in all-comers randomized clinical trials with a predictive marker.

PubMed

Choai, Yuki; Matsui, Shigeyuki

2015-03-01

Recent advances in genomics and biotechnologies have accelerated the development of molecularly targeted treatments and accompanying markers to predict treatment responsiveness. However, it is common at the initiation of a definitive phase III clinical trial that there is no compelling biological basis or early trial data for a candidate marker regarding its capability in predicting treatment effects. In this case, it is reasonable to include all patients as eligible for randomization, but to plan for prospective subgroup analysis based on the marker. One analysis plan in such all-comers designs is the so-called fallback approach that first tests for overall treatment efficacy and then proceeds to testing in a biomarker-positive subgroup if the first test is not significant. In this approach, owing to the adaptive nature of the analysis and a correlation between the two tests, a bias will arise in estimating the treatment effect in the biomarker-positive subgroup after a non-significant first overall test. In this article, we formulate the bias function and show a difficulty in obtaining unbiased estimators for a whole range of an associated parameter. To address this issue, we propose bias-corrected estimation methods, including those based on an approximation of the bias function under a bounded range of the parameter using polynomials. We also provide an interval estimation method based on a bivariate doubly truncated normal distribution. Simulation experiments demonstrated a success in bias reduction. Application to a phase III trial for lung cancer is provided. © 2014, The International Biometric Society.

Sunitinib-induced hypothyroidism predicts progression-free survival in metastatic renal cell carcinoma patients.

PubMed

Buda-Nowak, Anna; Kucharz, Jakub; Dumnicka, Paulina; Kuzniewski, Marek; Herman, Roman Maria; Zygulska, Aneta L; Kusnierz-Cabala, Beata

2017-04-01

Sunitinib is a tyrosine kinase inhibitor (TKI) used in treatment of metastatic renal cell carcinoma (mRCC), gastrointestinal stromal tumors and pancreatic neuroendocrine tumors. One of the most common side effects related to sunitinib is hypothyroidism. Recent trials suggest correlation between the incidence of hypothyroidism and treatment outcome in patients treated with TKI. This study evaluates whether development of hypothyroidism is a predictive marker of progression-free survival (PFS) in patients with mRCC treated with sunitinib. Twenty-seven patients diagnosed with clear cell mRCC, after nephrectomy and in 'good' or 'intermediate' MSKCC risk prognostic group, were included in the study. All patients received sunitinib as a first-line treatment on a standard schedule (initial dose 50 mg/day, 4 weeks on, 2 weeks off). The thyroid-stimulating hormone serum levels were obtained at the baseline and every 12 weeks of treatment. In statistic analyses, we used Kaplan-Meier method for assessment of progression-free survival; for comparison of survival, we used log-rank test. In our study, the incidence of hypothyroidism was 44%. The patients who had developed hypothyroidism had better median PFS to patients with normal thyroid function 28,3 months [95% (CI) 20.4-36.2 months] versus 9.8 months (6.4-13.1 months). In survival analysis, we perceive that thyroid dysfunction is a predictive factor of a progression-free survival (PFS). In the unified group of patients, the development of hypothyroidism during treatment with sunitinib is a positive marker for PFS. During that treatment, thyroid function should be evaluated regularly.

Advances in the management of venous thromboembolism.

PubMed

Schulman, Sam

2012-09-01

The past decade has witnessed important advances in the diagnosis and treatment of venous thromboembolism with excellent opportunities to apply evidence-based medicine for many of the steps in the management of the disease. This review discusses the clinical prediction rules that should be used to reduce utilization of imaging diagnosis for deep vein thrombosis or pulmonary embolism and the risk stratification for thrombolytic therapy or outpatient management of pulmonary embolism. The treatment options have increased and include low-molecular-weight heparin (LMWH), intravenous or subcutaneous unfractionated heparin - the latter either monitored or not monitored, fondaparinux and rivaroxaban for the initial phase. Thereafter, vitamin K antagonists (VKAs), LMWH, oral factor Xa or thrombin inhibitors are or will soon become available. The VKAs have been subjected to many randomised trial addressing the initiation, intensity, monitoring and self-management. Extended anticoagulation and the selection for that is finally reviewed. Copyright © 2012. Published by Elsevier Ltd.

Identifying risk factors for refractory febrile neutropenia in patients with lung cancer.

PubMed

Fujita, Masaki; Tokunaga, Shoji; Ikegame, Satoshi; Harada, Eiji; Matsumoto, Takemasa; Uchino, Junji; Watanabe, Kentaro; Nakanishi, Yoichi

2012-02-01

Information about the development of febrile neutropenia in patients with solid tumors remains insufficient. In this study, we tried to identify the risk factors for refractory febrile neutropenia in patients with lung cancer. A total of 59 neutropenic fever episodes associated with anti-tumor chemotherapy for lung cancer were retrospectively analyzed. We compared patient characteristics according to their initial response to treatment with antibiotics. For 34 of 59 (58%) episodes a response to initial antibiotics was obtained whereas 25 of 59 (42%) were refractory to treatment. Multivariate analysis demonstrated independent risk factors for refractory febrile neutropenia with lung cancer. These risk factors were the severity of febrile neutropenia (odds ratio (OR) 6.11; 95% confidence interval (CI) 1.85-20.14) and C-reactive protein more than 10 mg/dl (OR 4.39; 95% CI 1.22-15.74). These factors could predict outcome for patients with lung cancer who develop refractory febrile neutropenia.

Constitutional Delay Influences the Auxological Response to Growth Hormone Treatment in Children with Short Stature and Growth Hormone Sufficiency

PubMed Central

Gunn, Katherine C.; Cutfield, Wayne S.; Hofman, Paul L.; Jefferies, Craig A.; Albert, Benjamin B.; Gunn, Alistair J.

2014-01-01

In a retrospective, population based cohort study, we examined whether constitutional delay was associated with the growth response to growth hormone (GH) in children with short stature and normal GH responses. 70 patients were treated with 21 GH iu/m2/week from 1975 to 2013 throughout New Zealand. Demographic and auxological data were prospectively collected and standard deviation scores (SDS) were calculated for height (HtSDS), yearly growth velocity (GV-SDS), body mass index (BMI-SDS) and predicted adult height (PAH-SDS) at time of the last available bone age. In the first year, GH was associated with marked increase in HtSDS (+0.46 (0.19, 0.76), p < 0.001) and GV-SDS (from −1.9 (−3.6, −0.7) to +2.7 (0.45, 4.2), p < 0.001). The increase in HtSDS but not in GV-SDS was greatest with younger patients and greater bone age delay, with no effect of sex, BMI-SDS or baseline HtSDS. PAH-SDS increased with treatment (+0.94 (0.18, 1.5)); increased PAH-SDS was associated with less bone age delay and greater initial increase in HtSDS. This study shows that greater bone age delay was associated with greater initial improvement in height but less improvement in predicted adult heights, suggesting that children with very delayed bone ages may show accelerated maturation during GH treatment. PMID:25317732

Constitutional delay influences the auxological response to growth hormone treatment in children with short stature and growth hormone sufficiency.

PubMed

Gunn, Katherine C; Cutfield, Wayne S; Hofman, Paul L; Jefferies, Craig A; Albert, Benjamin B; Gunn, Alistair J

2014-08-14

In a retrospective, population based cohort study, we examined whether constitutional delay was associated with the growth response to growth hormone (GH) in children with short stature and normal GH responses. 70 patients were treated with 21 GH iu/m2/week from 1975 to 2013 throughout New Zealand. Demographic and auxological data were prospectively collected and standard deviation scores (SDS) were calculated for height (HtSDS), yearly growth velocity (GV-SDS), body mass index (BMI-SDS) and predicted adult height (PAH-SDS) at time of the last available bone age. In the first year, GH was associated with marked increase in HtSDS (+0.46 (0.19, 0.76), p < 0.001) and GV-SDS (from -1.9 (-3.6, -0.7) to +2.7 (0.45, 4.2), p < 0.001). The increase in HtSDS but not in GV-SDS was greatest with younger patients and greater bone age delay, with no effect of sex, BMI-SDS or baseline HtSDS. PAH-SDS increased with treatment (+0.94 (0.18, 1.5)); increased PAH-SDS was associated with less bone age delay and greater initial increase in HtSDS. This study shows that greater bone age delay was associated with greater initial improvement in height but less improvement in predicted adult heights, suggesting that children with very delayed bone ages may show accelerated maturation during GH treatment.

SfDronc, an initiator caspase involved in apoptosis in the fall armyworm Spodoptera frugiperda.

PubMed

Huang, Ning; Civciristov, Srgjan; Hawkins, Christine J; Clem, Rollie J

2013-05-01

Initiator caspases are the first caspases that are activated following an apoptotic stimulus, and are responsible for cleaving and activating downstream effector caspases, which directly cause apoptosis. We have cloned a cDNA encoding an ortholog of the initiator caspase Dronc in the lepidopteran insect Spodoptera frugiperda. The SfDronc cDNA encodes a predicted protein of 447 amino acids with a molecular weight of 51 kDa. Overexpression of SfDronc induced apoptosis in Sf9 cells, while partial silencing of SfDronc expression in Sf9 cells reduced apoptosis induced by baculovirus infection or by treatment with UV or actinomycin D. Recombinant SfDronc exhibited several expected biochemical characteristics of an apoptotic initiator caspase: 1) SfDronc efficiently cleaved synthetic initiator caspase substrates, but had very little activity against effector caspase substrates; 2) mutation of a predicted cleavage site at position D340 blocked autoprocessing of recombinant SfDronc and reduced enzyme activity by approximately 10-fold; 3) SfDronc cleaved the effector caspase Sf-caspase-1 at the expected cleavage site, resulting in Sf-caspase-1 activation; and 4) SfDronc was strongly inhibited by the baculovirus caspase inhibitor SpliP49, but not by the related protein AcP35. These results indicate that SfDronc is an initiator caspase involved in caspase-dependent apoptosis in S. frugiperda, and as such is likely to be responsible for the initiator caspase activity in S. frugiperda cells known as Sf-caspase-X. Copyright © 2013 Elsevier Ltd. All rights reserved.

Antiangiogenic Therapy for Glioblastoma: Current Status and Future Prospects

PubMed Central

Batchelor, Tracy T.; Reardon, David A.; de Groot, John F.; Wick, Wolfgang; Weller, Michael

2014-01-01

Glioblastoma is characterized by high expression levels of pro-angiogenic cytokines and microvascular proliferation, highlighting the potential value of treatments targeting angiogenesis. Antiangiogenic treatment likely achieves a beneficial impact through multiple mechanisms of action. Ultimately, however, alternative pro-angiogenic signal transduction pathways are activated leading to the development of resistance, even in tumors that initially respond. The identification of biomarkers or imaging parameters to predict response and to herald resistance is of high priority. Despite promising phase 2 clinical trial results and patient benefit in terms of clinical improvement and longer progression-free survival, an overall survival benefit has not been demonstrated in 4 randomized phase 3 trials of bevacizumab or cilengitide in newly diagnosed glioblastoma or cediranib or enzastaurin recurrent glioblastoma. However, future studies are warranted: predictive markers may allow appropriate patient enrichment, combination with chemotherapy may ultimately prove successful in improving overall survival, and novel agents targeting multiple pro-angiogenic pathways may prove effective. PMID:25398844

Outcome of treatment after first relapse in younger adults with acute myeloid leukemia initially treated by the ALFA-9802 trial.

PubMed

Thomas, Xavier; Raffoux, Emmanuel; Renneville, Aline; Pautas, Cécile; de Botton, Stéphane; de Revel, Thierry; Reman, Oumedaly; Terré, Christine; Gardin, Claude; Chelghoum, Youcef; Boissel, Nicolas; Quesnel, Bruno; Cordonnier, Catherine; Bourhis, Jean-Henri; Elhamri, Mohamed; Fenaux, Pierre; Preudhomme, Claude; Socié, Gérard; Michallet, Mauricette; Castaigne, Sylvie; Dombret, Hervé

2012-09-01

Forty-seven percent of adults with acute myeloid leukemia (AML) who entered the ALFA-9802 trial and achieved a first complete remission (CR) experienced a first relapse. We examined the outcome of these 190 adult patients. Eighty-four patients (44%) achieved a second CR. The median overall survival (OS) after relapse was 8.9 months with a 2-year OS at 25%. Factors predicting a better outcome after relapse were stem cell transplant (SCT) performed in second CR and a first CR duration >1 year. Risk groups defined at the time of diagnosis and treatment received in first CR also influenced the outcome after relapse. The best results were obtained in patients with core binding factor (CBF)-AML, while patients initially defined as favorable intermediate risk showed a similar outcome after relapse than those initially entering the poor risk group. We conclude that most adult patients with recurring AML could not be rescued using current available therapies, although allogeneic SCT remains the best therapeutic option at this stage of the disease. Copyright © 2012 Elsevier Ltd. All rights reserved.

Cost and mortality prediction using polymerase chain reaction pathogen detection in sepsis: evidence from three observational trials

PubMed Central

2010-01-01

Introduction Delays in adequate antimicrobial treatment contribute to high cost and mortality in sepsis. Polymerase chain reaction (PCR) assays are used alongside conventional cultures to accelerate the identification of microorganisms. We analyze the impact on medical outcomes and healthcare costs if improved adequacy of antimicrobial therapy is achieved by providing immediate coverage after positive PCR reports. Methods A mathematical prediction model describes the impact of PCR-based rapid adjustment of antimicrobial treatment. The model is applied to predict cost and medical outcomes for 221 sepsis episodes of 189 post-surgical and intensive care unit (ICU) sepsis patients with available PCR data from a prospective, observational trial of a multiplex PCR assay in five hospitals. While this trial demonstrated reduction of inadequate treatment days, data on outcomes associated with reduced inadequate initial antimicrobial treatment had to be obtained from two other, bigger, studies which involved 1,147 (thereof 316 inadequately treated) medical or surgical ICU patients. Our results are reported with the (5% to 95%) percentile ranges from Monte Carlo simulation in which the input parameters were randomly and independently varied according to their statistical characterization in the three underlying studies. The model allows predictions also for different patient groups or PCR assays. Results A total of 13.1% of PCR tests enabled earlier adequate treatment. We predict that cost for PCR testing (300 €/test) can be fully recovered for patients above 717 € (605 € to 1,710 €) daily treatment cost. A 2.6% (2.0 to 3.2%) absolute reduction of mortality is expected. Cost per incremental survivor calculates to 11,477 € (9,321 € to 14,977 €) and incremental cost-effectiveness ratio to 3,107 € (2,523 € to 4,055 €) per quality-adjusted life-year. Generally, for ICU patients with >25% incidence of inadequate empiric antimicrobial treatment, and at least 15% with a positive blood culture, PCR represents a cost-neutral adjunct method. Conclusions Rapid PCR identification of microorganisms has the potential to become a cost-effective component for managing sepsis. The prediction model tested with data from three observational trials should be utilized as a framework to deepen insights when integrating more complementary data associated with utilization of molecular assays in the management of sepsis. PMID:20950442

Adherence to antiretroviral therapy (ART) during the early months of treatment in rural Zambia: influence of demographic characteristics and social surroundings of patients

PubMed Central

2012-01-01

Background Around 70% of those living with HIV in need of treatment accessed antiretroviral therapy (ART) in Zambia by 2009. However, sustaining high levels of adherence to ART is a challenge. This study aimed to identify the predictive factors associated with ART adherence during the early months of treatment in rural Zambia. Methods This is a field based observational longitudinal study in Mumbwa district, which is located 150 km west of Lusaka, the capital of Zambia. Treatment naive patients aged over 15 years, who initiated treatment during September-November 2010, were enrolled. Patients were interviewed at the initiation and six weeks later. The treatment adherence was measured according to self-reporting by the patients. Multiple logistic regression analysis was performed to identify the predictive factors associated with the adherence. Results Of 157 patients, 59.9% were fully adherent to the treatment six weeks after starting ART. According to the multivariable analysis, full adherence was associated with being female [Adjusted Odds Ratio (AOR), 3.3; 95% Confidence interval (CI), 1.2-8.9], having a spouse who were also on ART (AOR, 4.4; 95% CI, 1.5-13.1), and experience of food insufficiency in the previous 30 days (AOR, 5.0; 95% CI, 1.8-13.8). Some of the most common reasons for missed doses were long distance to health facilities (n = 21, 53.8%), food insufficiency (n = 20, 51.3%), and being busy with other activities such as work (n = 15, 38.5%). Conclusions The treatment adherence continues to be a significant challenge in rural Zambia. Social supports from spouses and people on ART could facilitate their treatment adherence. This is likely to require attention by ART services in the future, focusing on different social influences on male and female in rural Zambia. In addition, poverty reduction strategies may help to reinforce adherence to ART and could mitigate the influence of HIV infection for poor patients and those who fall into poverty after starting ART. PMID:23270312

Initial presentation of type 2 diabetes in adolescents predicts durability of successful treatment with metformin monotherapy: Insights from the pediatric diabetes consortium T2D registry

USDA-ARS?s Scientific Manuscript database

Many adolescents with type 2 diabetes (T2D) have rapid deterioration of glycemic control on metformin monotherapy within 2 years of diagnosis. Enrollment data from the Pediatric Diabetes Consortium T2D registry were used to categorize 276 youth with a T2D duration >/-2 years into two groups: (1) par...

Modelling Precipitation Kinetics During Aging of Al-Mg-Si Alloys

NASA Astrophysics Data System (ADS)

Du, Qiang; Friis, Jepser

A classical Kaufmann-Wagner numerical model is employed to predict the evolution of precipitate size distribution during the aging treatment of Al-Mg-Si alloys. One feature of the model is its fully coupling with CALPHAD database, and with the input of interfacial energy from ab-initial calculation, it is able to capture the morphological change of the precipitates. The simulation results will be compared with the experimental measurements.

Monitoring of anti-cancer treatment with 18F-FDG and 18F-FLT PET: a comprehensive review of pre-clinical studies

PubMed Central

Jensen, Mette Munk; Kjaer, Andreas

2015-01-01

Functional imaging of solid tumors with positron emission tomography (PET) imaging is an evolving field with continuous development of new PET tracers and discovery of new applications for already implemented PET tracers. During treatment of cancer patients, a general challenge is to measure treatment effect early in a treatment course and by that to stratify patients into responders and non-responders. With 2-deoxy-2-[18F]fluoro-D-glucose (18F-FDG) and 3’-deoxy-3’-[18F]fluorothymidine(18F-FLT) two of the cancer hallmarks, altered energy metabolism and increased cell proliferation, can be visualized and quantified non-invasively by PET. With 18F-FDG and 18F-FLT PET changes in energy metabolism and cell proliferation can thereby be determined after initiation of cancer treatment in both clinical and pre-clinical studies in order to predict, at an early time-point, treatment response. It is hypothesized that decreases in glycolysis and cell proliferation may occur in tumors that are sensitive to the applied cancer therapeutics and that tumors that are resistant to treatment will show unchanged glucose metabolism and cell proliferation. Whether 18F-FDG and/or 18F-FLT PET can be used for prediction of treatment response has been analyzed in many studies both following treatment with conventional chemotherapeutic agents but also following treatment with different targeted therapies, e.g. monoclonal antibodies and small molecules inhibitors. The results from these studies have been most variable; in some studies early changes in 18F-FDG and 18F-FLT uptake predicted later tumor regression whereas in other studies no change in tracer uptake was observed despite the treatment being effective. The present review gives an overview of pre-clinical studies that have used 18F-FDG and/or 18F-FLT PET for response monitoring of cancer therapeutics. PMID:26550536

Exercise capacity before and after an 8-week multidisciplinary inpatient rehabilitation program in lung cancer patients: a pilot study.

PubMed

Spruit, Martijn A; Janssen, Paul P; Willemsen, Sonja C P; Hochstenbag, Monique M H; Wouters, Emiel F M

2006-05-01

Although lung cancer is a highly prevalent type of cancer, the effects of an inpatient multidisciplinary rehabilitation program on pulmonary function and exercise capacity have never been studied in these patients. Pulmonary function, 6-min walking distance and peak exercise capacity of 10 patients with a severely impaired pulmonary function following treatment of lung cancer were assessed in this pilot study before and after an 8-week inpatient multidisciplinary rehabilitation program. At baseline, patients had a restrictive pulmonary function and an apparent exercise intolerance (median 6-min walking distance: 63.6% predicted; median peak cycling load: 58.5% predicted). Despite the lack of change in median pulmonary function [FEV1: -0.01L, p = 0.5469], functional exercise capacity [145 m; 43.2% of the initial values, p=0.0020] and peak exercise capacity [26 W; 34.4% of the initial values, p = 0.0078] improved significantly compared to baseline. Future trials have to corroborate the present findings. Nevertheless, patients with lung cancer have a clear indication to start a comprehensive rehabilitation program following intensive treatment of their disease. In fact, based on the results of the present pilot study it appears that these patients are good candidates for pulmonary rehabilitation programs.

Homogenization kinetics of a nickel-based superalloy produced by powder bed fusion laser sintering

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

Zhang, Fan; Levine, Lyle E.; Allen, Andrew J.

2017-04-01

Additively manufactured (AM) metal components often exhibit fine dendritic microstructures and elemental segregation due to the initial rapid solidification and subsequent melting and cooling during the build process, which without homogenization would adversely affect materials performance. In this letter, we report in situ observation of the homogenization kinetics of an AM nickel-based superalloy using synchrotron small angle X-ray scattering. The identified kinetic time scale is in good agreement with thermodynamic diffusion simulation predictions using microstructural dimensions acquired by ex situ scanning electron microscopy. These findings could serve as a recipe for predicting, observing, and validating homogenization treatments in AM materials.

Homogenization Kinetics of a Nickel-based Superalloy Produced by Powder Bed Fusion Laser Sintering.

PubMed

Zhang, Fan; Levine, Lyle E; Allen, Andrew J; Campbell, Carelyn E; Lass, Eric A; Cheruvathur, Sudha; Stoudt, Mark R; Williams, Maureen E; Idell, Yaakov

2017-04-01

Additively manufactured (AM) metal components often exhibit fine dendritic microstructures and elemental segregation due to the initial rapid solidification and subsequent melting and cooling during the build process, which without homogenization would adversely affect materials performance. In this letter, we report in situ observation of the homogenization kinetics of an AM nickel-based superalloy using synchrotron small angle X-ray scattering. The identified kinetic time scale is in good agreement with thermodynamic diffusion simulation predictions using microstructural dimensions acquired by ex situ scanning electron microscopy. These findings could serve as a recipe for predicting, observing, and validating homogenization treatments in AM materials.

Repeat Gamma Knife Radiosurgery for Trigeminal Neuralgia

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

Aubuchon, Adam C., E-mail: acaubuchon@gmail.com; Chan, Michael D.; Lovato, James F.

2011-11-15

Purpose: Repeat gamma knife stereotactic radiosurgery (GKRS) for recurrent or persistent trigeminal neuralgia induces an additional response but at the expense of an increased incidence of facial numbness. The present series summarized the results of a repeat treatment series at Wake Forest University Baptist Medical Center, including a multivariate analysis of the data to identify the prognostic factors for treatment success and toxicity. Methods and Materials: Between January 1999 and December 2007, 37 patients underwent a second GKRS application because of treatment failure after a first GKRS treatment. The mean initial dose in the series was 87.3 Gy (range, 80-90).more » The mean retreatment dose was 84.4 Gy (range, 60-90). The dosimetric variables recorded included the dorsal root entry zone dose, pons surface dose, and dose to the distal nerve. Results: Of the 37 patients, 81% achieved a >50% pain relief response to repeat GKRS, and 57% experienced some form of trigeminal dysfunction after repeat GKRS. Two patients (5%) experienced clinically significant toxicity: one with bothersome numbness and one with corneal dryness requiring tarsorraphy. A dorsal root entry zone dose at repeat treatment of >26.6 Gy predicted for treatment success (61% vs. 32%, p = .0716). A cumulative dorsal root entry zone dose of >84.3 Gy (72% vs. 44%, p = .091) and a cumulative pons surface dose of >108.5 Gy (78% vs. 44%, p = .018) predicted for post-GKRS numbness. The presence of any post-GKRS numbness predicted for a >50% decrease in pain intensity (100% vs. 60%, p = .0015). Conclusion: Repeat GKRS is a viable treatment option for recurrent trigeminal neuralgia, although the patient assumes a greater risk of nerve dysfunction to achieve maximal pain relief.« less

Application of empirical Bayes methods to predict the rate of decline in ERG at the individual level among patients with retinitis pigmentosa.

PubMed

Qiu, Weiliang; Sandberg, Michael A; Rosner, Bernard

2018-05-31

Retinitis pigmentosa is one of the most common forms of inherited retinal degeneration. The electroretinogram (ERG) can be used to determine the severity of retinitis pigmentosa-the lower the ERG amplitude, the more severe the disease is. In practice for career, lifestyle, and treatment counseling, it is of interest to predict the ERG amplitude of a patient at a future time. One approach is prediction based on the average rate of decline for individual patients. However, there is considerable variation both in initial amplitude and in rate of decline. In this article, we propose an empirical Bayes (EB) approach to incorporate the variations in initial amplitude and rate of decline for the prediction of ERG amplitude at the individual level. We applied the EB method to a collection of ERGs from 898 patients with 3 or more visits over 5 or more years of follow-up tested in the Berman-Gund Laboratory and observed that the predicted values at the last (kth) visit obtained by using the proposed method based on data for the first k-1 visits are highly correlated with the observed values at the kth visit (Spearman correlation =0.93) and have a higher correlation with the observed values than those obtained based on either the population average decline rate or those obtained based on the individual decline rate. The mean square errors for predicted values obtained by the EB method are also smaller than those predicted by the other methods. Copyright © 2018 John Wiley & Sons, Ltd.

Clinical assessment is an accurate predictor of which patients will need septoplasty.

PubMed

Sedaghat, Ahmad R; Busaba, Nicolas Y; Cunningham, Michael J; Kieff, David A

2013-01-01

Septoplasty is a frequently performed surgical procedure with the most common indication being nasal airway obstruction. Almost universally, health insurance companies mandate a trial of medical therapy consisting of intranasal corticosteroids prior to performance of septoplasty regardless of clinical assessment. Evidence for this requirement is lacking. We sought to evaluate the initial clinical assessment as a predictor of response to this mandated trial of medical treatment. Retrospective review of prospectively collected data on 137 consecutive patients who presented with symptoms of nasal obstruction and a deviated nasal septum on physical examination. Patients were placed into one of three cohorts based on prediction of 1) failure of medical therapy with subsequent septoplasty, 2) success of medical therapy without subsequent septoplasty, or 3) unable to make a prediction. Patients from each cohort were assessed for subsequent response to medical therapy and ultimate need for septoplasty. Overall clinical assessment had a sensitivity of 86.9%, specificity of 91.8%, positive predictive value of 93.6%, and negative predictive value of 96.4% for detecting/predicting need for septoplasty. The accuracy of the overall clinical assessment is considerably better than severe deviation at any one septal anatomical site. Of patients whose response to medical therapy could not be predicted, 61.3% failed medical therapy and needed surgery; this is statistically equivalent to a 50/50 distribution between either needing septoplasty or not. Clinical assessment at initial presentation of patients with nasal obstruction and deviated septum is highly accurate in predicting which patients will need septoplasty. Copyright © 2012 The American Laryngological, Rhinological, and Otological Society, Inc.

Progression along the Bipolar Spectrum: A Longitudinal Study of Predictors of Conversion from Bipolar Spectrum Conditions to Bipolar I and II Disorders

PubMed Central

Alloy, Lauren B.; Urošević, Snežana; Abramson, Lyn Y.; Jager-Hyman, Shari; Nusslock, Robin; Whitehouse, Wayne G.; Hogan, Michael

2011-01-01

Little longitudinal research has examined progression to more severe bipolar disorders in individuals with “soft” bipolar spectrum conditions. We examine rates and predictors of progression to bipolar I and II diagnoses in a non-patient sample of college-age participants (n = 201) with high General Behavior Inventory scores and childhood or adolescent onset of “soft” bipolar spectrum disorders followed longitudinally for 4.5 years from the Longitudinal Investigation of Bipolar Spectrum (LIBS) project. Of 57 individuals with initial cyclothymia or bipolar disorder not otherwise specified (BiNOS) diagnoses, 42.1% progressed to a bipolar II diagnosis and 10.5% progressed to a bipolar I diagnosis. Of 144 individuals with initial bipolar II diagnoses, 17.4% progressed to a bipolar I diagnosis. Consistent with hypotheses derived from the clinical literature and the Behavioral Approach System (BAS) model of bipolar disorder, and controlling for relevant variables (length of follow-up, initial depressive and hypomanic symptoms, treatment-seeking, and family history), high BAS sensitivity (especially BAS Fun Seeking) predicted a greater likelihood of progression to bipolar II disorder, whereas early age of onset and high impulsivity predicted a greater likelihood of progression to bipolar I (high BAS sensitivity and Fun-Seeking also predicted progression to bipolar I when family history was not controlled). The interaction of high BAS and high Behavioral Inhibition System (BIS) sensitivities also predicted greater likelihood of progression to bipolar I. We discuss implications of the findings for the bipolar spectrum concept, the BAS model of bipolar disorder, and early intervention efforts. PMID:21668080

A longitudinal study about the body image and psychosocial adjustment of breast cancer patients during the course of the disease.

PubMed

Moreira, Helena; Canavarro, Maria Cristina

2010-09-01

The research of body image among breast cancer patients is characterized by some limitations, such as the lack of longitudinal studies or the absence of a multidimensional perspective of body image. This study intends to overcome these limitations, by examining the evolution of body image dimensions (investment, emotions and evaluations) from the period of surgery (T1) to 6-months after the treatment's ending (T2). It also aims to explore the predictors of body image at T2 and, simultaneously, the predictive role of initial body image to psychosocial adjustment at T2. A total of 56 breast cancer patients participated in both assessments and completed a battery of instruments that included measures of body image dimensions (appearance investment, self-consciousness of appearance, shame and appearance satisfaction) and psychosocial adjustment (quality of life and emotional distress). Within the dimensions of body image, only shame increased over time. In general, initial levels of investment predicted subsequent body image dimensions and having a mastectomy done was associated with higher shame and lower appearance satisfaction at T2. Initial body image did not predict later adjustment, with the exception of depression, where appearance investment played a relevant role. Our findings contributed to the advance of knowledge in this area, providing relevant data about the evolution of body image dimensions, its predictors and its predictive role on psychosocial adjustment among breast cancer patients. This study also suggested some clinical implications that can assist health professionals to implement strategies focused on body image throughout the disease.

Predicting response to physiotherapy treatment for musculoskeletal shoulder pain: protocol for a longitudinal cohort study

PubMed Central

2013-01-01

Background Shoulder pain affects all ages, with a lifetime prevalence of one in three. The most effective treatment is not known. Physiotherapy is often recommended as the first choice of treatment. At present, it is not possible to identify, from the initial physiotherapy assessment, which factors predict the outcome of physiotherapy for patients with shoulder pain. The primary objective of this study is to identify which patient characteristics and baseline measures, typically assessed at the first physiotherapy appointment, are related to the functional outcome of shoulder pain 6 weeks and 6 months after starting physiotherapy treatment. Methods/Design Participants with musculoskeletal shoulder pain of any duration will be recruited from participating physiotherapy departments. For this longitudinal cohort study, the participants care pathway, including physiotherapy treatment will be therapist determined. Potential prognostic variables will be collected from participants during their first physiotherapy appointment and will include demographic details, lifestyle, psychosocial factors, shoulder symptoms, general health, clinical examination, activity limitations and participation restrictions. Outcome measures (Shoulder Pain and Disability Index, Quick Disability of the Arm, Shoulder and Hand, and Global Impression of Change) will be collected by postal self-report questionnaires 6 weeks and 6 months after commencing physiotherapy. Details of attendance and treatment will be collected by the treating physiotherapist. Participants will be asked to complete an exercise dairy. An initial exploratory analysis will assess the relationship between potential prognostic factors at baseline and outcome using univariate statistical tests. Those factors significant at the 5% level will be further considered as prognostic factors using a general linear model. It is estimated that 780 subjects will provide more than 90% power to detect an effect size of less than 0.25 adjusted for other variables which have a co-efficient of determination (R-squared) with the outcome of up to 0.5. Assuming a 22% loss to follow up at 6 months, 1000 participants will initially be recruited. Discussion This study may offer service users and providers with guidance to help identify whether or not physiotherapy is likely to be of benefit. Clinicians may have some direction as to what key factors indicate a patient’s likely response to physiotherapy. PMID:23800352

Health services research in patients with breast cancer (CAMISS-prospective): study protocol for an observational prospective study.

PubMed

García-Gutierrez, Susana; Orive, Miren; Sarasqueta, Cristina; Legarreta, Maria Jose; Gonzalez, Nerea; Redondo, Maximino; Rivero, Amado; Serrano-Aguilar, Pedro; Castells, Xavier; Quintana, Jose Maria; Sala, Maria

2018-01-08

Though breast cancer remains a major health problem, there is a lack of information on health care provided to patients with this disease and associated costs. In addition, there is a need to update and validate risk stratification tools in Spain. Our purpose is to evaluate the health services provided for breast cancer in Spain, from screening and diagnosis to treatment and prognosis. Prospective cohort study involving 13 hospitals in Spain with a follow-up period of up to 5 years after diagnostic biopsy. Eligibility criteria: Patients diagnosed with breast cancer between April 2013 and May 2015 that have consented to participate in the study. Data will be collected on the following: pre-intervention medical history, biological, clinical, and sociodemographic characteristics, mode of cancer detection, hospital admission, treatment, and outcomes up to 5 years after initial treatment. Questionnaires about quality of life (EuroQoL EQ-5D-5 L, the European Organization For Research And Treatment Of Cancer Core Quality Of Life Questionnaire EORTC QLQ-C30 join to the specific breast cancer module (QLQ-BR23), as well as Hospital Anxiety and Depression Scale were completed by the patients before the beginning of the initial treatment and at the end of follow-up period, 2 years later. The end-points of the study were changes in health-related quality of life, recurrence, complications and readmissions at 2 and 5 years after initial treatment. Descriptive statistics will be calculated and multivariate models will be used where appropriate to adjust for potential confounders. In order to create and validate a prediction model, split validation and bootstrapping will be performed. Cost analysis will be carried out from the perspective of a national health system. The results of this coordinated project are expected to generate scientifically valid and clinically and socially important information to inform the decision-making of managers and the authorities responsible for ensuring equality in care processes as well in health outcomes. For clinicians, clinical prediction rules will be developed which are expected to serve as the basis for the development of software applications. NCT02439554 . Date of registration: May 8, 2015 (retrospectively registered) .

