Growth hormone combined with child-specific motor training improves motor development in infants with Prader-Willi syndrome: a randomized controlled trial.

PubMed

Reus, Linda; Pelzer, Ben J; Otten, Barto J; Siemensma, Elbrich P C; van Alfen-van der Velden, Janielle A A E M; Festen, Dederieke A M; Hokken-Koelega, Anita C S; Nijhuis-van der Sanden, Maria W G

2013-10-01

Although severe motor problems in infants with Prader-Willi syndrome (PWS) are striking, motor development has never been studied longitudinally and the results of growth hormone (GH) treatment on motor development are contradictory. The authors studied whether GH treatment can enhance the effect of physical training on motor development in infants with PWS. Twenty-two infants were followed for two years during a randomized controlled trial. The treatment and control groups began GH after baseline or following a control period, respectively. Both groups followed a child-specific physical training program. Motor performance was measured every three months. Multi-level regression analysis revealed that motor development differed significantly between infants (p<.001), and this could be partially explained by baseline motor developmental level (p<.01). GH treatment enhanced the effects of child-specific physical training on both motor developmental rate and motor developmental potential. Moreover, this effect was more pronounced when GH treatment was initiated at a younger age. Copyright © 2013 Elsevier Ltd. All rights reserved.

Can Kinesiological Activities Change "Pure" Motor Development in Preschool Children during One School Year?

PubMed

Krneta, Željko; Casals, Cristina; Bala, Gustav; Madić, Dejan; Pavlović, Slobodan; Drid, Patrik

2015-07-01

The purpose of this study was to evaluate the effects of an additional, organized, and more intensive kinesiological treatment on "pure" motor abilities in preschool children. In the present study an experimental treatment was carried out on a sample of 37 preschool boys by applying kinesiological activities. The 60 minute treatment was applied over a period of one school year (9 months), twice a week. A control group of 31 boys were trained according to the regular program for preschool institutions. Treatment effects were assessed by 8 motor ability tests and 5 anthropometric measures. The significant differences between the groups, which were observed after the final measurement and compared to the initial one, proved that the kinesiological treatment had a positive impact on the general development of "pure" motor abilities. The most significant effect of experimental kinesiological treatment was the improvement in whole body force, flexibility and coordination of preschool boys. These findings, obtained only in one school year, point to the importance of physical exercise and the application of additional kinesiological activities with various modalities, to improve motor development, even morphological growth and development in preschool children. The effects of the perennial application of kinesiological activities, under the supervision of kinesiological professionals, could be beneficial and could form the basis for a better biological and motor development in older age.

The topical treatment of psoriasis.

PubMed

van de Kerkhof, P C M; Vissers, W H P M

2003-01-01

According to the patients, improvement of efficacy, long-term safety and improvement of compliance are needed. The topical treatment has been innovated during the last decade. Most important are the introduction of two new classes of treatments: topical vitamin D(3) analogues and the retinoid tazarotene. To what extent, however, have we achieved developments which are in line with the needs as expressed by the patients? Improved efficacy has been realized by successful combinations of topical treatments. In particular, the combinations of dithranol, vitamin D(3) and tazarotene with a topical corticosteroid proved to be very effective with a reduced profile of side-effects. The efficacy of vitamin D(3) analogues and tazarotene is such that the efficacy of a potent corticosteroid (betamethasone-17-valerate) is approached; calcipotriol even showed an efficacy which is at least as good as this corticosteroid. The long-term safety of new compounds has been evaluated for at least 12 months in large studies. Remarkably for corticosteroids such information is available for only 12 weeks. However, intermittent applications of a topical corticosteroid in combination with another topical treatment provide an effective and safe long-term control of psoriasis. Compliance is a conditio sine qua non for an effective topical treatment. Important progress has been made to increase compliance. Short-contact dithranol has been popularized as an ambulatory treatment which is a highly effective approach as a care instruction programme. Formulations which are better from a cosmetical point of view have been developed for various topical treatments. Reduction of the frequency of applications proved to be possible for most treatments. Once daily applications for corticosteroids, vitamin D(3) analogues and retinoids have been developed, and intermittent applications, a few times per week, are possible for corticosteroids, which proved to be very effective with a reduced profile of side-effects, and are also developed for dithranol. Copyright 2003 S. Karger AG, Basel

Novel Strategies on Personalized Medicine for Breast Cancer Treatment: An Update.

PubMed

Chan, Carmen W H; Law, Bernard M H; So, Winnie K W; Chow, Ka Ming; Waye, Mary M Y

2017-11-15

Breast cancer is the most common cancer type among women worldwide. With breast cancer patients and survivors being reported to experience a repertoire of symptoms that are detrimental to their quality of life, the development of breast cancer treatment strategies that are effective with minimal side effects is therefore required. Personalized medicine, the treatment process that is tailored to the individual needs of each patient, is recently gaining increasing attention for its prospect in the development of effective cancer treatment regimens. Indeed, recent studies have identified a number of genes and molecules that may be used as biomarkers for predicting drug response and severity of common cancer-associated symptoms. These would provide useful clues not only for the determination of the optimal drug choice/dosage to be used in personalized treatment, but also for the identification of gene or molecular targets for the development of novel symptom management strategies, which ultimately would lead to the development of more personalized therapies for effective cancer treatment. In this article, recent studies that would provide potential new options for personalized therapies for breast cancer patients and survivors are reviewed. We suggest novel strategies, including the optimization of drug choice/dosage and the identification of genetic changes that are associated with cancer symptom occurrence and severity, which may help in enhancing the effectiveness and acceptability of the currently available cancer therapies.

Effects of catechins and caffeine on the development of atherosclerosis in mice.

PubMed

Liu, Litong; Nagai, Izumi; Gao, Ying; Matsushima, Yoshibumi; Kawai, Yoshichika; Sayama, Kazutoshi

2017-10-01

Atherosclerosis is one of the diseases related to metabolic syndrome which is caused by obesity. Previous reports have shown that green tea and its components have anti-obesity effect. We examined whether catechins and caffeine can prevent the development of atherosclerosis by oral administration, singly or in combination to the atherosclerosis model mice. Results demonstrated that the number of atherosclerotic regions in the aorta was significantly reduced by the combined treatment, and the atherosclerotic area was also improved. Serum HDL-C increased by caffeine single treatment, but no effect on the TG and TC by any treatments. Moreover, ECG illuviated to atheromatous lesions in aorta and the illuviation was enhanced by caffeine. The mRNA expression levels of LOX-1 and TNF-α showed a tendency to suppress by the combined treatment. These results indicated that the combined administration of catechins and caffeine has the inhibitory effect on the development of atherosclerosis in mice.

Anti-bacterial Treatments Using Peptide-Based Inhibitors of the STAT3-IL10 Pathway | NCI Technology Transfer Center | TTC

Cancer.gov

Tuberculosis (TB) is an infectious disease that typically affects the lungs. Current therapies include a panel of antibiotics given over a range of 6-9 months. As a result of the expense of treatment, the extended timeframe needed for effective treatment, and the scarcity of medicines in some developing countries, patient compliance with TB treatment is very low and results in multi-drug resistant TB (MDR-TB). There remains a need for a faster, more effective treatment for TB. NCI researchers seek licensing and/or co-development of peptide inhibitors of STAT3 and IL-10 developed to treat bacterial infections such as tuberculosis. See aslo: NIH inventions E-164-2007 and E-167-2010

ESTIMATING PERSON-CENTERED TREATMENT (PeT) EFFECTS USING INSTRUMENTAL VARIABLES: AN APPLICATION TO EVALUATING PROSTATE CANCER TREATMENTS

PubMed Central

BASU, ANIRBAN

2014-01-01

SUMMARY This paper builds on the methods of local instrumental variables developed by Heckman and Vytlacil (1999, 2001, 2005) to estimate person-centered treatment (PeT) effects that are conditioned on the person’s observed characteristics and averaged over the potential conditional distribution of unobserved characteristics that lead them to their observed treatment choices. PeT effects are more individualized than conditional treatment effects from a randomized setting with the same observed characteristics. PeT effects can be easily aggregated to construct any of the mean treatment effect parameters and, more importantly, are well suited to comprehend individual-level treatment effect heterogeneity. The paper presents the theory behind PeT effects, and applies it to study the variation in individual-level comparative effects of prostate cancer treatments on overall survival and costs. PMID:25620844

Effect of steroid treatment of endometrial cells on blastocyst development during co-culture.

PubMed

Goff, A K; Smith, L C

1998-04-01

The objective of this study was to determine if treatment of endometrial cells with progesterone or progesterone plus estradiol would improve the development of bovine embryos to the blastocyst stage during co-culture. After IVF, bovine embryos were cultured with oviduct epithelial cells for 3 d. In Experiment 1 the embryos were cultured with a) oviduct epithelial cells; b) endometrial epithelial cells (EEC); c) EEC with 10 ng/ml progesterone (EEC + P); or d) EEC with 10 ng/ml progesterone and 10 pg/ml estradiol (EEC + PE) for 6 d. In Experiment 2 the embryos were cultured with a) oviduct epithelial cells; b) endometrial stromal cells (ESC); c) ESC with 10 ng/ml progesterone (ESC + P); or d) ESC with 10 ng/ml progesterone and 10 pg/ml estradiol (ESC + PE) for 6 d. Results from Experiment 1 showed that endometrial epithelial cells supported development to the blastocyst stage as effectively as the oviduct cells; however, the size of the blastocysts was smaller for the endometrial cells. There was no effect of steroid hormone treatment on development to the blastocyst stage or on the size of the blastocysts. Results from Experiment 2 showed that stromal cells supported development to the blastocyst stage as effectively as oviduct cells. The hatching rate was lower when the embryos were co-cultured with stromal cells than oviduct epithelial cells; but there was no effect of steroid treatment. These data show that untreated endometrial epithelial cells are as effective as oviduct cells in maintaining embryo development to the blastocyst stage. However, embryo development was not improved by steroid treatment of the cells.

Consensus Treatments for Moderate Juvenile Dermatomyositis: Beyond the First Two Months

PubMed Central

Huber, Adam M.; Robinson, Angela B.; Reed, Ann M.; Abramson, Leslie; Bout-Tabaku, Sharon; Carrasco, Ruy; Curran, Megan; Feldman, Brian M.; Gewanter, Harry; Griffin, Thomas; Haines, Kathleen; Sanzari, Joseph M.; Hoeltzel, Mark F.; Isgro, Josephine; Kahn, Philip; Lang, Bianca; Lawler, Patti; Shaham, Bracha; Schmeling, Heinrike; Scuccimarri, Rosie; Shishov, Michael; Stringer, Elizabeth; Wohrley, Julie; Ilowite, Norman T.; Wallace, Carol

2011-01-01

Objectives To use consensus methods and the considerable expertise contained within the Children’s Arthritis and Rheumatology Research Alliance (CARRA) organization, to extend the 3 previously developed treatment plans for moderate juvenile dermatomyositis (JDM) to span the full course of treatment. Methods A consensus meeting was held in Chicago on April 23–24, 2010 involving 30 pediatric rheumatologists and 4 lay participants. Nominal group technique was used to achieve consensus on treatment plans which represented typical management of moderate JDM. A pre-conference survey of CARRA, completed by 151/272 (56%) members, was used to provide additional guidance to discussion. Results Consensus was reached on timing and rate of steroid tapering, duration of steroid therapy, and actions to be taken if patients were unchanged, worsening, experiencing medication side effects or disease complications. Of particular importance, a single, consensus steroid taper was developed. Conclusions We were able to develop consensus treatment plans which describe therapy for moderate JDM throughout the treatment course. These treatment plans can now be used clinically, and data collected prospectively regarding treatment effectiveness and toxicity. This will allow comparison of these treatment plans and facilitate the development of evidence-based treatment recommendations for moderate JDM. PMID:22076847

HETEROGENEITY IN TREATMENT EFFECT AND COMPARATIVE EFFECTIVENESS RESEARCH.

PubMed

Luo, Zhehui

2011-10-01

The ultimate goal of comparative effectiveness research (CER) is to develop and disseminate evidence-based information about which interventions are most effective for which patients under what circumstances. To achieve this goal it is crucial that researchers in methodology development find appropriate methods for detecting the presence and sources of heterogeneity in treatment effect (HTE). Comparing with the typically reported average treatment effect (ATE) in randomized controlled trials and non-experimental (i.e., observational) studies, identifying and reporting HTE better reflect the nature and purposes of CER. Methodologies of CER include meta-analysis, systematic review, design of experiments that encompasses HTE, and statistical correction of various types of estimation bias, which is the focus of this review.

Elevated temperature during reproductive development affects cone traits and progeny performance in Picea glauca x engelmannii complex.

PubMed

Webber, Joe; Ott, Peter; Owens, John; Binder, Wolfgang

2005-10-01

Two temperature regimes were applied during reproductive development of seed and pollen cones of interior spruce (Picea glauca (Moench) Voss and Picea engelmannii (Parry) complex) to determine temperature effects on the adaptive traits of progeny. In Experiment 1, identical crosses were made on potted interior spruce using untreated pollen followed by exposure to a day/night temperature of 22/8 or 14/8 degrees C with a 12-h photoperiod during the stages of reproductive development from post-pollination to early embryo development. Frost hardiness and growth of progeny from seed produced in the two temperature treatments were measured over a 4-year period. Elevated temperature significantly affected both seed-cone development and the adaptive properties of the progeny. Seed cones exposed to the 22/8 degrees C treatment reached the early embryo stage in 53 days versus 92 days in the 14/8 degrees C treatment. Seed yields, cotyledon emergence and percent germination were also significantly enhanced by the 22/8 degrees C treatment. Progeny from seed produced in the higher temperature treatment showed significantly reduced spring and fall frost hardiness, but the elevated temperature treatment had no significant effects on time of bud burst, growth patterns or final heights. In Experiment 2, single ramets of the same clone were subjected to a day/night temperature of 20/8 or 10/8 degrees C during pollen cone development, starting from meiosis and ending at pollen shedding. The two populations of pollen were then crossed with untreated seed cones. Compared with pollen cones exposed to the 10/8 degrees C treatment, pollen cones exposed to the 20/8 degrees C treatment during development reached the shedding stage 2-4 weeks earlier, whereas pollen yields, in vitro viability and fertility (seed set) were significantly lower; however, the resulting progeny displayed no treatment differences in frost hardiness or growth after 1 year. Results suggest that seed orchard after-effects could be caused by temperature differences between orchard site and parent tree origin and that this effect acts on maternal development. Gametophytic (pollen or megagametophyte or both) and early embryo (sporophytic) selection are possible mechanisms that may explain the observed results. Although the effects are biologically significant, they are relatively small and do not justify changes in current deployment strategies for seed orchard seed.

Linking ocean acidification and warming to the larval development of the American lobster (Homarus americanus)

NASA Astrophysics Data System (ADS)

Waller, J. D.; Fields, D.; Wahle, R.; Mcveigh, H.; Greenwood, S.

2016-02-01

The American lobster upholds the most culturally and economically iconic fishery in New England. Over the past three decades lobster landings have risen steadily in northern New England as lobster populations have shifted northward, leaving policy makers and coastal communities wondering what the future of this fishery may hold. The underlying causes of this population shift are likely due to a suite of environmental stressors including increasing temperature and ocean acidification. In this study we investigated the interactive effects of IPCC predicted temperature and pH on key aspects of larval lobster development (size, survival, development time, respiration rate, swimming speed, prey consumption and gene expression). Our experiments showed that larvae raised in the high temperature treatments (19 °C) experienced significantly higher mortality than larvae in our control treatments (16 °C) with 50% mortality occurring in the high temperature treatment one week after hatching. The larvae in these high temperature treatments developed twice as fast and experienced respiration rates that were three times higher in the third and fourth larval stages. While temperature had a distinct effect, pH treatment had few significant effects on any of our measured parameters. These data suggest that projected end-century warming will have greater adverse effects than acidification on early larval survival, despite the hurrying effect of higher temperatures on lobster larval development and increase in physiological activity. There were no significant treatment effects on carapace length, dry weight, or carbon and nitrogen content. Analysis of swimming speed and gene expression (through RNA sequencing) are in progress. Understanding how the most vulnerable life stages of the lobster life cycle responds to climate change is essential in connecting the northward geographic shifts projected by habitat quality models, and the underlying physiological and genetic mechanisms that drive their ecology.

Sub-lethal effects of pesticide residues in brood comb on worker honey bee (Apis mellifera) development and longevity.

PubMed

Wu, Judy Y; Anelli, Carol M; Sheppard, Walter S

2011-02-23

Numerous surveys reveal high levels of pesticide residue contamination in honey bee comb. We conducted studies to examine possible direct and indirect effects of pesticide exposure from contaminated brood comb on developing worker bees and adult worker lifespan. Worker bees were reared in brood comb containing high levels of known pesticide residues (treatment) or in relatively uncontaminated brood comb (control). Delayed development was observed in bees reared in treatment combs containing high levels of pesticides particularly in the early stages (day 4 and 8) of worker bee development. Adult longevity was reduced by 4 days in bees exposed to pesticide residues in contaminated brood comb during development. Pesticide residue migration from comb containing high pesticide residues caused contamination of control comb after multiple brood cycles and provided insight on how quickly residues move through wax. Higher brood mortality and delayed adult emergence occurred after multiple brood cycles in contaminated control combs. In contrast, survivability increased in bees reared in treatment comb after multiple brood cycles when pesticide residues had been reduced in treatment combs due to residue migration into uncontaminated control combs, supporting comb replacement efforts. Chemical analysis after the experiment confirmed the migration of pesticide residues from treatment combs into previously uncontaminated control comb. This study is the first to demonstrate sub-lethal effects on worker honey bees from pesticide residue exposure from contaminated brood comb. Sub-lethal effects, including delayed larval development and adult emergence or shortened adult longevity, can have indirect effects on the colony such as premature shifts in hive roles and foraging activity. In addition, longer development time for bees may provide a reproductive advantage for parasitic Varroa destructor mites. The impact of delayed development in bees on Varroa mite fecundity should be examined further.

Health economic evaluation of patients treated for nosocomial pneumonia caused by methicillin-resistant Staphylococcus aureus: secondary analysis of a multicenter randomized clinical trial of vancomycin and linezolid.

PubMed

Niederman, Michael S; Chastre, Jean; Solem, Caitlyn T; Wan, Yin; Gao, Xin; Myers, Daniela E; Haider, Seema; Li, Jim Z; Stephens, Jennifer M

2014-09-01

Results from studies comparing health care resource use (HCRU), costs of treatment, and cost-effectiveness of linezolid compared with vancomycin therapy in the treatment of hospitalized patients with methicillin-resistant Staphylococcus aureus (MRSA) nosocomial pneumonia are limited in the published literature. We therefore conducted an analysis to compare the HCRU, costs of treatment, and cost-effectiveness of linezolid compared with vancomycin in the treatment of hospitalized patients with MRSA nosocomial pneumonia using data from a Phase IV clinical trial. The economic effect of moderate to severe adverse events (MSAEs) and the development of renal failure were also evaluated. We performed a post hoc analysis of data from a Phase IV, double-blind, randomized, comparator-controlled, multicenter trial that compared linezolid and vancomycin treatment in patients with MRSA nosocomial pneumonia. HCRU and costs were compared based on treatment, development of MSAEs, and development of renal failure using data from the modified intent-to-treat population. Predictors of costs were evaluated using generalized linear models. A piggyback cost-effectiveness analysis was conducted to assess the incremental cost-effectiveness ratio of linezolid versus vancomycin, given the significantly higher clinical success of linezolid compared with vancomycin found in the trial. Overall, HCRU and costs were similar between the linezolid and vancomycin treatment groups; drug costs were significantly higher and dialysis costs significantly lower for linezolid- compared with vancomycin-treated patients. Total treatment costs were approximately $8000 higher (P = .046) for patients who developed renal failure compared with those who did not. Renal failure occurred more commonly in patients randomized to receive vancomycin (15%) compared with linezolid (4%; P < .001). Region, ventilator-associated pneumonia, clinical failure, and development of renal failure were associated with significantly higher total costs. The point estimate incremental cost-effectiveness ratio for linezolid compared with vancomycin was $16,516 per treatment success, with linezolid dominant in 24% and dominated in <2% of bootstrapped samples. This phase 4 clinical trial conducted in patients with MRSA-confirmed nosocomial pneumonia reveals that linezolid- compared with vancomycin-treated patients had similar HCRU and total overall costs. Fewer patients developed renal failure during the study while taking linezolid compared with vancomycin, and patients with a documented MSAE or renal failure had increased HCRU and costs. In summary, linezolid may be a cost-effective treatment strategy in MRSA-confirmed nosocomial pneumonia. Copyright © 2014 Elsevier HS Journals, Inc. All rights reserved.

The effects of combined application of transcranial magnetic stimulation and language training on children with language retardation.

PubMed

Qiu, Aizhen; Li, Xinjian; Yang, Zhongxiu; Li, Zhilin; Wang, Jiping; Yuan, Huanxia; Jin, Xin

2016-10-28

The objective of the present manuscript was to explore the effects of combined application of transcranial magnetic stimulation (TMS) and language training on children with language retardation. Forty-five children with language retardation were selected as subjects and randomly divided into the treatment group with 24 patients and the control group with 21 patients. The control group was treated with traditional language training, while the treatment group was treated with TMS combined with language training. According to Gesell pediatric neuropsychological development schedules, the development quotient of children in the two groups were observed and compared before and after two courses of treatment. The evaluation of mouth movement was conducted with Dr. Speech supervised by East China Normal University. Development quotient scores and mouth movement evaluation scores of all Gesell parameters of children in the two groups after treatment were significantly higher than those before treatment (P<0.05). The body movement ability, linguistic competence, development quotient scores, and mouth movement evaluation scores in the treatment group after treatment were higher than those of the control group, and the differences were statistically significant (P<0.05). The combined application of TMS and language training can effectively improve linguistic competence, action ability, and mouth movement in children with language retardation.

Representing growth response to fertilization in the Prognosis Model for Stand Development

Treesearch

Albert R. Stage; Nicholas L. Crookston; Bahman Shafii; James A. Moore; John Olson

1990-01-01

Capability to represent effects of fertilization has been added to the Prognosis Model for Stand Development. As implemented in version 6, the extension is calibrated only for applications of 200 lb nitrogen applied in the form of urea. Direct and indirect effects are based on growth 10 years after treatment for diameter effects, and 6 years after treatment for height...

Continuing clozapine treatment with lithium in schizophrenic patients with neutropenia or leukopenia: brief review of literature with case reports

PubMed Central

Aydin, Memduha; Ilhan, Bilge Cetin; Calisir, Saliha; Yildirim, Seda; Eren, Ibrahim

2016-01-01

Objective: Clozapine is a second-generation antipsychotic used for treatment-resistant schizophrenia. Despite its effectiveness, clozapine is largely underused due to serious side effects such as leukopenia or neutropenia. We aimed to review whether to continue, discontinue or rechallenge clozapine treatment after such haematological side effects. Methods: We reviewed and summarized the literature on the use of clozapine, how to deal with its side effects, and suitable options in case of any haematological problems. Then, we described several cases successfully treated with clozapine and lithium after development of neutropenia or leukopenia Results: We present three patients with treatment-resistant schizophrenia. While they had demonstrated poor response to multiple antipsychotic trials, clozapine was started. Clozapine induced neutropenia; or leukopenia developed in some cases that was successfully reversed after lithium onset. Increased serious side effects related with coprescription of lithium and clozapine were not observed. Conclusion: Lithium increases neutrophil and total white blood cell count as a side effect that may be useful in patients who develop neutropenia or leukopenia while being treated with clozapine. PMID:26913176

Continuing clozapine treatment with lithium in schizophrenic patients with neutropenia or leukopenia: brief review of literature with case reports.

PubMed

Aydin, Memduha; Ilhan, Bilge Cetin; Calisir, Saliha; Yildirim, Seda; Eren, Ibrahim

2016-02-01

Clozapine is a second-generation antipsychotic used for treatment-resistant schizophrenia. Despite its effectiveness, clozapine is largely underused due to serious side effects such as leukopenia or neutropenia. We aimed to review whether to continue, discontinue or rechallenge clozapine treatment after such haematological side effects. We reviewed and summarized the literature on the use of clozapine, how to deal with its side effects, and suitable options in case of any haematological problems. Then, we described several cases successfully treated with clozapine and lithium after development of neutropenia or leukopenia. We present three patients with treatment-resistant schizophrenia. While they had demonstrated poor response to multiple antipsychotic trials, clozapine was started. Clozapine induced neutropenia; or leukopenia developed in some cases that was successfully reversed after lithium onset. Increased serious side effects related with coprescription of lithium and clozapine were not observed. Lithium increases neutrophil and total white blood cell count as a side effect that may be useful in patients who develop neutropenia or leukopenia while being treated with clozapine.

The effect of growth hormone treatment or physical training on motor performance in Prader-Willi syndrome: a systematic review.

PubMed

Reus, Linda; van Vlimmeren, Leo A; Staal, J Bart; Otten, Barto J; Nijhuis-van der Sanden, Maria W G

2012-09-01

Although motor problems in Prader-Willi syndrome (PWS) are prominent in infants, and continue into childhood and adulthood, there is little insight into the factors important for clinical management. The literature was reviewed to: (1) provide an overview of the characteristics and prevalence of motor problems and (2) evaluate the effects of growth hormone (GH) treatment and physical training on motor performance. A systematic search revealed 34 papers: 13 on motor performance; 12 on GH treatment; and nine on physical training. In infants, motor development is 30-57% of the normal reference values, and children and adults also have significant problems in skill acquisition, muscle force, cardiovascular fitness, and activity level. GH treatment positively influenced motor performance in infants, children, and adults, although not all studies demonstrated an effect. All studies on physical training demonstrated beneficial effects in PWS patients. We suggest a combination of GH treatment and physical training to be started as soon as possible, especially in infants, to improve motor development as this will positively influence general development. Copyright © 2012 Elsevier Ltd. All rights reserved.

[Effect of dental arch length decrease during orthodontic treatment in the upper airway development. A review].

PubMed

Haddad, Stéphanie; Kerbrat, Jean-Baptiste; Schouman, Thomas; Goudot, Patrick

2017-03-01

A possible relation between an upper airway space decrease and the development of obstructive sleep apnea syndrom explains the importance to know the effect of the modification of dental arch length on the upper airway during orthodontic treatment. The aim of this article is to expose recent knowledge about upper airway development and dental arch length decrease factors, to determine the influence of this decrease on upper airway development. A review was done to determine the upper airway normal development, to define dental arch to specify if an ideal position of dental arch on apical base exists. All of the length dental arch decrease factors during orthodontic treatment (dental extraction, dental agenesis and dental malpositions) and their upper airway resounding were searched. Some authors found a diminution of upper airway space after premolars extractions while others didn't found this diminution after extractions premolars when incisor retraction is finished. A decrease of transversal maxillary diameter and nasal cavity may be due to absence of permanent teeth. The effect of dental arch length decrease during orthodontic treatment in the upper airway development was not scientifically proved. However we had to be vigilant and adapt our orthodontic treatment case by case to avoid an upper airway modification. © EDP Sciences, SFODF, 2017.

Oculomotor and Neuropsychological Effects of Antipsychotic Treatment for Schizophrenia

PubMed Central

Hill, S. Kristian; Reilly, James L.; Harris, Margret S. H.; Khine, Tin; Sweeney, John A.

2008-01-01

Cognitive enhancement has become an important target for drug therapies in schizophrenia. Treatment development in this area requires assessment approaches that are sensitive to procognitive effects of antipsychotic and adjunctive treatments. Ideally, new treatments will have translational characteristics for parallel human and animal research. Previous studies of antipsychotic effects on cognition have relied primarily on paper-and-pencil neuropsychological testing. No study has directly compared neurophysiological biomarkers and neuropsychological testing as strategies for assessing cognitive effects of antipsychotic treatment early in the course of schizophrenia. Antipsychotic-naive patients with schizophrenia were tested before treatment with risperidone and again 6 weeks later. Matched healthy participants were tested over a similar time period. Test-retest reliability, effect sizes of within-subject change, and multivariate/univariate analysis of variance were used to compare 3 neurophysiological tests (visually guided saccade, memory-guided saccade, and antisaccade) with neuropsychological tests covering 4 cognitive domains (executive function, attention, memory, and manual motor function). While both measurement approaches showed robust neurocognitive impairments in patients prior to risperidone treatment, oculomotor biomarkers were more sensitive to treatment-related effects on neurocognitive function than traditional neuropsychological measures. Further, unlike the pattern of modest generalized cognitive improvement suggested by neuropsychological measures, the oculomotor findings revealed a mixed pattern of beneficial and adverse treatment-related effects. These findings warrant further investigation regarding the utility of neurophysiological biomarkers for assessing cognitive outcomes of antipsychotic treatment in clinical trials and in early-phase drug development. PMID:17932088

Fluoxetine treatment is effective in a rat model of childhood-induced post-traumatic stress disorder.

PubMed

Ariel, Lior; Inbar, Sapir; Edut, Schachaf; Richter-Levin, Gal

2017-11-30

Although selective serotonin reuptake inhibitors (SSRIs) are first-line treatment for post-traumatic stress disorder (PTSD) patients, their therapeutic efficacy is limited. Childhood adversities are considered a risk factor for developing PTSD in adulthood but may trigger PTSD without additional trauma in some individuals. Nevertheless, just as childhood is considered a vulnerable period it may also be an effective period for preventive treatment. Using a rat model of childhood-induced PTSD, pre-pubertal stress (juvenile stress, JVS), we compared the therapeutic effects of fluoxetine and examined the effectiveness of 1 month of fluoxetine treatment following JVS and into adulthood compared to treatment in adulthood. Since not all individuals develop PTSD following a trauma, comparing only group means is not the adequate type of analysis. We employed a behavioral profiling approach, which analyzes individual differences compared to the normal behavior of a control group. Animals exposed to JVS exhibited a higher proportion of affected animals as measured using the elevated plus maze 8 weeks after JVS. Fluoxetine treatment following the JVS significantly decreased the proportion of affected animals as measured in adulthood. Fluoxetine treatment in adulthood was not effective. The results support the notion that childhood is not only a vulnerable period but also an effective period for preventive treatment.

Psychiatry's future: facing reality.

PubMed

Staton, D

1991-01-01

U.S. public and private health care costs, including mental health treatment costs, continue to rise at unacceptably high annual rates of increase. "Basic" health insurance plans presently being developed by both public and private payers, in response to this crisis, will include: (1) severely limited coverage for psychiatric care; and (2) coverage for specific categories of serious mental illness. Psychiatrists must develop cost-effective goals and treatment standards that achieve satisfactory outcomes for these high-priority conditions. Treatment standards must be compatible with economic reality. Psychiatry as a profession (i.e., all psychiatrists) must accept cost-effective treatment responsibility for society's most seriously mentally ill individuals. We need to train psychiatrists who are biologically-, crisis-, and rehabilitation-oriented and who can practice effectively and comfortably within society's treatment expectations and funding constraints.

The Effect of Treatment on Mental and Psychomotor Development of Marasmic Infants According to Age of Admission.

ERIC Educational Resources Information Center

Celedon, J. M.; And Others

1980-01-01

The mental and psychomotor development of 35 severely malnourished infants in Chile were examined during nutritional and psychological treatment. There was a significant difference between younger and older infants in their response to the treatment. (Author/DLS)

Agricultural chemicals: life changer for mosquito vectors in agricultural landscapes?

PubMed

Kibuthu, Tabitha W; Njenga, Sammy M; Mbugua, Amos K; Muturi, Ephantus J

2016-09-13

Although many mosquito species develop within agricultural landscapes where they are potentially exposed to agricultural chemicals (fertilizers and pesticides), the effects of these chemicals on mosquito biology remain poorly understood. This study investigated the effects of sublethal concentrations of four agricultural chemicals on the life history traits of Anopheles arabiensis and Culex quinquefasciatus mosquitoes. Field and laboratory experiments were conducted to examine how sublethal concentrations of four agricultural chemicals: an insecticide (cypermethrin), a herbicide (glyphosate), and two nitrogenous fertilizers (ammonium sulfate and diammonium phosphate) alter oviposition site selection, emergence rates, development time, adult body size, and longevity of An. arabiensis and Cx. quinquefasciatus. Both mosquito species had preference to oviposit in fertilizer treatments relative to pesticide treatments. Emergence rates for An. arabiensis were significantly higher in the control and ammonium sulfate treatments compared to cypermethrin treatment, while emergence rates for Cx. quinquefasciatus were significantly higher in the diammonium phosphate treatment compared to glyphosate and cypermethrin treatments. For both mosquito species, individuals from the ammonium sulfate and diammonium phosphate treatments took significantly longer time to develop compared to those from cypermethrin and glyphosate treatments. Although not always significant, males and females of both mosquito species tended to be smaller in the ammonium sulfate and diammonium phosphate treatments compared to cypermethrin and glyphosate treatments. There was no significant effect of the agrochemical treatments on the longevity of either mosquito species. These results demonstrate that the widespread use of agricultural chemicals to enhance crop production can have unexpected effects on the spatial distribution and abundance of mosquito vectors of malaria and lymphatic filariasis.

Measuring the individual benefit of a medical or behavioral treatment using generalized linear mixed-effects models.

PubMed

Diaz, Francisco J

2016-10-15

We propose statistical definitions of the individual benefit of a medical or behavioral treatment and of the severity of a chronic illness. These definitions are used to develop a graphical method that can be used by statisticians and clinicians in the data analysis of clinical trials from the perspective of personalized medicine. The method focuses on assessing and comparing individual effects of treatments rather than average effects and can be used with continuous and discrete responses, including dichotomous and count responses. The method is based on new developments in generalized linear mixed-effects models, which are introduced in this article. To illustrate, analyses of data from the Sequenced Treatment Alternatives to Relieve Depression clinical trial of sequences of treatments for depression and data from a clinical trial of respiratory treatments are presented. The estimation of individual benefits is also explained. Copyright © 2016 John Wiley & Sons, Ltd. Copyright © 2016 John Wiley & Sons, Ltd.

The Women's Recovery Group Study: a Stage I trial of women-focused group therapy for substance use disorders versus mixed-gender group drug counseling.

PubMed

Greenfield, Shelly F; Trucco, Elisa M; McHugh, R Kathryn; Lincoln, Melissa; Gallop, Robert J

2007-09-06

The aim of this Stage I Behavioral Development Trial was to develop a manual-based 12-session Women's Recovery Group (WRG) and to pilot test this new treatment in a randomized controlled trial against a mixed-gender Group Drug Counseling (GDC), an effective manual-based treatment for substance use disorders. After initial manual development, two pre-pilot groups of WRG were conducted to determine feasibility and initial acceptability of the treatment among subjects and therapists. In the pilot stage, women were randomized to either WRG or GDC. No significant differences in substance use outcomes were found between WRG and GDC during the 12-week group treatment. However, during the 6-month post-treatment follow-up, WRG members demonstrated a pattern of continued reductions in substance use while GDC women did not. In addition, pilot WRG women with alcohol dependence had significantly greater reductions in average drinks/drinking day than GDC women 6 months post-treatment (p<.03, effect size=0.81). While satisfaction with both groups was high, women were significantly more satisfied with WRG than GDC (p<.009, effect size=1.11). In this study, the newly developed 12-session women-focused WRG was feasible with high satisfaction among participants. It was equally effective as mixed-gender GDC in reducing substance use during the 12-week in-treatment phase, but demonstrated significantly greater improvement in reductions in drug and alcohol use over the post-treatment follow-up phase compared with GDC. A women-focused single-gender group treatment may enhance longer-term clinical outcomes among women with substance use disorders.

International stem cell tourism and the need for effective regulation. Part II: Developing sound oversight measures and effective patient support.

PubMed

Cohen, Cynthia B; Cohen, Peter J

2010-09-01

Part I of this article, published in the March 2010 issue of the Kennedy Institute of Ethics Journal, traces and addresses the provision of unproven stem cell treatments in Russia and India, examines the concept of innovative treatment, and concludes that stronger regulations are needed to protect the health and informed choices of patients. The current paper, Part II, proposes that the regulatory frameworks for the development of safe and efficacious treatments in effect in the United States and the United Kingdom provide examples of strong oversight measures from which countries seeking to obtain international credibility for their biotechnological competence could draw when developing regulations for stem cell treatments. Major sources of information available to persons who consider receiving such unproven treatments are explored in order to understand and address their concerns. The paper concludes with proposed measures to inform those considering the pursuit of unproven stem cell treatments abroad more accurately about their efficacy and safety and provide them with improved medical and social support in their home countries.

Effects of an Emotion Control Treatment on Academic Emotions, Motivation and Achievement in an Online Mathematics Course

ERIC Educational Resources Information Center

Kim, ChanMin; Hodges, Charles B.

2012-01-01

We designed and developed an emotion control treatment and investigated its effects on college students' academic emotions, motivation, and achievement in an online remedial mathematics course. The treatment group showed more positive emotions of enjoyment and pride than the control group. The treatment group also showed a higher level of…

Do trauma-focussed psychological interventions have an effect on psychotic symptoms? A systematic review and meta-analysis.

PubMed

Brand, Rachel M; McEnery, Carla; Rossell, Susan; Bendall, Sarah; Thomas, Neil

2018-05-01

There is growing recognition of the relationship between trauma, posttraumatic stress disorder (PTSD) and psychosis. There may be overlaps in causal mechanisms involved in the development of PTSD and psychosis following traumatic or adverse events. Trauma-focussed treatments found to be effective in treating PTSD may therefore represent a new direction in the psychological treatment of psychosis. This systematic review examined the literature on trauma-focussed treatments conducted with people with schizophrenia spectrum or psychotic disorders to determine effects on psychotic symptoms. Secondary outcomes were symptoms of PTSD, depression and anxiety. Twenty-five studies were included in the review, with 12 being included in the meta-analysis. Trauma-focussed treatments had a small, significant effect (g=0.31, CI [0.55, 0.06]) on positive symptoms immediately post-treatment, but the significance and magnitude of this effect was not maintained at follow-up (g=0.18, CI [0.42, -0.06]). Trauma-focussed treatments also had a small effect on delusions at both post-treatment (g=0.37, CI [0.87, -0.12]) and follow-up (g=0.38, CI [0.67, 0.10]), but this only reached significance at follow-up. Effects on hallucinations and negative symptoms were small and non-significant. Effects on PTSD symptoms were also small (post-treatment g=0.21, CI [0.70, -0.27], follow up g=0.31, CI [0.62, 0.00]) and only met significance at follow-up. No significant effects were found on symptoms of depression and anxiety. Results show promising effects of trauma-focussed treatments for the positive symptoms of psychosis, however further studies developing and evaluating trauma-focussed treatments for trauma-related psychotic symptoms are needed. Copyright © 2017 Elsevier B.V. All rights reserved.

New Developments in Cognitive-Behavioral Therapy for Social Anxiety Disorder.

PubMed

Stangier, Ulrich

2016-03-01

Social anxiety disorder (SAD) is a highly prevalent and chronic disorder that causes considerable psychosocial impairment. This article reviews recent changes in the definition of SAD in DSM-5 and summarizes the current evidence for effective cognitive-behavioral treatments in adults, children, and adolescents. Current data suggests that cognitive-behavioral therapy (CBT) is efficacious in the treatment of this condition. Among different CBT approaches, individual cognitive therapy may be associated with the largest effect sizes. In this review, interventions targeting dysfunctional cognitive processes that contribute to the effective treatment of SAD are discussed. Some recent findings from neuroimaging research and studies on the augmentation of CBT using neuroenhancers indicate that changes in emotion regulation as well as fear extinction are important psychological mediators of positive outcome. Furthermore, internet-delivered CBT is a promising field of technological innovation that may improve access to effective treatments. Despite the availability of effective treatments, treatment-resistant SAD remains a common problem in clinical practice that requires more research efforts. Finally, potential areas for further development of CBT as well as its dissemination in health care are summarized.

Transforming Pain Medicine: Adapting to Science and Society

PubMed Central

Borsook, David; Kalso, Eija

2013-01-01

The field of chronic pain medicine is currently facing enormous challenges. The incidence of chronic pain is increasing worldwide, particularly in the developed world. As a result, chronic pain is imposing a growing burden on Western societies in terms of cost of medical care and lost productivity. This burden is exacerbated by the fact that despite research efforts and a huge expenditure on treatment for chronic pain, clinicians have no highly effective treatments or definitive diagnostic measures for patients. The lack of an objective measure for pain impedes basic research into the biological and psychological mechanisms of chronic pain and clinical research into treatment efficacy. The development of objective measurements of pain and ability to predict treatment responses in the individual patient is critical to improving pain management. Finally, pain medicine must embrace the development of a new evidence-based therapeutic model that recognizes the highly individual nature of responsiveness to pain treatments, integrates bio-psycho-behavioral approaches, and requires proof of clinical effectiveness for the various treatments we offer our patients. In the long-term these approaches will contribute to providing better diagnoses and more effective treatments to lessen the current challenges in pain medicine. PMID:23468059

Development and Use of an Eating Disorder Assessment and Treatment Protocol

ERIC Educational Resources Information Center

Huebner, Lois A.; Weitzman, Lauren M.; Mountain, Lisa M.; Nelson, Kris L.; Oakley, Danielle R.; Smith, Michael L.

2006-01-01

Counseling centers have been challenged to effectively treat the growing number of college students who struggle with disordered eating. In response to this critical issue, an Eating Disorder Assessment and Treatment Protocol (EDATP) was developed to assist clinical disposition in the counseling center setting and identify treatment guidelines…

Recent Developments in the Assessment and Treatment of Pediatric Obsessive-Compulsive Disorder

ERIC Educational Resources Information Center

Berman, Noah C.; Abramowitz, Jonathan S.

2010-01-01

Although tremendous strides have recently been made in the development of assessment and treatment methods for pediatric obsessive-compulsive disorder (OCD), more accurate methods for diagnosis, more effective treatments, and more refined instruments for monitoring progress during therapy are still needed. The present commentary highlights the…

Experimental and early investigational drugs for androgenetic alopecia.

PubMed

Guo, Hongwei; Gao, Wendi Victor; Endo, Hiromi; McElwee, Kevin John

2017-08-01

Treatments for androgenetic alopecia constitute a multi-billion-dollar industry, however, currently available therapeutic options have variable efficacy. Consequently, in recent years small biotechnology companies and academic research laboratories have begun to investigate new or improved treatment methods. Research and development approaches include improved formulations and modes of application for current drugs, new drug development, development of cell-based treatments, and medical devices for modulation of hair growth. Areas covered: Here we review the essential pathways of androgenetic alopecia pathogenesis and collate the current and emerging therapeutic strategies using journal publications databases and clinical trials databases to gather information about active research on new treatments. Expert opinion: We propose that topically applied medications, or intra-dermal injected or implanted materials, are preferable treatment modalities, minimizing side effect risks as compared to systemically applied treatments. Evidence in support of new treatments is limited. However, we suggest therapeutics which reverse the androgen-driven inhibition of hair follicle signaling pathways, such as prostaglandin analogs and antagonists, platelet-rich plasma (PRP), promotion of skin angiogenesis and perfusion, introduction of progenitor cells for hair regeneration, and more effective ways of transplanting hair, are the likely near future direction of androgenetic alopecia treatment development.

Benchmarks for detecting 'breakthroughs' in clinical trials: empirical assessment of the probability of large treatment effects using kernel density estimation.

PubMed

Miladinovic, Branko; Kumar, Ambuj; Mhaskar, Rahul; Djulbegovic, Benjamin

2014-10-21

To understand how often 'breakthroughs,' that is, treatments that significantly improve health outcomes, can be developed. We applied weighted adaptive kernel density estimation to construct the probability density function for observed treatment effects from five publicly funded cohorts and one privately funded group. 820 trials involving 1064 comparisons and enrolling 331,004 patients were conducted by five publicly funded cooperative groups. 40 cancer trials involving 50 comparisons and enrolling a total of 19,889 patients were conducted by GlaxoSmithKline. We calculated that the probability of detecting treatment with large effects is 10% (5-25%), and that the probability of detecting treatment with very large treatment effects is 2% (0.3-10%). Researchers themselves judged that they discovered a new, breakthrough intervention in 16% of trials. We propose these figures as the benchmarks against which future development of 'breakthrough' treatments should be measured. 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.

[Effects of diazepam on mixed anxiety/depression state in male mice].

PubMed

Galiamina, A G; Smagin, D A; Kovalenko, I L; Bondar', N P; Kudriavtseva, N N

2013-11-01

Chronic social defeat stress in daily agonistic interactions leads to the development of mixed anxiety/depression state in male mice. This paper aimed to study the effects of chronic diazepam treatment on the psychoemotional state of these animals. Diazepam (0.5 mg/kg, i/p, Polfa Tarchomin S. A.) or saline was chronically injected into male mice for two weeks on the background of continuing agonistic interactions (preventive treatment) or into male mice with mixed anxiety/depression state after stopping of social confrontations (therapeutic treatment). Then, the animals were studied in the partition, plus-maze and Porsolt' tests, estimating the levels of communicativeness, anxiety and depressiveness, respectively. Preventive diazepam treatment had a weak protective anxiolytic and pro-depressive effect. The therapeutic diazepam treatment didn't influence on the anxiety and depression-like state. Chronic diazepam was ineffective for the treatment of the mixed anxiety/depression state in male mice. Different effects ofdiazepam on anxiety and depression-like states under preventive treatment confirmed our conclusion shown earlier about the independent development of these pathologies at least in our experimental paradigm.

Gene therapy for arthritis

PubMed Central

Traister, Russell S.

2008-01-01

Arthritis is among the leading causes of disability in the developed world. There remains no cure for this disease and the current treatments are only modestly effective at slowing the disease's progression and providing symptomatic relief. The clinical effectiveness of current treatment regimens has been limited by short half-lives of the drugs and the requirement for repeated systemic administration. Utilizing gene transfer approaches for the treatment of arthritis may overcome some of the obstacles associated with current treatment strategies. The present review examines recent developments in gene therapy for arthritis. Delivery strategies, gene transfer vectors, candidate genes, and safety are also discussed. PMID:18176779

Cost-effectiveness model for hepatitis C screening and treatment: Implications for Egypt and other countries with high prevalence

PubMed Central

Kim, David D.; Hutton, David W.; Raouf, Ahmed A.; Salama, Mohsen; Hablas, Ahmed; Seifeldin, Ibrahim A.; Soliman, Amr S.

2014-01-01

Hepatitis C Virus (HCV) infection is a major cause of cirrhosis and liver cancer, and many developing countries report intermediate-to-high prevalence. However, the economic impact of screening and treatment for HCV in high prevalence countries has not been well studied. Thus, we examined the cost-effectiveness of screening and treatment for HCV infection for asymptomatic, average-risk adults using a Markov decision analytic model. In our model, we collected age-specific prevalence, disease progression rates for Egyptians, and local cost estimates in Egypt, which has the highest prevalence of HCV infection (~15%) in the world. We estimated the incremental cost-effectiveness ratio (ICER) and conducted sensitivity analyses to determine how cost-effective HCV screening and treatment might be in other developing countries with high and intermediate prevalence. In Egypt, implementing a screening program using triple-therapy treatment (sofosbuvir with pegylated interferon and ribavirin) was dominant compared to no screening because it would have lower total costs and improve health outcomes. HCV screening and treatment would also be cost-effective in global settings with intermediate costs of drug treatment (~$8,000) and a higher sustained viral response rate (70–80%). PMID:25469976

Developmental exposure to methimazole increases anxiety behavior in zebrafish.

PubMed

Reider, Masha; Connaughton, Victoria P

2015-10-01

The role of thyroid hormones in vertebrate development has been well documented for several decades. As hypothyroidism during critical periods of development can cause defects to the development of every major organ system, including brain, eye, and general morphology, we hypothesized that hypothyroidism would affect specific behaviors. To assess this, we treated zebrafish with the hypothyroid drug methimazole (MMI) and examined changes in anxiety, shoaling, vision, and locomotion. Following low-dose MMI exposure for the first 10 days of life, a time of rapid and significant development, larvae were removed from treatment and allowed to develop until 1 month of age. Comparisons between treated and controls took place between 10 and 30 days postfertilization to examine times both during and after treatment. Using the novel tank and startle response tests, we found that anxiety behaviors are significantly increased following MMI treatment. These effects persisted for several days following removal from treatment and indicate a prolonged effect of early hypothyroidism. However, permanent MMI effects on anxiety were not observed, as anxiety behaviors of early treated zebrafish recovered to control levels following 10 days out of treatment. In contrast to the strong link between MMI treatment and anxiety, shoaling and visual behaviors were not significantly affected within our experimental parameters. This indicates that disruption of thyroid system functioning early in life can differentially affect behavior by specifically altering anxiety responses without producing indiscriminate changes to overall behavioral development. (c) 2015 APA, all rights reserved).

Effects of music therapy in the treatment of children with delayed speech development - results of a pilot study.

PubMed

Gross, Wibke; Linden, Ulrike; Ostermann, Thomas

2010-07-21

Language development is one of the most significant processes of early childhood development. Children with delayed speech development are more at risk of acquiring other cognitive, social-emotional, and school-related problems. Music therapy appears to facilitate speech development in children, even within a short period of time. The aim of this pilot study is to explore the effects of music therapy in children with delayed speech development. A total of 18 children aged 3.5 to 6 years with delayed speech development took part in this observational study in which music therapy and no treatment were compared to demonstrate effectiveness. Individual music therapy was provided on an outpatient basis. An ABAB reversal design with alternations between music therapy and no treatment with an interval of approximately eight weeks between the blocks was chosen. Before and after each study period, a speech development test, a non-verbal intelligence test for children, and music therapy assessment scales were used to evaluate the speech development of the children. Compared to the baseline, we found a positive development in the study group after receiving music therapy. Both phonological capacity and the children's understanding of speech increased under treatment, as well as their cognitive structures, action patterns, and level of intelligence. Throughout the study period, developmental age converged with their biological age. Ratings according to the Nordoff-Robbins scales showed clinically significant changes in the children, namely in the areas of client-therapist relationship and communication. This study suggests that music therapy may have a measurable effect on the speech development of children through the treatment's interactions with fundamental aspects of speech development, including the ability to form and maintain relationships and prosodic abilities. Thus, music therapy may provide a basic and supportive therapy for children with delayed speech development. Further studies should be conducted to investigate the mechanisms of these interactions in greater depth. The trial is registered in the German clinical trials register; Trial-No.: DRKS00000343.

Prevention, screening and treatment of colorectal cancer: a global and regional generalized cost effectiveness analysis

PubMed Central

2010-01-01

Background Regional generalized cost-effectiveness estimates of prevention, screening and treatment interventions for colorectal cancer are presented. Methods Standardised WHO-CHOICE methodology was used. A colorectal cancer model was employed to provide estimates of screening and treatment effectiveness. Intervention effectiveness was determined via a population state-transition model (PopMod) that simulates the evolution of a sub-regional population accounting for births, deaths and disease epidemiology. Economic costs of procedures and treatment were estimated, including programme overhead and training costs. Results In regions characterised by high income, low mortality and high existing treatment coverage, the addition of screening to the current high treatment levels is very cost-effective, although no particular intervention stands out in cost-effectiveness terms relative to the others. In regions characterised by low income, low mortality with existing treatment coverage around 50%, expanding treatment with or without screening is cost-effective or very cost-effective. Abandoning treatment in favour of screening (no treatment scenario) would not be cost effective. In regions characterised by low income, high mortality and low treatment levels, the most cost-effective intervention is expanding treatment. Conclusions From a cost-effectiveness standpoint, screening programmes should be expanded in developed regions and treatment programmes should be established for colorectal cancer in regions with low treatment coverage. PMID:20236531

Chronic Treatment With Aripiprazole Prevents Development of Dopamine Supersensitivity and Potentially Supersensitivity Psychosis

PubMed Central

Tadokoro, Shigenori; Okamura, Naoe; Sekine, Yoshimoto; Kanahara, Nobuhisa; Hashimoto, Kenji; Iyo, Masaomi

2012-01-01

Background: Long-term treatment of schizophrenia with antipsychotics is crucial for relapse prevention, but a prolonged blockade of D2 dopamine receptors may lead to the development of supersensitivity psychosis. We investigated the chronic effects of aripiprazole (ARI) on dopamine sensitivity. Methods: We administered ARI (1.5 mg/kg/d), haloperidol (HAL; 0.75 mg/kg/d), or vehicle (VEH) via minipump for 14 days to drug-naive rats or to rats pretreated with HAL (0.75 mg/kg/d) or VEH via minipump for 14 days. On the seventh day following treatment cessation, we examined the effects of the treatment conditions on the locomotor response to methamphetamine and on striatal D2 receptor density (N = 4-10/condition/experiment). Results: Chronic treatment with HAL led to significant increases in locomotor response and D2 receptor density, compared with the effects of chronic treatment with either VEH or ARI; there were no significant differences in either locomotor response or D2 density between the VEH- and ARI-treated groups. We also investigated the effects of chronic treatment with HAL, ARI, or VEH preceded by HAL or VEH treatment on locomotor response and D2 density. ANOVA analysis indicated that the rank ordering of groups for both locomotor response and D2 density was HAL-HAL > HAL-VEH > HAL-ARI > VEH-VEH. Conclusions: Chronic treatment with ARI prevents development of dopamine supersensitivity and potentially supersensitivity psychosis, suggesting that by reducing excessive sensitivity to dopamine and by stabilizing sensitivity for an extended period of time, ARI may be helpful for some patients with treatment-resistant schizophrenia. PMID:21402722

The New Era of Treatment for Obesity and Metabolic Disorders: Evidence and Expectations for Gut Microbiome Transplantation

PubMed Central

Jayasinghe, Thilini N.; Chiavaroli, Valentina; Holland, David J.; Cutfield, Wayne S.; O'Sullivan, Justin M.

2016-01-01

Key Points The microbiome has been implicated in the development of obesity.Conventional therapeutic methods have limited effectiveness for the treatment of obesity and prevention of related complications.Gut microbiome transplantation may represent an alternative and effective therapy for the treatment of obesity. Obesity has reached epidemic proportions. Despite a better understanding of the underlying pathophysiology and growing treatment options, a significant proportion of obese patients do not respond to treatment. Recently, microbes residing in the human gastrointestinal tract have been found to act as an “endocrine” organ, whose composition and functionality may contribute to the development of obesity. Therefore, fecal/gut microbiome transplantation (GMT), which involves the transfer of feces from a healthy donor to a recipient, is increasingly drawing attention as a potential treatment for obesity. Currently the evidence for GMT effectiveness in the treatment of obesity is preliminary. Here, we summarize benefits, procedures, and issues associated with GMT, with a special focus on obesity. PMID:26925392

Effects of ultralow oxygen and vacuum treatments on bed bug (Heteroptera: Cimicidae) survival

USDA-ARS?s Scientific Manuscript database

Control of bed bugs has always been problematic, balancing among efficacy, safety, and cost. In this study, ultralow oxygen (ULO) and vacuum treatments were tested on bed bugs to develop a safer, effective, and environmental friendly solution to bed bug infestations. ULO treatments were establishe...

A Century of Misunderstanding: The History of the Development of Post Traumatic Stress Disorder Understanding in the United States Military

DTIC Science & Technology

2015-06-12

development of treatment for servicemen and women suffering from PTSD, and the treatment methods unique to WWII, Korea, Vietnam, and the GWOT eras...the development of treatment for servicemen and women suffering from PTSD, and the treatment methods unique to WWII, Korea, Vietnam, and the GWOT...Army began to acknowledge the effects that PTSD has on the force, and implemented programs and procedures, medicinal and psychological, in order to

Preliminary study on the effectiveness of short group cognitive behavioral therapy (GCBT) on Indonesian older adults.

PubMed

Utoyo, Dharmayati Bambang; Lubis, Dharmayati Utoyo; Jaya, Edo Sebastian; Arjadi, Retha; Hanum, Lathifah; Astri, Kresna; Putri, Maha Decha Dwi

2013-01-01

This research aims to develop evidence based affordable psychological therapy for Indonesian older adults. An affordable psychological therapy is important as there is virtually no managed care or health insurance that covers psychological therapy in Indonesia. Multicomponent group cognitive behavior therapy (GCBGT) was chosen as a starting point due to its extensive evidence, short sessions, and success for a wide range of psychological problems. The group format was chosen to address both the economic and the cultural context of Indonesia. Then, the developed treatment is tested to common psychological problems in older adults' population (anxiety, chronic pain, depression, and insomnia). The treatment consists of 8 sessions with twice a week meetings for 2.5 hours. There are similarities and differences among the techniques used in the treatment for the different psychological problems. The final participants are 38 older adults that are divided into the treatment groups; 8 participants joined the anxiety treatment, 10 participants for the chronic pain treatment, 10 participants for depression treatment, and lastly, 10 participants joined the insomnia treatment. The research design is pre-test post-test with within group analysis. We used principal outcome measure that is specific for each treatment group, as well as additional outcome measures. Overall, the result shows statistical significance change with large effect size for the principal outcome measure. In addition, the result for the additional measures varies from slight improvement with small effect size to statistically significant improvement with large effect size. The result indicates that short multicomponent GCBT is effective in alleviating various common psychological problems in Indonesian older adults. Therefore, multicomponent GCBT may be a good starting point to develop an effective and affordable psychological therapy for Indonesian older adults. Lastly, this result adds to the accumulating body of evidence on the effectiveness of multicomponent GCBT outside western context.

Preliminary Study on the Effectiveness of Short Group Cognitive Behavioral Therapy (GCBT) on Indonesian Older Adults

PubMed Central

Lubis, Dharmayati Utoyo; Jaya, Edo Sebastian; Arjadi, Retha; Hanum, Lathifah; Astri, Kresna; Putri, Maha Decha Dwi

2013-01-01

This research aims to develop evidence based affordable psychological therapy for Indonesian older adults. An affordable psychological therapy is important as there is virtually no managed care or health insurance that covers psychological therapy in Indonesia. Multicomponent group cognitive behavior therapy (GCBGT) was chosen as a starting point due to its extensive evidence, short sessions, and success for a wide range of psychological problems. The group format was chosen to address both the economic and the cultural context of Indonesia. Then, the developed treatment is tested to common psychological problems in older adults' population (anxiety, chronic pain, depression, and insomnia). The treatment consists of 8 sessions with twice a week meetings for 2.5 hours. There are similarities and differences among the techniques used in the treatment for the different psychological problems. The final participants are 38 older adults that are divided into the treatment groups; 8 participants joined the anxiety treatment, 10 participants for the chronic pain treatment, 10 participants for depression treatment, and lastly, 10 participants joined the insomnia treatment. The research design is pre-test post-test with within group analysis. We used principal outcome measure that is specific for each treatment group, as well as additional outcome measures. Overall, the result shows statistical significance change with large effect size for the principal outcome measure. In addition, the result for the additional measures varies from slight improvement with small effect size to statistically significant improvement with large effect size. The result indicates that short multicomponent GCBT is effective in alleviating various common psychological problems in Indonesian older adults. Therefore, multicomponent GCBT may be a good starting point to develop an effective and affordable psychological therapy for Indonesian older adults. Lastly, this result adds to the accumulating body of evidence on the effectiveness of multicomponent GCBT outside western context. PMID:23437339

Central nervous system side effects associated with zolpidem treatment.

PubMed

Toner, L C; Tsambiras, B M; Catalano, G; Catalano, M C; Cooper, D S

2000-01-01

Zolpidem is one of the newer medications developed for the treatment of insomnia. It is an imidazopyridine agent that is an alternative to the typical sedative-hypnotic agents. Zolpidem use is gaining favor because of its efficacy and its side effect profile, which is milder and less problematic than that of the benzodiazepines and barbiturates used to treat insomnia. Still, side effects are not uncommon with zolpidem use. We report a series of cases in which the patients developed delirium, nightmares and hallucinations during treatment with zolpidem. We will review its pharmacology, discuss previous reports of central nervous system side effects, examine the impact of drug interactions with concurrent use of antidepressants, examine gender differences in susceptibility to side effects, and explore the significance of protein binding in producing side effects.

Cost-Effectiveness of Thrombolysis within 4.5 Hours of Acute Ischemic Stroke in China

PubMed Central

Zhao, Xingquan; Liao, Xiaoling; Wang, Chunjuan; Du, Wanliang; Liu, Gaifen; Liu, Liping; Wang, Chunxue; Wang, Yilong; Wang, Yongjun

2014-01-01

Background Previous economic studies conducted in developed countries showed intravenous tissue-type plasminogen activator (tPA) is cost-effective for acute ischemic stroke. The present study aimed to determine the cost-effectiveness of tPA treatment in China, the largest developing country. Methods A combination of decision tree and Markov model was developed to determine the cost-effectiveness of tPA treatment versus non-tPA treatment within 4.5 hours after stroke onset. Outcomes and costs data were derived from the database of Thrombolysis Implementation and Monitor of acute ischemic Stroke in China (TIMS-China) study. Efficacy data were derived from a pooled analysis of ECASS, ATLANTIS, NINDS, and EPITHET trials. Costs and quality-adjusted life-years (QALYs) were compared in both short term (2 years) and long term (30 years). One-way and probabilistic sensitivity analyses were performed to test the robustness of the results. Results Comparing to non-tPA treatment, tPA treatment within 4.5 hours led to a short-term gain of 0.101 QALYs at an additional cost of CNY 9,520 (US$ 1,460), yielding an incremental cost-effectiveness ratio (ICER) of CNY 94,300 (US$ 14,500) per QALY gained in 2 years; and to a long-term gain of 0.422 QALYs at an additional cost of CNY 6,530 (US$ 1,000), yielding an ICER of CNY 15,500 (US$ 2,380) per QALY gained in 30 years. Probabilistic sensitivity analysis showed that tPA treatment is cost-effective in 98.7% of the simulations at a willingness-to-pay threshold of CNY 105,000 (US$ 16,200) per QALY. Conclusions Intravenous tPA treatment within 4.5 hours is highly cost-effective for acute ischemic strokes in China. PMID:25329637

Development of an economic model to assess the cost-effectiveness of hawthorn extract as an adjunct treatment for heart failure in Australia

PubMed Central

Ford, Emily; Adams, Jon; Graves, Nicholas

2012-01-01

Objective An economic model was developed to evaluate the cost-effectiveness of hawthorn extract as an adjunctive treatment for heart failure in Australia. Methods A Markov model of chronic heart failure was developed to compare the costs and outcomes of standard treatment and standard treatment with hawthorn extract. Health states were defined by the New York Heart Association (NYHA) classification system and death. For any given cycle, patients could remain in the same NYHA class, experience an improvement or deterioration in NYHA class, be hospitalised or die. Model inputs were derived from the published medical literature, and the output was quality-adjusted life years (QALYs). Probabilistic sensitivity analysis was conducted. The expected value of perfect information (EVPI) and the expected value of partial perfect information (EVPPI) were conducted to establish the value of further research and the ideal target for such research. Results Hawthorn extract increased costs by $1866.78 and resulted in a gain of 0.02 QALYs. The incremental cost-effectiveness ratio was $85 160.33 per QALY. The cost-effectiveness acceptability curve indicated that at a threshold of $40 000 the new treatment had a 0.29 probability of being cost-effective. The average incremental net monetary benefit (NMB) was −$1791.64, the average NMB for the standard treatment was $92 067.49, and for hawthorn extract $90 275.84. Additional research is potentially cost-effective if research is not proposed to cost more than $325 million. Utilities form the most important target parameter group for further research. Conclusions Hawthorn extract is not currently considered to be cost-effective in as an adjunctive treatment for heart failure in Australia. Further research in the area of utilities is warranted. PMID:22942231

Development of an economic model to assess the cost-effectiveness of hawthorn extract as an adjunct treatment for heart failure in Australia.

PubMed

Ford, Emily; Adams, Jon; Graves, Nicholas

2012-01-01

An economic model was developed to evaluate the cost-effectiveness of hawthorn extract as an adjunctive treatment for heart failure in Australia. A Markov model of chronic heart failure was developed to compare the costs and outcomes of standard treatment and standard treatment with hawthorn extract. Health states were defined by the New York Heart Association (NYHA) classification system and death. For any given cycle, patients could remain in the same NYHA class, experience an improvement or deterioration in NYHA class, be hospitalised or die. Model inputs were derived from the published medical literature, and the output was quality-adjusted life years (QALYs). Probabilistic sensitivity analysis was conducted. The expected value of perfect information (EVPI) and the expected value of partial perfect information (EVPPI) were conducted to establish the value of further research and the ideal target for such research. Hawthorn extract increased costs by $1866.78 and resulted in a gain of 0.02 QALYs. The incremental cost-effectiveness ratio was $85 160.33 per QALY. The cost-effectiveness acceptability curve indicated that at a threshold of $40 000 the new treatment had a 0.29 probability of being cost-effective. The average incremental net monetary benefit (NMB) was -$1791.64, the average NMB for the standard treatment was $92 067.49, and for hawthorn extract $90 275.84. Additional research is potentially cost-effective if research is not proposed to cost more than $325 million. Utilities form the most important target parameter group for further research. Hawthorn extract is not currently considered to be cost-effective in as an adjunctive treatment for heart failure in Australia. Further research in the area of utilities is warranted.