Characterization of Neutropenia in Advanced Cancer Patients Following Palbociclib Treatment Using a Population Pharmacokinetic-Pharmacodynamic Modeling and Simulation Approach.

PubMed

Sun, Wan; O'Dwyer, Peter J; Finn, Richard S; Ruiz-Garcia, Ana; Shapiro, Geoffrey I; Schwartz, Gary K; DeMichele, Angela; Wang, Diane

2017-09-01

Neutropenia is the most commonly reported hematologic toxicity following treatment with palbociclib, a cyclin-dependent kinase 4/6 inhibitor approved for metastatic breast cancer. Using data from 185 advanced cancer patients receiving palbociclib in 3 clinical trials, a pharmacokinetic-pharmacodynamic model was developed to describe the time course of absolute neutrophil count (ANC) and quantify the exposure-response relationship for neutropenia. These analyses help in understanding neutropenia associated with palbociclib and its comparison with chemotherapy-induced neutropenia. In the model, palbociclib plasma concentration was related to its antiproliferative effect on precursor cells through drug-related parameters (ie, maximum estimated drug effect and concentration corresponding to 50% of the maximum effect), and neutrophil physiology was mimicked through system-related parameters (ie, mean transit time, baseline ANC, and feedback parameter). Sex and baseline albumin level were significant covariates for baseline ANC. It was demonstrated by different model evaluation approaches (eg, prediction-corrected visual predictive check and standardized visual predictive check) that the final model adequately described longitudinal ANC with good predictive capability. The established model suggested that higher palbociclib exposure was associated with lower longitudinal neutrophil counts. The ANC nadir was reached approximately 21 days after palbociclib treatment initiation. Consistent with their mechanisms of action, neutropenia associated with palbociclib (cytostatic) was rapidly reversible and noncumulative, with a notably weaker antiproliferative effect on precursor cells relative to chemotherapies (cytotoxic). This pharmacokinetic-pharmacodynamic model aids in predicting neutropenia and optimizing dosing for future palbociclib trials with different dosing regimen combinations. © 2017, The American College of Clinical Pharmacology.

In silico exploration of the impact of pasture larvae contamination and anthelmintic treatment on genetic parameter estimates for parasite resistance in grazing sheep.

PubMed

Laurenson, Y C S M; Kyriazakis, I; Bishop, S C

2012-07-01

A mathematical model was developed to investigate the impact of level of Teladorsagia circumcincta larval pasture contamination and anthelmintic treatment on genetic parameter estimates for performance and resistance to parasites in sheep. Currently great variability is seen for published correlations between performance and resistance, with estimates appearing to vary with production environment. The model accounted for host genotype and parasitism in a population of lambs, incorporating heritable between-lamb variation in host-parasite interactions, with genetic independence of input growth and immunological variables. An epidemiological module was linked to the host-parasite interaction module via food intake (FI) to create a grazing scenario. The model was run for a population of lambs growing from 2 mo of age, grazing on pasture initially contaminated with 0, 1,000, 3,000, or 5,000 larvae/kg DM, and given either no anthelmintic treatment or drenched at 30-d intervals. The mean population values for FI and empty BW (EBW) decreased with increasing levels of initial larval contamination (IL(0)), with non-drenched lambs having a greater reduction than drenched ones. For non-drenched lambs the maximum mean population values for worm burden (WB) and fecal egg count (FEC) increased and occurred earlier for increasing IL(0), with values being similar for all IL(0) at the end of the simulation. Drenching was predicted to suppress WB and FEC, and cause reduced pasture contamination. The heritability of EBW for non-drenched lambs was predicted to be initially high (0.55) and decreased over time with increasing IL(0), whereas drenched lambs remained high throughout. The heritability of WB and FEC for all lambs was initially low (∼0.05) and increased with time to ∼0.25, with increasing IL(0) leading to this value being reached at faster rates. The genetic correlation between EBW and FEC was initially ∼-0.3. As time progressed the correlation tended towards 0, before becoming negative by the end of the simulation for non-drenched lambs, with increasing IL(0) leading to increasingly negative correlations. For drenched lambs, the correlation remained close to 0. This study highlights the impact of IL(0) and anthelmintic treatment on genetic parameters for resistance. Along with factors affecting performance penalties due to parasitism and time of reporting, the results give plausible causes for variation in genetic parameter estimates previously reported.

[Role of TSH receptor autoantibodies for the diagnosis of Graves' disease and for the prediction of the course of hyperthyroidism and ophthalmopathy. Recommendations of the Thyroid Section of the German Society of Endocrinology].

PubMed

Eckstein, Anja; Mann, Klaus; Kahaly, George J; Grussendorf, Martin; Reiners, Christoph; Feldkamp, Joachim; Quadbeck, Beate; Bockisch, Andreas; Schott, Matthias

2009-05-15

Graves' disease (GD) is the only autoimmune disease where autoantibodies stimulate the target organs. Among the most common clinical manifestations are hyperthyroidism and orbitopathy (GO). To ensure the diagnosis of autoimmune hyperthyroidism, activity of TSH receptor autoantibodies (TRAb) should be determined. Because of their significantly improved sensitivity and equal specificity, second-generation TRAb assays (activity given in IU/l) should be preferred over first-generation assays (activity given in U/l). During follow-up of antithyroid drug therapy it is possible to predict outcome for some patients with high chances if TRAb levels are high. On this basis, thyreoablative treatment (operation or radioiodine) can already be indicated before the 1st year of antithyroid drug treatment has passed. If TRAb antibody titers are > 10 IU/l, it is possible to predict outcome as early as 6 months after initiation of antithyroid drug therapy. Below a certain threshold, depending on the time point of measurement, no representative risk analyses are available for TRAbs. TRAb measurement is also helpful to determine the course of GO. This may guide the physician through crucial treatment decisions, especially if the patient is at risk of deterioration.

Meditation-induced changes in high-frequency heart rate variability predict smoking outcomes

PubMed Central

Libby, Daniel J.; Worhunsky, Patrick D.; Pilver, Corey E.; Brewer, Judson A.

2012-01-01

Background: High-frequency heart rate variability (HF-HRV) is a measure of parasympathetic nervous system (PNS) output that has been associated with enhanced self-regulation. Low resting levels of HF-HRV are associated with nicotine dependence and blunted stress-related changes in HF-HRV are associated with decreased ability to resist smoking. Meditation has been shown to increase HF-HRV. However, it is unknown whether tonic levels of HF-HRV or acute changes in HF-HRV during meditation predict treatment responses in addictive behaviors such as smoking cessation. Purpose: To investigate the relationship between HF-HRV and subsequent smoking outcomes. Methods: HF-HRV during resting baseline and during mindfulness meditation was measured within two weeks of completing a 4-week smoking cessation intervention in a sample of 31 community participants. Self-report measures of smoking were obtained at a follow up 17-weeks after the initiation of treatment. Results: Regression analyses indicated that individuals exhibiting acute increases in HF-HRV from resting baseline to meditation smoked fewer cigarettes at follow-up than those who exhibited acute decreases in HF-HRV (b = −4.89, p = 0.008). Conclusion: Acute changes in HF-HRV in response to meditation may be a useful tool to predict smoking cessation treatment response. PMID:22457646

Adolescents’ thoughts about abstinence curb the return of marijuana use during and after treatment

PubMed Central

King, Kevin M.; Chung, Tammy; Maisto, Stephen A.

2009-01-01

Despite some evidence showing that readiness to change substance use predicts reductions in substance use among treated adolescents, there is little research on month-to-month changes in adolescents’ thoughts about abstinence and marijuana use during and after substance use treatment. The current study provides a test of the “snares” hypothesis, which posits that time-varying changes in adolescents’ motivation to abstain and perceived difficulty to abstain from marijuana use hinder, or snare, the return of regular marijuana use during and after treatment. Monthly data on thoughts about abstinence, marijuana use, and treatment utilization were collected over 6-month follow-up from 142 adolescents recruited from intensive outpatient treatment for substance use. Results provided some support for the snares hypothesis in that higher motivation to abstain (but not perceived difficulty) predicted fewer days of marijuana use, over and above both the adolescent’s average trajectory of marijuana use, the initial severity of their marijuana involvement, and the effects of treatment utilization. Moreover, this association was bi-directional, such that past-month marijuana use influenced both motivation to abstain and perceived difficulty to abstain. Study findings highlight the importance of abstinence-related cognitions as a key target of intervention during and after addictions treatment, and underscore the importance of considering recovery from substance use disorders as a dynamic process of change over time. PMID:19485595

Prediction as a humanitarian and pragmatic contribution from human cognitive neuroscience.

PubMed

Gabrieli, John D E; Ghosh, Satrajit S; Whitfield-Gabrieli, Susan

2015-01-07

Neuroimaging has greatly enhanced the cognitive neuroscience understanding of the human brain and its variation across individuals (neurodiversity) in both health and disease. Such progress has not yet, however, propelled changes in educational or medical practices that improve people's lives. We review neuroimaging findings in which initial brain measures (neuromarkers) are correlated with or predict future education, learning, and performance in children and adults; criminality; health-related behaviors; and responses to pharmacological or behavioral treatments. Neuromarkers often provide better predictions (neuroprognosis), alone or in combination with other measures, than traditional behavioral measures. With further advances in study designs and analyses, neuromarkers may offer opportunities to personalize educational and clinical practices that lead to better outcomes for people. Copyright © 2015 Elsevier Inc. All rights reserved.

[From prospective molecular diagnosis of enterovirus meningitis...to the prevention of antibiotic resistance].

PubMed

Peigue-Lafeuille, H; Archimbaud, C; Mirand, A; Chambon, M; Regagnon, C; Laurichesse, H; Clavelou, P; Labbé, A; Bailly, J-L; Henquell, C

2006-03-01

Meningitis initially presents with intense manifestations that are not generally specific to a given etiology. The first major question for the physician is to decide whether to initiate a probabilistic treatment. Enteroviruses are a major cause of aseptic meningitis, which is benign in immunocompetent patients. Molecular diagnosis is now becoming the gold standard and its prospective use at the time of patient admission, on the sole basis of clinical suspicion of meningitis, has yielded more reliable data. Cytological and biochemical data from CSF analyses are of low predictive value to influence the initial decision to treat with antibiotics. In addition, cases of meningitis during winter are not uncommon. Adults are concerned in about 25% of cases. Thus, if molecular diagnostic tools are not rapidly available, patient management may be inconsistent, leading to unnecessary scans, laboratory investigations and treatment (including overconsumption of antibiotics). Current progress in the automation and practicability of viral genomic detection yields the result within a few hours after admission. Rapid molecular viral diagnosis of a benign disease that does not require treatment but which is initially worrying is of unquestionable advantage. It is of benefit to both the patient and the community because of its input on health economics, the needless consumption of drugs and, as a result, resistance to antibiotics. The diagnosis of meningitis can no longer remain a retrospective diagnosis after elimination of all the possible causes, since not prescribing unnecessary laboratory tests and not treating are true therapeutic decisions.

Factors Predicting Visual Acuity Outcome in Intermediate, Posterior, and Panuveitis: The Multicenter Uveitis Steroid Treatment (MUST) Trial.

PubMed

Kempen, John H; Van Natta, Mark L; Altaweel, Michael M; Dunn, James P; Jabs, Douglas A; Lightman, Susan L; Thorne, Jennifer E; Holbrook, Janet T

2015-12-01

To identify factors associated with best-corrected visual acuity (BCVA) presentation and 2-year outcome in 479 intermediate, posterior, and panuveitic eyes. Cohort study using randomized controlled trial data. Multicenter Uveitis Steroid Treatment (MUST) Trial masked BCVA measurements at baseline and at 2 years follow-up used gold-standard methods. Twenty-three clinical centers documented characteristics per protocol, which were evaluated as potential predictive factors for baseline BCVA and 2-year change in BCVA. Baseline factors significantly associated with reduced BCVA included age ≥50 vs <50 years; posterior vs intermediate uveitis; uveitis duration >10 vs <6 years; anterior chamber (AC) flare >grade 0; cataract; macular thickening; and exudative retinal detachment. Over 2 years, eyes better than 20/50 and 20/50 or worse at baseline improved, on average, by 1 letter (P = .52) and 10 letters (P < .001), respectively. Both treatment groups and all sites of uveitis improved similarly. Factors associated with improved BCVA included resolution of active AC cells, resolution of macular thickening, and cataract surgery in an initially cataractous eye. Factors associated with worsening BCVA included longer duration of uveitis (6-10 or >10 vs <6 years), incident AC flare, cataract at both baseline and follow-up, pseudophakia at baseline, persistence or incidence of vitreous haze, and incidence of macular thickening. Intermediate, posterior, and panuveitis have a similarly favorable prognosis with both systemic and fluocinolone acetonide implant treatment. Eyes with more prolonged/severe inflammatory damage and/or inflammatory findings initially or during follow-up have a worse visual acuity prognosis. The results indicate the value of implementing best practices in managing inflammation. Copyright © 2015 Elsevier Inc. All rights reserved.

Individualized cost-effective conventional ovulation induction treatment in normogonadotrophic anovulatory infertility (WHO group 2).

PubMed

Eijkemans, Marinus J C; Polinder, Suzanne; Mulders, Annemarie G M G J; Laven, Joop S E; Habbema, J Dik F; Fauser, Bart C J M

2005-10-01

Conventional treatment in normogonadotrophic anovulatory infertility (WHO 2) consists of clomiphene citrate (CC), followed by exogenous gonadotrophins (FSH) and IVF. Response to these treatments may be predicted on the basis of individual patient characteristics. We aimed to devise a patient-tailored, cost-effective treatment algorithm involving the above-mentioned treatment modalities, based on individual patient characteristics. Sixteen prognostic groups are defined, according to the presence or absence of: age >30 years, amenorrhea, elevated androgen levels and obesity. The chances of response with each of the three treatments were calculated using prediction models. Treatment costs were based on the data of 240 patients visiting a specialist academic fertility unit. Outcome was an ongoing pregnancy within 12 months after initiation of treatment. The costs per pregnancy of three different strategies were compared, with a threshold for cost-effectiveness of 10 000. The strategy CC + FSH + IVF compared with FSH + IVF generated more pregnancies against lower costs. Compared with CC + IVF, it also produced more pregnancies, but at higher costs. For <30 years of age with normal androgen levels, costs per pregnancy were less than 10 000. For women >30 years old, costs per pregnancy were 25 000 and over 200 000, when presenting with normal or elevated androgen levels, respectively. The conventional treatment protocol is efficient for women aged <30 years with normal androgen levels. For women >30 years old with elevated androgen levels, FSH may be skipped.

Development of an Electronic Medical Record Based Alert for Risk of HIV Treatment Failure in a Low-Resource Setting

PubMed Central

Puttkammer, Nancy; Zeliadt, Steven; Balan, Jean Gabriel; Baseman, Janet; Destiné, Rodney; Domerçant, Jean Wysler; France, Garilus; Hyppolite, Nathaelf; Pelletier, Valérie; Raphael, Nernst Atwood; Sherr, Kenneth; Yuhas, Krista; Barnhart, Scott

2014-01-01

Background The adoption of electronic medical record systems in resource-limited settings can help clinicians monitor patients' adherence to HIV antiretroviral therapy (ART) and identify patients at risk of future ART failure, allowing resources to be targeted to those most at risk. Methods Among adult patients enrolled on ART from 2005–2013 at two large, public-sector hospitals in Haiti, ART failure was assessed after 6–12 months on treatment, based on the World Health Organization's immunologic and clinical criteria. We identified models for predicting ART failure based on ART adherence measures and other patient characteristics. We assessed performance of candidate models using area under the receiver operating curve, and validated results using a randomly-split data sample. The selected prediction model was used to generate a risk score, and its ability to differentiate ART failure risk over a 42-month follow-up period was tested using stratified Kaplan Meier survival curves. Results Among 923 patients with CD4 results available during the period 6–12 months after ART initiation, 196 (21.2%) met ART failure criteria. The pharmacy-based proportion of days covered (PDC) measure performed best among five possible ART adherence measures at predicting ART failure. Average PDC during the first 6 months on ART was 79.0% among cases of ART failure and 88.6% among cases of non-failure (p<0.01). When additional information including sex, baseline CD4, and duration of enrollment in HIV care prior to ART initiation were added to PDC, the risk score differentiated between those who did and did not meet failure criteria over 42 months following ART initiation. Conclusions Pharmacy data are most useful for new ART adherence alerts within iSanté. Such alerts offer potential to help clinicians identify patients at high risk of ART failure so that they can be targeted with adherence support interventions, before ART failure occurs. PMID:25390044

Development of an electronic medical record based alert for risk of HIV treatment failure in a low-resource setting.

PubMed

Puttkammer, Nancy; Zeliadt, Steven; Balan, Jean Gabriel; Baseman, Janet; Destiné, Rodney; Domerçant, Jean Wysler; France, Garilus; Hyppolite, Nathaelf; Pelletier, Valérie; Raphael, Nernst Atwood; Sherr, Kenneth; Yuhas, Krista; Barnhart, Scott

2014-01-01

The adoption of electronic medical record systems in resource-limited settings can help clinicians monitor patients' adherence to HIV antiretroviral therapy (ART) and identify patients at risk of future ART failure, allowing resources to be targeted to those most at risk. Among adult patients enrolled on ART from 2005-2013 at two large, public-sector hospitals in Haiti, ART failure was assessed after 6-12 months on treatment, based on the World Health Organization's immunologic and clinical criteria. We identified models for predicting ART failure based on ART adherence measures and other patient characteristics. We assessed performance of candidate models using area under the receiver operating curve, and validated results using a randomly-split data sample. The selected prediction model was used to generate a risk score, and its ability to differentiate ART failure risk over a 42-month follow-up period was tested using stratified Kaplan Meier survival curves. Among 923 patients with CD4 results available during the period 6-12 months after ART initiation, 196 (21.2%) met ART failure criteria. The pharmacy-based proportion of days covered (PDC) measure performed best among five possible ART adherence measures at predicting ART failure. Average PDC during the first 6 months on ART was 79.0% among cases of ART failure and 88.6% among cases of non-failure (p<0.01). When additional information including sex, baseline CD4, and duration of enrollment in HIV care prior to ART initiation were added to PDC, the risk score differentiated between those who did and did not meet failure criteria over 42 months following ART initiation. Pharmacy data are most useful for new ART adherence alerts within iSanté. Such alerts offer potential to help clinicians identify patients at high risk of ART failure so that they can be targeted with adherence support interventions, before ART failure occurs.

Biases in Global Reanalysis Datasets Undermine Intraseasonal Prediction Skill Xiouhua Fu1, Bin Wang, June-Yi Lee, Wanqiu Wang, and Li Gao 1International Pacific Research Center (IPRC), SOEST, University of Hawaii at Manoa

NASA Astrophysics Data System (ADS)

Fu, J. X.

2010-12-01

Predictability of Intra-Seasonal Oscillation (ISO) relies on both initial conditions and lower boundary conditions (or atmosphere-ocean interaction). The atmospheric reanalysis datasets are commonly used as initial conditions. Here, the biases of three reanalysis datasets (NCEP_R1, _R2, and ERA_Interim) in describing ISO were revealed and the impacts of these biases as initial conditions on ISO prediction skills were assessed. A signal recovery method is proposed to improve ISO prediction. All three reanalysis datasets underestimate the intensity of the equatorial eastward-propagating ISO. When these reanalyses are used as initial conditions in the ECHAM4-UH hybrid coupled model (UH_HCM hereinafter), skillful ISO prediction reaches only about one week for both the 850-hPa zonal winds (U850) and rainfall over Southeast Asia and the global tropics. An enhanced nudging of divergence field is shown to significantly improve the initial conditions, resulting in an extension of the skillful rainfall prediction by 2-3 days and U850 prediction by 5-10 days. After recovering the ISO signals in the original reanalyses, the resultant initial conditions contain ISO strength much closer to the observed. Use of these signal-recovered reanalyses as initial conditions extends the skillful prediction of U850 and rainfall, respectively, to 23 and 18 days over Southeast Asia, and to 20 and 10 days over the global tropics. This finding underlines the urgent need to improve data assimilation systems and observations in advancement of ISO prediction by offering better initial conditions. It is also found that small-scale synoptic weather disturbances in initial conditions generally increase ISO prediction skill. The UH_HCM has better rainfall prediction than the NCEP Climate Forecast System (CFS) over Southeast Asia and both models suffer the prediction barrier over the Maritime Continent.

Evaluation of immigration status, race and language barriers on chronic hepatitis C virus infection management and treatment outcomes.

PubMed

Giordano, Céline; Druyts, Eric F; Garber, Gary; Cooper, Curtis

2009-09-01

Hepatitis C virus (HCV) prevalence in certain Canadian immigrant populations is higher than that of the overall population. Disparities in care related to immigration status as well as to race and language are well recognized. Identifying and understanding these disparities is vital to the provision of optimal and inclusive HCV care. HCV RNA-positive patients assessed at The Ottawa Hospital Viral Hepatitis Clinic between June 2000 and June 2007 were identified using a clinical database. As measures of access to care, liver biopsy rates, treatment initiation rates, supportive care provision (i.e. erythropoietin for treatment-related anemia) and sustained virological response (SVR) rates were assessed as a function of immigration status, race and spoken language. Nine hundred and ten patients were evaluated, of which 20% were immigrants. Biopsy rates (54 vs. 51%), HCV treatment initiation (37 vs. 38%), erythropoietin prescription (13 vs. 18%) and SVR rates (52 vs. 51%) did not differ between immigrants and Canadian-born individuals. Spoken language and race did not influence access to treatment. SVR was predicted by genotype, HIV status and race. In the context of a multidisciplinary, multilingual universal health care system, by studying the influence of barriers to HCV investigation and successful therapy can be abrogated.

Youth motivation as a predictor of treatment outcomes in a community mental health system.

PubMed

Merrill, Brett M; Warren, Jared S; Garcia, Darren J; Hardy, Sam A

2017-03-01

The purpose of this study was to examine the relationship between youth motivation and psychotherapy outcomes in routine community mental health settings. One hundred fifty youth, ages 12-17, from three community mental health clinics completed the Youth Outcome Questionnaire and Treatment Support Measure at frequent intervals over the course of treatment. Increases in motivation followed a curvilinear trajectory. On average, youth motivation significantly increased over the course of therapy according to both self- and parent reports (p < .001). The slope for youth motivation over the course of therapy was negatively associated with the slope for mental health symptoms (p < .001). Initial youth motivation did not predict overall change or the rate of change in symptoms. However, there was significant individual variability in patterns of youth motivation. Our findings demonstrate that youth show increases in motivation over the course of therapy with most gains occurring in the first few sessions. Because increases in motivation over the course of therapy were related to decreases in mental health symptoms, further research is needed to examine how treatment interventions or other factors such as parent motivation may moderate this relationship. Additional research examining the likely complex relationship between initial youth motivation and treatment outcomes in community mental health settings is needed.

Validation of Models Used to Inform Colorectal Cancer Screening Guidelines: Accuracy and Implications.

PubMed

Rutter, Carolyn M; Knudsen, Amy B; Marsh, Tracey L; Doria-Rose, V Paul; Johnson, Eric; Pabiniak, Chester; Kuntz, Karen M; van Ballegooijen, Marjolein; Zauber, Ann G; Lansdorp-Vogelaar, Iris

2016-07-01

Microsimulation models synthesize evidence about disease processes and interventions, providing a method for predicting long-term benefits and harms of prevention, screening, and treatment strategies. Because models often require assumptions about unobservable processes, assessing a model's predictive accuracy is important. We validated 3 colorectal cancer (CRC) microsimulation models against outcomes from the United Kingdom Flexible Sigmoidoscopy Screening (UKFSS) Trial, a randomized controlled trial that examined the effectiveness of one-time flexible sigmoidoscopy screening to reduce CRC mortality. The models incorporate different assumptions about the time from adenoma initiation to development of preclinical and symptomatic CRC. Analyses compare model predictions to study estimates across a range of outcomes to provide insight into the accuracy of model assumptions. All 3 models accurately predicted the relative reduction in CRC mortality 10 years after screening (predicted hazard ratios, with 95% percentile intervals: 0.56 [0.44, 0.71], 0.63 [0.51, 0.75], 0.68 [0.53, 0.83]; estimated with 95% confidence interval: 0.56 [0.45, 0.69]). Two models with longer average preclinical duration accurately predicted the relative reduction in 10-year CRC incidence. Two models with longer mean sojourn time accurately predicted the number of screen-detected cancers. All 3 models predicted too many proximal adenomas among patients referred to colonoscopy. Model accuracy can only be established through external validation. Analyses such as these are therefore essential for any decision model. Results supported the assumptions that the average time from adenoma initiation to development of preclinical cancer is long (up to 25 years), and mean sojourn time is close to 4 years, suggesting the window for early detection and intervention by screening is relatively long. Variation in dwell time remains uncertain and could have important clinical and policy implications. © The Author(s) 2016.

Real-World Data on Prognostic Factors for Overall Survival in EGFR Mutation-Positive Advanced Non-Small Cell Lung Cancer Patients Treated with First-Line Gefitinib.

PubMed

Yao, Zong-Han; Liao, Wei-Yu; Ho, Chao-Chi; Chen, Kuan-Yu; Shih, Jin-Yuan; Chen, Jin-Shing; Lin, Zhong-Zhe; Lin, Chia-Chi; Chih-Hsin Yang, James; Yu, Chong-Jen

2017-09-01

This study aimed to identify independent prognostic factors for overall survival (OS) of patients with advanced non-small cell lung cancer (NSCLC) harboring an activating epidermal growth factor receptor (EGFR) mutation and receiving gefitinib as first-line treatment in real-world practice. We enrolled 226 patients from June 2011 to May 2013. During this period, gefitinib was the only EGFR-tyrosine kinase inhibitor reimbursed by the Bureau of National Health Insurance of Taiwan. The median progression-free survival and median OS were 11.9 months (95% confidence interval [CI]: 9.7-14.2) and 26.9 months (21.2-32.5), respectively. The Cox proportional hazards regression model revealed that postoperative recurrence, performance status (Eastern Cooperative Oncology Grade [ECOG] ≥2), smoking index (≥20 pack-years), liver metastasis at initial diagnosis, and chronic hepatitis C virus (HCV) infection were independent prognostic factors for OS (hazard ratio [95% CI] 0.3 [0.11-0.83], p  = .02; 2.69 [1.60-4.51], p  < .001; 1.92 [1.24-2.97], p  = .003; 2.26 [1.34-3.82], p  = .002; 3.38 [1.85-7.78], p  < .001, respectively). However, brain metastasis (BM) at initial diagnosis or intracranial progression during gefitinib treatment had no impact on OS (1.266 [0.83-1.93], p  = .275 and 0.75 [0.48-1.19], p  = .211, respectively). HCV infection, performance status (ECOG ≥2), newly diagnosed advanced NSCLC without prior operation, and liver metastasis predicted poor OS in EGFR mutation-positive advanced NSCLC patients treated with first-line gefitinib; however, neither BM at initial diagnosis nor intracranial progression during gefitinib treatment had an impact on OS. The finding that chronic hepatitis C virus (HCV) infection might predict poor overall survival (OS) in epidermal growth factor receptor mutation-positive advanced non-small cell lung cancer (NSCLC) patients treated with first-line gefitinib may raise awareness of benefit from anti-HCV treatment in this patient population. Brain metastasis in the initial diagnosis or intracranial progression during gefitinib treatment is not a prognostic factor for OS. This study, which enrolled a real-world population of NSCLC patients, including sicker patients who were not eligible for a clinical trial, may have impact on guiding usual clinical practice. © AlphaMed Press 2017.

What Happens in Session Doesn't Stay in Session: Changes within Exposures Predict Subsequent Improvement and Dropout

PubMed Central

Norton, Peter J.; Hayes-Skelton, Sarah A.; Klenck, Suzanne C.

2011-01-01

Previous exposure therapy research has suggested potential differences in emotional processing at different points in treatment (Hayes, Hope, & Heimberg, 2008). For example, indicators of emotional processing may be more related to outcome during the later exposure sessions than during the initial session. This is consistent with a growing body of psychotherapy research highlighting the importance of timing and change processes across therapy. The current study examined whether the learning-but-not-benefiting hypothesis is observed in a group based intervention for clients with a range of anxiety disorders. It was hypothesized that activation and within session habituation during later, but not the initial exposure session, would be related to outcome, whereas activation and within session habituation during the first session would be related to dropout status. Results revealed that lower activation and less habituation during the first exposure was associated with increased treatment discontinuation. Second, lower peak and, to a lesser extent greater activation and habituation, during exposures were generally associated with better treatment outcomes. These findings highlight the importance of examining the complexities and timing of the exposure process. PMID:21419597

Vocal fold pseudocyst: results of 46 cases undergoing a uniform treatment algorithm.

PubMed

Estes, Christine; Sulica, Lucian

2014-05-01

To describe treatment results and identify predictors of the need for surgical intervention in patients with vocal fold pseudocyst. Retrospective cohort study with longitudinal followup via survey. Clinical records were reviewed for demographic information, VHI-10 score, and degree of severity of dysphonia. Videostroboscopic examinations were evaluated for presence of vocal fold pseudocyst, along with additional clinical variables, including laterality, reactive lesion, paresis, varix, and hemorrhage. Follow-up surveys were sent to all participants to evaluate current VHI-10 score and degree of vocal limitation. Results were analyzed to determine predictors of surgery and recurrence of pathology. Forty-six patients (41F:5M) with pseudocyst (40 unilateral: 6 bilateral) were reviewed. Twenty-three (50%) had reactive lesions, nineteen (41%) had paresis by clinical criteria, 10 (22%) had varices, and 6 (13%) had hemorrhage on examination. All underwent initial behavioral management (2-12 sessions of voice therapy; mean of 8 sessions). Seventeen (37%) eventually required surgical intervention. No demographic or clinical variables proved predictive of surgical intervention. Follow-up surveys were completed by 63% of patients, and 79% agreed with the statement that they were not professionally limited by their voices. This experience supports behavioral management as an initial intervention in patients with pseudocyst, sufficient by itself to restore vocal function in approximately two out of three patients. Neither initial severity nor any of the studied clinical findings predicted the need for surgery. The large majority of patients with pseudocyst are able to be treated effectively without impact in their professional function. © 2013 The American Laryngological, Rhinological and Otological Society, Inc.

Initiation of growth hormone therapy in idiopathic short stature: do gender differences exist?

PubMed

Ben-Ari, Tal; Lebenthal, Yael; Phillip, Moshe; Lazar, Liora

2015-01-01

Growth hormone (GH) registries indicate that boys receive preferential GH treatment for idiopathic short stature (ISS). The aim was to determine whether age, auxological parameters, pubertal status, and target height differ between genders at GH initiation. Review of the computerized files of the endocrine department of a tertiary pediatric medical center identified 184 patients who started GH therapy for ISS between 2003-2011. Data on auxologic parameters, predicted height, parental height, and pubertal status were collected and compared between boys and girls. Boys accounted for a significantly higher percentage of the study group (65.8%, p<0.001). At onset of GH therapy, there were no significant differences between boys and girls in age (10.2±3.1 vs. 9.9±2.4 years), height-standard deviation score (SDS) (-2.64±0.5 vs. -2.79±0.5), body mass index-SDS[(-0.65±1.01) vs. (-0.80±1.13)], or pubertal status (66% vs. 63.5% prepubertal). Predicted height-SDS was significantly higher in boys (-1.95±1.05 vs. -2.56±0.73, p<0.001). Midparental height-SDS was similar in the two groups, as were paternal and maternal height. The similar age, height deficit, and pubertal status at onset of GH treatment in boys and girls suggests that gender differences do not exist. Male predominance may stem from family preferences to treat boys. Future studies are warranted to assess the psychosocial aspects in the decision to initiate therapy.

Results of intraoperative electron beam radiotherapy containing multimodality treatment for locally unresectable T4 rectal cancer: a pooled analysis of the Mayo Clinic Rochester and Catharina Hospital Eindhoven

PubMed Central

Holman, Fabian A.; Haddock, Michael G.; Gunderson, Leonard L.; Kusters, Miranda; Nieuwenhuijzen, Grard A. P.; van den Berg, Hetty A.; Nelson, Heidi

2016-01-01

Background The aim of this study is to analyse the pooled results of intraoperative electron beam radiotherapy (IOERT) containing multimodality treatment of locally advanced T4 rectal cancer, initially unresectable for cure, from the Mayo Clinic, Rochester, USA (MCR) and Catharina Hospital, Eindhoven, The Netherlands (CHE), both major referral centers for locally advanced rectal cancer. A rectal tumor is called locally unresectable for cure if after full clinical work-up infiltration into the surrounding structures or organs has been demonstrated, which would result in positive surgical margins if resection was the initial component of treatment. This was the reason to refer these patients to the IOERT program of one of the centers. Methods In the period from 1981 to 2010, 417 patients with locally unresectable T4 rectal carcinomas at initial presentation were treated with multimodality treatment including IOERT at either one of the two centres. The preferred treatment approach was preoperative (chemo) radiation and intended radical surgery combined with IOERT. Risk factors for local recurrence (LR), cancer specific survival, disease free survival and distant metastases (DM) were assessed. Results A total of 306 patients (73%) underwent a R0 resection. LRs and metastases occurred more frequently after an R1-2 resection (P<0.001 and P<0.001 respectively). Preoperative chemoradiation (preop CRT) was associated with a higher probability of having a R0 resection. Waiting time after preoperative treatment was inversely related with the chance of developing a LR, especially after R+ resection. In 16% of all cases a LR developed. Five-year disease free survival and overall survival (OS) were 55% and 56% respectively. Conclusions An acceptable survival can be achieved in treatment of patients with initially unresectable T4 rectal cancer with combined modality therapy that includes preop CRT and IOERT. Completeness of the resection is the most important predictive and prognostic factor in the treatment of T4 rectal cancer for all outcome parameters. IOERT can reduce the LR rate effectively, especially in R+ resected patients. PMID:28078113

Predicting the Initial Lapse Using a Mobile Health Application after Alcohol Detoxification

ERIC Educational Resources Information Center

Chih, Ming-Yuan

2013-01-01

The prediction and prevention of the initial lapse--which is defined as the first lapse after a period of abstinence--is important because the initial lapse often leads to subsequent lapses (within the same lapse episode) or relapse. The prediction of the initial lapse may allow preemptive intervention to be possible. This dissertation reports on…

Recurrence of CMV Infection and the Effect of Prolonged Antivirals in Organ Transplant Recipients.