Cost-effectiveness of thrombolysis within 4.5 hours of acute ischemic stroke in China.

PubMed

Pan, Yuesong; Chen, Qidong; Zhao, Xingquan; Liao, Xiaoling; Wang, Chunjuan; Du, Wanliang; Liu, Gaifen; Liu, Liping; Wang, Chunxue; Wang, Yilong; Wang, Yongjun

2014-01-01

Previous economic studies conducted in developed countries showed intravenous tissue-type plasminogen activator (tPA) is cost-effective for acute ischemic stroke. The present study aimed to determine the cost-effectiveness of tPA treatment in China, the largest developing country. A combination of decision tree and Markov model was developed to determine the cost-effectiveness of tPA treatment versus non-tPA treatment within 4.5 hours after stroke onset. Outcomes and costs data were derived from the database of Thrombolysis Implementation and Monitor of acute ischemic Stroke in China (TIMS-China) study. Efficacy data were derived from a pooled analysis of ECASS, ATLANTIS, NINDS, and EPITHET trials. Costs and quality-adjusted life-years (QALYs) were compared in both short term (2 years) and long term (30 years). One-way and probabilistic sensitivity analyses were performed to test the robustness of the results. Comparing to non-tPA treatment, tPA treatment within 4.5 hours led to a short-term gain of 0.101 QALYs at an additional cost of CNY 9,520 (US$ 1,460), yielding an incremental cost-effectiveness ratio (ICER) of CNY 94,300 (US$ 14,500) per QALY gained in 2 years; and to a long-term gain of 0.422 QALYs at an additional cost of CNY 6,530 (US$ 1,000), yielding an ICER of CNY 15,500 (US$ 2,380) per QALY gained in 30 years. Probabilistic sensitivity analysis showed that tPA treatment is cost-effective in 98.7% of the simulations at a willingness-to-pay threshold of CNY 105,000 (US$ 16,200) per QALY. Intravenous tPA treatment within 4.5 hours is highly cost-effective for acute ischemic strokes in China.

Simulated Seasonal Photoperiods and Fluctuating Temperatures Have Limited Effects on Blood Feeding and Life History in Aedes triseriatus (Diptera: Culicidae)

PubMed Central

Westby, K. M.

2015-01-01

Biotic and abiotic factors change seasonally and impact life history in temperate-zone ectotherms. Temperature and photoperiod are factors that change in predictable ways. Most studies testing for effects of temperature on vectors use constant temperatures and ignore potential correlated effects of photoperiod. In two experiments, we tested for effects of larval rearing environments creating ecologically relevant temperatures and photoperiods simulating early and late season conditions (June and August), or constant temperatures (cool and warm) with the June or August photoperiods, respectively. We determined effects on survivorship, development, size, and a composite performance index in a temperate-zone population of Aedes triseriatus (Say). We followed cohorts of resulting females, all held under the same environmental conditions, to assess carry-over effects of rearing conditions for larvae on longevity, blood feeding, and egg production. Larval survivorship was affected by treatment in one experiment. Development time was greater in the June and cool treatments, but the constant and fluctuating temperatures did not differ. Significantly larger mosquitoes were produced in fluctuating versus constant temperature treatments. There were no significant treatment effects on the composite performance index. Adult female longevity was lower after rearing at constant versus fluctuating temperature, but there was no difference between June and August, nor did size affect longevity. There was no effect of treatments on blood feeding and a limited effect on egg production. We conclude that seasonal temperatures and photoperiods during development have limited effects on this population of A. triseriatus and find little evidence of strong effects of fluctuating versus constant temperatures. PMID:26336255

Developing Coordinated, Multimodal, School Based Treatment for Young Adolescents with ADHD

ERIC Educational Resources Information Center

Evans, Steven W.; Timmins, Bebhinn; Sibley, Maggie; White, L. Casey; Serpell, Zewelanji N.; Schultz, Brandon

2006-01-01

Adolescents with ADHD experience serious impairment that taxes our education, mental health, and healthcare systems as well as the children and families. The development and evaluation of effective treatments for these youth have lagged far behind that of many other disorders and age groups. This manuscript describes the treatment development…

Cardiovascular disease after cancer therapy

PubMed Central

Aleman, Berthe M.P.; Moser, Elizabeth C.; Nuver, Janine; Suter, Thomas M.; Maraldo, Maja V.; Specht, Lena; Vrieling, Conny; Darby, Sarah C.

2014-01-01

Improvements in treatment and earlier diagnosis have both contributed to increased survival for many cancer patients. Unfortunately, many treatments carry a risk of late effects including cardiovascular diseases (CVDs), possibly leading to significant morbidity and mortality. In this paper we describe current knowledge of the cardiotoxicity arising from cancer treatments, outline gaps in knowledge, and indicate directions for future research and guideline development, as discussed during the 2014 Cancer Survivorship Summit organised by the European Organisation for Research and Treatment of Cancer (EORTC). Better knowledge is needed of the late effects of modern systemic treatments and of radiotherapy to critical structures of the heart, including the effect of both radiation dose and volume of the heart exposed. Research elucidating the extent to which treatments interact in causing CVD, and the mechanisms involved, as well as the extent to which treatments may increase CVD indirectly by increasing cardiovascular risk factors is also important. Systematic collection of data relating treatment details to late effects is needed, and great care is needed to obtain valid and generalisable results. Better knowledge of these cardiac effects will contribute to both primary and secondary prevention of late complications where exposure to cardiotoxic treatment is unavoidable. Also surrogate markers would help to identify patients at increased risk of cardiotoxicity. Evidence-based screening guidelines for CVD following cancer are also needed. Finally, risk prediction models should be developed to guide primary treatment choice and appropriate follow up after cancer treatment. PMID:26217163

Development of an autonomous treatment planning strategy for radiation therapy with effective use of population-based prior data.

PubMed

Wang, Huan; Dong, Peng; Liu, Hongcheng; Xing, Lei

2017-02-01

Current treatment planning remains a costly and labor intensive procedure and requires multiple trial-and-error adjustments of system parameters such as the weighting factors and prescriptions. The purpose of this work is to develop an autonomous treatment planning strategy with effective use of prior knowledge and in a clinically realistic treatment planning platform to facilitate radiation therapy workflow. Our technique consists of three major components: (i) a clinical treatment planning system (TPS); (ii) a formulation of decision-function constructed using an assemble of prior treatment plans; (iii) a plan evaluator or decision-function and an outer-loop optimization independent of the clinical TPS to assess the TPS-generated plan and to drive the search toward a solution optimizing the decision-function. Microsoft (MS) Visual Studio Coded UI is applied to record some common planner-TPS interactions as subroutines for querying and interacting with the TPS. These subroutines are called back in the outer-loop optimization program to navigate the plan selection process through the solution space iteratively. The utility of the approach is demonstrated by using clinical prostate and head-and-neck cases. An autonomous treatment planning technique with effective use of an assemble of prior treatment plans is developed to automatically maneuver the clinical treatment planning process in the platform of a commercial TPS. The process mimics the decision-making process of a human planner and provides a clinically sensible treatment plan automatically, thus reducing/eliminating the tedious manual trial-and-errors of treatment planning. It is found that the prostate and head-and-neck treatment plans generated using the approach compare favorably with that used for the patients' actual treatments. Clinical inverse treatment planning process can be automated effectively with the guidance of an assemble of prior treatment plans. The approach has the potential to significantly improve the radiation therapy workflow. © 2016 American Association of Physicists in Medicine.

Sub-Lethal Effects of Pesticide Residues in Brood Comb on Worker Honey Bee (Apis mellifera) Development and Longevity

PubMed Central

Wu, Judy Y.; Anelli, Carol M.; Sheppard, Walter S.

2011-01-01

Background Numerous surveys reveal high levels of pesticide residue contamination in honey bee comb. We conducted studies to examine possible direct and indirect effects of pesticide exposure from contaminated brood comb on developing worker bees and adult worker lifespan. Methodology/Principal Findings Worker bees were reared in brood comb containing high levels of known pesticide residues (treatment) or in relatively uncontaminated brood comb (control). Delayed development was observed in bees reared in treatment combs containing high levels of pesticides particularly in the early stages (day 4 and 8) of worker bee development. Adult longevity was reduced by 4 days in bees exposed to pesticide residues in contaminated brood comb during development. Pesticide residue migration from comb containing high pesticide residues caused contamination of control comb after multiple brood cycles and provided insight on how quickly residues move through wax. Higher brood mortality and delayed adult emergence occurred after multiple brood cycles in contaminated control combs. In contrast, survivability increased in bees reared in treatment comb after multiple brood cycles when pesticide residues had been reduced in treatment combs due to residue migration into uncontaminated control combs, supporting comb replacement efforts. Chemical analysis after the experiment confirmed the migration of pesticide residues from treatment combs into previously uncontaminated control comb. Conclusions/Significance This study is the first to demonstrate sub-lethal effects on worker honey bees from pesticide residue exposure from contaminated brood comb. Sub-lethal effects, including delayed larval development and adult emergence or shortened adult longevity, can have indirect effects on the colony such as premature shifts in hive roles and foraging activity. In addition, longer development time for bees may provide a reproductive advantage for parasitic Varroa destructor mites. The impact of delayed development in bees on Varroa mite fecundity should be examined further. PMID:21373182

Exercise and prostate cancer: From basic science to clinical applications.

PubMed

Campos, Christian; Sotomayor, Paula; Jerez, Daniel; González, Javier; Schmidt, Camila B; Schmidt, Katharina; Banzer, Winfried; Godoy, Alejandro S

2018-06-01

Prostate cancer (PCa) is a disease of increasing medical significance worldwide. In developed countries, PCa is the most common non-skin cancer in men, and one of the leading causes of cancer-related deaths. Exercise is one of the environmental factors that have been shown to influence cancer risk. Moreover, systemic reviews and meta-analysis have suggested that total physical activity is related to a decrease in the risk of developing PCa. In addition, epidemiological studies have shown that exercise, after diagnosis, has benefits regarding PCa development, and positive outcome in patients under treatment. The standard treatment for locally advanced or metastatic PCa is Androgen deprivation therapy (ADT). ADT produces diverse side effects, including loss of libido, changes in body composition (increase abdominal fat), and reduced muscle mass, and muscle tone. Analysis of numerous research publications showed that aerobic and/or resistance training improve patient's physical condition, such us, cardiorespiratory fitness, muscle strength, physical function, body composition, and fatigue. Therefore, exercise might counteract several ADT treatment-induced side effects. In addition of the aforementioned benefits, epidemiological, and in vitro studies have shown that exercise might decrease PCa development. Thus, physical activity might attenuate the risk of PCa and supervised exercise intervention might improve deleterious effects of cancer treatment, such as ADT side effects. This review article provides evidence indicating that exercise could complement, and potentiate, the current standard treatments for advanced PCa, probably by creating an unfavorable microenvironment that can negatively affect tumor development, and progression. © 2018 Wiley Periodicals, Inc.

Developing and Implementing a Positive Behavioral Reinforcement Intervention in Prison-Based Drug Treatment: Project BRITE

PubMed Central

Burdon, William M.; De Lore, Jef St.; Prendergast, Michael L.

2012-01-01

Within prison settings, the reliance on punishment for controlling inappropriate or non-compliant behavior is self-evident. What is not so evident is the similarity between this reliance on punishment and the use of positive reinforcements to increase desired behaviors. However, seldom do inmates receive positive reinforcement for engaging in prosocial behaviors or, for inmates receiving drug treatment, behaviors that are consistent with or support their recovery. This study provides an overview of the development and implementation of a positive behavioral reinforcement intervention in male and female prison-based drug treatment programs. The active involvement of institutional staff, treatment staff, and inmates enrolled in the treatment programs in the development of the intervention along with the successful branding of the intervention were effective at promoting support and participation. However, these factors may also have ultimately impacted the ability of the randomized design to reliably demonstrate the effectiveness of the intervention. PMID:22185038

Developing and implementing a positive behavioral reinforcement intervention in prison-based drug treatment: Project BRITE.

PubMed

Burdon, William M; St De Lore, Jef; Prendergast, Michael L

2011-09-01

Within prison settings, the reliance on punishment for controlling inappropriate or noncompliant behavior is self-evident. What is not so evident is the similarity between this reliance on punishment and the use of positive reinforcements to increase desired behaviors. However, seldom do inmates receive positive reinforcement for engaging in prosocial behaviors or, for inmates receiving drug treatment, behaviors that are consistent with or support their recovery. This study provides an overview of the development and implementation of a positive behavioral reinforcement intervention in male and female prison-based drug treatment programs. The active involvement of institutional staff, treatment staff, and inmates enrolled in the treatment programs in the development of the intervention along with the successful branding of the intervention were effective at promoting support and participation. However, these factors may also have ultimately impacted the ability of the randomized design to reliably demonstrate the effectiveness of the intervention.

Evaluation of an integrated group cognitive-behavioral treatment for comorbid mood, anxiety, and substance use disorders: A pilot study.

PubMed

Milosevic, Irena; Chudzik, Susan M; Boyd, Susan; McCabe, Randi E

2017-03-01

This paper presents the development and preliminary evaluation of an integrated group cognitive-behavioral treatment (CBT) for comorbid mood, anxiety, and substance use disorders. The 12-session, manualized treatment was developed collaboratively by a mental health program in a teaching hospital and a community-based addictions service and administered in both settings. Results from an uncontrolled effectiveness trial of 29 treatment completers suggest that integrated group CBT may reduce stress and alcohol use symptoms and improve substance refusal self-efficacy. Changes in symptoms of anxiety, depression, and drug use were not significant, although the effect size for anxiety reduction was in the medium range. Nonetheless, the clinical significance of treatment effects on mood, anxiety, and substance use symptoms was modest. Changes in coping skills and quality of life were not significant, although medium-to-large effects were observed for changes in several coping skills. Participants reported being highly satisfied with treatment, found the treatment strategies to be useful, and noted an improvement in their functioning, particularly socially. Methodological and sample size limitations warrant more rigorous follow-up investigations of this treatment. Results are considered in the context of the current literature on integrated psychological treatments for these common comorbidities. Copyright © 2016 Elsevier Ltd. All rights reserved.

The development of a 'best practice' service for women in a medium-secure psychiatric setting: treatment components and evaluation.

PubMed

Long, Clive G; Fulton, Barbara; Hollin, Clive R

2008-01-01

The inadequacy of inpatient facilities for women with severe psychiatric and co-morbid difficulties has been repeatedly documented. The establishment of effective therapeutic programmes for women in medium psychiatric facilities is also in their infancy, and little research has been undertaken. This article describes the development of a 'best practice' psychological treatment programme for women with a dual diagnosis. Emphasis is placed on the need to develop further intensive gender-specific services using an established model for effective therapeutic service development. In addition to a detailed description of the group therapy programme, staff training initiatives, methods for ensuring treatment integrity and a methodology for service evaluation is given. Copyright (c) 2008 John Wiley & Sons, Ltd.

Attention-Modulating Effects of Cognitive Enhancers

PubMed Central

Levin, Edward D.; Bushnell, Philip J.; Rezvani, Amir H.

2011-01-01

Attention can be readily measured in experimental animal models. Animal models of attention have been used to better understand the neural systems involved in attention, how attention is impaired, and how therapeutic treatments can ameliorate attentional deficits. This review focuses on the ways in which animal models are used to better understand the neuronal mechanism of attention and how to develop new therapeutic treatments for attentional impairment. Several behavioral test methods have been developed for experimental animal studies of attention, including a 5-choice serial reaction time task (5-CSRTT), a signal detection task (SDT), and a novel object recognition (NOR) test. These tasks can be used together with genetic, lesion, pharmacological and behavioral models of attentional impairment to test the efficacy of novel therapeutic treatments. The most prominent genetic model is the spontaneously hypertensive rat (SHR). Well-characterized lesion models include frontal cortical or hippocamapal lesions. Pharmacological models include challenge with the NMDA glutamate antagonist dizocilpine (MK-801), the nicotinic cholinergic antagonist mecamylamine and the muscarinic cholinergic antagonist scopolamine. Behavioral models include distracting stimuli and attenuated target stimuli. Important validation of these behavioral tests and models of attentional impairments for developing effective treatments for attentional dysfunction is the fact that stimulant treatments effective for attention deficit hyperactivity disorder (ADHD), such as methylphenidate (Ritalin®), are effective in the experimental animal models. Newer lines of treatment including nicotinic agonists, α4β2 nicotinic receptor desensitizers, and histamine H3 antagonists, have also been found to be effective in improving attention in these animal models. Good carryover has also been seen for the attentional improvement of nicotine in experimental animal models and in human populations. Animal models of attention can be effectively used for the development of new treatments of attentional impairment in ADHD and other syndromes in which have attentional impairments occur, such as Alzheimer’s disease and schizophrenia. PMID:21334367

Barrett's esophagus: endoscopic treatments II

PubMed Central

Greenwald, Bruce D.; Lightdale, Charles J.; Abrams, Julian A.; Horwhat, John D.; Chuttani, Ram; Komanduri, Srinadh; Upton, Melissa P.; Appelman, Henry D.; Shields, Helen M.; Shaheen, Nicholas J.; Sontag, Stephen J.

2013-01-01

The following on endoscopic treatments of Barrett's esophagus includes commentaries on animal experiments on cryotherapy; indications for cryotherapy, choice of dosimetry, number of sessions, and role in Barrett's esophagus and adenocarcinoma; recent technical developments of RFA technology and long-term effects; the comparative effects of diverse ablation procedures and the rate of recurrence following treatment; and the indications for treatment of dysplasia and the role of radiofrequency ablation. PMID:21950812

Analysis of External Treatment Methods and Technical Characteristics of External Treatment

NASA Astrophysics Data System (ADS)

Zhang, Rui; Miao, Mingsan; Bai, Ming

2018-01-01

Chinese medicine external therapy is a treatment method of Chinese medicine with Chinese characteristics. The effect of traditional Chinese medicine external treatment, convenient operation, external treatment and technology has great prospects for development. The traditional Chinese medicine external treatment method and technical characteristics were analyzed.

Tools to aid post-wildfire assessment and erosion-mitigation treatment decisions

Treesearch

Peter R. Robichaud; Louise E. Ashmun

2013-01-01

A considerable investment in post-fire research over the past decade has improved our understanding of wildfire effects on soil, hydrology, erosion and erosion-mitigation treatment effectiveness. Using this new knowledge, we have developed several tools to assist land managers with post-wildfire assessment and treatment decisions, such as prediction models, research...

Effects of American Ginseng on Preimplantation Development and Pregnancy in Mice.

PubMed

Belanger, Danyka; Calder, Michele D; Gianetto-Berruti, Alessandra; Lui, Edmund M; Watson, Andrew J; Feyles, Valter

2016-01-01

In North America, a high proportion of pregnant women use herbal medications including North American ginseng. This medicinal plant contains high amounts of triterpene saponins (ginsenosides), which are the main bioactive compounds. It is important to assess ginseng's impact on all reproductive functions to ensure the safety of pregnant women and fetuses. In this study, we defined the concentration-responsive effects of North American alcoholic and aqueous ginseng extracts on preimplantation development in vitro and on pregnancy and post-partum development in the mouse. Two-cell mouse embryos were cultured with 5 different concentrations of whole ginseng root extracts, or ginsenosides Rb1, Rg1 and Re alone, a combinatorial ginsenoside solution and a crude polysaccharide fraction solution. Embryonic development and recovery from each treatment was assessed. To investigate the in vivo effects of ginseng extracts, female mice were gavaged with 50[Formula: see text]mg/kg/day, 500[Formula: see text]mg/kg/day or 2000[Formula: see text]mg/kg/day of either extract (treatment) or water (sham) for 2 weeks prior to mating and throughout gestation. Gestation period, litter size, pup growth and pup sex ratio were evaluated. Oral ginseng consumption did not significantly affect fertility or pregnancy in the mouse. High doses of ginseng (2000[Formula: see text]mg/kg/day) decreased maternal weight gain. Direct treatment of preimplantation embryos in vitro demonstrated that ALC and AQ extract treatment reduced development in a concentration responsive manner, while only ALC extract effects were largely reversible. Treatments with individual or combinatorial ginsenosides, or the polysaccharide fraction solution alone did not impair preimplantation development, in vitro. In conclusion, maternal oral consumption of ginseng has little negative impact on pregnancy in the mouse, however, direct exposure to ginseng extract during mouse preimplantation development in vitro is detrimental.

Motivating the Drug Addict in Treatment

ERIC Educational Resources Information Center

St. Pierre, C. Andre

1971-01-01

Experience with numbers of drug addicts has shown them to be singularly unmotivated to discontinue drug use. To develop motivation, a treatment program is described in terms of motivational progression: (1) confrontation of the problem; (2) development of an intellectual understanding of the problem and its harmful effects; and (3) development of…

Consensus Treatment Plans for New-Onset Systemic Juvenile Idiopathic Arthritis

PubMed Central

DeWitt, Esi Morgan; Kimura, Yukiko; Beukelman, Timothy; Nigrovic, Peter A.; Onel, Karen; Prahalad, Sampath; Schneider, Rayfel; Stoll, Matthew L.; Angeles-Han, Sheila; Milojevic, Diana; Schikler, Kenneth N.; Vehe, Richard K.; Weiss, Jennifer E.; Weiss, Pamela; Ilowite, Norman T.; Wallace, Carol A.

2012-01-01

Objective There is wide variation in therapeutic approaches to systemic juvenile idiopathic arthritis (sJIA) among North American rheumatologists. Understanding the comparative effectiveness of the diverse therapeutic options available for treatment of sJIA can result in better health outcomes. The Childhood Arthritis and Rheumatology Research Alliance (CARRA) developed consensus treatment plans and standardized assessment schedules for use in clinical practice to facilitate such studies. Methods Case-based surveys were administered to CARRA members to identify prevailing treatments for new-onset sJIA. A 2-day consensus conference in April 2010 employed modified nominal group technique to formulate preliminary treatment plans and determine important data elements for collection. Follow-up surveys were employed to refine the plans and assess clinical acceptability. Results The initial case-based survey identified significant variability among current treatment approaches for new onset sJIA, underscoring the utility of standardized plans to evaluate comparative effectiveness. We developed four consensus treatment plans for the first 9 months of therapy, as well as case definitions and clinical and laboratory monitoring schedules. The four treatment regimens included glucocorticoids only, or therapy with methotrexate, anakinra or tocilizumab, with or without glucocorticoids. This approach was approved by >78% of CARRA membership. Conclusion Four standardized treatment plans were developed for new-onset sJIA. Coupled with data collection at defined intervals, use of these treatment plans will create the opportunity to evaluate comparative effectiveness in an observational setting to optimize initial management of sJIA. PMID:22290637

Computer Model Used to Help Customize Medicine

NASA Technical Reports Server (NTRS)

Stauber, Laurel J.; Veris, Jenise

2001-01-01

Dr. Radhakrishnan, a researcher at the NASA Glenn Research Center, in collaboration with biomedical researchers at the Case Western Reserve University School of Medicine and Rainbow Babies and Children's Hospital, is developing computational models of human physiology that quantitate metabolism and its regulation, in both healthy and pathological states. These models can help predict the effects of stresses or interventions, such as drug therapies, and contribute to the development of customized medicine. Customized medical treatment protocols can give more comprehensive evaluations and lead to more specific and effective treatments for patients, reducing treatment time and cost. Commercial applications of this research may help the pharmaceutical industry identify therapeutic needs and predict drug-drug interactions. Researchers will be able to study human metabolic reactions to particular treatments while in different environments as well as establish more definite blood metabolite concentration ranges in normal and pathological states. These computational models may help NASA provide the background for developing strategies to monitor and safeguard the health of astronauts and civilians in space stations and colonies. They may also help to develop countermeasures that ameliorate the effects of both acute and chronic space exposure.

The Charles F. Prentice Award Lecture 2010: A Case for Peripheral Optical Treatment Strategies for Myopia

PubMed Central

Smith, Earl L.

2011-01-01

It is well established that refractive development is regulated by visual feedback. However, most optical treatment strategies designed to reduce myopia progression have not produced the desired results, primarily because some of our assumptions concerning the operating characteristics of the vision-dependent mechanisms that regulate refractive development have been incorrect. In particular, because of the prominence of central vision in primates, it has generally been assumed that signals from the fovea determine the effects of vision on refractive development. However, experiments in laboratory animals demonstrate that ocular growth and emmetropization are mediated by local retinal mechanisms and that foveal vision is not essential for many vision-dependent aspects of refractive development. On the other hand, the peripheral retina, in isolation, can effectively regulate emmetropization and mediate many of the effects of vision on the eye’s refractive status. Moreover, when there are conflicting visual signals between the fovea and the periphery, peripheral vision can dominate refractive development. The overall pattern of results suggests that optical treatment strategies for myopia that take into account the effects of peripheral vision are likely to be more successful than strategies that effectively manipulate only central vision. PMID:21747306

An optical microfluidic platform for spatiotemporal biofilm treatment monitoring

NASA Astrophysics Data System (ADS)

Kim, Young Wook; Mosteller, Matthew P.; Subramanian, Sowmya; Meyer, Mariana T.; Bentley, William E.; Ghodssi, Reza

2016-01-01

Bacterial biofilms constitute in excess of 65% of clinical microbial infections, with the antibiotic treatment of biofilm infections posing a unique challenge due to their high antibiotic tolerance. Recent studies performed in our group have demonstrated that a bioelectric effect featuring low-intensity electric signals combined with antibiotics can significantly improve the efficacy of biofilm treatment. In this work, we demonstrate the bioelectric effect using sub-micron thick planar electrodes in a microfluidic device. This is critical in efforts to develop microsystems for clinical biofilm infection management, including both in vivo and in vitro applications. Adaptation of the method to the microscale, for example, can enable the development of localized biofilm infection treatment using microfabricated medical devices, while augmenting existing capabilities to perform biofilm management beyond the clinical realm. Furthermore, due to scale-down of the system, the voltage requirement for inducing the electric field is reduced further below the media electrolysis threshold. Enhanced biofilm treatment using the bioelectric effect in the developed microfluidic device elicited a 56% greater reduction in viable cell density and 26% further decrease in biomass growth compared to traditional antibiotic therapy. This biofilm treatment efficacy, demonstrated in a micro-scale device and utilizing biocompatible voltage ranges, encourages the use of this method for future clinical biofilm treatment applications.

Agent based modeling of the effects of potential treatments over the blood-brain barrier in multiple sclerosis.

PubMed

Pennisi, Marzio; Russo, Giulia; Motta, Santo; Pappalardo, Francesco

2015-12-01

Multiple sclerosis is a disease of the central nervous system that involves the destruction of the insulating sheath of axons, causing severe disabilities. Since the etiology of the disease is not yet fully understood, the use of novel techniques that may help to understand the disease, to suggest potential therapies and to test the effects of candidate treatments is highly advisable. To this end we developed an agent based model that demonstrated its ability to reproduce the typical oscillatory behavior observed in the most common form of multiple sclerosis, relapsing-remitting multiple sclerosis. The model has then been used to test the potential beneficial effects of vitamin D over the disease. Many scientific studies underlined the importance of the blood-brain barrier and of the mechanisms that influence its permeability on the development of the disease. In the present paper we further extend our previously developed model with a mechanism that mimics the blood-brain barrier behavior. The goal of our work is to suggest the best strategies to follow for developing new potential treatments that intervene in the blood-brain barrier. Results suggest that the best treatments should potentially prevent the opening of the blood-brain barrier, as treatments that help in recovering the blood-brain barrier functionality could be less effective. Copyright © 2015 Elsevier B.V. All rights reserved.

Repeated treatment with nitric oxide synthase inhibitor attenuates learned helplessness development in rats and increases hippocampal BDNF expression.

PubMed

Stanquini, Laura Alves; Biojone, Caroline; Guimarães, Francisco Silveira; Joca, Sâmia Regiane

2017-11-20

Nitric oxide synthase (NOS) inhibitors induce antidepressant-like effects in animal models sensitive to acute drug treatment such as the forced swimming test. However, it is not yet clear if repeated treatment with these drugs is required to induce antidepressant-like effects in preclinical models. The aim of this study was to test the effect induced by acute or repeated (7 days) treatment with 7-nitroindazole (7-NI), a preferential inhibitor of neuronal NOS, in rats submitted to the learned helplessness (LH) model. In addition, we aimed at investigating if 7-NI treatment would increase brain-derived neurotrophic factor (BDNF) protein levels in the hippocampus, similarly to the effect of prototype antidepressants. Animals were submitted to a pre-test (PT) session with inescapable footshocks or habituation (no shocks) to the experimental shuttle box. Six days later they were exposed to a test with escapable footshocks. Independent groups received acute (a single injection after PT or before test) or repeated (once a day for 7 days) treatment with vehicle or 7-NI (30 mg/kg). Repeated, but not acute, treatment with 7-NI attenuated LH development. The effect was similar to repeated imipramine treatment. Moreover, in an independent experimental group, only repeated treatment with 7-NI and imipramine increased BDNF protein levels in the hippocampus. The results suggest the nitrergic system could be a target for the treatment of depressive-like conditions. They also indicate that, similar to the positive control imipramine, the antidepressant-like effects of NOS inhibition could involve an increase in hippocampal BDNF levels.

Nanomedicine in GI

PubMed Central

Laroui, Hamed; Wilson, David S.; Dalmasso, Guillaume; Salaita, Khalid; Murthy, Niren; Sitaraman, Shanthi V.

2011-01-01

Recent advances in nanotechnology offer new hope for disease detection, prevention, and treatment. Nanomedicine is a rapidly evolving field wherein targeted therapeutic approaches using nanotechnology based on the pathophysiology of gastrointestinal diseases are being developed. Nanoparticle vectors capable of delivering drugs specifically and exclusively to regions of the gastrointestinal tract affected by disease for a prolonged period of time are likely to significantly reduce the side effects of existing otherwise effective treatments. This review aims at integrating various applications of the most recently developed nanomaterials that have tremendous potential for the detection and treatment of gastrointestinal diseases. PMID:21148398

New developments in psychosocial interventions for adults with unipolar depression.

PubMed

Lau, Mark A

2008-01-01

Depression treatment guidelines typically recommend cognitive behavioral therapy and/or interpersonal therapy for the acute treatment of mild-moderate depression. However, several new developments support an expanded role for psychotherapy in depression treatment. This article summarizes recent psychotherapy efficacy studies across the depression treatment continuum and the effectiveness of psychosocial interventions in community settings. New psychotherapies in the acute treatment of mild-moderate depression include emotion-focused therapy, self-system therapy, cognitive control training and positive psychotherapy. Furthermore, emerging evidence supports the use of psychotherapy for moderate-severe and treatment-resistant depression and for recurrent depression with a seasonal pattern. An important area of growth is the development and evaluation of continuation/maintenance treatments based on cognitive behavioral therapy and interpersonal therapy to reduce depressive relapse risk in recurrent and chronic depression. Finally, there is evidence supporting the effectiveness of stepped care, chronic disease management and collaborative care models in community settings. Emerging evidence supports an expanded role for the use of psychosocial interventions as acute and continuation/maintenance treatments for unipolar depression. Although further research is required to replicate these findings, a remaining challenge is to increase the availability of these treatments to the mental health consumer.

Medicinal Plants, Effective Plant Compounds (Compositions) and their Effects on Stomach Cancer.

PubMed

Aleebrahim-Dehkordy, Elahe; Nasri, Hamid; Baradaran, Azar; Nasri, Parto; Tamadon, Mohammad Reza; Hedaiaty, Mahrang; Beigrezaei, Sara; Rafieian-Kopaei, Mahmoud

2017-01-01

Medicinal plants have special importance around the world. Further, they have been noticed for nutrition and illness treatment such as preparation of anticancer new drugs. Therefore, a wide range of studies have been done on different plants, and their anticancer effects have been investigated. Nowadays, cancer is the most important factor of death rate in the developed and developing countries. Among them, stomach cancer is one of the most common malignancies around the world. At present, it is recognized as the fourth common cancer and the second factor of death rate due to cancer. So far, there has been wide range of effort for cancer treatment; however, in most cases, the response to the treatment has been very weak and often accompanied improper subsidiary effects. The present problems as a consequence of chemical treatment and radiotherapy and many subsidiary problems created due to their use for patients, and also, the resistance to the current treatment has motivated researchers to apply new medicines with more effect and less toxicity. The secondary metabolisms existent in the plants have an important role in the treatment of several diseases such as cancer. This study was conducted to investigate and collect scientific results for stomach cancer and to clarify the role of medicinal plants and secondary plant compounds on its treatment.

Prevention of age-related macular degeneration.

PubMed

Wong, Ian Yat Hin; Koo, Simon Chi Yan; Chan, Clement Wai Nang

2011-02-01

Age-related macular degeneration (AMD) is one of the leading causes of blindness in the developed world. Although effective treatment modalities such as anti-VEGF treatment have been developed for neovascular AMD, there is still no effective treatment for geographical atrophy, and therefore the most cost-effective management of AMD is to start with prevention. This review looks at current evidence on preventive measures targeted at AMD. Modalities reviewed include (1) nutritional supplements such as the Age-Related Eye Disease Study (AREDS) formula, lutein and zeaxanthin, omega-3 fatty acid, and berry extracts, (2) lifestyle modifications, including smoking and body-mass-index, and (3) filtering sunlight, i.e. sunglasses and blue-blocking intraocular lenses. In summary, the only proven effective preventive measures are stopping smoking and the AREDS formula.

Photo-thermal nanosystems for diseased cell treatment

NASA Astrophysics Data System (ADS)

Raeesi, Vahid

The prevalence of cancer and infectious disease demands for development of more effective treatment technologies. Current standard chemo- and radiotherapy for cancer offer only relative therapeutic efficacy at the cost of significant side-effects. On the other hand, resistance of microbes to current antibiotics has raised serious concern in public health sectors such as hospitals. Thermal therapy is an alternative technique that employs high temperatures to treat diseased cells via direct and indirect heat effects. Owing to its nature, this technique can offer enhanced therapeutic efficacy in local diseased regions via either mono- or combinatorial platforms and very minimal side-effects. However, existing bulk heating systems are limited in providing selective and controlled temperature rise in the desired region at tissue/cellular scales. This compromises the therapeutic efficacy of the treatment and increases the risk of off-target heating in healthy tissues. In this thesis, we propose the use of heat-generating nanoparticles to precisely target heat into small regions and study how they can be applied in cancer and bacteria treatment. Our model nanoparticle system generates heat by light stimulation. Different nanosystems based on this particle are developed and their thermal effects on therapeutic distribution are explored at tumor tissue and cellular scales. In addition, the thermal effect of these nanoparticles is utilized to overcome microbial resistance. By mechanistic understanding of nanoparticle thermal effects at different length scales, this research helps to rationalize proper design and development of heat- generating nanomedicine for cancer and microbial treatments.

Rebamipide ophthalmic suspension for the treatment of dry eye syndrome: a critical appraisal

PubMed Central

Kashima, Tomoyuki; Itakura, Hirotaka; Akiyama, Hideo; Kishi, Shoji

2014-01-01

Rebamipide was initially developed and approved for use in treating gastric ulcers and lesions associated with gastritis. Discovery of its ability to increase gastric mucin led to investigations of its effect on ocular surface mucin and the subsequent development for use in dry eye patients. Investigations have confirmed that rebamipide increases corneal and conjunctival mucin-like substances along with improving corneal and conjunctival injury. Clinically, rebamipide ophthalmic suspensions can effectively treat tear deficiency and mucin-caused corneal epithelial damage, and can restore the microstructure responsible for tear stability. Topical rebamipide has also been shown to be effective in treating other ocular surface disorders such as lagophthalmos, lid wiper epitheliopathy, and persistent corneal erosion. Rebamipide’s ability to modify epithelial cell function, improve tear stability, and suppress inflammation in the absence of any known major side effects suggest that it may be a beneficial first drug of choice for severe dry eye treatment and other ocular surface disorders. This review summarizes the history and development of this innovative dry eye treatment from its initial use as an effective stomach medication to its current use in the treatment of dry eye in Japan. PMID:24940041

Rebamipide ophthalmic suspension for the treatment of dry eye syndrome: a critical appraisal.

PubMed

Kashima, Tomoyuki; Itakura, Hirotaka; Akiyama, Hideo; Kishi, Shoji

2014-01-01

Rebamipide was initially developed and approved for use in treating gastric ulcers and lesions associated with gastritis. Discovery of its ability to increase gastric mucin led to investigations of its effect on ocular surface mucin and the subsequent development for use in dry eye patients. Investigations have confirmed that rebamipide increases corneal and conjunctival mucin-like substances along with improving corneal and conjunctival injury. Clinically, rebamipide ophthalmic suspensions can effectively treat tear deficiency and mucin-caused corneal epithelial damage, and can restore the microstructure responsible for tear stability. Topical rebamipide has also been shown to be effective in treating other ocular surface disorders such as lagophthalmos, lid wiper epitheliopathy, and persistent corneal erosion. Rebamipide's ability to modify epithelial cell function, improve tear stability, and suppress inflammation in the absence of any known major side effects suggest that it may be a beneficial first drug of choice for severe dry eye treatment and other ocular surface disorders. This review summarizes the history and development of this innovative dry eye treatment from its initial use as an effective stomach medication to its current use in the treatment of dry eye in Japan.

Cost-effectiveness of hepatitis C virus antiviral treatment for injection drug user populations.

PubMed

Martin, Natasha K; Vickerman, Peter; Miners, Alec; Foster, Graham R; Hutchinson, Sharon J; Goldberg, David J; Hickman, Matthew

2012-01-01

Injecting drug use is the main risk of hepatitis C virus (HCV) transmission in most developed countries. HCV antiviral treatment (peginterferon-α + ribavirin) has been shown to be cost-effective for patients with no reinfection risk. We examined the cost-effectiveness of providing antiviral treatment for injecting drug users (IDUs) as compared with treating ex/non-IDUs or no treatment. A dynamic model of HCV transmission and disease progression was developed, incorporating: a fixed number of antiviral treatments allocated at the mild HCV stage over 10 years, no retreatment after treatment failure, potential reinfection, and three baseline IDU HCV chronic prevalence scenarios (20%, 40%, and 60%). We performed a probabilistic cost-utility analysis estimating long-term costs and outcomes measured in quality adjusted life years (QALYs) and calculating the incremental cost-effectiveness ratio (ICER) comparing treating IDUs, ex/non-IDUs, or no treatment. Antiviral treatment for IDUs is the most cost-effective option in the 20% and 40% baseline chronic prevalence settings, with ICERs compared with no treatment of £ 521 and £ 2,539 per QALY saved, respectively. Treatment of ex/non-IDUs is dominated in these scenarios. At 60% baseline prevalence, treating ex/non-IDUs is slightly more likely to be the more cost-effective option (with an ICER compared with no treatment of £ 6,803), and treating IDUs dominated due to high reinfection. A sensitivity analysis indicates these rankings hold even when IDU sustained viral response rates as compared with ex/non-IDUs are halved. Despite the possibility of reinfection, the model suggests providing antiviral treatment to IDUs is the most cost-effective policy option in chronic prevalence scenarios less than 60%. Further research on how HCV treatment for injectors can be scaled up and its impact on prevalence is warranted. Copyright © 2011 American Association for the Study of Liver Diseases.

Interaction Between 2 Nutraceutical Treatments and Host Immune Status in the Pediatric Critical Illness Stress-Induced Immune Suppression Comparative Effectiveness Trial.

PubMed

Carcillo, Joseph A; Dean, J Michael; Holubkov, Richard; Berger, John; Meert, Kathleen L; Anand, Kanwaljeet J S; Zimmerman, Jerry J; Newth, Christopher J L; Harrison, Rick; Burr, Jeri; Willson, Douglas F; Nicholson, Carol; Bell, Michael J; Berg, Robert A; Shanley, Thomas P; Heidemann, Sabrina M; Dalton, Heidi; Jenkins, Tammara L; Doctor, Allan; Webster, Angie; Tamburro, Robert F

2017-11-01

The pediatric Critical Illness Stress-induced Immune Suppression (CRISIS) trial compared the effectiveness of 2 nutraceutical supplementation strategies and found no difference in the development of nosocomial infection and sepsis in the overall population. We performed an exploratory post hoc analysis of interaction between nutraceutical treatments and host immune status related to the development of nosocomial infection/sepsis. Children from the CRISIS trial were analyzed according to 3 admission immune status categories marked by decreasing immune competence: immune competent without lymphopenia, immune competent with lymphopenia, and previously immunocompromised. The comparative effectiveness of the 2 treatments was analyzed for interaction with immune status category. There were 134 immune-competent children without lymphopenia, 79 previously immune-competent children with lymphopenia, and 27 immunocompromised children who received 1 of the 2 treatments. A significant interaction was found between treatment arms and immune status on the time to development of nosocomial infection and sepsis ( P < .05) and on the rate of nosocomial infection and sepsis per 100 patient days ( P < .05). Whey protein treatment protected immune-competent patients without lymphopenia from infection and sepsis, both nutraceutical strategies were equivalent in immune-competent patients with lymphopenia, and zinc, selenium, glutamine, and metoclopramide treatment protected immunocompromised patients from infection and sepsis. The science of immune nutrition is more complex than previously thought. Future trial design should consider immune status at the time of trial entry because differential effects of nutraceuticals may be related to this patient characteristic.

The efficacy of topical and oral ivermectin in the treatment of human scabies.

PubMed

Panahi, Yunes; Poursaleh, Zohreh; Goldust, Mohamad

2015-01-01

Scabies is an itchy skin condition caused by the microscopic mite Sarcoptes scabei. The itching is caused by an allergic reaction to the mites. The treatment of choice is still controversial. It is commonly treated with topical insecticides. The aim of this study was to assess the efficacy of topical and oral ivermectin in the treatment of human scabies. We searched electronic databases (Cochrane Occupational Safety and Health Review Group Specialised Register, CENTRAL (The Cochrane Library), MEDLINE (Ovid), Pubmed, EMBASE, LILACS, CINAHL, Open Grey and WHO ICTRP) up to September 2014. Randomized controlled trials (RCTs) or cluster RCTs which compared the efficacy of ivermectin with other medications in the treatment of scabies. Interventions could be compared to each other, or to placebo or to no treatment. The author intended to extract dichotomous data (developed infection or did not develop infection) for the effects of interventions. We intended to report any adverse outcomes similarly. It has been sated that ivermectin was as effective as permethrin in the treatment of scabies. In comparison to other medications such as lindane, benzyl benzoate, crotamiton and malathion, ivermectin was more effective in the treatment of scabies. Ivermectin is an effective and cost-comparable alternative to topical agents in the treatment of scabies infection.

Novel technologies for reverse osmosis concentrate treatment: a review.

PubMed

Joo, Sung Hee; Tansel, Berrin

2015-03-01

Global water shortages due to droughts and population growth have created increasing interest in water reuse and recycling and, concomitantly, development of effective water treatment processes. Pressured membrane processes, in particular reverse osmosis, have been adopted in water treatment industries and utilities despite the relatively high operational cost and energy consumption. However, emerging contaminants are present in reverse osmosis concentrate in higher concentrations than in the feed water, and have created challenges for treatment of the concentrate. Further, standards and guidelines for assessment and treatment of newly identified contaminants are currently lacking. Research is needed regarding the treatment and disposal of emerging contaminants of concern in reverse osmosis concentrate, in order to develop cost-effective methods for minimizing potential impacts on public health and the environment. This paper reviews treatment options for concentrate from membrane processes. Barriers to emerging treatment options are discussed and novel treatment processes are evaluated based on a literature review. Copyright © 2014 Elsevier Ltd. All rights reserved.

Overview | Office of Cancer Genomics

Cancer.gov

The Therapeutically Applicable Research to Generate Effective Treatments (TARGET) initiative uses comprehensive molecular characterization to determine the genetic changes that drive the initiation and progression of hard-to-treat childhood cancers. TARGET aims to identify therapeutic targets and prognostic markers so that new, more effective treatment strategies can be developed and applied. Novel pediatric cancer treatments are needed because:

Developmental landmarks during floral ontogeny of jalapeño chili pepper (Capsicum annuum L.) and the effect of gibberellin on ovary growth.

PubMed

Sandoval-Oliveros, R; Guevara-Olvera, L; Beltrán, J P; Gómez-Mena, C; Acosta-García, G

2017-09-01

Pepper (Capsicum annuum L.) is an important horticultural crop in many regions of the world. The final shape and size of the fruit are known to be determined at a very early step of flower development. During flower development hormonal treatments using gibberellins seem to promote growth resulting in higher yield and fruit quality. However, the morphological changes that occur in the pepper flowers after these treatments are largely unknown. In the present study, we provide a description of floral development landmarks of jalapeño chili pepper (cultivar Huichol), divided in nine representative stages from its initiation until the opening of the bud. We established a correlation among external flower development and the time and pattern of reproductive organogenesis. Male and female gametogenesis progression was used to define specific landmarks during flower maturation. The pattern of expression of key genes involved in gibberellin metabolism and response was also evaluated in the nine flower stages. The proposed development framework was used to analyze the effect of gibberellin treatments in the development of the flower. We observed both an effect of the treatment in the histology of the ovary tissue and an increase in the level of expression of CaGA2ox1 and CaGID1b genes. The developmental stages we defined for this species are very useful to analyze the molecular and morphological changes after hormonal treatments.

Wastewater Treatment and Reuse Treatment Technology Evaluation and Development

EPA Science Inventory

This project will assess the effectiveness of a Biomass Concentrator Reactor (BCR) to remove endocrine disrupting chemicals (EDCs) from wastewater. This technology could provide an alternative to traditional wastewater treatment methods.

The challenge and promise of anti-epileptic therapy development in animal models

PubMed Central

Simonato, Michele; Brooks-Kayal, Amy R; Engel, Jerome; Galanopoulou, Aristea S; Jensen, Frances E; Moshé, Solomon L; O’Brien, Terence J; Pitkanen, Asla; Wilcox, Karen S; French, Jacqueline A

2016-01-01

Translation of successful target and compound validation studies into clinically effective therapies is a major challenge, with potential for costly clinical trial failures. This situation holds true for the epilepsies—complex diseases with different causes and symptoms. Although the availability of predictive animal models has led to the development of effective antiseizure therapies that are routinely used in clinical practice, showing that translation can be successful, several important unmet therapeutic needs still exist. Available treatments do not fully control seizures in a third of patients with epilepsy, and produce substantial side-effects. No treatment can prevent the development of epilepsy in at-risk patients or cure patients with epilepsy. And no specific treatment for epilepsy-associated comorbidities exists. To meet these demands, a redesign of translational approaches is urgently needed. PMID:25127174

Brief Report: Alternative Approaches to the Development of Effective Treatments for Autism.

ERIC Educational Resources Information Center

Rimland, Bernard; Baker, Sidney M.

1996-01-01

The most widely used "alternative" biomedical treatments for autism are reviewed, including: nutritional supplements, especially megadose vitamin B6 and magnesium; treatment of food allergies and intolerances; treatment of microbial infections; and treatment of immune system dysfunction. The Defeat Autism Now! project is briefly…

Transportability of imagery-enhanced CBT for social anxiety disorder.

PubMed

McEvoy, Peter M; Erceg-Hurn, David M; Barber, Kevin C; Dupasquier, Jessica R; Moscovitch, David A

2018-07-01

Pilot and open trials suggest that imagery-enhanced group cognitive behaviour therapy (CBT) is highly effective for social anxiety disorder (SAD). However, before being considered reliable and generalisable, the effects of the intervention need to be replicated by clinicians in a setting that is independent of the protocol developers. The current study compared outcomes from clients with a principal diagnosis of SAD at the Australian clinic where the protocol was developed (n = 123) to those from an independent Canadian clinic (n = 46) to investigate whether the large effects would generalise. Trainee clinicians from the independent clinic ran the groups using the treatment protocol without any input from its developers. The treatment involved 12 2-h group sessions plus a one-month follow-up. Treatment retention was comparable across both clinics (74% vs. 78%, ≥9/12 sessions) and the between-site effect size was very small and non-significant on the primary outcome (social interaction anxiety, d = 0.09, p = .752). Within-group effect sizes were very large in both settings (ds = 2.05 vs. 2.19), and a substantial minority (41%-44%) achieved clinically significant improvement at follow-up. Replication of treatment effects within an independent clinic and with trainee clinicians increases confidence that outcomes are generalisable. Copyright © 2018 Elsevier Ltd. All rights reserved.

Effect of treatment temperature on the microstructure of asphalt binders: insights on the development of dispersed domains.

PubMed

Menapace, I; Masad, E; Bhasin, A

2016-04-01

This paper offers important insights on the development of the microstructure in asphalt binders as a function of the treatment temperature. Different treatment temperatures are useful to understand how dispersed domains form when different driving energies for the mobility of molecular species are provided. Small and flat dispersed domains, with average diameter between 0.02 and 0.70 μm, were detected on the surface of two binders at room temperature, and these domains were observed to grow with an increase in treatment temperature (up to over 2 μm). Bee-like structures started to appear after treatment at or above 100°C. Moreover, the effect of the binder thickness on its microstructure at room temperature and at higher treatment temperatures was investigated and is discussed in this paper. At room temperature, the average size of the dispersed domains increased as the binder thickness decreased. A hypothesis that conciliates current theories on the origin and development of dispersed domains is proposed. Small dispersed domains (average diameter around 0.02 μm) are present in the bulk of the binder, whereas larger domains and bee-like structures develop on the surface, following heat treatment or mechanical disturbance that reduces the film thickness. Molecular mobility and association are the key factors in the development of binder microstructure. © 2015 The Authors Journal of Microscopy © 2015 Royal Microscopical Society.

Scale-Up Information for Gas-Phase Ammonia Treatment of Uranium in the Vadose Zone at the Hanford Site Central Plateau

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

Truex, Michael J.; Szecsody, James E.; Zhong, Lirong

Uranium is present in the vadose zone at the Hanford Central Plateau and is of concern for protection of groundwater. The Deep Vadose Zone Treatability Test Plan for the Hanford Central Plateau identified gas-phase treatment and geochemical manipulation as potentially effective treatment approaches for uranium and technetium in the Hanford Central Plateau vadose zone. Based on laboratory evaluation, use of ammonia vapor was selected as the most promising uranium treatment candidate for further development and field testing. While laboratory tests have shown that ammonia treatment effectively reduces the mobility of uranium, additional information is needed to enable deployment of thismore » technology for remediation. Of importance for field applications are aspects of the technology associated with effective distribution of ammonia to a targeted treatment zone, understanding the fate of injected ammonia and its impact on subsurface conditions, and identifying effective monitoring approaches. In addition, information is needed to select equipment and operational parameters for a field design. As part of development efforts for the ammonia technology for remediation of vadose zone uranium contamination, field scale-up issues were identified and have been addressed through a series of laboratory and modeling efforts. This report presents a conceptual description for field application of the ammonia treatment process, engineering calculations to support treatment design, ammonia transport information, field application monitoring approaches, and a discussion of processes affecting the fate of ammonia in the subsurface. The report compiles this information from previous publications and from recent research and development activities. The intent of this report is to provide technical information about these scale-up elements to support the design and operation of a field test for the ammonia treatment technology.« less

Effects of music therapy in the treatment of children with delayed speech development - results of a pilot study

PubMed Central

2010-01-01

Background Language development is one of the most significant processes of early childhood development. Children with delayed speech development are more at risk of acquiring other cognitive, social-emotional, and school-related problems. Music therapy appears to facilitate speech development in children, even within a short period of time. The aim of this pilot study is to explore the effects of music therapy in children with delayed speech development. Methods A total of 18 children aged 3.5 to 6 years with delayed speech development took part in this observational study in which music therapy and no treatment were compared to demonstrate effectiveness. Individual music therapy was provided on an outpatient basis. An ABAB reversal design with alternations between music therapy and no treatment with an interval of approximately eight weeks between the blocks was chosen. Before and after each study period, a speech development test, a non-verbal intelligence test for children, and music therapy assessment scales were used to evaluate the speech development of the children. Results Compared to the baseline, we found a positive development in the study group after receiving music therapy. Both phonological capacity and the children's understanding of speech increased under treatment, as well as their cognitive structures, action patterns, and level of intelligence. Throughout the study period, developmental age converged with their biological age. Ratings according to the Nordoff-Robbins scales showed clinically significant changes in the children, namely in the areas of client-therapist relationship and communication. Conclusions This study suggests that music therapy may have a measurable effect on the speech development of children through the treatment's interactions with fundamental aspects of speech development, including the ability to form and maintain relationships and prosodic abilities. Thus, music therapy may provide a basic and supportive therapy for children with delayed speech development. Further studies should be conducted to investigate the mechanisms of these interactions in greater depth. Trial registration The trial is registered in the German clinical trials register; Trial-No.: DRKS00000343 PMID:20663139

Mental health treatment outcome expectancies in Burundi.

PubMed

Irankunda, Pacifique; Heatherington, Laurie

2017-02-01

Best practices in global mental health stress the importance of understanding local values and beliefs. Research demonstrates that expectancies about the effectiveness of a given treatment significantly predicts outcome, beyond the treatment effect itself. To help inform the development of mental health interventions in Burundi, we studied expectancies about the effectiveness of four treatments: spiritual healing, traditional healing, medication, and selected evidence-based psychosocial treatments widely used in the US. Treatment expectancies were assessed for each of three key syndromes identified by previous research: akabonge (a set of depression-like symptoms), guhahamuka (a set of trauma-related symptoms), and ibisigo (a set of psychosis-like symptoms) . In individual interviews or written surveys in French or Kirundi with patients ( N = 198) awaiting treatment at the clinic, we described each disorder and the treatments in everyday language, asking standard efficacy expectations questions about each ("Would it work?" "Why or why not?"). Findings indicated uniformly high expectancies about the efficacy of spiritual treatment, relatively high expectancies for western evidence-based treatments (especially cognitive behavior therapy [CBT] for depression-like symptoms), lower expectancies for medicine, and especially low expectancies for traditional healing (except for traditional healing for psychosis-like symptoms). There were significant effects of gender but not of education level. Qualitative analyses of explanations provide insight into the basis of people's beliefs, their explanations about why a given treatment would or would not work varied by type of disorder, and reflected beliefs about underlying causes. Implications for program development and future research are discussed.

Adolescent silymarin treatment increases anxiety-like behaviors in adult mice.

PubMed

Kosari-Nasab, Morteza; Rabiei, Afshin; Doosti, Mohammad-Hossein; Salari, Ali-Akbar

2014-08-01

Adolescence is one of the most important periods of brain development in mammals. There is increasing evidence that some medicines during this period can affect brain and behavioral functions in adulthood. Silymarin (SM), a mixture of flavonolignans extracted from the milk thistle Silybum marianum, is known as a hepatoprotective, anti-inflammatory, and neuroprotective drug. Although researchers have extensively studied the effects of SM during adulthood, to date there is no information on the effects of this drug during the stages of brain development on behavioral functions in adulthood. In the current study, we investigated the effects of adolescent SM treatment on body weight and anxiety-like behaviors in adult male and female mice. Adolescent NMRI mice (postnatal day 30-50) were treated orally with water or SM (50 and 100 mg/kg). Animals were weighed during drug treatment and were then subjected to open field, elevated plus maze, and light-dark box tests from postnatal day 70. The results indicated that adolescent SM treatment increased anxiety-like behaviors in open field, elevated plus maze, and light-dark box in adult mice, while not altering body weight. Collectively, these findings suggest that adolescent SM treatment may have profound effects on the development of brain and behavior in adulthood.

Childhood Arthritis and Rheumatology Research Alliance consensus treatment plans for juvenile idiopathic arthritis-associated and idiopathic chronic anterior uveitis.

PubMed

Angeles-Han, Sheila T; Lo, Mindy S; Henderson, Lauren A; Lerman, Melissa A; Abramson, Leslie; Cooper, Ashley M; Parsa, Miriam F; Zemel, Lawrence S; Ronis, Tova; Beukelman, Timothy; Cox, Erika; Sen, H Nida; Holland, Gary N; Brunner, Hermine I; Lasky, Andrew; Rabinovich, C Egla

2018-05-28

Systemic immunosuppressive treatment of pediatric chronic anterior uveitis (CAU), both juvenile idiopathic arthritis (JIA)-associated and idiopathic varies, making it difficult to identify best treatments. The Childhood Arthritis and Rheumatology Research Alliance (CARRA) developed consensus treatment plans (CTPs) for CAU for the purpose of reducing practice variability and allowing future comparison of treatments by comparative effectiveness analysis techniques. A core group of pediatric rheumatologists, ophthalmologists with uveitis expertise, and a lay advisor comprised the CARRA uveitis workgroup who performed literature review on pharmacologic treatments, held teleconferences, and developed a case-based survey administered to the CARRA membership to delineate treatment practices. We utilized 3 face-to-face consensus meetings using nominal group technique to develop CTPs. The survey identified areas of treatment practice variability. We developed 2 CTPs for the treatment of CAU, case definitions, and monitoring parameters. The first CTP is directed at children naïve to steroid-sparing medication, and the second at children initiating biologic therapy with options for methotrexate, adalimumab and infliximab. We defined a core dataset and outcome measures with data collection at 3 and 6 months after therapy initiation. The CARRA membership voted acceptance of the CTPs with a >95% (N = 233) approval. Using consensus methodology, two standardized CTPs were developed for systemic immunosuppressive treatment of CAU. These CTPs are not meant as treatment guidelines, but are designed for further pragmatic research within the CARRA research network. Use of these CTPs in a prospective comparison effectiveness study should improve outcomes by identifying best practice options. This article is protected by copyright. All rights reserved. This article is protected by copyright. All rights reserved.

Developing Gene Silencing for the Study and Treatment of Dystonia

DTIC Science & Technology

2017-12-01

1 AWARD NUMBER: W81XWH-14-1-0282 TITLE: Developing Gene Silencing for the Study and Treatment of Dystonia PRINCIPAL INVESTIGATOR: Pedro...30/2014-9/29/2017 4. TITLE AND SUBTITLE Developing Gene Silencing for the Study and Treatment of Dystonia 5a. CONTRACT NUMBER 5b. GRANT NUMBER 5c...function. More importantly, we will check if no side effects or toxicity occurs. Successful completion of our studies will move us a step closer to

Recent developments in antibiotic agents for the treatment of complicated intra-abdominal infections.

PubMed

Lin, Shang-Yi; Huang, Chung-Hao; Ko, Wen-Chien; Chen, Yen-Hsu; Hsueh, Po-Ren

2016-01-01

Treatment of complicated intra-abdominal infections (cIAIs) is becoming increasingly difficult because of the widespread emergence of multidrug-resistant organisms. In this review, we discuss the effectiveness of several new antibiotics for the treatment of cIAIs, including new β-lactamase inhibitor combinations (BLICs) and tetracycline-class drugs, recently developed aminoglycosides and quinolones, and novel lipoglycopeptides and oxazolidinones. Of the new BLICs, ceftolozane/tazobactam is associated with adequate clinical cure rates in patients with cIAIs. Currently, two new β-lactamase inhibitors, namely avibactam and MK-7655, are under development for clinical use in the treatment of cIAIs. Eravacycline, a novel, fully synthetic tetracycline-class drug, has been shown in Phase II and III clinical trials to be more potent than tigecycline against a significant number of multidrug-resistant organisms causing cIAIs. Plazomicin, a next-generation aminoglycoside, is a promising agent for treatment of cIAIs due to multidrug-resistant pathogens. Of the recently developed quinolones, delafloxacin and finafloxacin have been shown to be effective against pathogens that survive and multiply in mildly acidic environments, although further clinical studies examining their clinical utility in the treatment of cIAIs are warranted. Oritavancin, a new semisynthetic lipoglycopeptide agent, has been demonstrated to be a potent antibiotic in the treatment of cIAIs due to drug-resistant Gram-positive organisms. Several other new antibiotics in development also show promise and will hopefully broaden the possibilities for treatment of complicated intra-abdominal infections due to MDR pathogens.

Task 7: Endwall treatment inlet flow distortion analysis

NASA Technical Reports Server (NTRS)

Hall, E. J.; Topp, D. A.; Heidegger, N. J.; McNulty, G. S.; Weber, K. F.; Delaney, R. A.

1996-01-01

The overall objective of this study was to develop a 3-D numerical analysis for compressor casing treatment flowfields, and to perform a series of detailed numerical predictions to assess the effectiveness of various endwall treatments for enhancing the efficiency and stall margin of modern high speed fan rotors. Particular attention was given to examining the effectiveness of endwall treatments to counter the undesirable effects of inflow distortion. Calculations were performed using three different gridding techniques based on the type of casing treatment being tested and the level of complexity desired in the analysis. In each case, the casing treatment itself is modeled as a discrete object in the overall analysis, and the flow through the casing treatment is determined as part of the solution. A series of calculations were performed for both treated and untreated modern fan rotors both with and without inflow distortion. The effectiveness of the various treatments were quantified, and several physical mechanisms by which the effectiveness of endwall treatments is achieved are discussed.

Theranostics for cancer therapy.

PubMed

Palekar-Shanbhag, Pradnya; Jog, Sneha V; Chogale, Manasi M; Gaikwad, Sujata S

2013-06-01

With over 10 million new cases per year worldwide, Cancer remains one of the most urgent health concerns and a difficult disease to treat. For an effective treatment, improved diagnostic and therapeutic techniques with minimal side-effects are required. Research and development in the areas of nanoscience and nanotechnology promise to provide innovative and more effective approaches for early diagnosis, imaging and therapy. An emerging trend in this direction is Theranostics which represents a combinatorial diagnosis and therapeutic approach to cancer disease and aims to eliminate multi-step procedures, reduce delays in treatment and improves patient care. It offers various advantages like improved diagnosis, tumor specific delivery of drugs, reduced lethal effects to normal tissues etc. Theranostic nanomedicines like nanoshells, plasmonic nanobubbles, quantum dots etc. can be used effectively for achieving these goals. With the advances in nano-imaging and nano-therapy new avenues for the development of effective cancer treatment will be opened.

Development of consensus treatment plans for juvenile localized scleroderma: a roadmap toward comparative effectiveness studies in juvenile localized scleroderma.

PubMed

Li, Suzanne C; Torok, Kathryn S; Pope, Elena; Dedeoglu, Fatma; Hong, Sandy; Jacobe, Heidi T; Rabinovich, C Egla; Laxer, Ronald M; Higgins, Gloria C; Ferguson, Polly J; Lasky, Andrew; Baszis, Kevin; Becker, Mara; Campillo, Sarah; Cartwright, Victoria; Cidon, Michael; Inman, Christi J; Jerath, Rita; O'Neil, Kathleen M; Vora, Sheetal; Zeft, Andrew; Wallace, Carol A; Ilowite, Norman T; Fuhlbrigge, Robert C

2012-08-01

Juvenile localized scleroderma (LS) is a chronic inflammatory skin disorder associated with substantial morbidity and disability. Although a wide range of therapeutic strategies has been reported in the literature, a lack of agreement on treatment specifics and accepted methods for clinical assessment has made it difficult to compare approaches and identify optimal therapy. Our objective was to develop standardized treatment plans, clinical assessments, and response criteria for active, moderate to high severity juvenile LS. A core group of pediatric rheumatologists, dermatologists, and a lay advisor was engaged by the Childhood Arthritis and Rheumatology Research Alliance (CARRA) to develop standardized treatment plans and assessment parameters for juvenile LS using consensus methods/nominal group techniques. Recommendations were validated in 2 face-to-face conferences with a larger group of practitioners with expertise in juvenile LS and with the full membership of CARRA, which encompasses the majority of pediatric rheumatologists in the US and Canada. Consensus was achieved on standardized treatment plans that reflect the prevailing treatment practices of CARRA members. Standardized clinical assessment methods and provisional treatment response criteria were also developed. Greater than 90% of pediatric rheumatologists responding to a survey (66% of CARRA membership) affirmed the final recommendations and agreed to utilize these consensus plans to treat patients with juvenile LS. Using consensus methodology, we have developed standardized treatment plans and assessment methods for juvenile LS. The high level of support among pediatric rheumatologists will support future comparative effectiveness studies and enable the development of evidence-based guidelines for the treatment of juvenile LS. Copyright © 2012 by the American College of Rheumatology.

A review of compliance to treatment in Alzheimer's disease: potential benefits of a transdermal patch.

PubMed

Small, Gary; Dubois, Bruno

2007-11-01

Following prescribed medication regimens is essential for the effective treatment of any medical condition. Unfortunately, patients often fail to follow recommendations, and treatment non-compliance represents a widespread, often underestimated problem, placing tremendous burden on the healthcare system. Compliance in Alzheimer's disease (AD), a chronic neurodegenerative disease typically afflicting older adults, is especially challenging. To review factors contributing to poor treatment compliance in AD, considering the prominent role care givers often play in treatment management; and acknowledging strategic approaches, particularly modern transdermal patches, to improve compliance in this particularly susceptible population. Articles were identified by searching MEDLINE in November 2006 (search limits: 1987-2007) using the terms: compliance; Alzheimer's; treatment; and transdermal. Additional resources included bibliographies of identified articles. Strategic approaches to improving treatment compliance include: simplifying treatment regimens, using reminder packaging, and developing more patient- or caregiver-friendly modes of administration. To date, AD therapies have been administered orally. However, recent developments in alternative modes of drug delivery, such as transdermal patches, may offer effective, well-tolerated treatment options with the potential to enhance compliance. A patch containing rivastigmine (Exelon), an established cholinesterase inhibitor, has been developed and demonstrated to have good efficacy and tolerability in patients with AD. In addition, initial caregiver experience suggests preference for the patch over oral administration. Transdermal patches may be an effective way to optimize treatment compliance for AD, as well as an increasing number of other chronic conditions that typically afflict the older population, offering the possibility of more sustained clinical benefits.

A Role for Cognitive Rehabilitation in Increasing the Effectiveness of Treatment for Alcohol Use Disorders

PubMed Central

Bates, Marsha E.; Buckman, Jennifer F.; Nguyen, Tam T.

2013-01-01

Neurocognitive impairments are prevalent in persons seeking treatment for alcohol use disorders (AUDs). These impairments and their physical, social, psychological and occupational consequences vary in severity across persons, much like those resulting from traumatic brain injury; however, due to their slower course of onset, alcohol-related cognitive impairments are often overlooked both within and outside of the treatment setting. Evidence suggests that cognitive impairments can impede treatment goals through their effects on treatment processes. Although some recovery of alcohol-related cognitive impairments often occurs after cessation of drinking (time-dependent recovery), the rate and extent of recovery is variable across cognitive domains and individuals. Following a long hiatus in scientific interest, a new generation of research aims to facilitate treatment process and improve AUD treatment outcomes by directly promoting cognitive recovery (experience-dependent recovery). This review updates knowledge about the nature and course of cognitive and brain impairments associated with AUD, including cognitive effects of adolescent AUD. We summarize current evidence for indirect and moderating relationships of cognitive impairment to treatment outcome, and discuss how advances in conceptual frameworks of brain-behavior relationships are fueling the development of novel AUD interventions that include techniques for cognitive remediation. Emerging evidence suggests that such interventions can be effective in promoting cognitive recovery in persons with AUD and other substance use disorders, and potentially increasing the efficacy of AUD treatments. Finally, translational approaches based on cognitive science, neurophysiology, and neuroscience research are considered as promising future directions for effective treatment development that includes cognitive rehabilitation. PMID:23412885

Prevention of age-related macular degeneration

PubMed Central

Koo, Simon Chi Yan; Chan, Clement Wai Nang

2010-01-01

Age-related macular degeneration (AMD) is one of the leading causes of blindness in the developed world. Although effective treatment modalities such as anti-VEGF treatment have been developed for neovascular AMD, there is still no effective treatment for geographical atrophy, and therefore the most cost-effective management of AMD is to start with prevention. This review looks at current evidence on preventive measures targeted at AMD. Modalities reviewed include (1) nutritional supplements such as the Age-Related Eye Disease Study (AREDS) formula, lutein and zeaxanthin, omega-3 fatty acid, and berry extracts, (2) lifestyle modifications, including smoking and body-mass-index, and (3) filtering sunlight, i.e. sunglasses and blue-blocking intraocular lenses. In summary, the only proven effective preventive measures are stopping smoking and the AREDS formula. PMID:20862519

Evaluating disease management programme effectiveness: an introduction to instrumental variables.

PubMed

Linden, Ariel; Adams, John L

2006-04-01

This paper introduces the concept of instrumental variables (IVs) as a means of providing an unbiased estimate of treatment effects in evaluating disease management (DM) programme effectiveness. Model development is described using zip codes as the IV. Three diabetes DM outcomes were evaluated: annual diabetes costs, emergency department (ED) visits and hospital days. Both ordinary least squares (OLS) and IV estimates showed a significant treatment effect for diabetes costs (P = 0.011) but neither model produced a significant treatment effect for ED visits. However, the IV estimate showed a significant treatment effect for hospital days (P = 0.006) whereas the OLS model did not. These results illustrate the utility of IV estimation when the OLS model is sensitive to the confounding effect of hidden bias.

[The effectiveness of psychosocial treatment approaches for alcohol dependence--a review].

PubMed

Bottlender, M; Köhler, J; Soyka, M

2006-01-01

Treatment approaches which are used in the context of inpatient alcoholism treatment are frequently neither theoretically justified nor empirically examined. In view of the enormous method variety the necessity exists for the development of treatment guidelines in order to offer indicators of promising treatment achievement for practitioners and pension funds. In a first step, it must be examined which treatments are effective, which are ineffective and which are possibly even counter-productive. This article aims to give a comprehensive review of randomized-controlled studies/meta-analysis on the efficacy of different treatment approaches. This article reporting the literature review is part of a larger programme to develop clinical practice guidelines for rehabilitation which is supported in form, content and finance by the German Pension Institute for Salaried Employees (Bundesversicherungsanstalt für Angestellte, BfA). Summing up, treatment is effective compared to no treatment. Cognitive behavioural therapy included in a multimodal treatment program is effective. There are a number of treatment protocols for which controlled research has consistently found positive results like social skills training, community reinforcement approaches, behaviour contracting, motivation-enhancing treatment, and family/marital therapy. There is also a number of commonly used treatment approaches that brought neither a positive result or were counter productive like relapse prevention, non-behavioural marital therapy, and insight psychotherapy, confrontational counseling, education, relaxation training, and milieu therapy. Support for matching to a specific treatment is weak, but interventions against alcohol problems should be differentiated according to the severity of the alcohol problem. Since treatment evaluation is mainly accomplished in the US and supplying structures with respect to the US and Germany are substantially different, a generalized transmission of US-American research results on Germany is to be evaluated carefully. Randomized-controlled studies are needed in Germany.

Nitroimidazoles for the treatment of TB: past, present and future

PubMed Central

Mukherjee, Tathagata; Boshoff, Helena

2011-01-01

Tuberculosis remains a leading cause of death resulting from an infectious agent, and the spread of multi- and extensively drug-resistant strains of Mycobacterium tuberculosis poses a threat to management of global health. New drugs that effectively shorten the duration of treatment and are active against drug-resistant strains of this pathogen are urgently required to develop effective chemotherapies to combat this disease. Two nitroimidazoles, PA-824 and OPC-67683, are currently in Phase II clinical trials for the treatment of TB and the outcome of these may determine the future directions of drug development for anti-tubercular nitroimidazoles. In this review we summarize the development of these nitroimidazoles and alternative analogs in these series that may offer attractive alternatives to PA-824 and OPC-67683 for further development in the drug-discovery pipeline. Lastly, the potential pitfalls in the development of nitroimidazoles as drugs for TB are discussed. PMID:21879846

Effect of the Combination Hot Water - Calcium Chloride on the In Vitro Growth of Colletotrichum gloeosporioides and the Postharvest Quality of Infected Papaya

PubMed Central

Ayón-Reyna, Lidia Elena; López-Valenzuela, José Ángel; Delgado-Vargas, Francisco; López-López, Martha Edith; Molina-Corral, Francisco Javier; Carrillo-López, Armando; Vega-García, Misael Odín

2017-01-01

Anthracnose of papaya fruit caused by the fungus Colletotrichum gloeosporioides is one of the most economically important postharvest diseases. Hot water immersion (HW) and calcium chloride (Ca) treatments have been used to control papaya postharvest diseases; however, the effect of the combination HW-Ca on the pathogen growth and the development of the disease in infected papaya fruit has been scarcely studied. The aim of this study was to evaluate the effect of the HW-Ca treatment on the in vitro growth of C. gloesporioides conidia and the quality of infected papaya. In vitro, the HW-Ca treated conidia showed reduced mycelial growth and germination. In vivo, the HW-Ca treatment of infected papaya delayed for 5 days the onset of the anthracnose symptoms and improved the papaya postharvest quality. The combined treatment HW-Ca was better than any of the individual treatments to inhibit the in vitro development of C. gloeosporioides and to reduce the negative effects of papaya anthracnose. PMID:29238280

TOXICITY APPROACHES TO ASSESSING MINING IMPACTS AND MINE WASTE TREATMENT EFFECTIVENESS

EPA Science Inventory

The USEPA Office of Research and Development's National Exposure Research Laboratory and National Risk Management Research Laboratory have been evaluating the impact of mining sites on receiving streams and the effectiveness of waste treatment technologies in removing toxicity fo...

Risk assessment of the National Institute of Standards and Technology petroleum crude oil standard water accommodated fraction: further application of a copepod-based, full life-cycle bioassay.

PubMed

Bejarano, Adriana C; Chandler, G Thomas; He, Lijian; Cary, Tawnya L; Ferry, John L

2006-07-01

The U.S. National Institute of Standards and Technology (NIST) petroleum crude oil was used to generate NIST water-accommodated hydrocarbon fractions (WAFs) for standardized assessment of crude oil effects on the copepod Amphiascus tenuiremis. Effects were assessed using a 96-well microplate, full life-cycle test. Briefly, nauplii (age, 24 h) were reared individually to adults (n > or =120 nauplii/treatment) in microplate wells containing 200 microl of treatment solution (seawater control [0%] or 10, 30, 50, or 100% NIST-WAF). Nauplii were monitored through development to adulthood, and mature virgin male:female pairs mated in wells containing original treatments (<30 d). A second bioassay using 0, 10, 30, and 50% WAFs (n > or =60 nauplii/treatment) was conducted to assess the effects of ultraviolet (UV) light on naupliar endpoints (<16 d). In the first experiment, nauplius-to-copepodite survival in exposures to 100% WAF was 27% +/- 6% lower than in controls (92% +/- 1%), but copepodite-to-adult survival was greater than 90% across all treatments. Analysis of development curves showed that nauplii in the 10% WAF developed into copepodites 25% faster, whereas nauplii in the 50 and 100% WAFs developed 17% slower, than controls. Copepodite development into male and female copepods was significantly delayed (2 and 4 d, respectively) in the 100% WAF compared to controls. Although none of the WAF exposures had significant effects on fertilization success or total viable production (p > 0.05), embryo hatching in the 100% WAF was significantly less (70.0% +/- 21.2%) than that in controls (87.0% +/- 19.4%). Results from the UV bioassay showed that relatively short exposures (<14 d) to 30 and 50% WAFs in the presence of UV light caused negative effects on copepod survival and development. Naupliar-stage survival and developmental endpoints were the most sensitive indicators of exposure to the NIST crude oil WAF

Drugs for Autoimmune Inflammatory Diseases: From Small Molecule Compounds to Anti-TNF Biologics

PubMed Central

Li, Ping; Zheng, Ying; Chen, Xin

2017-01-01

Although initially described as an anti-tumor mediator, tumor necrosis factor-alpha (TNF) is generally considered as the master pro-inflammatory cytokine. It plays a crucial role in the pathogenesis of inflammatory diseases, such as rheumatoid arthritis (RA), inflammatory bowel disease, ankylosing spondylitis (AS), and psoriasis. Consequently, anti-TNF therapy has become mainstay treatment for autoimmune diseases. Historically, anti-inflammatory agents were developed before the identification of TNF. Salicylates, the active components of Willow spp., were identified in the mid-19th century for the alleviation of pain, fever, and inflammatory responses. Study of this naturally occurring compound led to the discovery of aspirin, which was followed by the development of non-steroidal anti-inflammatory drugs (NSAIDs) due to the chemical advances in the 19th–20th centuries. Initially, the most of NSAIDs were organic acid, but the non-acidic compounds were also identified as NSAIDs. Although effective in the treatment of inflammatory diseases, NSAIDs have some undesirable and adverse effect, such as ulcers, kidney injury, and bleeding in the gastrointestinal tract. In the past two decades, anti-TNF biologics were developed. Drugs belong to this class include soluble TNF receptor 2 fusion protein and anti-TNF antibodies. The introduction of anti-TNF therapeutics has revolutionized the management of autoimmune diseases, such as RA, psoriatic arthritis (PsA), plaque psoriasis (PP), AS, CD and ulcerative colitis (UC). Nevertheless, up to 40% of patients have no response to anti-TNF treatment. Furthermore, this treatment is associated with some adverse effects such as increased risk of infection, and even triggered the de novo development of autoimmune diseases. Such harmful effect of anti-TNF treatment is likely caused by the global inhibition of TNF biological functions. Therefore, specific inhibition of TNF receptor (TNFR1 or TNFR2) may represent a safer and more effective treatment, as proposed by some recent studies. In this review article, the historical development of anti-inflammatory drugs after World War II as briefly described above will be reviewed and analyzed. The future trend in the development of novel TNF receptor-targeting therapeutics will be discussed in the context of latest progress in the research of TNF biology. PMID:28785220

Cervical Precancer Treatment in Low- and Middle-Income Countries: A Technology Overview

PubMed Central

Maza, Mauricio; Schocken, Celina M.; Bergman, Katherine L.; Randall, Thomas C.

2017-01-01

Cervical cancer is the fourth leading cause of cancer-related death in women worldwide, with 90% of cases occurring in low- and middle-income countries (LMICs). There has been a global effort to increase access to affordable screening in these settings; however, a corresponding increase in availability of effective and inexpensive treatment modalities for ablating or excising precancerous lesions is also needed to decrease mortality. This article reviews the current landscape of available and developing technologies for treatment of cervical precancer in LMICs. At present, the standard treatment of most precancerous lesions in LMICs is gas-based cryotherapy. This low-cost, effective technology is an expedient treatment in many areas; however, obtaining and transporting gas is often difficult, and unwieldy gas tanks are not conducive to mobile health campaigns. There are several promising ablative technologies in development that are gasless or require less gas than conventional cryotherapy. Although further evaluation of the efficacy and cost-effectiveness is needed, several of these technologies are safe and can now be implemented in LMICs. Nonsurgical therapies, such as therapeutic vaccines, antivirals, and topical applications, are also promising, but most remain in early-stage trials. The establishment of evidence-based standardized protocols for available treatments and the development and introduction of novel technologies are necessary steps in overcoming barriers to treatment in LMICs and decreasing the global burden of cervical cancer. Guidance from WHO on emerging treatment technologies is also needed. PMID:28831448

Cervical Precancer Treatment in Low- and Middle-Income Countries: A Technology Overview.

PubMed

Maza, Mauricio; Schocken, Celina M; Bergman, Katherine L; Randall, Thomas C; Cremer, Miriam L

2017-08-01

Cervical cancer is the fourth leading cause of cancer-related death in women worldwide, with 90% of cases occurring in low- and middle-income countries (LMICs). There has been a global effort to increase access to affordable screening in these settings; however, a corresponding increase in availability of effective and inexpensive treatment modalities for ablating or excising precancerous lesions is also needed to decrease mortality. This article reviews the current landscape of available and developing technologies for treatment of cervical precancer in LMICs. At present, the standard treatment of most precancerous lesions in LMICs is gas-based cryotherapy. This low-cost, effective technology is an expedient treatment in many areas; however, obtaining and transporting gas is often difficult, and unwieldy gas tanks are not conducive to mobile health campaigns. There are several promising ablative technologies in development that are gasless or require less gas than conventional cryotherapy. Although further evaluation of the efficacy and cost-effectiveness is needed, several of these technologies are safe and can now be implemented in LMICs. Nonsurgical therapies, such as therapeutic vaccines, antivirals, and topical applications, are also promising, but most remain in early-stage trials. The establishment of evidence-based standardized protocols for available treatments and the development and introduction of novel technologies are necessary steps in overcoming barriers to treatment in LMICs and decreasing the global burden of cervical cancer. Guidance from WHO on emerging treatment technologies is also needed.

Recent developments in sample preparation and data pre-treatment in metabonomics research.

PubMed

Li, Ning; Song, Yi peng; Tang, Huiru; Wang, Yulan

2016-01-01

Metabonomics is a powerful approach for biomarker discovery and an effective tool for pinpointing endpoint metabolic effects of external stimuli, such as pathogens and disease development. Due to its wide applications, metabonomics is required to deal with various biological samples of different properties. Hence sample preparation and corresponding data pre-treatment become important factors in ensuring validity of an investigation. In this review, we summarize some recent developments in metabonomics sample preparation and data-pretreatment procedures. Copyright © 2015 Elsevier Inc. All rights reserved.

Biotechnological advances in neuro-electro-stimulation for the treatment of hyposalivation and xerostomia.

PubMed

Lafaurie, Gloria; Fedele, Stefano; López, Rafael Martín-Granizo; Wolff, Andy; Strietzel, Frank; Porter, Stephen R; Konttinen, Yrjö T

2009-02-01

Treatment of xerostomia is a common clinical challenge in the oral medicine practice. Although some treatments have been used to improve the symptoms of xerostomia, none is completely satisfactory for the patients who suffer of this alteration. In the last years non-pharmacological treatments based on electro-stimulation for the treatment of xerostomia have been developed. This review is aimed at presenting new developments for the treatment of xerostomia, applying neuro-electro-stimulation by miniaturized intra-oral electro-stimulators. These devices increase salivary secretion and improve symptoms of oral dryness. Their effect is obtained by means of stimulation of the lingual nerve, in whose proximity the electrodes of the apparatus are placed. The objective of this mechanism is both to directly stimulate the salivary glands controlled by that nerve and to enhance the salivary reflex. Clinical studies have been carried out that have demonstrated the wetting effect of the method described in this article.

Overstory and understory development in thinned and underplanted Oregon Coast Range Douglas-fir stands.

Treesearch

S.S. Chan; D.J. Larson; K.G. Maas-Hebner; W.H. Emmingham; S.R. Johnston; D.A. Mikowski

2006-01-01

This study examined thinning effects on overstory and understory development for 8 years after treatment. Three 30- to 33-year-old Oregon Coast Range plantations were partitioned into four overstory treatments: (1) unthinned (~550 trees/ha) (2) light thin (~250 trees/ha), (3) moderate thin (~150 trees/ha), and (4) heavy thin (~75 trees/ha). Two understory treatments...

Information without Implementation: A Practical Example for Developing a Best Practice Education Control Group.

PubMed

Balderson, Benjamin H; McCurry, Susan M; Vitiello, Michael V; Shortreed, Susan M; Rybarczyk, Bruce D; Keefe, Francis J; Korff, Michael Von

2016-01-01

This article considers methodology for developing an education-only control group and proposes a simple approach to designing rigorous and well-accepted control groups. This approach is demonstrated in a large randomized trial. The Lifestyles trial (n = 367) compared three group interventions: (a) cognitive-behavioral treatment (CBT) for osteoarthritis pain, (b) CBT for osteoarthritis pain and insomnia, and (c) education-only control (EOC). EOC emulated the interventions excluding hypothesized treatment components and controlling for nonspecific treatment effects. Results showed this approach resulted in a control group that was highly credible and acceptable to patients. This approach can be an effective and practical guide for developing high-quality control groups in trials of behavioral interventions.

Effects of Three Insect Growth Regulators on Encarsia formosa (Hymenoptera: Aphelinidae), an Endoparasitoid of Bemisia tabaci (Hemiptera: Aleyrodidae).

PubMed

Wang, Q L; Liu, T-X

2016-12-01

Insect growth regulators (IGRs) disrupt the normal activity of the endocrine or hormone system of insects, affecting the development, reproduction, or metamorphosis of the target insects, and normally causing less detrimental effects to beneficial insects. The effects of three IGRs (pyriproxyfen, fenoxycarb, and buprofezin) on Encarsia formosa Gahan, an endoparasitoid of whiteflies, were determined using B. tabaci as a host. We assessed the effects of the IGRs on parasitoid's larval development, pupation, emergence, and contact effects of the dry residues on plant leaf and glass vial surface on adult mortality and parasitism. When the three IGRs were applied at larval stage, no or few larvae pupated in the pyriproxyfen treatments and the highest concentration of fenoxycarb, and a majority of larvae pupated in the buprofezin treatments; of those pupated, 62.3-88.1% became adults. When the IGRs were applied at the pupal stage, 2.3-17.5% developed to adults in the pyriproxyfen treatments, 59.7-89.0% in the fenoxycarb treatments, and 58.4-83.6% in the buprofezin treatments. The leaf residues of the IGRs had no appreciable effects on adults, whereas the residues on glass vial caused significantly lower adult survival than on plant leaves. The residues of pyriproxyfen and fenoxycarb slightly reduced parasitism as compared with buprofezin and controls. However, the rates of parasitoids that became adults were significantly lower, especially in the pyriproxyfen treatments. According to the standards of International Organization of Biological Control (IOBC), pyriproxyfen was harmful, while fenoxycarb and buprofezin were slightly or moderately harmful to larvae and harmless to E. formosa pupae. © The Authors 2016. Published by Oxford University Press on behalf of Entomological Society of America. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

Amphotericin B releasing topical nanoemulsion for the treatment of candidiasis and aspergillosis.

PubMed

Sosa, Lilian; Clares, Beatriz; Alvarado, Helen L; Bozal, Nuria; Domenech, Oscar; Calpena, Ana C

2017-10-01

The present study was designed to develop a nanoemulsion formulation of Amphotericin B (AmB) for the treatment of skin candidiasis and aspergillosis. Several ingredients were selected on the basis of AmB solubility and compatibility with skin. The formulation that exhibited the best properties was selected from the pseudo-ternary phase diagram. After physicochemical characterization its stability was assessed. Drug release and skin permeation studies were also accomplished. The antifungal efficacy and skin tolerability of developed AmB nanoemulsion was demonstrated. Finally, our results showed that the developed AmB formulation could provide an effective local antifungal effect without theoretical systemic absorption, based on its skin retention capacity, which might avoid related side effect. These results suggested that the nanoemulsion may be an optimal therapeutic alternative for the treatment of skin fungal infections with AmB. Copyright © 2017 Elsevier Inc. All rights reserved.

Single dose treatment of malaria - current status and perspectives.

PubMed

Mischlinger, Johannes; Agnandji, Selidji T; Ramharter, Michael

2016-07-01

Despite increased international efforts for control and ultimate elimination, malaria remains a major health problem. Currently, artemisinin-based combination therapies are the treatment of choice for uncomplicated malaria exhibiting high efficacy in clinical trial settings in sub-Saharan Africa. However, their administration over a three-day period is associated with important problems of treatment adherence resulting in markedly reduced effectiveness of currently recommended antimalarials under real world settings. Antimalarial drug candidates and antimalarial drug combinations currently under advanced clinical development for the indication as single dose antimalarial therapy. Expert commentary: Several new drug candidates and combinations are currently undergoing pivotal proof-of-concept studies or clinical development programmes. The development of a single dose combination therapy would constitute a breakthrough in the control of malaria. Such an innovative treatment approach would simultaneously close the effectiveness gap of current three-day therapies and revolutionize population based interventions in the context of malaria elimination campaigns.

Effects of nasal instillation of a nitric oxide-releasing solution or parenteral administration of tilmicosin on the nasopharyngeal microbiota of beef feedlot cattle at high-risk of developing respiratory tract disease.

PubMed

Timsit, E; Workentine, M; Crepieux, T; Miller, C; Regev-Shoshani, G; Schaefer, A; Alexander, T

2017-12-01

Nitric oxide has bactericidal and virucidal properties. Nasal instillation of a nitric oxide releasing solution (NORS) on arrival at the feedlot was recently reported as inferior to a parenteral injection of tilmicosin (macrolide antibiotic) for control of bovine respiratory disease (BRD) in cattle at high-risk of developing BRD. We hypothesized that this inferiority was due to differences between treatments with regards to their effects on the nasopharyngeal microbiota. The objective was to compare nasal instillation of NORS versus parenteral administration of tilmicosin regarding their effects on the nasopharyngeal microbiota of feedlot cattle at high-risk of developing BRD. Culture-independent community profiling (16S rRNA sequencing) and culture-based methods were used to evaluate treatment effects. High-risk Angus-cross heifers (n=20) were randomly allocated to 2 treatment groups on arrival at a feedlot and received either NORS or tilmicosin for prevention of BRD. Heifers were sampled using guarded deep nasal swabs immediately prior to treatment (day 0) and on days 1, 5 and 10 after treatment. Based on culture-independent community profiling, there was a distinct shift in composition of the nasopharyngeal microbiota during the first 10 d after arrival, with 116 OTUs changing over time, but no difference between treatment groups. However, culture-based methods detected a difference between treatment groups, with more cattle culture-positive for Pasteurellaceae in the NORS group at day 5 post-treatment. This difference in ability to inhibit colonization of the nasopharynx by Pasteurellaceae may be the basis for NORS being inferior to tilmicosin for control of BRD in high-risk cattle. Copyright © 2017 Elsevier Ltd. All rights reserved.

Interventional radiology in bone metastases.

PubMed

Chiras, J; Shotar, E; Cormier, E; Clarençon, F

2017-11-01

Interventional radiology plays a significant role in the treatment of bone metastases by various techniques, percutaneous or endovascular. Vertebroplasty is the most well-studied technique for stabilisation of spine metastases as it induces satisfactory stabilisation of the vertebra and offers clear improvement of the quality of life. Due to the success of this technique cementoplasty of other bones, mainly pelvic girdle, has been largely developed. The development of reinforced cementoplasty allows treatment of pre-fractural osteolysis of some long bones. The heat due to the polymerisation of the cement induces carcinolytic effect but this effect is not as important as that which results from radiofrequency destruction. This last technique appears currently as the most important development to definitively destroy bone metastases and is progressively replacing percutaneous alcoholic destruction of such lesions. Angiographic techniques, such as endovascular embolisation, can also be very useful to reduce the risk of surgical treatment of hyper vascular metastases. Chemoembolisation is currently developed to associate pain relief induced by Endovascular embolisation and the carcinolytic effect obtained by local endovascular chemotherapy. All these techniques should develop largely during the next years. © 2017 John Wiley & Sons Ltd.

Access to essential drugs in poor countries: a lost battle?

PubMed

Pécoul, B; Chirac, P; Trouiller, P; Pinel, J

1999-01-27

Drugs offer a simple, cost-effective solution to many health problems, provided they are available, affordable, and properly used. However, effective treatment is lacking in poor countries for many diseases, including African trypanosomiasis, Shigella dysentery, leishmaniasis, tuberculosis, and bacterial meningitis. Treatment may be precluded because no effective drug exists, it is too expensive, or it has been withdrawn from the market. Moreover, research and development in tropical diseases have come to a near standstill. This article focuses on the problems of access to quality drugs for the treatment of diseases that predominantly affect the developing world: (1) poor-quality and counterfeit drugs; (2) lack of availability of essential drugs due to fluctuating production or prohibitive cost; (3) need to develop field-based drug research to determine optimum utilization and remotivate research and development for new drugs for the developing world; and (4) potential consequences of recent World Trade Organization agreements on the availability of old and new drugs. These problems are not independent and unrelated but are a result of the fundamental nature of the pharmaceutical market and the way it is regulated.

The effectiveness of a voice treatment approach for teachers with self-reported voice problems.

PubMed

Gillivan-Murphy, Patricia; Drinnan, Michael J; O'Dwyer, Tadhg P; Ridha, Hayder; Carding, Paul

2006-09-01

Teachers are considered the professional group most at risk of developing voice-problems, but limited treatment effectiveness evidence exists. We studied prospectively the effectiveness of a 6-week combined treatment approach using vocal function exercises (VFEs) and vocal hygiene (VH) education with 20 teachers with self-reported voice problems. Twenty subjects were randomly assigned to a no-treatment control (n = 11) and a treatment group (n = 9). Fibreoptic endoscopic evaluation was carried out on all subjects before randomization. Two self-report voice outcome measures were used: the Voice-Related Quality of Life (VRQOL) and the Voice Symptom Severity Scale (VoiSS). A Voice Care Knowledge Visual Analogue Scale (VAS), developed specifically for the study, was also used to evaluate change in selected voice knowledge areas. A Student unpaired t test revealed a statistically significant (P < 0.05) improvement in the treatment group as measured by the VoiSS. There was not a significant improvement in the treatment group as measured by the V-RQOL. The difference in voice care knowledge areas was also significant for the treatment group (P < 0.05). This study suggests that a voice treatment approach of VFEs and VH education improved self-reported voice symptoms and voice care knowledge in a group of teachers.

Contributions of treatment theory and enablement theory to rehabilitation research and practice.

PubMed

Whyte, John

2014-01-01

Scientific theory is crucial to the advancement of clinical research. The breadth of rehabilitation treatment requires that many different theoretical perspectives be incorporated into the design and testing of treatment interventions. In this article, the 2 broad classes of theory relevant to rehabilitation research and practice are defined, and their distinct but complementary contributions to research and clinical practice are explored. These theory classes are referred to as treatment theories (theories about how to effect change in clinical targets) and enablement theories (theories about how changes in a proximal clinical target will influence distal clinical aims). Treatment theories provide the tools for inducing clinical change but do not specify how far reaching the ultimate impact of the change will be. Enablement theories model the impact of changes on other areas of function but provide no insight as to how treatment can create functional change. Treatment theories are more critical in the early stages of treatment development, whereas enablement theories become increasingly relevant in specifying the clinical significance and practical effectiveness of more mature treatments. Understanding the differences in the questions these theory classes address and how to combine their insights is crucial for effective research development and clinical practice. Copyright © 2014 American Congress of Rehabilitation Medicine. Published by Elsevier Inc. All rights reserved.

Novel treatment technologies for PFAS compounds: A critical review.

PubMed

Kucharzyk, Katarzyna H; Darlington, Ramona; Benotti, Mark; Deeb, Rula; Hawley, Elisabeth

2017-12-15

Perfluorinated compounds such as perfluorooctane sulfonate (PFOS) and perfluorooctanoic acid (PFOA) have recently drawn great attention due to their wide distribution in aquatic environments. The understanding of the physicochemical properties and fate and transport of PFAs in groundwater is still limited. Preliminary studies indicate that these compounds can readily bioaccumulate and pose human and animal health concerns. Due to their physicochemical properties, PFOS and PFOA are water soluble, nonvolatile and persistent in the environment, which is a cause of concern related to their treatment with conventional remediation technologies. Extraction with inefficient carbon adsorption is one of the most common treatment technologies for remediation of PFOS- or PFOA-impacted groundwater. Several other innovative and promising technologies, including sonochemistry, bioremediation and photolysis, have been tested for their effectiveness in removal of perfluorinated compounds. This paper provides a baseline for understanding research needs to better develop treatment technologies for PFOA and PFOS in groundwater. Frontiers for improving the state of practice for PFOA and PFOS treatment include the development of more cost-effective ex situ treatment methods and the development and demonstration of promising in situ treatment technologies at the pilot and full scale. Copyright © 2017 Elsevier Ltd. All rights reserved.

The application of latent curve analysis to testing developmental theories in intervention research.

PubMed

Curran, P J; Muthén, B O

1999-08-01

The effectiveness of a prevention or intervention program has traditionally been assessed using time-specific comparisons of mean levels between the treatment and the control groups. However, many times the behavior targeted by the intervention is naturally developing over time, and the goal of the treatment is to alter this natural or normative developmental trajectory. Examining time-specific mean levels can be both limiting and potentially misleading when the behavior of interest is developing systematically over time. It is argued here that there are both theoretical and statistical advantages associated with recasting intervention treatment effects in terms of normative and altered developmental trajectories. The recently developed technique of latent curve (LC) analysis is reviewed and extended to a true experimental design setting in which subjects are randomly assigned to a treatment intervention or a control condition. LC models are applied to both artificially generated and real intervention data sets to evaluate the efficacy of an intervention program. Not only do the LC models provide a more comprehensive understanding of the treatment and control group developmental processes compared to more traditional fixed-effects models, but LC models have greater statistical power to detect a given treatment effect. Finally, the LC models are modified to allow for the computation of specific power estimates under a variety of conditions and assumptions that can provide much needed information for the planning and design of more powerful but cost-efficient intervention programs for the future.

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.

Neuropsychological Care and Rehabilitation of Cancer Patients With Chemobrain: Strategies For Evaluation and Intervention Development

PubMed Central

Jean-Pierre, Pascal; Johnson-Greene, Douglas; Burish, Thomas G.

2014-01-01

Malignant tumors and their various treatments such as chemotherapy, radiotherapy and hormonal therapy can deleteriously affect a large number of cancer patients and survivors on multiple dimensions of psychosocial and neurocognitive functioning. Oncology researchers and clinicians are increasingly cognizant of the negative effects of cancer and its treatments on the brain and its mental processes and cognitive outcomes. Nevertheless, effective interventions to treat cancer and treatment-related neurocognitive dysfunction (CRND), also known as chemobrain, are still lacking. The paucity of data on effective treatments for CRND is due, at least partly, to difficulties understanding its etiology, and a lack of reliable methods for assessing its presence and severity. This paper provides an overview of the incidence, etiology, and magnitude of CRND, and discusses the plausible contributions of psychological, motor function, and linguistic and behavioral complications to CRND. Strategies for reliable neuropsychological screening and assessment, and development and testing of effective ways to mitigate CRND are also discussed. PMID:24671433

[Therapeutic effect of early applying hydrotherapy with Chinese drugs on children hypoxic ischemic encephalopathy].

PubMed

Ma, Yun-Zhi; Zhai, Hong-Yin; Su, Chun-Ya

2009-02-01

To observe the therapeutic effect of hydrotherapy with Chinese drugs (HT-C) in early intervention on children hypoxic ischemic encephalopathy (HIE). HIE children were assigned to the treatment group and the control group, 50 in each, at random depending on the willingness of patients' parents. Both groups received the conventional functional training, according to the "0 -3-year-old early intervention outline", but for the treatment group, HT-C was applied additionally. Indexes for quality of sleep, gross motor function, severity of spasm and intellectual development were observed and compared before and after treatment to assess the therapeutic effects. Therapeutic effect in the treatment group was better than that in the control group in all the indexes observed, showing statistical significance (all P <0.05). Early intervention of HT-C could improve clinical symptom, promote the functional recovery and intellectual development in children HIE, and also could reduce or prevent the sequelae occurrence of the nervous system in them.

Substance Abuse Disorders Treatment in El Salvador: Analysis of Policy-Making-Related Failure

PubMed Central

Dickson-Gómez, Julia

2016-01-01

Illicit drug use and substance abuse disorders have increased dramatically in developing countries during recent decades. Sadly, treatment for people diagnosed as manifesting and/or attributed with substance abuse disorders in developing countries is usually inadequate to meet demand, not evidence based, and of poor quality. In response, international health organizations have developed best-practice guidelines for substance user treatment in developing countries, although little research has evaluated their implementation. This opinion piece will examine one such effort to improve substance user treatment in El Salvador. It will be argued that the program failed (2007–2008) because of a lack of political will by the Salvadoran government through their Ministry of Health to effectively supervise, monitor, and subsidize substance user treatment. PMID:23186469

Lentiviral vectors for gene therapy of heart disease.

PubMed

Higuchi, Koji; Medin, Jeffrey A

2007-01-01

Technological advances in genetic engineering developed over the past few years have been applied to the research and treatment of cardiovascular diseases. In many animal models, gene therapy has been shown to be an effective treatment schema. Some of these gene therapy treatments are now being applied in clinical trials. Also, as the science of gene therapy has progressed, alternative vector systems such as lentiviruses have been developed and implemented. Here we focus on the emerging role of lentiviral vectors in the treatment of cardiovascular disease.

Gynaecomastia in two men on stable antiretroviral therapy who commenced treatment for tuberculosis.

PubMed

Kratz, Jeremy D; El-Shazly, Ahmad Y; Mambuque, Santos G; Demetria, Elpidio; Veldkamp, Peter; Anderson, Timothy S

2016-12-01

Gynaecomastia is a common clinical presentation that varies from benign presentations in stages of human development to hormonal pathology, mainly due to hepatic dysfunction, malignancy, and adverse pharmacologic effects. We describe the development of significant bilateral gynaecomastia after starting treatment for pulmonary tuberculosis (TB) in two males with WHO stage III Human Immunodeficiency Virus (HIV) infection on stable antiretroviral regimens. Emerging reports suggest that distinct hepatic impairment in efavirenz metabolism modulates oestrogenic activity, which may be potentiated by anti-tuberculosis therapy. Clinical application includes early recognition of efavirenz-induced gynaecomastia, especially after commencing tuberculosis treatment. To avoid decreased adherence resulting from the distressing side effect of gynecomastia, transition to an alternative ART regimen over the course of tuberculosis treatment should be considered.

Carbon dioxide exchange of buds and developing shoots of boreal Norway spruce exposed to elevated or ambient CO2 concentration and temperature in whole-tree chambers.

PubMed

Hall, Marianne; Räntfors, Mats; Slaney, Michelle; Linder, Sune; Wallin, Göran

2009-04-01

Effects of ambient and elevated temperature and atmospheric carbon dioxide concentration ([CO2]) on CO2 assimilation rate and the structural and phenological development of shoots during their first growing season were studied in 45-year-old Norway spruce trees (Picea abies (L.) Karst.) enclosed in whole-tree chambers. Continuous measurements of net assimilation rate (NAR) in individual buds and shoots were made from early bud development to late August in two consecutive years. The largest effect of elevated temperature (TE) was manifest early in the season as an earlier start and completion of shoot length development, and a 1-3-week earlier shift from negative to positive NAR compared with the ambient temperature (TA) treatments. The largest effect of elevated [CO2] (CE) was found later in the season, with a 30% increase in maximum NAR compared with trees in the ambient [CO2] treatments (CA), and shoots assimilating their own mass in terms of carbon earlier in the CE treatments than in the CA treatments. Once the net carbon assimilation compensation point (NACP) had been reached, TE had little or no effect on the development of NAR performance, whereas CE had little effect before the NACP. No interactive effects of TE and CE on NAR were found. We conclude that in a climate predicted for northern Sweden in 2100, current-year shoots of P. abies will assimilate their own mass in terms of carbon 20-30 days earlier compared with the current climate, and thereby significantly contribute to canopy assimilation during their first year.

Use of atypical antipsychotics for treatment-resistant major depressive disorder.

PubMed

Papakostas, George I; Shelton, Richard C

2008-12-01

Despite the progressive increase in the number of pharmacologic agents with potential antidepressant activity, many patients suffering from major depressive disorder (MDD) continue to be symptomatic. Clearly, an urgent need exists to develop safer, better tolerated, and more effective treatments for MDD. Use of atypical antipsychotic agents as adjunctive treatment for treatment-resistant MDD (TRD) represents one such effort toward novel pharmacotherapy development. Atypical antipsychotic agents have been hypothesized to be beneficial in treating mood disorders, including TRD, as a result of their complex mechanisms of action. After an initial series of positive case reports, series, and small clinical trials, subsequent larger-scale projects have yielded conflicting results. However, more recently, larger-scale clinical trials have supported the effectiveness of at least some of these medications. This review summarizes the existing data regarding the effectiveness of these medications in treating TRD, including biochemical rationale and clinical data.

The Kraken Wakes: induced EMT as a driver of tumour aggression and poor outcome.

PubMed

Redfern, Andrew D; Spalding, Lisa J; Thompson, Erik W

2018-06-08

Epithelial mesenchymal transition (EMT) describes the shift of cells from an epithelial form to a contact independent, migratory, mesenchymal form. In cancer the change is linked to invasion and metastasis. Tumour conditions, including hypoxia, acidosis and a range of treatments can trigger EMT, which is implicated in the subsequent development of resistance to those same treatments. Consequently, the degree to which EMT occurs may underpin the entire course of tumour progression and treatment response in a patient. In this review we look past the protective effect of EMT against the initial treatment, to the role of the mesenchymal state, once triggered, in promoting disease growth, spread and future treatment insensitivity. In patients a correlation was found between the propensity of a treatment to induce EMT and failure of that treatment to provide a survival benefit, implicating EMT induction in accelerated tumour progression after treatment cessation. Looking to the mechanisms driving this detrimental effect; increased proliferation, suppressed apoptosis, stem cell induction, augmented angiogenesis, enhanced metastatic dissemination, and immune tolerance, can all result from treatment-induced EMT and could worsen outcome. Evidence also suggests EMT induction with earlier therapies attenuates benefits of later treatments. Looking beyond epithelial tumours, de-differentiation also has therapy-attenuating effects and reversal thereof may yield similar rewards. A range of potential therapies are in development that may address the diverse mechanisms and molecular control systems involved in EMT-induced accelerated progression. Considering the broad reaching effects of mesenchymal shift identified, successful deployment of such treatments could substantially improve patient outcomes.

The Effects of Varying Levels of Treatment Integrity on Child Compliance during Treatment with a Three-Step Prompting Procedure

ERIC Educational Resources Information Center

Wilder, David A.; Atwell, Julie; Wine, Byron

2006-01-01

The effects of three levels of treatment integrity (100%, 50%, and 0%) on child compliance were evaluated in the context of the implementation of a three-step prompting procedure. Two typically developing preschool children participated in the study. After baseline data on compliance to one of three common demands were collected, a therapist…

Acoustic Treatment Design Scaling Methods. Volume 2; Advanced Treatment Impedance Models for High Frequency Ranges

NASA Technical Reports Server (NTRS)

Kraft, R. E.; Yu, J.; Kwan, H. W.

1999-01-01

The primary purpose of this study is to develop improved models for the acoustic impedance of treatment panels at high frequencies, for application to subscale treatment designs. Effects that cause significant deviation of the impedance from simple geometric scaling are examined in detail, an improved high-frequency impedance model is developed, and the improved model is correlated with high-frequency impedance measurements. Only single-degree-of-freedom honeycomb sandwich resonator panels with either perforated sheet or "linear" wiremesh faceplates are considered. The objective is to understand those effects that cause the simple single-degree-of- freedom resonator panels to deviate at the higher-scaled frequency from the impedance that would be obtained at the corresponding full-scale frequency. This will allow the subscale panel to be designed to achieve a specified impedance spectrum over at least a limited range of frequencies. An advanced impedance prediction model has been developed that accounts for some of the known effects at high frequency that have previously been ignored as a small source of error for full-scale frequency ranges.

Recent advances and future challenges in cancer immunotherapy.

PubMed

Okuyama, Namiko; Tamada, Koji; Tamura, Hideto

2016-01-01

Remarkable advances have been made in cancer immunotherapy. Recent treatment strategies, especially chimeric antigen receptor-T (CAR-T) cell therapy and immune checkpoint inhibitors, reportedly achieve higher objective responses and better survival rates than previous immunotherapies for patients with treatment-resistant malignancies, creating a paradigm shift in cancer treatment. Several clinical trials of cancer immunotherapy for patients with various malignancies are ongoing. However, those with certain malignancies, such as low-immunogenic cancers, cannot be successfully treated with T-cell immunotherapy, and subsets of immunotherapy-treated patients relapse, meaning that more effective immunotherapeutic strategies are needed for such patients. Furthermore, the safety, convenience, and cost of cancer immunotherapy need to be improved in the near future. Herein, we discuss recent advances and future challenges in cancer immunotherapy, i.e., the identification of neoantigens for the development of individualized immunotherapies, the development of new CAR-T cell therapies, including so-called armored CAR-T cells that can induce greater clinical effects and thereby achieve longer survival, the development of off-the-shelf treatment regimens using non-self cells or cell lines, and effective cancer immunotherapy combinations.

Process Evaluation in Corrections-Based Substance Abuse Treatment.

ERIC Educational Resources Information Center

Wolk, James L.; Hartmann, David J.

1996-01-01

Argues that process evaluation is needed to validate prison-based substance abuse treatment effectiveness. Five groups--inmates, treatment staff, prison staff, prison administration, and the parole board--should be a part of this process evaluation. Discusses these five groups relative to three stages of development of substance abuse treatment in…

Meta-STEPP: subpopulation treatment effect pattern plot for individual patient data meta-analysis.

PubMed

Wang, Xin Victoria; Cole, Bernard; Bonetti, Marco; Gelber, Richard D

2016-09-20

We have developed a method, called Meta-STEPP (subpopulation treatment effect pattern plot for meta-analysis), to explore treatment effect heterogeneity across covariate values in the meta-analysis setting for time-to-event data when the covariate of interest is continuous. Meta-STEPP forms overlapping subpopulations from individual patient data containing similar numbers of events with increasing covariate values, estimates subpopulation treatment effects using standard fixed-effects meta-analysis methodology, displays the estimated subpopulation treatment effect as a function of the covariate values, and provides a statistical test to detect possibly complex treatment-covariate interactions. Simulation studies show that this test has adequate type-I error rate recovery as well as power when reasonable window sizes are chosen. When applied to eight breast cancer trials, Meta-STEPP suggests that chemotherapy is less effective for tumors with high estrogen receptor expression compared with those with low expression. Copyright © 2016 John Wiley & Sons, Ltd. Copyright © 2016 John Wiley & Sons, Ltd.

Effects of rapamycin and curcumin treatment on the development of epilepsy after electrically induced status epilepticus in rats.

PubMed

Drion, Cato M; Borm, Lars E; Kooijman, Lieneke; Aronica, Eleonora; Wadman, Wytse J; Hartog, Aloysius F; van Vliet, Erwin A; Gorter, Jan A

2016-05-01

Inhibition of the mammalian target of rapamycin (mTOR) pathway has been suggested as a possible antiepileptogenic strategy in temporal lobe epilepsy (TLE). Here we aim to elucidate whether mTOR inhibition has antiepileptogenic and/or antiseizure effects using different treatment strategies in the electrogenic post-status epilepticus (SE) rat model. Effects of mTOR inhibitor rapamycin were tested using the following three treatment protocols: (1) "stop-treatment"-post-SE treatment (6 mg/kg/day) was discontinued after 3 weeks; rats were monitored for 5 more weeks thereafter, (2) "pretreatment"-rapamycin (3 mg/kg/day) was applied during 3 days preceding SE; and (3) "chronic phase-treatment"-5 days rapamycin treatment (3 mg/kg/day) in the chronic phase. We also tested curcumin, an alternative mTOR inhibitor with antiinflammatory and antioxidant effects, using chronic phase treatment. Seizures were continuously monitored using video-electroencephalography (EEG) recordings; mossy fiber sprouting, cell death, and inflammation were studied using immunohistochemistry. Blood was withdrawn regularly to assess rapamycin and curcumin levels with high performance liquid chromatography (HPLC). Stop-treatment led to a strong reduction of seizures during the 3-week treatment and a gradual reappearance of seizures during the following 5 weeks. Three days pretreatment did not prevent seizure development, whereas 5-day rapamycin treatment in the chronic phase reduced seizure frequency. Washout of rapamycin was slow and associated with a gradual reappearance of seizures. Rapamycin treatment (both 3 and 6 mg/kg) led to body growth reduction. Curcumin treatment did not reduce seizure frequency or lead to a decrease in body weight. The present study indicates that rapamycin cannot prevent epilepsy in the electrical stimulation post-SE rat model but has seizure-suppressing properties as long as rapamycin blood levels are sufficiently high. Oral curcumin treatment had no effect on chronic seizures, possibly because it did not reach the brain at adequate levels. Wiley Periodicals, Inc. © 2016 International League Against Epilepsy.

Skeletal effects in Angle Class II/1 patients treated with the functional regulator type II : Cephalometric and tensor analysis.

PubMed

Schulz, Simone; Koos, Bernd; Duske, Kathrin; Stahl, Franka

2016-11-01

The purpose of this work was to employ both cephalometric and tensor analysis in characterizing the skeletal changes experienced by patients with Angle Class II/1 malocclusion during functional orthodontic treatment with the functional regulator type II. A total of 23 patients with Class II/1 malocclusion based on lateral cephalograms obtained before and after treatment with the functional regulator type II were analyzed. Another 23 patients with Angle Class II/1 malocclusion who had not undergone treatment were included as controls. Our cephalometric data attest to significant therapeutic effects of the functional regulator type II on the skeletal mandibular system, including significant advancement of the mandible, increases in effective mandibular length with enhancement of the chin profile, and reduction of growth-related bite deepening. No treatment-related effects were observed at the cranial-base and midface levels. In addition, tensor analysis revealed significant stimulation of mandibular growth in sagittal directions, without indications of growth effects on the maxilla. Its growth-pattern findings differed from those of cephalometric analysis by indicating that the appliance did promote horizontal development, which supports the functional orthodontic treatment effect in Angle Class II/1 cases. Tensor analysis yielded additional insights into sagittal and vertical growth changes not identifiable by strictly cephalometric means. The functional regulator type II was an effective treatment modality for Angle Class II/1 malocclusion and influenced the skeletal development of these patients in favorable ways.

The anti-tumor effect of the quinoline-3-carboxamide tasquinimod: blockade of recruitment of CD11b(+) Ly6C(hi) cells to tumor tissue reduces tumor growth.

PubMed

Deronic, Adnan; Tahvili, Sahar; Leanderson, Tomas; Ivars, Fredrik

2016-07-11

Previous work has demonstrated immunomodulatory, anti-tumor, anti-metastatic and anti-angiogenic effects of the small molecule quinoline-3-carboxamide tasquinimod in pre-clinical cancer models. To better understand the anti-tumor effects of tasquinimod in transplantable tumor models, we have evaluated the impact of the compound both on recruitment of myeloid cells to tumor tissue and on tumor-induced myeloid cell expansion as these cells are known to promote tumor development. Mice bearing subcutaneous 4 T1 mammary carcinoma tumors were treated with tasquinimod in the drinking water. A BrdU-based flow cytometry assay was utilized to assess the impact of short-term tasquinimod treatment on myeloid cell recruitment to tumors. Additionally, long-term treatment was performed to study the anti-tumor effect of tasquinimod as well as its effects on splenic myeloid cells and their progenitors. Myeloid cell populations were also immune-depleted by in vivo antibody treatment. Short-term tasquinimod treatment did not influence the proliferation of splenic Ly6C(hi) and Ly6G(hi) cells, but instead reduced the influx of Ly6C(hi) cells to the tumor. Treatment with tasquinimod for various periods of time after tumor inoculation revealed that the anti-tumor effect of this compound mainly operated during the first few days of tumor growth. Similar to tasquinimod treatment, antibody-mediated depletion of Ly6C(hi) cells within that same time frame, caused reduced tumor growth, thereby confirming a significant role for these cells in tumor development. Additionally, long-term tasquinimod treatment reduced the splenomegaly and expansion of splenic myeloid cells during a later phase of tumor development. In this phase, tasquinimod normalized the tumor-induced alterations in myeloerythroid progenitor cells in the spleen but had only limited impact on the same populations in the bone marrow. Our results indicate that tasquinimod treatment reduces tumor growth by operating early after tumor inoculation and that this effect is at least partially caused by reduced recruitment of Ly6C(hi) cells to tumor tissue. Long-term treatment also reduces the number of splenic myeloid cells and myeloerythroid progenitors, but these effects did not influence established rapidly growing tumors.

Effect of alternative postharvest control treatments on the storability of 'Golden Delicious' apples.

PubMed

Moscetti, Roberto; Carletti, Letizia; Monarca, Danilo; Cecchini, Massimo; Stella, Elisabetta; Massantini, Riccardo

2013-08-30

Apples are subject to a high degree of fungal diseases, but the use of synthetic fungicides has been questioned because of public safety concerns, social rejection, and the development of resistance in pathogens. Thus, development of new postharvest treatments against apple fungal pathogens is necessary. Most studies have reported their effectiveness, but not all report the effects on the quality and storability of the fruit. In this study, the effects of physical (hot water), chemical (quercetin) and biological (yeast antagonist) microfungal control on the quality of 'Golden Delicious' apple during storage at 2 ± 0.5 °C, and 90 ± 2% of relative humidity, for 2 months were investigated and compared. Heat-treated apples exhibited peel fruit damage (surface browning and internal breakdown disorders) and promoted ripening in the fruit. The quercetin caustic spray caused the development of peel chemical burn in all treated fruit. Both yeast antagonist and quercetin treatments did not affect the apple ripening process but stimulated an increase in ethylene production and in respiratory activity. The data indicated that the effects on quality and storability were dependent on the method of treatment used, and antagonistic yeast was the best microfungal control because of it did not cause any disorders or negative effects on apple quality during storage. © 2013 Society of Chemical Industry.

Evolving Clinical Cancer Radiotherapy: Concerns Regarding Normal Tissue Protection and Quality Assurance

PubMed Central

Choi, Won Hoon

2016-01-01

Radiotherapy, which is one of three major cancer treatment methods in modern medicine, has continued to develop for a long period, more than a century. The development of radiotherapy means allowing the administration of higher doses to tumors to improve tumor control rates while minimizing the radiation doses absorbed by surrounding normal tissues through which radiation passes for administration to tumors, thereby reducing or removing the incidence of side effects. Such development of radiotherapy was accomplished by the development of clinical radiation oncology, the development of computers and machine engineering, the introduction of cutting-edge imaging technology, a deepened understanding of biological studies on the effects of radiation on human bodies, and the development of quality assurance (QA) programs in medical physics. The development of radiotherapy over the last two decades has been quite dazzling. Due to continuous improvements in cancer treatment, the average five-year survival rate of cancer patients has been close to 70%. The increases in cancer patients’ complete cure rates and survival periods are making patients’ quality of life during or after treatment a vitally important issue. Radiotherapy is implemented in approximately 1/3 to 2/3s of all cancer patients; and has improved the quality of life of cancer patients in the present age. Over the last century, as a noninvasive treatment, radiotherapy has unceasingly enhanced complete tumor cure rates and the side effects of radiotherapy have been gradually decreasing, resulting in a tremendous improvement in the quality of life of cancer patients. PMID:26908993

Does Early Mathematics Intervention Change the Processes Underlying Children’s Learning?

PubMed Central

Watts, Tyler W.; Clements, Douglas H.; Sarama, Julie; Wolfe, Christopher B.; Spitler, Mary Elaine; Bailey, Drew H.

2017-01-01

Early educational intervention effects typically fade in the years following treatment, and few studies have investigated why achievement impacts diminish over time. The current study tested the effects of a preschool mathematics intervention on two aspects of children’s mathematical development. We tested for separate effects of the intervention on “state” (occasion-specific) and “trait” (relatively stable) variability in mathematics achievement. Results indicated that, although the treatment had a large impact on state mathematics, the treatment had no effect on trait mathematics, or the aspect of mathematics achievement that influences stable individual differences in mathematics achievement over time. Results did suggest, however, that the intervention could affect the underlying processes in children’s mathematical development by inducing more transfer of knowledge immediately following the intervention for students in the treated group. PMID:29399243

Is administration of trastuzumab an independent risk factor for developing osteonecrosis of the jaw among metastatic breast cancer patients under zoledronic acid treatment?

PubMed

Pilanci, Kezban Nur; Alco, Gul; Ordu, Cetin; Sarsenov, Dauren; Celebi, Filiz; Erdogan, Zeynep; Agacayak, Filiz; Ilgun, Serkan; Tecimer, Coskun; Demir, Gokhan; Eralp, Yesim; Okkan, Sait; Ozmen, Vahit

2015-05-01

One of the most important adverse effects of zoledronic acid (ZA) is osteonecrosis of the jaw (ONJ). In previous literature, several risk factors have been identified in the development of ONJ. In this study, we aimed to determine the role of trastuzumab, an antiangiogenic agent, as an independent risk factor for the development of this serious side effect.Our study included 97 patients (mean age: 54 ± 10 years) with breast cancer, recorded in the archives of the Istanbul Florence Nightingale Breast Study Group, who received ZA therapy due to bone metastases between March 2006 and December 2013. We recorded the patients' ages, weights, duration of treatment with ZA, number of ZA infusions, dental procedures, anticancer treatments (chemotherapy, aromatase inhibitor, trastuzumab), the presence of diabetes mellitus or renal dysfunction, and smoking habits.Thirteen patients (13.40%) had developed ONJ. Among the patients with ONJ, the mean time of exposure to ZA was 41 months (range: 13-82) and the mean number of ZA infusions was 38 (range: 15-56). The duration of treatment with ZA and the use of trastuzumab were observed to be 2 factors that influenced the development of ONJ (P = 0.049 and P = 0.028, respectively).The development of ONJ under ZA treatment may be associated solely with the duration of ZA treatment and the concurrent administration of trastuzumab. These findings show that patients who are administered trastuzumab for metastatic breast cancer while undergoing ZA treatment are prone to developing ONJ. Therefore, we recommend intense clinical observation to avoid this particular condition in patients receiving ZA and trastuzumab.

Is Administration of Trastuzumab an Independent Risk Factor for Developing Osteonecrosis of the Jaw Among Metastatic Breast Cancer Patients Under Zoledronic Acid Treatment?

PubMed Central

Pilanci, Kezban Nur; Alco, Gul; Ordu, Cetin; Sarsenov, Dauren; Celebi, Filiz; Erdogan, Zeynep; Agacayak, Filiz; Ilgun, Serkan; Tecimer, Coskun; Demir, Gokhan; Eralp, Yesim; Okkan, Sait; Ozmen, Vahit

2015-01-01

Abstract One of the most important adverse effects of zoledronic acid (ZA) is osteonecrosis of the jaw (ONJ). In previous literature, several risk factors have been identified in the development of ONJ. In this study, we aimed to determine the role of trastuzumab, an antiangiogenic agent, as an independent risk factor for the development of this serious side effect. Our study included 97 patients (mean age: 54 ± 10 years) with breast cancer, recorded in the archives of the Istanbul Florence Nightingale Breast Study Group, who received ZA therapy due to bone metastases between March 2006 and December 2013. We recorded the patients’ ages, weights, duration of treatment with ZA, number of ZA infusions, dental procedures, anticancer treatments (chemotherapy, aromatase inhibitor, trastuzumab), the presence of diabetes mellitus or renal dysfunction, and smoking habits. Thirteen patients (13.40%) had developed ONJ. Among the patients with ONJ, the mean time of exposure to ZA was 41 months (range: 13–82) and the mean number of ZA infusions was 38 (range: 15–56). The duration of treatment with ZA and the use of trastuzumab were observed to be 2 factors that influenced the development of ONJ (P = 0.049 and P = 0.028, respectively). The development of ONJ under ZA treatment may be associated solely with the duration of ZA treatment and the concurrent administration of trastuzumab. These findings show that patients who are administered trastuzumab for metastatic breast cancer while undergoing ZA treatment are prone to developing ONJ. Therefore, we recommend intense clinical observation to avoid this particular condition in patients receiving ZA and trastuzumab. PMID:25950681

Nonparametric methods for doubly robust estimation of continuous treatment effects.

PubMed

Kennedy, Edward H; Ma, Zongming; McHugh, Matthew D; Small, Dylan S

2017-09-01

Continuous treatments (e.g., doses) arise often in practice, but many available causal effect estimators are limited by either requiring parametric models for the effect curve, or by not allowing doubly robust covariate adjustment. We develop a novel kernel smoothing approach that requires only mild smoothness assumptions on the effect curve, and still allows for misspecification of either the treatment density or outcome regression. We derive asymptotic properties and give a procedure for data-driven bandwidth selection. The methods are illustrated via simulation and in a study of the effect of nurse staffing on hospital readmissions penalties.

Estimating and testing mediation and moderation in within-subject designs.

PubMed

Judd, C M; Kenny, D A; McClelland, G H

2001-06-01

Analyses designed to detect mediation and moderation of treatment effects are increasingly prevalent in research in psychology. The mediation question concerns the processes that produce a treatment effect. The moderation question concerns factors that affect the magnitude of that effect. Although analytic procedures have been reasonably well worked out in the case in which the treatment varies between participants, no systematic procedures for examining mediation and moderation have been developed in the case in which the treatment varies within participants. The authors present an analytic approach to these issues using ordinary least squares estimation.

The effect of tamoxifen on pubertal bone development in adolescents with pubertal gynecomastia.

PubMed

Akgül, Sinem; Derman, Orhan; Kanbur, Nuray

2016-01-01

During puberty, estrogen has a biphasic effect on epiphyses; at low levels, it leads to an increase in height and bone mass, whereas at high levels, it leads to closure of the epiphysis. Tamoxifen is a selective estrogen receptor modulator that has been used in the treatment of pubertal gynecomastia. Although it has not been approved for this indication, studies have shown it to be both successful and safe. In males, the peak of pubertal bone development occurs during Tanner stage 3-4, which is also when pubertal gynecomastia reaches its highest prevalence. Thus tamoxifen treatment could potentially effect pubertal bone development. The aim of this study was to assess the effects of tamoxifen on bone mineral density (BMD) and skeletal maturation when used for pubertal gynecomastia. We evaluated 20 boys with pubertal gynecomastia receiving tamoxifen for at least 4 months. BMD was measured with dual-energy X-ray absorptiometry. Z-score and absolute BMD (g/cm(2)) was determined at baseline and 2 months after completing tamoxifen treatment. Bone age and height was evaluated before treatment and again one year later. Using absolute BMD (g/cm(2)), the mean difference from baseline was significant between the two groups both at spine (p=0.002) and femur (p=0.001), but not with the Z-score. This result was attributed to the expected increase during puberty according to sex and age. No significant effect on skeletal maturation was found (p=1.112). We conclude that when pubertal bone development is concerned, tamoxifen is safe for the treatment of pubertal gynecomastia as neither bone mineralization nor growth potential was affected.

Recent advances in behavioral addiction treatments: focusing on mechanisms of change.

PubMed

Longabaugh, Richard; Magill, Molly

2011-10-01

In the latter half of the 20th century, research on behavioral treatments for addictions aimed to develop and test effective treatments. Among the treatments found to be at least moderately effective, direct comparisons failed to reveal consistent superiority of one approach over another. This ubiquitous finding held true despite underlying theories that differed markedly in their proposed causal processes related to patient change. In the 21st century, the focus of treatment research is increasingly on how treatment works for whom rather than whether it works. Studies of active treatment ingredients and mechanisms of behavioral change, while promising, have yielded inconsistent results. Simple mediation analysis may need to be expanded via inclusion of models testing for moderated mediation, mediated moderation, and conditional indirect effects. Examples are offered as to how these more complex models can lead to increased understanding of the conditions under which specific treatment interventions will be effective and mechanisms of change operative in improving behavioral treatments for addictions.

Recent Advances in Behavioral Addiction Treatments: Focusing on Mechanisms of Change

PubMed Central

Longabaugh, Richard; Magill, Molly

2012-01-01

In the latter half of the 20th century, research on behavioral treatments for addictions aimed to develop and test effective treatments. Among treatments found to be at least moderately effective, direct comparisons failed to reveal consistent superiority of one approach over another. This ubiquitous finding held true despite underlying theories that differed markedly in their proposed causal processes related to patient change. In the 21st century the focus of treatment research is increasingly on how treatment works for whom, rather than whether it works. Studies of active treatment ingredients and mechanisms of behavioral change, while promising, have yielded inconsistent results. Simple mediation analysis may need to be expanded by inclusion of models testing for moderated mediation, mediated moderation, and conditional indirect effects. Examples are offered as to how these more complex models can lead to increased understanding of the conditions under which specific treatment interventions will be effective and mechanisms of change operative in improving behavioral treatments for addictions. PMID:21750958

[Efficacy of regular or intermittent inhalation of corticosteroids in treatment of asthma and its effects on growth and development in children].

PubMed

Li, Lin-Wei; Huang, Ying; Luo, Rong; Yan, Li; Li, Qu-Bei; Peng, Dong-Hong; Shu, Chang

2015-03-01

To observe the efficacy of regular or intermittent inhalation of salmeterol/fluticasone propionate (SM/FP) in the treatment of bronchial asthma and its effects on growth and development in children. A total of 112 children diagnosed with bronchial asthma between September 2012 and October 2013 were assigned to standardized treatment (standard group, n=56) and non-standardized treatment (intermittent group, n=56). Comparisons of clinical symptom scores and main pulmonary function indicators between the two groups were carried out before treatment and at 6 and 12 months after treatment. The growth velocity and changes in body mass index (BMI) were observed in the two groups. At 6 and 12 months after the treatment, the standard group had significantly reduced clinical symptom scores and significantly increased pulmonary function indicators (percentage of predicted peak expiratory flow, PEF%; percentage of forced expiratory volume in 1 second, FEV1%) (P<0.05); the intermittent group had significantly reduced clinical symptom scores and significantly increased FEV1% (P<0.05), but PEF% was significantly increased only at 6 months after treatment (P<0.05). At 12 months after treatment, the standard group had significantly lower clinical symptom scores and significantly higher PEF% and FEV1% when compared with the intermittent group (P<0.05). The growth velocity and BMI showed no significant differences between the two groups at 6 and 12 months after treatment (P>0.05). Compared with intermittent inhalation, long-term regular inhalation of SM/FP performs better in controlling clinical symptoms and enhancing pulmonary function in children with asthma. Inhalation of SM/FP for one year reveals no apparent effect on the growth and development of these children.

Effects of nitrate and atrazine on larval development and sexual differentiation in the northern leopard frog Rana pipiens.