PubMed

Natori, Yoichiro; Humar, Atul; Husain, Shahid; Rotstein, Coleman; Renner, Eberhard; Singer, Lianne; Kim, S Joseph; Kumar, Deepali

2017-06-01

Although initial therapy for cytomegalovirus (CMV) is usually successful, a significant subset of patients may have recurrent viremia. However, the epidemiology and risk factors for recurrence have not been fully defined, as well as the utility of prolonged antivirals after initial clearance. Solid organ transplant patients with first episode of CMV disease or asymptomatic viremia (≥1000 IU/mL) requiring treatment were identified by chart review. Clinical and virologic data were collected. The primary outcome was recurrence of CMV viremia or disease within 6 months of treatment discontinuation. The first episode of CMV viremia requiring antiviral therapy was assessed in 282 patients (147 CMV disease and 135 asymptomatic viremia). Cytomegalovirus occurred at 5.6 (0.63-27.7) months posttransplant. Recurrent CMV occurred in 30.5% patients at a median of 51 (0-160) days after discontinuation of therapy. Factors predictive of recurrence were treatment phase viral kinetics (P = 0.005), lung transplant (P = 0.002), CMV donor (D)+/recipient (R)- serostatus(P = 0.04) and recent acute rejection(P = 0.02). Prolonged antiviral therapy was given to 226 (80.1%) of 282 patients. Recurrence occurred in 73 (32.3%) of 226 patients that received prolonged antivirals versus 13 (23.2%) of 56 in those with no prolonged antivirals (P = 0.19). Recurrent CMV occurs in a significant percentage of patients after treatment of the first episode of CMV viremia/disease. CMV D+/R- serostatus, lung transplant, and treatment phase viral kinetics were significant predictors of recurrence. Continuation of prolonged antivirals beyond initial clearance was not associated with a reduced risk of recurrence.

Baseline predictors of persistence to first disease-modifying treatment in multiple sclerosis.

PubMed

Zettl, U K; Schreiber, H; Bauer-Steinhusen, U; Glaser, T; Hechenbichler, K; Hecker, M

2017-08-01

Patients with multiple sclerosis (MS) require lifelong therapy. However, success of disease-modifying therapies is dependent on patients' persistence and adherence to treatment schedules. In the setting of a large multicenter observational study, we aimed at assessing multiple parameters for their predictive power with respect to discontinuation of therapy. We analyzed 13 parameters to predict discontinuation of interferon beta-1b treatment during a 2-year follow-up period based on data from 395 patients with MS who were treatment-naïve at study onset. Besides clinical characteristics, patient-related psychosocial outcomes were assessed as well. Among patients without clinically relevant fatigue, males showed a higher persistence rate than females (80.3% vs 64.7%). Clinically relevant fatigue scores decreased the persistence rate in men and especially in women (71.4% and 51.2%). Besides gender and fatigue, univariable and multivariable analyses revealed further factors associated with interferon beta-1b therapy discontinuation, namely lower quality of life, depressiveness, and higher relapse rate before therapy initiation, while higher education, living without a partner, and higher age improved persistence. Patients with higher grades of fatigue and depressiveness are at higher risk to prematurely discontinue MS treatment; especially, women suffering from fatigue have an increased discontinuation rate. © 2016 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

[Surgical treatment of secondary peritonitis: A continuing problem. German version].

PubMed

van Ruler, O; Boermeester, M A

2016-01-01

Secondary peritonitis remains associated with high mortality and morbidity rates. Treatment of secondary peritonitis is still challenging even in the era of modern medicine. Surgical intervention for source control remains the cornerstone of treatment besides adequate antimicrobial therapy and when necessary intensive medical care measures and resuscitation. A randomized clinical trial showed that relaparotomy on demand (ROD) after initial emergency surgery was the preferred treatment strategy, irrespective of the severity and extent of peritonitis. The effective and safe use of ROD requires intensive monitoring of the patient in a setting where diagnostic tests and decision making about relaparotomy are guaranteed round the clock. The lack of knowledge on timely and adequate patient selection, together with the lack of use of easy but reliable monitoring tools seem to hamper full implementation of ROD. The accuracy of the relaparotomy decision tool is reasonable for prediction of the formation of peritonitis and necessary selection of patients for computed tomography (CT). The value of CT in the early postoperative phase is unclear. Future research and innovative technologies should focus on the additive value of CT after surgical treatment for secondary peritonitis and on the further optimization of bedside prediction tools to enhance adequate patient selection for interventions in a multidisciplinary setting.

Circulating complexes between tumour necrosis factor-alpha and etanercept predict long-term efficacy of etanercept in juvenile idiopathic arthritis.

PubMed

Kahn, Robin; Berthold, Elisabet; Gullstrand, Birgitta; Schmidt, Tobias; Kahn, Fredrik; Geborek, Pierre; Saxne, Tore; Bengtsson, Anders A; Månsson, Bengt

2016-04-01

The relationship between tumour necrosis factor-alpha (TNF-α) and drug survival had not been studied in juvenile idiopathic arthritis (JIA), and there were no laboratory tests to predict the long-term efficacy of biological drugs for JIA. We studied whether serum levels of TNF-α, free or bound to etanercept, could predict long-term efficacy of etanercept in children with JIA. We included 41 biologic-naïve patients with JIA who started treatment with etanercept at Skåne University Hospital between 1999 and 2010. Serum taken at the start of treatment and at the six-week follow-up were analysed for TNF-α and the long-term efficacy of etanercept was assessed using the drug survival time. Levels of TNF-α increased significantly at the six-week follow-up, and this was almost exclusively comprised of TNF-α in complex with etanercept. The increase in TNF-α showed a dose-dependent correlation to long-term drug survival (p < 0.01). Increasing levels of circulating TNF-α at treatment initiation predicted long-term efficacy of etanercept in children with JIA, which may have been due to different pathophysiological mechanisms of inflammation. Our result may provide a helpful clinical tool, as high levels of circulating TNF-α/etanercept complexes could be used as a marker for the long-term efficacy of etanercept. ©2015 The Authors. Acta Paediatrica published by John Wiley & Sons Ltd on behalf of Foundation Acta Paediatrica.

Inferring diagnosis and trajectory of wet age-related macular degeneration from OCT imagery of retina

NASA Astrophysics Data System (ADS)

Irvine, John M.; Ghadar, Nastaran; Duncan, Steve; Floyd, David; O'Dowd, David; Lin, Kristie; Chang, Tom

2017-03-01

Quantitative biomarkers for assessing the presence, severity, and progression of age-related macular degeneration (AMD) would benefit research, diagnosis, and treatment. This paper explores development of quantitative biomarkers derived from OCT imagery of the retina. OCT images for approximately 75 patients with Wet AMD, Dry AMD, and no AMD (healthy eyes) were analyzed to identify image features indicative of the patients' conditions. OCT image features provide a statistical characterization of the retina. Healthy eyes exhibit a layered structure, whereas chaotic patterns indicate the deterioration associated with AMD. Our approach uses wavelet and Frangi filtering, combined with statistical features that do not rely on image segmentation, to assess patient conditions. Classification analysis indicates clear separability of Wet AMD from other conditions, including Dry AMD and healthy retinas. The probability of correct classification of was 95.7%, as determined from cross validation. Similar classification analysis predicts the response of Wet AMD patients to treatment, as measured by the Best Corrected Visual Acuity (BCVA). A statistical model predicts BCVA from the imagery features with R2 = 0.846. Initial analysis of OCT imagery indicates that imagery-derived features can provide useful biomarkers for characterization and quantification of AMD: Accurate assessment of Wet AMD compared to other conditions; image-based prediction of outcome for Wet AMD treatment; and features derived from the OCT imagery accurately predict BCVA; unlike many methods in the literature, our techniques do not rely on segmentation of the OCT image. Next steps include larger scale testing and validation.

Personalized Circulating Tumor DNA Biomarkers Dynamically Predict Treatment Response and Survival In Gynecologic Cancers.

PubMed

Pereira, Elena; Camacho-Vanegas, Olga; Anand, Sanya; Sebra, Robert; Catalina Camacho, Sandra; Garnar-Wortzel, Leopold; Nair, Navya; Moshier, Erin; Wooten, Melissa; Uzilov, Andrew; Chen, Rong; Prasad-Hayes, Monica; Zakashansky, Konstantin; Beddoe, Ann Marie; Schadt, Eric; Dottino, Peter; Martignetti, John A

2015-01-01

High-grade serous ovarian and endometrial cancers are the most lethal female reproductive tract malignancies worldwide. In part, failure to treat these two aggressive cancers successfully centers on the fact that while the majority of patients are diagnosed based on current surveillance strategies as having a complete clinical response to their primary therapy, nearly half will develop disease recurrence within 18 months and the majority will die from disease recurrence within 5 years. Moreover, no currently used biomarkers or imaging studies can predict outcome following initial treatment. Circulating tumor DNA (ctDNA) represents a theoretically powerful biomarker for detecting otherwise occult disease. We therefore explored the use of personalized ctDNA markers as both a surveillance and prognostic biomarker in gynecologic cancers and compared this to current FDA-approved surveillance tools. Tumor and serum samples were collected at time of surgery and then throughout treatment course for 44 patients with gynecologic cancers, representing 22 ovarian cancer cases, 17 uterine cancer cases, one peritoneal, three fallopian tube, and one patient with synchronous fallopian tube and uterine cancer. Patient/tumor-specific mutations were identified using whole-exome and targeted gene sequencing and ctDNA levels quantified using droplet digital PCR. CtDNA was detected in 93.8% of patients for whom probes were designed and levels were highly correlated with CA-125 serum and computed tomography (CT) scanning results. In six patients, ctDNA detected the presence of cancer even when CT scanning was negative and, on average, had a predictive lead time of seven months over CT imaging. Most notably, undetectable levels of ctDNA at six months following initial treatment was associated with markedly improved progression free and overall survival. Detection of residual disease in gynecologic, and indeed all cancers, represents a diagnostic dilemma and a potential critical inflection point in precision medicine. This study suggests that the use of personalized ctDNA biomarkers in gynecologic cancers can identify the presence of residual tumor while also more dynamically predicting response to treatment relative to currently used serum and imaging studies. Of particular interest, ctDNA was an independent predictor of survival in patients with ovarian and endometrial cancers. Earlier recognition of disease persistence and/or recurrence and the ability to stratify into better and worse outcome groups through ctDNA surveillance may open the window for improved survival and quality and life in these cancers.

Association between Platelet Counts before and during Pharmacological Therapy for Patent Ductus Arteriosus and Treatment Failure in Preterm Infants.

PubMed

Sallmon, Hannes; Weber, Sven C; Dirks, Juliane; Schiffer, Tamara; Klippstein, Tamara; Stein, Anja; Felderhoff-Müser, Ursula; Metze, Boris; Hansmann, Georg; Bührer, Christoph; Cremer, Malte; Koehne, Petra

2018-01-01

The role of platelets for mediating closure of the ductus arteriosus in human preterm infants is controversial. Especially, the effect of low platelet counts on pharmacological treatment failure is still unclear. In this retrospective study of 471 preterm infants [<1,500 g birth weight (BW)], who were treated for a patent ductus arteriosus (PDA) with indomethacin or ibuprofen, we investigated whether platelet counts before or during pharmacological treatment had an impact on the successful closure of a hemodynamically significant PDA. The effects of other factors, such as sepsis, preeclampsia, gestational age, BW, and gender, were also evaluated. Platelet counts before initiation of pharmacological PDA treatment did not differ between infants with later treatment success or failure. However, we found significant associations between low platelet counts during pharmacological PDA therapy and treatment failure ( p  < 0.05). Receiver operating characteristic (ROC) curve analysis showed that platelet counts after the first, and before and after the second cyclooxygenase inhibitor (COXI) cycle were significantly associated with treatment failure (area under the curve of >0.6). However, ROC curve analysis did not reveal a specific platelet cutoff-value that could predict PDA treatment failure. Multivariate logistic regression analysis showed that lower platelet counts, a lower BW, and preeclampsia were independently associated with COXI treatment failure. We provide further evidence for an association between low platelet counts during pharmacological therapy for symptomatic PDA and treatment failure, while platelet counts before initiation of therapy did not affect treatment outcome.

Accumulating Data to Optimally Predict Obesity Treatment (ADOPT) Core Measures: Psychosocial Domain.

PubMed

Sutin, Angelina R; Boutelle, Kerri; Czajkowski, Susan M; Epel, Elissa S; Green, Paige A; Hunter, Christine M; Rice, Elise L; Williams, David M; Young-Hyman, Deborah; Rothman, Alexander J

2018-04-01

Within the Accumulating Data to Optimally Predict obesity Treatment (ADOPT) Core Measures Project, the psychosocial domain addresses how psychosocial processes underlie the influence of obesity treatment strategies on weight loss and weight maintenance. The subgroup for the psychosocial domain identified an initial list of high-priority constructs and measures that ranged from relatively stable characteristics about the person (cognitive function, personality) to dynamic characteristics that may change over time (motivation, affect). This paper describes (a) how the psychosocial domain fits into the broader model of weight loss and weight maintenance as conceptualized by ADOPT; (b) the guiding principles used to select constructs and measures for recommendation; (c) the high-priority constructs recommended for inclusion; (d) domain-specific issues for advancing the science; and (e) recommendations for future research. The inclusion of similar measures across trials will help to better identify how psychosocial factors mediate and moderate the weight loss and weight maintenance process, facilitate research into dynamic interactions with factors in the other ADOPT domains, and ultimately improve the design and delivery of effective interventions. © 2018 The Obesity Society.

Studying and Treating Schizophrenia Using Virtual Reality: A New Paradigm

PubMed Central

Freeman, Daniel

2008-01-01

Understanding schizophrenia requires consideration of patients’ interactions in the social world. Misinterpretation of other peoples’ behavior is a key feature of persecutory ideation. The occurrence and intensity of hallucinations is affected by the social context. Negative symptoms such as anhedonia, asociality, and blunted affect reflect difficulties in social interactions. Withdrawal and avoidance of other people is frequent in schizophrenia, leading to isolation and rumination. The use of virtual reality (VR)—interactive immersive computer environments—allows one of the key variables in understanding psychosis, social environments, to be controlled, providing exciting applications to research and treatment. Seven applications of virtual social environments to schizophrenia are set out: symptom assessment, identification of symptom markers, establishment of predictive factors, tests of putative causal factors, investigation of the differential prediction of symptoms, determination of toxic elements in the environment, and development of treatment. The initial VR studies of persecutory ideation, which illustrate the ascription of personalities and mental states to virtual people, are highlighted. VR, suitably applied, holds great promise in furthering the understanding and treatment of psychosis. PMID:18375568

Protective resources and long-term recovery from alcohol use disorders.

PubMed

Moos, Rudolf H; Moos, Bernice S

2007-01-05

This study examined indices of personal and social resources drawn from social learning, behavioral economics, and social control theories as predictors of medium- and long-term alcohol use disorder outcomes. Individuals (N = 461) who initiated help-seeking for alcohol-related problems were surveyed at baseline and 1, 3, 8, and 16 years later. At baseline and each follow-up, participants provided information about their personal and social resources and alcohol-related and psychosocial functioning. In general, protective resources associated with social learning (self-efficacy and approach coping), behavioral economics (health and financial resources and resources associated with Alcoholics Anonymous), and social control theory (bonding with family members, friends, and coworkers) predicted better alcohol-related and psychosocial outcomes. A summary index of protective resources associated with all three theories significantly predicted remission. Protective resources strengthened the positive influence of treatment on short-term remission and partially mediated the association between treatment and remission. Application of social learning, behavior economic, and social control theories may help to identify predictors of remission and thus to allocate treatment more efficiently.

Treatment Outcomes for Extensively Drug-Resistant Tuberculosis and HIV Co-infection

PubMed Central

Padayatchi, Nesri; Kvasnovsky, Charlotte; Werner, Lise; Master, Iqbal; Horsburgh, C. Robert

2013-01-01

High mortality rates have been reported for patients co-infected with extensively drug-resistant tuberculosis (XDR-TB) and HIV, but treatment outcomes have not been reported. We report treatment outcomes for adult XDR TB patients in KwaZulu-Natal Province, South Africa. Initial data were obtained retrospectively, and outcomes were obtained prospectively during 24 months of treatment. A total of 114 XDR TB patients were treated (median 6 drugs, range 3–9 drugs); 82 (73%) were HIV positive and 50 (61%) were receiving antiretroviral therapy. After receiving treatment for 24 months, 48 (42%) of 114 patients died, 25 (22%) were cured or successfully completed treatment, 19 (17%) withdrew from the study, and 22 (19%) showed treatment failure. A higher number of deaths occurred among HIV-positive patients not receiving antiretroviral therapy and among patients who did not show sputum culture conversion. Culture conversion was a major predictor of survival but was poorly predictive (51%) of successful treatment outcome. PMID:23622055

Cost-effectiveness of Apixaban Versus Other Oral Anticoagulants for the Initial Treatment of Venous Thromboembolism and Prevention of Recurrence.

PubMed

Lanitis, Tereza; Leipold, Robert; Hamilton, Melissa; Rublee, Dale; Quon, Peter; Browne, Chantelle; Cohen, Alexander T

2016-03-01

To assess the cost-effectiveness of apixaban versus rivaroxaban, low-molecular-weight heparin (LMWH)/dabigatran, and LMWH/vitamin K antagonist (VKA) for the initial treatment and prevention of recurrent thromboembolic events in patients with venous thromboembolism (VTE). A Markov model was developed to evaluate the pharmacoeconomic effect of 6 months of treatment with apixaban versus other anticoagulants over a lifetime horizon. Network meta-analyses were conducted using the results of the Apixaban after the Initial Management of Pulmonary Embolism and Deep Vein Thrombosis with First-Line Therapy (AMPLIFY), EINSTEIN-pooled, and RE-COVER I and II trials for the following end points: recurrent VTE, major bleeds, clinically relevant non-major bleeds, and treatment discontinuations. The analysis was conducted from the perspective of the United Kingdom National Health Service. The outcomes evaluated were the number of events avoided in a 1000-patient cohort, total costs, life years, quality-adjusted life years (QALYs), and cost per QALY gained over a patient's lifetime. Treatment for 6 months with apixaban was projected to result in fewer recurrent VTE and bleeding events in comparison to rivaroxaban, LMWH/dabigatran, and LMWH/VKA. Apixaban was cost-effective compared with LMWH/VKA at an incremental cost-effectiveness ratio of £2520 per QALY gained and was a dominant (ie, lower costs and higher QALYs) alternative to either rivaroxaban or LMWH/dabigatran. Sensitivity analysis indicated that results were robust over a wide range of inputs. The assessment of the effects and costs of apixaban in this study predicted that apixaban is a dominant alternative to rivaroxaban and LMWH/dabigatran and a cost-effective alternative to LMWH/VKA for 6 months of treatment of VTE and the prevention of recurrence. Copyright © 2016 Elsevier HS Journals, Inc. All rights reserved.

Predictors of pharmacological treatment outcomes with atomoxetine or methylphenidate in patients with attention-deficit/hyperactivity disorder from China, Egypt, Lebanon, Russian Federation, Taiwan, and United Arab Emirates.

PubMed

Treuer, T; Feng, Q; Desaiah, D; Altin, M; Wu, S; El-Shafei, A; Serebryakova, E; Gado, M; Faries, D

2014-09-01

The reduced availability of data from non-Western countries limits our ability to understand attention-deficit/hyperactivity disorder (ADHD) treatment outcomes, specifically, adherence and persistence of ADHD in children and adolescents. This analysis assessed predictors of treatment outcomes in a non-Western cohort of patients with ADHD treated with atomoxetine or methylphenidate. Data from a 12-month, prospective, observational study in outpatients aged 6-17 years treated with atomoxetine (N = 234) or methylphenidate (N = 221) were analysed post hoc to determine potential predictors of treatment outcomes. Participating countries included the Russian Federation, China, Taiwan, Egypt, United Arab Emirates and Lebanon. Factors associated with remission were analysed with stepwise multiple logistic regression and classification and regression trees (CART). Cox proportional hazards models with propensity score adjustment assessed differences in atomoxetine persistence among initial-dose cohorts. In patients treated with atomoxetine who had available dosing information (N = 134), Cox proportional hazards revealed lower (< 0.5 mg/kg) initial dose was significantly associated with shorter medication persistence (p < 0.01). multiple logistic regression analysis revealed greater rates of remission for atomoxetine-treated patients were associated with age (older), country (United Arab Emirates) and gender (female) (all p < 0.05). CART analysis confirmed older age and lack of specific phobias were associated with greater remission rates. For methylphenidate, greater baseline weight (highly correlated with the age factor found for atomoxetine) and prior atomoxetine use were associated with greater remission rates. These findings may help clinicians assess factors upon initiation of ADHD treatment to improve course prediction, proper dosing and treatment adherence and persistence. Observational study, therefore no registration. © 2014 John Wiley & Sons Ltd.

Waveform analysis-guided treatment versus a standard shock-first protocol for the treatment of out-of-hospital cardiac arrest presenting in ventricular fibrillation: results of an international randomized, controlled trial.

PubMed

Freese, John P; Jorgenson, Dawn B; Liu, Ping-Yu; Innes, Jennifer; Matallana, Luis; Nammi, Krishnakant; Donohoe, Rachael T; Whitbread, Mark; Silverman, Robert A; Prezant, David J

2013-08-27

Ventricular fibrillation (VF) waveform properties have been shown to predict defibrillation success and outcomes among patients treated with immediate defibrillation. We postulated that a waveform analysis algorithm could be used to identify VF unlikely to respond to immediate defibrillation, allowing selective initial treatment with cardiopulmonary resuscitation in an effort to improve overall survival. In a multicenter, double-blind, randomized study, out-of-hospital cardiac arrest patients in 2 urban emergency medical services systems were treated with automated external defibrillators using either a VF waveform analysis algorithm or the standard shock-first protocol. The VF waveform analysis used a predefined threshold value below which return of spontaneous circulation (ROSC) was unlikely with immediate defibrillation, allowing selective treatment with a 2-minute interval of cardiopulmonary resuscitation before initial defibrillation. The primary end point was survival to hospital discharge. Secondary end points included ROSC, sustained ROSC, and survival to hospital admission. Of 6738 patients enrolled, 987 patients with VF of primary cardiac origin were included in the primary analysis. No immediate or long-term survival benefit was noted for either treatment algorithm (ROSC, 42.5% versus 41.2%, P=0.70; sustained ROSC, 32.4% versus 33.4%, P=0.79; survival to admission, 34.1% versus 36.4%, P=0.46; survival to hospital discharge, 15.6% versus 17.2%, P=0.55, respectively). Use of a waveform analysis algorithm to guide the initial treatment of out-of-hospital cardiac arrest patients presenting in VF did not improve overall survival compared with a standard shock-first protocol. Further study is recommended to examine the role of waveform analysis for the guided management of VF.

Evaluation of Potential Continuation Rules for Mepolizumab Treatment of Severe Eosinophilic Asthma.

PubMed

Gunsoy, Necdet B; Cockle, Sarah M; Yancey, Steven W; Keene, Oliver N; Bradford, Eric S; Albers, Frank C; Pavord, Ian D

Mepolizumab significantly reduces exacerbations in patients with severe eosinophilic asthma. The early identification of patients likely to receive long-term benefit from treatment could ensure effective resource allocation. To assess potential continuation rules for mepolizumab in addition to initiation criteria defined as 2 or more exacerbations in the previous year and blood eosinophil counts of 150 cells/μL or more at initiation or 300 cells/μL or more in the previous year. This post hoc analysis included data from 2 randomized, double-blind, placebo-controlled studies (NCT01000506 and NCT01691521) of mepolizumab in patients with severe eosinophilic asthma (N = 1,192). Rules based on blood eosinophils, physician-rated response to treatment, FEV 1 , Asthma Control Questionnaire (ACQ-5) score, and exacerbation reduction were assessed at week 16. To assess these rules, 2 key metrics accounting for the effects observed in the placebo arm were developed. Patients not meeting continuation rules based on physician-rated response, FEV 1 , and the ACQ-5 score still derived long-term benefit from mepolizumab. Nearly all patients failing to reduce blood eosinophils had counts of 150 cells/μL or less at baseline. For exacerbations, assessment after 16 weeks was potentially premature for predicting future exacerbations. There was no evidence of a reliable physician-rated response, ACQ-5 score, or lung function-based continuation rule. The added value of changes in blood eosinophils at week 16 over baseline was marginal. Initiation criteria for mepolizumab treatment provide the best method for assessing patient benefit from mepolizumab treatment, and treatment continuation should be reviewed on the basis of a predefined reduction in long-term exacerbation frequency and/or oral corticosteroid dose. Copyright © 2017 The Authors. Published by Elsevier Inc. All rights reserved.

Gut Microbiome Function Predicts Response to Anti-integrin Biologic Therapy in Inflammatory Bowel Diseases.

PubMed

Ananthakrishnan, Ashwin N; Luo, Chengwei; Yajnik, Vijay; Khalili, Hamed; Garber, John J; Stevens, Betsy W; Cleland, Thomas; Xavier, Ramnik J

2017-05-10

The gut microbiome plays a central role in inflammatory bowel diseases (IBDs) pathogenesis and propagation. To determine whether the gut microbiome may predict responses to IBD therapy, we conducted a prospective study with Crohn's disease (CD) or ulcerative colitis (UC) patients initiating anti-integrin therapy (vedolizumab). Disease activity and stool metagenomes at baseline, and weeks 14, 30, and 54 after therapy initiation were assessed. Community α-diversity was significantly higher, and Roseburia inulinivorans and a Burkholderiales species were more abundant at baseline among CD patients achieving week 14 remission. Several significant associations were identified with microbial function; 13 pathways including branched chain amino acid synthesis were significantly enriched in baseline samples from CD patients achieving remission. A neural network algorithm, vedoNet, incorporating microbiome and clinical data, provided highest classifying power for clinical remission. We hypothesize that the trajectory of early microbiome changes may be a marker of response to IBD treatment. Copyright © 2017 Elsevier Inc. All rights reserved.

Combining medical informatics and bioinformatics toward tools for personalized medicine.

PubMed

Sarachan, B D; Simmons, M K; Subramanian, P; Temkin, J M

2003-01-01

Key bioinformatics and medical informatics research areas need to be identified to advance knowledge and understanding of disease risk factors and molecular disease pathology in the 21 st century toward new diagnoses, prognoses, and treatments. Three high-impact informatics areas are identified: predictive medicine (to identify significant correlations within clinical data using statistical and artificial intelligence methods), along with pathway informatics and cellular simulations (that combine biological knowledge with advanced informatics to elucidate molecular disease pathology). Initial predictive models have been developed for a pilot study in Huntington's disease. An initial bioinformatics platform has been developed for the reconstruction and analysis of pathways, and work has begun on pathway simulation. A bioinformatics research program has been established at GE Global Research Center as an important technology toward next generation medical diagnostics. We anticipate that 21 st century medical research will be a combination of informatics tools with traditional biology wet lab research, and that this will translate to increased use of informatics techniques in the clinic.

Model-based prediction of myelosuppression and recovery based on frequent neutrophil monitoring.

PubMed

Netterberg, Ida; Nielsen, Elisabet I; Friberg, Lena E; Karlsson, Mats O

2017-08-01

To investigate whether a more frequent monitoring of the absolute neutrophil counts (ANC) during myelosuppressive chemotherapy, together with model-based predictions, can improve therapy management, compared to the limited clinical monitoring typically applied today. Daily ANC in chemotherapy-treated cancer patients were simulated from a previously published population model describing docetaxel-induced myelosuppression. The simulated values were used to generate predictions of the individual ANC time-courses, given the myelosuppression model. The accuracy of the predicted ANC was evaluated under a range of conditions with reduced amount of ANC measurements. The predictions were most accurate when more data were available for generating the predictions and when making short forecasts. The inaccuracy of ANC predictions was highest around nadir, although a high sensitivity (≥90%) was demonstrated to forecast Grade 4 neutropenia before it occurred. The time for a patient to recover to baseline could be well forecasted 6 days (±1 day) before the typical value occurred on day 17. Daily monitoring of the ANC, together with model-based predictions, could improve anticancer drug treatment by identifying patients at risk for severe neutropenia and predicting when the next cycle could be initiated.

Psychopathology in methamphetamine-dependent adults 3 years after treatment.

PubMed

Glasner-Edwards, Suzette; Mooney, Larissa J; Marinelli-Casey, Patricia; Hillhouse, Maureen; Ang, Alfonso; Rawson, Richard A

2010-01-01

Although psychiatric symptoms are frequently observed in methamphetamine (MA) users, little is known about the prevalence of psychiatric disorders in MA-dependent individuals. This is the first study to examine the association of psychiatric disorders with substance use and psychosocial functioning in a large sample of MA users 3 years after treatment. We predicted that psychiatric diagnoses and severity would be associated with substance use and poorer overall functioning over the 3 year post-treatment course. Participants (N = 526) received psychosocial treatment for MA dependence as part of the Methamphetamine Treatment Project and were reassessed for psychosocial functioning and substance use at a mean of 3 years after treatment initiation. DSM-IV psychiatric diagnoses were assessed at follow-up using the Mini-International Neuropsychiatric Interview. Psychosocial functioning was assessed using the Addiction Severity Index. Overall, 48.1% of the sample met criteria for a current or past psychiatric disorder other than a substance use disorder. Consistent with prior reports from clinical samples of cocaine users, this rate was largely accounted for by mood disorders, anxiety disorders and antisocial personality. Those with an Axis I psychiatric disorder evidenced increased MA use and greater functional impairment over time relative to those without a psychiatric disorder. This initial investigation of psychiatric diagnoses in MA users after treatment indicates elevated rates of Axis I and II disorders in this population and underscores the need for integrated psychiatric assessment and intervention in drug abuse treatment settings.

Motives for sports participation as predictions of self-reported outcomes after anterior cruciate ligament injury of the knee.

PubMed

Roessler, K K; Andersen, T E; Lohmander, S; Roos, E M

2015-06-01

Aim of the study was to access how individual's motives for participation in sports impact on self-reported outcomes 2 years after an anterior cruciate ligament injury. Based on a longitudinal cohort study, this secondary analysis present data from the Knee Anterior Cruciate Ligament, Nonsurgical versus Surgical Treatment (KANON) study, a randomized controlled trial. At baseline, 121 patients recorded in an initial questionnaire that their motives for sports participation fell into four categories: achievement, health, social integration, or fun and well-being. These four categories were used as variables in the analyses. All 121 subjects completed the 2-year follow-up. The largest improvement was seen in the Knee Injury and Osteoarthritis Outcome Score (KOOS) subscale sports and recreation function, with an effect size of 2.43. KOOS sports and recreation function was also the subscale score best predicted by the motives for sports participation. Baseline motives achievement and fun and well-being predicted worse levels of pain and function 2 years after the injury, even after adjusting for age, gender, treatment and baseline scores. Psychological aspects, such as motives for participation in sport, can be factors in predicting of patient-reported outcomes 2 years after injury. Evaluating motives for sports participation may help predict the outcome 2 years after ACL injury. © 2014 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Growth in Temperament and Parenting as Predictors of Adjustment During Children’s Transition to Adolescence

PubMed Central

Lengua, Liliana J.

2014-01-01

The author examined relations among demographic risk (income, maternal education, single-parent status), growth in temperament (fear, irritability, effortful control), and parenting (rejection, inconsistent discipline) across 3 years and the prediction of children’s adjustment problems in a community sample (N = 190; ages 8–12 years at Time 1). Family income was related to higher initial levels of fear, irritability, rejection, and inconsistency and lower effortful control but was not related to changes in these variables. Higher initial rejection predicted increases in child fear and irritability. Higher initial fear predicted decreases in rejection and inconsistency. Higher initial irritability predicted increases in inconsistency, and higher initial effortful control predicted decreases in rejection. When growth of parenting and temperament were considered simultaneously, increases in effortful control and decreases in fear and irritability predicted lower Time 3 internalizing and externalizing problems. Increases in rejection and inconsistent discipline predicted higher Time 3 externalizing, although sometimes the effect appeared to be indirect through temperament. The findings suggest that temperament and parenting predict changes in each other and predict adjustment during the transition to adolescence. PMID:16953689

SWAB/NVALT (Dutch Working Party on Antibiotic Policy and Dutch Association of Chest Physicians) guidelines on the management of community-acquired pneumonia in adults.

PubMed

Wiersinga, W J; Bonten, M J; Boersma, W G; Jonkers, R E; Aleva, R M; Kullberg, B J; Schouten, J A; Degener, J E; Janknegt, R; Verheij, T J; Sachs, A P E; Prins, J M

2012-03-01

The Dutch Working Party on Antibiotic Policy (SWAB) and the Dutch Association of Chest Physicians (NVALT) convened a joint committee to develop evidence-based guidelines on the diagnosis and treatment of community acquired pneumonia (CAP). The guidelines are intended for adult patients with CAP who present at the hospital and are treated as outpatients as well as for hospitalised patients up to 72 hours after admission. Areas covered include current patterns of epidemiology and antibiotic resistance of causative agents of CAP in the Netherlands, the possibility to predict the causative agent of CAP on the basis of clinical data at first presentation, risk factors associated with specific pathogens, the importance of the severity of disease upon presentation for choice of initial treatment, the role of rapid diagnostic tests in treatment decisions, the optimal initial empiric treatment and treatment when a specific pathogen has been identified, the timeframe in which the first dose of antibiotics should be given, optimal duration of antibiotic treatment and antibiotic switch from the intravenous to the oral route. Additional recommendations are made on the role of radiological investigations in the diagnostic work-up of patients with a clinical suspicion of CAP, on the potential benefit of adjunctive immunotherapy, and on the policy for patients with parapneumonic effusions.

Moral dilemmas in neonatology as experienced by health care practitioners: a qualitative approach.