PubMed

Orton, Frances; Carr, James A; Handy, Richard D

2006-01-01

Pollution from agrochemicals may be contributing to the global decline in amphibian populations. Environmentally relevant concentrations of nitrate and/or atrazine on anuran development and gonadal differentiation were tested. Four replicates of 20 tadpoles per tank (80/treatment) were exposed from Taylor-Kollros stage 2 to 3 to stage 23 to 34 to either 10 mg/L nitrate, 10 microg/L atrazine, a combined exposure of 10 mg/L nitrate plus 10 microg/L atrazine, or untreated controls. No treatment-dependent effects on weight, snout-vent or hind limb length, or time to forelimb emergence were observed. The proportions of females increased in all treatments compared to the controls, especially in the combined treatment (chi2 = 17.90, df = 6, p = 0.0065, combined = 66.4% female, control = 41% female). The frequency of intersex was low in all treatments. No treatment-related effects on the total number of spermatogenic cells were observed, but the ratio of cell types differed in that testes from animals in the treated groups exhibited more spermatogonia, fewer spermatocytes, and more spermatids than the control (significantly different, Kruskal-Wallis, p < 0.05). Ovaries from animals treated with nitrate or atrazine exhibited larger immature (previtellogenic) and mature (vitellogenic) follicles, but ovaries from the combined treatment had larger immature follicles only. Testicular oocytes were observed in the nitrate-only and atrazine-only treatments, and the control treatment, but not the combined treatment. Overall, this study has demonstrated changes in sex ratios that are more marked in response to combined nitrate/atrazine exposure than with these chemicals alone. Histological evidence suggests that premature maturation of gonad may occur as a result of nitrate and/or atrazine exposure during larval development.

Treatment for Acquired Apraxia of Speech: Examination of Treatment Intensity and Practice Schedule

ERIC Educational Resources Information Center

Wambaugh, Julie L.; Nessler, Christina; Cameron, Rosalea; Mauszycki, Shannon C.

2013-01-01

Purpose: The authors designed this investigation to extend the development of a treatment for acquired apraxia of speech (AOS)--sound production treatment (SPT)--by examining the effects of 2 treatment intensities and 2 schedules of practice. Method: The authors used a multiple baseline design across participants and behaviors with 4 speakers with…

Development of vegetation in a young ponderosa pine plantation: effect of treatment duration and time since disturbance

Treesearch

Philip M. McDonald; Gary O. Fiddler

2007-01-01

The density and development of deerbrush (Ceanothus integerrimus Hook. & Arn.), other shrubs, forbs, graminoids, and ponderosa pine (Pinus ponderosa Dougl. ex Laws. var. ponderosa) seedlings were evaluated in a young plantation in northern California from 1988 through 1997. Treatment regimes consisted of...

Treatment Options for Primary Refractory/Recurrent Hodgkin Lymphoma in Children and Adolescents

MedlinePlus

... back). The treatment options also depend on: The child's age and sex. The risk of long-term side effects . Most ... Physical problems that affect the following: Development of sex and reproductive organs . Fertility (ability to have children). Bone and muscle growth and development. Thyroid , heart, ...

Abundance and fate of antibiotics and hormones in a vegetative treatment system receiving cattle feedlot runoff

USDA-ARS?s Scientific Manuscript database

Vegetative treatment systems (VTS) have been developed and built as an alternative to conventional holding pond systems for managing run-off from animal feeding operations. Initially developed to manage runoff nutrients via uptake by grasses, their effectiveness at removing other runoff contaminant...

BRCA-Monet: a breast cancer specific drug treatment mode-of-action network for treatment effective prediction using large scale microarray database

PubMed Central

2013-01-01

Background Connectivity map (cMap) is a recent developed dataset and algorithm for uncovering and understanding the treatment effect of small molecules on different cancer cell lines. It is widely used but there are still remaining challenges for accurate predictions. Method Here, we propose BRCA-MoNet, a network of drug mode of action (MoA) specific to breast cancer, which is constructed based on the cMap dataset. A drug signature selection algorithm fitting the characteristic of cMap data, a quality control scheme as well as a novel query algorithm based on BRCA-MoNet are developed for more effective prediction of drug effects. Result BRCA-MoNet was applied to three independent data sets obtained from the GEO database: Estrodial treated MCF7 cell line, BMS-754807 treated MCF7 cell line, and a breast cancer patient microarray dataset. In the first case, BRCA-MoNet could identify drug MoAs likely to share same and reverse treatment effect. In the second case, the result demonstrated the potential of BRCA-MoNet to reposition drugs and predict treatment effects for drugs not in cMap data. In the third case, a possible procedure of personalized drug selection is showcased. Conclusions The results clearly demonstrated that the proposed BRCA-MoNet approach can provide increased prediction power to cMap and thus will be useful for identification of new therapeutic candidates. Website: The web based application is developed and can be access through the following link http://compgenomics.utsa.edu/BRCAMoNet/ PMID:24564956

Space Adaptation Back Pain: A Retrospective Study

NASA Technical Reports Server (NTRS)

Kerstman, E. L.; Scheuring, R. A.; Barnes, M. G.; DeKorse, T. B.; Saile, L. G.

2008-01-01

Back pain is frequently reported by astronauts during the early phase of space flight as they adapt to the microgravity environment. However, the epidemiology of space adaptation back pain has not been well defined. The purpose of this retrospective study was to develop a case definition of space adaptation back pain, determine the incidence of space adaptation back pain, and determine the effectiveness of available treatments. Medical records from the Mercury, Apollo, Apollo-Soyuz Test Project (ASTP), Skylab, Mir, International Space Station (ISS), and Shuttle programs were reviewed. All episodes of in-flight back pain that met the criteria for space adaptation back pain were recorded. Pain characteristics, including intensity, location, and duration of the pain were noted. The effectiveness of specific treatments also was recorded. The incidence of space adaptation back pain among astronauts was determined to be 53% (384/722). Most of the affected astronauts reported mild pain (85%). Moderate pain was reported by 11% of the affected astronauts and severe pain was reported by only 4% of the affected astronauts. The most effective treatments were fetal positioning (91% effective) and the use of analgesic medications (85% effective). This retrospective study aids in the development of a case definition of space adaptation back pain and examines the epidemiology of space adaptation back pain. Space adaptation back pain is usually mild and self-limited. However, there is a risk of functional impairment and mission impact in cases of moderate or severe pain that do not respond to currently available treatments. Therefore, the development of preventive measures and more effective treatments should be pursued.

Evidence base for multimodal therapy in cachexia.

PubMed

Solheim, Tora S; Laird, Barry J A

2012-12-01

The lack of success of unimodal treatment studies in cachexia and the growing awareness that multiple components are responsible for the development of cachexia have led to the view that cachexia intervention should include multimodal treatment. The aim of this article is to examine the evidence for multimodal treatment in the management of cancer cachexia. There are some studies involving multimodal treatment that indicate significant effects on cachexia outcomes. There are, however, no randomized controlled trials to date that incorporate fully a structured exercise program, nutrition, good symptom treatment as well as drug treatment, to counteract the effects of altered metabolism. The effectiveness of any drug intervention for cancer cachexia probably will only be maximized if incorporated into multimodal treatment. Further, cachexia treatment trials should also aim to include patients at an early phase in their cachexia trajectory and use validated outcome measures.

Clinical effectiveness of decongestive treatments on excess arm volume and patient-centered outcomes in women with early breast cancer-related arm lymphedema: a systematic review

PubMed Central

Jeffs, Eunice; Ream, Emma; Taylor, Cath; Bick, Debra

2018-01-01

ABSTRACT Objective: To identify the effect of decongestive lymphedema treatment on excess arm volume or patient-centered outcomes in women presenting within either 12 months or a mean nine months of developing arm lymphedema following breast cancer treatment. Introduction: Lymphedema is a common consequence of breast cancer treatment requiring life-long treatment to reduce symptoms and prevent complications. Currently, evidence to inform the optimal decongestive lymphedema treatment package is lacking. Inclusion criteria: The review included studies on women who received lymphedema treatment within either 12 months or a mean of nine months of developing unilateral breast cancer-related arm lymphedema. The intervention was any decongestive lymphedema treatment delivered with the purpose of reducing arm lymphedema, compared to another form of lymphedema treatment (whether self or practitioner-administered), placebo or no treatment. The clinical outcome was excess arm volume; patient-centered outcomes were health-related quality of life, arm heaviness, arm function, patient-perceived benefit and satisfaction with treatment. Experimental study designs were eligible, including randomized and non-randomized controlled trials, quasi-experimental, prospective and retrospective before and after studies were considered. Methods: A three-step search strategy was utilized to find published and unpublished studies. The search identified studies published from the inception of each database to July 6, 2016. Reference lists were scanned to identify further eligible studies. Studies were critically appraised using appropriate standardized critical appraisal instruments from the Joanna Briggs Institute. Details describing each study and treatment results regarding outcomes of interest were extracted from papers included in the review using appropriate standardized data extraction tools from the Joanna Briggs Institute. Due to heterogeneity in included studies, results for similar outcome measures were not pooled in statistical meta-analysis. A narrative and tabular format was used to synthesize results from identified and included studies. Results: Seven studies reporting results for outcomes of interest were critically appraised and included in the review: five randomized controlled trials and two descriptive (uncontrolled) studies. Reported outcomes included excess arm volume (five studies), health-related quality of life (three studies), arm heaviness (one study), arm function (two studies) and patient-perceived benefit (two studies). There was some evidence that decongestive treatments were effective for women presenting within either 12 months or a mean of nine months of developing breast cancer-related arm lymphedema, but the wide range of data prevented comparison of treatment findings which limited our ability to answer the review questions. Conclusions: Weak evidence (grade B) for the impact of decongestive lymphedema treatment on women with early lymphedema (i.e. less than 12 months duration of BCRL symptoms) did not allow any conclusions to be drawn about the most effective treatment to be offered when these women first present for treatment. Findings provided no justification to support change to current practice. Future primary research needs to focus on the most effective treatment for women when they first present with lymphedema symptoms, e.g. treatment provided within 12 months of developing symptoms. Studies should be adequately powered and recruit women exclusively with less than 12 months duration of breast cancer-related lymphedema symptoms, provide longer follow-up to monitor treatment effect over time, with comparable treatment protocols, outcome measures and reporting methods. PMID:29419623

MO-D-213-02: Quality Improvement Through a Failure Mode and Effects Analysis of Pediatric External Beam Radiotherapy

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

Gray, J; Lukose, R; Bronson, J

2015-06-15

Purpose: To conduct a failure mode and effects analysis (FMEA) as per AAPM Task Group 100 on clinical processes associated with teletherapy, and the development of mitigations for processes with identified high risk. Methods: A FMEA was conducted on clinical processes relating to teletherapy treatment plan development and delivery. Nine major processes were identified for analysis. These steps included CT simulation, data transfer, image registration and segmentation, treatment planning, plan approval and preparation, and initial and subsequent treatments. Process tree mapping was utilized to identify the steps contained within each process. Failure modes (FM) were identified and evaluated with amore » scale of 1–10 based upon three metrics: the severity of the effect, the probability of occurrence, and the detectability of the cause. The analyzed metrics were scored as follows: severity – no harm = 1, lethal = 10; probability – not likely = 1, certainty = 10; detectability – always detected = 1, undetectable = 10. The three metrics were combined multiplicatively to determine the risk priority number (RPN) which defined the overall score for each FM and the order in which process modifications should be deployed. Results: Eighty-nine procedural steps were identified with 186 FM accompanied by 193 failure effects with 213 potential causes. Eighty-one of the FM were scored with a RPN > 10, and mitigations were developed for FM with RPN values exceeding ten. The initial treatment had the most FM (16) requiring mitigation development followed closely by treatment planning, segmentation, and plan preparation with fourteen each. The maximum RPN was 400 and involved target delineation. Conclusion: The FMEA process proved extremely useful in identifying previously unforeseen risks. New methods were developed and implemented for risk mitigation and error prevention. Similar to findings reported for adult patients, the process leading to the initial treatment has an associated high risk.« less

Development of frontage road yield treatment analysis tool (FRYTAT) database software.

DOT National Transportation Integrated Search

2009-03-01

The Texas Department of Transportation (TxDOT) sponsored Project 0-4986, An Assessment of Frontage Road : Yield Treatments, to assess the effectiveness of a wide variety of frontage roadexit ramp and frontage roadU-turn : yield treatments...

Incidence of caries lesions among patients treated with comprehensive orthodontics.

PubMed

Richter, Amy E; Arruda, Airton O; Peters, Mathilde C; Sohn, Woosung

2011-05-01

Dental caries, specifically decalcified white-spot lesions (WSL), is a well-known side-effect of orthodontic treatment. The incidence of labial incipient caries lesions and its relationship with various patient and treatment variables was investigated in patients treated with comprehensive orthodontics. Randomly selected orthodontic patient records (n = 350) were examined to determine incipient caries lesion development. Labial surfaces on pretreatment and posttreatment photographs were scored with a standardized scoring system. Independent variables were collected by chart abstraction. The incidence of patients who developed at least 1 new WSL during treatment was 72.9%, and this incidence was 2.3% for cavitated lesions. Treatment duration was significantly associated with new WSL development (P = 0.03). Development of WSL and cavitated lesions increased (both, P <0.00) despite increased attention to oral hygiene during treatment. Sex, age, extraction therapy, and various fluoridation sources were not associated with WSL development, but initial oral-hygiene score was moderately associated (P <0.06). The incidence of WSL in patients treated with comprehensive orthodontics was significantly high, and the preventive therapy provided appeared to be ineffective. This widespread problem is alarming and warrants significant attention from both patients and providers that should result in greatly increased emphasis on effective caries prevention. Copyright © 2011 American Association of Orthodontists. Published by Mosby, Inc. All rights reserved.

Tobacco alkaloids reduction by casings added/enzymatic hydrolysis treatments assessed through PLSR analysis.

PubMed

Lin, Shunshun; Zhang, Xiaoming; Song, Shiqing; Hayat, Khizar; Eric, Karangwa; Majeed, Hamid

2016-03-01

Based on encouraged development of potential reduced-exposure products (PREPs) by the US Institute of Medicine, casings (glucose and peptides) added treatments (CAT) and enzymatic (protease and xylanase) hydrolysis treatments (EHT) were developed to study their effect on alkaloids reduction in tobacco and cigarette mainstream smoke (MS) and further investigate the correlation between sensory attributes and alkaloids. Results showed that the developed treatments reduced nicotine by 14.5% and 24.4% in tobacco and cigarette MS, respectively, indicating that both CAT and EHT are potentially effective for developing lower-risk cigarettes. Sensory and electronic nose analysis confirmed the significant influence of treatments on sensory and cigarette MS components. PLSR analysis demonstrated that tobacco alkaloids were positively correlated to the off-taste, irritation and impact attributes, and negatively correlated to the aroma and softness attributes. Additionally, nicotine and anabasine from tobacco leaves positively contributed to the impact attribute, while they negatively contributed to the aroma attribute (P<0.05). Meanwhile, most alkaloids in cigarette MS positively contributed to the impact and irritation attributes (P<0.05). Hence, this study paved a way to better understand the correlation between tobacco alkaloids and sensory attributes. Copyright © 2015 Elsevier Inc. All rights reserved.

Antibiotics for the treatment of dysentery in children.

PubMed

Traa, Beatrix S; Walker, Christa L Fischer; Munos, Melinda; Black, Robert E

2010-04-01

Ciprofloxacin, ceftriaxone and pivmecillinam are the antibiotics currently recommended by the World Health Organization (WHO) for the treatment of dysentery in children; yet there have been no reviews of the clinical effectiveness of these antibiotics in recent years. We reviewed all literature reporting the effect of ciprofloxacin, ceftriaxone and pivmecillinam for the treatment of dysentery in children in the developing countries. We used a standardized abstraction and grading format and performed meta-analyses to determine the effect of treatment with these antibiotics on rates of treatment failure, bacteriological failure and bacteriological relapse. The CHERG Standard Rules were applied to determine the final effect of treatment with these antibiotics on diarrhoea mortality. Eight papers were selected for abstraction. Treatment with ciprofloxacin, ceftriaxone or pivmecillinam resulted in a cure rate of >99% while assessing clinical failure, bacteriological failure and bacteriological relapse. The antibiotics recommended by the WHO--ciprofloxacin, ceftriaxone and pivmecillinam--are effective in reducing the clinical and bacteriological signs and symptoms of dysentery and thus can be expected to decrease diarrhoea mortality attributable to dysentery.

Attachment and alliance in the treatment of depressed, sexually abused women.

PubMed

Smith, Phillip N; Gamble, Stephanie A; Cort, Natalie A; Ward, Erin A; He, Hua; Talbot, Nancy L

2012-02-01

Depression among women with sexual abuse histories is less treatment responsive than in general adult samples. One contributor to poorer treatment outcomes may be abused women's difficulties in forming and maintaining secure relationships, as reflected in insecure attachment styles, which could also impede the development of a positive therapeutic alliance. The current study examines how attachment orientation (i.e. anxiety and avoidance) and development of the working alliance are associated with treatment outcomes among depressed women with histories of childhood sexual abuse. Seventy women seeking treatment in a community mental health center who had Major Depressive Disorder and a childhood sexual abuse history were randomized to Interpersonal Psychotherapy or treatment as usual. Greater attachment avoidance and weaker working alliance were each related to worse depression symptom outcomes; these effects were independent of the presence of comorbid Borderline Personality Disorder and Post-Traumatic Stress Disorder. The effect of avoidant attachment on outcomes was not mediated by the working alliance. Further, working alliance had a stronger effect on depression outcomes in the Interpersonal Psychotherapy group. Understanding the influence of attachment style and the working alliance on treatment outcomes can inform efforts to improve the treatments for depressed women with a history of childhood sexual abuse. © 2012 Wiley Periodicals, Inc.

Development of Children at Risk for Adverse Outcomes Participating in Early Intervention in Developing Countries: A Randomized Controlled Trial

ERIC Educational Resources Information Center

Wallander, Jan L.; Bann, Carla M.; Biasini, Fred J.; Goudar, Shivaprasad S.; Pasha, Omrana; Chomba, Elwyn; McClure, Elizabeth; Carlo, Waldemar A.

2014-01-01

Background: Previous research has indicated positive effects of early developmental intervention (EDI) on the development of children in developing countries. Few studies, however, have examined longitudinally when differential treatment effects may be observed and whether differential outcomes are associated with exposure to different risk…

Cerebroprotective effect of combined treatment with pyrazidol and bemitil in craniocerebral trauma.

PubMed

Zarubina, I V; Kuritsyna, N A; Shabanov, P D

2004-07-01

Monotherapy of consequences of craniocerebral trauma with pyrazidol (1 mg/kg) produced an anxiolytic effect in animals highly resistant to hypoxia and activating effect on low resistant animals. Treatment with bemitil in a dose of 25 mg/kg produced a cerebroprotective effect and normalized individual behavioral characteristics, parameters of energy metabolism, and state of the antioxidant system in the brain of highly and low resistant rats. The effect of bemitil was most pronounced in highly resistant animals. During combined treatment, pyrazidol and bemitil had an additive effect in animals of both groups. They normalized behavioral reactions and prevented the development of metabolic disturbances in the brain.

Effects of Clinical Pilates Exercises on Patients Developing Lymphedema after Breast Cancer Treatment: A Randomized Clinical Trial.

PubMed

Şener, Hülya Özlem; Malkoç, Mehtap; Ergin, Gülbin; Karadibak, Didem; Yavuzşen, Tuğba

2017-01-01

The aim of the present study was to compare the effects of clinical Pilates exercises with those of the standard lymphedema exercises on lymphedema developing after breast cancer treatment. The study comprised 60 female patients with a mean age of 53.2±7.7 years who developed lymphedema after having breast cancer treatment. The patients were randomized into two groups: the clinical Pilates exercise group (n=30), and the control group (n=30). Before, and at the 8th week of treatment, the following parameters were measured: the severity of lymphedema, limb circumferences, body image using the Social Appearance Anxiety Scale, quality of life with the European Organization for Research and Treatment of Cancer (EORTC) quality of life questionnaire (QLQ-BR23), and upper extremity function using the Disabilities of the Arm, Shoulder and Hand (DASH) outcome measure. Both groups performed one-hour exercises three days a week for 8 weeks. After treatment, the symptoms recovered significantly in both groups. Reductions in the severity of lymphedema, improvements in the social appearance anxiety scale scores, quality of life scores, and upper extremity functions scores in the clinical Pilates exercise group were greater than those in the control group. Clinical Pilates exercises were determined to be more effective on the symptoms of patients with lymphedema than were standard lymphedema exercises. Clinical Pilates exercises could be considered a safe model and would contribute to treatment programs.

Effects of Clinical Pilates Exercises on Patients Developing Lymphedema after Breast Cancer Treatment: A Randomized Clinical Trial

PubMed Central

Şener, Hülya Özlem; Malkoç, Mehtap; Ergin, Gülbin; Karadibak, Didem; Yavuzşen, Tuğba

2017-01-01

Objective The aim of the present study was to compare the effects of clinical Pilates exercises with those of the standard lymphedema exercises on lymphedema developing after breast cancer treatment. Materials and Methods The study comprised 60 female patients with a mean age of 53.2±7.7 years who developed lymphedema after having breast cancer treatment. The patients were randomized into two groups: the clinical Pilates exercise group (n=30), and the control group (n=30). Before, and at the 8th week of treatment, the following parameters were measured: the severity of lymphedema, limb circumferences, body image using the Social Appearance Anxiety Scale, quality of life with the European Organization for Research and Treatment of Cancer (EORTC) quality of life questionnaire (QLQ-BR23), and upper extremity function using the Disabilities of the Arm, Shoulder and Hand (DASH) outcome measure. Both groups performed one-hour exercises three days a week for 8 weeks. Results After treatment, the symptoms recovered significantly in both groups. Reductions in the severity of lymphedema, improvements in the social appearance anxiety scale scores, quality of life scores, and upper extremity functions scores in the clinical Pilates exercise group were greater than those in the control group. Clinical Pilates exercises were determined to be more effective on the symptoms of patients with lymphedema than were standard lymphedema exercises. Conclusions Clinical Pilates exercises could be considered a safe model and would contribute to treatment programs. PMID:28331763

Using decision analysis to assess comparative clinical efficacy of surgical treatment of unstable ankle fractures.

PubMed

Michelson, James D

2013-11-01

The development of a robust treatment algorithm for ankle fractures based on well-established stability criteria has been shown to be prognostic with respect to treatment and outcomes. In parallel with the development of improved understanding of the biomechanical rationale of ankle fracture treatment has been an increased emphasis on assessing the effectiveness of medical and surgical interventions. The purpose of this study was to investigate the use of using decision analysis in the assessment of the cost effectiveness of operative treatment of ankle fractures based on the existing clinical data in the literature. Using the data obtained from a previous structured review of the ankle fracture literature, decision analysis trees were constructed using standard software. The decision nodes for the trees were based on ankle fracture stability criteria previously published. The outcomes were assessed by calculated Quality-Adjusted Life Years (QALYs) assigned to achieving normal ankle function, developing posttraumatic arthritis, or sustaining a postoperative infection. Sensitivity analysis was undertaken by varying the patient's age, incidence of arthritis, and incidence or infection. Decision analysis trees captured the essential aspects of clinical decision making in ankle fracture treatment in a clinically useful manner. In general, stable fractures yielded better outcomes with nonoperative treatment, whereas unstable fractures had better outcomes with surgery. These were consistent results over a wide range of postoperative infection rates. Varying the age of the patient did not qualitatively change the results. Between the ages of 30 and 80 years, surgery yielded higher expected QALYs than nonoperative care for unstable fractures, and generated lower QALYs than nonoperative care for stable fractures. Using local cost estimates for operative and nonoperative treatment, the incremental cost of surgery for unstable fractures was less than $40,000 per QALY (the usual cutoff for the determination of cost effectiveness) for patients aged up to 90 years. Decision analysis is a useful methodology in developing treatment guidelines. Numerous previous studies have indicated superior clinical outcomes when unstable ankle fractures underwent operative reduction and stabilization. What has been lacking was an examination of the cost effectiveness of such an approach, particularly in older patients who have fewer expected years of life. In light of the evidence for satisfactory outcomes for surgery of severe ankle fractures in older people, the justification for operative intervention is an obvious question that can be asked in the current increasingly cost-conscious environment. Using a decision-tree decision analysis structured around the stability-based ankle fracture classification system, in conjunction with a relatively simple cost effectiveness analysis, this study was able to demonstrate that surgical treatment of unstable ankle fractures in elderly patients is in fact cost effective. The clinical implication of the present analysis is that these existing treatment protocols for ankle fracture treatment are also cost effective when quality of life outcome measures are taken into account. Economic Level II. See Instructions for Authors for a complete description of levels of evidence.

New developments in the management of periocular capillary hemangioma in children.

PubMed

Ni, Nina; Wagner, Rudolph S; Langer, Paul; Guo, Suqin

2011-01-01

The authors describe the theories of pathogenesis for capillary hemangioma and discuss the benefits and side effects of current treatment options, such as systemic and intralesional corticosteroids, laser therapy, and surgical excision. They also evaluate the recent systemic and topical applications of beta-blockers to treat infantile hemangioma. Although no major adverse events from beta-blocker treatment have been reported, the incidence of potential side effects such as bronchospasm, hypoglycemia, heart block, bradycardia, and congestive heart failure is unknown due to the novelty of the treatment. It has been postulated that topical application for localized superficial tumor may reduce systemic effects. Further research is necessary to compare the effectiveness of different treatments and to find the optimal dosing and delivery methods to minimize adverse effects in the treatment of this disorder. Copyright 2011, SLACK Incorporated.

Protective effect of in ovo treatment with the chicken cathelicidin analog D-CATH-2 against avian pathogenic E. coli

PubMed Central

Cuperus, Tryntsje; van Dijk, Albert; Matthijs, Mieke G. R.; Veldhuizen, Edwin J. A.; Haagsman, Henk P.

2016-01-01

Increasing antibiotic resistance and ever stricter control on antibiotic use are a driving force to develop alternatives to antibiotics. One such strategy is the use of multifunctional Host Defense Peptides. Here we examined the protective effect of prophylactic treatment with the D analog of chicken cathelicidin-2 (D-CATH-2) against a respiratory E. coli infection. Chickens were treated with D-CATH-2 in ovo at day 18 of embryonic development or intramuscularly at days 1 and 4 after hatch. At 7 days of age, birds were challenged intratracheally with avian pathogenic E. coli. Protection was evaluated by recording mortality, morbidity (Mean Lesion Score) and bacterial swabs of air sacs at 7 days post-infection. In ovo D-CATH-2 treatment significantly reduced morbidity (63%) and respiratory bacterial load (>90%), while intramuscular treatment was less effective. D-CATH-2 increased the percentage of peripheral blood lymphocytes and heterophils by both administration routes. E. coli specific IgM levels were lower in in ovo treated animals compared to intramuscular D-CATH-2 treatment. In short, in ovo treatment with the Host Defense Peptide derived D-CATH-2 can partially protect chickens from E. coli infection, making this peptide an interesting starting point to develop alternatives to antibiotics for use in the poultry sector. PMID:27229866

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

Kuzma, I.; Siracka-Vesela, E.

Results are reported on the use of the antikinetic agent Marzine (1- diphenylmethyl-4-methylpiperazine) in the treatment of 47 patients, who developed radiation sickness in the course of the radiation treatment for malignant tumors. Marzine was effective in causing total disappearance of the symptoms in 82% of cases or a significant regression of symptoms in 31%. The influence of Marzine was usually noticed after oral application of three 50-mg tablets a day; only a few cases required six tablets a day. A two-day treatment sufficed in some cases for the total disappearance of the symptoms. Most cases, however, required treatment formore » 4 or 5 days, some even longer. During this time the symptoms disappeared or in some cases persisted in a milder form. After withdrawal of Marzine some patients developed symptoms of radiation sickness again and further Marzine treatment led to their disappearance. The patients did not develop habituation to Marzine and no side effects were noted. In only two cases Marzine failed, and in these the symptomatology was due to advanced carcinoma rather than irradiation. The mo st favorable effect was noticed in cases manifesting vomiting and nausea, followed by those with insomnia and vertigo. These were the most unpleasant attendant symptoms and often caused the irradiation schedule to be discontinued. The radiation treatment of patients administered Marzine did not have to be discontinued because of radiation sickness in any case. (BBB)« less

Centralised, decentralised or hybrid sanitation systems? Economic evaluation under urban development uncertainty and phased expansion.

PubMed

Roefs, Ivar; Meulman, Brendo; Vreeburg, Jan H G; Spiller, Marc

2017-02-01

Sanitation systems are built to be robust, that is, they are dimensioned to cope with population growth and other variability that occurs throughout their lifetime. It was recently shown that building sanitation systems in phases is more cost effective than one robust design. This phasing can take place by building small autonomous decentralised units that operate closer to the actual demand. Research has shown that variability and uncertainty in urban development does affect the cost effectiveness of this approach. Previous studies do not, however, consider the entire sanitation system from collection to treatment. The aim of this study is to assess the economic performance of three sanitation systems with different scales and systems characteristics under a variety of urban development pathways. Three systems are studied: (I) a centralised conventional activated sludge treatment, (II) a community on site source separation grey water and black water treatment and (III) a hybrid with grey water treatment at neighbourhood scale and black water treatment off site. A modelling approach is taken that combines a simulation of greenfield urban growth, a model of the wastewater collection and treatment infrastructure design properties and a model that translates design parameters into discounted asset lifetime costs. Monte Carlo simulations are used to evaluate the economic performance under uncertain development trends. Results show that the conventional system outperforms both of the other systems when total discounted lifetime costs are assessed, because it benefits from economies of scale. However, when population growth is lower than expected, the source-separated system is more cost effective, because of reduced idle capacity. The hybrid system is not competitive under any circumstance due to the costly double piping and treatment. Copyright © 2016 Elsevier Ltd. All rights reserved.

Electroconvulsive Therapy: A Primer for Mental Health Counselors.

ERIC Educational Resources Information Center

Leinbaugh, Tracy C.

2001-01-01

Electroconvulsive therapy is the treatment of choice for severe depressive episodes. Although little definitive research exists to explain its effectiveness, since its development in 1938 it has proven effective for the treatment of depression with psychotic features and suicidal ideation. Explains the procedure and discusses implications for the…

Screening, prevention and treatment of cervical cancer -- a global and regional generalized cost-effectiveness analysis.

PubMed

Ginsberg, Gary Michael; Edejer, Tessa Tan-Torres; Lauer, Jeremy A; Sepulveda, Cecilia

2009-10-09

The paper calculates regional generalized cost-effectiveness estimates of screening, prevention, treatment and combined interventions for cervical cancer. Using standardised WHO-CHOICE methodology, a cervical cancer model was employed to provide estimates of screening, vaccination and treatment effectiveness. Intervention effectiveness was determined via a population state-transition model (PopMod) that simulates the evolution of a sub-regional population accounting for births, deaths and disease epidemiology. Economic costs of procedures and treatment were estimated, including programme overhead and training costs. In regions characterized by high income, low mortality and high existing treatment coverage, the addition of any screening programme to the current high treatment levels is very cost-effective. However, based on projections of the future price per dose (representing the economic costs of the vaccination excluding monopolistic rents and vaccine development cost) vaccination is the most cost-effective intervention. In regions characterized by low income, low mortality and existing treatment coverage around 50%, expanding treatment with or without combining it with screening appears to be cost-effective or very cost-effective. Abandoning treatment in favour of screening in a no-treatment scenario would not be cost-effective. Vaccination is usually the most cost-effective intervention. Penta or tri-annual PAP smears appear to be cost-effective, though when combined with HPV-DNA testing they are not cost-effective. In regions characterized by low income, high mortality and low treatment levels, expanding treatment with or without adding screening would be very cost-effective. A one off vaccination plus expanding treatment was usually very cost-effective. One-off PAP or VIA screening at age 40 are more cost-effective than other interventions though less effective overall. From a cost-effectiveness perspective, consideration should be given to implementing vaccination (depending on cost per dose and longevity of efficacy) and screening programmes on a worldwide basis to reduce the burden of disease from cervical cancer. Treatment should also be increased where coverage is low.

Does fertility treatment increase the risk of uterine cancer? A meta-analysis.

PubMed

Saso, Srdjan; Louis, Louay S; Doctor, Farah; Hamed, Ali Hassan; Chatterjee, Jayanta; Yazbek, Joseph; Bora, Shabana; Abdalla, Hossam; Ghaem-Maghami, Sadaf; Thum, Meen-Yau

2015-12-01

An ongoing debate over the last two decades has focused on whether fertility treatment in women may lead to an increased risk of developing uterine cancer over a period of time. Uterine cancer (including mainly endometrial carcinoma and the less common uterine sarcoma) is the commonest reproductive tract cancer and the fourth commonest cancer in women in the UK. Our objective was to assess the association between fertility drugs used in the treatment of female infertility (both as an independent therapy and during in vitro fertilization cycles) and the development of uterine cancer. A literature search was performed using Medline, Embase, Cochrane Library and Google Scholar databases for comparative studies until December 2014 to investigate a clinical significance of fertility treatment on the incidence of developing uterine cancer. General and MESH search headings, as well as the 'related articles' function were applied. All comparative studies of 'fertility treatment' versus 'non-fertility treatment' reporting the incidence of uterine cancer as an outcome were included. Uterine cancer incorporated the following terms: uterine cancer, uterine body tumours, uterine sarcomas and endometrial cancers. The primary outcome of interest was the uterine cancer incidence in all 'fertility treatment' versus 'non-fertility treatment' patient groups. Secondary outcomes of interest were: (a) uterine cancer incidence in 'IVF' versus 'non-IVF' patient groups; and (b) uterine cancer incidence according to type of fertility drug used. Odds ratio was the summary statistic. Random-effects modelling, graphical exploration and sensitivity analysis were used to evaluate the consistency of the calculated treatment effect. We included six studies in our final analysis, which comprised 776,224 patients in total. Of these, 103,758 had undergone fertility treatment and 672,466 had not. There was 100% agreement between the two reviewers regarding the data extraction. All the studies contained groups that were comparable in age, although the criteria of reporting age varied. Taking all studies into account, the incidence of uterine cancer was 0.14% (150 of 103,758) in the fertility treatment group and 2.22% (14,918 of 672,466) in the non-fertility treatment group. Using the random-effect model to analyze uterine cancer incidence, this difference was not found to be of statistical significance: OR 0.78 (95% CI, 0.39-1.57). The degree of heterogeneity was high (I(2)=68%). The risk for the development of uterine and in particular endometrial cancer posed by infertility and an unopposed oestrogen state is widely recognized. The present analysis aimed to perceive whether standard fertility drugs were also a risk to future uterine cancer development. The treatment does increase the concentrations of unopposed oestrogen for a short periods of time but if successful leads to fertility. This meta-analysis points to a non-deleterious effect of fertility drugs towards the development of uterine cancer, a conclusion strongly supported by our sub-group analysis. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

Overview | Office of Cancer Genomics

Cancer.gov

The Therapeutically Applicable Research to Generate Effective Treatments (TARGET) initiative employed comprehensive molecular characterization to determine the genetic changes that drive the initiation and progression of hard-to-treat childhood cancers. TARGET makes the data generated available to the research community with a goal to identify therapeutic targets and prognostic markers so that novel, more effective treatment strategies can be developed and applied. Improved pediatric cancer treatments are needed because:

Development and In Vitro Characterization of a Gemcitabine-loaded MUC4-targeted Immunoliposome Against Pancreatic Ductal Adenocarcinoma.

PubMed

Urey, Carlos; Hilmersson, Katarzyma Said; Andersson, Bodil; Ansari, Daniel; Andersson, Roland

2017-11-01

Pancreatic Ductal adeno-carcinoma (PDAC) is a devastating disease. Gemcitabine is the standard chemotherapeutic agent against PDAC but has only limited effectiveness. The aim of the study was to develop and study the targeting affinity and in vitro antiproliferative effect of a MUC4-targeted gemcitabine-loaded immuno-liposome for treatment of PDAC. Gemcitabine-loaded immunoliposomes were developed by grafting anti-MUC4 antibodies to the liposomal surface. Targeting affinity was compared in vitro between immunoliposomes and non-targeted liposomes and anti-proliferative effect was compared in vitro between free drug, non-targeted liposomal gemcitabine and MUC4-targeted immunoliposomal gemcitabine on a MUC4-positive pancreatic cancer cell line, Capan-1. Development of a MUC4-targeted immunoliposome was confirmed and characterized by immunoblots and size characterization. The MUC4-targeted immunoliposome showed a significantly higher targeting affinity compared to the non-targeted liposomes and also showed an improved antiproliferative effect compared to free and non-targeted liposomal drug. Successful development and characterization of a MUC4-targeted immunoliposome shows promising results for a targeted treatment and improved retention of gemcitabine for treatment of PDAC. Copyright© 2017, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.

Effects of Chronic Central Arginine Vasopressin (AVP) on Maternal Behavior in Chronically Stressed Rat Dams

PubMed Central

Coverdill, Alexander J.; McCarthy, Megan; Bridges, Robert S.; Nephew, Benjamin C.

2012-01-01

Exposure of mothers to chronic stressors during pregnancy or the postpartum period often leads to the development of depression, anxiety, or other related mood disorders. The adverse effects of mood disorders are often mediated through maternal behavior and recent work has identified arginine vasopressin (AVP) as a key neuropeptide hormone in the expression of maternal behavior in both rats and humans. Using an established rodent model that elicits behavioral and physiological responses similar to human mood disorders, this study tested the effectiveness of chronic AVP infusion as a novel treatment for the adverse effects of exposure to chronic social stress during lactation in rats. During early (day 3) and mid (day 10) lactation, AVP treatment significantly decreased the latency to initiate nursing and time spent retrieving pups, and increased pup grooming and total maternal care (sum of pup grooming and nursing). AVP treatment was also effective in decreasing maternal aggression and the average duration of aggressive bouts on day 3 of lactation. Central AVP may be an effective target for the development of treatments for enhancing maternal behavior in individuals exposed to chronic social stress. PMID:24349762

Physiotherapy in the intensive care unit: an evidence-based, expert driven, practical statement and rehabilitation recommendations

PubMed Central

Sommers, Juultje; Engelbert, Raoul HH; Dettling-Ihnenfeldt, Daniela; Gosselink, Rik; Spronk, Peter E; Nollet, Frans; van der Schaaf, Marike

2015-01-01

Objective: To develop evidence-based recommendations for effective and safe diagnostic assessment and intervention strategies for the physiotherapy treatment of patients in intensive care units. Methods: We used the EBRO method, as recommended by the ‘Dutch Evidence Based Guideline Development Platform’ to develop an ‘evidence statement for physiotherapy in the intensive care unit’. This method consists of the identification of clinically relevant questions, followed by a systematic literature search, and summary of the evidence with final recommendations being moderated by feedback from experts. Results: Three relevant clinical domains were identified by experts: criteria to initiate treatment; measures to assess patients; evidence for effectiveness of treatments. In a systematic literature search, 129 relevant studies were identified and assessed for methodological quality and classified according to the level of evidence. The final evidence statement consisted of recommendations on eight absolute and four relative contra-indications to mobilization; a core set of nine specific instruments to assess impairments and activity restrictions; and six passive and four active effective interventions, with advice on (a) physiological measures to observe during treatment (with stopping criteria) and (b) what to record after the treatment. Conclusions: These recommendations form a protocol for treating people in an intensive care unit, based on best available evidence in mid-2014. PMID:25681407

Physiotherapy in the intensive care unit: an evidence-based, expert driven, practical statement and rehabilitation recommendations.

PubMed

Sommers, Juultje; Engelbert, Raoul H H; Dettling-Ihnenfeldt, Daniela; Gosselink, Rik; Spronk, Peter E; Nollet, Frans; van der Schaaf, Marike

2015-11-01

To develop evidence-based recommendations for effective and safe diagnostic assessment and intervention strategies for the physiotherapy treatment of patients in intensive care units. We used the EBRO method, as recommended by the 'Dutch Evidence Based Guideline Development Platform' to develop an 'evidence statement for physiotherapy in the intensive care unit'. This method consists of the identification of clinically relevant questions, followed by a systematic literature search, and summary of the evidence with final recommendations being moderated by feedback from experts. Three relevant clinical domains were identified by experts: criteria to initiate treatment; measures to assess patients; evidence for effectiveness of treatments. In a systematic literature search, 129 relevant studies were identified and assessed for methodological quality and classified according to the level of evidence. The final evidence statement consisted of recommendations on eight absolute and four relative contra-indications to mobilization; a core set of nine specific instruments to assess impairments and activity restrictions; and six passive and four active effective interventions, with advice on (a) physiological measures to observe during treatment (with stopping criteria) and (b) what to record after the treatment. These recommendations form a protocol for treating people in an intensive care unit, based on best available evidence in mid-2014. © The Author(s) 2015.

The Influence of Ghrelin on the Development of Dextran Sodium Sulfate-Induced Colitis in Rats

PubMed Central

Matuszyk, Aleksandra; Ceranowicz, Dagmara; Warzecha, Zygmunt; Ceranowicz, Piotr; Fyderek, Krzysztof; Gałązka, Krystyna; Cieszkowski, Jakub; Bonior, Joanna; Jaworek, Jolanta; Pihut, Małgorzata; Dembiński, Artur

2015-01-01

Ghrelin has protective and therapeutic effects in the gut. The aim of present studies was to investigate the effect of treatment with ghrelin on the development of colitis evoked by dextran sodium sulfate (DSS). Methods. Studies have been performed on rats. Colitis was induced by adding 5% DSS to the drinking water for 5 days. During this period animals were treated intraperitoneally twice a day with saline or ghrelin given at the dose of 8 nmol/kg/dose. On the sixth day, animals were anesthetized and the severity of colitis was assessed. Results. Treatment with ghrelin during administration of DSS reduced the development of colitis. Morphological features of colonic mucosa exhibited a reduction in the area and deep of mucosal damage. Ghrelin reversed the colitis-induced decrease in blood flow, DNA synthesis, and superoxide dismutase activity in colonic mucosa. These effects were accompanied by a decrease in the colitis-evoked increase in mucosal concentration of interleukin-1β and malondialdehyde. Treatment with ghrelin reversed the DSS-induced reduction in body weight gain. Conclusions. Administration of ghrelin exhibits the preventive effect against the development of DSS-induced colitis. This effect seems to be related to ghrelin's anti-inflammatory and antioxidative properties. PMID:26713317

Is testosterone replacement therapy in males with hypogonadism cost-effective? An analysis in Sweden.

PubMed

Arver, Stefan; Luong, Ba; Fraschke, Anina; Ghatnekar, Ola; Stanisic, Sanja; Gultyev, Dmitry; Müller, Elvira

2014-01-01

Testosterone replacement therapy (TRT) has been recommended for the treatment of primary and secondary hypogonadism. However, long-term implications of TRT have not been investigated extensively. The aim of this analysis was to evaluate health outcomes and costs associated with life-long TRT in patients suffering from Klinefelter syndrome and late-onset hypogonadism (LOH). A Markov model was developed to assess cost-effectiveness of testosterone undecanoate (TU) depot injection treatment compared with no treatment. Health outcomes and associated costs were modeled in monthly cycles per patient individually along a lifetime horizon. Modeled health outcomes included development of type 2 diabetes, depression, cardiovascular and cerebrovascular complications, and fractures. Analysis was performed for the Swedish health-care setting from health-care payer's and societal perspective. One-way sensitivity analyses evaluated the robustness of results. The main outcome measures were quality-adjusted life-years (QALYs) and total cost in TU depot injection treatment and no treatment cohorts. In addition, outcomes were also expressed as incremental cost per QALY gained for TU depot injection therapy compared with no treatment (incremental cost-effectiveness ratio [ICER]). TU depot injection compared to no-treatment yielded a gain of 1.67 QALYs at an incremental cost of 28,176 EUR (37,192 USD) in the Klinefelter population. The ICER was 16,884 EUR (22,287 USD) per QALY gained. Outcomes in LOH population estimated benefits of TRT at 19,719 EUR (26,029 USD) per QALY gained. Results showed to be considerably robust when tested in sensitivity analyses. Variation of relative risk to develop type 2 diabetes had the highest impact on long-term outcomes in both patient groups. This analysis suggests that lifelong TU depot injection therapy of patients with hypogonadism is a cost-effective treatment in Sweden. Hence, it can support clinicians in decision making when considering appropriate treatment strategies for patients with testosterone deficiency. © 2013 International Society for Sexual Medicine.

Optimizing spatial and temporal treatments to maintain effective fire and non-fire fuels treatments at landscape scales

Treesearch

J. Greg Jones; Woodam Chung; Carl Seielstad; Janet Sullivan; Kurt Krueger

2010-01-01

There is a recognized need to apply and maintain fuel treatments to reduce catastrophic wildland fires. A number of models and decision support systems have been developed for addressing different aspects of fuel treatments while considering other important resource management issues and constraints. Although these models address diverse aspects of the fuel treatment-...

Concurrent Treatment of Substance Use and PTSD.

PubMed

Flanagan, Julianne C; Korte, Kristina J; Killeen, Therese K; Back, Sudie E

2016-08-01

Substance use disorders (SUD) and posttraumatic stress disorder (PTSD) are chronic, debilitating conditions that frequently co-occur. Individuals with co-occurring SUD and PTSD suffer a more complicated course of treatment and less favorable treatment outcomes compared to individuals with either disorder alone. The development of effective psychosocial and pharmacological interventions for co-occurring SUD and PTSD is an active and critically important area of investigation. Several integrated psychosocial treatments for co-occurring SUD and PTSD have demonstrated promising outcomes. While recent studies examining medications to treat co-occurring SUD and PTSD have yielded encouraging findings, there remain substantial gaps in the evidence base regarding the treatment of co-occurring SUD and PTSD. This review will summarize the findings from clinical trials targeting a reduction in SUD and PTSD symptoms simultaneously. These results may improve our knowledge base and subsequently enhance our ability to develop effective interventions for this complex comorbid condition.

Effects of alpha-tocopherol treatment on newborn rat lung development and injury in hyperoxia.

PubMed

Bucher, J R; Roberts, R J

1982-01-01

The efficacy of alpha-tocopherol treatment to influence the pattern or extent of lung injury resulting during exposure of newborn rats to hyperoxia was assessed following six-day exposures to FIO2 0.21, 0.4, and greater than 0.95. Alpha-Tocopherol treatment was found incapable of preventing the developmental arrest of the lung that occurs during hyperoxic exposure, shown by assessments of wet lung weights, lung DNA, lung volumes, and the progress of secondary septal and capillary development. However alpha-tocopherol treatment was found effective in preventing the hyperoxic-induced lessening of lung compliance and in preventing the deterioration of gas exchange capacity in the lung of the hyperoxic-exposed newborn rat. These findings suggest alpha-tocopherol treatment may not be capable of preventing major alterations in lung morphology in infants with chronic lung disease may be lessened by preserving gas exchange capabilities.

Modification of mitochondrial function, cytoplasmic lipid content and cryosensitivity of bovine embryos by resveratrol.

PubMed

Abe, Takahito; Kawahara-Miki, Ryouka; Hara, Tomotaka; Noguchi, Tatsuo; Hayashi, Takeshi; Shirasuna, Koumei; Kuwayama, Takehito; Iwata, Hisataka

2017-10-18

Resveratrol is a potent activator of NAD-dependent deacetyltransferase sirtuin-1 (SIRT1) and affects lipid metabolism and ATP generation in somatic cells. In the present study, the effects of supplementing culture medium with resveratrol on lipid metabolism, ATP generation, and cryosensitivity of bovine in vitro produced embryos were investigated. Bovine early cleaved-stage embryos were cultured in medium containing 0 or 0.5 µM resveratrol for 1 or 5 days. Resveratrol treatment for both 1 day and 5 days increased the expression levels of SIRT1 and phosphorylated AMP-activated protein kinase (pAMPK) in the embryos. Furthermore, resveratrol treatment was effective to increase ATP generation and reduce lipid content of the embryos. The effects of resveratrol treatment were diminished by the SIRT1 inhibitor "EX527", and the reduced lipid content was reversed by treatment with etomoxir (a potent inhibitor of beta-oxidation). Blastocysts developed after resveratrol treatment showed low levels reactive oxygen species and increased cryotolerance. These results demonstrate that resveratrol improves in vitro development of bovine embryos, while reducing cytoplasmic lipid content through activation of beta-oxidation, thereby effective for production of bovine blastocysts with enhanced cryotolerance.

Test equality in binary data for a 4 × 4 crossover trial under a Latin-square design.

PubMed

Lui, Kung-Jong; Chang, Kuang-Chao

2016-10-15

When there are four or more treatments under comparison, the use of a crossover design with a complete set of treatment-receipt sequences in binary data is of limited use because of too many treatment-receipt sequences. Thus, we may consider use of a 4 × 4 Latin square to reduce the number of treatment-receipt sequences when comparing three experimental treatments with a control treatment. Under a distribution-free random effects logistic regression model, we develop simple procedures for testing non-equality between any of the three experimental treatments and the control treatment in a crossover trial with dichotomous responses. We further derive interval estimators in closed forms for the relative effect between treatments. To evaluate the performance of these test procedures and interval estimators, we employ Monte Carlo simulation. We use the data taken from a crossover trial using a 4 × 4 Latin-square design for studying four-treatments to illustrate the use of test procedures and interval estimators developed here. Copyright © 2016 John Wiley & Sons, Ltd. Copyright © 2016 John Wiley & Sons, Ltd.

Black hairy tongue associated with olanzapine treatment: a case report.

PubMed

Tamam, Lut; Annagur, Bilge Burcak

2006-10-01

Olanzapine is an atypical antipsychotic drug approved for acute and long-term treatment of bipolar disorder. Although relatively safe as compared to other classical antipsychotic medications, there are a number of uncommon adverse effects of olanzapine such as oral cavity lesions. In addition to the relatively common side effect of dry mouth, several articles have reported an association between olanzapine treatment and the development of oral lesions such as apthous stomatitis, pharyngitis, glossitis and oral ulceration. Although there are several cases in which the tongue was affected in conjunction with stomatitis or pharyngitis, we could not find a case report indicating a direct relationship between olanzapine use and a tongue lesion. We present here the case of a patient with bipolar disorder, who developed recurrent black hairy tongue on two different occasions following the addition of olanzapine to lithium treatment. In the present case, xerostomia (dry mouth), which is an adverse reaction of both olanzapine and lithium, may have played a role in the development of black hairy tongue. All agents with a possible side effect of xerostomia may predispose patients to black hairy tongue, especially when they are administered in combination. To preclude the development of this complication with such drugs, extra time and effort should be given to improving oral hygiene.

Bioassimilable sulphur provides effective control of Oidium neolycopersici in tomato, enhancing the plant immune system.

PubMed

Llorens, Eugenio; Agustí-Brisach, Carlos; González-Hernández, Ana I; Troncho, Pilar; Vicedo, Begonya; Yuste, Teresa; Orero, Mayte; Ledó, Carlos; García-Agustín, Pilar; Lapeña, Leonor

2017-05-01

Developments of alternatives to the use of chemical pesticides to control pests are focused on the induction of natural plant defences. The study of new compounds based on liquid bioassimilable sulphur and its effect as an inductor of the immune system of plants would provide an alternative option to farmers to enhance plant resistance against pathogen attacks such as powdery mildew. In order to elucidate the efficacy of this compound in tomato against powdery mildew, we tested several treatments: curative foliar, preventive foliar, preventive in soil drench and combining preventive in soil drench and curative foliar. In all cases, treated plants showed lower infection development, better physiological parameters and a higher level of chlorophyll. We also observed better performance in parameters involved in plant resistance such as antioxidant response, callose deposition and hormonal levels. The results indicate that preventive and curative treatments can be highly effective for the prevention and control of powdery mildew in tomato plants. Foliar treatments are able to stop the pathogen development when they are applied as curative. Soil drench treatments induce immune response mechanisms of plants, increasing significantly callose deposition and promoting plant development. © 2016 Society of Chemical Industry. © 2016 Society of Chemical Industry.

Effects of 17alpha-methyltestosterone on seminal vesicle development and semen release response in the African catfish, Clarias gariepinus.

PubMed

Viveiros, A T; Eding, E H; Komen, J

2001-11-01

The effects of 17alpha-methyltestosterone on seminal vesicle development in the African catfish, Clarias gariepinus, were investigated in an attempt to improve semen collection from this species. Treatment of larvae with dietary 17alpha-methyltestosterone at 50 mg kg(-1) for days 12-33 or days 12-40 after hatching, or at 20 mg kg(-1) for days 12-26, 12-33, 12-40 or 12-47 after hatching inhibited the development of the seminal vesicle finger-like extensions in male catfish, but did not affect the sex ratio. The minimum effective dose and period of treatment to inhibit seminal vesicle development in all male catfish treated with 17alpha-methyltestosterone was 20 mg kg(-1) for days 12-40 after hatching. Male catfish from this treatment group developed normal testes that, in some cases, contained a few oocytes, which tended to disappear before sexual maturation. After sexual maturation, the semen release response was evaluated in males with incomplete seminal vesicles. Fluid with viable spermatozoa was obtained after two consecutive injections of carp pituitary suspension, from 10 of 19 males that had been fed 20 mg 17alpha-methyltestosterone kg(-1) for days 12-40 or days 12-47 after hatching, but from only 4 of 15 males that did not receive any dietary steroid. Intratesticular semen quality was not affected by 17alpha-methyltestosterone treatment. The results of this study demonstrate that the absence of seminal vesicle extensions induced by treatment with 17alpha-methyltestosterone facilitated the collection of semen by stripping from this species of fish.

Treatment effect expressed as the novel Delay of Event measure is associated with high willingness to initiate preventive treatment - A randomized survey experiment comparing effect measures.

PubMed

Berglund, Erik; Westerling, Ragnar; Sundström, Johan; Lytsy, Per

2016-12-01

This study aimed to investigate patients' willingness to initiate a preventive treatment and compared two established effect measures to the newly developed Delay of Events (DoE) measure that expresses treatment effect as a gain in event-free time. In this cross-sectional, randomized survey experiment in the general Swedish population,1079 respondents (response rate 60.9%) were asked to consider a preventive cardiovascular treatment. Respondents were randomly allocated to one of three effect descriptions: DoE, relative risk reduction (RRR), or absolute risk reduction (ARR). Univariate and multivariate analyses were performed investigating willingness to initiate treatment, views on treatment benefit, motivation and importance to adhere and willingness to pay for treatment. Eighty-one percent were willing to take the medication when the effect was described as DoE, 83.0% when it was described as RRR and 62.8% when it was described as ARR. DoE and RRR was further associated with positive views on treatment benefit, motivation, importance to adhere and WTP. Presenting treatment effect as DoE or RRR was associated with a high willingness to initiate treatment. An approach based on the novel time-based measure DoE may be of value in clinical communication and shared decision making. Copyright © 2016 The Authors. Published by Elsevier Ireland Ltd.. All rights reserved.

Effect of x-ray irradiation on the physical and chemical quality of America red globe grape

USDA-ARS?s Scientific Manuscript database

The use of irradiation as a phytosanitary treatment has expanded in recent years. It plays important roles in developed and developing countries, facilitating international trade in irradiated fresh fruit. To evaluate the potential of X-ray irradiation as a quarantine treatment for ‘America Red Glob...

Evidence-Based Pharmacologic Treatment of Pediatric Bipolar Disorder.

PubMed

Findling, Robert L

2016-01-01

Pharmacotherapy is an important component of treatment for children and adolescents with bipolar disorder. The body of evidence supporting safe and effective treatments in this population is growing. Available data provide information on the risks and benefits of pharmacologic agents used for acute manic, mixed, and depressive episodes as well as for maintenance treatment. Lithium, anticonvulsants, and antipsychotics comprise the armamentarium for treating pediatric bipolar disorder. When selecting treatment, clinicians must consider the efficacy and side effect profile of potential pharmacotherapies, as well as the patient's history, including the presence of comorbidities, in order to develop a treatment plan that will ensure optimal outcomes. © Copyright 2016 Physicians Postgraduate Press, Inc.

European Psychiatric Association Guidance on psychotherapy in chronic depression across Europe.

PubMed

Jobst, A; Brakemeier, E-L; Buchheim, A; Caspar, F; Cuijpers, P; Ebmeier, K P; Falkai, P; Jan van der Gaag, R; Gaebel, W; Herpertz, S; Kurimay, T; Sabaß, L; Schnell, K; Schramm, E; Torrent, C; Wasserman, D; Wiersma, J; Padberg, F

2016-03-01

Patients with chronic depression (CD) by definition respond less well to standard forms of psychotherapy and are more likely to be high utilizers of psychiatric resources. Therefore, the aim of this guidance paper is to provide a comprehensive overview of current psychotherapy for CD. The evidence of efficacy is critically reviewed and recommendations for clinical applications and research are given. We performed a systematic literature search to identify studies on psychotherapy in CD, evaluated the retrieved documents and developed evidence tables and recommendations through a consensus process among experts and stakeholders. We developed 5 recommendations which may help providers to select psychotherapeutic treatment options for this patient group. The EPA considers both psychotherapy and pharmacotherapy to be effective in CD and recommends both approaches. The best effect is achieved by combined treatment with psychotherapy and pharmacotherapy, which should therefore be the treatment of choice. The EPA recommends psychotherapy with an interpersonal focus (e.g. the Cognitive Behavioural Analysis System of Psychotherapy [CBASP]) for the treatment of CD and a personalized approach based on the patient's preferences. The DSM-5 nomenclature of persistent depressive disorder (PDD), which includes CD subtypes, has been an important step towards a more differentiated treatment and understanding of these complex affective disorders. Apart from dysthymia, ICD-10 still does not provide a separate entity for a chronic course of depression. The differences between patients with acute episodic depression and those with CD need to be considered in the planning of treatment. Specific psychotherapeutic treatment options are recommended for patients with CD. Patients with chronic forms of depression should be offered tailored psychotherapeutic treatments that address their specific needs and deficits. Combination treatment with psychotherapy and pharmacotherapy is the first-line treatment recommended for CD. More research is needed to develop more effective treatments for CD, especially in the longer term, and to identify which patients benefit from which treatment algorithm. Copyright © 2015 Elsevier Masson SAS. All rights reserved.

Placebo treatment facilitates social trust and approach behavior.

PubMed

Yan, Xinyuan; Yong, Xue; Huang, Wenhao; Ma, Yina

2018-05-29

Placebo effect refers to beneficial changes induced by the use of inert treatment, such as placebo-induced relief of physical pain and attenuation of negative affect. To date, we know little about whether placebo treatment could facilitate social functioning, a crucial aspect for well-being of a social species. In the present study, we develop and validate a paradigm to induce placebo effects on social trust and approach behavior (social placebo effect), and show robust evidence that placebo treatment promotes trust in others and increases preference for a closer interpersonal distance. We further examine placebo effects in real-life social interaction and show that placebo treatment makes single, but not pair-bonded, males keep closer to an attractive first-met female and perceive less social anxiety in the female. Finally, we show evidence that the effects of placebo treatment on social trust and approach behavior can be as strong as the effect of intranasal administration of oxytocin, a neuropeptide known for its function in facilitating social cognition and behavior. The finding of the social placebo effect extends our understanding of placebo effects on improvement of physical, mental, and social well-being and suggests clinical potentials in the treatment of social dysfunction.

Atypical depressive symptoms as a predictor of treatment response to exercise in Major Depressive Disorder.

PubMed

Rethorst, Chad D; Tu, Jian; Carmody, Thomas J; Greer, Tracy L; Trivedi, Madhukar H

2016-08-01

Effective treatment of Major Depressive Disorder (MDD) will require the development of alternative treatments and the ability for clinicians to match patients with the treatment likely to produce the greatest effect. We examined atypical depression subtype as a predictor of treatment response to aerobic exercise augmentation in persons with non-remitted MDD. Our results revealed a small-to-moderate effect, particularly in a group assigned to high-dose exercise (semi-partial eta-squared =0.0335, p=0.0735), indicating that those with atypical depression tended to have larger treatment response to exercise. Through this hypothesis-generating analysis, we indicate the need for research to examine depression subtype, along with other demographic, clinical and biological factors as predictors of treatment response to exercise. Copyright © 2016 Elsevier B.V. All rights reserved.

Innovative pharmaceutical development based on unique properties of nanoscale delivery formulation

PubMed Central

Mozhi, Anbu; Zhang, Xu; Zhao, Yuanyuan; Xue, Xiangdong; Hao, Yanli; Zhang, Xiaoning; Wang, Paul C.; Liang, Xing-Jie

2014-01-01

The advent of nanotechnology has reignited interest in the field of pharmaceutical science for the development of nanomedicine. Nanomedicinal formulations are nanometer-sized carrier materials designed for increasing the drug tissue bioavailability, thereby improving the treatment of systemically applied chemotherapeutic drugs. Nanomedicine is a new approach to deliver the pharmaceuticals through different routes of administration with safer and more effective therapies compared to conventional methods. To date, various kinds of nanomaterials have been developed over the years to make delivery systems more effective for the treatment of various diseases. Even though nanomaterials have significant advantages due to their unique nanoscale properties, there are still significant challenges in the improvement and development of nanoformulations with composites and other materials. Here in this review, we highlight the nanomedicinal formulations aiming to improve the balance between the efficacy and the toxicity of therapeutic interventions through different routes of administration and how to design nanomedicine for safer and more effective ways to improve the treatment quality. We also emphasize the environmental and health prospects of nanomaterials for human health care. PMID:23860639

Innovative pharmaceutical development based on unique properties of nanoscale delivery formulation

NASA Astrophysics Data System (ADS)

Kumar, Anil; Chen, Fei; Mozhi, Anbu; Zhang, Xu; Zhao, Yuanyuan; Xue, Xiangdong; Hao, Yanli; Zhang, Xiaoning; Wang, Paul C.; Liang, Xing-Jie

2013-08-01

The advent of nanotechnology has reignited interest in the field of pharmaceutical science for the development of nanomedicine. Nanomedicinal formulations are nanometer-sized carrier materials designed for increasing the drug tissue bioavailability, thereby improving the treatment of systemically applied chemotherapeutic drugs. Nanomedicine is a new approach to deliver the pharmaceuticals through different routes of administration with safer and more effective therapies compared to conventional methods. To date, various kinds of nanomaterials have been developed over the years to make delivery systems more effective for the treatment of various diseases. Even though nanomaterials have significant advantages due to their unique nanoscale properties, there are still significant challenges in the improvement and development of nanoformulations with composites and other materials. Here in this review, we highlight the nanomedicinal formulations aiming to improve the balance between the efficacy and the toxicity of therapeutic interventions through different routes of administration and how to design nanomedicine for safer and more effective ways to improve the treatment quality. We also emphasize the environmental and health prospects of nanomaterials for human health care.

Biofouling of Water Treatment Membranes: A Review of the Underlying Causes, Monitoring Techniques and Control Measures

PubMed Central

Nguyen, Thang; Roddick, Felicity A.; Fan, Linhua

2012-01-01

Biofouling is a critical issue in membrane water and wastewater treatment as it greatly compromises the efficiency of the treatment processes. It is difficult to control, and significant economic resources have been dedicated to the development of effective biofouling monitoring and control strategies. This paper highlights the underlying causes of membrane biofouling and provides a review on recent developments of potential monitoring and control methods in water and wastewater treatment with the aim of identifying the remaining issues and challenges in this area. PMID:24958430

[Treatment of posterior noninfectious uveitis : Current situation and future developments].

PubMed

Pleyer, U; Pohlmann, D; Stübiger, N

2016-05-01

Treatment of autoimmune diseases has undergone significant changes and developments in recent years. New classes of active substances, in particular biologics and small molecules have resulted in previously unknown success in the treatment of many diseases. In particular patients suffering from autoimmune rheumatic or dermatological diseases have benefited. For autoimmune uveitis there are numerous reports indicating excellent therapeutic and preventive effects; however, statutory approval for therapy in adults is still pending. This article outlines recent advances and future therapeutic options for the treatment of posterior segment noninfectious uveitis.

Development of the Plutonium-DTPA biokinetic model

DOE PAGES

Konzen, Kevin; Brey, Richard

2015-06-01

Estimating radionuclide intakes from bioassays following chelation treatment presents a challenge to the dosimetrist due to the observed excretion enhancement of the particular radionuclide of concern, where no standard biokinetic model exists. This document provides a Pu-DTPA biokinetic model that may be used for making such determination for plutonium intakes. The Pu-DTPA biokinetic model is intended to supplement the standard recommended biokinetic models. The model was used to evaluate several chelation strategies that resulted in providing recommendations for effective treatment. These recommendations supported early treatment for soluble particle inhalations and an initial 3-day treatment series of DTPA treatments for wounds.more » Several late chelation strategies were also compared where reduced treatment frequencies proved to be as effective as multiple treatments. Furthermore, the Pu-DTPA biokinetic model can be used to assist in estimating initial intakes of transuranic radionuclides, and for studying the effects of different treatment strategies.« less

A review of health behaviour theories: how useful are these for developing interventions to promote long-term medication adherence for TB and HIV/AIDS?

PubMed Central

Munro, Salla; Lewin, Simon; Swart, Tanya; Volmink, Jimmy

2007-01-01

Background Suboptimal treatment adherence remains a barrier to the control of many infectious diseases, including tuberculosis and HIV/AIDS, which contribute significantly to the global disease burden. However, few of the many interventions developed to address this issue explicitly draw on theories of health behaviour. Such theories could contribute to the design of more effective interventions to promote treatment adherence and to improving assessments of the transferability of these interventions across different health issues and settings. Methods This paper reviews behaviour change theories applicable to long-term treatment adherence; assesses the evidence for their effectiveness in predicting behaviour change; and examines the implications of these findings for developing strategies to improve TB and HIV/AIDS medication adherence. We searched a number of electronic databases for theories of behaviour change. Eleven theories were examined. Results Little empirical evidence was located on the effectiveness of these theories in promoting adherence. However, several models have the potential to both improve understanding of adherence behaviours and contribute to the design of more effective interventions to promote adherence to TB and HIV/AIDS medication. Conclusion Further research and analysis is needed urgently to determine which models might best improve adherence to long-term treatment regimens. PMID:17561997

ELF (Extremely Low Frequency) Communications System Ecological Monitoring Program: Summary of 1987 Progress

DTIC Science & Technology

1989-04-01

Development . Prenatal developmental stages are especially sensitive to environmental perturbations. At present, there is conflicting evidence of direct EM...effects on embryonic or fetal development . In addition, possible effects of the ELF system on parental behavior could also have an indirect effect on... development . The purpose of this element is to determine the incidence of abnormalities in embryonic development in tree swallows at treatment and control

The expanding cognitive-behavioural therapy treatment umbrella for the anxiety disorders: disorder-specific and transdiagnostic approaches.

PubMed

Rector, Neil A; Man, Vincent; Lerman, Bethany

2014-06-01

Cognitive-behavioural therapy (CBT) is an empirically supported treatment for anxiety disorders. CBT treatments are based on disorder-specific protocols that have been developed to target individual anxiety disorders, despite that anxiety disorders frequently co-occur and are comorbid with depression. Given the high rates of diagnostic comorbidity, substantial overlap in dimensional symptom ratings, and extensive evidence that the mood and anxiety disorders share a common set of psychological and biological vulnerabilities, transdiagnostic CBT protocols have recently been developed to treat the commonalities among the mood and anxiety disorders. We conducted a selective review of empirical developments in the transdiagnostic CBT treatment of anxiety and depression (2008-2013). Preliminary evidence suggests that theoretically based transdiagnostic CBT approaches lead to large treatment effects on the primary anxiety disorder, considerable reduction of diagnostic comorbidity, and some preliminary effects regarding the impact on the putative, shared psychological mechanisms. However, the empirical literature remains tentative owing to relatively small samples, limited direct comparisons with disorder-specific CBT protocols, and the relative absence of the study of disorder-specific compared with shared mechanisms of action in treatment. We conclude with a treatment conceptualization of the new transdiagnostic interventions as complementary, rather than contradictory, to disorder-specific CBT.

[Research and development of portable hypertension therapeutic apparatus based on biofeedback mechanism].

PubMed

Huang, Rong; He, Hongmei; Pi, Xitian; Diao, Ziji; Zhao, Suwen

2014-06-01

Non-drug treatment of hypertension has become a research hotspot, which might overcome the heavy economic burden and side effects of drug treatment for the patients. Because of the good treatment effect and convenient operation, a new treatment based on slow breathing training is increasingly becoming a kind of physical therapy for hypertension. This paper explains the principle of hypertension treatment based on slow breathing training method, and introduces the overall structure of the portable blood pressure controlling instrument, including breathing detection circuit, the core control module, audio module, memory module and man-machine interaction module. We give a brief introduction to the instrument and the software in this paper. The prototype testing results showed that the treatment had a significant effect on controlling the blood pressure.

Effects of manual therapy on treatment duration and motor development in infants with severe nonsynostotic plagiocephaly: a randomised controlled pilot study.

PubMed

Cabrera-Martos, I; Valenza, M C; Valenza-Demet, G; Benítez-Feliponi, A; Robles-Vizcaíno, C; Ruiz-Extremera, A

2016-11-01

Despite growing evidence regarding nonsynostotic plagiocephaly and their repercussions on motor development, there is little evidence to support the use of manual therapy as an adjuvant option. The aim of this study was to evaluate the effects of a therapeutic approach based on manual therapy as an adjuvant option on treatment duration and motor development in infants with severe nonsynostotic plagiocephaly. This is a randomised controlled pilot study. The study was conducted at a university hospital. Forty-six infants with severe nonsynostotic plagiocephaly (types 4-5 of the Argenta scale) referred to the Early Care and Monitoring Unit were randomly allocated to a control group receiving standard treatment (repositioning and an orthotic helmet) or to an experimental group treated with manual therapy added to standard treatment. Infants were discharged when the correction of the asymmetry was optimal taken into account the previous clinical characteristics. The outcome measures were treatment duration and motor development assessed with the Alberta Infant Motor Scale (AIMS) at baseline and at discharge. Asymmetry after the treatment was minimal (type 0 or 1 according to the Argenta scale) in both groups. A comparative analysis showed that treatment duration was significantly shorter (p < 0.001) in the experimental group (109.84 ± 14.45 days) compared to the control group (148.65 ± 11.53 days). The motor behaviour was normal (scores above the 16th percentile of the AIMS) in all the infants after the treatment. Manual therapy added to standard treatment reduces the treatment duration in infants with severe nonsynostotic plagiocephaly.

Developing adaptive interventions for adolescent substance use treatment settings: protocol of an observational, mixed-methods project.

PubMed

Grant, Sean; Agniel, Denis; Almirall, Daniel; Burkhart, Q; Hunter, Sarah B; McCaffrey, Daniel F; Pedersen, Eric R; Ramchand, Rajeev; Griffin, Beth Ann

2017-12-19

Over 1.6 million adolescents in the United States meet criteria for substance use disorders (SUDs). While there are promising treatments for SUDs, adolescents respond to these treatments differentially in part based on the setting in which treatments are delivered. One way to address such individualized response to treatment is through the development of adaptive interventions (AIs): sequences of decision rules for altering treatment based on an individual's needs. This protocol describes a project with the overarching goal of beginning the development of AIs that provide recommendations for altering the setting of an adolescent's substance use treatment. This project has three discrete aims: (1) explore the views of various stakeholders (parents, providers, policymakers, and researchers) on deciding the setting of substance use treatment for an adolescent based on individualized need, (2) generate hypotheses concerning candidate AIs, and (3) compare the relative effectiveness among candidate AIs and non-adaptive interventions commonly used in everyday practice. This project uses a mixed-methods approach. First, we will conduct an iterative stakeholder engagement process, using RAND's ExpertLens online system, to assess the importance of considering specific individual needs and clinical outcomes when deciding the setting for an adolescent's substance use treatment. Second, we will use results from the stakeholder engagement process to analyze an observational longitudinal data set of 15,656 adolescents in substance use treatment, supported by the Substance Abuse and Mental Health Services Administration, using the Global Appraisal of Individual Needs questionnaire. We will utilize methods based on Q-learning regression to generate hypotheses about candidate AIs. Third, we will use robust statistical methods that aim to appropriately handle casemix adjustment on a large number of covariates (marginal structural modeling and inverse probability of treatment weights) to compare the relative effectiveness among candidate AIs and non-adaptive decision rules that are commonly used in everyday practice. This project begins filling a major gap in clinical and research efforts for adolescents in substance use treatment. Findings could be used to inform the further development and revision of influential multi-dimensional assessment and treatment planning tools, or lay the foundation for subsequent experiments to further develop or test AIs for treatment planning.

[Development of performance evaluation and management system on advanced schistosomiasis medical treatment].

PubMed

Zhou, Xiao-Rong; Huang, Shui-Sheng; Gong, Xin-Guo; Cen, Li-Ping; Zhang, Cong; Zhu, Hong; Yang, Jun-Jing; Chen, Li

2012-04-01

To construct a performance evaluation and management system on advanced schistosomiasis medical treatment, and analyze and evaluate the work of the advanced schistosomiasis medical treatment over the years. By applying the database management technique and C++ programming technique, we inputted the information of the advanced schistosomiasis cases into the system, and comprehensively evaluated the work of the advanced schistosomiasis medical treatment through the cost-effect analysis, cost-effectiveness analysis, and cost-benefit analysis. We made a set of software formula about cost-effect analysis, cost-effectiveness analysis, and cost-benefit analysis. This system had many features such as clear building, easy to operate, friendly surface, convenient information input and information search. It could benefit the performance evaluation of the province's advanced schistosomiasis medical treatment work. This system can satisfy the current needs of advanced schistosomiasis medical treatment work and can be easy to be widely used.

Treatment of Sexual Offenders: Research, Best Practices, and Emerging Models

ERIC Educational Resources Information Center

Yates, Pamela M.

2013-01-01

Treatment of sexual offenders has evolved substantially over the years; various theoretical and practice models of treatment been developed, modified, refined, and proposed over time. The predominant current recommended approach, supported by research, adheres to specific principles of effective correctional intervention, follows a…

Do in vitro fertilization treatments result in healthy babies?

PubMed

Kaartinen, Noora; Tinkanen, Helena

In Finland, the proportion of children born as a result of in vitro fertilization treatments is annually approximately 3.3%, and the percentage proportion of the population is growing. Their general somatic health status and cognitive development do not differ from spontaneously fertilized children. In vitro fertilization treatments are, however, associated with a slightly elevated risk of preterm delivery, low birth weight and structural abnormalities. The risk of childhood cancer does not appear to be increased in IVF children. The in vitro fertilization process affects the embryonic epigenome, which organizes itself during early embryonic development. These changes may influence the phenotype and health profile of the unborn child. The effect of in vitro fertilization treatments on an individual's long-term health is poorly understood, requiring prospective follow-up studies with sufficiently large datasets. In vitro fertilization treatments are the most effective way to treat infertility, and the treatments are generally safe both for the future mother and the baby being born.

Maximum mouth opening and trismus in 143 patients treated for oral cancer: a 1-year prospective study.

PubMed

Wetzels, Jan-Willem G H; Merkx, Matthias A W; de Haan, Anton F J; Koole, Ron; Speksnijder, Caroline M

2014-12-01

Patients with oral cancer can develop restricted mouth opening (trismus) because of the oncologic treatment. Maximum mouth opening (MMO) was measured in 143 patients shortly before treatment and 0, 6, and 12 months posttreatment, and the results were analyzed using a linear mixed-effects model. In every patient, MMO decreased after treatment. The patients who underwent surgery, recovered partially by 6 and 12 months after treatment, whereas the patients who received both surgery and radiotherapy or primary radiotherapy did not recover. Tumor location, tumor size, and alcohol consumption had independent effects on MMO. Having trismus (MMO <35 mm) 1 year after treatment was associated most strongly with pretreatment MMO, receiving both surgery and radiotherapy, and maxillary or mandibular tumor involvement. Postoperative radiotherapy and maxillary or mandibular tumor involvement are the highest contributing risk factors to decreasing MMO and the subsequent development of trismus after oral cancer treatment. © 2014 Wiley Periodicals, Inc.

Interventions for Posttraumatic Stress With Children Exposed to Violence: Factors Associated With Treatment Success.

PubMed

Miller-Graff, Laura E; Campion, Karen

2016-03-01

In the past 15 years, there have been a substantial number of rigorous studies examining the effectiveness of various treatments for child trauma and posttraumatic stress disorder (PTSD). Although a number of review articles exist, many have focused on randomized controlled trials or specific treatment methodologies, both of which limit the ability to draw conclusions across studies and the statistical power to test the effect of particular treatment characteristics on treatment outcomes. The current study is a review and meta-analysis of 74 studies examining treatments for children exposed to violence. After reviewing the literature, we examined the relationship of a variety of treatment characteristics (e.g., group or individual treatments) and sample characteristics (e.g., average age) on treatment effect sizes. Results indicated that individual therapies and those with exposure paradigms within a cognitive-behavioral therapy or skills-building framework show the most promise, but treatment is somewhat less effective for those with more severe symptomology and for younger children. Future treatments should consider the developmental and social contexts that may impede treatment progress for young children and consider how best to develop the effectiveness of group interventions that can be readily delivered in settings of mass trauma. © 2015 Wiley Periodicals, Inc.

Cross-fostering: Elucidating the effects of gene×environment interactions on phenotypic development.

PubMed

McCarty, Richard

2017-02-01

Cross-fostering of litters from soon after birth until weaning is a valuable tool to study the ways in which gene×environment interactions program the development of neural, physiological and behavioral characteristics of mammalian species. In laboratory mice and rats, the primary focus of this review, cross-fostering of litters between mothers of different strains or treatment groups (intraspecific) or between mothers of different species (interspecific) has been conducted over the past 9 decades. Areas of particular interest have included maternal effects on emotionality, social preferences, responses to stressful stimulation, nutrition and growth, blood pressure regulation, and epigenetic effects on brain development and behavior. Results from these areas of research highlight the critical role of the postnatal maternal environment in programming the development of offspring phenotypic characteristics. In addition, experimental paradigms that have included cross-fostering have permitted investigators to tease apart prenatal versus postnatal effects of various treatments on offspring development and behavior. Copyright © 2016 Elsevier Ltd. All rights reserved.

Development of the Juvenile Justice Anger Management Treatment for Girls

PubMed Central

Goldstein, Naomi E. S.; Serico, Jennifer M.; Riggs Romaine, Christina L.; Zelechoski, Amanda D.; Kalbeitzer, Rachel; Kemp, Kathleen; Lane, Christy

2016-01-01

Female juvenile offenders exhibit high levels of anger, relational aggression, and physical aggression, but the population has long been ignored in research and practice. No anger management treatments have been developed specifically for this population, and no established anger management treatments are empirically supported for use with delinquent girls. Thus, to alleviate anger and reduce the frequency and severity of aggressive behaviors in this underserved population, we developed the gender-specific, Juvenile Justice Anger Management (JJAM) Treatment for Girls. This cognitive-behavioral intervention was adapted from the Coping Power Program (Lochman & Wells, 2002), a school-based anger management treatment for younger children that has established efficacy and effectiveness findings with its target populations. This paper describes how the content of JJAM was developed to meet the unique needs of adolescent girls in residential juvenile justice placements. It also traces the process of developing a manualized treatment and the steps taken to enhance efficacy and clinical utility. An overview of the treatment, a session-by-session outline, an example session activity, and an example homework assignment are provided. A randomized controlled trial is currently being conducted to evaluate the efficacy of the JJAM Treatment for Girls. PMID:27642247

Effectiveness and cost-effectiveness of salicylic acid and cryotherapy for cutaneous warts. An economic decision model.

PubMed

Thomas, K S; Keogh-Brown, M R; Chalmers, J R; Fordham, R J; Holland, R C; Armstrong, S J; Bachmann, M O; Howe, A H; Rodgers, S; Avery, A J; Harvey, I; Williams, H C

2006-08-01

To estimate the costs of commonly used treatments for cutaneous warts, as well as their health benefits and risk. To create an economic decision model to evaluate the cost-effectiveness of these treatments, and, as a result, assess whether a randomised controlled trial (RCT) would be feasible and cost-effective. Focus groups, structured interviews and observation of practice. Postal survey sent to 723 patients. A recently updated Cochrane systematic review and published cost and prescribing data. Primary and secondary data collection methods were used to inform the development of an economic decision model. Data from the postal survey provided estimates of the effectiveness of wart treatments in a primary care setting. These estimates were compared with outcomes reported in the Cochrane review of wart treatment, which were largely obtained from RCTs conducted in secondary care. A decision model was developed including a variety of over-the-counter (OTC) and GP-prescribed treatments. The model simulated 10,000 patients and adopted a societal perspective. OTC treatments were used by a substantial number of patients (57%) before attending the GP surgery. By far the most commonly used OTC preparation was salicylic acid (SA). The results of the economic model suggested that of the treatments prescribed by a GP, the most cost-effective treatment was SA, with an incremental cost-effectiveness ratio (ICER) of 2.20 pound/% cured. The ICERs for cryotherapy varied widely (from 1.95 to 7.06 pound/% cured) depending on the frequency of applications and the mode of delivery. The most cost-effective mode of delivery was through nurse-led cryotherapy clinics (ICER = 1.95 pound/% cured) and this could be a cost-effective alternative to GP-prescribed SA. Overall, the OTC therapies were the most cost-effective treatment options. ICERs ranged from 0.22 pound/% cured for OTC duct tape and 0.76 pound/% cured for OTC cryotherapy to 1.12 pound/% cured for OTC SA. However, evidence in support of OTC duct tape and OTC cryotherapy is very limited. Side-effects were commonly reported for both SA and cryotherapy, particularly a burning sensation, pain and blistering. Cryotherapy delivered by a doctor is an expensive option for the treatment of warts in primary care. Alternative options such as GP-prescribed SA and nurse-led cryotherapy clinics provide more cost-effective alternatives, but are still expensive compared with self-treatment. Given the minor nature of most cutaneous warts, coupled with the fact that the majority spontaneously resolve in time, it may be concluded that a shift towards self-treatment is warranted. Although both duct tape and OTC cryotherapy appear promising new self-treatment options from both a cost and an effectiveness perspective, more research is required to confirm the efficacy of these two methods of wart treatment. If these treatments are shown to be as cost-effective as or more cost-effective than conventional treatments, then a shift in service delivery away from primary care towards more OTC treatment is likely. A public awareness campaign would be useful to educate patients about the self-limiting nature of warts and the possible alternative OTC treatment options available. Two future RCTs are recommended for consideration: a trial of SA compared with nurse-led cryotherapy in primary care, and a trial of home treatments. Greater understanding of the efficacy of these home treatments will give doctors a wider choice of treatment options, and may help to reduce the overall demand for cryotherapy in primary care.

The development of evidence-based guidelines in dentistry.

PubMed

Faggion, C M

2013-02-01

Use of guidelines is an important means of reducing the gap between research and clinical practice. Sound and unbiased information should be available to enable dental professionals to provide better clinical treatment for their patients. The development of clinical guidelines in dentistry should follow standard and transparent methodology. The purpose of this article is to propose important steps for developing evidence-based clinical recommendations in dentistry. Initially, dental guidelines should be extensively sought and assessed to answer focused clinical questions. If there is a paucity of guidelines or if existing guidelines are not of good methodological quality, systematic reviews should be searched or conducted to serve as a basis for the development of evidence-based guidelines. When systematic reviews are produced, they should be rigorous in order to provide the best evidence possible. In the last phase of the process, the overall quality of evidence should be scrutinized and assessed, together with other factors (balance between treatment effects and side effects, patients' values, and cost-effectiveness of therapy) to determine the strength of recommendations. It is expected this approach will result in the development of sound clinical guidelines and consequent improvement of dental treatment.

Overcoming barriers to nicotine dependence treatment.

PubMed

Ferry, L H

1999-09-01

Tobacco dependence is the most overlooked and undertreated preventable cause of chronic disease in the developed world. Three barriers to effective treatment must be overcome: the reluctance of nicotine addicts to seek help; inadequate training of health professionals to treat hard core smokers; and a health care system that does not acknowledge the need for professional treatment of nicotine addiction. Effective physicians are equipped with the knowledge and skills to identify high-risk smokers who need more assistance to quit. All smokers should be engaged in a tailored office intervention based on their needs. Adoption of simple clinical protocols can eliminate the barriers that prevent effective counseling and treatment in the office setting.

Emerging drugs for the treatment of obesity.

PubMed

Martinussen, Christoffer; Bojsen-Moller, Kirstine Nyvold; Svane, Maria Saur; Dejgaard, Thomas Fremming; Madsbad, Sten

2017-03-01

The increasing prevalence of obesity represents a huge threat to public health and the current pharmacological treatment options are limited. Bariatric surgery is by far the most effective treatment for severe obesity, highlighting the urgent need for new and improved drug therapies. Areas covered: Based on the physiological regulation of energy homeostasis, pharmacological strategies to treat obesity are evaluated with focus on drugs in phase 2 and 3 clinical development. The potential impact of these drugs on current treatment standards and the barriers for development are discussed and set in a historical perspective of previous antiobesity medications. Expert opinion: The radical effects of bariatric surgery have extended our understanding of the mechanisms controlling appetite and boosted the search for new drug targets in obesity treatment. Accordingly, several compounds targeting the central nervous system and/or periphery are in pipeline for obesity. These drugs should be evaluated over a wide array of end-points; in particular, long-term safety monitoring is necessary as serious adverse events may appear. Combination therapy targeting more than one pathway controlling energy balance might be necessary to achieve substantial weight loss while minimising side effects.

Development and characterization of targeted poly(NIPAm) nanoparticles for delivery of anti-inflammatory peptides in peripheral artery disease and osteoarthritis

NASA Astrophysics Data System (ADS)

McMasters, James F.

Inflammation is the underlying cause of several severe diseases including cardiovascular disease and osteoarthritis. Peripheral artery disease (PAD) is characterized by atherosclerotic occlusions within the peripheral vasculature. Current treatment for severe PAD involves mechanical widening of the artery via percutaneous transluminal angioplasty. Unfortunately, deployment of the balloon damages the endothelial layer, exposing the underlying collagenous matrix. Circulating platelets can bind to this collagen and become activated, releasing proinflammatory cytokines that promote proliferation of local smooth muscle cells. These proliferating cells eventually reocclude the vessel, resulting in restenosis and necessitating the need for a second procedure to reopen the vessel. Current treatments for moderate osteoarthritis include local injection of anti-inflammatory compounds such as glucocorticoids. Unfortunately, prolonged treatment carries with it significant side effects including osteoporosis, and cardiovascular complications. Our lab has developed an anti-inflammatory cell-penetrating peptide that inhibits mitogen-activated protein kinase activated protein kinase 2 (MK2). MK2 is implicated in the inflammatory cascade of atherosclerosis and osteoarthritis, making it a potentially effective strategy for reducing inflammation in both disease states. Unfortunately, these peptides are untargeted and quickly degraded in the presence of serum proteases, making the development of an effective delivery system of paramount importance. The overall goal of the research presented here is to detail the development of a poly(N-isopropylacrylamide) nanoparticle that is able to effectively load and release anti-inflammatory peptides for the treatment of these inflammatory diseases. In this dissertation, I will discuss the development of a collagen-binding nanoparticle that is able to inhibit platelet binding following angioplasty, thereby halting the initial inflammatory cascade. Additionally, these particles demonstrate the ability to reduce inflammation by through the loading and release of MK2-inhibiting cell-penetrating peptides. Additionally, I will cover the development of a hollow nanoparticle system that is designed to load increased quantities of these anti-inflammatory peptides for the treatment of osteoarthritis. This particle demonstrated increased macrophage uptake and prolonged drug release, resulting in a progressive inhibition of osteoarthritic inflammation over 8 days. The results presented here advance our understanding of these nanoparticle platforms, and suggest that they may serve at effective platforms for the treatment of restenosis following angioplasty, as well as osteoarthritis.

Experimental and clinical evidence for loss of effect (tolerance) during prolonged treatment with antiepileptic drugs.

PubMed

Löscher, Wolfgang; Schmidt, Dieter

2006-08-01

Development of tolerance (i.e., the reduction in response to a drug after repeated administration) is an adaptive response of the body to prolonged exposure to the drug, and tolerance to antiepileptic drugs (AEDs) is no exception. Tolerance develops to some drug effects much more rapidly than to others. The extent of tolerance depends on the drug and individual (genetic?) factors. Tolerance may lead to attenuation of side effects but also to loss of efficacy of AEDs and is reversible after discontinuation of drug treatment. Different experimental approaches are used to study tolerance in laboratory animals. Development of tolerance depends on the experimental model, drug, drug dosage, and duration of treatment, so that a battery of experimental protocols is needed to evaluate fully whether tolerance to effect occurs. Two major types of tolerance are known. Pharmacokinetic (metabolic) tolerance, due to induction of AED-metabolizing enzymes has been shown for most first-generation AEDs, and is easy to overcome by increasing dosage. Pharmacodynamic (functional) tolerance is due to "adaptation" of AED targets (e.g., by loss of receptor sensitivity) and has been shown experimentally for all AEDs that lose activity during prolonged treatment. Functional tolerance may lead to complete loss of AED activity and cross-tolerance to other AEDs. Convincing experimental evidence indicates that almost all first-, second-, and third-generation AEDs lose their antiepileptic activity during prolonged treatment, although to a different extent. Because of diverse confounding factors, detecting tolerance in patients with epilepsy is more difficult but can be done with careful assessment of decline during long-term individual patient response. After excluding confounding factors, tolerance to antiepileptic effect for most modern and old AEDs can be shown in small subgroups of responders by assessing individual or group response. Development of tolerance to the antiepileptic activity of an AED may be an important reason for failure of drug treatment. Knowledge of tolerance to AED effects as a mechanism of drug resistance in previous responders is important for patients, physicians, and scientists.

A Bayesian adaptive design for biomarker trials with linked treatments.

PubMed

Wason, James M S; Abraham, Jean E; Baird, Richard D; Gournaris, Ioannis; Vallier, Anne-Laure; Brenton, James D; Earl, Helena M; Mander, Adrian P

2015-09-01

Response to treatments is highly heterogeneous in cancer. Increased availability of biomarkers and targeted treatments has led to the need for trial designs that efficiently test new treatments in biomarker-stratified patient subgroups. We propose a novel Bayesian adaptive randomisation (BAR) design for use in multi-arm phase II trials where biomarkers exist that are potentially predictive of a linked treatment's effect. The design is motivated in part by two phase II trials that are currently in development. The design starts by randomising patients to the control treatment or to experimental treatments that the biomarker profile suggests should be active. At interim analyses, data from treated patients are used to update the allocation probabilities. If the linked treatments are effective, the allocation remains high; if ineffective, the allocation changes over the course of the trial to unlinked treatments that are more effective. Our proposed design has high power to detect treatment effects if the pairings of treatment with biomarker are correct, but also performs well when alternative pairings are true. The design is consistently more powerful than parallel-groups stratified trials. This BAR design is a powerful approach to use when there are pairings of biomarkers with treatments available for testing simultaneously.

Development of a patient decision aid for people with refractory angina: protocol for a three-phase pilot study

PubMed Central

2014-01-01

Background Refractory angina is a severe chronic disease, defined as angina which cannot be controlled by usual treatments for heart disease. This disease is frightening, debilitating, and difficult to manage. Many people suffering refractory have inadequate pain relief, continually revisit emergency departments for help, undergo repeated cardiac investigations, and struggle with obtaining appropriate care. There is no clear framework to help people understand the risks and benefits of available treatment options in Canada. Some treatments for refractory angina are invasive, while others are not covered by provincial health insurance plans. Effective care for refractory angina sufferers in Canada is critically underdeveloped; it is important that healthcare professionals and refractory angina sufferers alike understand the treatment options and their implications. This proposal builds on the recent Canadian practice guidelines for the management of refractory angina. We propose to develop a decision support tool in order to help people suffering from refractory angina make well-informed decisions about their healthcare and reduce their uncertainty about treatment options. Methods This project will be conducted in three phases: a) development of the support tool with input from clinical experts, the Canadian refractory angina guidelines, and people living with refractory angina, b) pilot testing of the usability of the tool, and c) formal preliminary evaluation of the effectiveness of the support tool to help people make informed decisions about treatment options. Discussion A decision support tool for refractory angina is needed and the available data suggest that by developing such a tool, we may be able to help refractory angina sufferers better understand their condition and the effectiveness of available treatment options (in their respective clinical settings) as well as their implications (e.g. risks vs. benefits). By virtue of this tool, we may also be able to facilitate identification and inclusion of patients’ values and preferences in the decision making process. This is particularly important as refractory angina is an intractable condition, necessitating that the selected course of treatment be lifelong. This study will yield a much needed patient decision aid for people living with refractory angina and pilot data to support a subsequent effectiveness study. PMID:24920518

Estimation of treatment effect in a subpopulation: An empirical Bayes approach.

PubMed

Shen, Changyu; Li, Xiaochun; Jeong, Jaesik

2016-01-01

It is well recognized that the benefit of a medical intervention may not be distributed evenly in the target population due to patient heterogeneity, and conclusions based on conventional randomized clinical trials may not apply to every person. Given the increasing cost of randomized trials and difficulties in recruiting patients, there is a strong need to develop analytical approaches to estimate treatment effect in subpopulations. In particular, due to limited sample size for subpopulations and the need for multiple comparisons, standard analysis tends to yield wide confidence intervals of the treatment effect that are often noninformative. We propose an empirical Bayes approach to combine both information embedded in a target subpopulation and information from other subjects to construct confidence intervals of the treatment effect. The method is appealing in its simplicity and tangibility in characterizing the uncertainty about the true treatment effect. Simulation studies and a real data analysis are presented.

Probiotics and Atopic Dermatitis: An Overview.

PubMed

Rather, Irfan A; Bajpai, Vivek K; Kumar, Sanjay; Lim, Jeongheui; Paek, Woon K; Park, Yong-Ha

2016-01-01

Atopic dermatitis (AD) is a common, recurrent, chronic inflammatory skin disease that is a cause of considerable economic and social burden. Its prevalence varies substantially among different countries with an incidence rate proclaimed to reach up to 20% of children in developed countries and continues to escalate in developing nations. This increased rate of incidence has changed the focus of research on AD toward epidemiology, prevention, and treatment. The effects of probiotics in the prevention and treatment of AD remain elusive. However, evidence from different research groups show that probiotics could have positive effect on AD treatment, if any, that depend on multiple factors, such as specific probiotic strains, time of administration (onset time), duration of exposure, and dosage. However, till date we still lack strong evidence to advocate the use of probiotics in the treatment of AD, and questions remain to be answered considering its clinical use in future. Based on updated information, the processes that facilitate the development of AD and the topic of the administration of probiotics are addressed in this review.

Advances in Therapeutic Development for Radiation Cystitis.

PubMed

Rajaganapathy, Bharathi Raja; Jayabalan, Nirmal; Tyagi, Pradeep; Kaufman, Jonathan; Chancellor, Michael B

2014-01-01

Radiation treatment for pelvic malignancies is typically associated with radiation injury to urinary bladder that can ultimately lead to radiation cystitis (RC). The late sequelae of radiation therapy may take many years to develop and include bothersome storage symptoms such as hematuria, which may be life-threatening in severe cases of hemorrhagic cystitis. Although no definitive treatment is currently available, various interventions are used for radiation and hemorrhagic cystitis including blood transfusion, bladder irrigation, intravesical instillation of substances such as alum, silver nitrate, prostaglandins or formalin, and fulguration of intravesical bleeding sites and surgery options such as supravesical urinary diversions and cystectomy. Effects of non-surgical treatments for radiation and hemorrhagic cystitis are of modest success and studies are lacking to control the effects caused by RC. When such measures have proven ineffective, use of bladder botulinum toxin injection has been reported. New therapy, such as intravesical immunosuppression with local tacrolimus formulation is being developed for the treatment of radiation hemorrhagic cystitis. © 2013 Wiley Publishing Asia Pty Ltd.

Ipilimumab associated colitis: an IpiColitis case series at MedStar Georgetown University Hospital.

PubMed

Rastogi, Pawan; Sultan, Mohamed; Charabaty, Aline J; Atkins, Michael B; Mattar, Mark C

2015-04-14

Although ipilimumab has been shown to improve survival in patients with metastatic melanoma and cause regression of metastatic renal cell carcinoma, the associated immune-related toxicities are of concern. The resultant T cell activation by this monoclonal antibody causes an increased immune response, which has been associated with many immune-regulated adverse effects. One of the most concerning effects is the development of colitis. Upwards to 8% of patients have been reported to develop colitis, with 5% being severe (Grades 3-4). While initial treatment of such adverse effects is generally comprised of supportive and symptomatic treatment, more severe cases warrant the use of high dose steroids. Furthermore, use of anti-TNF agents is usually reserved for those cases that prove to be refractory to steroids. We describe a systematic case review of seven patients who developed gastrointestinal symptoms following initiation of ipilimumab immunotherapy, and present the steps in their evaluation, treatment and outcomes at our institution.

Evaluations and Comparisons of Treatment Effects Based on Best Combinations of Biomarkers with Applications to Biomedical Studies

PubMed Central

Chen, Xiwei; Yu, Jihnhee

2014-01-01

Abstract Many clinical and biomedical studies evaluate treatment effects based on multiple biomarkers that commonly consist of pre- and post-treatment measurements. Some biomarkers can show significant positive treatment effects, while other biomarkers can reflect no effects or even negative effects of the treatments, giving rise to a necessity to develop methodologies that may correctly and efficiently evaluate the treatment effects based on multiple biomarkers as a whole. In the setting of pre- and post-treatment measurements of multiple biomarkers, we propose to apply a receiver operating characteristic (ROC) curve methodology based on the best combination of biomarkers maximizing the area under the receiver operating characteristic curve (AUC)-type criterion among all possible linear combinations. In the particular case with independent pre- and post-treatment measurements, we show that the proposed method represents the well-known Su and Liu's (1993) result. Further, proceeding from derived best combinations of biomarkers' measurements, we propose an efficient technique via likelihood ratio tests to compare treatment effects. We show an extensive Monte Carlo study that confirms the superiority of the proposed test in comparison with treatment effects based on multiple biomarkers in a paired data setting. For practical applications, the proposed method is illustrated with a randomized trial of chlorhexidine gluconate on oral bacterial pathogens in mechanically ventilated patients as well as a treatment study for children with attention deficit-hyperactivity disorder and severe mood dysregulation. PMID:25019920

Potential of Nanotechnology based water treatment solutions for the improvement of drinking water supplies in developing countries

NASA Astrophysics Data System (ADS)

Dutta, Joydeep; Bhattacharya, Prosun; Bundschuh, Jochen

2016-04-01

Over the last decades explosive population growth in the world has led to water scarcity across the globe putting additional pressure already scarce ground water resources and is pushing scientists and researchers to come up with new alternatives to monitor and treat water for use by mankind and for food security. Nearly 4 billion people around the world are known to lack access to clean water supply. Systematic water quality data is important for the assessment of health risks as well as for developing appropriate and affordable technologies for waste and drinking water treatments, and long-term decision making policy against water quality management. Traditional water treatment technologies are generally chemical-intensive processes requiring extremely large infrastructural support thus limiting their effective applications in developing nations which creates an artificial barrier to the application of technological solutions for the provision of clean water. Nanotechnology-based systems are in retrospect, smaller, energy and resource efficient. Economic impact assessment of the implementation of nanotechnology in water treatment and studies on cost-effectiveness and environmental and social impacts is of key importance prior to its wide spread acceptance. Government agencies and inter-governmental bodies driving research and development activities need to measure the effective potential of nanotechnology as a solution to global water challenges in order to effectively engage in fiscal, economic and social issues at national and international levels for different types of source waters with new national and international initiatives on nanotechnology and water need to be launched. Environmental pollution and industrialization in global scale is further leading to pollution of available water sources and thus hygienically friendly purification technologies are the need of the hour. Thus cost-effective treatment of pollutants for the transformation of hazardous substances into benign forms that can potentially be addressed through Nanotechnology based filters utilizing photocatalytic or electrocatalytic systems could be further explored. Development of these techniques together with other superadsorbants would make it possible to install delocalized systems with very little capital investment and operation and maintenance costs suitable for installation in less developed countries.

Long-term safety and efficacy of stereotactic radiosurgery for vestibular schwannomas: evaluation of 440 patients more than 10 years after treatment with Gamma Knife surgery.

PubMed

Hasegawa, Toshinori; Kida, Yoshihisa; Kato, Takenori; Iizuka, Hiroshi; Kuramitsu, Shunichiro; Yamamoto, Takashi

2013-03-01

Object Little is known about long-term outcomes, including tumor control and adverse radiation effects, in patients harboring vestibular schwannomas (VSs) treated with stereotactic radiosurgery > 10 years previously. The aim of this study was to confirm whether Gamma Knife surgery (GKS) for VSs continues to be safe and effective > 10 years after treatment. Methods A total of 440 patients with VS (including neurofibromatosis Type 2) treated with GKS between May 1991 and December 2000 were evaluable. Of these, 347 patients (79%) underwent GKS as an initial treatment and 93 (21%) had undergone prior resection. Three hundred fifty-eight patients (81%) had a solid tumor and 82 (19%) had a cystic tumor. The median tumor volume was 2.8 cm(3) and the median marginal dose was 12.8 Gy. Results The median follow-up period was 12.5 years. The actuarial 5- and ≥ 10-year progression-free survival was 93% and 92%, respectively. No patient developed treatment failure > 10 years after treatment. According to multivariate analysis, significant factors related to worse progression-free survival included brainstem compression with a deviation of the fourth ventricle (p < 0.0001), marginal dose ≤ 13 Gy (p = 0.01), prior treatment (p = 0.02), and female sex (p = 0.02). Of 287 patients treated at a recent optimum dose of ≤ 13 Gy, 3 (1%) developed facial palsy, including 2 with transient palsy and 1 with persistent palsy after a second GKS, and 3 (1%) developed facial numbness, including 2 with transient and 1 with persistent facial numbness. The actuarial 10-year facial nerve preservation rate was 97% in the high marginal dose group (> 13 Gy) and 100% in the low marginal dose group (≤ 13 Gy). Ten patients (2.3%) developed delayed cyst formation. One patient alone developed malignant transformation, indicating an incidence of 0.3%. Conclusions In this study GKS was a safe and effective treatment for the majority of patients followed > 10 years after treatment. Special attention should be paid to cyst formation and malignant transformation as late adverse radiation effects, although they appeared to be rare. However, it is necessary to collect further long-term follow-up data before making conclusions about the long-term safety and efficacy of GKS, especially for young patients with VSs.

Effectiveness of brief VR treatment for PTSD in war-fighters: a case study.

PubMed

Miyahira, Sarah D; Folen, Raymond A; Hoffman, Hunter G; Garcia-Palacios, Azucena; Schaper, Kim M

2010-01-01

War-fighters exposed to combat are at high risk for developing posttraumatic stress disorder (PTSD), a complex and challenging condition to treat. Cognitive behavioral therapies (CBT) have been empirically validated as effective treatments for PTSD resulting from sexual assault, vehicular accidents, and disasters. Exposure, imaginal or in vivo, to the traumatic event is a central component of successful CBT treatment. Early studies indicate that CBT with brief virtual reality exposure (VRE) is beneficial in treating PTSD. The case study examined the effectiveness of brief VRE in treating combat-related PTSD.

Methodological Controversies in the Treatment of Panic Disorder.

ERIC Educational Resources Information Center

McNally, Richard J.

1996-01-01

Although the National Institutes of Health Consensus Development Conference on the Treatment of Panic Disorder endorsed the effectiveness of cognitive-behavior therapy (CBT), D. F. Klein argues that fatal flaws in all but one CBT study undermine claims about the effectiveness of CBT for panic disorder. This article critiques Klein's arguments and…

The role of neuropsychology in UK pediatric HIV care: Relevance to clinical practice and research.

PubMed

Freeman, Anita

2017-11-01

There has been a dramatic improvement in the survival of children with perinatally-acquired HIV (PHIV) following the introduction of effective treatment in 1990s. The care for children living with PHIV is now focused on more accurately understanding the effects of both HIV and HIV treatment on the developing body and brain. An evaluation of current HIV neuroimaging, and neurocognitive research, when combined with clinical experience in the area of HIV, could help to inform United Kingdom (UK) PHIV service provision. This paper argues that an understanding from a neuropsychological perspective will help these young people to optimize their health, quality of life, and future functioning. The aim of the paper is to bring together research and clinical understanding of HIV and its treatment effects on the developing brain, together with an understanding of other potential neurological risk factors. It is argued here that there is a need for targeted neuropsychology assessment and preventative interventions, supported by clinical and preliminary research on the neurocognitive effects of HIV and its treatments.

[Prospective study of ketogenic diet in treatment of children with global developmental delay].

PubMed

Zhu, Deng-Na; Li, Ping; Wang, Jun; Yuan, Jun-Ying; Zhang, Guang-Yu; Liang, Jiang-Fang; Wang, Ming-Mei; Zhao, Yun-Xia; An, Shuang; Ma, Na; Ma, Dan-Dan

2017-10-01

To study the effect of ketogenic diet (KD) on neurobehavioral development, emotional and social behaviors, and life ability in children with global developmental delay (GDD). A prospective case-control study was performed for hospitalized children with GDD, who were randomly divided into KD treatment group (n=40) and conventional treatment group (n=37). The children in both groups were given comprehensive rehabilitation training, and those in the KD treatment group were given modified Atkins diet in addition to the comprehensive rehabilitation training. The children in both groups were assessed with the Gesell Developmental Scale, Chinese version of Urban Infant-Toddler Social and Emotional Assessment (CITSEA)/Achenbach Child Behavior Checklist (CBCL), and Infants-Junior High School Students' Social Life Abilities Scale (S-M scale) before treatment and after 3, 6, and 9 months of treatment. The two groups were compared in terms of the improvements in neurobehavioral development, emotional and social behaviors, and social life ability. After 3, 6, and 9 months of treatment, the KD treatment group had significantly greater improvements in the scores of the adaptive, fine motor, and language quotients of the Gesell Developmental Scale compared with the conventional treatment group (P<0.05); the KD treatment group had significantly greater improvements in CITSEA/CBCL scores than the conventional treatment group (P<0.05). The KD treatment group had a greater improvement in the score of the S-M scale after 9 months of treatment (P<0.05). During the KD treatment, 6 children experienced diarrhea and 1 experienced mild urinary stones. KD can improve the neurobehavioral development and behavioral and emotional behaviors in children with GDD, and it has few adverse effects.

Treatment of uveal melanoma: where are we now?

PubMed Central

Yang, Jessica; Manson, Daniel K.; Marr, Brian P.; Carvajal, Richard D.

2018-01-01

Uveal melanoma, a rare subset of melanoma, is the most common primary intraocular malignancy in adults. Despite effective primary therapy, nearly 50% of patients will develop metastatic disease. Outcomes for those with metastatic disease remain dismal due to a lack of effective therapies. The unique biology and immunology of uveal melanoma necessitates the development of dedicated management and treatment approaches. Ongoing efforts seek to optimize the efficacy of targeted therapy and immunotherapy in both the adjuvant and metastatic setting. This review provides a comprehensive, updated overview of disease biology and risk stratification, the management of primary disease, options for adjuvant therapy, and the current status of treatment strategies for metastatic disease. PMID:29497459

Development and evaluation of a behavioral pain management treatment program in a Veterans Affairs Medical Center.

PubMed

Stratton, Kelcey J; Bender, Mark C; Cameron, Jennifer J; Pickett, Treven C

2015-03-01

Chronic pain complaints are highly prevalent among Veterans seeking Veterans Affairs health care, and the implementation of effective behavioral health interventions is vital to meet patient needs. Research supports the use of cognitive behavioral therapy for the treatment of chronic pain; however, varying guidelines regarding length of treatment and modality (i.e., group vs. individual) complicate clinical planning and program development. This study aimed to evaluate treatment outcomes and equivalence of 3 variations (12, 10, and 6 weeks of group treatment) of cognitive behavioral therapy for chronic pain using clinical program data collected from Veterans enrolled in Veterans Affairs health services in a large tertiary care setting. Across groups, Veterans showed improvements in negative pain-related thinking and decreases in pain-related disability and distress. In general, patient outcomes regarding pain-related distress and disability for the 6-week group were equivalent or better than the 12- and 10-week groups. Preliminary results support the effectiveness of brief behavioral interventions for chronic pain. The findings have important practical implications, as briefer treatments may offer comparable therapeutic impact as longer, more time-intensive treatment protocols. This study offers a unique examination of treatment development and evaluation processes informed by real-world clinical needs and patient feedback. Reprint & Copyright © 2015 Association of Military Surgeons of the U.S.

An evaluation of substance misuse treatment providers used by an employee assistance program.

PubMed

Miller, N A

1992-05-01

Structural measures of access, continuity, and quality of substance misuse treatment services were compared in 30 fee-for-service (FFS) facilities and nine health maintenance organizations (HMOs). Probit models related effects of the provider system (FFS or HMO) and the system's structural characteristics to 243 employees' access to and outcomes from treatment. Access was decreased in Independent Practice Association (IPA)/network HMOs and in all facilities which did not employ an addictionologist or provide coordinated treatment services. When bivariate correlations were examined, both use of copayments and imposing limits to the levels of treatment covered were negatively related to access, while a facility's provision of ongoing professional development was positively associated with access. These correlations did not remain significant in the multivariate probits. Receiving treatment in a staff model HMO and facing limits to the levels of treatment covered were negatively associated with attaining sufficient progress, while receiving treatment in a facility which provided ongoing professional development was positively related to progress: these effects did not remain significant in multivariate analyses. Implications for employee assistance program (EAP) staff in their role as case managers and for EAP staff and employers in their shared role as purchasers of treatment are discussed.

Update on pharmacology of obesity: benefits and risks.

PubMed

Cabrerizo García, Lucio; Ramos-Leví, Ana; Moreno Lopera, Carmen; Rubio Herrera, Miguel A

2013-09-01

The prevalence of obesity in Western countries has increased at a much greater pace than the development of new efficient and safe drugs, beyond mere lifestyle changes, for the treatment of overweight. Numerous different types of drugs which had been used in the past for the treatment of obesity have currently been withdrawn due to undesirable long-term side effects. The only available drug in Europe is orlistat, which serves only as an aid for the treatment of obesity. In the USA, however, a few central adrenergic-mediators, for instance, diethylpropion and phentermine, have been available for decades to treat obesity during a short-term period (less than 12 weeks). The Food and Drug Administration (FDA) has recently approved lorcaserin and the combination phentermine/ topiramate for the treatment of obesity. The first one is a selective serotonin 2C receptor agonist that works by decreasing food intake with few side effects. Its outcomes on weight are modest, but may be helpful in certain selected patients. The phentermine/topiramate combination has proved to be highly effective, achieving a 10% reduction in weight in the majority of patients, although attention must be drawn to the possible development of side effects in both the short and the long-term follow-up. Further investigation regarding the mechanisms involved in weight balance will anticipate the development of new expectations for the treatment of obesity in the near future. Copyright © AULA MEDICA EDICIONES 2013. Published by AULA MEDICA. All rights reserved.

Development of an evidence-based decision pathway for vestibular schwannoma treatment options.

PubMed

Linkov, Faina; Valappil, Benita; McAfee, Jacob; Goughnour, Sharon L; Hildrew, Douglas M; McCall, Andrew A; Linkov, Igor; Hirsch, Barry; Snyderman, Carl

To integrate multiple sources of clinical information with patient feedback to build evidence-based decision support model to facilitate treatment selection for patients suffering from vestibular schwannomas (VS). This was a mixed methods study utilizing focus group and survey methodology to solicit feedback on factors important for making treatment decisions among patients. Two 90-minute focus groups were conducted by an experienced facilitator. Previously diagnosed VS patients were recruited by clinical investigators at the University of Pittsburgh Medical Center (UPMC). Classical content analysis was used for focus group data analysis. Providers were recruited from practices within the UPMC system and were surveyed using Delphi methods. This information can provide a basis for multi-criteria decision analysis (MCDA) framework to develop a treatment decision support system for patients with VS. Eight themes were derived from these data (focus group + surveys): doctor/health care system, side effects, effectiveness of treatment, anxiety, mortality, family/other people, quality of life, and post-operative symptoms. These data, as well as feedback from physicians were utilized in building a multi-criteria decision model. The study illustrated steps involved in the development of a decision support model that integrates evidence-based data and patient values to select treatment alternatives. Studies focusing on the actual development of the decision support technology for this group of patients are needed, as decisions are highly multifactorial. Such tools have the potential to improve decision making for complex medical problems with alternate treatment pathways. Copyright © 2016 Elsevier Inc. All rights reserved.

Estimating the average treatment effect on survival based on observational data and using partly conditional modeling.

PubMed

Gong, Qi; Schaubel, Douglas E

2017-03-01

Treatments are frequently evaluated in terms of their effect on patient survival. In settings where randomization of treatment is not feasible, observational data are employed, necessitating correction for covariate imbalances. Treatments are usually compared using a hazard ratio. Most existing methods which quantify the treatment effect through the survival function are applicable to treatments assigned at time 0. In the data structure of our interest, subjects typically begin follow-up untreated; time-until-treatment, and the pretreatment death hazard are both heavily influenced by longitudinal covariates; and subjects may experience periods of treatment ineligibility. We propose semiparametric methods for estimating the average difference in restricted mean survival time attributable to a time-dependent treatment, the average effect of treatment among the treated, under current treatment assignment patterns. The pre- and posttreatment models are partly conditional, in that they use the covariate history up to the time of treatment. The pre-treatment model is estimated through recently developed landmark analysis methods. For each treated patient, fitted pre- and posttreatment survival curves are projected out, then averaged in a manner which accounts for the censoring of treatment times. Asymptotic properties are derived and evaluated through simulation. The proposed methods are applied to liver transplant data in order to estimate the effect of liver transplantation on survival among transplant recipients under current practice patterns. © 2016, The International Biometric Society.

Attenuation of postoperative adhesions using a modeled manual therapy.

PubMed

Bove, Geoffrey M; Chapelle, Susan L; Hanlon, Katherine E; Diamond, Michael P; Mokler, David J

2017-01-01

Postoperative adhesions are pathological attachments that develop between abdominopelvic structures following surgery. Considered unavoidable and ubiquitous, postoperative adhesions lead to bowel obstructions, infertility, pain, and reoperations. As such, they represent a substantial health care challenge. Despite over a century of research, no preventive treatment exists. We hypothesized that postoperative adhesions develop from a lack of movement of the abdominopelvic organs in the immediate postoperative period while rendered immobile by surgery and opiates, and tested whether manual therapy would prevent their development. In a modified rat cecal abrasion model, rats were allocated to receive treatment with manual therapy or not, and their resulting adhesions were quantified. We also characterized macrophage phenotype. In separate experiments we tested the safety of the treatment on a strictureplasty model, and also the efficacy of the treatment following adhesiolysis. We show that the treatment led to reduced frequency and size of cohesive adhesions, but not other types of adhesions, such as those involving intraperitoneal fatty structures. This effect was associated with a delay in the appearance of trophic macrophages. The treatment did not inhibit healing or induce undesirable complications following strictureplasty. Our results support that that maintained movements of damaged structures in the immediate postoperative period has potential to act as an effective preventive for attenuating cohesive postoperative adhesion development. Our findings lay the groundwork for further research, including mechanical and pharmacologic approaches to maintain movements during healing.

Empirical risk factors for delinquency and best treatments: where do we go from here?

PubMed

Zagar, Robert John; Busch, Kenneth G; Hughes, John Russell

2009-02-01

Youth development and prevention of violence are two sides of the same public policy issue. A great deal of theoretical and empirical effort has focused on identification of risk factors for delinquency and development of interventions for general risks. Recent calls for changes in public policy are evaluated here--and challenged--in light of new comprehensive, longitudinal empirical data on urban violent delinquency. Treatments such as prenatal care, home visitation, prevention of bullying, prevention of alcohol and/or drug abuse, promotion of alternative thinking, mentoring, life skills training, rewards for graduation and employment, functional family therapy, and multidimensional foster care are effective because they prevent or ameliorate risks for delinquency occurring during development. At present, the best treatments yield 10 to 40% reductions in delinquent recidivism. Better controlled application of developmentally appropriate treatments in higher doses, with narrow targeting of the highest-risk youth based on actuarial testing--rather than less accurate clinical judgment--should result in higher effectiveness. Such a focused approach in a geographical area with high homicide rates should be cost-effective. A prediction of cost-benefit outcomes for a carefully constructed example of a large-scale program is presented.

Harnessing cognitive neuroscience to develop new treatments for improving cognition in schizophrenia: CNTRICS selected cognitive paradigms for animal models.

PubMed

Moore, Holly; Geyer, Mark A; Carter, Cameron S; Barch, Deanna M

2013-11-01

Over the past two decades, the awareness of the disabling and treatment-refractory effects of impaired cognition in schizophrenia has increased dramatically. In response to this still unmet need in the treatment of schizophrenia, the Cognitive Neuroscience Treatment Research to Improve Cognition in Schizophrenia (CNTRICS) initiative was developed. The goal of CNTRICS is to harness cognitive neuroscience to develop a brain-based set of tools for measuring cognition in schizophrenia and to test new treatments. CNTRICS meetings focused on development of tasks with cognitive construct validity for use in both human and animal model studies. This special issue presents papers discussing the cognitive testing paradigms selected by CNTRICS for animal model systems. These paradigms are designed to measure cognitive constructs within the domains of perception, attention, executive function, working memory, object/relational long-term memory, and social/affective processes. Copyright © 2013. Published by Elsevier Ltd.

Harnessing cognitive neuroscience to develop new treatments for improving cognition in schizophrenia: CNTRICS selected cognitive paradigms for animal models

PubMed Central

Moore, Holly; Geyer, Mark A.; Carter, Cameron S.; Barch, Deanna M.

2014-01-01

Over the past two decades, the awareness of the disabling and treatment-refractory effects of impaired cognition in schizophrenia has increased dramatically. In response to this still unmet need in the treatment of schizophrenia, the Cognitive Neuroscience Treatment Research to Improve Cognition in Schizophrenia (CNTRICS) initiative was developed. The goal of CNTRICS is to harness cognitive neuroscience to develop a brain-based set of tools for measuring cognition in schizophrenia and to test new treatments. CNTRICS meetings focused on development of tasks with cognitive construct validity for use in both human and animal model studies. This special issue presents papers discussing the cognitive testing paradigms selected by CNTRICS for animal model systems. These paradigms are designed to measure cognitive constructs within the domains of perception, attention, executive function, working memory, object/relational long-term memory, and social/affective processes. PMID:24090823

Heating uniformity and differential heating of insects in almonds associated with radio frequency energy

USDA-ARS?s Scientific Manuscript database

Radio frequency (RF) treatments have potential as alternatives to chemical fumigation for phytosanitary disinfestation treatments in the dried nut industry. To develop effective RF treatment protocols for almonds, it is desirable to determine heating uniformity and the occurrence of differential hea...

Emergency Planning for Municipal Wastewater Treatment Facilities.

ERIC Educational Resources Information Center

Lemon, R. A.; And Others

This manual for the development of emergency operating plans for municipal wastewater treatment systems was compiled using information provided by over two hundred municipal treatment systems. It covers emergencies caused by natural disasters, civil disorders and strikes, faulty maintenance, negligent operation, and accidents. The effects of such…

Electromagnetic Treatment of Loblolly Pine Seeds

Treesearch

James P. Barnett; Stanley L. Krugman

1989-01-01

Loblolly pine (Pinus taeda L.) seeds were exposed to an electromagnetic radiation treatment (Energy Transfer Process, marketed by the Energy Transfer Corporation), and the effects of the treatments on seed germination, seedling development, disease resistance, and field performance of seedlings were evaluated. None of the evaluated variables showed...

Proven Alternatives for Aboveground Treatment of Arsenic in Groundwater

EPA Pesticide Factsheets

This issue paper, developed for EPA's Engineering Forum, identifies and summarizes experiences with proven aboveground treatment alternatives for arsenic in groundwater, and provides information on their relative effectiveness and cost.

Differential roles of regulatory light chain and myosin binding protein-C phosphorylations in the modulation of cardiac force development

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

Colson, Brett A.; Locher, Matthew R.; Bekyarova, Tanya

2010-05-25

Phosphorylation of myosin regulatory light chain (RLC) by myosin light chain kinase (MLCK) and myosin binding protein-C (cMyBP-C) by protein kinase A (PKA) independently accelerate the kinetics of force development in ventricular myocardium. However, while MLCK treatment has been shown to increase the Ca{sup 2+} sensitivity of force (pCa{sub 50}), PKA treatment has been shown to decrease pCa{sub 50}, presumably due to cardiac troponin I phosphorylation. Further, MLCK treatment increases Ca{sup 2+}-independent force and maximum Ca{sup 2+}-activated force, whereas PKA treatment has no effect on either force. To investigate the structural basis underlying the kinase-specific differential effects on steady-state force,more » we used synchrotron low-angle X-ray diffraction to compare equatorial intensity ratios (I{sub 1,1}/I{sub 1,0}) to assess the proximity of myosin cross-bridge mass relative to actin and to compare lattice spacings (d{sub 1,0}) to assess the inter-thick filament spacing in skinned myocardium following treatment with either MLCK or PKA. As we showed previously, PKA phosphorylation of cMyBP-C increases I{sub 1,1}/I{sub 1,0} and, as hypothesized, treatment with MLCK also increased I{sub 1,1}/I{sub 1,0}, which can explain the accelerated rates of force development during activation. Importantly, interfilament spacing was reduced by {approx}2 nm ({Delta} 3.5%) with MLCK treatment, but did not change with PKA treatment. Thus, RLC or cMyBP-C phosphorylation increases the proximity of cross-bridges to actin, but only RLC phosphorylation affects lattice spacing, which suggests that RLC and cMyBP-C modulate the kinetics of force development by similar structural mechanisms; however, the effect of RLC phosphorylation to increase the Ca{sup 2+} sensitivity of force is mediated by a distinct mechanism, most probably involving changes in interfilament spacing.« less

Challenges of assessment and treatment of ultra high risk for psychosis in an adolescent.

PubMed

Boričević Maršanić, Vlatka; Jukić, Josipa; Flander, Mia

2018-06-01

The onset of psychosis is typically preceded by a prodromal phase that is characterised by the emergence of "attenuated" psychotic symptoms. This phase is described as ultra-high risk (UHR) or at-risk mental state (ARMS) of psychosis. Criteria have been established for identifying these young people who are at clinical high risk. People at ultra-high risk (UHR) of psychosis have about 30% chance of developing the illness within two years. This category was introduced with the goal of developing treatments for prevention of psychotic disorders. Recent research suggests that early interventions appear to be effective in delaying and even preventing the onset of psychosis. These treatments include antipsychotic medication, nutritional supplements such as omega-3 fatty acids and psychological treatment. Cognitive behavioral therapy (CBT) has been tested as a potentially effective intervention in this group. Here we describe a case of a male adolescent with UHR psychotic symptoms with focus on challenges of assessing the UHR in adolescents and issues of providing effective age appropriate interventions.

A new early cognitive screening measure to detect cognitive side-effects of electroconvulsive therapy?

PubMed

Martin, Donel M; Katalinic, Natalie; Ingram, Anna; Schweitzer, Isaac; Smith, Deidre J; Hadzi-Pavlovic, Dusan; Loo, Colleen K

2013-12-01

Cognitive side-effects from electroconvulsive therapy (ECT) can be distressing for patients and early detection may have an important role in guiding treatment decisions over the ECT course. This prospective study examined the utility of an early cognitive screening battery for predicting cognitive side-effects which develop later in the ECT course. The screening battery, together with the Mini Mental Status Examination (MMSE), was administered to 123 patients at baseline and after 3 ECT treatments. A more detailed cognitive battery was administered at baseline, after six treatments (post ECT 6) and after the last ECT treatment (post treatment) to assess cognitive side-effects across several domains: global cognition, anterograde memory, executive function, speed and concentration, and retrograde memory. Multivariate analyses examined the predictive utility of change on items from the screening battery for later cognitive changes at post ECT 6 and post treatment. Results showed that changes on a combination of items from the screening battery were predictive of later cognitive changes at post treatment, particularly for anterograde memory (p < 0.01), after controlling for patient and treatment factors. Change on the MMSE predicted cognitive changes at post ECT 6 but not at post treatment. A scoring method for the new screening battery was tested for discriminative ability in a sub-sample of patients. This study provides preliminary evidence that a simple and easy-to-administer measure may potentially be used to help guide clinical treatment decisions to optimise efficacy and cognitive outcomes. Further development of this measure and validation in a more representative ECT clinical population is required. Copyright © 2013 Elsevier Ltd. All rights reserved.

Disinfection of Streptococcus mutans Biofilm by a Non-Thermal Atmospheric Plasma Brush

NASA Astrophysics Data System (ADS)

Hong, Qing; Dong, Xiaoqing; Chen, Meng; Xu, Yuanxi; Sun, Hongmin; Hong, Liang; Yu, Qingsong

2015-09-01

This study investigated the argon plasma treatment effect on disinfecting dental biofilm by using an atmospheric pressure plasma brush. S. mutans biofilms were developed for 3 days on the surfaces of hydroxyapatite discs, which were used to simulate human tooth enamel. After plasma treatment, cell viability in the S. mutans biofilms was characterized by using MTT assay and confocal laser scanning microscopy (CLSM). Compared with the untreated control group, about 90% and 95% bacterial reduction in the biofilms was observed after 1 and 5 min plasma treatment, respectively. Scanning electron microscopy examination indicated severe cell damages occurred on the top surface of the plasma treated biofilms. CLSM showed that plasma treatment was effective as deep as 20 μm into the biofilms. When combined with 0.2% chlorhexidine digluconate solution, the plasma treatment became more effective and over 96% bacterial reduction was observed with 1 min plasma treatment. These results indicate that plasma treatment is effective and promising in dental biofilm disinfection.

Drug and Nondrug Treatment in Tension-type Headache

PubMed Central

2009-01-01

Tension-type headache (TTH) is a common primary headache with tremendous socioeconomic impact. Establishment of an accurate diagnosis is important before initiation of any treatment. Nondrug management is crucial. Information, reassurance and identification of trigger factors may be rewarding. Psychological treatments with scientific evidence for efficacy include relaxation training, EMG biofeedback and cognitive-behavioural therapy. Physical therapy and acupuncture are widely used, but the scientific evidence for efficacy is sparse. Simple analgesics are the mainstays for treatment of episodic TTH. Combination analgesics, triptans, muscle relaxants and opioids should not be used, and it is crucial to avoid frequent and excessive use of simple analgesics to prevent the development of medication-overuse headache. The tricyclic antidepressant amitriptyline is drug of first choice for the prophylactic treatment of chronic TTH. The efficacy is modest and treatment is often hampered by side effects. Thus, treatment of frequent TTH is often difficult and multidisciplinary treatment strategies can be useful. The development of specific nonpharmacological and pharmacological managements for TTH with higher efficacy and fewer side effects is urgently needed. Future studies should also examine the relative efficacy of the various treatment modalities; for example, psychological, physical and pharmacological treatments, and clarify how treatment programs should be optimized to best suit the individual patient. PMID:21179525

Cutaneous side effects of doxycycline: a pediatric case series.

PubMed

Bayhan, Gulsum Iclal; Akbayram, Sinan; Ozaydin Yavuz, Goknur; Oner, Ahmet Fayik

2017-06-01

Brucellosis is highly endemic in Turkey and doxycycline is commonly used for its treatment. The present study aimed at documenting the cutaneous side effects of doxycycline in pediatric brucellosis patients in Turkey. Pediatric patients with brucellosis that were treated between February 2014 and January 2016 were analyzed retrospectively, and those that developed doxycycline-related cutaneous side effects were identified. Demographic data, epidemiological history, physical examination findings, laboratory test results, anti-brucellosis treatment regimen, duration of follow up and outcome were recorded. Among the 189 brucellosis patients, 141 treated with doxycycline plus rifampicin. Seven patients (5%) (two female and five male) developed doxycycline-related cutaneous side effects. Mean duration of treatment before the onset of cutaneous side effects was 9.5 weeks. Doxycycline therapy was continued in five of these patients and was changed in two patients. In the patients that continued to receive doxycycline the cutaneous side effects gradually improved. Cutaneous side effects of doxycycline should always be a consideration, especially in regions in which brucellosis is endemic and doxycycline is commonly used to treat it.

Efficacy of Boric Acid as a Treatment of Choice for Chronic Suppurative Otitis Media and Its Ototoxicity.

PubMed

Adriztina, Indri; Adenin, Linda Irwani; Lubis, Yuliani Mardiati

2018-01-01

Chronic suppurative otitis media (CSOM) is one of the most common chronic infectious diseases worldwide, especially affecting children. The patients or the parents of the affected children are often worried about the cost of medical visits, prescription medicines, or inconsistently effective medication. The complications of CSOM have been greatly reduced because of the development of antibiotics; however, the irrational use of antibiotics has led to the emergence of organisms resistant to the commonly used drugs. Owing to the increase in antibiotic resistance, the development of new treatments that will efficiently eradicate infectious microorganisms has become imperative. Boric acid solutions are effective in the treatment of CSOM because of their acidic effect. Various databases, such as the PubMed, The Cochrane Library, and SciELO, were searched for references related to the efficacy of boric acid in the treatment of mucosal CSOM, as well as its ototoxicity. The search revealed that boric acid is relatively effective in treating CSOM, especially at a high concentration. Boric acid in distilled water was found safe in animal studies. However, the ototoxicity of boric acid concentrations higher than 4% needs further evaluation, considering the effectivity of boric acid at high concentrations.

Efficacy of Boric Acid as a Treatment of Choice for Chronic Suppurative Otitis Media and Its Ototoxicity

PubMed Central

Adenin, Linda Irwani; Lubis, Yuliani Mardiati

2018-01-01

Chronic suppurative otitis media (CSOM) is one of the most common chronic infectious diseases worldwide, especially affecting children. The patients or the parents of the affected children are often worried about the cost of medical visits, prescription medicines, or inconsistently effective medication. The complications of CSOM have been greatly reduced because of the development of antibiotics; however, the irrational use of antibiotics has led to the emergence of organisms resistant to the commonly used drugs. Owing to the increase in antibiotic resistance, the development of new treatments that will efficiently eradicate infectious microorganisms has become imperative. Boric acid solutions are effective in the treatment of CSOM because of their acidic effect. Various databases, such as the PubMed, The Cochrane Library, and SciELO, were searched for references related to the efficacy of boric acid in the treatment of mucosal CSOM, as well as its ototoxicity. The search revealed that boric acid is relatively effective in treating CSOM, especially at a high concentration. Boric acid in distilled water was found safe in animal studies. However, the ototoxicity of boric acid concentrations higher than 4% needs further evaluation, considering the effectivity of boric acid at high concentrations. PMID:29383205

Clinical Trials: More than an Assessment of Treatment Effect – LXV Edward Jackson Memorial Lecture

PubMed Central

Ferris, Frederick L.