PubMed

van Zuuren, Florence J; van Manen, Eeke

2006-01-01

During the last two decades there has been an enormous development in treatment possibilities in the field of neonatology, particularly for (extremely) premature infants. Although there are cross-cultural differences in treatment strategy, an overview of the literature suggests that every country is confronted with moral dilemmas in this area. These concern decisions to initiate or withhold treatment directly at birth and, later on, decisions to withdraw treatment with the possible consequence that the child will die. Given that the neonate cannot express his or her own will, who will decide? And on the basis of what information, values and norms? We explored some of these issues in daily practice by interviewing a small sample of health care practitioners in a Dutch university Neonatal Intensive Care Unit (NICU). It turned out that experiencing moral dilemmas is part of their daily functioning. Nurses underline the suffering of the newborn, whereas physicians stress uncertainty in treatment outcome. To make the best of it, nurses focus on their caring task, whereas physicians hope that future follow-up research will lead to more predictable outcomes. As for their own offspring, part of these professionals would hesitate to bring their own extremely premature newborn to a NICU. For the most oppressing dilemma reported - terminating an already initiated treatment - we propose the concept of 'evidence shift' to clarify the ambiguous position of uncertainty in decision making.

KRAS and BRAF mutation analysis in metastatic colorectal cancer: a cost-effectiveness analysis from a Swiss perspective.

PubMed

Blank, Patricia R; Moch, Holger; Szucs, Thomas D; Schwenkglenks, Matthias

2011-10-01

Monoclonal antibodies against the epidermal growth factor receptor (EGFR), such as cetuximab, have led to significant clinical benefits for metastatic colorectal cancer (mCRC) patients but have also increased treatment costs considerably. Recent evidence associates KRAS and BRAF mutations with resistance to EGFR antibodies. We assessed the cost-effectiveness of predictive testing for KRAS and BRAF mutations, prior to cetuximab treatment of chemorefractory mCRC patients. A life-long Markov simulation model was used to estimate direct medical costs (€) and clinical effectiveness [quality-adjusted life-years (QALY)] of the following strategies: KRAS testing, KRAS testing with subsequent BRAF testing of KRAS wild-types (KRAS/BRAF), cetuximab treatment without testing. Comparison was against no cetuximab treatment (reference strategy). In the testing strategies, cetuximab treatment was initiated if no mutations were detected. Best supportive care was given to all patients. Survival times/utilities were derived from published randomized clinical trials. Costs were assessed from the perspective of the Swiss health system. Average remaining lifetime costs ranged from €3,983 (no cetuximab) to €38,662 (no testing). Cetuximab treatment guided by KRAS/BRAF achieved gains of 0.491 QALYs compared with the reference strategy. The KRAS testing strategy achieved an additional gain of 0.002 QALYs compared with KRAS/BRAF. KRAS/BRAF testing was the most cost-effective approach when compared with the reference strategy (incremental cost-effectiveness ratio: €62,653/QALY). New predictive tests for KRAS and BRAF status are currently being introduced in pathology. Despite substantial costs of predictive testing, it is economically favorable to identify patients with KRAS and BRAF wild-type status. ©2011 AACR

Identification of 7 Proteins in Sera of RA Patients with Potential to Predict ETA/MTX Treatment Response

PubMed Central

Obry, Antoine; Hardouin, Julie; Lequerré, Thierry; Jarnier, Frédérique; Boyer, Olivier; Fardellone, Patrice; Philippe, Peggy; Marcelli, Christian; Loët, Xavier Le; Vittecoq, Olivier; Cosette, Pascal

2015-01-01

Objective: The recent growth of innovating biologics has opened fascinating avenues for the management of patients. In rheumatoid arthritis, many biologics are currently available, the choice of which being mostly determined empirically. Importantly, a given biologic may not be active in a fraction of patients and may even provoke side effects. Here, we conducted a comparative proteomics study in attempt to identify a predictive theranostic signature of non-response in patients with rheumatoid arthritis treated by etanercept/methotrexate combination. Methods: A serum sample was collected prior to treatment exposure from a cohort of 22 patients with active RA. A proteomic “label free” approach was then designed to quantitate protein biomarkers using mass spectrometry. To verify these results, a relative quantification followed by an absolute quantification of interesting protein candidates were performed on a second cohort. The criterion of judgment was the response to etanercept/methotrexate combination according to the EULAR criteria assessed at 6 months of treatment. Results: These investigations led to the identification of a set of 12 biomarkers with capacity to predict treatment response. A targeted quantitative analysis allowed to confirm the potential of 7 proteins from the latter combination on a new cohort of 16 patients. Two highly discriminating proteins, PROS and CO7, were further evaluated by ELISA on this second cohort. By combining the concentration threshold of each protein associated to a right classification (responders vs non-responders), the sensitivity and specificity reached 88.9 % and 100 %, respectively. Conclusion: Prior to methotrexate/etanercept treatment, abundance of several sera proteins, notably PROS and CO7, were associated to response status of RA patients 6 month after treatment initiation. PMID:26379787

Ultrasonographic Changes at 12 Weeks of Anti-TNF Drugs Predict 1-year Sonographic Response and Clinical Outcome in Crohn's Disease: A Multicenter Study.

PubMed

Ripollés, Tomás; Paredes, José M; Martínez-Pérez, María J; Rimola, Jordi; Jauregui-Amezaga, Arantza; Bouzas, Rosa; Martin, Gregorio; Moreno-Osset, Eduardo

2016-10-01

The objective was to assess the long-term effect of biological treatment on transmural lesions of Crohn's disease evaluated with ultrasound, including contrast-enhanced ultrasound. Fifty-one patients with active Crohn's disease were included in a prospective multicenter longitudinal study. All patients underwent a clinical assessment and sonographic examination at baseline, 12 weeks after treatment initiation, and after 1-year of treatment. Patients were clinically followed at least 2 years from inclusion until the end of the study. Ultrasonographic evaluation included bowel wall thickness, color Doppler grade, parietal enhancement, and presence of transmural complications or stenosis. Sonographic changes after treatment were classified as normalization, improvement, or lack of response. Improvement at 52 weeks was more frequent in patients with improvement at final of induction (12 weeks) compared with patients who did not improve (85% versus 28%; P < 0.0001). One-year sonographic evolution correlated with clinical response; 28 of the 29 (96.5%) patients with sonographic improvement at 52 weeks showed clinical remission or response. Patients without sonographic improvement at 52 weeks of treatment were more likely to have a change or intensification in medication or surgery (13/20, 65%) during the next year of follow-up than patients with improvement on the sonography (3/28, 11%). Stricturing behavior was the only sonographic feature associated to a negative predictive value of response (P = 0.0001). Sonographic response after 12 weeks of therapy is more pronounced and predicts 1-year sonographic response. Sonographic response at 1-year examination correlates with 1-year clinical response and is a predictor of further treatment's efficacy, 1-year or longer period of follow-up.

Rapid response predicts 12-month post-treatment outcomes in binge-eating disorder: theoretical and clinical implications

PubMed Central

Grilo, C. M.; White, M. A.; Wilson, G. T.; Gueorguieva, R.; Masheb, R. M.

2011-01-01

Background We examined rapid response in obese patients with binge-eating disorder (BED) in a clinical trial testing cognitive behavioral therapy (CBT) and behavioral weight loss (BWL). Method Altogether, 90 participants were randomly assigned to CBT or BWL. Assessments were performed at baseline, throughout and post-treatment and at 6- and 12-month follow-ups. Rapid response, defined as ≥70% reduction in binge eating by week four, was determined by receiver operating characteristic curves and used to predict outcomes. Results Rapid response characterized 57% of participants (67% of CBT, 47% of BWL) and was unrelated to most baseline variables. Rapid response predicted greater improvements across outcomes but had different prognostic significance and distinct time courses for CBT versus BWL. Patients receiving CBT did comparably well regardless of rapid response in terms of reduced binge eating and eating disorder psychopathology but did not achieve weight loss. Among patients receiving BWL, those without rapid response failed to improve further. However, those with rapid response were significantly more likely to achieve binge-eating remission (62% v. 13%) and greater reductions in binge-eating frequency, eating disorder psychopathology and weight loss. Conclusions Rapid response to treatment in BED has prognostic significance through 12-month follow-up, provides evidence for treatment specificity and has clinical implications for stepped-care treatment models for BED. Rapid responders who receive BWL benefit in terms of both binge eating and short-term weight loss. Collectively, these findings suggest that BWL might be a candidate for initial intervention in stepped-care models with an evaluation of progress after 1 month to identify non-rapid responders who could be advised to consider a switch to a specialized treatment. PMID:21923964

Tumour necrosis factor-α/etanercept complexes in serum predict long-term efficacy of etanercept treatment in seronegative rheumatoid arthritis.

PubMed

Berthold, E; Månsson, B; Gullstrand, B; Geborek, P; Saxne, T; Bengtsson, A A; Kahn, R

2018-01-01

To study whether serum levels of tumour necrosis factor-α (TNF-α), free or bound to etanercept, in biological-naïve adults with rheumatoid arthritis (RA) could predict the long-term efficacy of etanercept, measured as drug survival. We identified 145 biological-naïve patients with RA starting treatment with etanercept at the Department of Rheumatology, Skåne University Hospital (1999-2008), of whom 16 had seronegative and 129 seropositive RA. TNF-α in serum was quantified using enzyme-linked immunosorbent assay in samples from the onset of treatment and at 6 week follow-up. Drug survival time was used to evaluate the long-term efficacy of etanercept. Levels of TNF-α were significantly increased at follow-up compared to at the start. At the 6 week follow-up, circulating TNF-α mainly comprised TNF-α in complex with etanercept. Longer drug survival time correlated with increased TNF-α at 6 week follow-up in the patients with seronegative RA, but not in the seropositive patients. We demonstrated that levels of circulating TNF-α increased in almost all individuals after initiation of treatment with etanercept and that this increase mainly comprised TNF-α in complex with etanercept. More importantly, this increase may predict drug survival in adults with seronegative, but not seropositive, RA and suggests that measuring TNF-α/etanercept complexes in serum may be relevant in patients with seronegative RA.

A new threshold of apparent diffusion coefficient values in white matter after successful tissue plasminogen activator treatment for acute brain ischemia.

PubMed

Sato, Atsushi; Shimizu, Yusaku; Koyama, Junichi; Hongo, Kazuhiro

2017-06-01

Tissue plasminogen activator (tPA) is effective for the treatment of acute brain ischemia, but may trigger fatal brain edema or hemorrhage if the brain ischemia results in a large infarct. Herein, we attempted to predict the extent of infarcts by determining the optimal threshold of ADC values on DWI that predictively distinguishes between infarct and reversible areas, and by reconstructing color-coded images based on this threshold. The study subjects consisted of 36 patients with acute brain ischemia in whom MRA had confirmed reopening of the occluded arteries in a short time (mean: 99min) after tPA treatment. We measured the apparetnt diffusion coefficient (ADC) values in several small regions of interest over the white matter within high-intensity areas on the initial diffusion weighted image (DWI); then, by comparing the findings to the follow-up images, we obtained the optimal threshold of ADC values using receiver-operating characteristic analysis. The threshold obtained (583×10 -6 m 2 /s) was lower than those previously reported; this threshold could distinguish between infarct and reversible areas with considerable accuracy (sensitivity: 0.87, specificity: 0.94). The threshold obtained and the reconstructed images were predictive of the final radiological result of tPA treatment, and this threshold may be helpful in determining the appropriate management of patients with acute brain ischemia. Copyright © 2017 Elsevier Masson SAS. All rights reserved.

Edge-to-edge repair for prevention and treatment of mitral valve systolic anterior motion.

PubMed

Myers, Patrick O; Khalpey, Zain; Maloney, Ann M; Brinster, Derek R; D'Ambra, Michael N; Cohn, Lawrence H

2013-10-01

The edge-to-edge technique has been proposed to prevent systolic anterior motion (SAM) of the mitral valve. There is limited clinical data available on outcomes of this technique for this indication. We reviewed the midterm results of this technique for SAM prevention and treatment. A total of 2226 patients had mitral valve repair between 2000 and 2011, 1148 of which were for myxomatous mitral regurgitation. Beginning in 2000, predictability of postrepair SAM based on the prebypass, intraoperative transesophageal echocardiogram arose in our program. The edge-to-edge technique was used in 65 patients (5.7%) for SAM management, in 53 patients preemptively for transesophageal echocardiogram-based SAM prediction, and in 12 patients for postrepair SAM treatment. There was no operative mortality. Postoperative mitral regurgitation was significantly improved in all patients compared with the preoperative grade (P < .001). SAM was completely eliminated, the mean mitral regurgitation grade in the postoperative period was 0.7 ± 0.9, and the mean transmitral gradient was 1.3 ± 2.2 mm Hg. During a mean follow-up of 26 months, 1 patient in the SAM treatment group presented late recurrence of SAM and no patients developed mitral stenosis (mean transmitral gradient, 2.0 ± 2.6 mm Hg; P = .12). Without SAM prediction and preemptive edge-to-edge technique, the expected rate of SAM would have been 5.7%; however, the observed rate was 1% (12 of 1148 patients). Initiating an expectation for prebypass SAM prediction, combined with a surgical SAM prevention strategy, resulted in a reduced prevalence of SAM compared with our model of observed to-expected-ratios and to published norms. Copyright © 2013 The American Association for Thoracic Surgery. Published by Mosby, Inc. All rights reserved.

Seizure threshold increases can be predicted by EEG quality in right unilateral ultrabrief ECT.

PubMed

Gálvez, Verònica; Hadzi-Pavlovic, Dusan; Waite, Susan; Loo, Colleen K

2017-12-01

Increases in seizure threshold (ST) over a course of brief pulse ECT can be predicted by decreases in EEG quality, informing ECT dose adjustment to maintain adequate supra-threshold dosing. ST increases also occur over a course of right unilateral ultrabrief (RUL UB) ECT, but no data exist on the relationship between ST increases and EEG indices. This study (n = 35) investigated if increases in ST over RUL UB ECT treatments could be predicted by a decline in seizure quality. ST titration was performed at ECT session one and seven, with treatment dosing maintained stable (at 6-8 times ST) in intervening sessions. Seizure quality indices (slow-wave onset, mid-ictal amplitude, regularity, stereotypy, and post-ictal suppression) were manually rated at the first supra-threshold treatment, and last supra-threshold treatment before re-titration, using a structured rating scale, by a single trained rater blinded to the ECT session being rated. Twenty-one subjects (60%) had a ST increase. The association between ST changes and EEG quality indices was analysed by logistic regression, yielding a significant model (p < 0.001). Initial ST (p < 0.05) and percentage change in mid-ictal amplitude (p < 0.05) were significant predictors of change in ST. Percentage change in post-ictal suppression reached trend level significance (p = 0.065). Increases in ST over a RUL UB ECT course may be predicted by decreases in seizure quality, specifically decline in mid-ictal amplitude and potentially in post-ictal suppression. Such EEG indices may be able to inform when dose adjustments are necessary to maintain adequate supra-threshold dosing in RUL UB ECT.

Glioblastoma multiforme (GBM) in the elderly: initial treatment strategy and overall survival.

PubMed

Glaser, Scott M; Dohopolski, Michael J; Balasubramani, Goundappa K; Flickinger, John C; Beriwal, Sushil

2017-08-01

The EORTC trial which solidified the role of external beam radiotherapy (EBRT) plus temozolomide (TMZ) in the management of GBM excluded patients over age 70. Randomized studies of elderly patients showed that hypofractionated EBRT (HFRT) alone or TMZ alone was at least equivalent to conventionally fractionated EBRT (CFRT) alone. We sought to investigate the practice patterns and survival in elderly patients with GBM. We identified patients age 65-90 in the National Cancer Data Base (NCDB) with histologically confirmed GBM from 1998 to 2012 and known chemotherapy and radiotherapy status. We analyzed factors predicting treatment with EBRT alone vs. EBRT plus concurrent single-agent chemotherapy (CRT) using multivariable logistic regression. Similarly, within the EBRT alone cohort we compared CFRT (54-65 Gy at 1.7-2.1 Gy/fraction) to HFRT (34-60 Gy at 2.5-5 Gy/fraction). Multivariable Cox proportional hazards model (MVA) with propensity score adjustment was used to compare survival. A total of 38,862 patients were included. Initial treatments for 1998 versus 2012 were: EBRT alone = 50 versus 10%; CRT = 6 versus 50%; chemo alone = 1.6% (70% single-agent) versus 3.2% (94% single-agent). Among EBRT alone patients, use of HFRT (compared to CFRT) increased from 13 to 41%. Numerous factors predictive for utilization of CRT over EBRT alone and for HFRT over CFRT were identified. Median survival and 1-year overall survival were higher in the CRT versus EBRT alone group at 8.6 months vs. 5.1 months and 36.0 versus 15.7% (p < 0.0005 by log-rank, multivariable HR 0.65 [95% CI = 0.61-0.68, p < 0.0005], multivariable HR with propensity adjustment 0.66 [95% CI = 0.63-0.70, p < 0.0005]). For elderly GBM patients in the United States, CRT is the most common initial treatment and appears to offer a survival advantage over EBRT alone. Adoption of hypofractionation has increased over time but continues to be low.

Exposure and non-fear emotions: A randomized controlled study of exposure-based and rescripting-based imagery in PTSD treatment.

PubMed

Langkaas, Tomas Formo; Hoffart, Asle; Øktedalen, Tuva; Ulvenes, Pål G; Hembree, Elizabeth A; Smucker, Mervin

2017-10-01

Interventions involving rescripting-based imagery have been proposed as a better approach than exposure-based imagery when posttraumatic stress disorder (PTSD) is associated with emotions other than fear. Prior research led to the study's hypotheses that (a) higher pretreatment non-fear emotions would predict relatively better response to rescripting as compared to exposure, (b) rescripting would be associated with greater reduction in non-fear emotions, and (c) pretreatment non-fear emotions would predict poor response to exposure. A clinically representative sample of 65 patients presenting a wide range of traumas was recruited from patients seeking and being offered PTSD treatment in an inpatient setting. Subjects were randomly assigned to 10 weeks of treatment involving either rescripting-based imagery (Imagery Rescripting; IR) or exposure-based imagery (Prolonged Exposure; PE). Patients were assessed on outcome and emotion measures at pretreatment, posttreatment and 12 months follow-up. Comparison to control benchmarks indicated that both treatments were effective, but no outcome differences between them appeared. None of the initial hypotheses were supported. The results from this study challenge previous observations and hypotheses about exposure mainly being effective for fear-based PTSD and strengthen the notion that exposure-based treatment is a generally effective treatment for all types of PTSD. Copyright © 2017 Elsevier Ltd. All rights reserved.

Opioid Attentional Bias and Cue-Elicited Craving Predict Future Risk of Prescription Opioid Misuse Among Chronic Pain Patients*

PubMed Central

Garland, Eric L.; Howard, Matthew O.

2014-01-01

Background Some chronic pain patients receiving long-term opioid analgesic pharmacotherapy are at risk for misusing opioids. Like other addictive behaviors, risk of opioid misuse may be signaled by an attentional bias (AB) towards drug-related cues. The purpose of this study was to examine opioid AB as a potential predictor of opioid misuse among chronic pain patients following behavioral treatment. Methods Chronic pain patients taking long-term opioid analgesics (N = 47) completed a dot probe task designed to assess opioid AB, as well as self-report measures of opioid misuse and pain severity, and then participated in behavioral treatment. Regression analyses examined opioid AB and cue-elicited craving as predictors of opioid misuse at 3-months posttreatment follow-up. Results Patients who scored high on a measure of opioid misuse risk following treatment exhibited significantly greater opioid AB scores than patients at low risk for opioid misuse. Opioid AB for 200 ms cues and cue-elicited craving significantly predicted opioid misuse risk 20 weeks later, even after controlling for pre-treatment opioid dependence diagnosis, opioid misuse, and pain severity (Model R2 = .50). Conclusion Biased initial attentional orienting to prescription opioid cues and cue-elicited craving may reliably signal future opioid misuse risk following treatment. These measures may therefore provide potential prognostic indicators of treatment outcome. PMID:25282309

Decision making in a multidisciplinary cancer team: does team discussion result in better quality decisions?

PubMed

Kee, Frank; Owen, Tracy; Leathem, Ruth

2004-01-01

To establish whether treatment recommendations made by clinicians concur with the best outcomes predicted from their prognostic estimates and whether team discussion improves the quality or outcome of their decision making, the authors studied real-time decision making by a lung cancer team. Clinicians completed pre- and postdiscussion questionnaires for 50 newly diagnosed patients. For each patient/doctor pairing, a decision model determined the expected patient outcomes from the clinician's prognostic estimates. The difference between the expected utility of the recommended treatment and the maximum utility derived from the clinician's predictions of the outcomes (the net utility loss) following all potential treatment modalities was calculated as an indicator of quality of the decision. The proportion of treatment decisions changed by the multidisciplinary team discussion was also calculated. Insofar as the change in net utility loss brought about by multidisciplinary team discussion was not significantly different from zero, team discussion did not improve the quality of decision making overall. However, given the modest power of the study, these findings must be interpreted with caution. In only 23 of 87 instances (26%) in which an individual specialist's initial treatment preference differed from the final group judgment did the specialist finally concur with the group treatment choice after discussion. This study does not support the theory that team discussion improves decision making by closing a knowledge gap.

Prediction of short-term changes in symptom severity by baseline plasma homovanillic acid levels in schizophrenic patients receiving clozapine.

PubMed

Sumiyoshi, T; Hasegawa, M; Jayathilake, K; Meltzer, H Y

1997-03-24

The relationship between pretreatment levels of plasma homovanillic acid (pHVA) and the outcome of clozapine treatment was studied in 18 male patients with schizophrenia who were resistant to treatment with conventional neuroleptics. After 6 months of clozapine treatment, 7 patients demonstrated > or = 20% decrease in the Brief Psychiatric Rating Scale (BPRS) (responders), while 11 patients did not (non-responders). Responders and non-responders did not differ with respect to the baseline pHVA level. The BPRS Positive Symptom scores at 6 weeks and 3 months, but not those at baseline and 6 months, following initiation of clozapine treatment negatively correlated with pHVA levels for all patients. The correlations became stronger when only responders were included. No significant correlation between Positive Symptom scores and pHVA levels was observed for non-responders. The BPRS Total and Negative Symptom scores did not correlate with pHVA for all patients, responders or non-responders at any time. The percent decrease in the BPRS Positive Symptom scores from baseline at 6 weeks following clozapine treatment correlated significantly with pHVA levels in responders. These results suggest that pretreatment levels of pHVA can be used to predict relatively short-term changes in the positive symptoms of patients with schizophrenia receiving clozapine treatment, particularly for clozapine responders.

Pretreatment Growth Rate Predicts Radiation Response in Vestibular Schwannomas

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

Niu, Nina N.; Harvard Medical School, Department of Medicine, Brigham and Women's Hospital, Boston, Massachusetts; Niemierko, Andrzej

Purpose: Vestibular schwannomas (VS) are often followed without initial therapeutic intervention because many tumors do not grow and radiation therapy is associated with potential adverse effects. In an effort to determine whether maximizing initial surveillance predicts for later treatment response, the predictive value of preirradiation growth rate of VS on response to radiation therapy was assessed. Methods and Materials: Sixty-four patients with 65 VS were treated with single-fraction stereotactic radiation surgery or fractionated stereotactic radiation therapy. Pre- and postirradiation linear expansion rates were estimated using volumetric measurements on sequential magnetic resonance images (MRIs). In addition, postirradiation tumor volume change wasmore » classified as demonstrating shrinkage (ratio of volume on last follow-up MRI to MRI immediately preceding irradiation <80%), stability (ratio 80%-120%), or expansion (ratio >120%). The median pre- and postirradiation follow-up was 20.0 and 27.5 months, respectively. Seven tumors from neurofibromatosis type 2 (NF2) patients were excluded from statistical analyses. Results: In the 58 non-NF2 patients, there was a trend of correlation between pre- and postirradiation volume change rates (slope on linear regression, 0.29; P=.06). Tumors demonstrating postirradiation expansion had a median preirradiation growth rate of 89%/year, and those without postirradiation expansion had a median preirradiation growth rate of 41%/year (P=.02). As the preirradiation growth rate increased, the probability of postirradiation expansion also increased. Overall, 24.1% of tumors were stable, 53.4% experienced shrinkage, and 22.5% experienced expansion. Predictors of no postirradiation tumor expansion included no prior surgery (P=.01) and slower tumor growth rate (P=.02). The control of tumors in NF2 patients was only 43%. Conclusions: Radiation therapy is an effective treatment for VS, but tumors that grow quickly preirradiation may be more likely to increase in size. Clinicians should take into account tumor growth rate when counseling patients about treatment options.« less

No evidence for sperm priming responses under varying sperm competition risk or intensity in guppies

NASA Astrophysics Data System (ADS)

Evans, Jonathan P.

2009-07-01

Sperm competition theory predicts that males should tailor their investment in ejaculates according to the number of rival males competing to fertilize a female’s eggs. Research spanning several taxa supports this prediction by showing that males are often sensitive to the level of sperm competition and adjust their investment in sperm numbers accordingly. More recent work has revealed that males may also tailor the quality of sperm according to the number of males competing for fertilization. Here I test for both effects in guppies ( Poecilia reticulata) in an experiment that simultaneously evaluates the risk and intensity models of sperm competition. The experiment determined whether male guppies adjust the number (stripped ejaculate size) and quality (sperm velocity and viability) of sperm that are primed over a 3-day period according to experimental changes in the perceived level of sperm competition. A total of 136 focal males were initially stripped of all retrievable sperm and assayed for these sperm traits before being allocated at random to one of four treatments simulating different levels of sperm competition risk and intensity. During the 3-day treatment phase, focal males had visual and olfactory access to a sexually receptive (initially virgin) female maintained with different numbers of stimulus males to simulate variation in the risk and intensity of sperm competition. Following this, males were assayed again for the sperm traits. Contrary to predictions, there was no significant change in any of the measured variables among treatments, although qualitatively the patterns for sperm velocity and viability did conform to expectation. The lack of any trend for the number of sperm primed was unequivocal and future work examining the effects of sperm competition on sperm production should focus on whether males differentially allocate sperm numbers among matings that differ in the level of sperm competition.

Plaque Brachytherapy for Uveal Melanoma: A Vision Prognostication Model

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

Khan, Niloufer; Khan, Mohammad K.; Bena, James

Purpose: To generate a vision prognostication model after plaque brachytherapy for uveal melanoma. Methods and Materials: All patients with primary single ciliary body or choroidal melanoma treated with iodine-125 or ruthenium-106 plaque brachytherapy between January 1, 2005, and June 30, 2010, were included. The primary endpoint was loss of visual acuity. Only patients with initial visual acuity better than or equal to 20/50 were used to evaluate visual acuity worse than 20/50 at the end of the study, and only patients with initial visual acuity better than or equal to 20/200 were used to evaluate visual acuity worse than 20/200more » at the end of the study. Factors analyzed were sex, age, cataracts, diabetes, tumor size (basal dimension and apical height), tumor location, and radiation dose to the tumor apex, fovea, and optic disc. Univariate and multivariable Cox proportional hazards were used to determine the influence of baseline patient factors on vision loss. Kaplan-Meier curves (log rank analysis) were used to estimate freedom from vision loss. Results: Of 189 patients, 92% (174) were alive as of February 1, 2011. At presentation, visual acuity was better than or equal to 20/50 and better than or equal to 20/200 in 108 and 173 patients, respectively. Of these patients, 44.4% (48) had post-treatment visual acuity of worse than 20/50 and 25.4% (44) had post-treatment visual acuity worse than 20/200. By multivariable analysis, increased age (hazard ratio [HR] of 1.01 [1.00-1.03], P=.05), increase in tumor height (HR of 1.35 [1.22-1.48], P<.001), and a greater total dose to the fovea (HR of 1.01 [1.00-1.01], P<.001) were predictive of vision loss. This information was used to develop a nomogram predictive of vision loss. Conclusions: By providing a means to predict vision loss at 3 years after treatment, our vision prognostication model can be an important tool for patient selection and treatment counseling.« less

Accuracy of tracheal aspirate gram stain in predicting Staphylococcus aureus infection in ventilator-associated pneumonia.

PubMed

Seligman, Renato; Seligman, Beatriz Graeff Santos; Konkewicz, Loriane; Dos Santos, Rodrigo Pires

2015-01-01

The Gram stain can be used to direct initial empiric antimicrobial therapy when complete culture is not available. This rapid test could prevent the initiation of inappropriate therapy and adverse outcomes. However, several studies have attempted to determine the value of the Gram stain in the diagnosis and therapy of bacterial infection in different populations of patients with ventilator-associated pneumonia (VAP) with conflicting results. The objective of this study is to evaluate the accuracy of the Gram stain in predicting the existence of Staphylococcus aureus infections from cultures of patients suspected of having VAP. This prospective single-center open cohort study enrolled 399 patients from December 2005 to December 2010. Patients suspected of having VAP by ATS IDSA criteria were included. Respiratory secretion samples were collected by tracheal aspirate (TA) for standard bacterioscopic analysis by Gram stain and culture. Respiratory secretion samples collected by tracheal aspirates of 392 patients were analyzed by Gram stain and culture. When Gram-positive cocci were arranged in clusters, the sensitivity was 68.4%, specificity 97.8%, positive predictive value 88.1% and negative predictive value 92.8% for predicting the presence of Staphylococcus aureus in culture (p < 0.001). A tracheal aspirate Gram stain can be used to rule out the presence of Staphylococcus aureus in patients with a clinical diagnosis of VAP with a 92.8% Negative Predictive Value. Therefore, 7.2% of patients with Staphylococcus aureus would not be protected by an empiric treatment that limits antimicrobial coverage to Staphylococcus aureus only when Gram positive cocci in clusters are identified.

A predictive model for diagnosing bipolar disorder based on the clinical characteristics of major depressive episodes in Chinese population.

PubMed

Gan, Zhaoyu; Diao, Feici; Wei, Qinling; Wu, Xiaoli; Cheng, Minfeng; Guan, Nianhong; Zhang, Ming; Zhang, Jinbei

2011-11-01

A correct timely diagnosis of bipolar depression remains a big challenge for clinicians. This study aimed to develop a clinical characteristic based model to predict the diagnosis of bipolar disorder among patients with current major depressive episodes. A prospective study was carried out on 344 patients with current major depressive episodes, with 268 completing 1-year follow-up. Data were collected through structured interviews. Univariate binary logistic regression was conducted to select potential predictive variables among 19 initial variables, and then multivariate binary logistic regression was performed to analyze the combination of risk factors and build a predictive model. Receiver operating characteristic (ROC) curve was plotted. Of 19 initial variables, 13 variables were preliminarily selected, and then forward stepwise exercise produced a final model consisting of 6 variables: age at first onset, maximum duration of depressive episodes, somatalgia, hypersomnia, diurnal variation of mood, irritability. The correct prediction rate of this model was 78% (95%CI: 75%-86%) and the area under the ROC curve was 0.85 (95%CI: 0.80-0.90). The cut-off point for age at first onset was 28.5 years old, while the cut-off point for maximum duration of depressive episode was 7.5 months. The limitations of this study include small sample size, relatively short follow-up period and lack of treatment information. Our predictive models based on six clinical characteristics of major depressive episodes prove to be robust and can help differentiate bipolar depression from unipolar depression. Copyright © 2011 Elsevier B.V. All rights reserved.

CBT Specific Process in Exposure-Based Treatments: Initial Examination in a Pediatric OCD Sample

PubMed Central

Benito, Kristen Grabill; Conelea, Christine; Garcia, Abbe M.; Freeman, Jennifer B.

2012-01-01

Cognitive-Behavioral theory and empirical support suggest that optimal activation of fear is a critical component for successful exposure treatment. Using this theory, we developed coding methodology for measuring CBT-specific process during exposure. We piloted this methodology in a sample of young children (N = 18) who previously received CBT as part of a randomized controlled trial. Results supported the preliminary reliability and predictive validity of coding variables with 12 week and 3 month treatment outcome data, generally showing results consistent with CBT theory. However, given our limited and restricted sample, additional testing is warranted. Measurement of CBT-specific process using this methodology may have implications for understanding mechanism of change in exposure-based treatments and for improving dissemination efforts through identification of therapist behaviors associated with improved outcome. PMID:22523609

Best cost-effectiveness and worker productivity with initial triple DMARD therapy compared with methotrexate monotherapy in early rheumatoid arthritis: cost-utility analysis of the tREACH trial.

PubMed

de Jong, Pascal H P; Hazes, Johanna M; Buisman, Leander R; Barendregt, Pieternella J; van Zeben, Derkjen; van der Lubbe, Peter A; Gerards, Andreas H; de Jager, Mike H; de Sonnaville, Peter B J; Grillet, Bernard A; Luime, Jolanda J; Weel, Angelique E A M

2016-12-01

To evaluate direct and indirect costs per quality adjusted life year (QALY) for different initial treatment strategies in very early RA. The 1-year data of the treatment in the Rotterdam Early Arthritis Cohort trial were used. Patients with a high probability (>70%) according to their likelihood of progressing to persistent arthritis, based on the prediction model of Visser, were randomized into one of following initial treatment strategies: (A) initial triple DMARD therapy (iTDT) with glucocorticoids (GCs) intramuscular (n = 91); (B) iTDT with an oral GC tapering scheme (n = 93); and (C) initial MTX monotherapy (iMM) with GCs similar to B (n = 97). Data on QALYs, measured with the Dutch EuroQol, and direct and indirect cost were used. Direct costs are costs of treatment and medical consumption, whereas indirect costs are costs due to loss of productivity. Average QALYs (sd) for A, B and C were, respectively, 0.75 (0.12), 0.75 (0.10) and 0.73 (0.13) for Dutch EuroQol. Highest total costs per QALY (sd) were, respectively, €12748 (€18767), €10 380 (€15 608) and €17 408 (€21 828) for strategy A, B and C (P = 0.012, B vs C). Direct as well as indirect costs were higher with iMM (strategy C) compared with iTDT (strategy B). Higher direct costs were due to ∼40% more biologic usage over time. Higher indirect costs, on the other hand, were caused by more long-term sickness and reduction in contract hours. iTDT was >95% cost-effective across all willingness-to-pay thresholds compared with iMM. iTDT was more cost-effective and had better worker productivity compared with iMM. © The Author 2016. Published by Oxford University Press on behalf of the British Society for Rheumatology. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

Urinary β2 microglobulin can predict tenofovir disoproxil fumarate-related renal dysfunction in HIV-1-infected patients who initiate tenofovir disoproxil fumarate-containing antiretroviral therapy.

PubMed

Nishijima, Takeshi; Kurosawa, Takuma; Tanaka, Noriko; Kawasaki, Yohei; Kikuchi, Yoshimi; Oka, Shinichi; Gatanaga, Hiroyuki

2016-06-19

In nephrotoxicity induced by tenofovir disoproxil fumarate (TDF), tubular dysfunction precedes the decline in GFR, suggesting that tubular markers are more sensitive than estimated glomerular filtration rate (eGFR). The hypothesis that urinary β2 microglobulin (β2 M), a tubular function marker, can predict TDF-renal dysfunction in HIV-1-infected patients was tested. A single-center observational study. The inclusion criteria were: HIV-1-infected patients who started TDF-containing antiretroviral therapy from 2004 to 2013, urinary β2 M after and closest to the day of TDF initiation within 180 days (termed 'β2 M after TDF') was measured. The associations between 'β2 M after TDF' and four renal end points (>10 ml/min per 1.73 m decrement in eGFR relative to baseline, >20 decrement, >25% decrement, and eGFR < 60) were estimated with logistic regression model. The association between 'β2 M after TDF' and longitudinal changes in eGFR after initiation of TDF was estimated with a mixed-model. A total 655 study patients were analyzed (96% men, median age 38, median CD4 238 cells/μl, 63% treatment naïve). The median baseline eGFR was 117 ml/min per 1.73 m (IQR 110-125), and the median duration of TDF use was 3.32 years (IQR 2.02-5.31). 'β2 M after TDF' was significantly associated with more than 20 decrement in eGFR (P = 0.024) and more than 25% decrement (P = 0.014), and was marginally associated with eGFR less than 60 (P = 0.076). It was also significantly associated with the longitudinal eGFR after initiation of TDF (P < 0.0001). 'β2 M after TDF' of 1700 μg/l was identified as the optimal cutoff value for the prediction of longitudinal eGFR. Urinary β2 M measured within 180 days after initiation of TDF predicts renal dysfunction related to long-term TDF use.

Impact of hypothermia on implementation of CPAP for neonatal respiratory distress syndrome in a low-resource setting.

PubMed

Carns, Jennifer; Kawaza, Kondwani; Quinn, M K; Miao, Yinsen; Guerra, Rudy; Molyneux, Elizabeth; Oden, Maria; Richards-Kortum, Rebecca

2018-01-01

Neonatal hypothermia is widely associated with increased risks of morbidity and mortality, but remains a pervasive global problem. No studies have examined the impact of hypothermia on outcomes for preterm infants treated with CPAP for respiratory distress syndrome (RDS). This retrospective analysis assessed the impact of hypothermia on outcomes of 65 neonates diagnosed with RDS and treated with either nasal oxygen (N = 17) or CPAP (N = 48) in a low-resource setting. A classification tree approach was used to develop a model predicting survival for subjects diagnosed with RDS. Survival to discharge was accurately predicted based on three variables: mean temperature, treatment modality, and mean respiratory rate. None of the 23 neonates with a mean temperature during treatment below 35.8°C survived to discharge, regardless of treatment modality. Among neonates with a mean temperature exceeding 35.8°C, the survival rate was 100% for the 31 neonates treated with CPAP and 36.4% for the 11 neonates treated with nasal oxygen (p<0.001). For neonates treated with CPAP, outcomes were poor if more than 50% of measured temperatures indicated hypothermia (5.6% survival). In contrast, all 30 neonates treated with CPAP and with more than 50% of temperature measurements above 35.8°C survived to discharge, regardless of initial temperature. The results of our study suggest that successful implementation of CPAP to treat RDS in low-resource settings will require aggressive action to prevent persistent hypothermia. However, our results show that even babies who are initially cold can do well on CPAP with proper management of hypothermia.

Method of predicting the mean lung dose based on a patient's anatomy and dose-volume histograms

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

Zawadzka, Anna, E-mail: a.zawadzka@zfm.coi.pl; Nesteruk, Marta; Department of Radiation Oncology, University Hospital Zurich and University of Zurich, Zurich

The aim of this study was to propose a method to predict the minimum achievable mean lung dose (MLD) and corresponding dosimetric parameters for organs-at-risk (OAR) based on individual patient anatomy. For each patient, the dose for 36 equidistant individual multileaf collimator shaped fields in the treatment planning system (TPS) was calculated. Based on these dose matrices, the MLD for each patient was predicted by the homemade DosePredictor software in which the solution of linear equations was implemented. The software prediction results were validated based on 3D conformal radiotherapy (3D-CRT) and volumetric modulated arc therapy (VMAT) plans previously prepared formore » 16 patients with stage III non–small-cell lung cancer (NSCLC). For each patient, dosimetric parameters derived from plans and the results calculated by DosePredictor were compared. The MLD, the maximum dose to the spinal cord (D{sub max} {sub cord}) and the mean esophageal dose (MED) were analyzed. There was a strong correlation between the MLD calculated by the DosePredictor and those obtained in treatment plans regardless of the technique used. The correlation coefficient was 0.96 for both 3D-CRT and VMAT techniques. In a similar manner, MED correlations of 0.98 and 0.96 were obtained for 3D-CRT and VMAT plans, respectively. The maximum dose to the spinal cord was not predicted very well. The correlation coefficient was 0.30 and 0.61 for 3D-CRT and VMAT, respectively. The presented method allows us to predict the minimum MLD and corresponding dosimetric parameters to OARs without the necessity of plan preparation. The method can serve as a guide during the treatment planning process, for example, as initial constraints in VMAT optimization. It allows the probability of lung pneumonitis to be predicted.« less

Potential impact of initialization on decadal predictions as assessed for CMIP5 models

NASA Astrophysics Data System (ADS)

Branstator, Grant; Teng, Haiyan

2012-06-01

To investigate the potential for initialization to improve decadal range predictions, we quantify the initial value predictability of upper 300 m temperature in the two northern ocean basins for 12 models from Coupled Model Intercomparison Project phase 5 (CMIP5), and we contrast it with the forced predictability in Representative Concentration Pathways (RCP) 4.5 climate change projections. We use a recently introduced method that produces predictability estimates from long control runs. Many initial states are considered, and we find on average 1) initialization has the potential to improve skill in the first 5 years in the North Pacific and the first 9 years in the North Atlantic, and 2) the impact from initialization becomes secondary compared to the impact of RCP4.5 forcing after 6 1/2 and 8 years in the two basins, respectively. Model-to-model and spatial variations in these limits are, however, substantial.

Decadal climate prediction in the large ensemble limit

NASA Astrophysics Data System (ADS)

Yeager, S. G.; Rosenbloom, N. A.; Strand, G.; Lindsay, K. T.; Danabasoglu, G.; Karspeck, A. R.; Bates, S. C.; Meehl, G. A.

2017-12-01

In order to quantify the benefits of initialization for climate prediction on decadal timescales, two parallel sets of historical simulations are required: one "initialized" ensemble that incorporates observations of past climate states and one "uninitialized" ensemble whose internal climate variations evolve freely and without synchronicity. In the large ensemble limit, ensemble averaging isolates potentially predictable forced and internal variance components in the "initialized" set, but only the forced variance remains after averaging the "uninitialized" set. The ensemble size needed to achieve this variance decomposition, and to robustly distinguish initialized from uninitialized decadal predictions, remains poorly constrained. We examine a large ensemble (LE) of initialized decadal prediction (DP) experiments carried out using the Community Earth System Model (CESM). This 40-member CESM-DP-LE set of experiments represents the "initialized" complement to the CESM large ensemble of 20th century runs (CESM-LE) documented in Kay et al. (2015). Both simulation sets share the same model configuration, historical radiative forcings, and large ensemble sizes. The twin experiments afford an unprecedented opportunity to explore the sensitivity of DP skill assessment, and in particular the skill enhancement associated with initialization, to ensemble size. This talk will highlight the benefits of a large ensemble size for initialized predictions of seasonal climate over land in the Atlantic sector as well as predictions of shifts in the likelihood of climate extremes that have large societal impact.

Clinical characteristics of patients assessed within an Improving Access to Psychological Therapies (IAPT) service: results from a naturalistic cohort study (Predicting Outcome Following Psychological Therapy; PROMPT).

PubMed

Hepgul, Nilay; King, Sinead; Amarasinghe, Myanthi; Breen, Gerome; Grant, Nina; Grey, Nick; Hotopf, Matthew; Moran, Paul; Pariante, Carmine M; Tylee, André; Wingrove, Janet; Young, Allan H; Cleare, Anthony J

2016-02-27

A substantial number of patients do not benefit from first line psychological therapies for the treatment of depression and anxiety. Currently, there are no clear predictors of treatment outcomes for these patients. The PROMPT project aims to establish an infrastructure platform for the identification of factors that predict outcomes following psychological treatment for depression and anxiety. Here we report on the first year of recruitment and describe the characteristics of our sample to date. One hundred and forty-seven patients awaiting treatment within an Improving Access to Psychological Therapies (IAPT) service were recruited between February 2014 and February 2015 (representing 48 % of those eligible). Baseline assessments were conducted to collect information on a variety of clinical, psychological and social variables including a diagnostic interview using the Mini International Neuropsychiatric Interview (MINI). Our initial findings showed that over a third of our sample were not presenting to IAPT services for the first time, and 63 % had been allocated to receive higher intensity IAPT treatments. Approximately half (46 %) were taking prescribed psychotropic medication (most frequently antidepressants). Co-morbidity was common: 72 % of the sample met criteria for 2 or more current MINI diagnoses. Our initial data also indicated that 16 % met criteria for borderline personality disorder and 69 % were at high risk of personality disorder. Sixty-one percent scored above the screening threshold for bipolarity. Over half of participants (55 %) reported experiencing at least one stressful life event in the previous 12 months, whilst 67 % reported experiencing at least one form of childhood trauma. Our results to date highlight the complex nature of patients seen within an urban IAPT service, with high rates of psychiatric comorbidity, personality disorder, bipolarity and childhood trauma. Whilst there are significant challenges associated with researching IAPT populations, we have also confirmed the feasibility of undertaking such research.

Non-linear mixed effects modeling of antiretroviral drug response after administration of lopinavir, atazanavir and efavirenz containing regimens to treatment-naïve HIV-1 infected patients.

PubMed

Röshammar, Daniel; Simonsson, Ulrika S H; Ekvall, Håkan; Flamholc, Leo; Ormaasen, Vidar; Vesterbacka, Jan; Wallmark, Eva; Ashton, Michael; Gisslén, Magnus

2011-12-01

The objective of this analysis was to compare three methods of handling HIV-RNA data below the limit of quantification (LOQ) when describing the time-course of antiretroviral drug response using a drug-disease model. Treatment naïve Scandinavian HIV-positive patients (n = 242) were randomized to one of three study arms. Two nucleoside reverse transcriptase inhibitors were administrated in combination with 400/100 mg lopinavir/ritonavir twice daily, 300/100 mg atazanavir/ritonavir once a day or 600 mg efavirenz once a day. The viral response was monitored at screening, baseline and at 1, 2, 3, 4, 12, 24, 48, 96, 120, and 144 weeks after study initiation. Data up to 400 days was fitted using a viral dynamics non-linear mixed effects drug-disease model in NONMEM. HIV-RNA data below LOQ of 50 copies/ml plasma (39%) was omitted, replaced by LOQ/2 or included in the analysis using a likelihood-based method (M3 method). Including data below LOQ using the M3 method substantially improved the model fit. The drug response parameter expressing the fractional inhibition of viral replication was on average (95% CI) estimated to 0.787 (0.721-0.864) for lopinavir and atazanavir treatment arms and 0.868 (0.796-0.923) for the efavirenz containing regimen. At 400 days after treatment initiation 90% (76-100) of the lopinavir and atazanavir treated patients were predicted to have undetectable viral levels and 96% (89-100%) for the efavirenz containing treatment. Including viral data below the LOQ rather than omitting or replacing data provides advantages such as better model predictions and less biased parameter estimates which are of importance when quantifying antiretroviral drug response.

Clinical Prediction Model for Time in Therapeutic Range While on Warfarin in Newly Diagnosed Atrial Fibrillation.

PubMed

Williams, Brent A; Evans, Michael A; Honushefsky, Ashley M; Berger, Peter B

2017-10-12

Though warfarin has historically been the primary oral anticoagulant for stroke prevention in newly diagnosed atrial fibrillation (AF), several new direct oral anticoagulants may be preferred when anticoagulation control with warfarin is expected to be poor. This study developed a prediction model for time in therapeutic range (TTR) among newly diagnosed AF patients on newly initiated warfarin as a tool to assist decision making between warfarin and direct oral anticoagulants. This electronic medical record-based, retrospective study included newly diagnosed, nonvalvular AF patients with no recent warfarin exposure receiving primary care services through a large healthcare system in rural Pennsylvania. TTR was estimated as the percentage of time international normalized ratio measurements were between 2.0 and 3.0 during the first year following warfarin initiation. Candidate predictors of TTR were chosen from data elements collected during usual clinical care. A TTR prediction model was developed and temporally validated and its predictive performance was compared with the SAMe-TT 2 R 2 score (sex, age, medical history, treatment, tobacco, race) using R 2 and c-statistics. A total of 7877 newly diagnosed AF patients met study inclusion criteria. Median (interquartile range) TTR within the first year of starting warfarin was 51% (32, 67). Of 85 candidate predictors evaluated, 15 were included in the final validated model with an R 2 of 15.4%. The proposed model showed better predictive performance than the SAMe-TT 2 R 2 score ( R 2 =3.0%). The proposed prediction model may assist decision making on the proper mode of oral anticoagulant among newly diagnosed AF patients. However, predicting TTR on warfarin remains challenging. © 2017 The Authors. Published on behalf of the American Heart Association, Inc., by Wiley.

Value of gastrografin in adhesive small bowel obstruction after unsuccessful conservative treatment: A prospective evaluation

PubMed Central

Choi, Hok-Kwok; Law, Wai-Lun; Ho, Judy Wai-Chu; Chu, Kin-Wah

2005-01-01

AIM: Gastrografin is a hyperosmolar water-soluble contrast medium. Besides its predictive value for the need for operative treatment, a potential therapeutic role of this agent in adhesive small bowel obstruction has been suggested. This study aimed at evaluating the effectiveness of gastrografin in adhesive small bowel obstruction when conservative treatment failed. METHODS: Patients with adhesive small bowel obstruction were given trial conservative treatment unless there was fear of bowel strangulation. Those responded in the initial 48 h had conservative treatment continued. Patients who showed no improvement in the initial 48 h were given 100 mL of gastrografin through nasogastric tube followed by serial abdominal radiographs. Patients with the contrast appeared in large bowel within 24 h were regarded as having partial obstruction and conservative treatment was continued. Patients in which the contrast failed to reach large bowel within 24 h were considered to have complete obstruction and laparotomy was performed. RESULTS: Two hundred and twelve patients with 245 episodes of adhesive obstruction were included. Fifteen patients were operated on soon after admission due to fear of strangulation. One hundred and eighty-six episodes of obstruction showed improvement in the initial 48 h and conservative treatment was continued. Two patients had subsequent operations because of persistent obstruction. Forty-four episodes of obstruction showed no improvement within 48 h and gastrografin was administered. Seven patients underwent complete obstruction surgery. Partial obstruction was demonstrated in 37 other cases, obstruction resolved subsequently in all of them except one patient who required laparotomy because of persistent obstruction. The overall operative rate in this study was 10%. There was no complication that could be attributed to the use of gastrografin. CONCLUSION: The use of gastrografin in adhesive small bowel obstruction after unsuccessful conservative treatment is safe and reduces the need for surgical intervention. PMID:15968731

Factors associated with pre-treatment HIV RNA: application for the use of abacavir and rilpivirine as the first-line regimen for HIV-infected patients in resource-limited settings.

PubMed

Kiertiburanakul, Sasisopin; Boettiger, David; Ng, Oon Tek; Van Kinh, Nguyen; Merati, Tuti Parwati; Avihingsanon, Anchalee; Wong, Wing-Wai; Lee, Man Po; Chaiwarith, Romanee; Kamarulzaman, Adeeba; Kantipong, Pacharee; Zhang, Fujie; Choi, Jun Yong; Kumarasamy, Nagalingeswaran; Ditangco, Rossana; Cuong, Do Duy; Oka, Shinichi; Sim, Benedict Lim Heng; Ratanasuwan, Winai; Ly, Penh Sun; Yunihastuti, Evy; Pujari, Sanjay; Ross, Jeremy L; Law, Matthew; Sungkanuparph, Somnuek

2017-01-01

Abacavir and rilpivirine are alternative antiretroviral drugs for treatment-naïve HIV-infected patients. However, both drugs are only recommended for the patients who have pre-treatment HIV RNA <100,000 copies/mL. In resource-limited settings, pre-treatment HIV RNA is not routinely performed and not widely available. The aims of this study are to determine factors associated with pre-treatment HIV RNA <100,000 copies/mL and to construct a model to predict this outcome. HIV-infected adults enrolled in the TREAT Asia HIV Observational Database were eligible if they had an HIV RNA measurement documented at the time of ART initiation. The dataset was randomly split into a derivation data set (75% of patients) and a validation data set (25%). Factors associated with pre-treatment HIV RNA <100,000 copies/mL were evaluated by logistic regression adjusted for study site. A prediction model and prediction scores were created. A total of 2592 patients were enrolled for the analysis. Median [interquartile range (IQR)] age was 35.8 (29.9-42.5) years; CD4 count was 147 (50-248) cells/mm 3 ; and pre-treatment HIV RNA was 100,000 (34,045-301,075) copies/mL. Factors associated with pre-treatment HIV RNA <100,000 copies/mL were age <30 years [OR 1.40 vs. 41-50 years; 95% confidence interval (CI) 1.10-1.80, p = 0.01], body mass index >30 kg/m 2 (OR 2.4 vs. <18.5 kg/m 2 ; 95% CI 1.1-5.1, p = 0.02), anemia (OR 1.70; 95% CI 1.40-2.10, p < 0.01), CD4 count >350 cells/mm 3 (OR 3.9 vs. <100 cells/mm 3 ; 95% CI 2.0-4.1, p < 0.01), total lymphocyte count >2000 cells/mm 3 (OR 1.7 vs. <1000 cells/mm 3 ; 95% CI 1.3-2.3, p < 0.01), and no prior AIDS-defining illness (OR 1.8; 95% CI 1.5-2.3, p < 0.01). Receiver-operator characteristic (ROC) analysis yielded area under the curve of 0.70 (95% CI 0.67-0.72) among derivation patients and 0.69 (95% CI 0.65-0.74) among validation patients. A cut off score >25 yielded the sensitivity of 46.7%, specificity of 79.1%, positive predictive value of 67.7%, and negative predictive value of 61.2% for prediction of pre-treatment HIV RNA <100,000 copies/mL among derivation patients. A model prediction for pre-treatment HIV RNA <100,000 copies/mL produced an area under the ROC curve of 0.70. A larger sample size for prediction model development as well as for model validation is warranted.

High Tumor Volume to Fetal Weight Ratio Is Associated with Worse Fetal Outcomes and Increased Maternal Risk in Fetuses with Sacrococcygeal Teratoma.

PubMed

Gebb, Juliana S; Khalek, Nahla; Qamar, Huma; Johnson, Mark P; Oliver, Edward R; Coleman, Beverly G; Peranteau, William H; Hedrick, Holly L; Flake, Alan W; Adzick, N Scott; Moldenhauer, Julie S

2018-03-01

Tumor volume to fetal weight ratio (TFR) > 0.12 before 24 weeks has been associated with poor outcome in fetuses with sacrococcygeal teratoma (SCT). We evaluated TFR in predicting poor fetal outcome and increased maternal operative risk in our cohort of SCT pregnancies. This is a retrospective, single-center review of fetuses seen with SCT from 1997 to 2015. Patients who chose termination of pregnancy (TOP), delivered elsewhere, or had initial evaluation at > 24 weeks were excluded. Receiver operating characteristic (ROC) analysis determined the optimal TFR to predict poor fetal outcome and increased maternal operative risk. Poor fetal outcome included fetal demise, neonatal demise, or fetal deterioration warranting open fetal surgery or delivery < 32 weeks. Increased maternal operative risk included cases necessitating open fetal surgery, classical cesarean delivery, or ex utero intrapartum treatment (EXIT). Of 139 pregnancies with SCT, 27 chose TOP, 14 delivered elsewhere, and 40 had initial evaluation at > 24 weeks. Thus, 58 fetuses were reviewed. ROC analysis revealed that at ≤24 weeks, TFR > 0.095 was predictive of poor fetal outcome and TFR > 0.12 was predictive of increased maternal operative risk. This study supports the use of TFR at ≤24 weeks for risk stratification of pregnancies with SCT. © 2018 S. Karger AG, Basel.

Psychological factors and treatment effectiveness in resistant anxiety disorders in highly comorbid inpatients

PubMed Central

Ociskova, Marie; Prasko, Jan; Latalova, Klara; Kamaradova, Dana; Grambal, Ales

2016-01-01

Background Anxiety disorders are a group of various mental syndromes that have been related with generally poor treatment response. Several psychological factors may improve or hinder treatment effectiveness. Hope has a direct impact on the effectiveness of psychotherapy. Also, dissociation is a significant factor influencing treatment efficiency in this group of disorders. Development of self-stigma could decrease treatment effectiveness, as well as several temperamental and character traits. The aim of this study was to explore a relationship between selected psychological factors and treatment efficacy in anxiety disorders. Subjects and methods A total of 109 inpatients suffering from anxiety disorders with high frequency of comorbidity with depression and/or personality disorder were evaluated at the start of the treatment by the following scales: the Mini-International Neuropsychiatric Interview, the Internalized Stigma of Mental Illness scale, the Adult Dispositional Hope Scale, and the Temperament and Character Inventory – revised. The participants, who sought treatment for anxiety disorders, completed the following scales at the beginning and end of an inpatient-therapy program: Clinical Global Impression (objective and subjective) the Beck Depression Inventory – second edition, the Beck Anxiety Inventory, and the Dissociative Experiences Scale. The treatment consisted of 25 group sessions and five individual sessions of cognitive behavioral therapy or psychodynamic therapy in combination with pharmacotherapy. There was no randomization to the type of group-therapy program. Results Greater improvement in psychopathology, assessed by relative change in objective Clinical Global Impression score, was connected with low initial dissociation level, harm avoidance, and self-stigma, and higher amounts of hope and self-directedness. Also, individuals without a comorbid personality disorder improved considerably more than comorbid patients. According to backward-stepwise multiple regression, the best significant predictor of treatment effectiveness was the initial level of self-stigma. Conclusion The initial higher levels of self-stigma predict a lower effectiveness of treatment in resistant-anxiety-disorder patients with high comorbidity with depression and/or personality disorder. The results suggest that an increased focus on self-stigma during therapy could lead to better treatment outcomes. PMID:27445474

Predicting radiotherapy outcomes using statistical learning techniques

NASA Astrophysics Data System (ADS)

El Naqa, Issam; Bradley, Jeffrey D.; Lindsay, Patricia E.; Hope, Andrew J.; Deasy, Joseph O.

2009-09-01

Radiotherapy outcomes are determined by complex interactions between treatment, anatomical and patient-related variables. A common obstacle to building maximally predictive outcome models for clinical practice is the failure to capture potential complexity of heterogeneous variable interactions and applicability beyond institutional data. We describe a statistical learning methodology that can automatically screen for nonlinear relations among prognostic variables and generalize to unseen data before. In this work, several types of linear and nonlinear kernels to generate interaction terms and approximate the treatment-response function are evaluated. Examples of institutional datasets of esophagitis, pneumonitis and xerostomia endpoints were used. Furthermore, an independent RTOG dataset was used for 'generalizabilty' validation. We formulated the discrimination between risk groups as a supervised learning problem. The distribution of patient groups was initially analyzed using principle components analysis (PCA) to uncover potential nonlinear behavior. The performance of the different methods was evaluated using bivariate correlations and actuarial analysis. Over-fitting was controlled via cross-validation resampling. Our results suggest that a modified support vector machine (SVM) kernel method provided superior performance on leave-one-out testing compared to logistic regression and neural networks in cases where the data exhibited nonlinear behavior on PCA. For instance, in prediction of esophagitis and pneumonitis endpoints, which exhibited nonlinear behavior on PCA, the method provided 21% and 60% improvements, respectively. Furthermore, evaluation on the independent pneumonitis RTOG dataset demonstrated good generalizabilty beyond institutional data in contrast with other models. This indicates that the prediction of treatment response can be improved by utilizing nonlinear kernel methods for discovering important nonlinear interactions among model variables. These models have the capacity to predict on unseen data. Part of this work was first presented at the Seventh International Conference on Machine Learning and Applications, San Diego, CA, USA, 11-13 December 2008.

The field size matters: low dose external beam radiotherapy for thumb carpometacarpal osteoarthritis : Importance of field size.

PubMed

Kaltenborn, Alexander; Bulling, Elke; Nitsche, Mirko; Carl, Ulrich Martin; Hermann, Robert Michael

2016-08-01

The purpose of this work was to evaluate the efficacy of low-dose radiotherapy (RT) for thumb carpometacarpal osteoarthritis (rhizarthrosis). The responses of 84 patients (n = 101 joints) were analyzed 3 months after therapy (n = 65) and at 12 months (n = 27). Patients were treated with 6 fractions of 1 Gy, two times a week, with a linear accelerator. At the end of therapy, about 70 % of patients reported a response (partial remission or complete remission), 3 months later about 60 %, and 1 year after treatment 70 %. In univariate regression analysis, higher patient age and field size greater than 6 × 4 cm were associated with response to treatment, while initial increase of pain under treatment was predictive for treatment failure. Duration of RT series (more than 18 days), gender, time of symptoms before RT, stress pain or rest pain, or prior ortheses use, injections, or surgery of the joint were not associated with treatment efficacy. In multivariate regression analysis, only field size and initial pain increase were highly correlated with treatment outcome. In conclusion, RT represents a useful treatment option for patients suffering from carpometacarpal osteoarthritis. In contrast to other benign indications, a larger field size (>6 × 4 cm) seems to be more effective than smaller fields and should be evaluated in further prospective studies.

Feasibility of implementing molecular-guided therapy for the treatment of patients with relapsed or refractory neuroblastoma

PubMed Central

Saulnier Sholler, Giselle L; Bond, Jeffrey P; Bergendahl, Genevieve; Dutta, Akshita; Dragon, Julie; Neville, Kathleen; Ferguson, William; Roberts, William; Eslin, Don; Kraveka, Jacqueline; Kaplan, Joel; Mitchell, Deanna; Parikh, Nehal; Merchant, Melinda; Ashikaga, Takamaru; Hanna, Gina; Lescault, Pamela Jean; Siniard, Ashley; Corneveaux, Jason; Huentelman, Matthew; Trent, Jeffrey

2015-01-01

The primary objective of the study was to evaluate the feasibility and safety of a process which would utilize genome-wide expression data from tumor biopsies to support individualized treatment decisions. Current treatment options for recurrent neuroblastoma are limited and ineffective, with a survival rate of <10%. Molecular profiling may provide data which will enable the practitioner to select the most appropriate therapeutic option for individual patients, thus improving outcomes. Sixteen patients with neuroblastoma were enrolled of which fourteen were eligible for this study. Feasibility was defined as completion of tumor biopsy, pathological evaluation, RNA quality control, gene expression profiling, bioinformatics analysis, generation of a drug prediction report, molecular tumor board yielding a treatment plan, independent medical monitor review, and treatment initiation within a 21 day period. All eligible biopsies passed histopathology and RNA quality control. Expression profiling by microarray and RNA sequencing were mutually validated. The average time from biopsy to report generation was 5.9 days and from biopsy to initiation of treatment was 12.4 days. No serious adverse events were observed and all adverse events were expected. Clinical benefit was seen in 64% of patients as stabilization of disease for at least one cycle of therapy or partial response. The overall response rate was 7% and the progression free survival was 59 days. This study demonstrates the feasibility and safety of performing real-time genomic profiling to guide treatment decision making for pediatric neuroblastoma patients. PMID:25720842

Pulmonary Function in Middle-Aged Patients With Idiopathic Scoliosis With Onset Before the Age of 10 Years.

PubMed

Danielsson, Aina J; Ekerljung, Linda; Hallerman, Kerstin Lofdahl

2015-09-01

Consecutive patients with idiopathic scoliosis diagnosed before age 10 attended a clinical follow-up at least 10 years after treatment. To evaluate the pulmonary function in adulthood after treatment with brace or surgery before maturity. Long-term studies of these patients have not been published. One hundred twenty-four patients (69% of the original group) underwent radiography, spirometry, and answered symptom questionnaires. A total of 73 patients had spirometries before treatment enabling longitudinal evaluation. Overall, 68 braced only (BT) and 56 surgically treated (ST) were analyzed in detail. A population-based control group was used. At follow-up, the mean age was 41.5 years and the mean curve size 36 degrees (26% of the curves >45 degrees). The full patient group had a significantly reduced pulmonary function (as measured by the forced vital capacity [FVC], percentage of predicted) compared with the control group, mean 85% versus 102% (p < .0001). Both subgroups of BT and ST patients showed a significant reduction, more in the ST than the BT group (means 79% and 90%, respectively, p = .0003). The most important risk factor for a low lung function at follow-up was a low initial FVC value. Initial curve size correlated with pulmonary function both before treatment and at follow-up. Most surgically treated patients, who had larger curves before treatment, did not improve their pulmonary function after surgery. Both braced and surgically treated patients had reduced pulmonary function at the age of around 40 years. The pulmonary function did not worsen over time in most patients. There was no difference in terms of symptoms between patient groups and controls. Initial curve size was found to be of great importance for pulmonary function. Initial spirometry and follow-up in selected patients is important. III. Copyright © 2015 Scoliosis Research Society. Published by Elsevier Inc. All rights reserved.

Diazepam and halazepam in anxiety: some prognostic indicators.

PubMed

Rickels, K; Case, W G; Chung, H; Downing, R W; Vlahovich, J

1978-01-01

A multiple step-search regression procedure was applied to data obtained with 37 diazepam and 42 halazepam treated anxious outpatients. Good treatment outcome was predicted for those patients who reported a more adequate family adjustment, the presence of precipitating stress, and who either had no prior psychotropic drug treatment, or if they had received such treatment, had experienced a good response. Probably of greatest interest to the practicing clinician was the observation that patients high in initial anxiety but low in initial interpersonal problems improved the most with both medications. Differential drug effects indicated halazepam to do particularly poorly in less anxious patients and in those patients given a good prognosis by the doctor. Diazepam response was much less affected by these variables. It is speculated that the excessive sedating effect of the daily halazepam dosage (160 mg/d) used in this study may explain these differential drug effects. In the dosages employed, namely, diazepam 20 mg/d and halazepam 160 mg/d, diazepam produced the more consistent anti-anxiety effects. The indication that halazepam 160 mg/d was more effective than diazepam 20 mg/d in the initially sicker patients, while of interest, is probably simply a dose-related phenomenon, indicating that diazepam 20 mg/d was too low a daily dosage for severely anxious patients, a fact well known by most clinicians.

Predictive modeling of treatment resistant depression using data from STAR*D and an independent clinical study.

PubMed

Nie, Zhi; Vairavan, Srinivasan; Narayan, Vaibhav A; Ye, Jieping; Li, Qingqin S

2018-01-01

Identification of risk factors of treatment resistance may be useful to guide treatment selection, avoid inefficient trial-and-error, and improve major depressive disorder (MDD) care. We extended the work in predictive modeling of treatment resistant depression (TRD) via partition of the data from the Sequenced Treatment Alternatives to Relieve Depression (STAR*D) cohort into a training and a testing dataset. We also included data from a small yet completely independent cohort RIS-INT-93 as an external test dataset. We used features from enrollment and level 1 treatment (up to week 2 response only) of STAR*D to explore the feature space comprehensively and applied machine learning methods to model TRD outcome at level 2. For TRD defined using QIDS-C16 remission criteria, multiple machine learning models were internally cross-validated in the STAR*D training dataset and externally validated in both the STAR*D testing dataset and RIS-INT-93 independent dataset with an area under the receiver operating characteristic curve (AUC) of 0.70-0.78 and 0.72-0.77, respectively. The upper bound for the AUC achievable with the full set of features could be as high as 0.78 in the STAR*D testing dataset. Model developed using top 30 features identified using feature selection technique (k-means clustering followed by χ2 test) achieved an AUC of 0.77 in the STAR*D testing dataset. In addition, the model developed using overlapping features between STAR*D and RIS-INT-93, achieved an AUC of > 0.70 in both the STAR*D testing and RIS-INT-93 datasets. Among all the features explored in STAR*D and RIS-INT-93 datasets, the most important feature was early or initial treatment response or symptom severity at week 2. These results indicate that prediction of TRD prior to undergoing a second round of antidepressant treatment could be feasible even in the absence of biomarker data.

Reduction of initial shock in decadal predictions using a new initialization strategy

NASA Astrophysics Data System (ADS)

He, Yujun; Wang, Bin

2017-04-01

Initial shock is a well-known problem occurring in the early years of a decadal prediction when assimilating full-field observations into a coupled model, which directly affects the prediction skill. For the purpose to alleviate this problem, we propose a novel full-field initialization method based on dimension-reduced projection four-dimensional variational data assimilation (DRP-4DVar). Different from the available solution strategies including anomaly assimilation and bias correction, it substantially reduces the initial shock through generating more consistent initial conditions for the coupled model, which, along with the model trajectory in one-month windows, best fit the monthly mean analysis data of oceanic temperature and salinity. We evaluate the performance of initialized hindcast experiments according to three proposed indices to measure the intensity of the initial shock. The results indicate that this strategy can obviously reduce the initial shock in decadal predictions by FGOALS-g2 (the Flexible Global Ocean-Atmosphere-Land System model, Grid-point Version 2) compared with the commonly-used nudging full-field initialization for the same model as well as the different full-field initialization strategies for other CMIP5 (the fifth phase of the Coupled Model Intercomparison Project) models whose decadal prediction results are available. It is also comparable to or even better than the anomaly initialization methods. Better hindcasts of global mean surface air temperature anomaly are obtained due to the reduction of initial shock by the new initialization scheme.