2008-01-01

Purpose To review the development of clinical trials and demonstrate their value beyond the assessment of the treatment effect. Design Retrospective literature review Methods Retrospective literature review Results There has been a rapid increase in the number of clinical trials in ophthalmology as assessed by the number of ophthalmic publications and the number of ongoing National Eye Institute (NEI) sponsored clinical trials over the last four decades. The public health significance of the results of these NEI clinical trials goes beyond the demonstration of treatment effects and side effects. From these trials we learn about the clinical course and risk factors of disease allowing us to better determine who and when to treat. Furthermore, the collaboration of investigators, as they develop and carry out protocols, facilitates incorporation of new ideas into the practice of medicine. Conclusions The practice of medicine is increasingly dependent on the results of carefully designed clinical trials. The determination as to whether a new treatment is safe and effective is important, but the additional information we can obtain regarding natural history, risk factors, and patient satisfaction adds immeasurably to our ability to care for our patients. PMID:19100353

Treatment evolution and new standards of care: implications for cost-effectiveness analysis.

PubMed

Shechter, Steven M

2011-01-01

Traditional approaches to cost-effectiveness analysis have not considered the downstream possibility of a new standard of care coming out of the research and development pipeline. However, the treatment landscape for patients may change significantly over the course of their lifetimes. To present a Markov modeling framework that incorporates the possibility of treatment evolution into the incremental cost-effectiveness ratio (ICER) that compares treatments available at the present time. . Markov model evaluated by matrix algebra. Measurements. The author evaluates the difference between the new and traditional ICER calculations for patients with chronic diseases facing a lifetime of treatment. The bias of the traditional ICER calculation may be substantial, with further testing revealing that it may be either positive or negative depending on the model parameters. The author also performs probabilistic sensitivity analyses with respect to the possible timing of a new treatment discovery and notes the increase in the magnitude of the bias when the new treatment is likely to appear sooner rather than later. Limitations. The modeling framework is intended as a proof of concept and therefore makes simplifying assumptions such as time stationarity of model parameters and consideration of a single new drug discovery. For diseases with a more active research and development pipeline, the possibility of a new treatment paradigm may be at least as important to consider in sensitivity analysis as other parameters that are often considered.

Overuse of Psychotropic Medications among Children and Adolescents with Autism Spectrum Disorders: Perspective from a Developing Country

ERIC Educational Resources Information Center

Memari, Amir Hossein; Ziaee, Vahid; Beygi, Sara; Moshayedi, Pouria; Mirfazeli, Fatemeh Sadat

2012-01-01

Psychopharmacotherapy can be an effective part of the treatment for individuals with autism spectrum disorders (ASDs). However debate continues over the potential benefits and costs of these treatments; additionally little is known about the pattern of psychotropic medication use in developing countries. We aimed to survey the use of psychotropic…

Seed treatments enhance photosynthesis in maize seedlings by reducing infection with Fusarium spp. and consequent disease development in maize

USDA-ARS?s Scientific Manuscript database

The effects of a seed treatment on early season growth, seedling disease development, incidence Fusarium spp. infection, and photosynthetic performance of maize were evaluated at two locations in Iowa in 2007. Maize seed was either treated with Cruiser 2Extreme 250 ® (fludioxonil + azoxystrobin + me...

Detecting Responses of Loblolly Pine Stand Development to Site-Preparation Intensity: A Modeling Approach

Treesearch

Mingguang Xu; Timothy B. Harrington; M. Boyd Edwards

1997-01-01

Data from an existing site preparation experiment in the Georgia Piedmont were subjected to a modeling approach to analyze effects of site preparation intensity on stand development of loblolly pine (Pinus taeda L.) 5 to 12 years since treatment. An average stand height model that incorporated indicator variables for treatment provided an accurate...

How Comparative Effectiveness Research Can Help To Advance ‘Personalized Medicine’ In Cancer Treatment

PubMed Central

Ramsey, Scott D.; Veenstra, David L.; Tunis, Sean R.; Garrison, Louis P.; Crowley, John J.; Baker, Laurence H.

2012-01-01

The use of biomarkers to “personalize” cancer treatment —identifying discrete genes, proteins, or other indicators that can differentiate one type of cancer from another and enable the use of highly tailored therapies -- offers tremendous potential for improved outcomes and lower treatment costs. However, the rapid development of cancer biomarker, or genomic, tests— combined with a paucity of evidence to support the effectiveness of the tests—presents a challenge for patients, clinicians and other stakeholders. In this article, we propose that comparative effectiveness research be used to strengthen what is now a haphazard process for developing and marketing cancer biomarker tests. We suggest novel funding approaches and a systematic process for moving from regulatory approval to the generation of evidence that meets the needs of stakeholders and, ultimately, patients. PMID:22147853

Antidepressant-like effects of long-term sarcosine treatment in rats with or without chronic unpredictable stress.

PubMed

Chen, Kuang-Ti; Wu, Ching-Hsiang; Tsai, Mang-Hung; Wu, Ya-Chieh; Jou, Ming-Jia; Huang, Chih-Chia; Wei, I-Hua

2017-01-01

Sarcosine, an N-methyl-d-aspartate receptor enhancer, can improve depression-like behavior in rodent models and depression in humans. We found that a single dose of sarcosine exerted antidepressant-like effects with rapid concomitant increases in the mammalian target of rapamycin (mTOR) signaling pathway activation and enhancement of α-amino-3-hydroxy-5-methylisoxazole-4-propionate receptor (AMPAR) membrane insertion. Sarcosine may play a crucial role in developing novel therapy for depression. For a detailed understanding of sarcosine, this study examined the effects of long-term sarcosine treatment on the forced swim test (FST), mTOR signaling, and AMPAR membrane insertion in rats. The effects of long-term sarcosine treatment were examined in naive rats and rats exposed to chronic unpredictable stress (CUS). Long-term sarcosine treatment (560mg/kg/d for 21 d) significantly ameliorated the increased immobility induced by CUS in the FST, reaffirming the potential role of sarcosine as an antidepressant for depressed patients. The same long-term treatment exhibited no such effect in naive rats despite increased mTOR activation and AMPAR membrane insertion in both groups. Our findings clearly show CUS-exposed rats are sensitive to long-term sarcosine treatment in FST and the response at the same dose is absent in naïve rats. Nevertheless, the distinct sensitivity to long-term sarcosine treatment in rats with or without CUS is not associated with the activated mTOR signaling pathway or increased AMPAR membrane insertion. Additionally, understanding the behavioral and molecular basis of distinct responses is vital important for developing personalized treatment programs to increase the probability of success when treating depression. Copyright © 2016. Published by Elsevier B.V.

Long-term effects of different type and rates of organic amendments on reclamation of copper mine tailing in Central Chile.

NASA Astrophysics Data System (ADS)

Arellano, Eduardo; Garreton, Bruna; Ginocchio, Rosanna

2016-04-01

A study was conducted to evaluate the long-term effects of a single application of organic amendments on a copper mine tailings. Seven years after seeding of a mix of herbaceous plant and planting of ten native trees, and the application of organic amendment, plant community and soil fertility was measured in replicated plots that received six different treatments of waste water treatment plant biosolids (100 ton/ha, and 200 ton/ha), olive oil waste (100 ton/ha, and 200 ton/ha) and pisco grapes waste (90 ton/ha, and 200 ton/ha). A control treatment that received no organic amendment was also measured after seven years. Field measurements demonstrated that application of biosolids and pisco grapes waste, at both rates significantly improved vegetation coverage in comparison to the control treatment (80 and 100% vs control, 25%). The high rates of pisco waste had the highest vegetation diversity and survival in comparison to the other treatments. The high rate of olive oil waste had a negative effect on vegetation development in comparison to the control treatment. The application of organic amendment improved soil fertility in the long-term. All the treatments had a significant higher nitrogen concentration in comparison to the control treatment. The high rates of biosolids and pisco grape waste had a significantly effect of soil carbon concentration. Soil macro-aggregate in the high rate of pisco grape waste were also higher than the control, showing a positive relation between soil recover and vegetation development. We can conclude assisted phytostabilization of mine tailings is likely a technically effective solution for the valorisation of organic residues.

Selection of target mutation in rat gastrointestinal tract E. coli by minute dosage of enrofloxacin.

PubMed

Lin, Dachuan; Chen, Kaichao; Li, Ruichao; Liu, Lizhang; Guo, Jiubiao; Yao, Wen; Chen, Sheng

2014-01-01

It has been suggested that bacterial resistance is selected within a mutation selection window of antibiotics. More recent studies showed that even extremely low concentration of antibiotic could select resistant bacteria in vitro. Yet little is known about the exact antibiotic concentration range that can effectively select for resistant organisms in animal gastrointestinal (GI) tract. In this study, the effect of different dosages of enrofloxacin on resistance and mutation development in rat GI tract E. coli was investigated by determining the number of resistant E. coli recoverable from rat fecal samples. Our data showed that high dose antibiotic treatment could effectively eliminate E. coli with single gyrA mutation in the early course of treatment, yet the eradication effects diminished upon prolonged treatment. Therapeutic and sub-therapeutic dose (1/10 and 1/100 of therapeutic doses) of enrofloxacin could effectively select for mutation in GI tract E. coli at the later course of enrofloxacin treatment and during the cessation periods. Surprisingly, very low dose of enrofloxacin (1/1000 therapeutic dose) could also select for mutation in GI tract E. coli at the later course of enrofloxacin treatment, only with slightly lower efficiency. No enrofloxacin-resistant E. coli could be selected at all test levels of enrofloxacin during long term treatment and the strength of antibiotic treatment does not alter the overall level of E. coli in rat GI tract. This study demonstrated that long term antibiotic treatment seems to be the major trigger for the development of target mutations in GI tract E. coli, which provided insight into the rational use of antibiotics in animal husbandry.

Cost-effectiveness of additional catheter-directed thrombolysis for deep vein thrombosis.

PubMed

Enden, T; Resch, S; White, C; Wik, H S; Kløw, N E; Sandset, P M

2013-06-01

Additional treatment with catheter-directed thrombolysis (CDT) has recently been shown to reduce post-thrombotic syndrome (PTS). To estimate the cost effectiveness of additional CDT compared with standard treatment alone. Using a Markov decision model, we compared the two treatment strategies in patients with a high proximal deep vein thrombosis (DVT) and a low risk of bleeding. The model captured the development of PTS, recurrent venous thromboembolism and treatment-related adverse events within a lifetime horizon and the perspective of a third-party payer. Uncertainty was assessed with one-way and probabilistic sensitivity analyzes. Model inputs from the CaVenT study included PTS development, major bleeding from CDT and utilities for post DVT states including PTS. The remaining clinical inputs were obtained from the literature. Costs obtained from the CaVenT study, hospital accounts and the literature are expressed in US dollars ($); effects in quality adjusted life years (QALY). In base case analyzes, additional CDT accumulated 32.31 QALYs compared with 31.68 QALYs after standard treatment alone. Direct medical costs were $64,709 for additional CDT and $51,866 for standard treatment. The incremental cost-effectiveness ratio (ICER) was $20,429/QALY gained. One-way sensitivity analysis showed model sensitivity to the clinical efficacy of both strategies, but the ICER remained < $55,000/QALY over the full range of all parameters. The probability that CDT is cost effective was 82% at a willingness to pay threshold of $50,000/QALY gained. Additional CDT is likely to be a cost-effective alternative to the standard treatment for patients with a high proximal DVT and a low risk of bleeding. © 2013 International Society on Thrombosis and Haemostasis.

Cost-effectiveness of additional catheter-directed thrombolysis for deep vein thrombosis

PubMed Central

ENDEN, T.; RESCH, S.; WHITE, C.; WIK, H. S.; KLØW, N. E.; SANDSET, P. M.

2013-01-01

Summary Background Additional treatment with catheter-directed thrombolysis (CDT) has recently been shown to reduce post-thrombotic syndrome (PTS). Objectives To estimate the cost effectiveness of additional CDT compared with standard treatment alone. Methods Using a Markov decision model, we compared the two treatment strategies in patients with a high proximal deep vein thrombosis (DVT) and a low risk of bleeding. The model captured the development of PTS, recurrent venous thromboembolism and treatment-related adverse events within a lifetime horizon and the perspective of a third-party payer. Uncertainty was assessed with one-way and probabilistic sensitivity analyzes. Model inputs from the CaVenT study included PTS development, major bleeding from CDT and utilities for post DVT states including PTS. The remaining clinical inputs were obtained from the literature. Costs obtained from the CaVenT study, hospital accounts and the literature are expressed in US dollars ($); effects in quality adjusted life years (QALY). Results In base case analyzes, additional CDT accumulated 32.31 QALYs compared with 31.68 QALYs after standard treatment alone. Direct medical costs were $64 709 for additional CDT and $51 866 for standard treatment. The incremental cost-effectiveness ratio (ICER) was $20 429/QALY gained. One-way sensitivity analysis showed model sensitivity to the clinical efficacy of both strategies, but the ICER remained < $55 000/QALY over the full range of all parameters. The probability that CDT is cost effective was 82% at a willingness to pay threshold of $50 000/QALY gained. Conclusions Additional CDT is likely to be a cost-effective alternative to the standard treatment for patients with a high proximal DVT and a low risk of bleeding. PMID:23452204

Interstitial laser immunotherapy for treatment of metastatic mammary tumors in rats

NASA Astrophysics Data System (ADS)

Figueroa, Daniel; Joshi, Chet; Wolf, Roman F.; Walla, Jonny; Goddard, Jessica; Martin, Mallory; Kosanke, Stanley D.; Broach, Fred S.; Pontius, Sean; Brown, Destiny; Li, Xiaosong; Howard, Eric; Nordquist, Robert E.; Hode, Tomas; Chen, Wei R.

2011-03-01

Thermal therapy has been used for cancer treatment for more than a century. While thermal effect can be direct, immediate, and controllable, it is not sufficient to completely eradicate tumors, particularly when tumors have metastasized locally or to the distant sites. Metastases are the major cause of treatment failure and cancer deaths. Current available therapies, such as surgery, radiation, and chemotherapy, only have limited curative effects in patients with late-stage, metastatic cancers. Immunotherapy has been considered as the ultimate approach for cancer treatment since a systemic, anti-tumor, immunological response can be induced. Using the combination of photothermal therapy and immunotherapy, laser immunotherapy (LIT),a novel immunotherapy modality for late-stage cancer treatment, has been developed. LIT has shown great promise in pre-clinical studies and clinical breast cancer and melanoma pilot trials. However, the skin color and the depth of the tumor have been challenges for effective treatment with LIT. To induce a thermal destruction zone of appropriate size without causing thermal damage on the skin, we have developed interstitial laser immunotherapy (ILIT) using a cylindrical diffuser. To determine the effectiveness of ILIT, we treated the DMBA-4 metastatic tumors in rats. The thermal damage in tumor tissue was studied using TTC immersion and hematoxolin and eosin (H & E) staining. Also observed was the overall survival of the treated animals. Our results demonstrated that the ILIT could impact a much larger tumor area, and it significantly reduced the surface damage compared with the early version of non-invasive LIT. The survival data also indicate that ILIT has the potential to become an effective tool for the treatment of deeper, larger, and metastatic tumors, with reduced side effects.

21 CFR 250.201 - Preparations for the treatment of pernicious anemia.

Code of Federal Regulations, 2014 CFR

2014-04-01

... be markedly deleterious effects on the nervous system. It is well established that whereas the development of anemia is completely reversible with adequate treatment, the involvement of the nervous system...

21 CFR 250.201 - Preparations for the treatment of pernicious anemia.

Code of Federal Regulations, 2010 CFR

2010-04-01

... be markedly deleterious effects on the nervous system. It is well established that whereas the development of anemia is completely reversible with adequate treatment, the involvement of the nervous system...

21 CFR 250.201 - Preparations for the treatment of pernicious anemia.

Code of Federal Regulations, 2012 CFR

2012-04-01

... be markedly deleterious effects on the nervous system. It is well established that whereas the development of anemia is completely reversible with adequate treatment, the involvement of the nervous system...

21 CFR 250.201 - Preparations for the treatment of pernicious anemia.

Code of Federal Regulations, 2013 CFR

2013-04-01

... be markedly deleterious effects on the nervous system. It is well established that whereas the development of anemia is completely reversible with adequate treatment, the involvement of the nervous system...

21 CFR 250.201 - Preparations for the treatment of pernicious anemia.

Code of Federal Regulations, 2011 CFR

2011-04-01

... be markedly deleterious effects on the nervous system. It is well established that whereas the development of anemia is completely reversible with adequate treatment, the involvement of the nervous system...

Cognitive Impairment in Bipolar Disorder: Treatment and Prevention Strategies

PubMed Central

Solé, Brisa; Jiménez, Esther; Torrent, Carla; Reinares, Maria; Bonnin, Caterina del Mar; Torres, Imma; Varo, Cristina; Grande, Iria; Valls, Elia; Salagre, Estela; Sanchez-Moreno, Jose; Martinez-Aran, Anabel; Carvalho, André F

2017-01-01

Abstract Over the last decade, there has been a growing appreciation of the importance of identifying and treating cognitive impairment associated with bipolar disorder, since it persists in remission periods. Evidence indicates that neurocognitive dysfunction may significantly influence patients’ psychosocial outcomes. An ever-increasing body of research seeks to achieve a better understanding of potential moderators contributing to cognitive impairment in bipolar disorder in order to develop prevention strategies and effective treatments. This review provides an overview of the available data from studies examining treatments for cognitive dysfunction in bipolar disorder as well as potential novel treatments, from both pharmacological and psychological perspectives. All these data encourage the development of further studies to find effective strategies to prevent and treat cognitive impairment associated with bipolar disorder. These efforts may ultimately lead to an improvement of psychosocial functioning in these patients. PMID:28498954

New developments in epidemiology, diagnosis, and treatment of fascioliasis.

PubMed

Cabada, Miguel M; White, A Clinton

2012-10-01

This review focuses on the recent developments in the epidemiology, burden of disease, diagnostic tests, and treatment of fascioliasis. Recent epidemiologic data suggest that either the endemic areas are expanding or disease is being recognized in areas where it was not previously observed. In addition, recent data highlight the effects of fascioliasis on childhood anemia and nutrition. Diagnosis remains problematic, but newer diagnostic tests including antibody, antigen, and DNA detection tests may facilitate earlier diagnosis. Recent studies suggest that point-of-care testing may soon be possible. Treatment with triclabendazole is effective, but resistance is emerging in livestock and may pose a threat for patients. Fascioliasis continues to emerge as an important neglected disease, with new studies highlighting the under-recognized burden of disease. Further studies are needed on burden of disease, improved diagnosis, and alternative to triclabendazole treatment.

Sample Size Calculations for Micro-randomized Trials in mHealth

PubMed Central

Liao, Peng; Klasnja, Predrag; Tewari, Ambuj; Murphy, Susan A.

2015-01-01

The use and development of mobile interventions are experiencing rapid growth. In “just-in-time” mobile interventions, treatments are provided via a mobile device and they are intended to help an individual make healthy decisions “in the moment,” and thus have a proximal, near future impact. Currently the development of mobile interventions is proceeding at a much faster pace than that of associated data science methods. A first step toward developing data-based methods is to provide an experimental design for testing the proximal effects of these just-in-time treatments. In this paper, we propose a “micro-randomized” trial design for this purpose. In a micro-randomized trial, treatments are sequentially randomized throughout the conduct of the study, with the result that each participant may be randomized at the 100s or 1000s of occasions at which a treatment might be provided. Further, we develop a test statistic for assessing the proximal effect of a treatment as well as an associated sample size calculator. We conduct simulation evaluations of the sample size calculator in various settings. Rules of thumb that might be used in designing a micro-randomized trial are discussed. This work is motivated by our collaboration on the HeartSteps mobile application designed to increase physical activity. PMID:26707831

Laser-heat puncturing as highly effective method of post-tuberculous cystalgia treatment

NASA Astrophysics Data System (ADS)

Koultchavenia, Ekaterina V.

1999-07-01

The tuberculosis of an urine bladder in men develops is authentic less often, and recovery is authentic more often, than in the women. In 39,1 percent of the women with nephrotuberculosis and urocystis and urocystis tuberculosis a specific cystitides is finished in development of post- tuberculous cystalgia. One of starting mechanism of dysuria after the transferred urocystis tuberculosis in the women in menopause is hormonal insufficiency. The method of laser heat puncturing, developed by us, for the treatment this complication is highly effective, does not require additional introduction of medicines, can be executed as in hospitals, and in our-patient.

Development of the Plutonium-DTPA Biokinetic Model.

PubMed

Konzen, Kevin; Brey, Richard

2015-06-01

Estimating radionuclide intakes from bioassays following chelation treatment presents a challenge to the dosimetrist due to the observed excretion enhancement of the particular radionuclide of concern where no standard biokinetic model exists. This document provides a Pu-DTPA biokinetic model that may be used for making such determination for plutonium intakes. The Pu-DTPA biokinetic model is intended to supplement the standard recommended biokinetic models. The model was used to evaluate several chelation strategies that resulted in providing recommendations for effective treatment. These recommendations supported early treatment for soluble particle inhalations and an initial 3-day series of DTPA treatments for wounds. Several late chelation strategies were also compared where reduced treatment frequencies proved to be as effective as multiple treatments. The Pu-DTPA biokinetic model can be used to assist in estimating initial intakes of transuranic radionuclides and for studying the effects of different treatment strategies.

Detecting treatment-subgroup interactions in clustered data with generalized linear mixed-effects model trees.

PubMed

Fokkema, M; Smits, N; Zeileis, A; Hothorn, T; Kelderman, H

2017-10-25

Identification of subgroups of patients for whom treatment A is more effective than treatment B, and vice versa, is of key importance to the development of personalized medicine. Tree-based algorithms are helpful tools for the detection of such interactions, but none of the available algorithms allow for taking into account clustered or nested dataset structures, which are particularly common in psychological research. Therefore, we propose the generalized linear mixed-effects model tree (GLMM tree) algorithm, which allows for the detection of treatment-subgroup interactions, while accounting for the clustered structure of a dataset. The algorithm uses model-based recursive partitioning to detect treatment-subgroup interactions, and a GLMM to estimate the random-effects parameters. In a simulation study, GLMM trees show higher accuracy in recovering treatment-subgroup interactions, higher predictive accuracy, and lower type II error rates than linear-model-based recursive partitioning and mixed-effects regression trees. Also, GLMM trees show somewhat higher predictive accuracy than linear mixed-effects models with pre-specified interaction effects, on average. We illustrate the application of GLMM trees on an individual patient-level data meta-analysis on treatments for depression. We conclude that GLMM trees are a promising exploratory tool for the detection of treatment-subgroup interactions in clustered datasets.

Antibiotics for the treatment of dysentery in children

PubMed Central

Traa, Beatrix S; Walker, Christa L Fischer; Munos, Melinda; Black, Robert E

2010-01-01

Background Ciprofloxacin, ceftriaxone and pivmecillinam are the antibiotics currently recommended by the World Health Organization (WHO) for the treatment of dysentery in children; yet there have been no reviews of the clinical effectiveness of these antibiotics in recent years. Methods We reviewed all literature reporting the effect of ciprofloxacin, ceftriaxone and pivmecillinam for the treatment of dysentery in children in the developing countries. We used a standardized abstraction and grading format and performed meta-analyses to determine the effect of treatment with these antibiotics on rates of treatment failure, bacteriological failure and bacteriological relapse. The CHERG Standard Rules were applied to determine the final effect of treatment with these antibiotics on diarrhoea mortality. Results Eight papers were selected for abstraction. Treatment with ciprofloxacin, ceftriaxone or pivmecillinam resulted in a cure rate of >99% while assessing clinical failure, bacteriological failure and bacteriological relapse. Conclusions The antibiotics recommended by the WHO—ciprofloxacin, ceftriaxone and pivmecillinam—are effective in reducing the clinical and bacteriological signs and symptoms of dysentery and thus can be expected to decrease diarrhoea mortality attributable to dysentery. PMID:20348130

Nonpharmacological, somatic treatments of depression: electroconvulsive therapy and novel brain stimulation modalities

PubMed Central

Eitan, Renana; Lerer, Bernard

2006-01-01

Until recently, a review of nonpharmacological, somatic treatments of psychiatric disorders would have included only electroconvulsive therapy (ECT). This situation is now changing very substantially Although ECT remains the only modality in widespread clinical use, several new techniques are under investigation. Their principal indication in the psychiatric context is the treatment of major depression, but other applications are also being studied. All the novel treatments involve brain stimulation, which is achieved by different technological methods. The treatment closest to the threshold of clinical acceptability is transcranial magnetic stimulation (TMS). Although TMS is safe and relatively easy to administer, its efficacy has still to be definitively established. Other modalities, at various stages of research development, include magnetic seizure therapy (MST), deep brain stimulation (DBS), and vagus nerve stimulation (VNS). We briefly review the development and technical aspects of these treatments, their potential role in the treatment of major depression, adverse effects, and putative mechanism of action. As the only one of these treatment modalities that is in widespread clinical use, more extended consideration is given to ECT. Although more than half a century has elapsed since ECT was first introduced, it remains the most effective treatment for major depression, with efficacy in patients refractory to antidepressant drugs and an acceptable safety profile. Although they hold considerable promise, the novel brain stimulation techniques reviewed here will be need to be further developed before they achieve clinical acceptability. PMID:16889109

The Childhood Arthritis and Rheumatology Research Alliance Consensus Treatment Plans: Toward Comparative Effectiveness in the Pediatric Rheumatic Diseases.

PubMed

Ringold, Sarah; Nigrovic, Peter A; Feldman, Brian M; Tomlinson, George A; von Scheven, Emily; Wallace, Carol A; Huber, Adam M; Schanberg, Laura E; Li, Suzanne C; Weiss, Pamela F; Fuhlbrigge, Robert C; Morgan, Esi M; Kimura, Yukiko

2018-05-01

The pediatric rheumatic diseases are a heterogeneous group of rare diseases, posing a number of challenges for the use of traditional clinical and translational research methods. Innovative comparative effectiveness approaches are needed to efficiently study treatment strategies and disease outcomes. The Childhood Arthritis and Rheumatology Research Alliance (CARRA) developed the consensus treatment plan (CTP) approach as a comparative effectiveness tool for research in pediatric rheumatology. CTPs are treatment strategies, developed by consensus methods among CARRA members, intended to reduce variation in treatment approaches, standardize outcome measurements, and allow for comparison of the effectiveness of different approaches with the goal of improving disease outcomes. To date, CTPs have been published for 8 different diseases and disease manifestations. The approach has been successfully piloted for juvenile localized scleroderma, systemic juvenile idiopathic arthritis (JIA), polyarticular JIA, dermatomyositis, and lupus nephritis. Large-scale studies are underway for systemic JIA and polyarticular JIA, with the CARRA patient registry serving as the data collection platform. These studies have been designed with stakeholder involvement, including active input from CARRA providers, patients, and parents, with the goal of increasing feasibility and ensuring the relevance of the outcomes. These studies include ancillary biologic specimen collection intended to support additional translational and mechanistic studies. Data from these ongoing CTP studies will provide more information on the ability of this approach to identify effective treatment strategies and improve outcomes in the pediatric rheumatic diseases. © 2018, American College of Rheumatology.

Research- and Practice-Based Nutrition Education and Cooking Workshops in Pediatric Oncology: Protocol for Implementation and Development of Curriculum

PubMed Central

Chaput, Cynthia; Beaulieu-Gagnon, Sabrina; Bélanger, Véronique; Drouin, Simon; Bertout, Laurence; Lafrance, Lucie; Olivier, Cinthia; Robitaille, Marthe; Laverdière, Caroline; Sinnett, Daniel; Marquis, Marie

2018-01-01

Background Progresses in childhood cancer treatment, diagnosis, and management have resulted in childhood cancer survival rates of over 80%. However, this therapeutic success comes with a heavy price: two-thirds of childhood cancer survivors will be affected by further complications, including cardiovascular and metabolic diseases. Adequate nutrition during cancer treatment is essential to ensure the child’s optimal development, improve tolerance to treatments, and can contribute to lower the risk of developing cardiometabolic diseases. Side effects of cancer treatments can negatively impact children’s nutritional intake and eating behaviors. Involving the families of childhood cancer patients in educational workshops could be a promising avenue to promote healthy eating during and after cancer treatment. Objective The objectives of this study were to develop, validate, and implement a family-based nutrition education and cooking workshop curriculum in a pediatric oncology setting that addresses the nutritional issues encountered during treatments while promoting the adoption of healthy eating habits for the prevention of long-term cardiometabolic effects. Methods The workshops were developed and validated following an 8-step iterative process, including a review of the literature and consultations with a steering committee. An evaluation tool was also developed. A nonrandomized study protocol was elaborated to implement the workshops and measure their impact. The themes of the 6 research- and practice-based lessons are as follows: meal fortification during cancer treatment, changes in taste during cancer therapy and their impact on children, adapting diet to eating-related side effects of treatments, nutritional support during cancer treatment, Mediterranean diet and health, and planning quick and economic meals. The validation process included consultations with the institution’s clinical nutrition professionals. Self-administered post questionnaires were developed according to the content of each workshop to measure short-term outcomes, namely, participants’ perception of knowledge acquisition, behavioral intention, and satisfaction. Medium-term outcomes that will be evaluated are participants’ anthropometric profile, quality of the diet, and circulating biomarkers of metabolic health. Results The project was funded in 2016 and enrollment will be completed in 2021. Data analysis is currently under way and the first results are expected to be submitted for publication in 2019. Conclusions This research- and practice-based nutrition education and cooking demonstration curriculum could be a valuable complement to a multidisciplinary lifestyle intervention for the prevention of long-term cardiometabolic complications in childhood cancer. PMID:29317383

Restoration of miR-30a expression inhibits growth, tumorigenicity of medulloblastoma cells accompanied by autophagy inhibition.

PubMed

Singh, Satishkumar Vishram; Dakhole, Aditi Nigam; Deogharkar, Akash; Kazi, Sadaf; Kshirsagar, Rohan; Goel, Atul; Moiyadi, Aliasgar; Jalali, Rakesh; Sridhar, Epari; Gupta, Tejpal; Shetty, Prakash; Gadewal, Nikhil; Shirsat, Neelam Vishwanath

2017-09-30

Medulloblastoma is a highly malignant pediatric brain tumor. About 30% patients have metastasis at diagnosis and respond poorly to treatment. Those that survive, suffer long term neurocognitive, endocrine and developmental defects due to the cytotoxic treatment to developing child brain. It is therefore necessary to develop targeted treatment strategies based on underlying biology for effective treatment of medulloblastoma with minimal side effects. Medulloblastomas are believed to be the result of deregulated nervous system development as evident from the role of WNT and SHH developmental signaling pathways in pathogenesis of medulloblastomas. MicroRNAs are known to play vital roles in nervous system development as well as in cancer. MicroRNA profiling of medulloblastomas identified miR-30 family members' expression to be downregulated in medulloblastomas belonging to the four known molecular subgroups viz. WNT, SHH, Group 3 and Group 4 as compared to that in normal brain tissues. Furthermore, established medulloblastoma cell lines Daoy, D283 and D425 were also found to underexpress miR-30a. Restoration of miR-30a expression using inducible lentiviral vector inhibited proliferation, clonogenic potential and tumorigenicity of medulloblastoma cells. MiR-30a is known to target Beclin1, a mediator of autophagy. MiR-30a expression was found to downregulate Beclin1 expression and inhibit autophagy in the medulloblastoma cell lines as judged by downregulation of LC3B expression and its turnover upon chloroquine treatment and starvation induced autophagy induction. MiR-30a therefore could serve as a novel therapeutic agent for the effective treatment of medulloblastoma by inhibiting autophagy that is known to play important role in cancer cell growth, survival and malignant behavior. Copyright © 2017 Elsevier Inc. All rights reserved.

SUPERFUND TREATABILITY CLEARINGHOUSE: FINAL REPORT: DEVELOPMENT OF OPTIMUM TREATMENT SYSTEM FOR WASTEWATER LAGOONS PHASE II - SOLVENT EXTRACTION LABORATORY TESTING

EPA Science Inventory

The U.S. Army surveyed innovative treatment techniques for restoration of hazardous waste lagoons and selected solvent extraction as cost-effective restoration for further study. This treatability study focuses on treatment of organic (explosive) contaminated lagoon sediments w...

OptFuels: Fuel treatment optimization

Treesearch

Greg Jones

2011-01-01

Scientists at the USDA Forest Service, Rocky Mountain Research Station, in Missoula, MT, in collaboration with scientists at the University of Montana, are developing a tool to help forest managers prioritize forest fuel reduction treatments. Although several computer models analyze fuels and fire behavior, stand-level effects of fuel treatments, and priority planning...

Computerized algorithms for partial cuts

Treesearch

R.L. Ernst; S.L. Stout

1991-01-01

Stand density, stand structure (diameter distribution), and species composition are all changed by intermediate treatments in forest stands. To use computer stand-growth simulators to assess the effects of different treatments on stand growth and development, users must be able to duplicate silviculturally realistic treatments in the simulator. In this paper, we review...

Alopecia Areata: Review of Epidemiology, Clinical Features, Pathogenesis, and New Treatment Options

PubMed Central

Darwin, Evan; Hirt, Penelope A; Fertig, Raymond; Doliner, Brett; Delcanto, Gina; Jimenez, Joaquin J

2018-01-01

Alopecia areata (AA) is a complex autoimmune condition that causes nonscarring hair loss. It typically presents with sharply demarcated round patches of hair loss and may present at any age. In this article, we review the epidemiology, clinical features, pathogenesis, and new treatment options of AA, with a focus on the immunologic mechanism underlying the treatment. While traditional treatment options such as corticosteroids are moderately effective, a better understanding of the disease pathogenesis may lead to the development of new treatments that are more directed and effective against AA. Sources were gathered from PubMed, Embase, and the Cochrane database using the keywords: alopecia, alopecia areata, hair loss, trichoscopy, treatments, pathogenesis, and epidemiology. PMID:29769777

Developing Content Knowledge in Struggling Readers: Differential Effects of Strategy Instruction for Younger and Older Elementary Students

ERIC Educational Resources Information Center

Elleman, Amy M.; Olinghouse, Natalie G.; Gilbert, Jennifer K.; Spencer, Jane Lawrence; Compton, Donald L.

2017-01-01

This study compared the effects of 2 strategy-based comprehension treatments intended to promote vocabulary and content knowledge for elementary students at risk for developing reading difficulties (N = 105) with a traditional content approach. The study examined the effectiveness of strategy versus nonstrategy instruction on reading…

Non-pharmacological biological treatment approaches to difficult-to-treat depression.

PubMed

Fitzgerald, Paul B

2013-09-16

There has been substantial recent interest in novel brain stimulation treatments for difficult-to-treat depression. Electroconvulsive therapy (ECT) is a well established, effective treatment for severe depression. ECT's problematic side-effect profile and questions regarding optimal administration methods continue to be investigated. Magnetic seizure therapy, although very early in development, shows promise, with potentially similar efficacy to ECT but fewer side effects. Vagus nerve stimulation (VNS) and repetitive transcranial magnetic stimulation (rTMS) are clinically available in some countries. Limited research suggests VNS has potentially long-lasting antidepressant effects in a small group of patients. Considerable research supports the efficacy of rTMS. Both techniques require further study of optimal treatment parameters. Transcranial direct current stimulation may provide a low-cost antidepressant option if its efficacy is substantiated in larger samples. Deep brain stimulation is likely to remain reserved for patients with the most severe and difficult-to-treat depression, requiring further exploration of administration methods and its role in depression therapy. New and innovative forms of brain stimulation, including low-intensity ultrasound, low-field magnetic stimulation and epidural stimulation of the cortical surface, are in early stages of exploration and are yet to move into the clinical domain. Ongoing work is required to define which brain stimulation treatments are likely to be most useful, and in which patient groups. Clinical service development of brain stimulation treatments will likely be inconsistent and variable.

Needle aspiration of calcific deposits (NACD) for calcific tendinitis is safe and effective: Six months follow-up of clinical results and complications in a series of 431 patients.

PubMed

Oudelaar, Bart W; Schepers-Bok, Relinde; Ooms, Edwin M; Huis In 't Veld, Rianne; Vochteloo, Anne J H

2016-04-01

Although needle aspiration of calcific deposits (NACD) has proven to be an effective treatment for calcific tendinitis of the rotator cuff (CTRC) in patients who are resistant to conservative treatment, little is known about the effectiveness of NACD in terms of complete relief of symptoms and the effectiveness of repeated NACD procedures. Furthermore, analyses of complications of the procedure in large series are scarce. 431 consecutive patients with symptomatic CTRC treated by NACD were included in this retrospective cohort study. Short-term effects were assessed at two weeks post-treatment by using an 11-point numeric rating scale (NRS). The six months outcome was determined on a dichotomous symptom scale (symptom free or persistence of symptoms). NACD procedures performed within six months of a previous NACD procedure were considered repeated procedures. All complications that occurred within six months of the NACD procedure were registered. At two weeks post-treatment, a significant improvement of pain scores was noted (mean reduction of NRS: 4.4 points; p<0.001). 74% of patients had complete relief of symptoms at six months post-treatment. 143 (33.2%) patients required multiple treatments. These repeated procedures were equally effective as the primary procedure. Complications of the NACD procedure were seen in 31 (7.2%) patients: 21 patients (4.9%) developed a subacromial bursitis, seven patients (1.6%) a frozen shoulder and three patients (0.7%) developed a septic bursitis. Needle aspiration of calcific deposits (NACD) is an effective treatment for calcific tendinitis of the rotator cuff in the majority of patients. Approximately one third of the patients will require multiple treatments, which were equally effective as the primary procedure. Based on this, patients should not be withheld a second or even a third treatment in case of persistent symptoms. Furthermore, NACD has a low complication rate, the risk of infection should, however, always be accounted for. Retrospective study, level IV. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

Early, but not late, treatment with human umbilical cord blood-derived mesenchymal stem cells attenuates cisplatin nephrotoxicity through immunomodulation.

PubMed

Park, Ji Hyeon; Jang, Hye Ryoun; Kim, Do Hee; Kwon, Ghee Young; Lee, Jung Eun; Huh, Wooseong; Choi, Soo Jin; Oh, Wonil; Oh, Ha Young; Kim, Yoon-Goo

2017-10-01

Preemptive treatment with mesenchymal stem cells (MSCs) can attenuate cisplatin-induced acute kidney injury (AKI). However, it is uncertain whether MSC treatment after the development of renal dysfunction prevents AKI progression or if MSC immunomodulatory properties contribute to MSC therapy. In this study, human umbilical cord blood (hUCB)-derived MSCs were used to compare the effects and mechanisms of early and late MSC therapy in a murine model. After cisplatin injection into C57BL/6 mice, hUCB-MSCs were administered on day 1 (early treatment) or day 3 (late treatment). With early treatment, cisplatin nephrotoxicity was attenuated as evidenced by decreased blood urea nitrogen (BUN) and reduced apoptosis and tubular injury scores on day 3 Early treatment resulted in downregulation of intrarenal monocyte chemotactic protein-1 and IL-6 expression and upregulation of IL-10 and VEGF expression. Flow cytometric analysis showed similar populations of infiltrated immune cells in both groups; however, regulatory T-cell (Treg) infiltration was 2.5-fold higher in the early treatment group. The role of Tregs was confirmed by the blunted effect of early treatment on renal injury after Treg depletion. In contrast, late treatment (at a time when BUN levels were 2-fold higher than baseline levels) showed no renoprotective effects on day 6 Neither the populations of intrarenal infiltrating immune cells (including Tregs) nor cytokine expression levels were affected by late treatment. Our results suggest that early MSC treatment attenuates renal injury by Treg induction and immunomodulation, whereas a late treatment (i.e., after the development of renal dysfunction) does not prevent AKI progression or alter the intrarenal inflammatory micromilieu. Copyright © 2017 the American Physiological Society.

Effects of elevated seawater pCO2 on early development of scallop Argopecten irradias (Lamarck, 1819)

NASA Astrophysics Data System (ADS)

Wang, Weimin; Liu, Guangxing; Zhang, Tianwen; Chen, Hongju; Tang, Liao; Mao, Xuewei

2016-12-01

To investigate the effects of elevated seawater pCO2 on the early developmental stages of marine benthic calcifying organisms, we exposed the eggs and larvae of Argopecten irradias, an important bivalve species in Chinese aquaculture, in seawater equilibrated with CO2-enriched (1000 ppm) gas mixtures. We demonstrated that elevated seawater pCO2 significantly interfered with fertilization and larval development and resulted in an increased aberration rate. Fertilization in the treatment (pH 7.6) was 74.3% ± 3.8%, which was 9.7% lower than that in the control (pH 8.3) (84.0% ±3.0%). Hatching success decreased by 23.7%, and aberration rate increased by 30.3% under acidic condition. Larvae in acidified seawater still developed a shell during the post-embryonic phase. However, the shell length and height in the treatment were smaller than those in the control. The development of embryos differed significantly at 12 h after fertilization between the two experimental groups. Embryos developed slower in acidified seawater. Nearly half of the embryos in the control developed into D-shaped larvae at 48 h after fertilization, which were considerably more than those in the treatment (11.7%). Results suggest that future ocean acidification (OA) would cause detrimental effects on the early development of A. irradias.

A Case of Subacute Encephalopathy Developing After Treatment With Clofarabine and Methotrexate That Resolved With Corticosteroids.

PubMed

Tzachanis, Dimitrios; Haider, Mintallah; Papazisis, Georgios

2016-01-01

This is the case of a 24-year-old woman with relapsed acute undifferentiated leukemia who developed subacute encephalopathy with hemiparesis and dysarthria after treatment with high dose and intrathecal methotrexate, clofarabine, and cytarabine that resolved rapidly and completely after the administration of corticosteroids. We hypothesize that clofarabine might predispose to methotrexate-induced central nervous system toxicity by increasing endothelial permeability (capillary leak syndrome) and suggest that corticosteroids are effective in the treatment of this type of encephalopathy.

Motion induced interplay effects for VMAT radiotherapy.

PubMed

Edvardsson, Anneli; Nordström, Fredrik; Ceberg, Crister; Ceberg, Sofie

2018-04-19

The purpose of this study was to develop a method to simulate breathing motion induced interplay effects for volumetric modulated arc therapy (VMAT), to verify the proposed method with measurements, and to use the method to investigate how interplay effects vary with different patient- and machine specific parameters. VMAT treatment plans were created on a virtual phantom in a treatment planning system (TPS). Interplay effects were simulated by dividing each plan into smaller sub-arcs using an in-house developed software and shifting the isocenter for each sub-arc to simulate a sin 6 breathing motion in the superior-inferior direction. The simulations were performed for both flattening-filter (FF) and flattening-filter free (FFF) plans and for different breathing amplitudes, period times, initial breathing phases, dose levels, plan complexities, CTV sizes, and collimator angles. The resulting sub-arcs were calculated in the TPS, generating a dose distribution including the effects of motion. The interplay effects were separated from dose blurring and the relative dose differences to 2% and 98% of the CTV volume (ΔD 98% and ΔD 2% ) were calculated. To verify the simulation method, measurements were carried out, both static and during motion, using a quasi-3D phantom and a motion platform. The results of the verification measurements during motion were comparable to the results of the static measurements. Considerable interplay effects were observed for individual fractions, with the minimum ΔD 98% and maximum ΔD 2% being  -16.7% and 16.2%, respectively. The extent of interplay effects was larger for FFF compared to FF and generally increased for higher breathing amplitudes, larger period times, lower dose levels, and more complex treatment plans. Also, the interplay effects varied considerably with the initial breathing phase, and larger variations were observed for smaller CTV sizes. In conclusion, a method to simulate motion induced interplay effects was developed and verified with measurements, which allowed for a large number of treatment scenarios to be investigated. The simulations showed large interplay effects for individual fractions and that the extent of interplay effects varied with the breathing pattern, FFF/FF, dose level, CTV size, collimator angle, and the complexity of the treatment plan.

Motion induced interplay effects for VMAT radiotherapy

NASA Astrophysics Data System (ADS)

Edvardsson, Anneli; Nordström, Fredrik; Ceberg, Crister; Ceberg, Sofie

2018-04-01

The purpose of this study was to develop a method to simulate breathing motion induced interplay effects for volumetric modulated arc therapy (VMAT), to verify the proposed method with measurements, and to use the method to investigate how interplay effects vary with different patient- and machine specific parameters. VMAT treatment plans were created on a virtual phantom in a treatment planning system (TPS). Interplay effects were simulated by dividing each plan into smaller sub-arcs using an in-house developed software and shifting the isocenter for each sub-arc to simulate a sin6 breathing motion in the superior–inferior direction. The simulations were performed for both flattening-filter (FF) and flattening-filter free (FFF) plans and for different breathing amplitudes, period times, initial breathing phases, dose levels, plan complexities, CTV sizes, and collimator angles. The resulting sub-arcs were calculated in the TPS, generating a dose distribution including the effects of motion. The interplay effects were separated from dose blurring and the relative dose differences to 2% and 98% of the CTV volume (ΔD98% and ΔD2%) were calculated. To verify the simulation method, measurements were carried out, both static and during motion, using a quasi-3D phantom and a motion platform. The results of the verification measurements during motion were comparable to the results of the static measurements. Considerable interplay effects were observed for individual fractions, with the minimum ΔD98% and maximum ΔD2% being  ‑16.7% and 16.2%, respectively. The extent of interplay effects was larger for FFF compared to FF and generally increased for higher breathing amplitudes, larger period times, lower dose levels, and more complex treatment plans. Also, the interplay effects varied considerably with the initial breathing phase, and larger variations were observed for smaller CTV sizes. In conclusion, a method to simulate motion induced interplay effects was developed and verified with measurements, which allowed for a large number of treatment scenarios to be investigated. The simulations showed large interplay effects for individual fractions and that the extent of interplay effects varied with the breathing pattern, FFF/FF, dose level, CTV size, collimator angle, and the complexity of the treatment plan.

Emerging treatments in neurogastroenterology: a multidisciplinary working group consensus statement on opioid-induced constipation

PubMed Central

CAMILLERI, M.; DROSSMAN, D. A.; BECKER, G.; WEBSTER, L. R.; DAVIES, A. N.; MAWE, G. M.

2015-01-01

Background Opioids are effective for acute and chronic pain conditions, but their use is associated with often difficult-to-manage constipation and other gastrointestinal (GI) effects due to effects on peripheral μ-opioid receptors in the gut. The mechanism of opioid-induced constipation (OIC) differs from that of functional constipation (FC), and OIC may not respond as well to most first-line treatments for FC. The impact of OIC on quality of life (QoL) induces some patients to decrease or stop their opioid therapy to relieve or avoid constipation. Purpose At a roundtable meeting on OIC, a working group developed a consensus definition for OIC diagnosis across disciplines and reviewed current OIC treatments and the potential of treatments in development. By consensus, OIC is defined as follows: ‘A change when initiating opioid therapy from baseline bowel habits that is characterized by any of the following: reduced bowel movement frequency, development or worsening of straining to pass bowel movements, a sense of incomplete rectal evacuation, or harder stool consistency’. The working group noted the prior validation of a patient response outcome and end point for clinical trials and recommended future efforts to create treatment guidelines and QoL measures specific for OIC. Details from the working group’s discussion and consensus recommendations for patient care and research are presented in this article. PMID:25164154

From political controversy to a technical problem? Fifteen years of opioid substitution treatment in Finland.

PubMed

Selin, Jani; Hakkarainen, Pekka; Partanen, Airi; Tammi, Tuukka; Tigerstedt, Christoffer

2013-11-01

The aim of the article is to analyze changes in opioid substitution treatments (OST) in Finland. OST spread in Finland in the late 1990s and early 2000s (Phase 1). Since then, OST has become an integrated part of Finnish drug policy and is provided in various substance abuse treatment units as well as in municipal health centers (Phase 2). The paper analyses the policy around the implementation of opioid substitution treatment in Finland, focusing on identifying the key factors and the relations between them that have contributed to the implementation of OST in Finland. OST has become accepted in Finland during the past ten years as a crucial element of a harm reduction strategy. Present incentives behind this development are not as clearly related to drug-specific policies as in the late 1990s; rather, they stem from both the restructuring of health care services (e.g. cost-effectiveness) and the strengthening of the medical or technico-administrative approach to the development of OST. Since the early 2000s, the development of substitution treatment in Finland has not taken place under explicit drug-political guidance, but largely as a result of many differing intended and unintended effects. One of the unintended effects is the fact that buprenorphine has replaced heroin as the most commonly misused opioid in Finland. Copyright © 2013 Elsevier B.V. All rights reserved.

Incorporating social network effects into cost-effectiveness analysis: a methodological contribution with application to obesity prevention

PubMed Central

Konchak, Chad; Prasad, Kislaya

2012-01-01

Objectives To develop a methodology for integrating social networks into traditional cost-effectiveness analysis (CEA) studies. This will facilitate the economic evaluation of treatment policies in settings where health outcomes are subject to social influence. Design This is a simulation study based on a Markov model. The lifetime health histories of a cohort are simulated, and health outcomes compared, under alternative treatment policies. Transition probabilities depend on the health of others with whom there are shared social ties. Setting The methodology developed is shown to be applicable in any healthcare setting where social ties affect health outcomes. The example of obesity prevention is used for illustration under the assumption that weight changes are subject to social influence. Main outcome measures Incremental cost-effectiveness ratio (ICER). Results When social influence increases, treatment policies become more cost effective (have lower ICERs). The policy of only treating individuals who span multiple networks can be more cost effective than the policy of treating everyone. This occurs when the network is more fragmented. Conclusions (1) When network effects are accounted for, they result in very different values of incremental cost-effectiveness ratios (ICERs). (2) Treatment policies can be devised to take network structure into account. The integration makes it feasible to conduct a cost-benefit evaluation of such policies. PMID:23117559

Childhood amblyopia: current management and new trends

PubMed Central

Tailor, Vijay; Bossi, Manuela; Greenwood, John A.; Dahlmann-Noor, Annegret

2016-01-01

Abstract Introduction or background With a prevalence of 2–5%, amblyopia is the most common vision deficit in children in the UK and the second most common cause of functional low vision in children in low-income countries. Sources of data Pubmed, Cochrane library and clinical trial registries (clinicaltrials.gov, ISRCTN, UKCRN portfolio database). Areas of agreement Screening and treatment at the age of 4–5 years are cost efficient and clinically effective. Optical treatment (glasses) alone can improve visual acuity, with residual amblyopia treated by part-time occlusion or pharmacological blurring of the better-seeing eye. Treatment after the end of the conventional ‘critical period’ can improve vision, but in strabismic amblyopia carries a low risk of double vision. Areas of controversy It is not clear whether earlier vision screening would be cost efficient and associated with better outcomes. Optimization of treatment by individualized patching regimes or early start of occlusion, and novel binocular treatment approaches may enhance adherence to treatment, provide better outcomes and shorten treatment duration. Growing points Binocular treatments for amblyopia. Areas timely for developing research Impact of amblyopia on education and quality of life; optimal screening timing and tests; optimal administration of conventional treatments; development of child-friendly, effective and safe binocular treatments. PMID:27543498

IncobotulinumtoxinA treatment of facial nerve palsy after neurosurgery.

PubMed

Akulov, Mihail A; Orlova, Ol'ga R; Orlova, Aleksandra S; Usachev, Dmitrij J; Shimansky, Vadim N; Tanjashin, Sergey V; Khatkova, Svetlana E; Yunosha-Shanyavskaya, Anna V

2017-10-15

This study evaluates the effect of incobotulinumtoxinA in the acute and chronic phases of facial nerve palsy after neurosurgical interventions. Patients received incobotulinumtoxinA injections (active treatment group) or standard rehabilitation treatment (control group). Functional efficacy was assessed using House-Brackmann, Yanagihara System and Sunnybrook Facial Grading scales, and Facial Disability Index self-assessment. Significant improvements on all scales were seen after 1month of incobotulinumtoxinA treatment (active treatment group, р<0.05), but only after 3months of rehabilitation treatment (control group, р<0.05). At 1 and 2years post-surgery, the prevalence of synkinesis was significantly higher in patients in the control group compared with those receiving incobotulinumtoxinA treatment (р<0.05 and р<0.001, respectively). IncobotulinumtoxinA treatment resulted in significant improvements in facial symmetry in patients with facial nerve injury following neurosurgical interventions. Treatment was effective for the correction of the compensatory hyperactivity of mimic muscles on the unaffected side that develops in the acute period of facial nerve palsy, and for the correction of synkinesis in the affected side that develops in the long-term period. Appropriate dosing and patient education to perform exercises to restore mimic muscle function should be considered in multimodal treatment. Copyright © 2017 Elsevier B.V. All rights reserved.

Choosing a Control Group in Effectiveness Trials of Behavioral Drug Abuse Treatments

PubMed Central

Brigham, Gregory S.; Feaster, Daniel J.; Wakim, Paul G.; Dempsey, Catherine L.

2009-01-01

Effectiveness trials are an important step in the scientific process of developing and evaluating behavioral treatments. The focus on effectiveness research presents a different set of requirements on the research design when compared with efficacy studies. The choice of a control condition has many implications for a clinical trial's internal and external validity. The purpose of this manuscript is to provide a discussion of the issues involved in choosing a control group for effectiveness trials of behavioral interventions in substance abuse treatment. The authors provide a description of four trial designs and a discussion of the advantages and disadvantages of each. PMID:19553062

Laser heat puncturing as highly effective method of post-tuberculous cystalgia treatment

NASA Astrophysics Data System (ADS)

Koultchavenia, Ekaterina V.; Krasnov, Vladimir A.

1999-09-01

The tuberculosis of an urine bladder in men develops less often, and recovery is authentic more often, than in women. In 39.1% of the female patients with nephrotuberculosis, a specific cystitis is finished in postturberculous cystalgia. One of starting mechanisms of disuria after urocystis tuberculosis in the women in menopause is hormonal insufficiency. The method of laserheatpuncturing, developed by us, for the treatment this complication is highly effective, does not require additional introduction of medicines, can be executed as in hospitals, and in out-patient.

Systematic review of catatonia treatment.

PubMed

Pelzer, Anne Cm; van der Heijden, Frank Mma; den Boer, Erik

2018-01-01

To investigate the evidence-based treatment of catatonia in adults. The secondary aim is to develop a treatment protocol. A systematic review of published treatment articles (case series, cohort or randomized controlled studies) which examined the effects of particular interventions for catatonia and/or catatonic symptoms in adult populations and used valid outcome measures was performed. The articles for this review were selected by searching the electronic databases of the Cochrane Library, MEDLINE, EMBASE and PSYCHINFO. Thirty-one articles met the inclusion criteria. Lorazepam and electroconvulsive therapy (ECT) proved to be the most investigated treatment interventions. The response percentages in Western studies varied between 66% and 100% for studies with lorazepam, while in Asian and Indian studies, they were 0% and 100%. For ECT, the response percentages are 59%-100%. There does not seem to be evidence for the use of antipsychotics in catatonic patients without any underlying psychotic disorder. Lorazepam and ECT are effective treatments for which clinical evidence is found in the literature. It is not possible to develop a treatment protocol because the evidence for catatonia management on the basis of the articles reviewed is limited. Stringent treatment studies on catatonia are warranted.

Systematic review of catatonia treatment

PubMed Central

Pelzer, Anne CM; van der Heijden, Frank MMA; den Boer, Erik

2018-01-01

Objective To investigate the evidence-based treatment of catatonia in adults. The secondary aim is to develop a treatment protocol. Materials and methods A systematic review of published treatment articles (case series, cohort or randomized controlled studies) which examined the effects of particular interventions for catatonia and/or catatonic symptoms in adult populations and used valid outcome measures was performed. The articles for this review were selected by searching the electronic databases of the Cochrane Library, MEDLINE, EMBASE and PSYCHINFO. Results Thirty-one articles met the inclusion criteria. Lorazepam and electroconvulsive therapy (ECT) proved to be the most investigated treatment interventions. The response percentages in Western studies varied between 66% and 100% for studies with lorazepam, while in Asian and Indian studies, they were 0% and 100%. For ECT, the response percentages are 59%–100%. There does not seem to be evidence for the use of antipsychotics in catatonic patients without any underlying psychotic disorder. Conclusion Lorazepam and ECT are effective treatments for which clinical evidence is found in the literature. It is not possible to develop a treatment protocol because the evidence for catatonia management on the basis of the articles reviewed is limited. Stringent treatment studies on catatonia are warranted. PMID:29398916

Effects of logging debris treatments on five-year development of competing vegetation and planted Douglas-fir

Treesearch

Timothy B. Harrington; Stephen H. Schoenholtz

2010-01-01

Although considerable research has focused on the influences of logging debris treatments on soil and forest regeneration responses, few studies have identified whether debris effects are mediated by associated changes in competing vegetation abundance. At sites near Matlock, Washington, and Molalla, Oregon, studies were initiated after timber harvest to quantify the...

The Design of an Effective Family Reintegration and Aftercare Program for Youth Successfully Leaving Residential Care.

ERIC Educational Resources Information Center

Roley, Jeffrey H.

The lack of support services following the release of adolescent youths from a residential treatment center back to their families is examined in this practicum. Consequently, the development of a family reintegration program for the treatment center is focused on the concept that effective aftercare begins at intake. Understandably, families…

Effects of Once-Daily Oral and Transdermal Methylphenidate on Sleep Behavior of Children with ADHD

ERIC Educational Resources Information Center

Faraone, Stephen V.; Glatt, Stephen J.; Bukstein, Oscar G.; Lopez, Frank A.; Arnold, L. Eugene; Findling, Robert L.

2009-01-01

Objective: Methylphenidate is a leading first-line treatment for ADHD (AD/HD). This stimulant has long been suspected to adversely affect sleeping patterns of treated individuals, especially children. There are few studies on the effects of recently developed longer-acting methylphenidate treatments, such as once-daily oral or transdermal…

Disrupting nicotine reinforcement: from cigarette to brain.

PubMed

Rose, Jed E

2008-10-01

Cigarette smoking is a tenacious addiction that is maintained to a significant extent by the reinforcing effects of nicotine. An emerging theme in smoking cessation treatment is the development of methods for interfering with these reinforcing effects. By attenuating nicotine reinforcement, treatments may enhance a smoker's chances of successfully remaining abstinent. Several treatment approaches will be described, including the use of denicotinized cigarettes, nicotine vaccines, nicotinic receptor agonists and antagonists, and modulators of brain reinforcement processes. These techniques highlight the numerous sites along the path between the cigarette and the brain that can be targeted for intervention. In addition to unimodal therapies, treatment combinations will be discussed that might more effectively block cigarette reward and thereby further enhance smoking abstinence.

Proton Radiotherapy for Solid Tumors of Childhood

PubMed Central

Cotter, Shane E.; McBride, Sean M.; Yock, Torunn I.

2012-01-01

The increasing efficacy of pediatric cancer therapy over the past four decades has produced many long-term survivors that now struggle with serious treatment related morbidities affecting their quality of life. Radiation therapy is responsible for a significant proportion of these late effects, but a relatively new and emerging modality, proton radiotherapy hold great promise to drastically reduce these treatment related late effects in long term survivors by sparing dose to normal tissues. Dosimetric studies of proton radiotherapy compared with best available photon based treatment show significant dose sparing to developing normal tissues. Furthermore, clinical data are now emerging that begin to quantify the benefit in decreased late treatment effects while maintaining excellent cancer control rates. PMID:22417062

Treatment planning for heavy ion radiotherapy: clinical implementation and application.

PubMed

Jäkel, O; Krämer, M; Karger, C P; Debus, J

2001-04-01

The clinical implementation and application of a novel treatment planning system (TPS) for scanned ion beams is described, which is in clinical use for carbon ion treatments at the German heavy ion facility (GSI). All treatment plans are evaluated on the basis of biologically effective dose distributions. For therapy control, in-beam positron emission tomography (PET) and an online monitoring system for the beam intensity and position are used. The absence of a gantry restricts the treatment plans to horizontal beams. Most of the treatment plans consist of two nearly opposing lateral fields or sometimes orthogonal fields. In only a very few cases a single beam was used. For patients with very complex target volumes lateral and even distal field patching techniques were applied. Additional improvements can be achieved when the patient's head is fixed in a tilted position, in order to achieve sparing of the organs at risk. In order to test the stability of dose distributions in the case of patient misalignments we routinely simulate the effects of misalignments for patients with critical structures next to the target volume. The uncertainties in the range calculation are taken into account by a margin around the target volume of typically 2-3 mm, which can, however, be extended if the simulation demonstrates larger deviations. The novel TPS developed for scanned ion beams was introduced into clinical routine in December 1997 and was used for the treatment planning of 63 patients with head and neck tumours until July 2000. Planning strategies and methods were developed for this tumour location that facilitate the treatment of a larger number of patients with the scanned heavy ion beam in a clinical setting. Further developments aim towards a simultaneous optimization of the treatment field intensities and more effective procedures for the patient set-up. The results demonstrate that ion beams can be integrated into a clinical environment for treatment planning and delivery.

Survival analysis using inverse probability of treatment weighted methods based on the generalized propensity score.

PubMed

Sugihara, Masahiro

2010-01-01

In survival analysis, treatment effects are commonly evaluated based on survival curves and hazard ratios as causal treatment effects. In observational studies, these estimates may be biased due to confounding factors. The inverse probability of treatment weighted (IPTW) method based on the propensity score is one of the approaches utilized to adjust for confounding factors between binary treatment groups. As a generalization of this methodology, we developed an exact formula for an IPTW log-rank test based on the generalized propensity score for survival data. This makes it possible to compare the group differences of IPTW Kaplan-Meier estimators of survival curves using an IPTW log-rank test for multi-valued treatments. As causal treatment effects, the hazard ratio can be estimated using the IPTW approach. If the treatments correspond to ordered levels of a treatment, the proposed method can be easily extended to the analysis of treatment effect patterns with contrast statistics. In this paper, the proposed method is illustrated with data from the Kyushu Lipid Intervention Study (KLIS), which investigated the primary preventive effects of pravastatin on coronary heart disease (CHD). The results of the proposed method suggested that pravastatin treatment reduces the risk of CHD and that compliance to pravastatin treatment is important for the prevention of CHD. (c) 2009 John Wiley & Sons, Ltd.

Effects of sulfate chitosan derivatives on nonalcoholic fatty liver disease

NASA Astrophysics Data System (ADS)

Yu, Mingming; Wang, Yuanhong; Jiang, Tingfu; Lv, Zhihua

2014-06-01

Sulfate chitosan derivatives have good solubility and therapeutic effect on the cell model of NAFLD. The aim of this study was to examine the therapeutic effect of sulfate chitosan derivatives on NAFLD. The male Wistar rats were orally fed high fat emulsion and received sulfate chitosan derivatives for 5 weeks to determine the pre-treatment effect of sulfate chitosan derivatives on NAFLD. To evaluate the therapeutic effect of sulfate chitosan derivatives on NAFLD, the rats were orally fed with high concentration emulsion for 5 weeks, followed by sulfate chitosan derivatives for 3 weeks. Histological analysis and biomedical assays showed that sulfate chitosan derivatives can dramatically prevent the development of hepatic steatosis in hepatocyte cells. In animal studies, pre-treatment and treatment with sulfate chitosan derivatives significantly protected against hepatic steatohepatitis induced by high fat diet according to histological analysis. Furthermore, increased TC, ALT, MDA, and LEP in NAFLD were significantly ameliorated by pre-treatment and treatment with sulfate chitosan derivatives. Furthermore, increased TG, AST, and TNF-α in NAFLD were significantly ameliorated by treatment with sulfate chitosan derivatives. Sulfate chitosan derivatives have good pre-treatment and therapeutic effect on NAFLD.

Ramipril retards development of aortic valve stenosis in a rabbit model: mechanistic considerations.

PubMed

Ngo, Doan Tm; Stafford, Irene; Sverdlov, Aaron L; Qi, Weier; Wuttke, Ronald D; Zhang, Yuan; Kelly, Darren J; Weedon, Helen; Smith, Malcolm D; Kennedy, Jennifer A; Horowitz, John D

2011-02-01

Aortic valve stenosis (AVS) is associated with significant cardiovascular morbidity and mortality. To date, no therapeutic modality has been shown to be effective in retarding AVS progression. We evaluated the effect of angiotensin-converting enzyme inhibition with ramipril on disease progression in a recently developed rabbit model of AVS. The effects of 8 weeks of treatment with either vitamin D₂ at 25,000 IU for 4 days a week alone or in combination with ramipril (0.5 mg·kg⁻¹) on aortic valve structure and function were examined in New Zealand white rabbits. Echocardiographic aortic valve backscatter (AV(BS)) and aortic valve:outflow tract flow velocity ratio were utilized to quantify changes in valve structure and function. Treatment with ramipril significantly reduced AV(BS) and improved aortic valve :outflow tract flow velocity ratio. The intravalvular content of the pro-oxidant thioredoxin-interacting protein was decreased significantly with ramipril treatment. Endothelial function, as measured by asymmetric dimethylarginine concentrations and vascular responses to ACh, was improved significantly with ramipril treatment. Ramipril retards the development of AVS, reduces valvular thioredoxin-interacting protein accumulation and limits endothelial dysfunction in this animal model. These findings provide important insights into the mechanisms of AVS development and an impetus for future human studies of AVS retardation using an angiotensin-converting enzyme inhibitor. © 2011 The Authors. British Journal of Pharmacology © 2011 The British Pharmacological Society.

Anti-proliferative effect of biogenic gold nanoparticles against breast cancer cell lines (MDA-MB-231 & MCF-7)

NASA Astrophysics Data System (ADS)

K. S., Uma Suganya; Govindaraju, K.; Ganesh Kumar, V.; Prabhu, D.; Arulvasu, C.; Stalin Dhas, T.; Karthick, V.; Changmai, Niranjan

2016-05-01

Breast cancer is a major complication in women and numerous approaches are being developed to overcome this problem. In conventional treatments such as chemotherapy and radiotherapy the post side effects cause an unsuitable effect in treatment of cancer. Hence, it is essential to develop a novel strategy for the treatment of this disease. In the present investigation, a possible route for green synthesis of gold nanoparticles (AuNPs) using leaf extract of Mimosa pudica and its anticancer efficacy in the treatment of breast cancer cell lines is studied. The synthesized nanoparticles were found to be effective in killing cancer cells (MDA-MB-231 & MCF-7) which were studied using various anticancer assays (MTT assay, cell morphology determination, cell cycle analysis, comet assay, Annexin V-FITC/PI staining and DAPI staining). Cell morphological analysis showed the changes occurred in cancer cells during the treatment with AuNPs. Cell cycle analysis revealed apoptosis in G0/G1 to S phase. Similarly in Comet assay, there was an increase in tail length in treated cells in comparison with the control. Annexin V-FITC/PI staining assay showed prompt fluorescence in treated cells indicating the translocation of phosphatidylserine from the inner membrane. PI and DAPI staining showed the DNA damage in treated cells.

In vivo treatment with interleukin 12 protects mice from immune abnormalities observed during murine acquired immunodeficiency syndrome (MAIDS)

PubMed Central

1994-01-01

Lymphoproliferation, chronic B cell activation resulting in hypergammaglobulinemia, and profound immunodeficiency are prominent features of a retrovirus-induced syndrome designated murine acquired immunodeficiency syndrome (MAIDS). In vivo treatment of infected mice with recombinant interleukin 12 (IL-12) beginning at the time of infection or up to 9 wk after virus inoculation markedly inhibited the development of splenomegaly and lymphadenopathy, as well as B cell activation and Ig secretion. Treatment with IL-12 also had major effects in preventing induction of several immune defects including impaired production of interferon gamma (IFN-gamma) and IL-2 and depressed proliferative responses to various stimuli. The therapeutic effects of IL-12 on the immune system of mice with MAIDS were also associated with reduced expression of the retrovirus that causes this disease (BM5def), with lesser effects on expression of ecotropic MuLV. IL-12 treatment was not effective in IFN-gamma knockout mice or in infected mice treated simultaneously with IL-12 and anti-IFN-gamma. These results demonstrate that induction and progression of MAIDS are antagonized by IL-12 through high-level expression of IFN-gamma and may provide an experimental basis for developing treatments of retrovirus- induced immune disorders with similar immunopathogenic mechanisms. PMID:7964495

Apomorphine conditioning and sensitization: the paired/unpaired treatment order as a new major determinant of drug conditioned and sensitization effects.

PubMed

de Matos, Liana Wermelinger; Carey, Robert J; Carrera, Marinete Pinheiro

2010-09-01

Repeated treatments with psychostimulant drugs generate behavioral sensitization. In the present study we employed a paired/unpaired protocol to assess the effects of repeated apomorphine (2.0 mg/kg) treatments upon locomotion behavior. In the first experiment we assessed the effects of conditioning upon apomorphine sensitization. Neither the extinction of the conditioned response nor a counter-conditioning procedure in which we paired an inhibitory treatment (apomorphine 0.05 mg/kg) with the previously established conditioned stimulus modified the sensitization response. In the second experiment, we administered the paired/unpaired protocol in two phases. In the second phase, we reversed the paired/unpaired protocol. Following the first phase, the paired group alone exhibited conditioned locomotion in the vehicle test and a sensitization response. In the second phase, the initial unpaired group which received 5 paired apomorphine trials during the reversal phase did not develop a conditioned response but developed a potentiated sensitization response. This disassociation of the conditioned response from the sensitization response is attributed to an apomorphine anti-habituation effect that can generate a false positive Pavlovian conditioned response effect. The potentiated sensitization response induced by the treatment reversal protocol points to an important role for the sequential experience of the paired/unpaired protocol in behavioral sensitization. 2010 Elsevier Inc. All rights reserved.

Development of Gene Therapeutics for Head and Neck Cancer in China: From Bench to Bedside.

PubMed

Guo, Wei; Song, Hao

2018-02-01

Head and neck cancer represents the seventh most common cancer worldwide. Although multidisciplinary sequential treatments have been used, there is still an urgent need for new treatment approaches that can effectively improve the outcomes of patients with advanced stages of head and neck cancer. Gene therapy is a rapidly evolving field in cancer therapy that has been shown to improve the efficacy of antitumor treatment. China is at the forefront in clinical trials and practice of gene therapy. Chinese researchers have mainly focused on gene therapeutics based on oncolytic virus and recombinant adenovirus expressing p53, antiangiogenesis factor or herpes simplex virus-thymidine kinase. Currently, two gene therapy drugs, Gendicine and Oncorine, have been marketed in China, and a number of upcoming gene therapy agents are under development for the treatment of head and neck cancer. Most gene therapy agents have demonstrated excellent tolerance. However, the therapeutic effects need further improvement. With current innovations in tumor biology and knowledge, gene therapy has great potential as a safe and effective anticancer treatment. In recent years, new gene therapy agents with promising effects have been incorporated into clinical trials in China. Thus, gene therapy may become an important part of anticancer therapy and is expected to improve the therapeutic effect of head and neck cancers in the near future.

Robust estimation of the proportion of treatment effect explained by surrogate marker information.

PubMed

Parast, Layla; McDermott, Mary M; Tian, Lu

2016-05-10

In randomized treatment studies where the primary outcome requires long follow-up of patients and/or expensive or invasive obtainment procedures, the availability of a surrogate marker that could be used to estimate the treatment effect and could potentially be observed earlier than the primary outcome would allow researchers to make conclusions regarding the treatment effect with less required follow-up time and resources. The Prentice criterion for a valid surrogate marker requires that a test for treatment effect on the surrogate marker also be a valid test for treatment effect on the primary outcome of interest. Based on this criterion, methods have been developed to define and estimate the proportion of treatment effect on the primary outcome that is explained by the treatment effect on the surrogate marker. These methods aim to identify useful statistical surrogates that capture a large proportion of the treatment effect. However, current methods to estimate this proportion usually require restrictive model assumptions that may not hold in practice and thus may lead to biased estimates of this quantity. In this paper, we propose a nonparametric procedure to estimate the proportion of treatment effect on the primary outcome that is explained by the treatment effect on a potential surrogate marker and extend this procedure to a setting with multiple surrogate markers. We compare our approach with previously proposed model-based approaches and propose a variance estimation procedure based on a perturbation-resampling method. Simulation studies demonstrate that the procedure performs well in finite samples and outperforms model-based procedures when the specified models are not correct. We illustrate our proposed procedure using a data set from a randomized study investigating a group-mediated cognitive behavioral intervention for peripheral artery disease participants. Copyright © 2015 John Wiley & Sons, Ltd.

Pharmacotherapy in Generalized Anxiety Disorder: Novel Experimental Medicine Models and Emerging Drug Targets.

PubMed

Baldwin, David S; Hou, Ruihua; Gordon, Robert; Huneke, Nathan T M; Garner, Matthew

2017-04-01

Many pharmacological and psychological approaches have been found efficacious in patients with generalized anxiety disorder (GAD), but many treatment-seeking patients will not respond and others will relapse despite continuing with interventions that initially had beneficial effects. Other patients will respond but then stop treatment early because of untoward effects such as sexual dysfunction, drowsiness, and weight gain. There is much scope for the development of novel approaches that could have greater overall effectiveness or acceptability than currently available interventions or that have particular effectiveness in specific clinical subgroups. 'Experimental medicine' studies in healthy volunteers model disease states and represent a proof-of-concept approach for the development of novel therapeutic interventions: they determine whether to proceed to pivotal efficacy studies and so can reduce delays in translating innovations into clinical practice. Investigations in healthy volunteers challenged with the inhalation of air 'enriched' with 7.5% carbon dioxide (CO 2 ) indicate this technique provides a validated and robust experimental medicine model, mirroring the subjective, autonomic, and cognitive features of GAD. The anxiety response during CO 2 challenge probably involves both central noradrenergic neurotransmission and effects on acid-base sensitive receptors and so may stimulate development of novel agents targeted at central chemosensors. Increasing awareness of the potential role of altered cytokine balance in anxiety and the interplay of cytokines with monoaminergic mechanisms may also encourage the investigation of novel agents with modulating effects on immunological profiles. Although seemingly disparate, these two approaches to treatment development may pivot on a shared mechanism in exerting anxiolytic-like effects through pharmacological effects on acid-sensing ion channels.

Effect of Randomized Lipid Lowering With Simvastatin and Ezetimibe on Cataract Development (from the Simvastatin and Ezetimibe in Aortic Stenosis Study).

PubMed

Bang, Casper N; Greve, Anders M; La Cour, Morten; Boman, Kurt; Gohlke-Bärwolf, Christa; Ray, Simon; Pedersen, Terje; Rossebø, Anne; Okin, Peter M; Devereux, Richard B; Wachtell, Kristian

2015-12-15

Recent American College of Cardiology/American Heart Association guidelines on statin initiation on the basis of total atherosclerotic cardiovascular disease risk argue that the preventive effect of statins on cardiovascular events outweigh the side effects, although this is controversial. Studies indicate a possible effect of statin therapy on reducing risk of lens opacities. However, the results are conflicting. The Simvastatin and Ezetimibe in Aortic Stenosis study (NCT00092677) enrolled 1,873 patients with asymptomatic aortic stenosis and no history of diabetes, coronary heart disease, or other serious co-morbidities were randomized (1:1) to double-blind 40 mg simvastatin plus 10 mg ezetimibe versus placebo. The primary end point in this substudy was incident cataract. Univariate and multivariate Cox models were used to analyze: (1) if the active treatment reduced the risk of the primary end point and (2) if time-varying low-density lipoproteins (LDL) cholesterol lowering (annually assessed) was associated with less incident cataract per se. During an average follow-up of 4.3 years, 65 patients (3.5%) developed cataract. Mean age at baseline was 68 years and 39% were women. In Cox multivariate analysis adjusted for age, gender, prednisolone treatment, smoking, baseline LDL cholesterol and high sensitivity C-reactive protein; simvastatin plus ezetimibe versus placebo was associated with 44% lower risk of cataract development (hazard ratio 0.56, 95% confidence interval 0.33 to 0.96, p = 0.034). In a parallel analysis substituting time-varying LDL-cholesterol with randomized treatment, lower intreatment LDL-cholesterol was in itself associated with lower risk of incident cataract (hazard ratio 0.78 per 1 mmol/ml lower total cholesterol, 95% confidence interval 0.64 to 0.93, p = 0.008). In conclusion, randomized treatment with simvastatin plus ezetimibe was associated with a 44% lower risk of incident cataract development. This effect should perhaps be considered in the risk-benefit ratio of statin treatment. Copyright © 2015 Elsevier Inc. All rights reserved.

Effect of heat treatment of wood on the morphology, surface roughness and penetration of simulated and human blood.

PubMed

Rekola, J; Lassila, L V J; Nganga, S; Ylä-Soininmäki, A; Fleming, G J P; Grenman, R; Aho, A J; Vallittu, P K

2014-01-01

Wood has been used as a model material for the development of novel fiber-reinforced composite bone substitute biomaterials. In previous studies heat treatment of wood was perceived to significantly increase the osteoconductivity of implanted wood material. The objective of this study was to examine some of the changing attributes of wood materials that may contribute to improved biological responses gained with heat treatment. Untreated and 140°C and 200°C heat-treated downy birch (Betula pubescens Ehrh.) were used as the wood materials. Surface roughness and the effect of pre-measurement grinding were measured with contact and non-contact profilometry. Liquid interaction was assessed with a dipping test using two manufactured liquids (simulated blood) as well as human blood. SEM was used to visualize possible heat treatment-induced changes in the hierarchical structure of wood. The surface roughness was observed to significantly decrease with heat treatment. Grinding methods had more influence on the surface contour and roughness than heat treatment. The penetration of the human blood in the 200°C heat-treated exceeded that in the untreated and 140°C heat-treated materials. SEM showed no significant change due to heat treatment in the dry-state morphology of the wood. The results of the liquid penetration test support previous findings in literature concerning the effects of heat treatment on the biological response to implanted wood. Heat-treatment has only a marginal effect on the surface contour of wood. The highly specialized liquid conveyance system of wood may serve as a biomimetic model for the further development of tailored fiber-composite materials.

Cost-effectiveness of a barrier-strengthening moisturizing cream as maintenance therapy vs. no treatment after an initial steroid course in patients with atopic dermatitis in Sweden--with model applications for Denmark, Norway and Finland.

PubMed

Hjalte, F; Asseburg, C; Tennvall, G R

2010-04-01

Atopic dermatitis (AD) affects health and quality of life and it has great impact on both health-care costs and costs to the society. The objective of this study was to develop a model to analyse the cost-effectiveness of a barrier-strengthening moisturizing cream as maintenance therapy compared with no treatment after initial treatment with betamethasone valerate in adult patients with AD in Sweden. A further aim was to apply a similar health-economic analysis for Denmark, Norway and Finland. A Markov simulation model was developed including data from three sources: (i) efficacy data from a randomized controlled trial including patients with moderate AD treated with either a moisturizing cream or no treatment, (ii) resource utilization and quality of life data, and (iii) unit prices from official price lists. A societal perspective was used and the analysis was performed according to treatment practice in Sweden. The model simulation was also applied for Denmark, Norway and Finland with inclusion of country-specific unit costs. Sensitivity analyses were performed to test the robustness of the results. The results from the present analyses of treatment for patients with moderate AD indicate that maintenance treatment with a moisturizing cream during eczema-free periods could be cost-effective in a societal perspective. Similar results were obtained for Sweden, Denmark, Norway and Finland. According to the analysis, treatment with a moisturizing cream was found to be a cost-effective option compared with no treatment in eczema-free periods in adult patients with AD in the four Nordic countries.

Enhancing the Effectiveness of Smoking Treatment Research: Conceptual Bases and Progress

PubMed Central

Baker, Timothy B.; Collins, Linda M.; Mermelstein, Robin; Piper, Megan E.; Schlam, Tanya R.; Cook, Jessica W.; Bolt, Daniel M.; Smith, Stevens S.; Jorenby, Douglas E.; Fraser, David; Loh, Wei-Yin; Theobald, Wendy E.; Fiore, Michael C.

2015-01-01

Background and aims A chronic care strategy could potentially enhance the reach and effectiveness of smoking treatment by providing effective interventions for all smokers, including those who are initially unwilling to quit. This paper describes the conceptual bases of a National Cancer Institute-funded research program designed to develop an optimized, comprehensive, chronic care smoking treatment. Methods This research is grounded in three methodological approaches: 1) the Phase-Based Model, which guides the selection of intervention components to be experimentally evaluated for the different phases of smoking treatment (motivation, preparation, cessation, and maintenance); 2) the Multiphase Optimization Strategy (MOST), which guides the screening of intervention components via efficient experimental designs and, ultimately, the assembly of promising components into an optimized treatment package; and 3) pragmatic research methods, such as electronic health record recruitment, that facilitate the efficient translation of research findings into clinical practice. Using this foundation and working in primary care clinics, we conducted three factorial experiments (reported in three accompanying articles) to screen 15 motivation, preparation, cessation, and maintenance phase intervention components for possible inclusion in a chronic care smoking treatment program. Results This research identified intervention components with relatively strong evidence of effectiveness at particular phases of smoking treatment and it demonstrated the efficiency of the MOST approach in terms both of the number of intervention components tested and of the richness of the information yielded. Conclusions A new, synthesized research approach efficiently evaluates multiple intervention components to identify promising components for every phase of smoking treatment. Many intervention components interact with one another, supporting the use of factorial experiments in smoking treatment development. PMID:26581974

Effects of a Family-Implemented Treatment on the Repetitive Behaviors of Children with Autism

PubMed Central

McDonough, Stephen G.; Rupp, Betty; Khan, Faraaz; Bodfish, James W.

2013-01-01

The restricted and repetitive behaviors of children with autism can interfere with family functioning as well as learning and socialization opportunities for the child. To date, neither pharmacological nor comprehensive behavioral treatments have been found to be consistently effective at significantly reducing children’s engagement in repetitive behaviors. We developed Family-Implemented Treatment for Behavioral Inflexibility (FITBI) to target the full variety of repetitive behaviors found in autism. For the current study, a therapist and parents of five children with autism (mean age = 48 months) co-implemented FITBI in a clinic setting over a 12-week treatment period. Using single case design methodology, significant reductions in repetitive behaviors were found for all participants and maintenance of treatment effects for 4 of 5 participants. PMID:21161576

Glutamate Receptor Antagonists as Fast-Acting Therapeutic Alternatives for the Treatment of Depression: Ketamine and Other Compounds

PubMed Central

Niciu, Mark J.; Henter, Ioline D.; Luckenbaugh, David A.; Zarate, Carlos A.; Charney, Dennis S.

2014-01-01

The N-methyl-d-aspartate (NMDA) receptor antagonist ketamine has rapid and potent antidepressant effects in treatment-resistant major depressive disorder and bipolar depression. These effects are in direct contrast to the more modest effects seen after weeks of treatment with classic monoaminergic antidepressants. Numerous open-label and case studies similarly validate ketamine’s antidepressant properties. These clinical findings have been reverse-translated into preclinical models in an effort to elucidate ketamine’s antidepressant mechanism of action, and three important targets have been identified: mammalian target of rapamycin (mTOR), eukaryotic elongation factor 2 (eEF2), and glycogen synthase kinase-3 (GSK-3). Current clinical and preclinical research is focused on (a) prolonging/maintaining ketamine’s antidepressant effects, (b) developing more selective NMDA receptor antagonists free of ketamine’s adverse effects, and (c) identifying predictor, mediator/moderator, and treatment response biomarkers of ketamine’s antidepressant effects. PMID:24392693

Eicosanoid signalling pathways in the development and progression of colorectal cancer: novel approaches for prevention/intervention.

PubMed

Cathcart, Mary-Clare; Lysaght, Joanne; Pidgeon, Graham P

2011-12-01

Arachidonic acid metabolism through cyclooxygenase (COX), lipoxygenase (LOX) and cytochrome P-450 epoxygenase (EPOX) pathways leads to the generation of biologically active eicosanoids, including prostanoids, leukotrienes, hydroxyeicosatetraenoic acid, epoxyeicosatrienoic acid and hydroperoxyeicosatetraenoic acids. Eicosanoid expression levels vary during tumor development and progression of a range of malignancies, including colorectal cancer. The actions of these autocoids are also directly influenced by diet, as demonstrated by recent evidence for omega-3 fatty acids in colorectal cancer (CRC) prevention and/or treatment. Eicosanoids regulate CRC development and progression, while inhibition of these pathways has generally been shown to inhibit tumor growth/progression. A progressive sequence of colorectal cancer development has been identified, ranging from normal colon, to colitis, dysplasia, and carcinoma. While both COX and LOX inhibition are both promising candidates for colorectal cancer prevention and/or treatment, there is an urgent need to understand the mechanisms through which these signalling pathways mediate their effects on tumorigenesis. This will allow identification of safer, more effective strategies for colorectal cancer prevention and/or treatment. In particular, binding to/signalling through prostanoid receptors have recently been the subject of considerable interest in this area. In this review, we discuss the role of the eicosanoid signalling pathways in the development and progression of colorectal cancer. We discuss the effects of the eicosanoids on tumor cell proliferation, their roles in cell death induction, effects on angiogenesis, migration, invasion and their regulation of the immune response. Signal transduction pathways involved in these processes are also discussed. Finally, novel approaches targeting these arachidonic acid-derived eicosanoids (using pharmacological or natural agents) for chemoprevention and/or treatment of colorectal cancer are outlined.

Effect of antibiotics on clinical, pathologic and immunologic responses in murine Potomac horse fever: protective effects of doxycycline.

PubMed

Rikihisa, Y; Jiang, B M

1989-03-01

Effects of three antibiotics on clinical, pathologic and immunologic responses in murine Potomac horse fever caused by Ehrlichia risticii infection were examined. When antibiotics were given after the development of clinical signs, antibiotics ranked in the order of reducing clinical signs and in preventing body weight loss and an intestinal enlargement were doxycycline, demeclocycline and rifampin. Infected mice treated with doxycycline and demeclocycline developed greater splenomegaly than rifampin-treated or untreated infected mice. All antibiotics used prevented thymic atrophy due to E. risticii infection. Indirect fluorescent antibody titers were highest with doxycycline treatment. Mice treated with demeclocycline and rifampin produced higher antibody titer than those without treatment. Ehrlichia risticii was reisolated from the spleens of both untreated and rifampin-treated infected mice. The effects of administering single doses of doxycycline at different times after infection were examined. Body weight loss was prevented by the drug given at every treatment day examined, i.e. Days 3, 5 and 7 post-infection (PI). Thymic atrophy was minimum in mice treated at Day 5 PI, while splenomegaly was found on every treatment day. Splenocyte proliferative response to concanavalin A and lipopolysaccharide, and specific antibody development against E. risticii was best in mice treated at Day 5 PI followed by those treated at Day 3 and Day 7 PI.

A strategic plan to accelerate development of acute stroke treatments.

PubMed

Marler, John R

2012-09-01

In order to reenergize acute stroke research and accelerate the development of new treatments, we need to transform the usual design and conduct of clinical trials to test for small but significant improvements in effectiveness, and treat patients as soon as possible after stroke onset when treatment effects are most detectable. This requires trials that include thousands of acute stroke patients. A plan to make these trials possible is proposed. There are four components: (1) free access to the electronic medical record; (2) a large stroke emergency network and clinical trial coordinating center connected in real time to hundreds of emergency departments; (3) a clinical trial technology development center; and (4) strategic leadership to raise funds, motivate clinicians to participate, and interact with politicians, insurers, legislators, and other national and international organizations working to advance the quality of stroke care. © 2012 New York Academy of Sciences.

The relationship between agreeableness and the development of the working alliance in patients with borderline personality disorder.

PubMed

Hirsh, Jacob B; Quilty, Lena C; Bagby, R Michael; McMain, Shelley F

2012-08-01

The working alliance between therapist and patient is an important component of effective interventions for borderline personality disorder (BPD). The current study examines whether client personality affects the development of the working alliance during the treatment of BPD, and whether this influences treatment effectiveness. Data was based on 87 patients with BPD who were participants in a randomized controlled trial comparing Dialectical Behavior Therapy (DBT) and general psychiatric management. Higher levels of trait Agreeableness were associated with steeper increases in working alliance throughout treatment, but only in the DBT condition. Increases in working alliance were in turn associated with better clinical outcomes. Mediation models revealed a significant indirect path from Agreeableness to better clinical outcomes, mediated through larger improvements in working alliance over time. These results highlight the role that patient personality can play during the therapeutic process, with a specific focus on the importance of Agreeableness for alliance development.

Evaluation of tannins interactions in grape (Vitis vinifera L.) skins.

PubMed

Rustioni, Laura; Fiori, Simone; Failla, Osvaldo

2014-09-15

Tannins have a central role in grapevine berries both for their physiological and enological implications. In the skin tissue they can be in vacuolar solution, or associated to the cell walls through weak or strong physicochemical interactions. The present work aims to separate vacuolar, non-covalently and covalently bonded tannins fractions. A specific extraction procedure was developed. A first extraction in ethanol at low temperature allowed the quantification of vacuolar tannins. An urea treatment followed by an ethanol extraction at room temperature was able to separate non-covalently bonded compounds. Finally an acid catalysis was used to break down proanthocyanidin covalent bonds. The method was validated on ripe grape samples of three cultivars, on berries developed in two sun exposure conditions. The Ethephon treatment effect was also evaluated. Beside the method development, a preliminary evaluation of the cultivar, exposition and Ethephon treatment effects are discussed. Copyright © 2014 Elsevier Ltd. All rights reserved.

Impact of tofacitinib treatment on human B-cells in vitro and in vivo.

PubMed

Rizzi, Marta; Lorenzetti, Raquel; Fischer, Kathleen; Staniek, Julian; Janowska, Iga; Troilo, Arianna; Strohmeier, Valentina; Erlacher, Miriam; Kunze, Mirjam; Bannert, Bettina; Kyburz, Diego; Voll, Reinhard E; Venhoff, Nils; Thiel, Jens

2017-02-01

B-cells are pivotal to the pathogenesis of rheumatoid arthritis and tofacitinib, a JAK inhibitor, is effective and safe in its treatment. Tofacitinib interferes with signal transduction via cytokine receptors using the common γ-chain. Despite extensive data on T-lymphocytes, the impact of tofacitinib on B-lymphocytes is poorly understood. In this study we assessed the effect of tofacitinib on B-lymphocyte differentiation and function. Tofacitinib treatment strongly impaired in vitro plasmablast development, immunoglobulin secretion and induction of B-cell fate determining transcription factors, Blimp-1, Xbp-1, and IRF-4, in naïve B-cells. Interestingly, class switch and activation-induced cytidine deaminase (AICDA) induction was only slightly reduced in activated naïve B-cells. The effect of tofacitinib on plasmablast formation, immunoglobulin secretion and proliferation was less profound, when peripheral blood B-cells, including not only naïve but also memory B-cells, were stimulated. In line with these in vitro results, the relative distribution of B-cell populations remained stable in tofacitinib treated patients. Nevertheless, a temporary increase in absolute B-cell numbers was observed 6-8 weeks after start of treatment. In addition, B-cells isolated from tofacitinib treated patients responded rapidly to in vitro activation. We demonstrate that tofacitinib has a direct impact on human naïve B-lymphocytes, independently from its effect on T-lymphocytes, by impairing their development into plasmablasts and immunoglobulin secretion. The major effect of tofacitinib on naïve B-lymphocyte development points to the potential inability of tofacitinib-treated patients to respond to novel antigens, and suggests planning vaccination strategies prior to tofacitinib treatment. Copyright © 2016 Elsevier Ltd. All rights reserved.

Successful oral desensitization with osimertinib following osimertinib-induced fever and hepatotoxicity: a case report.

PubMed

Hirabayashi, Ryosuke; Fujimoto, Daichi; Satsuma, Yukari; Hirabatake, Masaki; Tomii, Keisuke

2018-05-02

Osimertinib is a standard second-line therapy for patients who develop EGFR Thr790Met resistance mutation after treatment with first-line epidermal growth factor receptor tyrosine kinase inhibitors. Although no other effective targeted treatment option exists for these patients, osimertinib might be permanently discontinued owing to the onset of severe drug-induced toxicities like hepatotoxicity. Herein, we report a case of successful oral desensitization with osimertinib after the patient developed osimertinib-induced fever and hepatotoxicity. In the present case report, a 62-year-old Japanese woman received osimertinib as the sixth-line therapy for non-small cell lung carcinoma harboring EGFR Thr790Met-mutation. After 15 days of treatment, she developed general malaise. Although we reduced the drug at a lower dose, she again presented with high fever and elevated serum AST/ALT levels three days after re-initiating treatment. We then attempted oral desensitization with osimertinib over a two-week period. Thereafter, the patient continued osimertinib treatment for 6 months without the recurrence of side effects. In conclusion, oral desensitization may be a useful method in treating hepatotoxicity and drug fever caused by osimertinib.

Precision Medicine for CRC Patients in the Veteran Population: State-of-the-Art, Challenges and Research Directions.

PubMed

Mohapatra, Shyam S; Batra, Surinder K; Bharadwaj, Srinivas; Bouvet, Michael; Cosman, Bard; Goel, Ajay; Jogunoori, Wilma; Kelley, Michael J; Mishra, Lopa; Mishra, Bibhuti; Mohapatra, Subhra; Patel, Bhaumik; Pisegna, Joseph R; Raufman, Jean-Pierre; Rao, Shuyun; Roy, Hemant; Scheuner, Maren; Singh, Satish; Vidyarthi, Gitanjali; White, Jon

2018-05-01

Colorectal cancer (CRC) accounts for ~9% of all cancers in the Veteran population, a fact which has focused a great deal of the attention of the VA's research and development efforts. A field-based meeting of CRC experts was convened to discuss both challenges and opportunities in precision medicine for CRC. This group, designated as the VA Colorectal Cancer Cell-genomics Consortium (VA4C), discussed advances in CRC biology, biomarkers, and imaging for early detection and prevention. There was also a discussion of precision treatment involving fluorescence-guided surgery, targeted chemotherapies and immunotherapies, and personalized cancer treatment approaches. The overarching goal was to identify modalities that might ultimately lead to personalized cancer diagnosis and treatment. This review summarizes the findings of this VA field-based meeting, in which much of the current knowledge on CRC prescreening and treatment was discussed. It was concluded that there is a need and an opportunity to identify new targets for both the prevention of CRC and the development of effective therapies for advanced disease. Also, developing methods integrating genomic testing with tumoroid-based clinical drug response might lead to more accurate diagnosis and prognostication and more effective personalized treatment of CRC.

Erectile Dysfunction after Radical Prostatectomy: Prevalence, Medical Treatments, and Psychosocial Interventions

PubMed Central

Emanu, Jessica C.; Avildsen, Isabelle K.; Nelson, Christian J.

2016-01-01

Purpose of review This review will discuss erectile dysfunction (ED) in prostate cancer patients following radical prostatectomy (RP). It will focus on the prevalence and current treatments for ED as well as the emotional impact of ED and the current psychosocial interventions designed to help patients cope with this side effect. Recent findings While there is a large discrepancy in prevalence rates of ED after RP, several recent studies have cited rates as high as 85%. The concept of “penile rehabilitation” is now the standard of practice to treat ED following RP. However, many men avoid seeking help or utilizing ED treatments. This avoidance is related to the shame, frustration, and distress many men with ED and their partners experience. Recent psychosocial interventions have been developed to facilitate the use of treatments and help men cope with ED. These interventions have shown initial promise, however, continued intervention development is needed to reduce distress and improve long-term erectile function (EF) outcomes. Summary ED is a significant problem following prostate cancer surgery. While there are effective medical treatments, the development of psychosocial interventions should continue to evolve to maximize the assistance we can give to men and their partners. PMID:26808052

Efficacy of REACH Forgiveness across cultures.

PubMed

Lin, Yin; Worthington, Everett L; Griffin, Brandon J; Greer, Chelsea L; Opare-Henaku, Annabella; Lavelock, Caroline R; Hook, Joshua N; Ho, Man Yee; Muller, Holly

2014-09-01

This study investigates the efficacy of the 6-hour REACH Forgiveness intervention among culturally diverse undergraduates. Female undergraduates (N = 102) and foreign extraction (46.2%) and domestic (43.8%) students in the United States were randomly assigned to immediate treatment or waitlist conditions. Treatment efficacy and the effect of culture on treatment response were assessed using measures of emotional and decisional forgiveness across 3 time periods. Students in the treatment condition reported greater improvement in emotional forgiveness, but not decisional forgiveness, relative to those in the waitlist condition. Gains were maintained at a 1-week follow-up. Although culture did not moderate the effect of treatment, a main effect of culture on emotional forgiveness and marginally significant interaction effect of culture on decisional forgiveness were found. The REACH Forgiveness intervention was efficacious for college students from different cultural backgrounds when conducted in the United States. However, some evidence may warrant development of culturally adapted forgiveness interventions. © 2014 Wiley Periodicals, Inc.

The use of ECT and MST in treating depression.

PubMed

Allan, Charlotte L; Ebmeier, Klaus P

2011-10-01

Electroconvulsive therapy (ECT) has been used clinically since 1938. Its most common use is in the treatment of depression: first line treatment where rapid recovery is a priority, but more frequently as an effective treatment for patients who do not respond to pharmacological and psychological approaches. Whilst it is widely hailed as an effective treatment, concerns about its effect on cognition remain. The development of magnetic seizure therapy (MST) over the past decade has attempted to devise a therapy with comparable efficacy to ECT, but without the associated cognitive side effects. The rationale for this is that MST uses magnetic fields to induce seizures in the cortex, without electrical stimulation of brain structures involved with memory. MST has been used successfully in the treatment of depression, yet there is a dearth of literature in comparison with ECT. We present a systematic review of the literature on ECT (from 2009-2011) and MST (from 2001-2011).

A Bayesian adaptive design for biomarker trials with linked treatments

PubMed Central

Wason, James M S; Abraham, Jean E; Baird, Richard D; Gournaris, Ioannis; Vallier, Anne-Laure; Brenton, James D; Earl, Helena M; Mander, Adrian P

2015-01-01

Background: Response to treatments is highly heterogeneous in cancer. Increased availability of biomarkers and targeted treatments has led to the need for trial designs that efficiently test new treatments in biomarker-stratified patient subgroups. Methods: We propose a novel Bayesian adaptive randomisation (BAR) design for use in multi-arm phase II trials where biomarkers exist that are potentially predictive of a linked treatment's effect. The design is motivated in part by two phase II trials that are currently in development. The design starts by randomising patients to the control treatment or to experimental treatments that the biomarker profile suggests should be active. At interim analyses, data from treated patients are used to update the allocation probabilities. If the linked treatments are effective, the allocation remains high; if ineffective, the allocation changes over the course of the trial to unlinked treatments that are more effective. Results: Our proposed design has high power to detect treatment effects if the pairings of treatment with biomarker are correct, but also performs well when alternative pairings are true. The design is consistently more powerful than parallel-groups stratified trials. Conclusions: This BAR design is a powerful approach to use when there are pairings of biomarkers with treatments available for testing simultaneously. PMID:26263479

Fit-for-purpose wastewater treatment: Testing to implementation of decision support tool (II).

PubMed

Chhipi-Shrestha, Gyan; Hewage, Kasun; Sadiq, Rehan

2017-12-31

This paper is the second in a series of two papers. In Paper I, a decision support tool (DST), FitWater, was developed for evaluating the potential of wastewater treatment (WWT) trains for various water reuse applications. In the present paper, the proposed DST has been tested and implemented. FitWater has been tested with several existing WWT plants in Canada and the USA, demonstrating FitWater's effectiveness in estimating life cycle cost (LCC), health risk, and energy use. FitWater has also been implemented in a newly planned neighbourhood in the Okanagan Valley (BC, Canada) by developing 12 alternative WWT trains for water reuse in lawn and public parks irrigation. The results show that FitWater can effectively rank WWT train alternatives based on LCC, health risk, amount of reclaimed water, energy use, and carbon emissions. Moreover, functions have been developed for the variation of unit annualized LCC and energy intensity per unit log removal of microorganisms in different treatment technologies with varying plant capacities. The functions have power relations, showing the economies of scale. FitWater can be applied to identify a cost-effective, risk-acceptable, and energy efficient wastewater treatment train with a plant capacity of 500m 3 /day or more. Furthermore, FitWater can be used to assess potential economic impacts of developing microbiologically stringent effluent standards. The capability of FitWater can be enhanced by including physio-chemical quality of wastewater, additional treatment technologies, and carbon emissions from wastewater decomposition processes. Copyright © 2017 Elsevier B.V. All rights reserved.

BRCA-Monet: a breast cancer specific drug treatment mode-of-action network for treatment effective prediction using large scale microarray database.

PubMed

Ma, Chifeng; Chen, Hung-I; Flores, Mario; Huang, Yufei; Chen, Yidong

2013-01-01

Connectivity map (cMap) is a recent developed dataset and algorithm for uncovering and understanding the treatment effect of small molecules on different cancer cell lines. It is widely used but there are still remaining challenges for accurate predictions. Here, we propose BRCA-MoNet, a network of drug mode of action (MoA) specific to breast cancer, which is constructed based on the cMap dataset. A drug signature selection algorithm fitting the characteristic of cMap data, a quality control scheme as well as a novel query algorithm based on BRCA-MoNet are developed for more effective prediction of drug effects. BRCA-MoNet was applied to three independent data sets obtained from the GEO database: Estrodial treated MCF7 cell line, BMS-754807 treated MCF7 cell line, and a breast cancer patient microarray dataset. In the first case, BRCA-MoNet could identify drug MoAs likely to share same and reverse treatment effect. In the second case, the result demonstrated the potential of BRCA-MoNet to reposition drugs and predict treatment effects for drugs not in cMap data. In the third case, a possible procedure of personalized drug selection is showcased. The results clearly demonstrated that the proposed BRCA-MoNet approach can provide increased prediction power to cMap and thus will be useful for identification of new therapeutic candidates.

Changes in Cerebral Cortex of Children Treated for Medulloblastoma

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

Liu, Arthur K.; Marcus, Karen J.; Department of Radiation Oncology, Dana Farber Cancer Institute, Harvard Medical School, Boston, MA

2007-07-15

Purpose: Children with medulloblastoma undergo surgery, radiotherapy, and chemotherapy. After treatment, these children have numerous structural abnormalities. Using high-resolution magnetic resonance imaging, we measured the thickness of the cerebral cortex in a group of medulloblastoma patients and a group of normally developing children. Methods and Materials: We obtained magnetic resonance imaging scans and measured the cortical thickness in 9 children after treatment of medulloblastoma. The measurements from these children were compared with the measurements from age- and gender-matched normally developing children previously scanned. For additional comparison, the pattern of thickness change was compared with the cortical thickness maps from amore » larger group of 65 normally developing children. Results: In the left hemisphere, relatively thinner cortex was found in the perirolandic region and the parieto-occipital lobe. In the right hemisphere, relatively thinner cortex was found in the parietal lobe, posterior superior temporal gyrus, and lateral temporal lobe. These regions of cortical thinning overlapped with the regions of cortex that undergo normal age-related thinning. Conclusion: The spatial distribution of cortical thinning suggested that the areas of cortex that are undergoing development are more sensitive to the effects of treatment of medulloblastoma. Such quantitative methods may improve our understanding of the biologic effects that treatment has on the cerebral development and their neuropsychological implications.« less

Combining Pharmacological Countermeasures to Attenuate the Acute Radiation Syndrome-A Concise Review.

PubMed

Hofer, Michal; Hoferová, Zuzana; Depeš, Daniel; Falk, Martin

2017-05-19

The goal of combined pharmacological approaches in the treatment of the acute radiation syndrome (ARS) is to obtain an effective therapy producing a minimum of undesirable side effects. This review summarizes important data from studies evaluating the efficacy of combining radioprotective agents developed for administration prior to irradiation and therapeutic agents administered in a post-irradiation treatment regimen. Many of the evaluated results show additivity, or even synergism, of the combined treatments in comparison with the effects of the individual component administrations. It can be deduced from these findings that the research in which combined treatments with radioprotectors/radiomitigators are explored, tested, and evaluated is well-founded. The requirement for studies highly emphasizing the need to minimize undesirable side effects of the radioprotective/radiomitigating therapies is stressed.

The economic evaluation of personalised oncology medicines: ethical challenges.

PubMed

Lewis, Jan R R; Lipworth, Wendy L; Kerridge, Ian H; Day, Richard O

2013-10-07

Insights into the molecular drivers of cancer are providing opportunities for the development of new targeted treatments and more personalised approaches to cancer management. Drugs targeting mutant epidermal growth factor receptors, such as erlotinib and gefitinib, may provide more effective, safer and better tolerated treatment options compared with chemotherapy among appropriately selected patients with advanced non-small cell lung cancer (NSCLC). First-line access to these newer treatments remains unfunded after several considerations by the Pharmaceutical Benefits Advisory Committee and their assessment that these are not cost-effective treatments. We suggest that there may be evidentiary and ethical challenges associated with the assessment of the cost-effectiveness of personalised oncology medicines in Australia, and that a new approach is needed to determine the value and cost-effectiveness of personalised medicine.

Adoptive cell transfer: a clinical path to effective cancer immunotherapy

PubMed Central

Rosenberg, Steven A.; Restifo, Nicholas P.; Yang, James C.; Morgan, Richard A.; Dudley, Mark E.

2008-01-01

Adoptive cell therapy (ACT) using autologous tumour-infiltrating lymphocytes has emerged as the most effective treatment for patients with metastatic melanoma and can mediate objective cancer regression in approximately 50% of patients. The use of donor lymphocytes for ACT is an effective treatment for immunosuppressed patients who develop post-transplant lymphomas. The ability to genetically engineer human lymphocytes and use them to mediate cancer regression in patients, which has recently been demonstrated, has opened possibilities for the extension of ACT immunotherapy to patients with a wide variety of cancer types and is a promising new approach to cancer treatment. PMID:18354418

Using Video to Bridge the Gap Between Problem Behavior and a Delayed Time-out Procedure.

PubMed

Coppage, Sara; Meindl, James N

2017-09-01

Treatment plans focused on problem behavior often include punishment contingencies to decrease problem behavior. Immediate punishers are typically more effective than delayed punishers, but immediate delivery of a punisher is not always possible. Strategies need to be developed to increase the suppressive effects of delayed punishers. This study demonstrated the effectiveness of a treatment package involving replaying a video recording of problem behavior immediately before delivering a 15 min delayed time-out. This treatment package may prove to be an accessible and inexpensive strategy when using delayed punishers.

New Agents, Emerging Late Effects, and the Development of Precision Survivorship.

PubMed

Chow, Eric J; Antal, Zoltan; Constine, Louis S; Gardner, Rebecca; Wallace, W Hamish; Weil, Brent R; Yeh, Jennifer M; Fox, Elizabeth

2018-06-06

Incremental improvements in the treatment of children and adolescents with cancer have led to 5-year survival rates reaching nearly 85%. In the past decade, impressive progress has been made in understanding the biology of many pediatric cancers. With that understanding, multiple new agents have become available that offer the promise of more-effective and less-toxic treatment. These include agents that target various cell surface antigens and engage the adaptive immune system, as well as those that interfere with key signaling pathways involved in tumor development and growth. For local control, surgery and radiation techniques also have evolved, becoming less invasive or featuring new techniques and particles that more precisely target the tumor and limit the dose to normal tissue. Nevertheless, targeted agents, like conventional chemotherapy, radiotherapy, and surgery, may have off-target effects and deserve long-term follow-up of their safety and efficacy. These include injury to the endocrine, cardiovascular, and immunologic systems. New radiation and surgical techniques that theoretically reduce morbidity and improve long-term quality of life must also be validated with actual patient outcomes. Finally, with advances in genomics, information on host susceptibility to late effects is beginning to emerge. Such knowledge, coupled with improved metrics that better describe the spectrum of potential late effects across the entire lifespan, can lead to the development of decision models that project the potential long-term health outcomes associated with various treatment and follow-up strategies. These developments will help extend the current focus on precision medicine to precision survivorship, where clinicians, patients, and families will have a better grasp of the potential risks, benefits, and tradeoffs associated with the growing number of cancer treatment options.

The Impact of Cancer and its Treatment on the Growth and Development of the Pediatric Patient.

PubMed

Brand, Sarah; Wolfe, Joanne; Samsel, Chase

2017-01-01

Cancer treatment can have profound effects on the growth and development of pediatric patients. Different models of psychosocial development and behavioral treatment approaches aid children receiving medical treatment. Providing education, anticipatory guidance, and individualized support to child and their families is a psychosocial standard. Clarify the different models of psychosocial development and applicable psychosocial interventions to better prepare and tailor cancer treatment to pediatric patients. Authors reviewed existing evidenced-based literature in oncology, psychology, developmental, and psychiatric while drawing on case examples and expert knowledge to illustrate the impact of cancer treatment on pediatric patients, analyze developmentally individualized needs, and describe facilitative interventions. Pediatric patients of all ages cope and adjust better to all phases of treatment when their care is delivered in a developmentally-informed and psychosocially thoughtful way. Providers can comprehensively prepare their patients and families for treatment better by utilizing a psychosocially- and developmentally-informed framework while meeting individualized unique needs of patients. An integrated multidisciplinary psychosocial support team is facilitative in anticipating and meeting the needs of pediatric cancer patients and has recently become a psychosocial standard of care. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

Suspected side effects of doxycycline use in dogs - a retrospective study of 386 cases.

PubMed

Schulz, B S; Hupfauer, S; Ammer, H; Sauter-Louis, C; Hartmann, K

2011-08-27

This study investigated doxycycline-related side effects in a large population of dogs. Data from 386 dogs that had received doxycycline for the treatment of various infectious diseases were analysed retrospectively. Potential side effects that developed during treatment were documented, and correlations with signalment, dose, duration of treatment, frequency of application, doxycycline preparation and use of additional drugs were investigated. Vomiting was reported in 18.3 per cent of dogs, 7.0 per cent developed diarrhoea and 2.5 per cent developed anorexia. While being treated with doxycycline, 39.4 per cent of dogs showed an increase in alanine aminotransferase (ALT) activity and 36.4 per cent showed an increase in alkaline phosphatase (ALP) activity. There was a dose-related risk of an increase in ALP activity (P=0.011, odds ratio [OR]=1.27, 95 per cent confidence interval [CI] 1.06 to 1.53), and older dogs treated with doxycycline were more likely to develop an increase in ALT activity (P=0.038, OR=1.23, 95 per cent CI 1.01 to 1.50) and vomiting (P=0.017, OR=1.11, 95 per cent CI 1.02 to 1.21).

Day patient treatment for traumatic grief: preliminary evaluation of a one-year treatment programme for patients with multiple and traumatic losses

PubMed Central

de Heus, Annemiek; Hengst, Sophie M. C.; de la Rie, Simone M.; Djelantik, A. A. A. Manik J.; Boelen, Paul A.; Smid, Geert E.

2017-01-01

ABSTRACT Background: Bereaved individuals who have lost a loved one under traumatic circumstances can develop symptoms of Persistent Complex Bereavement Disorder (PCBD) and/or Posttraumatic Stress Disorder (PTSD). This is particularly common in refugees, as they frequently have been confronted with multiple traumatic losses. For patients with severe PTSD and traumatic grief a treatment programme was developed, embedding individual traumatic grief focused therapy in a group-based multidisciplinary day patient treatment programme. The day patient treatment comprised a weekly five-hour programme consisting of three phases with a duration of four months each. Objective: To evaluate the feasibility and potential effectiveness of the treatment programme. Method: Data were analyzed from 16 participants treated between October 2013 and March 2014. PTSD severity and PTSD/PCBD diagnoses were measured during the initial and final phases of treatment using the Clinician-Administered PTSD Scale for DSM-IV (CAPS) and the Traumatic Grief Inventory Self Report (TGI-SR). One clinical case is presented in more detail. Treatment attendance was also registered and therapist satisfaction was evaluated in a focus group. Results: Thirteen patients (81%) completed the treatment. Each day of the treatment programme was attended by a mean of 76% of the participants. In the focus group, therapists noted symptom reduction in their patients and they therefore regarded Brief Eclectic Psychotherapy for Traumatic Grief (BEP-TG) as an effective therapy for their patients. During treatment, significant decreases in PTSD severity as well as diagnosable PTSD and PCBD were observed. Conclusions: Results support the feasibility and potential effectiveness of the day patient treatment programme for traumatic grief. The programme appears to be particularly suitable for refugees with severe PTSD and PCBD psychopathology, who may not benefit enough from usual care. PMID:29038679

[Antiepileptic drugs in North America].

PubMed

Akiyama, Tomoyuki; Otsubo, Hiroshi

2010-05-01

In this review study, second-generation antiepileptic drugs (AEDs) (levetiracetam, gabapentin, topiramate, lamotrigine, zonisamide, oxcarbazepine, vigabatrin, pregabalin, rufinamide, tiagabine, lacosamide, and felbamate) and injectable AEDs (levetiracetam, lacosamide, fosphenytoin, lorazepam, and valproic acid) available in North America were compared with those available in Japan. Three second-generation AEDs (gabapentin, topiramate, and lamotrigine) were recently approved in Japan. Levetiracetam is currently under review for approval by the Japanese regulatory agency. An ideal AED would have a broad-spectrum activity to control multiple types of seizures, favorable safety profile, limited potential for drug-drug interaction, many bioequivalent formulations, long half life to allow infrequent administration, and antiepileptogenic effects that may provide a fundamental cure of epileptic patients by suppressing the development of epileptogenic network and neutralizing previously established epileptogenic foci in the brain. The second-generation AEDs have been developed to possess some of these ideal properties. All the second-generation AEDs are efficacious for the treatment of patients with partial seizures. In addition, levetiracetam, topiramate, lamotrigine, and zonisamide are effective for the treatment of patients with generalized tonic-clonic seizures, absences, myoclonic seizures, Lennox-Gastaut syndrome, and West syndrome; however, lamotrigine is not effective for the treatment of patients with myoclonic seizures. Rufinamide and felbamate are useful for the treatment of patients with Lennox-Gastaut syndrome; however owing to its serious adverse effects, including aplastic anemia and hepatic failure, felbamate is used as the last resort for the treatment of patients with intractable seizures. Vigabatrin is particularly effective for the treatment of patients with West syndrome; however, the patients need to be regularly monitored for the development of peripheral visual field defect. Gabapentin, oxcarbazepine, vigabatrin, and tiagabine are ineffective for the treatment of patients with absences and/or myoclonic seizures and may aggravate these conditions. Treatment with levetiracetam or topiramate (off-label use) is the new option for patients with refractory status epilepticus, which is characterized by downregulation of the inhibitory gamma-aminobutyric acid system, because these drugs act via different mechanisms and are rapidly titratable, especially intravenous levetiracetam. The pharmacokinetic profiles of levetiracetam, gabapentin, and pregabalin are favorable: these drugs exhibit minimal protein binding, do not undergo hepatic metabolism, are not involved in any clinically relevant drug interactions, and rarely lead to the development of serious adverse effects. In general, levetiracetam is probably the closest to being the ideal AED because of its broad-spectrum favorable pharmacokinetic profile and safety profile as well as because of the availability of its parenteral formulation. Among the injectable AEDs, fosphenytoin is a water-soluble prodrug and is used to treat patients with status epilepticus. Systemic and local side effects of this drug are fewer than those of phenytoin. Lorazepam, a benzodiazepine is used as the first-line AED for the treatment of patients with status epilepticus. The effects of this drug are more prolonged than those of diazepam. Intravenous administration of valproic acid is regarded as a new treatment option for patients with status epilepticus, because sedative and negative effects on the cardiorespiratory system of this drug are lesser than those of the traditional injectable AEDs. These novel medications will aid the improvement of the quality of life of epileptic patients through improved seizure control and reduced adverse effects.

Small-molecule inhibitors of the receptor tyrosine kinases: promising tools for targeted cancer therapies.

PubMed

Hojjat-Farsangi, Mohammad

2014-08-08

Chemotherapeutic and cytotoxic drugs are widely used in the treatment of cancer. In spite of the improvements in the life quality of patients, their effectiveness is compromised by several disadvantages. This represents a demand for developing new effective strategies with focusing on tumor cells and minimum side effects. Targeted cancer therapies and personalized medicine have been defined as a new type of emerging treatments. Small molecule inhibitors (SMIs) are among the most effective drugs for targeted cancer therapy. The growing number of approved SMIs of receptor tyrosine kinases (RTKs) i.e., tyrosine kinase inhibitors (TKIs) in the clinical oncology imply the increasing attention and application of these therapeutic tools. Most of the current approved RTK-TKIs in preclinical and clinical settings are multi-targeted inhibitors with several side effects. Only a few specific/selective RTK-TKIs have been developed for the treatment of cancer patients. Specific/selective RTK-TKIs have shown less deleterious effects compared to multi-targeted inhibitors. This review intends to highlight the importance of specific/selective TKIs for future development with less side effects and more manageable agents. This article provides an overview of: (1) the characteristics and function of RTKs and TKIs; (2) the recent advances in the improvement of specific/selective RTK-TKIs in preclinical or clinical settings; and (3) emerging RTKs for targeted cancer therapies by TKIs.

Role of adiponectin in delayed embryonic development of the short-nosed fruit bat, Cynopterus sphinx.

PubMed

Anuradha; Krishna, Amitabh

2014-12-01

The aim of this study was to evaluate the role of adiponectin in the delayed embryonic development of Cynopterus sphinx. Adiponectin receptor (ADIPOR1) abundance was first observed to be lower during the delayed versus non-delayed periods of utero-embryonic unit development. The effects of adiponectin treatment on embryonic development were then evaluated during the period of delayed development. Exogenous treatment increased the in vivo rate of embryonic development, as indicated by an increase in weight, ADIPOR1 levels in the utero-embryonic unit, and histological changes in embryonic development. Treatment with adiponectin during embryonic diapause showed a significant increase in circulating progesterone and estradiol concentrations, and in production of their receptors in the utero-embryonic unit. The adiponectin-induced increase in estradiol synthesis was correlated with increased cell survival (BCL2 protein levels) and cell proliferation (PCNA protein levels) in the utero-embryonic unit, suggesting an indirect effect of adiponectin via estradiol synthesis by the ovary. An in vitro study further confirmed the in vivo findings that adiponectin treatment increases PCNA levels together with increased uptake of glucose by increasing the abundance of glucose transporter 8 (GLUT8) in the utero-embryonic unit. The in vitro study also revealed that adiponectin, together with estradiol but not alone, significantly increased ADIPOR1 protein levels. Thus, adiponectin works in concert with estradiol to increase glucose transport to the utero-embryonic unit and promote cell proliferation, which together accelerate embryonic development. © 2014 Wiley Periodicals, Inc.

Psychotherapy integration in the treatment of personality disorders: a commentary.

PubMed

Nelson, Dana L; Beutler, Larry E; Castonguay, Louis G

2012-02-01

Whereas research on the treatment of personality disorders over the past several decades has focused primarily on comparing the efficacy of various treatment packages associated with different theoretical models, there is increasing evidence that the field would benefit from focusing more attention on developing integrative treatments that are both informed by research and capable of scientific verification. The articles assembled for this special section each propose a different approach to integrative treatment for personality disorders. In this commentary, we outline a number of reasons for making such a shift to more integrative treatments, consider some of the potential challenges to integration, and discuss the different approaches to integration illustrated in these articles. We highlight some of the difficult tradeoffs that must be made in developing an integrative approach and discuss similarities and differences in the response to such challenges by the contributors to this special section. Finally, we point to several areas for future research that we believe will contribute to the development of increasingly effective treatments for individuals with personality disorders.

A New Aging Treatment for Improving Cryogenic Toughness of the Main Structural Alloy of the Super Lightweight Tank

NASA Technical Reports Server (NTRS)

Chen, P. S.; Stanton, W. P.

1996-01-01

Marshall Space Flight Center (MSFC) has developed a new technique that can enhance cryogenic fracture toughness and reduce the statistical spread of toughness values in alloy 2195. This aging treatment can control the location and size of strengthening precipitate T1, making improvements possible in cryogenic fracture toughness (CFT) and fracture toughness ratio (FTR). At the start of this program, design of experiments (DOE) ingot No. 10 was used as a baseline for aging process development and optimization. The new aging treatment was found to be very effective, improving CFT by approximately 15 to 20 percent for DOE ingot No. 10. To further evaluate the repeatability and effectiveness of this new treatment, the investigators selected and tested three more lots of alloy 2195, using 1.75-in-thick gauge plates with FTR values ranging from 0.85 to 1.07. The new aging treatment effectively enhanced CFT and FTR values for all three lots. In one instance, the material was considered rejectable because it did not meet the minimum FTR value (1.0) of the super lightweight tank (SLWT). The new aging treatment improved its FTR from 0.85 to 1.01, making this material acceptable for use in the SLWT.

Short- and long-term outcome of interferon therapy for chronic hepatitis B infection

PubMed Central

Seo, Yasushi; Yano, Yoshihiko

2014-01-01

Hepatitis B virus (HBV) infection is a serious clinical problem worldwide. Conventional interferon (IFN)-α has been approved for the treatment of chronic hepatitis B (CHB). Short-term studies have demonstrated that IFN-based therapy is moderately effective in inducing the loss of hepatitis e antigen (HBeAg) or seroconversion (30%-40%) in HBeAg-positive patients and also produces sustained HBV DNA suppression (20%-30%) in HBeAg-negative patients. Many studies have reported a correlation between the HBV genotype and response to IFN treatment. The highest response rate to IFN treatment was found in patients infected with HBV genotype A, followed by HBV genotypes B, C, and D. The long-term effect of IFN-α on CHB has not yet been elucidated. The ability of IFN-α treatment to prevent new cirrhosis, complications associated with cirrhosis, and development of hepatocellular carcinoma (HCC) is controversial. The beneficial effect of IFN-α treatment in reducing the development of HCC has mainly been observed in treatment responders who already have cirrhosis. These inconsistent findings may be attributed to the inevitable limitations of comparisons across studies, including differences in the baseline characteristics of the study and the moderate suppression of HBV replication by IFN-α relative to nucleoside/nucleos(t)ide analogs. PMID:25309065

Developing standardized corticosteroid treatment for Duchenne muscular dystrophy.

PubMed

Guglieri, Michela; Bushby, Kate; McDermott, Michael P; Hart, Kimberly A; Tawil, Rabi; Martens, William B; Herr, Barbara E; McColl, Elaine; Wilkinson, Jennifer; Kirschner, Janbernd; King, Wendy M; Eagle, Michele; Brown, Mary W; Willis, Tracey; Hirtz, Deborah; Shieh, Perry B; Straub, Volker; Childs, Anne-Marie; Ciafaloni, Emma; Butterfield, Russell J; Horrocks, Iain; Spinty, Stefan; Flanigan, Kevin M; Kuntz, Nancy L; Baranello, Giovanni; Roper, Helen; Morrison, Leslie; Mah, Jean K; Manzur, Adnan Y; McDonald, Craig M; Schara, Ulrike; von der Hagen, Maja; Barohn, Richard J; Campbell, Craig; Darras, Basil T; Finkel, Richard S; Vita, Giuseppe; Hughes, Imelda; Mongini, Tiziana; Pegoraro, Elena; Wicklund, Matthew; Wilichowski, Ekkehard; Bryan Burnette, W; Howard, James F; McMillan, Hugh J; Thangarajh, Mathula; Griggs, Robert C

2017-07-01

Despite corticosteroids being the only treatment documented to improve strength and function in boys with Duchenne muscular dystrophy (DMD) corticosteroid prescription is inconsistent and in some countries, corticosteroids are not prescribed. We are conducting a clinical trial that (1) compares the 3 most frequently prescribed corticosteroid regimes; (2) standardizes treatment of DMD complications; and (3) standardizes prevention of corticosteroid side effects. Investigators at 38 sites in 5 countries plan to recruit 300 boys aged 4-7 who are randomly assigned to one of three regimens: daily prednisone; daily deflazacort; or intermittent prednisone (10days on/10days off). Boys are followed for a minimum of 3years to assess the relative effectiveness and adverse event profiles of the different regimens. The primary outcome is a 3-dimensional variable consisting of log-transformed time to rise from the floor, forced vital capacity, and subject/parent satisfaction with treatment, each averaged over all post-baseline visits. The study protocol includes evidence- and consensus-based treatment of DMD complications and of corticosteroid side effects. This study seeks to establish a standard corticosteroid regimen for DMD. Since all new interventions for DMD are being developed as add-on therapies to corticosteroids, defining the optimum regimen is of importance for all new treatments. Copyright © 2017. Published by Elsevier Inc.

Developing and implementing a high precision setup system

NASA Astrophysics Data System (ADS)

Peng, Lee-Cheng

The demand for high-precision radiotherapy (HPRT) was first implemented in stereotactic radiosurgery using a rigid, invasive stereotactic head frame. Fractionated stereotactic radiotherapy (SRT) with a frameless device was developed along a growing interest in sophisticated treatment with a tight margin and high-dose gradient. This dissertation establishes the complete management for HPRT in the process of frameless SRT, including image-guided localization, immobilization, and dose evaluation. The most ideal and precise positioning system can allow for ease of relocation, real-time patient movement assessment, high accuracy, and no additional dose in daily use. A new image-guided stereotactic positioning system (IGSPS), the Align RT3C 3D surface camera system (ART, VisionRT), which combines 3D surface images and uses a real-time tracking technique, was developed to ensure accurate positioning at the first place. The uncertainties of current optical tracking system, which causes patient discomfort due to additional bite plates using the dental impression technique and external markers, are found. The accuracy and feasibility of ART is validated by comparisons with the optical tracking and cone-beam computed tomography (CBCT) systems. Additionally, an effective daily quality assurance (QA) program for the linear accelerator and multiple IGSPSs is the most important factor to ensure system performance in daily use. Currently, systematic errors from the phantom variety and long measurement time caused by switching phantoms were discovered. We investigated the use of a commercially available daily QA device to improve the efficiency and thoroughness. Reasonable action level has been established by considering dosimetric relevance and clinic flow. As for intricate treatments, the effect of dose deviation caused by setup errors remains uncertain on tumor coverage and toxicity on OARs. The lack of adequate dosimetric simulations based on the true treatment coordinates from the treatment planning system (TPS) has limited adaptive treatments. A reliable and accurate dosimetric simulation using TPS and in-house software in uncorrected errors has been developed. In SRT, the calculated dose deviation is compared to the original treatment dose with the dose-volume histogram to investigate the dose effect of rotational errors. In summary, this work performed a quality assessment to investigate the overall accuracy of current setup systems. To reach the ideal HPRT, the reliable dosimetric simulation, an effective daily QA program and effective, precise setup systems were developed and validated.

Cell and molecular mechanisms of pathogenesis and treatment of cancer.

PubMed Central

Rew, D. A.

1998-01-01

Surgery remains the mainstay of treatment for most classes of human solid tumours, with the principal exception of lymphomas, but it is insufficient in many cases to guarantee cure. With few exceptions, recurrent and metastatic solid tumours continue to defy attempts to develop effective adjuvant therapies. Recent insights into tumour biology reveal an increasingly complex picture of cell and molecular processes which confer heterogeneity and resistance to treatment upon tumours. These insights may also yield new targets for more effective adjuvant therapies. PMID:9616488

The epidemiology of smoking: health consequences and benefits of cessation.

PubMed

Fagerström, Karl

2002-01-01

Tobacco use is the single most important preventable health risk in the developed world, and an important cause of premature death worldwide. Smoking causes a wide range of diseases, including many types of cancer, chronic obstructive pulmonary disease, coronary heart disease, stroke, peripheral vascular disease, and peptic ulcer disease. In addition, smoking during pregnancy adversely affects fetal and neonatal growth and development. Recent decades have seen a massive expansion in tobacco use in the developing world and accelerating growth in smoking among women in the developed world. Globally, smoking-related mortality is set to rise from 3 million annually (1995 estimate) to 10 million annually by 2030, with 70% of these deaths occurring in developing countries. Many of the adverse health effects of smoking are reversible, and smoking cessation treatments represent some of the most cost effective of all healthcare interventions. Although the greatest benefit accrues from ceasing smoking when young, even quitting in middle age avoids much of the excess healthcare risk associated with smoking. In order to improve smoking cessation rates, effective behavioural and pharmacological treatments, coupled with professional counselling and advice, are required. Since smoking duration is the principal risk factor for smoking-related morbidity, the treatment goal should be early cessation and prevention of relapse.

Effects of Sulfamethoxazole-Trimethoprim on Airway Colonization with Pneumocystis jirovecii.

PubMed

Kushima, Hisako; Ishii, Hiroshi; Tokimatsu, Issei; Umeki, Kenji; Sato, Takako; Kadota, Jun-Ichi

2016-05-20

Reactivation of latent infection is considered to be the main mechanism underlying the development of Pneumocystis pneumonia in immunosuppressed patients. We retrospectively assessed the effects of prophylactic administration of sulfamethoxazole-trimethoprim on the development of P. pneumonia and airway colonization with P. jirovecii in patients undergoing examinations to diagnose or rule out P. pneumonia. Polymerase chain reaction was performed to detect P. jirovecii in bronchoalveolar lavage fluid or sputum of 60 consecutive patients between 2004 and 2012. No patients who received the prophylactic administration of sulfamethoxazole-trimethoprim (n = 10) developed P. pneumonia or demonstrated airway colonization with P. jirovecii, and none of the patients who developed P. pneumonia (n = 11) or showed colonization (n = 9) had received prophylactic treatment. Furthermore, 20 (40%) of 50 patients without prophylactic treatment showed positive results on the P. jirovecii DNA polymerase chain reaction, but all 10 patients who had prophylactic treatment showed negative results (Fisher's exact test, P = 0.02). Therefore, the prophylactic administration of sulfamethoxazole-trimethoprim has potential to be effective in preventing P. pneumonia as well as eliminating airway colonization with P. jirovecii. Further studies targeting large cohorts of patients with a variety of underlying diseases are required to develop recommendations regarding the prophylactic administration of sulfamethoxazole-trimethoprim.