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

Mandapaka, A; Ghebremedhin, A; Patyal, B

Purpose: To validate the treatment planning system predicted proton dose beyond a heterogeneity (n-BCA glue) by making a measurement in a custom acrylic phantom. Methods: A custom cubic acrylic phantom was designed for this experiment. A container was designed to fit in the phantom. This container was filled with TRUFILL™ n-Butyl Cyanoacrylate(n-BCA) glue. When the container was placed in the phantom, its center was at a distance of 7.4cm from the entrance. This depth allows us to make measurements around the center of modulation of a 126 MeV proton beam with a 3cm spread-out-Bragg peak. To make measurements at othermore » beam energies, additional acrylic can be added in front of the phantom, to adjust the depth of the heterogeneity. A diamond detector was cross calibrated against a standard cylindrical ion chamber in a 126MeV beam. The diamond detector was then used to make dose measurements beyond the inhomogeneity. The measurement was repeated with the container filled with water. Several measurements were made at each setup, to check reproducibility of measurements. Results: For the same number of Tic3R1 counts, the dose measured with the diamond detector beyond n-BCA glue was 1.053 times the dose measured beyond the water filled container. This result is in agreement with the measured stopping power of glue (1.06). These measurements were in agreement with the dose predicted by the treatment planning system when the electron density of the heterogeneity was replaced with 1.06 before the dose calculation. Conclusion: Our initial measurements validate the dose predicted by our treatment plan in the presence of heterogeneity in a phantom. The material tested (n-BCA glue) is commonly used in the treatment of AVM’s prior to an SRS treatment. An error in dose predicted by the treatment plan in the presence of the glue can be detrimental in a single fraction high dose SRS treatment I received the n-BCA liquid embolic system samples from Codman and Shurtleff, Inc.« less

Precision Medicine-Nobody Is Average.

PubMed

Vinks, A A

2017-03-01

Medicine gets personal and tailor-made treatments are underway. Hospitals have started to advertise their advanced genomic testing capabilities and even their disruptive technologies to help foster a culture of innovation. The prediction in the lay press is that in decades from now we may look back and see 2017 as the year precision medicine blossomed. It is all part of the Precision Medicine Initiative that takes into account individual differences in people's genes, environments, and lifestyles. © 2017 ASCPT.

GRAPPA 2015 Research and Education Project Reports.

PubMed

Mease, Philip J; Helliwell, Philip S; Boehncke, Wolf-Henning; Coates, Laura C; FitzGerald, Oliver; Gladman, Dafna D; Deodhar, Atul A; Callis Duffin, Kristina

2016-05-01

At the 2015 annual meeting of the Group for Research and Assessment of Psoriasis and Psoriatic Arthritis (GRAPPA), attendees were presented with brief updates on several ongoing initiatives, including educational projects. Updates were presented on the treatment recommendations project, the development of simple criteria to identify inflammatory musculoskeletal disease, new patient/physician Delphi exercises, and BIODAM (identifying biomarkers that predict progressive structural joint damage). The publication committee also gave a report. Herein we summarize those project updates.

Effects of ocean initial perturbation on developing phase of ENSO in a coupled seasonal prediction model

NASA Astrophysics Data System (ADS)

Lee, Hyun-Chul; Kumar, Arun; Wang, Wanqiu

2018-03-01

Coupled prediction systems for seasonal and inter-annual variability in the tropical Pacific are initialized from ocean analyses. In ocean initial states, small scale perturbations are inevitably smoothed or distorted by the observational limits and data assimilation procedures, which tends to induce potential ocean initial errors for the El Nino-Southern Oscillation (ENSO) prediction. Here, the evolution and effects of ocean initial errors from the small scale perturbation on the developing phase of ENSO are investigated by an ensemble of coupled model predictions. Results show that the ocean initial errors at the thermocline in the western tropical Pacific grow rapidly to project on the first mode of equatorial Kelvin wave and propagate to the east along the thermocline. In boreal spring when the surface buoyancy flux weakens in the eastern tropical Pacific, the subsurface errors influence sea surface temperature variability and would account for the seasonal dependence of prediction skill in the NINO3 region. It is concluded that the ENSO prediction in the eastern tropical Pacific after boreal spring can be improved by increasing the observational accuracy of subsurface ocean initial states in the western tropical Pacific.

Evaluation of early weight loss thresholds for identifying nonresponders to an intensive lifestyle intervention.

PubMed

Unick, Jessica L; Hogan, Patricia E; Neiberg, Rebecca H; Cheskin, Lawrence J; Dutton, Gareth R; Evans-Hudnall, Gina; Jeffery, Robert; Kitabchi, Abbas E; Nelson, Julie A; Pi-Sunyer, F Xavier; West, Delia Smith; Wing, Rena R

2014-07-01

Weight losses in lifestyle interventions are variable, yet prediction of long-term success is difficult. The utility of using various weight loss thresholds in the first 2 months of treatment for predicting 1-year outcomes was examined. Participants included 2327 adults with type 2 diabetes (BMI:35.8 ± 6.0) randomized to the intensive lifestyle intervention (ILI) of the Look AHEAD trial. ILI included weekly behavioral sessions designed to increase physical activity and reduce caloric intake. 1-month, 2-month, and 1-year weight changes were calculated. Participants failing to achieve a ≥2% weight loss at Month 1 were 5.6 (95% CI:4.5, 7.0) times more likely to also not achieve a ≥10% weight loss at Year 1, compared to those losing ≥2% initially. These odds were increased to 11.6 (95% CI:8.6, 15.6) when using a 3% weight loss threshold at Month 2. Only 15.2% and 8.2% of individuals failing to achieve the ≥2% and ≥3% thresholds at Months 1 and 2, respectively, go on to achieve a ≥10% weight loss at Year 1. Given the association between initial and 1-year weight loss, the first few months of treatment may be an opportune time to identify those who are unsuccessful and utilize rescue efforts. clinicaltrials.gov Identifier: NCT00017953. © 2014 The Obesity Society.

FERTILITY TREATMENT RESPONSE: IS IT BETTER TO BE MORE OPTIMISTIC OR LESS PESSIMISTIC?

PubMed Central

Bleil, Maria E.; Pasch, Lauri A.; Gregorich, Steven E.; Millstein, Susan G.; Katz, Patricia P.; Adler, Nancy E.

2011-01-01

Objective To evaluate the prospective relation between dispositional traits of optimism and pessimism and IVF treatment failure among women seeking medical intervention for infertility. Methods Among 198 women (ages 24-45, M=35.1[4.1]; 77% white), the outcome of each participant’s first IVF treatment cycle was examined. Treatment outcome was classified as being successful (vs. failed) if the woman either delivered a baby or was pregnant as a result of the cycle by the end of the 18-month study period. At baseline, optimism and pessimism were measured as a single bipolar dimension and as separate unipolar dimensions according to the Life Orientation Test (LOT) total score and the optimism and pessimism subscale scores, respectively. Results Optimism/pessimism, measured as a single bipolar dimension, predicted IVF treatment failure initially (B = -.09; p = .02; OR = 0.917; 95% CI = 0.851 – 0.988), but this association attenuated following statistical control for trait negative affect (B = -.06; p = .13; OR = 0.938; 95% CI = 0.863 – 1.020). When examined as separate unipolar dimensions, pessimism (B = .14; p = .04; OR = 1.146; 95% CI = 1.008 – 1.303), but not optimism (B = -.09; p = .12; OR = 0.912; 95% CI = 0.813 – 1.023), predicted IVF treatment failure independently of risk factors for poor IVF treatment response as well as trait negative affect. Conclusions Being pessimistic may be a risk factor for IVF treatment failure. Future research should attempt to delineate the biological and behavioral mechanisms by which pessimism may negatively affect treatment outcomes. PMID:22286845

Clinical initiatives linking Japanese and Swedish healthcare resources on cancer studies utilizing Biobank Repositories.

PubMed

Nishimura, Toshihide; Kawamura, Takeshi; Sugihara, Yutaka; Bando, Yasuhiko; Sakamoto, Shigeru; Nomura, Masaharu; Ikeda, Norihiko; Ohira, Tatsuo; Fujimoto, Junichiro; Tojo, Hiromasa; Hamakubo, Takao; Kodama, Tatsuhiko; Andersson, Roland; Fehniger, Thomas E; Kato, Harubumi; Marko-Varga, György

2014-12-01

The Tokyo Medical University Hospital in Japan and the Lund University hospital in Sweden have recently initiated a research program with the objective to impact on patient treatment by clinical disease stage characterization (phenotyping), utilizing proteomics sequencing platforms. By sharing clinical experiences, patient treatment principles, and biobank strategies, our respective clinical teams in Japan and Sweden will aid in the development of predictive and drug related protein biomarkers. Data from joint lung cancer studies are presented where protein expression from Neuro- Endocrine lung cancer (LCNEC) phenotype patients can be separated from Small cell- (SCLC) and Large Cell lung cancer (LCC) patients by deep sequencing and spectral counting analysis. LCNEC, a subtype of large cell carcinoma (LCC), is characterized by neuroendocrine differentiation that small cell lung carcinoma (SCLC) shares. Pre-therapeutic histological distinction between LCNEC and SCLC has so far been problematic, leading to adverse clinical outcome. An establishment of protein targets characteristic of LCNEC is quite helpful for decision of optimal therapeutic strategy by diagnosing individual patients. Proteoform annotation and clinical biobanking is part of the HUPO initiative (http://www.hupo.org) within chromosome 10 and chromosome 19 consortia.

Management of Primary Tectal Plate Low-Grade Glioma in Pediatric Patients: Results of the Multicenter Treatment Study SIOP-LGG 2004.

PubMed

Kaufmann, Ariane; Gerber, Nicolas U; Kandels, Daniela; Azizi, Amedeo A; Schmidt, Rene; Warmuth-Metz, Monika; Pietsch, Torsten; Kortmann, Rolf-Dieter; Gnekow, Astrid K; Grotzer, Michael A

2018-06-11

 Tectal plate low-grade gliomas (LGGs) most often present with increased intracranial pressure and sometimes as incidental findings from brain imaging. Prognostic factors predicting outcome are largely unknown.  From 2004 until 2012, 71 patients with tectal plate LGG from Germany and Switzerland were followed within the SIOP-LGG 2004 study. Median age at diagnosis was 9.7 (range: 0.1-17.5) years, and median follow-up time of surviving patients was 6.3 (interquartile range: 4.9-8.3) years.  A total of 41 out of 71 patients received no tumor treatment (12 with and 29 without biopsy). The 10-year event-free survival (EFS) rate (± standard error ) for patients with an initial tumor volume of ≤3 cm 3 was 56% (±7%), as opposed to 12% (±8%) for those with tumors >3 cm 3 ( p  < 0.001). The 10-year EFS for patients without contrast enhancement on initial magnetic resonance imaging (MRI) was 52% (±9%), and for those with enhancement, it was 23% (±9%) ( p  = 0.003). The 10-year overall survival rate was 96% (±3%) (death due to disease, 1; ventriculoperitoneal shunt infection, 1). Sixty-three (89%) patients had at least one cerebrospinal fluid diversion procedure.  More than half of patients were managed without tumor treatment. Favorable prognostic factors for EFS were small initial tumor volume (≤3cm 3 ) and the absence of initial contrast enhancement on MRI. Overall survival was excellent. Georg Thieme Verlag KG Stuttgart · New York.

Response to novelty as a predictor of cocaine sensitization and conditioning in rats: a correlational analysis.

PubMed

Carey, Robert J; DePalma, Gail; Damianopoulos, Ernest

2003-07-01

An animal's response to novelty has been suggested to be a predictor of its response to drugs of abuse. The possible relationship between an individual's behavioral response to novelty and its subsequent behavioral response to cocaine has not been subjected to a detailed correlational analysis. To use a repeated cocaine treatment protocol to induce cocaine sensitization and conditioned cocaine locomotor stimulant effects and to assess the relationship of these effects to pre-cocaine locomotor behavior in a novel environment. In two separate experiments, rats were given a 20-min test in a novel open-field environment. Subsequently, the rats were given a series of additional tests in conjunction with either saline or cocaine (10 mg/kg) treatments to induce cocaine sensitization and conditioned effects. The repeated cocaine treatments induced cocaine behavioral sensitization and conditioned effects. Correlational analyses showed that the initial 20-min novel environment test proved to be a strong predictor of an animal's subsequent saline activity level but did not predict the rats' behavioral acute and sensitized response to cocaine. When change in activity was used as the dependent variable, initial activity level was reliably negatively correlated with activity changes on cocaine tests as well as cocaine conditioning tests. The negative correlation between initial activity in a novel environment and the change in activity induced by cocaine indicates that low responders to environmental novelty tend to have the strongest response to cocaine. These results appear consistent with the classic initial value and response rate dependent analyses of stimulant drug effects.

Consensus statement: Using laryngeal electromyography for the diagnosis and treatment of vocal cord paralysis.

PubMed

Munin, Michael C; Heman-Ackah, Yolanda D; Rosen, Clark A; Sulica, Lucian; Maronian, Nicole; Mandel, Steven; Carey, Bridget T; Craig, Earl; Gronseth, Gary

2016-06-01

The purpose of this study was to develop an evidence-based consensus statement regarding use of laryngeal electromyography (LEMG) for diagnosis and treatment of vocal fold paralysis after recurrent laryngeal neuropathy (RLN). Two questions regarding LEMG were analyzed: (1) Does LEMG predict recovery in patients with acute unilateral or bilateral vocal fold paralysis? (2) Do LEMG findings change clinical management in these individuals? A systematic review was performed using American Academy of Neurology criteria for rating of diagnostic accuracy. Active voluntary motor unit potential recruitment and presence of polyphasic motor unit potentials within the first 6 months after lesion onset predicted recovery. Positive sharp waves and/or fibrillation potentials did not predict outcome. The presence of electrical synkinesis may decrease the likelihood of recovery, based on 1 published study. LEMG altered clinical management by changing the initial diagnosis from RLN in 48% of cases. Cricoarytenoid fixation and superior laryngeal neuropathy were the most common other diagnoses observed. If prognostic information is required in a patient with vocal fold paralysis that is more than 4 weeks and less than 6 months in duration, then LEMG should be performed. LEMG may be performed to clarify treatment decisions for vocal fold immobility that is presumed to be caused by RLN. Muscle Nerve 53: 850-855, 2016. © 2016 Wiley Periodicals, Inc.

Molecular classification of gastric adenocarcinoma: translating new insights from the cancer genome atlas research network.

PubMed

Sunakawa, Yu; Lenz, Heinz-Josef

2015-04-01

Gastric cancer is a heterogenous cancer, which may be classified into several distinct subtypes based on pathology and epidemiology, each with different initiating pathological processes and each possibly having different tumor biology. A classification of gastric cancer should be important to select patients who can benefit from the targeted therapies or to precisely predict prognosis. The Cancer Genome Atlas (TCGA) study collaborated with previous reports regarding subtyping gastric cancer but also proposed a refined classification based on molecular characteristics. The addition of the new molecular classification strategy to a current classical subtyping may be a promising option, particularly stratification by Epstein-Barr virus (EBV) and microsatellite instability (MSI) statuses. According to TCGA study, EBV gastric cancer patients may benefit the programmed cell death protein 1 (PD-1)/programmed death-ligand 1 (PD-L1) antibodies or phosphoinositide 3-kinase (PI3K) inhibitors which are now being developed. The discoveries of predictive biomarkers should improve patient care and individualized medicine in the management since the targeted therapies may have the potential to change the landscape of gastric cancer treatment, moreover leading to both better understanding of the heterogeneity and better outcomes. Patient enrichment by predictive biomarkers for new treatment strategies will be critical to improve clinical outcomes. Additionally, liquid biopsies will be able to enable us to monitor in real-time molecular escape mechanism, resulting in better treatment strategies.

Evidence-based medical oncology and interventional radiology paradigms for liver-dominant colorectal cancer metastases

PubMed Central

Sag, Alan Alper; Selcukbiricik, Fatih; Mandel, Nil Molinas

2016-01-01

Colorectal cancer metastasizes predictably, with liver predominance in most cases. Because liver involvement has been shown to be a major determinant of survival in this population, liver-directed therapies are increasingly considered even in cases where there is (limited) extrahepatic disease. Unfortunately, these patients carry a known risk of recurrence in the liver regardless of initial therapy choice. Therefore, there is a demand for minimally invasive, non-surgical, personalized cancer treatments to preserve quality of life in the induction, consolidation, and maintenance phases of cancer therapy. This report aims to review evidence-based conceptual, pharmacological, and technological paradigm shifts in parenteral and percutaneous treatment strategies as well as forthcoming evidence regarding next-generation systemic, locoregional, and local treatment approaches for this patient population. PMID:27003990

A realistic treatment of geomagnetic Cherenkov radiation from cosmic ray air showers

NASA Astrophysics Data System (ADS)

Werner, Klaus; de Vries, Krijn D.; Scholten, Olaf

2012-09-01

We present a macroscopic calculation of coherent electro-magnetic radiation from air showers initiated by ultra-high energy cosmic rays, based on currents obtained from three-dimensional Monte Carlo simulations of air showers in a realistic geo-magnetic field. We discuss the importance of a correct treatment of the index of refraction in air, given by the law of Gladstone and Dale, which affects the pulses enormously for certain configurations, compared to a simplified treatment using a constant index. We predict in particular a geomagnetic Cherenkov radiation, which provides strong signals at high frequencies (GHz), for certain geometries together with "normal radiation" from the shower maximum, leading to a double peak structure in the frequency spectrum. We also provide some information about the numerical procedures referred to as EVA 1.0.

SU-F-P-20: Predicting Waiting Times in Radiation Oncology Using Machine Learning

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

Joseph, A; Herrera, D; Hijal, T

Purpose: Waiting times remain one of the most vexing patient satisfaction challenges facing healthcare. Waiting time uncertainty can cause patients, who are already sick or in pain, to worry about when they will receive the care they need. These waiting periods are often difficult for staff to predict and only rough estimates are typically provided based on personal experience. This level of uncertainty leaves most patients unable to plan their calendar, making the waiting experience uncomfortable, even painful. In the present era of electronic health records (EHRs), waiting times need not be so uncertain. Extensive EHRs provide unprecedented amounts ofmore » data that can statistically cluster towards representative values when appropriate patient cohorts are selected. Predictive modelling, such as machine learning, is a powerful approach that benefits from large, potentially complex, datasets. The essence of machine learning is to predict future outcomes by learning from previous experience. The application of a machine learning algorithm to waiting time data has the potential to produce personalized waiting time predictions such that the uncertainty may be removed from the patient’s waiting experience. Methods: In radiation oncology, patients typically experience several types of waiting (eg waiting at home for treatment planning, waiting in the waiting room for oncologist appointments and daily waiting in the waiting room for radiotherapy treatments). A daily treatment wait time model is discussed in this report. To develop a prediction model using our large dataset (with more than 100k sample points) a variety of machine learning algorithms from the Python package sklearn were tested. Results: We found that the Random Forest Regressor model provides the best predictions for daily radiotherapy treatment waiting times. Using this model, we achieved a median residual (actual value minus predicted value) of 0.25 minutes and a standard deviation residual of 6.5 minutes. This means that the majority of our estimates are within 6.5 minutes of the actual wait time. Conclusion: The goal of this project was to define an appropriate machine learning algorithm to estimate waiting times based on the collective knowledge and experience learned from previous patients. Our results offer an opportunity to improve the information that is provided to patients and family members regarding the amount of time they can expect to wait for radiotherapy treatment at our centre. AJ acknowledges support by the CREATE Medical Physics Research Training Network grant of the Natural Sciences and Engineering Research Council (Grant number: 432290) and from the 2014 Q+ Initiative of the McGill University Health Centre.« less

Mode of entry to an early intervention service for psychotic disorders: determinants and impact on outcome.

PubMed

Pira, Shamira; Durr, Georges; Pawliuk, Nicole; Joober, Ridha; Malla, Ashok

2013-11-01

Specialized early intervention services for first-episode psychosis should treat a proportion of patients without using inpatient beds. This study compared such service users by their initial mode of treatment before entry-inpatient (N=157) or outpatient (N=102). On entry to a Montreal early intervention service, the groups were compared on baseline clinical and functional variables and on hospitalizations during two years of treatment. Initial presentation at an emergency service, shorter duration of untreated psychosis, lower functioning level, and aggressive and bizarre behavior were associated with the inpatient entry mode to early intervention services. During follow-up, individuals entering as inpatients spent more days hospitalized than those entering as outpatients, and their time to rehospitalization was shorter. Results suggest that entry into early intervention services via the hospital emergency department and presentation with behavioral and functional disturbances were more predictive than core psychotic symptoms of hospital inpatient status on referral to an early intervention service.

The influence of gene expression profiling on decisional conflict in decision making for early-stage breast cancer chemotherapy.

PubMed

MacDonald, Karen V; Bombard, Yvonne; Deal, Ken; Trudeau, Maureen; Leighl, Natasha; Marshall, Deborah A

2016-07-01

Women with early-stage breast cancer, of whom only 15% will experience a recurrence, are often conflicted or uncertain about taking chemotherapy. Gene expression profiling (GEP) of tumours informs risk prediction, potentially affecting treatment decisions. We examined whether receiving a GEP test score reduces decisional conflict in chemotherapy treatment decision making. A general population sample of 200 women completed the decisional conflict scale (DCS) at baseline (no GEP test score scenario) and after (scenario with GEP test score added) completing a discrete choice experiment survey for early-stage breast cancer chemotherapy. We scaled the 16-item DCS total scores and subscores from 0 to 100 and calculated means, standard deviations and change in scores, with significance (p < 0.05) based on matched pairs t-tests. We identified five respondent subgroups based on preferred treatment option; almost 40% did not change their chemotherapy decision after receiving GEP testing information. Total score and all subscores (uncertainty, informed, values clarity, support, and effective decision) decreased significantly in the respondent subgroup who were unsure about taking chemotherapy initially but changed to no chemotherapy (n =33). In the subgroup of respondents (n = 25) who chose chemotherapy initially but changed to unsure, effective decision subscore increased significantly. In the overall sample, changes in total and all subscores were non-significant. GEP testing adds value for women initially unsure about chemotherapy treatment with a decrease in decisional conflict. However, for women who are confident about their treatment decisions, GEP testing may not add value. Decisions to request GEP testing should be personalised based on patient preferences. Copyright © 2016 Elsevier Ltd. All rights reserved.

Prediction of Febrile Neutropenia after Chemotherapy Based on Pretreatment Risk Factors among Cancer Patients

PubMed Central

Aagaard, Theis; Roen, Ashley; Daugaard, Gedske; Brown, Peter; Sengeløv, Henrik; Mocroft, Amanda; Lundgren, Jens; Helleberg, Marie

2017-01-01

Abstract Background Febrile neutropenia (FN) is a common complication to chemotherapy associated with a high burden of morbidity and mortality. Reliable prediction of individual risk based on pretreatment risk factors allows for stratification of preventive interventions. We aimed to develop such a risk stratification model to predict FN in the 30 days after initiation of chemotherapy. Methods We included consecutive treatment-naïve patients with solid cancers and diffuse large B-cell lymphomas at Copenhagen University Hospital, 2010–2015. Data were obtained from the PERSIMUNE repository of electronic health records. FN was defined as neutrophils ≤0.5 × 10E9/L ​at the time of either a blood culture sample or death. Time from initiation of chemotherapy to FN was analyzed using Fine-Gray models with death as a competing event. Risk factors investigated were: age, sex, body surface area, haemoglobin, albumin, neutrophil-to-lymphocyte ratio, Charlson Comorbidity Index (CCI) and chemotherapy drugs. Parameter estimates were scaled and summed to create the risk score. The scores were grouped into four: low, intermediate, high and very high risk. Results Among 8,585 patients, 467 experienced FN, incidence rate/30 person-days 0.05 (95% CI, 0.05–0.06). Age (1 point if > 65 years), albumin (1 point if < 39 g/L), CCI (1 point if > 2) and chemotherapy (range -5 to 6 points/drug) predicted FN. Median score at inclusion was 2 points (range –5 to 9). The cumulative incidence and the incidence rates and hazard ratios of FN are shown in Figure 1 and Table 1, respectively. Conclusion We developed a risk score to predict FN the first month after initiation of chemotherapy. The score is easy to use and provides good differentiation of risk groups; the score needs independent validation before routine use. Disclosures All authors: No reported disclosures.

Parent compliance: a bad predictor of resolution and a problem in the application of EAU guidelines on vesicoureteral reflux in children.

PubMed

Prisca, Radu Alexandru; Gozar, Horea; Prisca, Ana Maria; Moldovan, Cosmin; Borda, Angela

2017-05-01

Primary vesicoureteral reflux (VUR) is a controversial pathology. Current management of VUR is ruled by EAU guidelines elaborated in 2012. They defined and analyzed the risk factors and enunciated three risk groups, developing the initial treatment indications. Continuous antibiotic prophylaxis (CAP) is recommended as the initial treatment option in patients classified in moderate-risk group without low urinary tract disorder. The compliance with medication use is a concern for using CAP. The aim of the present study is to quantify the compliance of the parents of VUR patients, to analyze its impact on treatment and the applicability of EAU guidelines in our patients. This is a 4-year prospective study, which includes 202 patients aged between 1 and 174 months, diagnosed with primary VUR without LUTD. To quantify parent compliance with treatment, an algorithm was developed. Out of 202 children, 60.9% were girls. A rate of 54% patients was declared cured. In terms of compliance, incompliant patients tend toward worsening (p = 0.0001), most of them being unfollowed. Logistic regression demonstrated that the evolution of children with VUR is dependent on compliance. In conclusion, parent's compliance must be considered in EAU guidelines application, being a negative predictive factor in VUR resolution.

Predictors of response to neuroleptic treatment in schizophrenia.

PubMed

Stern, R G; Kahn, R S; Davidson, M

1993-06-01

Baseline symptom severity, early reduction in symptom severity, initial subjective response to neuroleptic treatment, the degree of brain atrophy, and early changes in pHVA levels appear to predict treatment outcome in schizophrenic patients. Computerized EEG results, neuropsychological and neurophysiologic tests, and baseline pHVA concentrations require further examination. Only a limited proportion of variance in treatment response, however, could be explained by either of the nine predictors alone or combined. Therefore, further research is necessary to discover yet unidentified determinants of treatment response. Future studies should test the validity and reliability of these five promising predictors in large groups of male and female patients, employ high standards for assessment reliability of clinical parameters, and use absolute rating scores on psychopathology as well as functional scales for the definition of good and poor treatment response. Furthermore, the statistical approach for data analysis should take in consideration the need for appropriate corrections when multiple correlations are performed and should test the extent to which these predictors are interdependent.

SU-E-T-23: A Developing Australian Network for Datamining and Modelling Routine Radiotherapy Clinical Data and Radiomics Information for Rapid Learning and Clinical Decision Support

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

Thwaites, D; Holloway, L; Bailey, M

2015-06-15

Purpose: Large amounts of routine radiotherapy (RT) data are available, which can potentially add clinical evidence to support better decisions. A developing collaborative Australian network, with a leading European partner, aims to validate, implement and extend European predictive models (PMs) for Australian practice and assess their impact on future patient decisions. Wider objectives include: developing multi-institutional rapid learning, using distributed learning approaches; and assessing and incorporating radiomics information into PMs. Methods: Two initial standalone pilots were conducted; one on NSCLC, the other on larynx, patient datasets in two different centres. Open-source rapid learning systems were installed, for data extraction andmore » mining to collect relevant clinical parameters from the centres’ databases. The European DSSs were learned (“training cohort”) and validated against local data sets (“clinical cohort”). Further NSCLC studies are underway in three more centres to pilot a wider distributed learning network. Initial radiomics work is underway. Results: For the NSCLC pilot, 159/419 patient datasets were identified meeting the PM criteria, and hence eligible for inclusion in the curative clinical cohort (for the larynx pilot, 109/125). Some missing data were imputed using Bayesian methods. For both, the European PMs successfully predicted prognosis groups, but with some differences in practice reflected. For example, the PM-predicted good prognosis NSCLC group was differentiated from a combined medium/poor prognosis group (2YOS 69% vs. 27%, p<0.001). Stage was less discriminatory in identifying prognostic groups. In the good prognosis group two-year overall survival was 65% in curatively and 18% in palliatively treated patients. Conclusion: The technical infrastructure and basic European PMs support prognosis prediction for these Australian patient groups, showing promise for supporting future personalized treatment decisions, improved treatment quality and potential practice changes. The early indications from the distributed learning and radiomics pilots strengthen this. Improved routine patient data quality should strengthen such rapid learning systems.« less

Eliciting regret improves decision making at the end of life.

PubMed

Djulbegovic, Benjamin; Tsalatsanis, Athanasios; Mhaskar, Rahul; Hozo, Iztok; Miladinovic, Branko; Tuch, Howard

2016-11-01

Management choices at the end of life are high-stake decisions fraught with emotions, chief among is regret. Our objective in this paper is to test the utility of a regret-based model to facilitate referral to hospice care while helping patients clarify their preferences on how they wish to spend the remaining days of their lives. A prospective cohort study that enrolled consecutive adult patients (n = 178) aware of the terminal nature of their disease. The patients were at the point in care where they had to decide between continuing potentially 'curative/life-prolonging' treatment (Rx) versus hospice care. Preferences were elicited using a Dual Visual Analog Scale regarding the level of regret of omission versus commission (RgO/RgC) towards hospice care and Rx. Each patient's RgO/RgC was contrasted against the predictive probability of death to suggest a management plan, which was then compared with the patient's actual choice. The probability of death was estimated using validated Palliative Performance Scale predictive model. Eighty-five percent (151/178) of patients agreed with the model's recommendations (p < 0.000001). Model predicted the actual choices for 72% (128/178) of patients (p < 0.00001). Logistic regression analysis showed that people who were initially inclined to be referred to hospice and were predicted to choose hospice over disease-directed treatment by the regret model have close to 98% probability of choosing hospice care at the end of their lives. No other factors (age, gender, race, educational status and pain level) affected their choice. Using regret to elicit choices in the end-of-life setting is both descriptively and prescriptively valid. People with terminal disease who are initially inclined to choose hospice and do not regret such a choice will select hospice care with high level of certainty. Copyright © 2016 The Author(s). Published by Elsevier Ltd.. All rights reserved.

Development of diagnostic prediction tools for bacteraemia caused by third-generation cephalosporin-resistant enterobacteria in suspected bacterial infections: a nested case-control study.

PubMed

Rottier, W C; van Werkhoven, C H; Bamberg, Y R P; Dorigo-Zetsma, J W; van de Garde, E M; van Hees, B C; Kluytmans, J A J W; Kuck, E M; van der Linden, P D; Prins, J M; Thijsen, S F T; Verbon, A; Vlaminckx, B J M; Ammerlaan, H S M; Bonten, M J M

2018-03-23

Current guidelines for the empirical antibiotic treatment predict the presence of third-generation cephalosporin-resistant enterobacterial bacteraemia (3GCR-E-Bac) in case of infection only poorly, thereby increasing unnecessary carbapenem use. We aimed to develop diagnostic scoring systems which can better predict the presence of 3GCR-E-Bac. A retrospective nested case-control study was performed that included patients ≥18 years of age from eight Dutch hospitals in whom blood cultures were obtained and intravenous antibiotics were initiated. Each patient with 3GCR-E-Bac was matched to four control infection episodes within the same hospital, based on blood-culture date and onset location (community or hospital). Starting from 32 commonly described clinical risk factors at infection onset, selection strategies were used to derive scoring systems for the probability of community- and hospital-onset 3GCR-E-Bac. 3GCR-E-Bac occurred in 90 of 22 506 (0.4%) community-onset infections and in 82 of 8110 (1.0%) hospital-onset infections, and these cases were matched to 360 community-onset and 328 hospital-onset control episodes. The derived community-onset and hospital-onset scoring systems consisted of six and nine predictors, respectively. With selected score cut-offs, the models identified 3GCR-E-Bac with sensitivity equal to existing guidelines (community-onset: 54.3%; hospital-onset: 81.5%). However, they reduced the proportion of patients classified as at risk for 3GCR-E-Bac (i.e. eligible for empirical carbapenem therapy) with 40% (95%CI 21-56%) and 49% (95%CI 39-58%) in, respectively, community-onset and hospital-onset infections. These prediction scores for 3GCR-E-Bac, specifically geared towards the initiation of empirical antibiotic treatment, may improve the balance between inappropriate antibiotics and carbapenem overuse. Copyright © 2018 European Society of Clinical Microbiology and Infectious Diseases. Published by Elsevier Ltd. All rights reserved.

Studying the effect of material initial conditions on drying induced stresses

NASA Astrophysics Data System (ADS)

Heydari, M.; Khalili, K.; Ahmadi-Brooghani, S. Y.

2018-02-01

Cracking as a result of non-uniform deformation during drying is one of defects that may occur during drying and has to be dealt with by proper drying treatment. In the current study the effect of initial condition has been investigated on stress-strain induced by drying. The convective drying of a porous clay-like material has been simulated by using a mathematical model. Mass and heat transfer along with the mechanical behavior of the object being dried make the phenomenon a highly coupled problem. The coupling variables are the solid displacement, moisture content and temperature of the porous medium. A numerical solution is sought and employed to predict the influence of initial conditions of material on the drying induced stresses, the moisture content, and the temperature variations. Simulation results showed that increasing the initial temperature is an effective way to reduce the stresses induced by drying and to obtain products with good quality without significant change in drying curve and in comparison this is more effective than intermittent drying.

Efficacy and Safety of Second-Line 5-Day Dactinomycin in Case of Methotrexate Failure for Gestational Trophoblastic Neoplasia.

PubMed

Prouvot, Catherine; Golfier, François; Massardier, Jérôme; You, Benoit; Lotz, Jean-Pierre; Patrier, Sophie; Devouassoux, Mojgan; Schott, Anne-Marie; Hajri, Touria; Bolze, Pierre-Adrien

2018-06-01

The objective of this study was to evaluate the characteristics and outcomes of patients treated for gestational trophoblastic neoplasia (GTN) with second-line 5-day dactinomycin after failed first-line 8-day methotrexate. From 1999 to 2017, patients with methotrexate resistant GTN treated with second line dactinomycin were identified at the French Trophoblastic Disease Reference Center. Using univariate and multivariate analysis, we identified significant predictive factors of second line dactinomycin failure. A total of 877 GTN patients were treated with first-line 8-day methotrexate, of which 103 required second-line 5-day dactinomycin for methotrexate failure. Complete response was observed in 78 patients (75.7% [95% confidence interval, 66.3-83.6]; P < 0.0001), whereas 25 needed third-line treatment, 13 for dactinomycin resistance and 12 for post-dactinomycin relapse. Overall survival of patients treated with dactinomycin was 100%. An interval of greater than or equal to 7 months between antecedent pregnancy termination and methotrexate initiation was a predictive factor significantly associated with second-line dactinomycin failure in multivariate analysis (exact odds ratio, 9.17 [95% confidence interval, 1.98-50.70]; P = 0.0029). No grades 4 and 5 adverse effects were experienced and the most common toxicity being grade 1 nausea (14.6%). Given a 75.7% complete response rate in methotrexate failed low-risk GTN patients treated with second-line dactinomycin and an overall survival rate of 100% after third-line treatment, the use of dactinomycin should be favored as second-line, regardless of human chorionic gonadotropin level at the time of dactinomycin initiation. However, an interval between the termination of the antecedent pregnancy and methotrexate initiation longer than 6 months should encourage considering alternative therapeutic strategies.

Intrinsic platelet reactivity before start with clopidogrel as predictor for on-clopidogrel platelet function and long-term clinical outcome.

PubMed

Hochholzer, Willibald; Valina, Christian M; Bömicke, Timo; Amann, Michael; Stratz, Christian; Nührenberg, Thomas; Trenk, Dietmar; Neumann, Franz-Josef

2015-07-01

High on-clopidogrel platelet reactivity is associated with worse clinical outcome. Previous data suggest that intrinsic platelet reactivity before initiation of clopidogrel contributes significantly to on-clopidogrel platelet reactivity. It is unknown whether intrinsic reactivity can sufficiently predict on-clopidogrel reactivity and therefore identify patients with insufficient response to clopidogrel before initiation of treatment and at risk for worse clinical outcome. This analysis included 765 consecutive patients undergoing elective coronary stent implantation. Platelet reactivity was assessed by light transmission aggregometry (5 µM ADP) before administration of clopidogrel 600mg and after intake of first maintenance dose of clopidogrel on day 1 following coronary stenting. Patients were followed for up to seven years. The combined primary endpoint was death of any cause or non-fatal myocardial infarction. Intrinsic and on-clopidogrel platelet reactivity were significant correlated (r=0.31; p < 0.001). Among all tested clinical and genetic factors including the cytochrome P450 2C19*2 polymorphism, intrinsic platelet reactivity was the strongest predictor for on-clopidogrel platelet reactivity. However, intrinsic platelet reactivity could only explain 8 % of variability of on-clopidogrel platelet function. Only on-treatment platelet reactivity was predictive for long-term clinical outcome (HR 1.47, 95 % CI 1.05-2.05; p = 0.02) whereas intrinsic platelet reactivity was not (HR 1.03, 95 % CI 0.74-1.43; p = 0.86). In conclusion, intrinsic platelet reactivity before initiation of clopidogrel is the strongest predictor of early on-clopidogrel platelet reactivity but can only explain a minor proportion of its variability and is not significantly associated with clinical outcome. Thus, baseline testing cannot substitute on-clopidogrel platelet function testing.

Predictive Model and Methodology for Heat Treatment Distortion Final Report CRADA No. TC-298-92

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

Nikkel, D. J.; McCabe, J.

This project was a multi-lab, multi-partner CRADA involving LLNL, Los Alamos National Laboratory, Sandia National Laboratories, Oak Ridge National Laboratory, Martin Marietta Energy Systems and the industrial partner, The National Center of Manufacturing Sciences (NCMS). A number of member companies of NCMS participated including General Motors Corporation, Ford Motor Company, The Torrington Company, Gear Research, the Illinois Institute of Technology Research Institute, and Deformation Control Technology •. LLNL was the lead laboratory for metrology technology used for validation of the computational tool/methodology. LLNL was also the lead laboratory for the development of the software user interface , for the computationalmore » tool. This report focuses on the participation of LLNL and NCMS. The purpose of the project was to develop a computational tool/methodology that engineers would use to predict the effects of heat treatment on the _size and shape of industrial parts made of quench hardenable alloys. Initially, the target application of the tool was gears for automotive power trains.« less

[The Predictive Factors of Stent Failure in the Treatment of Malignant Extrinsc Ureteral Obstruction Using Internal Ureteral Stents].

PubMed

Matsuura, Hiroshi; Arase, Shigeki; Hori, Yasuhide; Tochigi, Hiromi

2017-12-01

In this study, we retrospectively reviewed the experiences at our single institute in the treatment of malignant extrinsic ureteral obstruction (MUO) using ureteral stents to investigate the clinical outcomes and the predictive factors of stent failure. In 52 ureters of 38 patients who had radiologically significant hydronephrosis due to MUO, internal ureteral stents (The BARD(R) INLAY(TM) ureteral stent set) were inserted. The median follow-up interval after the initial stent insertion was 124.5 days (4-1,120). Stent failure occurred in 8 ureters (15.4%) of the 7 patients. The median interval from the first stent insertion to stent failure was 88 days (1-468). A Cox regression multivariate analysis showed that the significant predictors of stent failure were bladder invasion. Based on the possibility of stent failure, the adaptation of the internal ureteral stent placement should be considered especially in a patient with MUO combined with bladder invasion.

Investigation of a Suicide Ideation Risk Profile in People With Co-occurring Depression and Substance Use Disorder.

PubMed

Handley, Tonelle E; Kay-Lambkin, Frances J; Baker, Amanda L; Lewin, Terry J; Kelly, Brian J; Inder, Kerry J; Attia, John R; Kavanagh, David J

2016-11-01

Disengagement from services is common before suicide, hence identifying factors at treatment presentation that predict future suicidality is important. This article explores risk profiles for suicidal ideation among treatment seekers with depression and substance misuse. Participants completed assessments at baseline and 6 months. Baseline demographics, psychiatric history, and current symptoms were entered into a decision tree to predict suicidal ideation at follow-up. Sixty-three percent of participants at baseline and 43.5% at follow-up reported suicidal ideation. Baseline ideation most salient when psychiatric illness began before adulthood, increasing the rate of follow-up ideation by 16%. Among those without baseline ideation, dysfunctional attitudes were the most important risk factor, increasing rates of suicidal ideation by 35%. These findings provide evidence of factors beyond initial diagnoses that increase the likelihood of suicidal ideation and are worthy of clinical attention. In particular, providing suicide prevention resources to those with high dysfunctional attitudes may be beneficial.

Reduction of initial shock in decadal predictions using a new initialization strategy

NASA Astrophysics Data System (ADS)

He, Yujun; Wang, Bin; Liu, Mimi; Liu, Li; Yu, Yongqiang; Liu, Juanjuan; Li, Ruizhe; Zhang, Cheng; Xu, Shiming; Huang, Wenyu; Liu, Qun; Wang, Yong; Li, Feifei

2017-08-01

A novel full-field initialization strategy based on the dimension-reduced projection four-dimensional variational data assimilation (DRP-4DVar) is proposed to alleviate the well-known initial shock occurring in the early years of decadal predictions. It generates consistent initial conditions, which best fit the monthly mean oceanic analysis data along the coupled model trajectory in 1 month windows. Three indices to measure the initial shock intensity are also proposed. Results indicate that this method does reduce the initial shock in decadal predictions by Flexible Global Ocean-Atmosphere-Land System model, Grid-point version 2 (FGOALS-g2) compared with the three-dimensional variational data assimilation-based nudging full-field initialization for the same model and is comparable to or even better than the different initialization strategies for other fifth phase of the Coupled Model Intercomparison Project (CMIP5) models. Better hindcasts of global mean surface air temperature anomalies can be obtained than in other FGOALS-g2 experiments. Due to the good model response to external forcing and the reduction of initial shock, higher decadal prediction skill is achieved than in other CMIP5 models.

Impact of ethics and economics on end-of-life decisions in an Indian neonatal unit.

PubMed

Miljeteig, Ingrid; Sayeed, Sadath Ali; Jesani, Amar; Johansson, Kjell Arne; Norheim, Ole Frithjof

2009-08-01

The aim of this article was to describe how providers in an Indian NICU reach life-or-death treatment decisions. Qualitative in-depth interviews, field observations, and document analysis were conducted at an Indian nonprofit private tertiary institution that provided advanced neonatal care under conditions of resource scarcity. Compared with American and European units with similar technical capabilities, the unit studied maintained a much higher threshold for treatment initiation and continuation (range: 28-32 completed gestational weeks). We observed that complex, interrelated socioeconomic reasons influenced specific treatment decisions. Providers desired to protect families and avoid a broad range of perceived harms: they were reluctant to risk outcomes with chronic disability; they openly factored scarcity of institutional resources; they were sensitive to local, culturally entrenched intrafamilial dynamics; they placed higher regard for "precious" infants; and they felt relatively powerless to prevent gender discrimination. Formal or regulatory guidelines were either lacking or not controlling. In a tertiary-level academic Indian NICU, multiple factors external to predicted clinical survival of a preterm newborn influence treatment decisions. Providers adjust their decisions about withdrawing or withholding treatment on the basis of pragmatic considerations. Numerous issues related to resource scarcity are relevant, and providers prioritize outcomes that affect stakeholders other than the newborn. These findings may have implications for initiatives that seek to improve global neonatal health.

Prediction of the Efficacy of Antihistamines in Chronic Spontaneous Urticaria Based on Initial Suppression of the Histamine- Induced Wheal.

PubMed

Sánchez, J; Zakzuk, J; Cardona, R

2016-01-01

Antihistamines are the first line of treatment for chronic spontaneous urticaria. However, there is no effective method to predict whether an antihistamine will have a beneficial clinical effect or not. To assess whether the change in histamine-induced wheal and flare measurements 24 hours after administration of antihistamine can predict the efficacy of treatment. We performed a multicenter, triple-blind, randomized study. Patients received a daily oral dose of cetirizine, fexofenadine, bilastine, desloratadine, or ebastine over 8 weeks. After 4 weeks, a higher dose of antihistamine was administered to patients who did not experience a clinical response. A histamine skin prick test was carried out at baseline and 24 hours after the first dose of antihistamine. Disease severity (Urticaria Activity Score [UAS]), response to the histamine skin prick test, and impact on the patient's quality of life (Dermatology Life Quality Index [DLQI]) were determined every 2 weeks. The study population comprised 150 patients (30 per group) and 30 controls. Twenty-four hours after administration of antihistamine, inhibition of the histamine wheal by >75% was significantly associated with better UAS and DLQI scores. The safety and efficacy of the 5 antihistamines were similar. After updosing, rates of disease control (DLQI score <5) increased from 58.7% to 76.7%. Measurement of the histamine-induced wheal can predict which patients will have a strong clinical response to antihistamines but has limited utility for identifying nonresponders. The clinical significance of these data could be relevant in the search for new urticaria treatment regimens.

Clinical results of excimer laser photorefractive keratectomy: a multicenter study of 265 eyes.

PubMed

Aron-Rosa, D S; Colin, J; Aron, B; Burin, N; Cochener, B; Febraro, J L; Gallinaro, C; Ganem, S; Valdes, R

1995-11-01

Efficacy, predictability, and safety of excimer laser photorefractive keratectomy were evaluated at centers in Paris and Brest, France. Photoablation was performed with the VISX laser on 265 eyes (151 at the Paris center and 114 at the Brest center). The eyes were clinically and statistically evaluated over a six month follow-up. Initial myopia ranged from -0.7 to -19.4 diopters (D) (mean spherical equivalent [SE] -5.9 D) in the Paris center and from -0.9 to -14.5 D (SE -4.5 D) in the Brest center. At both centers, the mean uncorrected visual acuity was worse than 20/200; over 90% of cases in each center had a best uncorrected visual acuity of 20/100 or worse. Results are reported globally and for subgroups of myopia: Group A, SE better than or equal to -3.0 D; Group B, SE worse than -3.0 D and better than or equal to -7.0 D; Group C, SE worse than -7.0 D. Uncorrected visual acuity was significantly improved in the patients followed for six months; 64% of Paris cases and 62% of Brest cases obtained an uncorrected visual acuity of 20/40 or better. Predictability of the treatment was good; 67% of Paris eyes and 74% of Brest eyes were less than 1.0 D from the intended correction after six months. The data suggest that the initial myopia affected the efficacy and predictability of the treatment; results in the mild to moderate myopia eyes were significantly better than results in the severe myopia eyes. One case of visual acuity regression (less than one line) was observed in the two groups. This was associated with corneal haze of moderate intensity.

Brain Metastasis from Colorectal Cancer: Predictors and Treatment Outcomes.

PubMed

Nozawa, Hiroaki; Ishihara, Soichiro; Kawai, Kazushige; Sasaki, Kazuhito; Murono, Koji; Otani, Kensuke; Nishikawa, Takeshi; Tanaka, Toshiaki; Kiyomatsu, Tomomichi; Hata, Keisuke; Watanabe, Toshiaki

2017-01-01

Difficulties are associated with the management of brain metastasis (BM), which portends a poor prognosis in the treatment of colorectal cancer (CRC). The aim of the present study was to identify risk factors for BM in CRC and evaluate the outcomes of various treatment modalities. We retrospectively reviewed data on a total of 2,238 patients with primary CRC who underwent surgical resection at our hospital between 1999 and 2014. Predictive factors for BM and prognostic factors after the diagnosis of BM were examined by univariate and multivariate analyses using Cox proportional hazards models. Three patients (0.1%) had BM at the initial diagnosis, and 23 patients (1.2%) developed metachronous BM during the median follow-up period of 44.6 months. Lung and bone metastases were identified as independent predictive factors for BM. Median survival after the diagnosis of BM was 7.4 months. Stereotactic radiosurgery, administered to 41% of the patients with BM, was associated with a better postdiagnostic survival. CRC patients with metastasis to the lung or bone were at a higher risk of BM. Because the survival is still limited, it is crucial to determine the treatment strategy in consideration of the characteristics of each therapy and quality of life in CRC patients with BM. © 2017 S. Karger AG, Basel.

Parental influence on children with attention-deficit/hyperactivity disorder: II. Results of a pilot intervention training parents as friendship coaches for children.

PubMed

Mikami, Amori Yee; Lerner, Matthew D; Griggs, Marissa Swaim; McGrath, Alison; Calhoun, Casey D

2010-08-01

We report findings from a pilot intervention that trained parents to be "friendship coaches" for their children with Attention-Deficit/Hyperactivity Disorder (ADHD). Parents of 62 children with ADHD (ages 6-10; 68% male) were randomly assigned to receive the parental friendship coaching (PFC) intervention, or to be in a no-treatment control group. Families of 62 children without ADHD were included as normative comparisons. PFC was administered in eight, 90-minute sessions to parents; there was no child treatment component. Parents were taught to arrange a social context in which their children were optimally likely to develop good peer relationships. Receipt of PFC predicted improvements in children's social skills and friendship quality on playdates as reported by parents, and peer acceptance and rejection as reported by teachers unaware of treatment status. PFC also predicted increases in observed parental facilitation and corrective feedback, and reductions in criticism during the child's peer interaction, which mediated the improvements in children's peer relationships. However, no effects for PFC were found on the number of playdates hosted or on teacher report of child social skills. Findings lend initial support to a treatment model that targets parental behaviors to address children's peer problems.

Medications Development for the Treatment of Alcohol Use Disorder: Insights into the Predictive Value of Animal and Human Laboratory Models

PubMed Central

Yardley, Megan M.; Ray, Lara A.

2016-01-01

Development of effective treatments for alcohol use disorder (AUD) represents an important public health goal. This review provides a summary of completed preclinical and clinical studies testing pharmacotherapies for treatment of AUD. We discuss opportunities for improving the translation from preclinical findings to clinical trial outcomes, focusing on the validity and predictive value of animal and human laboratory models of AUD. Specifically, while preclinical studies of medications development have offered important insights into the neurobiology of the disorder and alcohol's molecular targets, limitations include the lack of standardized methods and streamlined processes whereby animal studies can readily inform human studies. Behavioral pharmacology studies provide a less expensive and valuable opportunity to assess the feasibility of a pharmacotherapy prior to initiating larger scale clinical trials by providing insights into the mechanism of the drug, which can then inform recruitment, analyses, and assessments. Summary tables are provided to illustrate the wide range of preclinical, human laboratory, and clinical studies of medications development for alcoholism. Taken together, this review highlights the challenges associated with animal paradigms, human laboratory studies and clinical trials with the overarching goal of advancing treatment development and highlighting opportunities to bridge the gap between preclinical and clinical research. PMID:26833803

ENSO Predictions in an Intermediate Coupled Model Influenced by Removing Initial Condition Errors in Sensitive Areas: A Target Observation Perspective

NASA Astrophysics Data System (ADS)

Tao, Ling-Jiang; Gao, Chuan; Zhang, Rong-Hua

2018-07-01

Previous studies indicate that ENSO predictions are particularly sensitive to the initial conditions in some key areas (socalled "sensitive areas"). And yet, few studies have quantified improvements in prediction skill in the context of an optimal observing system. In this study, the impact on prediction skill is explored using an intermediate coupled model in which errors in initial conditions formed to make ENSO predictions are removed in certain areas. Based on ideal observing system simulation experiments, the importance of various observational networks on improvement of El Niño prediction skill is examined. The results indicate that the initial states in the central and eastern equatorial Pacific are important to improve El Ni˜no prediction skill effectively. When removing the initial condition errors in the central equatorial Pacific, ENSO prediction errors can be reduced by 25%. Furthermore, combinations of various subregions are considered to demonstrate the efficiency on ENSO prediction skill. Particularly, seasonally varying observational networks are suggested to improve the prediction skill more effectively. For example, in addition to observing in the central equatorial Pacific and its north throughout the year, increasing observations in the eastern equatorial Pacific during April to October is crucially important, which can improve the prediction accuracy by 62%. These results also demonstrate the effectiveness of the conditional nonlinear optimal perturbation approach on detecting sensitive areas for target observations.

Salivary Cytokine Levels and Oral Mucositis in Head and Neck Cancer Patients Treated With Chemotherapy and Radiation Therapy

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

Bossi, Paolo, E-mail: Paolo.bossi@istitutotumori.mi.it; Bergamini, Cristiana; Miceli, Rosalba

Purpose: We assessed the presence of salivary cytokines, their modulation during chemoradiation therapy (CTRT), and their association with oral mucositis severity in patients with head and neck cancer (HNC). Methods and Materials: The present prospective observational study enrolled 55 patients with locally advanced HNC requiring CTRT. We also studied 10 healthy volunteers and 10 patients with other cancers. The salivary levels of 13 cytokines were analyzed. We constructed a cytokine predictive score of oral mucositis severity. Results: The baseline salivary cytokine levels were not associated with the severity of treatment-induced oral mucositis. The cytokine levels overall increased during treatment, especiallymore » in patients with worse mucositis. In particular, on univariable analysis, an increase of interleukin (IL)-1β (area under the curve [AUC] 0.733; P=.009), IL-6 (AUC 0.746; P=.005), and tumor necrosis factor-α (AUC 0.710; P=.005) at the third week of treatment was significantly associated with the development of severe oral mucositis. On multivariable analysis, the predictive score based on the IL-1β and IL-6 changes from baseline to week 3 was an early strong predictor of higher grade oral mucositis. Conclusions: The treatment of HNC patients with concurrent CTRT induces a significant increase in the salivary levels of IL-1β, IL-6, and tumor necrosis factor-α, all positively associated with the severity of mucosal toxicity. A greater increase of IL-1β and IL-6 3 weeks after treatment initiation is predictive of worse oral mucositis, representing a potential tool for the early identification of patients at risk.« less

Reduced tyrosine kinase inhibitor dose is predicted to be as effective as standard dose in chronic myeloid leukemia: A simulation study based on phase 3 trial data.

PubMed

Fassoni, Artur C; Baldow, Christoph; Roeder, Ingo; Glauche, Ingmar

2018-06-28

Continuing tyrosine kinase inhibitor mediated targeting of the BCR-ABL1 oncoprotein is the standard therapy for chronic myeloid leukemia and allows for a sustained disease control in the majority of patients. While therapy cessation for patients appeared as a safe option for about half of the optimally responding patients, a systematic assessment of long-term tyrosine kinase inhibitor dose de-escalation is missing. We use a mathematical model to analyze and consistently describe biphasic treatment responses from tyrosine kinase inhibitor treated patients from two independent clinical phase-3 trials. Scale estimates reveal that drug efficiency determines the initial response while the long-term behavior is limited by the rare activation of leukemic stem cells. We use this mathematical framework to investigate the influence of different dosing regimens on the treatment outcome. We provide strong evidence suggesting that tyrosine kinase inhibitor dose de-escalation (at least 50%) does not lead to a reduction of long-term treatment efficiency for most patients, which have already achieved sustained remission, and maintains the secondary decline of BCR-ABL1 levels. We demonstrate that continuous BCR-ABL1 monitoring provides patient-specific predictions of an optimal reduced dose not decreasing the anti-leukemic effect on residual leukemic stem cells. Our results are consistent with the interim results of the DESTINY trial and provide clinically testable predictions. Our results suggest that dose halving should be considered as a long-term treatment option for well-responding chronic myeloid leukemia patients under continuing maintenance therapy with tyrosine kinase inhibitors. We emphasize the clinical potential of this approach to reduce treatment-related side-effects and therapy costs. Copyright © 2018, Ferrata Storti Foundation.

Predicting Development of Mathematical Word Problem Solving Across the Intermediate Grades

PubMed Central

Tolar, Tammy D.; Fuchs, Lynn; Cirino, Paul T.; Fuchs, Douglas; Hamlett, Carol L.; Fletcher, Jack M.

2012-01-01

This study addressed predictors of the development of word problem solving (WPS) across the intermediate grades. At beginning of 3rd grade, 4 cohorts of students (N = 261) were measured on computation, language, nonverbal reasoning skills, and attentive behavior and were assessed 4 times from beginning of 3rd through end of 5th grade on 2 measures of WPS at low and high levels of complexity. Language skills were related to initial performance at both levels of complexity and did not predict growth at either level. Computational skills had an effect on initial performance in low- but not high-complexity problems and did not predict growth at either level of complexity. Attentive behavior did not predict initial performance but did predict growth in low-complexity, whereas it predicted initial performance but not growth for high-complexity problems. Nonverbal reasoning predicted initial performance and growth for low-complexity WPS, but only growth for high-complexity WPS. This evidence suggests that although mathematical structure is fixed, different cognitive resources may act as limiting factors in WPS development when the WPS context is varied. PMID:23325985

Epidemiologic trends in chronic renal replacement therapy over forty years: a Swiss dialysis experience.

PubMed

Lehmann, Petra Rhyn; Ambühl, Manon; Corleto, Domenica; Klaghofer, Richard; Ambühl, Patrice M

2012-07-02

Long term longitudinal data are scarce on epidemiological characteristics and patient outcomes in patients on maintenance dialysis, especially in Switzerland. We examined changes in epidemiology of patients undergoing renal replacement therapy by either hemodialysis or peritoneal dialysis over four decades. Single center retrospective study including all patients which initiated dialysis treatment for ESRD between 1970 and 2008. Analyses were performed for subgroups according to dialysis vintage, based on stratification into quartiles of date of first treatment. A multivariate model predicting death and survival time, using time-dependent Cox regression, was developed. 964 patients were investigated. Incident mean age progressively increased from 48 ± 14 to 64 ± 15 years from 1st to 4th quartile (p < 0.001), with a concomitant decrease in 3- and 5-year survival from 72.2 to 67.7%, and 64.1 to 54.8%, respectively. Nevertheless, live span continuously increased from 57 ± 13 to 74 ± 11 years (p < 0.001). Patients transplanted at least once were significantly younger at dialysis initiation, with significantly better survival, however, shortened live span vs. individuals remaining on dialysis. Among age at time of initiating dialysis therapy, sex, dialysis modality and transplant status, only transplant status is a significant independent covariate predicting death (HR: 0.10 for transplanted vs. non-transplanted patients, p = 0.001). Dialysis vintage was associated with better survival during the second vs. the first quartile (p = 0.026). We document an increase of a predominantly elderly incident and prevalent dialysis population, with progressively shortened survival after initiation of renal replacement over four decades, and, nevertheless, a prolonged lifespan. Analysis of the data is limited by lack of information on comorbidity in the study population. Survival in patients on renal replacement therapy seems to be affected not only by medical and technical advances in dialysis therapy, but may mostly reflect progressively lower mortality of individuals with cardiovascular and metabolic complications, as well as a policy of accepting older and polymorbid patients for dialysis in more recent times. This is relevant to make demographic predictions in face of the ESRD epidemic nephrologists and policy makers are facing in industrialized countries.

Epidemiologic trends in chronic renal replacement therapy over forty years: A Swiss dialysis experience

PubMed Central

2012-01-01

Background Long term longitudinal data are scarce on epidemiological characteristics and patient outcomes in patients on maintenance dialysis, especially in Switzerland. We examined changes in epidemiology of patients undergoing renal replacement therapy by either hemodialysis or peritoneal dialysis over four decades. Methods Single center retrospective study including all patients which initiated dialysis treatment for ESRD between 1970 and 2008. Analyses were performed for subgroups according to dialysis vintage, based on stratification into quartiles of date of first treatment. A multivariate model predicting death and survival time, using time-dependent Cox regression, was developed. Results 964 patients were investigated. Incident mean age progressively increased from 48 ± 14 to 64 ± 15 years from 1st to 4th quartile (p < 0.001), with a concomitant decrease in 3- and 5-year survival from 72.2 to 67.7%, and 64.1 to 54.8%, respectively. Nevertheless, live span continuously increased from 57 ± 13 to 74 ± 11 years (p < 0.001). Patients transplanted at least once were significantly younger at dialysis initiation, with significantly better survival, however, shortened live span vs. individuals remaining on dialysis. Among age at time of initiating dialysis therapy, sex, dialysis modality and transplant status, only transplant status is a significant independent covariate predicting death (HR: 0.10 for transplanted vs. non-transplanted patients, p = 0.001). Dialysis vintage was associated with better survival during the second vs. the first quartile (p = 0.026). Discussion We document an increase of a predominantly elderly incident and prevalent dialysis population, with progressively shortened survival after initiation of renal replacement over four decades, and, nevertheless, a prolonged lifespan. Analysis of the data is limited by lack of information on comorbidity in the study population. Conclusions Survival in patients on renal replacement therapy seems to be affected not only by medical and technical advances in dialysis therapy, but may mostly reflect progressively lower mortality of individuals with cardiovascular and metabolic complications, as well as a policy of accepting older and polymorbid patients for dialysis in more recent times. This is relevant to make demographic predictions in face of the ESRD epidemic nephrologists and policy makers are facing in industrialized countries. PMID:22747751

Methylation of HOXA9 and ISL1 Predicts Patient Outcome in High-Grade Non-Invasive Bladder Cancer

PubMed Central

Kitchen, Mark O.; Bryan, Richard T.; Haworth, Kim E.; Emes, Richard D.; Luscombe, Christopher; Gommersall, Lyndon; Cheng, K. K.; Zeegers, Maurice P.; James, Nicholas D.; Devall, Adam J.; Fryer, Anthony A.; Farrell, William E.

2015-01-01

Introduction Inappropriate DNA methylation is frequently associated with human tumour development, and in specific cases, is associated with clinical outcomes. Previous reports of DNA methylation in low/intermediate grade non-muscle invasive bladder cancer (NMIBC) have suggested that specific patterns of DNA methylation may have a role as diagnostic or prognostic biomarkers. In view of the aggressive and clinically unpredictable nature of high-grade (HG) NMIBC, and the current shortage of the preferred treatment option (Bacillus:Calmette-Guerin), novel methylation analyses may similarly reveal biomarkers of disease outcome that could risk-stratify patients and guide clinical management at initial diagnosis. Methods Promoter-associated CpG island methylation was determined in primary tumour tissue of 36 initial presentation high-grade NMIBCs, 12 low/intermediate-grade NMIBCs and 3 normal bladder controls. The genes HOXA9, ISL1, NKX6-2, SPAG6, ZIC1 and ZNF154 were selected for investigation on the basis of previous reports and/or prognostic utility in low/intermediate-grade NMIBC. Methylation was determined by Pyrosequencing of sodium-bisulphite converted DNA, and then correlated with gene expression using RT-qPCR. Methylation was additionally correlated with tumour behaviour, including tumour recurrence and progression to muscle invasive bladder cancer or metastases. Results The ISL1 genes’ promoter-associated island was more frequently methylated in recurrent and progressive high-grade tumours than their non-recurrent counterparts (60.0% vs. 18.2%, p = 0.008). ISL1 and HOXA9 showed significantly higher mean methylation in recurrent and progressive tumours compared to non-recurrent tumours (43.3% vs. 20.9%, p = 0.016 and 34.5% vs 17.6%, p = 0.017, respectively). Concurrent ISL1/HOXA9 methylation in HG-NMIBC reliably predicted tumour recurrence and progression within one year (Positive Predictive Value 91.7%), and was associated with disease-specific mortality (DSM). Conclusions In this study we report methylation differences and similarities between clinical sub-types of high-grade NMIBC. We report the potential ability of methylation biomarkers, at initial diagnosis, to predict tumour recurrence and progression within one year of diagnosis. We found that specific biomarkers reliably predict disease outcome and therefore may help guide patient treatment despite the unpredictable clinical course and heterogeneity of high-grade NMIBC. Further investigation is required, including validation in a larger patient cohort, to confirm the clinical utility of methylation biomarkers in high-grade NMIBC. PMID:26332997

Ovulation induction in normogonadotropic anovulation (PCOS).

PubMed

van Santbrink, Evert J P; Fauser, Bart C J M

2006-06-01

Treatment of normogonadotropic anovulatory infertility (World Health Organization class 2, or WHO2) is by induction of ovulation using clomiphene citrate (CC), followed by follicle-stimulating hormone (FSH) in cases of treatment failure. Not all patients will become ovulatory or will conceive with this treatment. Others, exhibiting multifollicular instead of monofollicular development, may encounter complications such as ovarian hyperstimulation and multiple pregnancy. Recently introduced alternative treatment interventions-such as insulin-sensitizing drugs, aromatase inhibitors, or laparoscopic electrocautery of the ovaries-may offer the possibility of improving the efficacy of the classical ovulation induction algorithm. Based on initial patient characteristics, it may be possible to identify specific patient subgroups with altered chances of success or complications while using one of these interventions. Regarding CC and FSH ovulation induction, this has been performed using multivariate prediction models. This approach may enable us to improve safety, cost-effectiveness, and patient convenience in future ovulation induction.

Symptomatic reversal of peripheral neuropathy in patients with diabetes.

PubMed

Kochman, Alan B; Carnegie, Dale H; Burke, Thomas J

2002-03-01

Forty-nine consecutive subjects with established diabetic peripheral neuropathy were treated with monochromatic near-infrared photo energy (MIRE) to determine if there was an improvement of sensation. Loss of protective sensation characterized by Semmes-Weinstein monofilament values of 4.56 and above was present in 100% of subjects (range, 4.56 to 6.45), and 42 subjects (86%) had Semmes-Weinstein values of 5.07 or higher. The ability to discriminate between hot and cold sensation was absent (54%) or impaired (46%) in both groups prior to the initiation of MIRE treatment. On the basis of Semmes-Weinstein monofilament values, 48 subjects (98%) exhibited improved sensation after 6 treatments, and all subjects had improved sensation after 12 treatments. Therefore, MIRE may be a safe, drug-free, noninvasive treatment for the consistent and predictable improvement of sensation in diabetic patients with peripheral neuropathy of the feet.

A pilot study of the effects of behavioral weight loss treatment on fibromyalgia symptoms.

PubMed

Shapiro, Jennifer R; Anderson, Drew A; Danoff-Burg, Sharon

2005-11-01

Previous studies have found a relation between weight loss and pain severity in various chronic pain populations. However, there has been little research examining the relation between body mass index (BMI) and fibromyalgia syndrome (FMS). The purpose of this pilot study was to investigate the relationship between BMI and FMS symptoms and to determine if FMS symptoms would decrease following weight loss. Overweight and obese women participated in a 20-week behavioral weight loss treatment. Participants, on average, lost 9.2 lbs (4.4% of their initial weight), and there were significant pre-postimprovements on several outcome measures. Although weight was not significantly related to pain at baseline, weight loss significantly predicted a reduction in FMS, pain interference, body satisfaction, and quality of life (QOL). Findings suggest that behavioral weight loss treatment could be included in the treatment for overweight/obese women with FMS.

Initial subjective reward to alcohol in Sprague-Dawley rats.

PubMed

Nentwig, Todd B; Myers, Kevin P; Grisel, Judith E

2017-02-01

Initial subjective response to the rewarding properties of alcohol predicts voluntary consumption and the risk for alcohol use disorders. We assessed the initial subjective reward to alcohol in rats using a single exposure conditioned place preference (SE-CPP) paradigm. Sprague-Dawley rats demonstrate preference for a context paired with a single systemic injection of ethanol (1.0 g/kg, delivered intraperitoneally). However, expression of SE-CPP in males depended on pairing ethanol with the first exposure of two (ethanol; saline) to the conditioning apparatus and procedures, while conditioning day did not appreciably affect SE-CPP in females, consistent with the view that females experience heightened addiction vulnerability. This model offers researchers a high throughput assay for investigating factors that influence alcohol reward and may point the way toward more effective prevention and treatment efforts. Copyright © 2016 Elsevier Inc. All rights reserved.

Therapeutic value of gastrografin in adhesive small bowel obstruction after unsuccessful conservative treatment: a prospective randomized trial.

PubMed

Choi, Hok-Kwok; Chu, Kin-Wah; Law, Wai-Lun

2002-07-01

To assess the therapeutic value of Gastrografin in the management of adhesive small bowel obstruction after unsuccessful conservative treatment. Gastrografin is a hyperosmolar water-soluble contrast medium. Besides its predictive value for the need for surgery, there is probably a therapeutic role of this contrast medium in adhesive small bowel obstruction. Patients with clinical evidence of adhesive small bowel obstruction were given trial conservative treatment unless there was suspicion of strangulation. Those who responded in the initial 48 hours had conservative treatment continued. Patients showing no clinical and radiologic improvement in the initial 48 hours were randomized to undergo either Gastrografin meal and follow-through study or surgery. Contrast that appeared in the large bowel within 24 hours was regarded as a partial obstruction, and conservative treatment was continued. Patients in whom contrast failed to reach the large bowel within 24 hours were considered to have complete obstruction, and laparotomy was performed. For patients who had conservative treatment for more than 48 hours with or without Gastrografin, surgery was performed when there was no continuing improvement. One hundred twenty-four patients with a total of 139 episodes of adhesive obstruction were included. Three patients underwent surgery soon after admission for suspected bowel strangulation. Strangulating obstruction was confirmed in two patients. One hundred one obstructive episodes showed improvement in the initial 48 hours and conservative treatment was continued. Only one patient required surgical treatment subsequently after conservative treatment for 6 days. Thirty-five patients showed no improvement within 48 hours. Nineteen patients were randomized to undergo Gastrografin meal and follow-through study and 16 patients to surgery. Gastrografin study revealed partial obstruction in 14 patients. Obstruction resolved subsequently in all of them after a mean of 41 hours. The other five patients underwent laparotomy because the contrast study showed complete obstruction. The use of Gastrografin significantly reduced the need for surgery by 74%. There was no complication that could be attributed to the use of Gastrografin. No strangulation of bowel occurred in either group. The use of Gastrografin in adhesive small bowel obstruction is safe and reduces the need for surgery when conservative treatment fails.

Motivational stage of change in young patients undergoing day treatment for eating disorders.

PubMed

Bustin, Lisa A; Lane-Loney, Susan E; Hollenbeak, Christopher S; Ornstein, Rollyn M

2013-01-01

The objective was to determine whether motivation to change is significantly altered over the course of partial hospitalization in children and adolescents with eating disorders (EDs). This study was a retrospective chart review of 30 sets of adolescents and their parents who completed the Motivational Stage of Change for Adolescents Recovering from an Eating Disorder (MSCARED) at both intake and discharge from partial hospitalization. The main outcome variables included change in stage of change (SOC) for patients and their parents. Secondary outcomes included correlations between SOC and other baseline variables, as well as changes in SOC and psychological test scores. The SOC was significantly higher at discharge than at intake in both the patients and parents, but the two groups were not in agreement at discharge. The change in the SOC was correlated with change in Children's Eating Attitudes Test scores. Assessment of decisional balance showed correlations with SOC. Age, change in weight, and psychiatric diagnoses did not correlate with initial SOC. The MSCARED may be a useful tool for monitoring young ED patients' psychological improvements with day treatment. Initial SOC is not predictive of treatment outcomes.

Virtual Treatment of Basilar Aneurysms Using Shape Memory Polymer Foam

NASA Astrophysics Data System (ADS)

Ortega, J. M.; Hartman, J.; Rodriguez, J. N.; Maitland, D. J.

2012-11-01

Numerical simulations are performed on patient-specific basilar aneurysms that are treated with shape memory polymer (SMP) foam. In order to assess the post-treatment hemodynamics, two modeling approaches are employed. In the first, the foam geometry is obtained from a micro-CT scan and the pulsatile blood flow within the foam is simulated for both Newtonian and non-Newtonian viscosity models. In the second, the foam is represented as a porous media continuum, which has permeability properties that are determined by computing the pressure gradient through the foam geometry over a range of flow speeds comparable to those of in vivo conditions. Virtual angiography and additional post-processing demonstrate that the SMP foam significantly reduces the blood flow speed within the treated aneurysms, while eliminating the high-frequency velocity fluctuations that are present prior to treatment. A prediction of the initial locations of thrombus formation throughout the SMP foam is obtained by means of a low fidelity thrombosis model that is based upon the residence time and shear rate of blood. The two modeling approaches capture similar qualitative trends for the initial locations of thrombus within the SMP foam.

Lower NIH stroke scale scores are required to accurately predict a good prognosis in posterior circulation stroke.

PubMed

Inoa, Violiza; Aron, Abraham W; Staff, Ilene; Fortunato, Gilbert; Sansing, Lauren H

2014-01-01

The NIH stroke scale (NIHSS) is an indispensable tool that aids in the determination of acute stroke prognosis and decision making. Patients with posterior circulation (PC) strokes often present with lower NIHSS scores, which may result in the withholding of thrombolytic treatment from these patients. However, whether these lower initial NIHSS scores predict better long-term prognoses is uncertain. We aimed to assess the utility of the NIHSS at presentation for predicting the functional outcome at 3 months in anterior circulation (AC) versus PC strokes. This was a retrospective analysis of a large prospectively collected database of adults with acute ischemic stroke. Univariate and multivariate analyses were conducted to identify factors associated with outcome. Additional analyses were performed to determine the receiver operating characteristic (ROC) curves for NIHSS scores and outcomes in AC and PC infarctions. Both the optimal cutoffs for maximal diagnostic accuracy and the cutoffs to obtain >80% sensitivity for poor outcomes were determined in AC and PC strokes. The analysis included 1,197 patients with AC stroke and 372 with PC stroke. The median initial NIHSS score for patients with AC strokes was 7 and for PC strokes it was 2. The majority (71%) of PC stroke patients had baseline NIHSS scores ≤4, and 15% of these 'minor' stroke patients had a poor outcome at 3 months. ROC analysis identified that the optimal NIHSS cutoff for outcome prediction after infarction in the AC was 8 and for infarction in the PC it was 4. To achieve >80% sensitivity for detecting patients with a subsequent poor outcome, the NIHSS cutoff for infarctions in the AC was 4 and for infarctions in the PC it was 2. The NIHSS cutoff that most accurately predicts outcomes is 4 points higher in AC compared to PC infarctions. There is potential for poor outcomes in patients with PC strokes and low NIHSS scores, suggesting that thrombolytic treatment should not be withheld from these patients based solely on the NIHSS. © 2014 S. Karger AG, Basel. © 2014 S. Karger AG, Basel.

A retrospective observational analysis to identify patient and treatment-related predictors of outcomes in a community mental health programme.

PubMed

Green, Stuart A; Honeybourne, Emmi; Chalkley, Sylvia R; Poots, Alan J; Woodcock, Thomas; Price, Geraint; Bell, Derek; Green, John

2015-05-20

This study aims to identify patient and treatment factors that affect clinical outcomes of community psychological therapy through the development of a predictive model using historic data from 2 services in London. In addition, the study aims to assess the completeness of data collection, explore how treatment outcomes are discriminated using current criteria for classifying recovery, and assess the feasibility and need for undertaking a future larger population analysis. Observational, retrospective discriminant analysis. 2 London community mental health services that provide psychological therapies for common mental disorders including anxiety and depression. A total of 7388 patients attended the services between February 2009 and May 2012, of which 4393 (59%) completed therapy, or there was an agreement to end therapy, and were included in the study. Different combinations of the clinical outcome scores for anxiety Generalised Anxiety Disorder-7 and depression Patient Health Questionnaire-9 were used to construct different treatment outcomes. The predictive models were able to assign a positive or negative clinical outcome to each patient based on 5 independent pre-treatment variables, with an accuracy of 69.4% and 79.3%, respectively: initial severity of anxiety and depression, ethnicity, deprivation and gender. The number of sessions attended/missed were also important factors identified in recovery. Predicting whether patients are likely to have a positive outcome following treatment at entry might allow suitable modification of scheduled treatment, possibly resulting in improvements in outcomes. The model also highlights factors not only associated with poorer outcomes but inextricably linked to prevalence of common mental disorders, emphasising the importance of social determinants not only in poor health but also poor recovery. 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.

Esthetic Rehabilitation of Anterior Teeth with Laminates Composite Veneers

PubMed Central

Riva, Giancarlo

2014-01-01

No- or minimal-preparation veneers associated with enamel preservation offer predictable results in esthetic dentistry; indirect additive anterior composite restorations represent a quick, minimally invasive, inexpensive, and repairable option for a smile enhancement treatment plan. Current laboratory techniques associated with a strict clinical protocol satisfy patients' restorative and esthetic needs. The case report presented describes minimal invasive treatment of four upper incisors with laminate nanohybrid resin composite veneers. A step-by-step protocol is proposed for diagnostic evaluation, mock-up fabrication and trial, teeth preparation and impression, and adhesive cementation. The resolution of initial esthetic issues, patient satisfaction, and nice integration of indirect restorations confirmed the success of this anterior dentition rehabilitation. PMID:25013730

Performance of immunological response in predicting virological failure.

PubMed

Ingole, Nayana; Mehta, Preeti; Pazare, Amar; Paranjpe, Supriya; Sarkate, Purva

2013-03-01

In HIV-infected individuals on antiretroviral therapy (ART), the decision on when to switch from first-line to second-line therapy is dictated by treatment failure, and this can be measured in three ways: clinically, immunologically, and virologically. While viral load (VL) decreases and CD4 cell increases typically occur together after starting ART, discordant responses may be seen. Hence the current study was designed to determine the immunological and virological response to ART and to evaluate the utility of immunological response to predict virological failure. All treatment-naive HIV-positive individuals aged >18 years who were eligible for ART were enrolled and assessed at baseline, 6 months, and 12 months clinically and by CD4 cell count and viral load estimations. The patients were categorized as showing concordant favorable (CF), immunological only (IO), virological only (VO), and concordant unfavorable responses (CU). The efficiency of immunological failure to predict virological failure was analyzed across various levels of virological failure (VL>50, >500, and >5,000 copies/ml). At 6 months, 87(79.81%), 7(5.5%), 13 (11.92%), and 2 (1.83%) patients and at 12 months 61(69.3%), 9(10.2%), 16 (18.2%), and 2 (2.3%) patients had CF, IO, VO, and CU responses, respectively. Immunological failure criteria had a very low sensitivity (11.1-40%) and positive predictive value (8.3-25%) to predict virological failure. Immunological criteria do not accurately predict virological failure resulting in significant misclassification of therapeutic responses. There is an urgent need for inclusion of viral load testing in the initiation and monitoring of ART.

Absence of verbal recall or memory for symptom acquisition in fear and trauma exposure: a conceptual case for fear conditioning and learned nonuse in assessment and treatment.

PubMed

Seifert, A Ronald

2012-01-01

Absence of memory or verbal recall for symptom acquisition in fear and trauma exposure, as well as absence of successful coping behavior for life events, is associated with a number of diagnoses, including traumatic brain injury, posttraumatic stress disorder, pain, and anxiety. The difficulty with diagnosis and treatment planning based on the absence of recall, memory, and successful coping behavior is threefold: (1) these assessments do not distinguish between disruption of behavior and lack of capacity, (2) the absence of verbal recall and memory complicates cognitive-based treatment, and (3) a confounding issue is the same absent behavior can be observed at different times and contexts. While memory of the specific details of the initial traumatic event(s) may not be available to verbal report, the existence of time- and context-dependent relationships for the initial as well as subsequent experiences is arguable. The absence of memory or lack of verbal recall does not rule out measurable physiological bodily responses for the initial trauma(s), nor does it help to establish the effects of subsequent experiences for symptom expression. Also, the absence of memory must include the prospect of fear-based learning that does not require or involve the cortex. It is posited that the literatures of fear conditioning and learned nonuse provide complementary illustrations of how the time and context of the initial trauma(s) and subsequent experiences affect behavior, which is not dependent on the effected individual being able to provide a memory-based verbal report. The replicated clinical application demonstrates that, without scientific demonstration, neither neuroanatomy nor verbal report can be assumed sufficient to predict overt behavior or physiologic responses. For example, while commonly assumed to be predictively so, autonomic nervous system innervation is insufficient to define the unique stimulus- and context-dependent physiological responses of an individual. By recording simultaneous physiological responses to the controlled presentation of a context-dependent stimulus, the unique relationships of physiology and overt behaviors for the individual can be demonstrated. Using this process also allows more complex virtual reality or other in vivo stimulus assessments to be incorporated for the development of individually tailored assessments and therapeutic plans. Thus, with or without memory or verbal recall, the use of multiple time- and context-specific simultaneous physiological measures and overt behavior can guide clinical effort as well as serve to objectively assess the ongoing treatment and its outcome.

Predicting running away in girls who are victims of commercial sexual exploitation.

PubMed

Hershberger, Alexandra R; Sanders, Jasmyn; Chick, Crisanna; Jessup, Megan; Hanlin, Hugh; Cyders, Melissa A

2018-05-01

Youth that are victims of commercial sexual exploitation of children (CSEC) have a host of clinical problems and often run away from home, residential care, and treatment, which complicates and limits treatment effectiveness. No research to date has attempted to predict running away in CSEC victims. The present study aimed to 1) characterize a clinically referred sample of girls who were victims of CSEC and compare them to other high-risk girls (i.e., girls who also have a history of trauma and running away, but deny CSEC); and 2) examine the utility of using the Youth Level of Service/Case Management Inventory (YLS/CMI) to predict future running away. Data were collected from de-identified charts of 80 girls (mean age = 15.38, SD = 1.3, 37.9% White, 52.5% CSEC victims) who were referred for psychological assessment by the Department of Child Services. Girls in the CSEC group were more likely to have experienced sexual abuse (χ 2  = 6.85, p = .009), an STI (χ 2  = 6.45, p = .01), a post-traumatic stress disorder diagnosis (χ 2  = 11.84, p = .001), and a substance use disorder diagnosis (χ 2  = 11.32, p = .001) than high-risk girls. Moderated regression results indicated that YLS/CMI scores significantly predicted future running away among the CSEC group (β = 0.23, SE = .06, p = .02), but not the high-risk group (β = -.008, SE = .11, p =.90). The YLS/CMI shows initial promise for predicting future running away in girls who are CSEC victims. Predicting running away can help identify those at risk for and prevent running away and improve treatment outcomes. We hope current findings stimulate future work in this area. Copyright © 2018 Elsevier Ltd. All rights reserved.

Behavioral Impulsivity Does Not Predict Naturalistic Alcohol Consumption or Treatment Outcomes

PubMed Central

Mullen, Jillian; Mathias, Charles W.; Karns, Tara E.; Liang, Yuanyuan; Hill-Kapturczak, Nathalie; Roache, John D.; Lamb, Richard J.; Dougherty, Donald M.

2016-01-01

Objective The purpose of this study was to determine if behavioral impulsivity under multiple conditions (baseline, after alcohol consumption or after serotonin depletion) predicted naturalistic alcohol use or treatment outcomes from a moderation-based contingency management intervention. Method The current data analysis pulls information from three phases of a large study: 1) Phase 1 examined baseline and the effects of alcohol use and serotonin depletion on three types of behavioral impulsivity: response initiation (IMT task), response inhibition (GoStop task), and delay discounting (SKIP task); 2) Phase 2 involved 28 days of naturalistic drinking; and 3) Phase 3 involved 3 months of contingency management. During phases 2 and 3 alcohol use was measured objectively using transdermal alcohol monitors. The results of each individual phase has been previously published showing that at a group level the effects of alcohol consumption on impulsivity were dependent on the component of impulsivity being measured and the dose of alcohol consumed but serotonin depletion had no effect on impulsivity, and that a moderation-based contingency management intervention reduced heavy drinking. Results The current analysis combining data from those who completed all three phases (n = 67) showed that impulsivity measured at baseline, after alcohol consumption, or after serotonin depletion did not predict naturalistic drinking or treatment outcomes from a moderation-based CM treatment. Conclusions Contingency management interventions may prove to be an effective intervention for impulsive individuals, however, normal variations in measured impulsivity do not seem to relate to normal variations in drinking pattern or response to moderation-based contingency management. PMID:27746702

Metformin Accumulation Correlates with Organic Cation Transporter 2 Protein Expression and Predicts Mammary Tumor Regression in Vivo

PubMed Central

Checkley, L. Allyson; Rudolph, Michael C.; Wellberg, Elizabeth A.; Giles, Erin D.; Wahdan-Alaswad, Reema S.; Houck, Julie A.; Edgerton, Susan M.; Thor, Ann D.; Schedin, Pepper; Anderson, Steven M.; MacLean, Paul S.

2017-01-01

Several epidemiological studies have associated metformin treatment with a reduction in breast cancer incidence in pre-diabetic and type II diabetic populations. Uncertainty exists regarding which patient populations and/or tumor subtypes will benefit from metformin treatment, and most preclinical in vivo studies have given little attention to the cellular pharmacology of intratumoral metformin uptake. Epidemiological reports consistently link western-style high fat diets, which drive overweight and obesity, with increased risk of breast cancer. We used a rat model of high fat diet (HFD) induced overweight and mammary carcinogenesis to define intratumoral factors that confer metformin sensitivity. Mammary tumors were initiated with N-methyl-N-nitrosourea (MNU), and rats were randomized into metformin-treated (2 mg/ml drinking water) or control groups (water only) for 8 weeks. Two-thirds of existing mammary tumors responded to metformin treatment with decreased tumor volumes (p<0.05), reduced proliferative index (p<0.01), and activated AMPK (p<0.05). Highly responsive tumors accumulated 3-fold greater metformin amounts (p<0.05) that were positively correlated with organic cation transporter-2 (OCT2) protein expression (r=0.57, P=0.038). Importantly, intratumoral metformin concentration negatively associated with tumor volume (P=0.03), and each 10 pmol increase in intratumoral metformin predicted >0.11 cm3 reduction in tumor volume. Metformin treatment also decreased proinflammatory arachidonic acid >1.5 fold in responsive tumors (P=0.023). Collectively, these preclinical data provide evidence for a direct effect of metformin in vivo and suggest that OCT2 expression may predict metformin uptake and tumor response. PMID:28154203

High-b-value diffusion-weighted MR imaging for pretreatment prediction and early monitoring of tumor response to therapy in mice.

PubMed

Roth, Yiftach; Tichler, Thomas; Kostenich, Genady; Ruiz-Cabello, Jesus; Maier, Stephan E; Cohen, Jack S; Orenstein, Arie; Mardor, Yael

2004-09-01

To evaluate the use of diffusion-weighted magnetic resonance (MR) imaging with standard and high b values for pretreatment prediction and early detection of tumor response to various antineoplastic therapies in an animal model. Mice bearing C26 colon carcinoma tumors were treated with doxorubicin (n = 25) and with aminolevulinic acid-based photodynamic therapy (n = 23). Fourteen mice served as controls. Conventional T2-weighted fast spin-echo and diffusion-weighted MR images were acquired once before therapy and at 6, 24, and 48 hours after treatment. Pretreatment and early (1-2 days) posttreatment water diffusion parameters were calculated and compared with later changes in tumor volumes measured on conventional MR images by using the Pearson correlation test. In chemotherapy-treated tumors, a significant correlation (P <.002, r = 0.6) was observed between diffusion parameters that reflected tumor viability, measured prior to treatment, and changes in tumor volumes after therapy. This correlation implies that tumors with high pretreatment viability will respond better to chemotherapy than more necrotic tumors. In tumors treated with photodynamic therapy, no such correlation was found. Changes observed in water diffusion 1-2 days after treatment significantly correlated with later tumor growth rate for both therapies (P <.002, r = 0.54 for photodynamic therapy; P <.0003, r = 0.61 for chemotherapy). High-b-value diffusion-weighted MR imaging has potential use for the early detection of response to therapy and for predicting treatment outcome prior to initiation of chemotherapy. Copyright RSNA, 2004

Opiate v CNS depressant therapy in neonatal drug abstinence syndrome.

PubMed

Kandall, S R; Doberczak, T M; Mauer, K R; Strashun, R H; Korts, D C

1983-04-01

Paregoric and phenobarbital, administered randomly in 153 passively addicted neonates, initially appeared to control neonatal abstinence signs equally well. However, seven of the 62 phenobarbital-treated newborns had abstinence-associated seizures within the first month of life, while none of 49 paregoric-treated neonates had seizures. Forty-two neonates initially requiring no specific pharmacotherapy for abstinence signs were born to mothers taking less methadone hydrochloride just before delivery. Five of those 42 neonates, however, had seizures within the first 14 days of life. Seizure occurrence could not be predicted from analysis of early abstinence patterns. We consider paregoric to be the treatment of choice for the neonatal abstinence syndrome. Phenobarbital use should be monitored with serum drug levels and modification of recommended dosage regimens considered.

Cell Fate Reprogramming by Control of Intracellular Network Dynamics

PubMed Central

Zañudo, Jorge G. T.; Albert, Réka

2015-01-01

Identifying control strategies for biological networks is paramount for practical applications that involve reprogramming a cell’s fate, such as disease therapeutics and stem cell reprogramming. Here we develop a novel network control framework that integrates the structural and functional information available for intracellular networks to predict control targets. Formulated in a logical dynamic scheme, our approach drives any initial state to the target state with 100% effectiveness and needs to be applied only transiently for the network to reach and stay in the desired state. We illustrate our method’s potential to find intervention targets for cancer treatment and cell differentiation by applying it to a leukemia signaling network and to the network controlling the differentiation of helper T cells. We find that the predicted control targets are effective in a broad dynamic framework. Moreover, several of the predicted interventions are supported by experiments. PMID:25849586

Comparative Risk Predictions of Second Cancers After Carbon-Ion Therapy Versus Proton Therapy

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

Eley, John G., E-mail: jeley@som.umaryland.edu; University of Texas Graduate School of Biomedical Sciences, Houston, Texas; Department of Radiation Oncology, University of Maryland School of Medicine, Baltimore, Maryland

Purpose: This work proposes a theoretical framework that enables comparative risk predictions for second cancer incidence after particle beam therapy for different ion species for individual patients, accounting for differences in relative biological effectiveness (RBE) for the competing processes of tumor initiation and cell inactivation. Our working hypothesis was that use of carbon-ion therapy instead of proton therapy would show a difference in the predicted risk of second cancer incidence in the breast for a sample of Hodgkin lymphoma (HL) patients. Methods and Materials: We generated biologic treatment plans and calculated relative predicted risks of second cancer in the breastmore » by using two proposed methods: a full model derived from the linear quadratic model and a simpler linear-no-threshold model. Results: For our reference calculation, we found the predicted risk of breast cancer incidence for carbon-ion plans-to-proton plan ratio, , to be 0.75 ± 0.07 but not significantly smaller than 1 (P=.180). Conclusions: Our findings suggest that second cancer risks are, on average, comparable between proton therapy and carbon-ion therapy.« less

Comparative Risk Predictions of Second Cancers After Carbon-Ion Therapy Versus Proton Therapy.

PubMed

Eley, John G; Friedrich, Thomas; Homann, Kenneth L; Howell, Rebecca M; Scholz, Michael; Durante, Marco; Newhauser, Wayne D

2016-05-01

This work proposes a theoretical framework that enables comparative risk predictions for second cancer incidence after particle beam therapy for different ion species for individual patients, accounting for differences in relative biological effectiveness (RBE) for the competing processes of tumor initiation and cell inactivation. Our working hypothesis was that use of carbon-ion therapy instead of proton therapy would show a difference in the predicted risk of second cancer incidence in the breast for a sample of Hodgkin lymphoma (HL) patients. We generated biologic treatment plans and calculated relative predicted risks of second cancer in the breast by using two proposed methods: a full model derived from the linear quadratic model and a simpler linear-no-threshold model. For our reference calculation, we found the predicted risk of breast cancer incidence for carbon-ion plans-to-proton plan ratio, , to be 0.75 ± 0.07 but not significantly smaller than 1 (P=.180). Our findings suggest that second cancer risks are, on average, comparable between proton therapy and carbon-ion therapy. Copyright © 2016 Elsevier Inc. All rights reserved.

Bidirectional Relationships Between Fatigue and Everyday Experiences in Persons Living With HIV.

PubMed

Cook, Paul F; Hartson, Kimberly R; Schmiege, Sarah J; Jankowski, Catherine; Starr, Whitney; Meek, Paula

2016-06-01

Fatigue symptoms are very common among persons living with HIV (PLWH). Fatigue is related to functional and psychological problems and to treatment nonadherence. Using secondary data from ecological momentary assessment, we examined fatigue as a predictor of PLWH everyday experiences. In bidirectional analyses based on the shape shifters model, we also examined these experiences as predictors of fatigue. Data were examined from 67 PLWH who completed daily surveys on a handheld computer. Brief validated scales were used to assess participants' control beliefs, mood, stress, coping, social support, experience of stigma, and motivation. At the beginning and end of the study, fatigue was measured with two CES-D items that have been used in past HIV symptom research. Multilevel models and logistic regression were used to test reciprocal predictive relationships between variables. Moderate to severe fatigue affected 45% of PLWH in the study. Initial fatigue predicted PLWH subsequent overall level of control beliefs, mood, stress, coping, and social support, all p < .05. These state variables remained relatively constant over time, regardless of participants' initial fatigue. In tests for reciprocal relationships with 33 PLWH, average daily stress, OR = 4.74, and stigma, OR = 4.86, also predicted later fatigue. Fatigue predicted several daily survey variables including stress and social support. Stress and support in turn predicted fatigue at a later time, suggesting a self-perpetuating cycle but also a possible avenue for intervention. Future studies should examine daily variation in fatigue among PLWH and its relation to other everyday experiences and behaviors. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.

Pharmacogenetics: A strategy for personalized medicine for autoimmune diseases.

PubMed

Tavakolpour, S; Darvishi, M; Ghasemiadl, M

2018-03-01

For many years, a considerable number of patients with autoimmune diseases (ADs) have suffered from a lack of drug response and drug-related toxicity. Despite the emergence of new therapeutic options such as biological agents, patients continue to struggle with these problems. Unfortunately, new challenges, including the paradoxical effects of biological drugs, have complicated the situation. In recent decades, efforts have been made to predict drug response as well as drug-related side effects. Thanks to the many advances in genetics, evaluation of markers to predict drug response/toxicity before the initiation of treatment may be an avenue toward personalizing treatments. Implementing pharmacogenetics and pharmacogenomics in the clinic could improve clinical care; however, obstacles remain to effective personalized medicine for ADs. The present study attempted to clarify the concept of pharmacogenetics/pharmacogenomics for ADs. After an overview on the pathogenesis of the most common types of treatments, this paper focuses on pharmacogenetic studies related to the selected ADs. Bridging the gap between pharmacogenetics and personalized medicine is also discussed. Moreover, the advantages, disadvantages and recommendations related to making personalized medicine practical for ADs have been addressed. © 2017 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

What do predict anxiety and depression in breast cancer patients? A follow-up study.

PubMed

Vahdaninia, Mariam; Omidvari, Sepideh; Montazeri, Ali

2010-03-01

Psychological adjustment following cancer occurrence remains a key issue among the survivors. This study aimed to investigate psychological distress in patients with breast cancer following completion of breast cancer treatments and to determine its associated factors. This was a prospective study of anxiety and depression in breast cancer patients. Anxiety and depression were measured using the Hospital Anxiety and Depression Scale at three points in time: baseline (pre-diagnosis), 3 months after initial treatment and 1 year after completion of treatment (in all 18 months follow-up). At baseline, the questionnaires were administered to all the suspected patients while both patients and the interviewer were blind to the final diagnosis. Socio-demographic and clinical data included age, education, marital status, disease stage and initial treatment. Repeated measure analysis was performed to compare anxiety and depression over the study period. Logistic regression analysis was performed to determine variables that predict anxiety and depression. Altogether 167 patients were diagnosed with breast cancer. The mean age of breast cancer patients was 47.2 (SD = 13.5) years, and the vast majority underwent mastectomy (82.6%). At 18 months follow-up, data for 99 patients were available. The results showed that anxiety and depression improved over the time (P < 0.001) although at 18-month follow-up, 38.4% and 22.2% of the patients presented with severe anxiety and depression, respectively. 'Fatigue' was found to be a risk factor for developing anxiety and depression at 3 months follow-up [odds ratio (OR) = 1.04, 95% Confidence interval (CI) = 1.01-1.07 and OR = 1.04, 95% CI = 1.02-1.07 respectively]. At 18 months follow-up, anxiety was predicted by 'pain' (OR = 1.02, 95% CI = 1.00-1.05), whereas depression was predicted by both 'fatigue' (OR = 1.06, 95% CI = 1.02-1.09) and 'pain' (OR = 1.05, 95% CI = 1.01-1.08). Although the findings indicated that the levels of anxiety and depression decreased over time, a significant number of women had elevated anxiety and depression at the 18 months follow-up. This suggests that all women should be routinely screened for psychological distress and that quality cancer care include processes to treat that 30% of women who have elevated psychological distress. In addition, if breast cancer patients indicated that they are suffering from fatigue or pain, these women who are at particular risk should be especially screened.

The initial effectiveness of liposomal amphotericin B (AmBisome) and miltefosine combination for treatment of visceral leishmaniasis in HIV co-infected patients in Ethiopia: A retrospective cohort study.

PubMed

Abongomera, Charles; Diro, Ermias; de Lima Pereira, Alan; Buyze, Jozefien; Stille, Kolja; Ahmed, Fareed; van Griensven, Johan; Ritmeijer, Koert

2018-05-01

North-west Ethiopia faces the highest burden world-wide of visceral leishmaniasis (VL) and HIV co-infection. VL-HIV co-infected patients have higher (initial) parasitological failure and relapse rates than HIV-negative VL patients. Whereas secondary prophylaxis reduces the relapse rate, parasitological failure rates remain high with the available antileishmanial drugs, especially when administered as monotherapy. We aimed to determine the initial effectiveness (parasitologically-confirmed cure) of a combination of liposomal amphotericin B (AmBisome) and miltefosine for treatment of VL in HIV co-infected patients. We conducted a retrospective cohort study at a Médecins Sans Frontières-supported health center in north-west Ethiopia. We included VL-HIV co-infected adults, treated for VL between January 2011 and August 2014, with AmBisome infusion (30 mg/kg total dose) and miltefosine orally for 28 days (100 mg/day). Proportions of initial treatment outcome categories were calculated. Predictors of initial parasitological failure and of death were determined using multivariable logistic regression. Of the 173 patients included, 170 (98.3%) were male and the median age was 32 years. The proportion of patients with primary VL (48.0%) and relapse VL (52.0%) were similar. The majority had advanced HIV disease (n = 111; 73.5%) and were on antiretroviral therapy prior to VL diagnosis (n = 106; 64.2%). Initial cure rate was 83.8% (95% confidence interval [CI], 77.6-88.6); death rate 12.7% (95% CI, 8.5-18.5) and parasitological failure rate 3.5% (95% CI, 1.6-7.4). Tuberculosis co-infection at VL diagnosis was predictive of parasitological failure (adjusted odds ratio (aOR), 8.14; p = 0.02). Predictors of death were age >40 years (aOR, 5.10; p = 0.009), hemoglobin ≤6.5 g/dL (aOR, 5.20; p = 0.002) and primary VL (aOR, 8.33; p = 0.001). Initial parasitological failure rates were very low with AmBisome and miltefosine combination therapy. This regimen seems a suitable treatment option. Knowledge of predictors of poor outcome may facilitate better management. These findings remain to be confirmed in clinical trials.

The Incorporation and Initialization of Cloud Water/ice in AN Operational Forecast Model

NASA Astrophysics Data System (ADS)

Zhao, Qingyun

Quantitative precipitation forecasts have been one of the weakest aspects of numerical weather prediction models. Theoretical studies show that the errors in precipitation calculation can arise from three sources: errors in the large-scale forecasts of primary variables, errors in the crude treatment of condensation/evaporation and precipitation processes, and errors in the model initial conditions. A new precipitation parameterization scheme has been developed to investigate the forecast value of improved precipitation physics via the introduction of cloud water and cloud ice into a numerical prediction model. The main feature of this scheme is the explicit calculation of cloud water and cloud ice in both the convective and stratiform precipitation parameterization. This scheme has been applied to the eta model at the National Meteorological Center. Four extensive tests have been performed. The statistical results showed a significant improvement in the model precipitation forecasts. Diagnostic studies suggest that the inclusion of cloud ice is important in transferring water vapor to precipitation and in the enhancement of latent heat release; the latter subsequently affects the vertical motion field significantly. Since three-dimensional cloud data is absent from the analysis/assimilation system for most numerical models, a method has been proposed to incorporate observed precipitation and nephanalysis data into the data assimilation system to obtain the initial cloud field for the eta model. In this scheme, the initial moisture and vertical motion fields are also improved at the same time as cloud initialization. The physical initialization is performed in a dynamical initialization framework that uses the Newtonian dynamical relaxation method to nudge the model's wind and mass fields toward analyses during a 12-hour data assimilation period. Results from a case study showed that a realistic cloud field was produced by this method at the end of the data assimilation period. Precipitation forecasts have been significantly improved as a result of the improved initial cloud, moisture and vertical motion fields.

Callus remodelling model

NASA Astrophysics Data System (ADS)

Miodowska, Justyna; Bielski, Jan; Kromka-Szydek, Magdalena

2018-01-01

The objective of this paper is to investigate the healing process of the callus using bone remodelling approach. A new mathematical model of bone remodelling is proposed including both underload and overload resorption, as well as equilibrium and bone growth states. The created model is used to predict the stress-stimulated change in the callus density. The permanent and intermittent loading programs are considered. The analyses indicate that obtaining a sufficiently high values of the callus density (and hence the elasticity) modulus is only possible using time-varying load parameters. The model predictions also show that intermittent loading program causes delayed callus healing. Understanding how mechanical conditions influence callus remodelling process may be relevant in the bone fracture treatment and initial bone loading during rehabilitation.

Initializing decadal climate predictions over the North Atlantic region

NASA Astrophysics Data System (ADS)

Matei, Daniela Mihaela; Pohlmann, Holger; Jungclaus, Johann; Müller, Wolfgang; Haak, Helmuth; Marotzke, Jochem

2010-05-01

Decadal climate prediction aims to predict the internally-generated decadal climate variability in addition to externally-forced climate change signal. In order to achieve this it is necessary to start the predictions from the current climate state. In this study we investigate the forecast skill of the North Atlantic decadal climate predictions using two different ocean initialization strategies. First we apply an assimilation of ocean synthesis data provided by the GECCO project (Köhl and Stammer, 2008) as initial conditions for the coupled model ECHAM5/MPI-OM. Hindcast experiments are then performed over the period 1952-2001. An alternative approach is one in which the subsurface ocean temperature and salinity are diagnosed from an ensemble of ocean model runs forced by the NCEP-NCAR atmospheric reanalyzes for the period 1948-2007, then nudge into the coupled model to produce initial conditions for the hindcast experiments. An anomaly coupling scheme is used in both approaches to avoid the hindcast drift and the associated initial shock. Differences between the two assimilation approaches are discussed by comparing them with the observational data in key regions and processes. We asses the skill of the initialized decadal hindcast experiments against the prediction skill of the non-initialized hindcasts simulation. We obtain an overview of the regions with the highest predictability from the regional distribution of the anomaly correlation coefficients and RMSE for the SAT. For the first year the hindcast skill is increased over almost all ocean regions in the NCEP-forced approach. This increase in the hindcast skill for the 1 year lead time is somewhat reduced in the GECCO approach. At lead time 5yr and 10yr, the skill enhancement is still found over the North Atlantic and North Pacific regions. We also consider the potential predictability of the Atlantic Meridional Overturning Circulation (AMOC) and Nordic Seas Overflow by comparing the predicted values to the respective assimilation experiments. Hindcasts of Atlantic MOC and Denmark Strait Overflow show higher predictability than the comparison experiments without initialization and damped persistence predictions up to about 5-6 years.