Tavaborole, a Novel Boron-Containing Small Molecule Pharmaceutical Agent for Topical Treatment of Onychomycosis: I. Reproductive and Developmental Toxicity Studies.

PubMed

Ciaravino, Vic; Coronado, Dina; Lanphear, Cheryl; Hoberman, Alan; Chanda, Sanjay

2016-09-01

Tavaborole is a topical antifungal agent approved by the US Food and Drug Administration for the treatment of toenail onychomycosis. As part of the nonclinical development program, reproductive and developmental toxicity studies were conducted (rat oral fertility and early embryonic development, rat (oral) and rabbit (dermal) embryo-fetal development). There were no effects on fertility or reproductive performance at doses up to 300 mg/kg/d (107 times the maximum recommended human dose [MRHD] based on mean area under the plasma concentration-time curve comparisons). In the rat embryo-fetal development toxicity studies, teratogenicity was not observed at doses up to 100 mg/kg/d (29 times the MRHD). However, several treatment-related skeletal malformations and variations were observed at 300 mg/kg/d (570 times the MRHD). In rabbit embryo-fetal development toxicity studies dosed via oral or dermal administration, the no observable adverse effect level for maternal toxicity and embryo-fetal toxicity was 50 mg/kg/d (16 times the MRHD) and 5% (26 times the MRHD), respectively. © The Author(s) 2016.

Aluminum Potassium Sulfate and Tannic Acid Injection for Hemorrhoids

PubMed Central

2012-01-01

A quick hemostatic effect, as well as sclerosing and shrinkage of hemorrhoids, can be attained when internal hemorrhoids are treated by using injection therapy with aluminum potassium sulfate and tannic acid (ALTA), the outcomes of treatment may be similar to those of a hemorrhoidectomy. However, if the type of hemorrhoid or the method of injection is not appropriate for ALTA treatment, complications peculiar to ALTA or recurrence may develop. Accordingly, sufficient understanding of the treatment mechanism of ALTA injection and repeated training for injection are required for effective use of the ALTA treatment. PMID:22606645

Kinetics and mechanism of nickel ferrite formation under high temperature ultrasonic treatment.

PubMed

Baranchikov, Alexander Ye; Ivanov, Vladimir K; Tretyakov, Yuri D

2007-02-01

The effect of simultaneous ultrasonic and thermal treatment on kinetics and mechanism of nickel ferrite formation was studied. It was established that sonication leads to notable increase of the mean rate of this reaction and decrease of effective activation energy from 190+/-5 to 125+/-7 kJ/mol. XRD data show that ultrasonic treatment significantly affects the microstructure of both initial reagent (Fe(2)O(3)) and reaction product (NiFe(2)O(4)) thus promoting formation of well developed reaction zone. A general model of ferrite formation mechanism under high temperature ultrasonic treatment was proposed.

Theories and treatment of drug dependency: a neurochemical perspective.

PubMed

Pakdaman, Sheila; Wilcox, Richard E; Miller, Joseph D

2014-01-01

Treatment of chemical dependence ("addiction") requires an understanding of its effects on the brain. To guide research in the area of chemical dependence, several foundational theories have been developed. These include the incentive salience, receptor down-regulation, opponent process, and psychomotor stimulant theories. These have been important both in summarizing and in guiding investigations. However, the extant theories do not provide a single unified framework nor have they yielded all of the guidance necessary for effective chemical dependence treatment. The present paper summarizes and then integrates these theories and suggests some implications for the treatment followed by this integration.

A new sensitizer DVDMS combined with multiple focused ultrasound treatments: an effective antitumor strategy

NASA Astrophysics Data System (ADS)

Xiong, Wenli; Wang, Pan; Hu, Jianmin; Jia, Yali; Wu, Lijie; Chen, Xiyang; Liu, Quanhong; Wang, Xiaobing

2015-12-01

Sonodynamic therapy (SDT) was developed as a promising noninvasive approach. The present study investigated the antitumor effect of a new sensitizer (sinoporphyrin sodium, referred to as DVDMS) combined with multiple ultrasound treatments on sarcoma 180 both in vitro and in vivo. The combined treatment significantly suppressed cell viability, potentiated apoptosis, and markedly inhibited angiogenesis in vivo. In vivo, the tumor weight inhibition ratio reached 89.82% fifteen days after three sonication treatments plus DVDMS. This effect was stronger than one ultrasound alone (32.56%) and than one round of sonication plus DVDMS (59.33%). DVDMS combined with multiple focused ultrasound treatments initiated tumor tissue destruction, induced cancer cell apoptosis, inhibited tumor angiogenesis, suppressed cancer cell proliferation, and decreased VEGF and PCNA expression levels. Moreover, the treatment did not show obvious signs of side effects or induce a drop in body weight. These results indicated that DVDMS combined with multiple focused ultrasounds may be a promising strategy against solid tumor.

Integrated programs for mothers with substance abuse issues and their children: a systematic review of studies reporting on child outcomes.

PubMed

Niccols, Alison; Milligan, Karen; Smith, Ainsley; Sword, Wendy; Thabane, Lehana; Henderson, Joanna

2012-04-01

Integrated treatment programs (those that include on-site pregnancy-, parenting-, or child-related services with addiction services) were developed to break the intergenerational cycle of addiction, potential child maltreatment, and poor outcomes for children. To examine the impact and effects of integrated programs for women with substance abuse issues and their children, we performed a systematic review of studies published from 1990 to 2011. Literature search strategies included online bibliographic database searches, checking printed sources, and requests to researchers. Studies were included if all participants were mothers with substance abuse problems at baseline; the treatment program included at least 1 specific substance use treatment and at least 1 parenting or child treatment service; the study design was randomized, quasi-experimental, or cohort; and there were quantitative data on child outcomes. We summarized data on child development, growth, and emotional and behavioral outcomes. Thirteen studies (2 randomized trials, 3 quasi-experimental studies, 8 cohort studies; N=775 children) were included in the review. Most studies using pre-post design indicated improvements in child development (with small to large effects, ds=0.007-1.132) and emotional and behavioral functioning (with most available effect sizes being large, ds=0.652-1.132). Comparison group studies revealed higher scores for infants of women in integrated programs than those not in treatment, with regard to development and most growth parameters (length, weight, and head circumference; with all available effect sizes being large, ds=1.16-2.48). In studies comparing integrated to non-integrated programs, most improvements in emotional and behavioral functioning favored integrated programs and, where available, most effect sizes indicated that this advantage was small (ds=0.22-0.45). Available evidence supports integrated programs, as findings suggest that they are associated with improvements in child development, growth, and emotional and behavioral functioning. More research is required comparing integrated to non-integrated programs. This review highlights the need for improved methodology, study quality, and reporting to improve our understanding of how best to meet the needs of children of women with substance abuse issues. Copyright © 2012 Elsevier Ltd. All rights reserved.

Prophylactic laser in age-related macular degeneration: the past, the present and the future.

PubMed

Findlay, Quan; Jobling, Andrew I; Vessey, Kirstan A; Greferath, Ursula; Phipps, Joanna A; Guymer, Robyn H; Fletcher, Erica L

2018-05-01

The presence of drusen in the posterior eye is a hallmark feature of the early stages of age-related macular degeneration and their size is an indicator of risk of progression to vision-threatening forms of the disease. Since the initial observations that laser treatment can resolve drusen, there has been great interest in whether laser treatment can be used to reduce the progression of age-related macular degeneration. In this article, we review the development of lasers for the treatment of those with age-related macular degeneration. We provide an overview of the clinical trial results that demonstrated drusen resolution but that had mixed effects on progression of disease. In addition, we provide a summary of the recent developments in pulsed lasers that are designed to reduce the energy applied to the posterior eye to provide the therapeutic effects of conventional continuous wave lasers while reducing the secondary tissue effects.

Anaerobic digestion for sustainable development: a natural approach.

PubMed

Gljzen, H J

2002-01-01

After the discovery of methane gas by Alessandro Volta in 1776, it took about 100 years before anaerobic processes for the treatment of wastewater and sludges were introduced. The development of high rate anaerobic digesters for the treatment of sewage and industrial wastewater took until the nineteen-seventies and for solid waste even till the nineteen-eighties. All digesters have in common that they apply natural anaerobic consortia of microorganisms for degradation and transformation processes. In view of this, it could be rewarding to evaluate the efficiency of natural ecosystems for their possible application. Examples of high rate anaerobic natural systems include the forestomach of ruminants and the hindgut of certain insects, such as termites and cockroaches. These 'natural reactors' exhibit volumetric methane production rates as high as 35 l/l.d. The development of anaerobic reactors based on such natural anaerobic systems could produce eco-technologies for the effective management of a wide variety of solid wastes and industrial wastewater. Important limitations of anaerobic treatment of domestic sewage relate to the absence of nutrient and pathogen removal. A combination of anaerobic pre-treatment followed by photosynthetic posttreatment is proposed for the effective recovery of energy and nutrients from sewage. This eco-technology approach is based on the recognition that the main nutrient assimilating capacity is housed in photosynthetic plants. The proposed anaerobic-photosynthetic process is energy efficient, cost effective and applicable under a wide variety of rural and urban conditions. a natural systems approach towards waste management could generate affordable eco-technologies for effective treatment and resource recovery.

Response Generalization in Apraxia of Speech Treatments: Taking Another Look.

ERIC Educational Resources Information Center

Ballard, Kirrie J.

2001-01-01

This article presents a critical review and reanalysis of response generalization effects in studies of treatment efficacy in apraxia of speech. The discussion focuses on the influence of the theoretical basis used to develop hypotheses and select behavior to test predictions, the complexity of the treatment task/s, and patient characteristics.…

Pivotal Response Treatments for Autism: Communication, Social, and Academic Development

ERIC Educational Resources Information Center

Koegel, Robert L.; Kern Koegel, Lynn

2006-01-01

Recognized as one of the top state-of-the-art treatments for autism in the United States, the innovative Pivotal Response Treatment uses natural learning opportunities to target and modify key behaviors in children with autism, leading to widespread positive effects on communication, behavior, and social skills. The product of 20 years of…

Causes and Management of Treatment-Resistant Panic Disorder and Agoraphobia: A Survey of Expert Therapists

ERIC Educational Resources Information Center

Sanderson, William C.; Bruce, Timothy J.

2007-01-01

Cognitive behavior therapy (CBT) is recognized as an effective psychological treatment for panic disorder (PD). Despite its efficacy, some clients do not respond optimally to this treatment. Unfortunately, literatures on the prediction, prevention, and management of suboptimal response are not well developed. Considering this lack of empirical…

Fracture resistance behaviour of gamma-irradiation sterilized cortical bone protected with a ribose pre-treatment

NASA Astrophysics Data System (ADS)

Woodside, Carman Mitchell

Structural bone allograft reconstructions are often implemented to repair large skeletal defects. To ensure the biological safety of the patient, allograft material is routinely sterilized with gamma-irradiation prior to implantation. The sterilization process damages the tissue, specifically the collagen protein network, leading to severe losses in the mechanical properties of the bone. Our lab has begun developing a ribose pre-treatment that can protect bone from these harmful effects. The goals of the present study were to develop a method to measure the fracture toughness of bone, an important clinical failure mode, and implement it to determine the effectiveness of the ribose pre-treatment on fracture toughness. We have shown that the ribose pre-treatment is successful at protecting some of the original fracture toughness of sterilized bone, and that the connectivity of the collagen network is an important contributor to the fracture resistance of bone.

Cognitive Impairment in Bipolar Disorder: Treatment and Prevention Strategies.

PubMed

Solé, Brisa; Jiménez, Esther; Torrent, Carla; Reinares, Maria; Bonnin, Caterina Del Mar; Torres, Imma; Varo, Cristina; Grande, Iria; Valls, Elia; Salagre, Estela; Sanchez-Moreno, Jose; Martinez-Aran, Anabel; Carvalho, André F; Vieta, Eduard

2017-08-01

Over the last decade, there has been a growing appreciation of the importance of identifying and treating cognitive impairment associated with bipolar disorder, since it persists in remission periods. Evidence indicates that neurocognitive dysfunction may significantly influence patients' psychosocial outcomes. An ever-increasing body of research seeks to achieve a better understanding of potential moderators contributing to cognitive impairment in bipolar disorder in order to develop prevention strategies and effective treatments. This review provides an overview of the available data from studies examining treatments for cognitive dysfunction in bipolar disorder as well as potential novel treatments, from both pharmacological and psychological perspectives. All these data encourage the development of further studies to find effective strategies to prevent and treat cognitive impairment associated with bipolar disorder. These efforts may ultimately lead to an improvement of psychosocial functioning in these patients. © The Author 2017. Published by Oxford University Press on behalf of CINP.

Recent progress in ankylosing spondylitis treatment.

PubMed

Toussirot, Eric; Wendling, Daniel

2003-01-01

Ankylosing spondylitis (AS) is a systemic inflammatory rheumatic disease responsible for back pain, stiffness and loss of functional capacity. The therapeutic management of AS includes regular physical exercise together with the use of NSAIDs. Second-line treatments, such as sulfasalazine, are required in cases of NSAID-refractory AS. Some patients have severe and inadequately controlled disease, explaining the need for the development of new treatments. This therapeutic development in AS involves the assessment of new NSAIDs, namely COX2 selective agents and new second-line treatments, such as methotrexate (MTX), pamidronate and anti-TNFalpha agents. Controlled studies are lacking for MTX. Pamidronate showed to be effective in NSAID refractory AS patients in open and controlled trials. Anti-TNFalpha agents (infliximab and etanercept) gave promising results with dramatic improvement of AS symptoms in open and preliminary controlled trials, but further studies are required to evaluate the real long-term effects and tolerability of these drugs.

Free treatment, rapid malaria diagnostic tests and malaria village workers can hasten progress toward achieving the malaria related millennium development goals: the Médecins Sans Frontières experience from Chad, Sierra-Leone and Mali

PubMed Central

Tayler-Smith, Katie; Kociejowski, Alice; de Lamotte, Nadine; Gerard, Seco; Ponsar, Frederique; Philips, Mit; Zachariah, Rony

2011-01-01

Halving the burden of malaria by 2015 and ensuring that 80% of people with malaria receive treatment is among the health related targets of the Millennium Development Goals (MDGs). Despite political momentum toward achieving this target, progress is slow and many with malaria (particularly in poor and rural communities in Africa) are still without access to effective treatment. Finding ways to improve access to anti-malarial treatment in Africa is essential to achieve the malaria related and other MDG targets. During its work in Chad, Sierra Leone and Mali in the period 2004 to 2008, Médecins Sans Frontières showed that it was possible to significantly improve access to effective malaria treatment through: i) the removal of health centre level user fees for essential healthcare for vulnerable population groups, ii) the introduction of free community based treatment for children using malaria village workers to diagnose and treat simple malaria in communities where geographical and financial barriers limited access to effective malaria care, iii) the improved diagnosis and treatment of malaria using rapid diagnosis tests and artemisinin based combination therapy, at both health facilities and in the community. This paper describes and discusses these strategies and their related impact. PMID:28299053

Antibiotics for asymptomatic bacteriuria in pregnancy.

PubMed

Smaill, F

2000-01-01

Up to 30% of mothers develop acute pyelonephritis if asymptomatic bacteriuria is untreated. Asymptomatic bacteriuria may have a role in preterm birth, or it may be a marker for low socioeconomic status and thus, low birth weight. The objective of this review was to assess the effect of antibiotic treatment for asymptomatic bacteriuria on persistent bacteriuria during pregnancy, the risk of preterm delivery and the development of pyelonephritis after delivery. I searched the Cochrane Pregnancy and Childbirth Group trials register. Randomised trials comparing antibiotic treatment with placebo or no treatment in pregnant women with asymptomatic bacteriuria found on antenatal screening. Trial quality was assessed. Thirteen studies were included. Overall the study quality was not strong. Antibiotic treatment compared to placebo or no treatment was effective in clearing asymptomatic bacteriuria (odds ratio 0.07, 95% confidence interval 0.05 to 0.10). The incidence of pyelonephritis was reduced (odds ratio 0.25, 95% confidence interval 0.19 to 0.32). Antibiotic treatment was also associated with a reduction in the incidence of preterm delivery or low birth weight babies (odds ratio 0.60, 95% confidence interval 0.45 to 0.80). Antibiotic treatment appears to be effective in reducing the risk of pyelonephritis in pregnancy. An apparent reduction in preterm delivery is consistent with current theories about the role of infection in preterm birth, but this association should be interpreted with caution.

Antibiotics for asymptomatic bacteriuria in pregnancy.

PubMed

Smaill, F

2001-01-01

Up to 30% of mothers develop acute pyelonephritis if asymptomatic bacteriuria is untreated. Asymptomatic bacteriuria may have a role in preterm birth or it may be a marker for low socioeconomic status which is associated with low birth weight. The objective of this review was to assess the effect of antibiotic treatment for asymptomatic bacteriuria on persistent bacteriuria during pregnancy, the risk of preterm delivery, and the development of pyelonephritis. I searched the Cochrane Pregnancy and Childbirth Group trials register. Date of last search: December 2000. Randomised trials comparing antibiotic treatment with placebo or no treatment in pregnant women with asymptomatic bacteriuria found on antenatal screening. Trial quality was assessed. Fourteen studies were included. Overall the study quality was not strong. Antibiotic treatment compared to placebo or no treatment was effective in clearing asymptomatic bacteriuria (odds ratio 0.07, 95% confidence interval 0.05 to 0.10). The incidence of pyelonephritis was reduced (odds ratio 0.24, 95% confidence interval 0.19 to 0.32). Antibiotic treatment was also associated with a reduction in the incidence of preterm delivery or low birth weight babies (odds ratio 0.60, 95% confidence interval 0.45 to 0.80). Antibiotic treatment is effective in reducing the risk of pyelonephritis in pregnancy. An apparent reduction in preterm delivery is consistent with current theories about the role of infection in preterm birth, but this association should be interpreted with caution.

Antibiotics for asymptomatic bacteriuria in pregnancy.

PubMed

Smaill, F; Vazquez, J C

2007-04-18

Asymptomatic bacteriuria occurs in 2% to 10% of pregnancies and, if not treated, up to 30% of mothers will develop acute pyelonephritis. Asymptomatic bacteriuria has been associated with low birthweight and preterm delivery. To assess the effect of antibiotic treatment for asymptomatic bacteriuria on persistent bacteriuria during pregnancy, the development of pyelonephritis and the risk of low birthweight and preterm delivery. We searched the Cochrane Pregnancy and Childbirth Group's Trials Register (January 2007). Randomized trials comparing antibiotic treatment with placebo or no treatment in pregnant women with asymptomatic bacteriuria found on antenatal screening. We assessed trial quality. Fourteen studies were included. Overall the study quality was poor. Antibiotic treatment compared to placebo or no treatment was effective in clearing asymptomatic bacteriuria (risk ratio (RR) 0.25, 95% confidence interval (CI) 0.14 to 0.48). The incidence of pyelonephritis was reduced (RR 0.23, 95% CI 0.13 to 0.41). Antibiotic treatment was also associated with a reduction in the incidence of low birthweight babies (RR 0.66, 95% CI 0.49 to 0.89) but a difference in preterm delivery was not seen. Antibiotic treatment is effective in reducing the risk of pyelonephritis in pregnancy. A reduction in low birthweight is consistent with current theories about the role of infection in adverse pregnancy outcomes, but this association should be interpreted with caution given the poor quality of the included studies.

Cost-Effectiveness of Immune Checkpoint Inhibition in BRAF Wild-Type Advanced Melanoma

PubMed Central

Zeichner, Simon B.; Chen, Qiushi; Montero, Alberto J.; Goldstein, Daniel A.; Flowers, Christopher R.

2017-01-01

Purpose Patients who are diagnosed with stage IV metastatic melanoma have an estimated 5-year relative survival rate of only 17%. Randomized controlled trials of recent US Food and Drug Administration–approved immune checkpoint inhibitors—pembrolizumab (PEM), nivolumab (NIVO), and ipilumumab (IPI)—demonstrate improved patient outcomes, but the optimal treatment sequence in patients with BRAF wild-type metastatic melanoma remains unclear. To inform policy makers about the value of these treatments, we developed a Markov model to compare the cost-effectiveness of different strategies for sequencing novel agents for the treatment of advanced melanoma. Materials and Methods We developed Markov models by using a US-payer perspective and lifetime horizon to estimate costs (2016 US$) and quality-adjusted life years (QALYs) for treatment sequences with first-line NIVO, IPI, NIVO + IPI, PEM every 2 weeks, and PEM every 3 weeks. Health states were defined for initial treatment, first and second progression, and death. Rates for drug discontinuation, frequency of adverse events, disease progression, and death obtained from randomized phase III trials were used to determine the likelihood of transition between states. Deterministic and probabilistic sensitivity analyses were conducted to evaluate model uncertainty. Results PEM every 3 weeks followed by second-line IPI was both more effective and less costly than dacarbazine followed by IPI then NIVO, or IPI followed by NIVO. Compared with the first-line dacarbazine treatment strategy, NIVO followed by IPI produced an incremental cost effectiveness ratio of $90,871/QALY, and first-line NIVO + IPI followed by carboplatin plus paclitaxel chemotherapy produced an incremental cost effectiveness ratio of $198,867/QALY. Conclusion For patients with treatment-naive BRAF wild-type advanced melanoma, first-line PEM every 3 weeks followed by second-line IPI or first-line NIVO followed by second-line IPI are the most cost-effective, immune-based treatment strategies for metastatic melanoma. PMID:28221865

New Directions in the Cognitive-Behavioral Treatment of OCD: Theory, Research, and Practice.

PubMed

Abramowitz, Jonathan S; Blakey, Shannon M; Reuman, Lillian; Buchholz, Jennifer L

2018-05-01

The beneficial effects of cognitive-behavioral interventions (particularly exposure and response prevention) for OCD are among the most consistent research findings in the mental health literature. Nevertheless, even after an adequate trial, many individuals experience residual symptoms, and others never receive adequate treatment due to limited access. These and other issues have prompted clinicians and researchers to search for ways to improve the conceptual and practical aspects of existing treatment approaches, as well as look for augmentation strategies. In the present article, we review a number of recent developments and new directions in the psychological treatment of OCD, including (a) the application of inhibitory learning approaches to exposure therapy, (b) the development of acceptance-based approaches, (c) involvement of caregivers (partners and parents) in treatment, (d) pharmacological cognitive enhancement of exposure therapy, and (e) the use of technology to disseminate effective treatment. We focus on both the conceptual/scientific and practical aspects of these topics so that clinicians and researchers alike can assess their relative merits and disadvantages. Copyright © 2017. Published by Elsevier Ltd.

Cold atmospheric plasma treatment inhibits growth in colorectal cancer cells.

PubMed

Schneider, Christin; Arndt, Stephanie; Zimmermann, Julia L; Li, Yangfang; Karrer, Sigrid; Bosserhoff, Anja-Katrin

2018-06-01

Plasma oncology is a relatively new field of research. Recent developments have indicated that cold atmospheric plasma (CAP) technology is an interesting new therapeutic approach to cancer treatment. In this study, p53 wildtype (LoVo) and human p53 mutated (HT29 and SW480) colorectal cancer cells were treated with the miniFlatPlaSter - a device particularly developed for the treatment of tumor cells - that uses the Surface Micro Discharge (SMD) technology for plasma production in air. The present study analyzed the effects of plasma on colorectal cancer cells in vitro and on normal colon tissue ex vivo. Plasma treatment had strong effects on colon cancer cells, such as inhibition of cell proliferation, induction of cell death, and modulation of p21 expression. In contrast, CAP treatment of murine colon tissue ex vivo for up to 2 min did not show any toxic effect on normal colon cells compared to H2O2 positive control. In summary, these results suggest that the miniFlatPlaSter plasma device is able to kill colorectal cancer cells independent of their p53 mutation status. Thus, this device presents a promising new approach in colon cancer therapy.

Therapeutic Potential of Tea Tree Oil for Scabies

PubMed Central

Thomas, Jackson; Carson, Christine F.; Peterson, Greg M.; Walton, Shelley F.; Hammer, Kate A.; Naunton, Mark; Davey, Rachel C.; Spelman, Tim; Dettwiller, Pascale; Kyle, Greg; Cooper, Gabrielle M.; Baby, Kavya E.

2016-01-01

Globally, scabies affects more than 130 million people at any time. In the developed world, outbreaks in health institutions and vulnerable communities result in a significant economic burden. A review of the literature demonstrates the emergence of resistance toward classical scabicidal treatments and the lack of effectiveness of currently available scabicides in reducing the inflammatory skin reactions and pyodermal progression that occurs in predisposed patient cohorts. Tea tree oil (TTO) has demonstrated promising acaricidal effects against scabies mites in vitro and has also been successfully used as an adjuvant topical medication for the treatment of crusted scabies, including cases that did not respond to standard treatments. Emerging acaricide resistance threatens the future usefulness of currently used gold standard treatments (oral ivermectin and topical permethrin) for scabies. The imminent development of new chemical entities is doubtful. The cumulative acaricidal, antibacterial, antipruritic, anti-inflammatory, and wound healing effects of TTO may have the potential to successfully reduce the burden of scabies infection and the associated bacterial complications. This review summarizes current knowledge on the use of TTO for the treatment of scabies. On the strength of existing data for TTO, larger scale, randomized controlled clinical trials are warranted. PMID:26787146

Therapeutic Potential of Tea Tree Oil for Scabies.

PubMed

Thomas, Jackson; Carson, Christine F; Peterson, Greg M; Walton, Shelley F; Hammer, Kate A; Naunton, Mark; Davey, Rachel C; Spelman, Tim; Dettwiller, Pascale; Kyle, Greg; Cooper, Gabrielle M; Baby, Kavya E

2016-02-01

Globally, scabies affects more than 130 million people at any time. In the developed world, outbreaks in health institutions and vulnerable communities result in a significant economic burden. A review of the literature demonstrates the emergence of resistance toward classical scabicidal treatments and the lack of effectiveness of currently available scabicides in reducing the inflammatory skin reactions and pyodermal progression that occurs in predisposed patient cohorts. Tea tree oil (TTO) has demonstrated promising acaricidal effects against scabies mites in vitro and has also been successfully used as an adjuvant topical medication for the treatment of crusted scabies, including cases that did not respond to standard treatments. Emerging acaricide resistance threatens the future usefulness of currently used gold standard treatments (oral ivermectin and topical permethrin) for scabies. The imminent development of new chemical entities is doubtful. The cumulative acaricidal, antibacterial, antipruritic, anti-inflammatory, and wound healing effects of TTO may have the potential to successfully reduce the burden of scabies infection and the associated bacterial complications. This review summarizes current knowledge on the use of TTO for the treatment of scabies. On the strength of existing data for TTO, larger scale, randomized controlled clinical trials are warranted. © The American Society of Tropical Medicine and Hygiene.

Childhood Arthritis and Rheumatology Research Alliance consensus treatment plans for new-onset polyarticular juvenile idiopathic arthritis.

PubMed

Ringold, Sarah; Weiss, Pamela F; Colbert, Robert A; DeWitt, Esi Morgan; Lee, Tzielan; Onel, Karen; Prahalad, Sampath; Schneider, Rayfel; Shenoi, Susan; Vehe, Richard K; Kimura, Yukiko

2014-07-01

There is no standardized approach to the initial treatment of polyarticular juvenile idiopathic arthritis (JIA) among pediatric rheumatologists. Understanding the comparative effectiveness of the diverse therapeutic options available will result in better health outcomes for polyarticular JIA. The Childhood Arthritis and Rheumatology Research Alliance (CARRA) developed consensus treatment plans (CTPs) for use in clinical practice to facilitate such studies. A case-based survey was administered to CARRA members to identify the common treatment approaches for new-onset polyarticular JIA. Two face-to-face consensus conferences employed modified nominal group technique to identify treatment strategies, operational case definition, end points, and data elements to be collected. A core workgroup reviewed the relevant literature, refined plans, and developed medication dosing and monitoring recommendations. The initial case-based survey identified significant variability among treatment approaches for new-onset polyarticular JIA. We developed 3 CTPs based on treatment strategies for the first 12 months of therapy, as well as case definitions and clinical and laboratory monitoring schedules. The CTPs include a step-up plan (nonbiologic disease-modifying antirheumatic drug [DMARD] followed by a biologic DMARD), an early combination plan (nonbiologic and biologic DMARD combined within a month of treatment initiation), and a biologic only plan. This approach was approved by 96% of the CARRA JIA Research Committee members attending the 2013 CARRA face-to-face meeting. Three standardized CTPs were developed for new-onset polyarticular JIA. Coupled with data collection at defined intervals, use of these CTPs will enable the study of their comparative effectiveness in an observational setting to optimize initial management of polyarticular JIA. Copyright © 2014 by the American College of Rheumatology.

Overview of air biofiltration - basic technology, economics and integration with other control technologies for effective treatment of air toxics

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

Govind, R.; Bishop, D.F.

1996-12-31

This paper provides an overview of air biofiltration with experimental data on the performance of peat/compost, pelletized packed bed and structured media biofilters. It is shown that use of high surface area per unit volume structured media results in higher contaminant treatment rates per unit biofilter volume. Peat/compost biofilters exhibit lower removal efficiencies at high (> 100 ppmv) inlet contaminant concentrations and require control of media moisture content. Increase of temperature results in increasing biodegradation rates. It is shown that use of structured ceramic media allows effective control of biomass buildup by continuous removal of biomass from the biofilter mediamore » and that the biomass removal rate depends on nutrient flowrate. An experimental system is presented which enables biofilm kinetics to be determined and a simple biofilter model is developed in this paper. A group contribution approach has been developed to estimate biokinetic parameter which allows biofiltration effectiveness to be determined for a variety of volatile organic compounds (VOCs). Finally, a procedure is presented, illustrated by an example, which is used to develop an integrated process for effective treatment of air contaminants. 22 refs., 12 figs., 4 tabs.« less

Water Stress Affects Development Time but Not Takeoff Performance in the Butterfly Pararge aegeria.

PubMed

Lailvaux, Simon P; Breuker, Casper J; Van Damme, Raoul

Most organisms are limited in the amount and type of resources they are able to extract from the environment. The juvenile environment is particularly important in this regard, as conditions over ontogeny can influence the adult phenotype. Whole-organism performance traits, such as locomotion, are susceptible to such environmental effects, yet the specific biotic and abiotic factors driving performance plasticity have received little attention. We tested whether speckled wood Pararge aegeria L. butterflies reared under conditions of water stress exhibited poorer flight morphology and performance than control individuals. Despite large differences in mortality between treatments, we found no effects of water stress treatment on takeoff performance and only minor treatment effects on flight morphology. However, butterflies reared on water-stressed diets exhibited both significantly greater mortality and longer development times than did control individuals. Pararge aegeria larvae may compensate for this stress by prolonging development, resulting in similar realized performance capacities at least in takeoff performance in surviving adult butterflies; other measures of flight performance remain to be considered. Alternatively, the adult phenotype may be insulated from environmental effects at the larval stage in these insects.

Prevention of oral mucositis due to 5-fluorouracil treatment with oral cryotherapy.

PubMed

Baydar, Mustafa; Dikilitas, Mustafa; Sevinc, Alper; Aydogdu, Ismet

2005-08-01

One of the most common and important side effects of 5-fluorouracil (5-FU) is mucositis with ulcerations in the oral cavity. We investigated the effects of local cryotherapy on mucositis incidence administrated durng 5-FU treatment. In a total of 99 courses, 5-FU and folinic acid combination chemotherapy was given to 40 patients. In our study, we considered every course as a single case, and cryotherapy was given to the same patient in one course but not given in the next. While mucositis developed in 6.7% of the courses given with cryotherapy, this ratio was 38.9% in courses given without cryotherapy. In the logistic regression analysis, development of mucositis had been found to correlate only with cryotherapy. Odds ratio (OR) = 11.5; in the 95% confidence interval (CI) = 3.2 - 41.9; (p = 0.001). Results of initial studies evaluating the effects of cryotherapy in preventing mucositis due to 5-FU based chemotherapy regimens were promising. We concluded that oral cooling prevents 5-FU induced mucositis. This effective prophylactic treatment should be used in patients who are at increased risk for developing 5-FU induced mucositis.

Prevention of oral mucositis due to 5-fluorouracil treatment with oral cryotherapy.

PubMed Central

Baydar, Mustafa; Dikilitas, Mustafa; Sevinc, Alper; Aydogdu, Ismet

2005-01-01

INTRODUCTION: One of the most common and important side effects of 5-fluorouracil (5-FU) is mucositis with ulcerations in the oral cavity. We investigated the effects of local cryotherapy on mucositis incidence administrated durng 5-FU treatment. METHODS: In a total of 99 courses, 5-FU and folinic acid combination chemotherapy was given to 40 patients. In our study, we considered every course as a single case, and cryotherapy was given to the same patient in one course but not given in the next. RESULTS: While mucositis developed in 6.7% of the courses given with cryotherapy, this ratio was 38.9% in courses given without cryotherapy. In the logistic regression analysis, development of mucositis had been found to correlate only with cryotherapy. Odds ratio (OR) = 11.5; in the 95% confidence interval (CI) = 3.2 - 41.9; (p = 0.001). DISCUSSION: Results of initial studies evaluating the effects of cryotherapy in preventing mucositis due to 5-FU based chemotherapy regimens were promising. We concluded that oral cooling prevents 5-FU induced mucositis. This effective prophylactic treatment should be used in patients who are at increased risk for developing 5-FU induced mucositis. PMID:16173332

Organizer formation in Hydra is disrupted by thalidomide treatment.

PubMed

Brooun, Maria; Manoukian, Armen; Shimizu, Hiroshi; Bode, Hans R; McNeill, Helen

2013-06-01

Thalidomide is a drug that is well known for its teratogenic properties in humans. Surprisingly, thalidomide does not have teratogenic effects on mouse development. We investigated the effect of thalidomide on patterning in hydra, an early metazoan with a very simple axial symmetry. Hydra develops asexually via Wnt-dependent organizer formation, leading to the budding of a new organism. We observe both induction and inhibition of organizer formation depending on cellular context. Interestingly, thalidomide treatment altered budding and the developing organizer, but had little effect on the adult. Expression of Hybra1, a marker of the organizer increased upon thalidomide treatment. However when the organizer is induced by ectopic activation of Wnt signaling via GSK3 inhibition, thalidomide suppresses induction. We show that inhibition of Wnt signaling is not mediated by induction of the BMP pathway. We show that thalidomide activity on organizer formation in hydra depends on the activity of casein kinase1 and the abundance of β-catenin. Finally, we find that interstitial cells, multipotent cells which give rise to nemoatocytes, neural, digestive and germline cells, are partially responsible for the inhibitory effect of thalidomide. Copyright © 2013 Elsevier Inc. All rights reserved.

Skeletal muscle mitochondrial energetics in obesity and type 2 diabetes mellitus: endocrine aspects.

PubMed

Aguer, Céline; Harper, Mary-Ellen

2012-12-01

During the development of type 2 diabetes mellitus, skeletal muscle is a major site of insulin resistance. The latter has been linked to mitochondrial dysfunction and impaired fatty acid oxidation. Some hormones like insulin, thyroid hormones and adipokines (e.g., leptin, adiponectin) have positive effects on muscle mitochondrial bioenergetics through their direct or indirect effects on mitochondrial biogenesis, mitochondrial protein expression, mitochondrial enzyme activities and/or AMPK pathway activation--all of which can improve fatty acid oxidation. It is therefore not surprising that treatment with these hormones has been proposed to improve muscle and whole body insulin sensitivity. However, treatment of diabetic patients with leptin and adiponectin has no effect on muscle mitochondrial bioenergetics showing resistance to these hormones during type 2 diabetes. Furthermore, treatment with most thyroid hormones has unexpectedly revealed negative effects on muscle insulin sensitivity. Future research should focus on development of agents that improve metabolic dysfunction downstream of hormone receptors. Copyright © 2012 Elsevier Ltd. All rights reserved.

Clozapine Associated with Autoimmune Reaction, Fever and Low Level Cardiotoxicity – A Case Report

PubMed Central

GERASIMOU, CHARILAOS; PHAEDRA VITALI, GEORGIA; D. VAVOUGIOS, GEORGE; PAPAGEORGIOU, CHARALABOS; DOUZENIS, ATHANASIOS; I. KOKORIS, STYLIANI; LIAPPAS, IOANNIS; RIZOS, EMMANOUIL

2017-01-01

Background: Clozapine is a second-generation antipsychotic drug used in treatment-resistant schizophrenia. Fever induced by clozapine is a rather frequent side-effect which usually occurs in the first 4 weeks of treatment. Despite its effectiveness, there are potentially life-threatening adverse effects, such as cardiotoxicity. Case Report: We present the case of a 31- year-old caucasian male with refractory schizophrenia who developed benign fever, increase of C-reactive protein and high troponin levels, without presenting any other signs to myocarditis, on the 13th day under clozapine treatment, which declined progressively upon discontinuation of the drug. Discussion: This case hints at the presence of initially subclinical cardiotoxicity as an underlying factor in patients developing fever. Conclusion: Taking advantage of more sensitive methods for measuring troponin, clinicians would be promptly aware of this possible side-effect. This would allow for significant reduction of the risk of cardiac dysfunction, further attained by carefully monitoring the patient. PMID:28064233

Clozapine Associated with Autoimmune Reaction, Fever and Low Level Cardiotoxicity - A Case Report.

PubMed

Gerasimou, Charilaos; Vitali, Georgia Phaedra; Vavougios, George D; Papageorgiou, Charalabos; Douzenis, Athanasios; Kokoris, Styliani I; Liappas, Ioannis; Rizos, Emmanouil

2017-01-02

Clozapine is a second-generation antipsychotic drug used in treatment-resistant schizophrenia. Fever induced by clozapine is a rather frequent side-effect which usually occurs in the first 4 weeks of treatment. Despite its effectiveness, there are potentially life-threatening adverse effects, such as cardiotoxicity. We present the case of a 31-year-old caucasian male with refractory schizophrenia who developed benign fever, increase of C-reactive protein and high troponin levels, without presenting any other signs to myocarditis, on the 13th day under clozapine treatment, which declined progressively upon discontinuation of the drug. This case hints at the presence of initially subclinical cardiotoxicity as an underlying factor in patients developing fever. Taking advantage of more sensitive methods for measuring troponin, clinicians would be promptly aware of this possible side-effect. This would allow for significant reduction of the risk of cardiac dysfunction, further attained by carefully monitoring the patient. Copyright© 2017, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.

Cost-effectiveness of sequenced treatment of rheumatoid arthritis with targeted immune modulators.

PubMed

Jansen, Jeroen P; Incerti, Devin; Mutebi, Alex; Peneva, Desi; MacEwan, Joanna P; Stolshek, Bradley; Kaur, Primal; Gharaibeh, Mahdi; Strand, Vibeke

2017-07-01

To determine the cost-effectiveness of treatment sequences of biologic disease-modifying anti-rheumatic drugs or Janus kinase/STAT pathway inhibitors (collectively referred to as bDMARDs) vs conventional DMARDs (cDMARDs) from the US societal perspective for treatment of patients with moderately to severely active rheumatoid arthritis (RA) with inadequate responses to cDMARDs. An individual patient simulation model was developed that assesses the impact of treatments on disease based on clinical trial data and real-world evidence. Treatment strategies included sequences starting with etanercept, adalimumab, certolizumab, or abatacept. Each of these treatment strategies was compared with cDMARDs. Incremental cost, incremental quality-adjusted life-years (QALYs), and incremental cost-effectiveness ratios (ICERs) were calculated for each treatment sequence relative to cDMARDs. The cost-effectiveness of each strategy was determined using a US willingness-to-pay (WTP) threshold of $150,000/QALY. For the base-case scenario, bDMARD treatment sequences were associated with greater treatment benefit (i.e. more QALYs), lower lost productivity costs, and greater treatment-related costs than cDMARDs. The expected ICERs for bDMARD sequences ranged from ∼$126,000 to $140,000 per QALY gained, which is below the US-specific WTP. Alternative scenarios examining the effects of homogeneous patients, dose increases, increased costs of hospitalization for severely physically impaired patients, and a lower baseline Health Assessment Questionnaire (HAQ) Disability Index score resulted in similar ICERs. bDMARD treatment sequences are cost-effective from a US societal perspective.

Generalized semiparametric varying-coefficient models for longitudinal data

NASA Astrophysics Data System (ADS)

Qi, Li

In this dissertation, we investigate the generalized semiparametric varying-coefficient models for longitudinal data that can flexibly model three types of covariate effects: time-constant effects, time-varying effects, and covariate-varying effects, i.e., the covariate effects that depend on other possibly time-dependent exposure variables. First, we consider the model that assumes the time-varying effects are unspecified functions of time while the covariate-varying effects are parametric functions of an exposure variable specified up to a finite number of unknown parameters. The estimation procedures are developed using multivariate local linear smoothing and generalized weighted least squares estimation techniques. The asymptotic properties of the proposed estimators are established. The simulation studies show that the proposed methods have satisfactory finite sample performance. ACTG 244 clinical trial of HIV infected patients are applied to examine the effects of antiretroviral treatment switching before and after HIV developing the 215-mutation. Our analysis shows benefit of treatment switching before developing the 215-mutation. The proposed methods are also applied to the STEP study with MITT cases showing that they have broad applications in medical research.

Callous-unemotional traits and early life stress predict treatment effects on stress and sex hormone functioning in incarcerated male adolescents.

PubMed

Johnson, Megan; Vitacco, Michael J; Shirtcliff, Elizabeth A

2018-03-01

The stress response system is highly plastic, and hormone rhythms may "adaptively calibrate" in response to treatment. This investigation assessed whether stress and sex hormone diurnal rhythms changed over the course of behavioral treatment, and whether callous-unemotional (CU) traits and history of early adversity affected treatment results on diurnal hormone functioning in a sample of 28 incarcerated adolescent males. It was hypothesized that the treatment would have beneficial effects, such that healthier diurnal rhythms would emerge post-treatment. Diurnal cortisol, testosterone, and dehydroepiandrosterone (DHEA) were sampled two weeks after admission to the correctional/treatment facility, and again approximately four months later. Positive treatment effects were detected for the whole sample, such that testosterone dampened across treatment. CU traits predicted a non-optimal hormone response to treatment, potentially indicating biological preparedness to respond to acts of social dominance and aggression. The interaction between CU traits and adversity predicted a promising and sensitized response to treatment including increased cortisol and a steeper testosterone drop across treatment. Results suggest that stress and sex hormones are highly receptive to treatment during this window of development.

Clinical Response to Ingenol Mebutate in Patients With Actinic Keratoses.

PubMed

Batalla, A; Flórez, Á; Feal, C; Peón, G; Abalde, M T; Salgado-Boquete, L; de la Torre, C

2015-12-01

Cryotherapy is the most common treatment for actinic keratosis, but its effect is limited to individual lesions. Several topical drugs, however, are available that, in addition to treating individual actinic keratoses, target field cancerization and thereby act on subclinical lesions. Examples are 5-fluorouracil, imiquimod, diclofenac, and ingenol mebutate. We report on 17 patients with actinic keratoses treated with ingenol mebutate and describe our findings on treatment effectiveness, adherence, and tolerance. Complete and partial response rates were 35% and 53%, respectively. Ninety-four percent of patients fully adhered to treatment and 18% developed severe local reactions. Ingenol mebutate is an effective treatment for actinic keratosis. Although it has a similar rate of local reactions to other treatments available for actinic keratosis, its short treatment regimen favors better adherence. Copyright © 2014 Elsevier España, S.L.U. y AEDV. All rights reserved.

Development of high-efficiency solar cells on silicon web

NASA Technical Reports Server (NTRS)

Rohatgi, A.; Meier, D. L.; Campbell, R. B.; Seidensticker, R. G.; Rai-Choudhury, P.

1985-01-01

High-efficiency dendritic cells were discussed. The influence of twin planes and heat treatment on the location and effect of trace impurities was of particular interest. Proper heat treatment often increases efficiency by causing impurities to pile up at twin planes. Oxide passivation had a beneficial effect on efficiency. A very efficient antireflective (AR) coating of zinc selenide and magnesium fluoride was designed and fabricated. An aluminum back-surface reflector was also effective.

Trypanosoma cruzi: effects of azadirachtin and ecdysone on the dynamic development in Rhodnius prolixus larvae.

PubMed

Cortez, M R; Provençano, A; Silva, C E; Mello, C B; Zimmermann, L T; Schaub, G A; Garcia, E S; Azambuja, P; Gonzalez, M S

2012-07-01

The effects of azadirachtin and ecdysone on the Trypanosoma cruzi population in the Rhodnius prolixus gut were investigated. T. cruzi were rarely found in the gut compartments of azadirachtin-treated larvae. High parasite numbers were observed in the stomach of the control and ecdysone groups until 10 days after treatment and in the small intestine and rectum until 25 days after treatment. High percentages of round forms developed in the stomachs of all groups, whereas azadirachtin blocked the development of protozoan intermediate forms. This effect was counteracted by ecdysone therapy. In the small intestine and rectum, epimastigotes predominated for all groups, but more of their intermediates developed in the control and ecdysone groups. Azadirachtin supported the development of round forms and their intermediates into trypomastigotes. In the rectum, trypomastigotes did not develop in the azadirachtin group and developed much later after ecdysone therapy. The parallel between the effects of azadirachtin and ecdysone on the host and parasite development is discussed on the basis of the present results because ecdysone appears to act directly or indirectly in determining the synchronic development of T. cruzi forms from round to epimastigotes, but not metacyclic trypomastigotes, in the invertebrate vector. Copyright © 2012 Elsevier Inc. All rights reserved.

Antibiotics for the treatment of Cholera, Shigella and Cryptosporidium in children.

PubMed

Das, Jai K; Ali, Anum; Salam, Rehana A; Bhutta, Zulfiqar A

2013-01-01

Diarrhea is a major contributor to the burden of morbidity and mortality in children; it accounts for a median of 11% of all deaths among children aged less than 5 years, amounting to approximately 0.8 million deaths per year. Currently there is a dearth of literature exploring the effectiveness of antibiotics for diarrhea due to Cholera, Shigella and cryptosporidiosis in children. We reviewed the literature reporting the effect of antibiotics for the treatment of diarrhea due to Cholera, Shigella and Cryptosporidium in children under five years. We used a standardized abstraction and grading format and performed meta-analyses to determine the effect of the treatment with various antibiotics on mortality and rates of clinical and bacteriological/parasitological failure. The CHERG Standard Rules were applied to determine the final effect of treatment with antibiotics on diarrhea morbidity and mortality. For Cholera; the evidence was weak to recommend any effect on mortality. For Shigella; there was no data on mortality; either all-cause or cause specific, hence we used clinical failure rates as a proxy for Shigella deaths and propose that treatment of Shigella dysentery with antibiotics can result in a 82% reduction in diarrhea mortality due to Shigella. For cryptosporidiosis; there was data on all-cause mortality but the evidence was weak hence we used clinical failure rates as a proxy for mortality to estimate that antimicrobial treatment of diarrhea due to cryptosporidiosis can result in a 54% reduction in mortality. There is evidence to recommend antibiotic use for reduction of morbidity and mortality due to Cholera, Shigella and Cryptosporidium. We recommend that more clinical trials should be conducted to evaluate the efficacy and safety of first- and second- line drugs currently in use for treatment for diarrhea and dysentery in both developing and developed countries.

Antitumour action on human glioblastoma A1235 cells through cooperation of bee venom and cisplatin.

PubMed

Gajski, Goran; Čimbora-Zovko, Tamara; Rak, Sanjica; Osmak, Maja; Garaj-Vrhovac, Vera

2016-08-01

Cisplatin (cDDP) is one of the most widely used anticancer-drugs in both therapy and research. However, cDDP-resistance is the greatest obstacle for the successful treatment of cancer patients. In the present study, the possible joint anticancer effect of bee venom (BV), as a natural toxin, and cDDP towards human glioblastoma A1235 cells was evaluated. Treatment with BV alone in concentrations of 2.5-30 μg/ml displayed dose-dependent cytotoxicity towards A1235 cells, as evaluated with different cytotoxicity assays (MTT, Cristal violet and Trypan blue exclusion assay), with an IC50 value of 22.57 μg/ml based on the MTT results. Furthermore, BV treatment induced necrosis, which was confirmed by typical morphological features and fast staining with ethidium-bromide dye. Pre-treatment with BV induced cell sensitization to cDDP, indicating that BV could improve the killing effect of selected cells when combined with cDDP. The isobologram method used to determine the extent of synergism in combining two agents to examine their possible therapeutic effect showed that combined treatment induced an additive and/or synergistic effect towards selected cells depending on the concentration of both. Hence, a greater anticancer effect could be triggered if BV was used in the course of chemotherapy. The obtained results indicate that joint treatment with BV could be useful from the point of minimizing the cDDP concentration during chemotherapy, thus reducing and/or postponing the development of drug resistance. Our data, in accordance with previously reported results, suggests that BV could be used in the development of a new strategy for cancer treatment.

Fetal and Neonatal Iron Deficiency Exacerbates Mild Thyroid Hormone Insufficiency Effects on Male Thyroid Hormone Levels and Brain Thyroid Hormone-Responsive Gene Expression

PubMed Central

Bastian, Thomas W.; Prohaska, Joseph R.; Georgieff, Michael K.

2014-01-01

Fetal/neonatal iron (Fe) and iodine/TH deficiencies lead to similar brain developmental abnormalities and often coexist in developing countries. We recently demonstrated that fetal/neonatal Fe deficiency results in a mild neonatal thyroidal impairment, suggesting that TH insufficiency contributes to the neurodevelopmental abnormalities associated with Fe deficiency. We hypothesized that combining Fe deficiency with an additional mild thyroidal perturbation (6-propyl-2-thiouracil [PTU]) during development would more severely impair neonatal thyroidal status and brain TH-responsive gene expression than either deficiency alone. Early gestation pregnant rats were assigned to 7 different treatment groups: control, Fe deficient (FeD), mild TH deficient (1 ppm PTU), moderate TH deficient (3 ppm PTU), severe TH deficient (10 ppm PTU), FeD/1 ppm PTU, or FeD/3 ppm PTU. FeD or 1 ppm PTU treatment alone reduced postnatal day 15 serum total T4 concentrations by 64% and 74%, respectively, without significantly altering serum total T3 concentrations. Neither treatment alone significantly altered postnatal day 16 cortical or hippocampal T3 concentrations. FeD combined with 1 ppm PTU treatment produced a more severe effect, reducing serum total T4 by 95%, and lowering hippocampal and cortical T3 concentrations by 24% and 31%, respectively. Combined FeD/PTU had a more severe effect on brain TH-responsive gene expression than either treatment alone, significantly altering Pvalb, Dio2, Mbp, and Hairless hippocampal and/or cortical mRNA levels. FeD/PTU treatment more severely impacted cortical and hippocampal parvalbumin protein expression compared with either individual treatment. These data suggest that combining 2 mild thyroidal insults during development significantly disrupts thyroid function and impairs TH-regulated brain gene expression. PMID:24424046

Effects of canopy treatments on early growth of planted longleaf pine seedlings and ground vegetation in North Carolina: a preliminary study

Treesearch

Huifeng Hu; Benjamin O. Knapp; G. Geoff Wang; Joan L. Walker

2013-01-01

We installed a field experiment to support the development of protocols to restore longleaf pine (Pinus palustris Mill.) to existing mature loblolly pine (P. taeda L.) stands at Camp Lejeune, NC. Seven canopy treatments included four uniform and three gap treatments. The four uniform treatments were defined by target residual basal...

Effect of Porous Media and Fluid Properties on Dense Non-Aqueous Phase Liquid Migration and Dilution Mass Flux

DTIC Science & Technology

2005-08-01

Research and iii Development Program, Department of Defense, who in part funded this research (CU- 1295: Impacts of DNAPL Source Zone Treatment : Experimental...Trichlorosilane Treatment and Retardation Factor ....................... 46 Results and D iscussion... treatments . Water entry rates were then experimentally measured for various media treatments altering contact angle. With all other data known, contact

The cost-effectiveness of immediate treatment or watch and wait with deferred chemotherapy for advanced asymptomatic follicular lymphoma.

PubMed

Prettyjohns, Matthew; Hoskin, Peter; McNamara, Christopher; Linch, David

2018-01-01

Recent evidence has shown that immediate treatment with rituximab induction, with and without maintenance, substantially reduces the need for further treatment in patients with advanced asymptomatic follicular lymphoma. This analysis estimates the cost-effectiveness of immediate treatment approaches in comparison to a watch and wait approach from the perspective of the UK National Health Service. A Markov decision model was developed to estimate the cost-effectiveness of treatment strategies in patients with asymptomatic follicular lymphoma. The model was populated using effectiveness data from a systematic literature review with the key clinical data sourced from a randomised trial, in which the treatment strategies were compared. Costs were estimated using UK national sources. In comparison to watchful waiting, both rituximab strategies were found to be more effective and cost saving. In comparison to rituximab induction, the addition of rituximab maintenance marginally increased effectiveness but substantially increased costs, resulting in an incremental cost-effectiveness ratio (ICER) of £69 406 per quality-adjusted life year (QALY). In probabilistic sensitivity analysis, rituximab induction was found to have a 68% probability of being cost-effective at a threshold of £20 000 per QALY. In conclusion, active treatment with rituximab induction is a cost-effective strategy to adopt in patients with asymptomatic follicular lymphoma. © 2017 John Wiley & Sons Ltd.

Toward Treatment Integrity: Developing an Approach to Measure the Treatment Integrity of a Dialectical Behavior Therapy Intervention With Homeless Youth in the Community.

PubMed

McCay, Elizabeth; Carter, Celina; Aiello, Andria; Quesnel, Susan; Howes, Carol; Johansson, Bjorn

2016-10-01

The current paper discusses an approach to measuring treatment integrity of dialectical behavioral therapy (DBT) when implemented within two programs providing services to street-involved youth in the community. Measuring treatment integrity is a critical component of effective implementation of evidence-based interventions in clinical practice, since sound treatment integrity increases confidence in client outcomes and intervention replicability. Despite being an essential part of implementation science, few studies report on treatment integrity, with limited research addressing either measurement tools or maintenance of treatment integrity. To address the lack of available treatment integrity measures, researchers in the current study developed and piloted a treatment integrity measure which pertain to the individual and group components of DBT. A total of 20 recordings were assessed using the treatment integrity measure. Results indicate that the community agency staff (e.g. youth workers, social workers & nurses) implemented the intervention as intended; increasing confidence in the outcome variables, the staffs' training and the replicability of the intervention. This article offers one approach to addressing treatment integrity when implementing evidence-based interventions, such as DBT in a community setting, and discusses the need for effective and feasible integrity measures that can be adopted in order to strengthen mental health practice in community settings. Copyright © 2016 Elsevier Inc. All rights reserved.

Will Sofosbuvir/Ledipasvir (Harvoni) Be Cost-Effective and Affordable for Chinese Patients Infected with Hepatitis C Virus? An Economic Analysis Using Real-World Data.

PubMed

Chen, Guo-Feng; Wei, Lai; Chen, Jing; Duan, Zhong-Ping; Dou, Xiao-Guang; Xie, Qing; Zhang, Wen-Hong; Lu, Lun-Gen; Fan, Jian-Gao; Cheng, Jun; Wang, Gui-Qiang; Ren, Hong; Wang, Jiu-Ping; Yang, Xing-Xiang; Jia, Zhan-Sheng; Fu, Qing-Chun; Wang, Xiao-Jin; Shang, Jia; Zhang, Yue-Xin; Han, Ying; Du, Ning; Shao, Qing; Ji, Dong; Li, Fan; Li, Bing; Liu, Jia-Liang; Niu, Xiao-Xia; Wang, Cheng; Wu, Vanessa; Wong, April; Wang, Yu-Dong; Hou, Jin-Lin; Jia, Ji-Dong; Zhuang, Hui; Lau, George

2016-01-01

Little is known on the cost-effectiveness of novel regimens for hepatitis C virus (HCV) compared with standard-of-care with pegylated interferon (pegIFN) and ribavirin (RBV) therapy in developing countries. We evaluated cost-effectiveness of sofosbuvir/ledipasvir for 12 weeks compared with a 48-week pegIFN-RBV regimen in Chinese patients with genotype 1b HCV infection by economic regions. A decision analytic Markov model was developed to estimate quality-adjusted-life-years, lifetime cost of HCV infection and incremental cost-effectiveness ratios (ICERs). SVR rates and direct medical costs were obtained from real-world data. Parameter uncertainty was assessed by one-way and probabilistic sensitivity analyses. Threshold analysis was conducted to estimate the price which can make the regimen cost-effective and affordable. Sofosbuvir/ledipasvir was cost-effective in treatment-experienced patients with an ICER of US$21,612. It varied by economic regions. The probability of cost-effectiveness was 18% and 47% for treatment-naive and experienced patients, and it ranged from 15% in treatment-naïve patients in Central-China to 64% in treatment-experienced patients in Eastern-China. The price of 12-week sofosbuvir/ledipasvir treatment needs to be reduced by at least 81% to US$18,185 to make the regimen cost-effective in all patients at WTP of one time GDP per capita. The price has to be US$105 to make the regimen affordable in average patients in China. Sofosbuvir/ledipasvir regimen is not cost-effective in most Chinese patients with genotype 1b HCV infection. The results vary by economic regions. Drug price of sofosbuvir/ledipasvir needs to be substantially reduced when entering the market in China to ensure the widest accessibility.

Skating to where the puck is going to be: a plan for clinical trials and translation research in mood disorders.

PubMed

Frank, Ellen; Rush, A John; Blehar, Mary; Essock, Susan; Hargreaves, William; Hogan, Michael; Jarrett, Robin; Johnson, Robert L; Katon, Wayne J; Lavori, Phillip; McNulty, James P; Niederehe, George; Ryan, Neal; Stuart, Gail; Thomas, Stephen B; Tollefson, Gary D; Vitiello, Benedetto

2002-09-15

As part of the National Institute of Mental Health Strategic Plan for Mood Disorders Research effort, the Clinical Trials and Translation Workgroup was asked to define priorities for clinical trials in mood disorders and for research on how best to translate the results of such research to clinical practice settings. Through two face-to-face meetings and a series of conference calls, we established priorities based on the literature to date and what was known about research currently in progress in this area. We defined five areas of priority that cut across developmental stages, while noting that research on adult mood disorders was at a more advanced stage in each of these areas than research on child or geriatric disorders. The five areas of priority are: 1) maximizing the effectiveness and cost-effectiveness of initial (acute) treatments for mood disorders already known to be efficacious in selected populations and settings when they are applied across all populations and care settings; 2) learning what further treatments or services are most likely to reduce symptoms and improve functioning when the first treatment is delivered well, but the mood disorder does not remit or show adequate improvement; 3) learning what treatments or services are most cost-effective in preventing recurrence or relapse and maintaining optimal functioning after a patient's mood disorder has remitted or responded maximally to treatment; 4) developing and validating clinical, psychosocial, biological, or other markers that predict: a) which treatments are most effective, b) course of illness, c) risk of adverse events/tolerability and acceptability for individual patients or well-defined subgroups of patients; 5) developing clinical trial designs and methods that result in lower research costs and greater generalizability earlier in the treatment development and testing process. A rationale for the importance of each of these priorities is provided.

Cognitive therapy and eye movement desensitization and reprocessing for reducing psychopathology among disaster-bereaved individuals: study protocol for a randomized controlled trial.

PubMed

Lenferink, Lonneke I M; Piersma, Eline; de Keijser, Jos; Smid, Geert E; Boelen, Paul A

2017-01-01

Background : Confrontation with a traumatic (e.g. disaster-related) loss is a risk factor for the development of psychopathology, including symptoms of prolonged grief (PG), posttraumatic stress (PTS), and depression. Although interventions have been developed for reducing post-loss psychopathology, more research into the effectiveness of treatment is needed to improve care for bereaved persons. Cognitive therapy (CT) and eye movement desensitization and reprocessing (EMDR) have been shown to be effective in trauma-exposed populations. We hypothesize that CT and EMDR are also effective in reducing symptoms among people exposed to traumatic loss. Objective : In this article we describe the rationale of a randomized controlled trial (RCT) to examine (1) treatment effects of CT and EMDR for reducing PG, PTS, and depression among traumatically bereaved people, and (2) the associations between improvements in PG, PTS, and depression symptoms on the one hand and tentative mechanisms of change, including a sense of unrealness, negative cognitions, avoidance behaviour, and intrusive memories, on the other hand. Method : A two-armed (intervention versus waiting list controls) RCT will be conducted. Participants will be asked to fill in questionnaires prior to treatment, during treatment, and one, 12, and 24 weeks post-treatment. Potential participants are people who have lost one or multiple significant other(s) in the Ukrainian plane disaster in 2014 with clinically significant levels of self-rated PG, PTS, and/or depression. Multiple regression, including analysis of covariance, and multilevel regression analyses will be used. Discussion : There is a need for treatment for psychopathology following traumatic loss. Strengths of this study are the development of a treatment that targets grief and trauma-related complaints and the examination of potential mechanisms of change in CT and EMDR. Bereaved people, clinicians, and researchers could benefit from the results of this study.

DA-9701: A New Multi-Acting Drug for the Treatment of Functional Dyspepsia

PubMed Central

Kwon, Yong Sam; Son, Miwon

2013-01-01

Motilitone® (DA-9701) is a new herbal drug that was launched for the treatment of functional dyspepsia in December 2011 in Korea. The heterogeneous symptom pattern and multiple causes of functional dyspepsia have resulted in multiple drug target strategies for its treatment. DA-9701, a compound consisting of a combination of Corydalis Tuber and Pharbitidis Semen, has being developed for treatment of functional dyspepsia. It has multiple mechanisms of action such as fundus relaxation, visceral analgesia, and prokinetic effects. Furthermore, it was found to significantly enhance meal-induced gastric accommodation and increase gastric compliance in dogs. DA-9701 also showed an analgesic effect in rats with colorectal distension induced visceral hypersensitivity and an antinociceptive effect in beagle dogs with gastric distension-induced nociception. The pharmacological effects of DA-9701 also include conventional effects, such as enhanced gastric emptying and gastrointestinal transit. The safety profi le of DA-9701 is also preferable to that of other treatments. PMID:24265862

[Pharmacological approaches for correction of thyroid dysfunctions in diabetes mellitus].

PubMed

Shpakov, A O

2017-05-01

Thyroid diseases are closely associated with the development of types 1 and 2 diabetes mellitus (DM), and as a consequence, the development of effective approaches for their treatment is one of the urgent problems of endocrinology. Traditionally, thyroid hormones (TH) are used to correct functions of the thyroid system. However, they are characterized by many side effects, such as their negative effect on the cardiovascular system as well as the ability of TH to enhance insulin resistance and to disturb insulin-producing function of pancreas, exacerbating thereby diabetic pathology. Therefore, the analogues of TH, selective for certain types of TH receptors, that do not have these side effects, are being developed. The peptide and low-molecular weight regulators of thyroid-stimulating hormone receptor, which regulate the activity of the thyroid axis at the stage of TH synthesis and secretion in thyrocytes, are being created. Systemic and intranasal administration of insulin, metformin therapy and drugs with antioxidant activity are effective for the treatment of thyroid pathology in types 1 and 2 DM. In the review, the literature data and the results of own investigations on pharmacological approaches for the treatment and prevention of thyroid diseases in patients with types 1 and 2 DM are summarized and analyzed.

Effects of ayahuasca on the development of ethanol-induced behavioral sensitization and on a post-sensitization treatment in mice.

PubMed

Oliveira-Lima, A J; Santos, R; Hollais, A W; Gerardi-Junior, C A; Baldaia, M A; Wuo-Silva, R; Yokoyama, T S; Costa, J L; Malpezzi-Marinho, E L A; Ribeiro-Barbosa, P C; Berro, L F; Frussa-Filho, R; Marinho, E A V

2015-04-01

Hallucinogenic drugs were used to treat alcoholic patients in the past, and recent developments in the study of hallucinogens led to a renewal of interest regarding the application of these drugs in the treatment of addiction. In this scenario, accumulating evidence suggests that the hallucinogenic brew ayahuasca (Aya) may have therapeutic effects on substance abuse problems. We investigated the effects of Aya on spontaneous locomotor activity and ethanol(Eth)-induced hyperlocomotion and subsequent locomotor sensitization by a two-injection protocol. Additionally, we tested the effect of Aya on an 8-day counter-sensitization protocol to modify sensitized responses induced by a repeated treatment with Eth (1.8g/kg) for 8 alternate days. Aya showed high sensitivity in preventing the development of Eth-induced behavioral sensitization, attenuating it at all doses (30, 100, 200, 300 or 500 mg/kg) without modifying spontaneous locomotor activity. At the highest doses (300 and 500 mg/kg), Aya also showed selectivity to both acute and sensitized Eth responses. Finally, a counter-sensitization strategy with 100 or 300 mg/kg of Aya for 8 consecutive days after the establishment of Eth-induced behavioral sensitization was effective in blocking its subsequent expression on an Eth challenge. We demonstrated that Aya not only inhibits early behaviors associated with the initiation and development of Eth addiction, but also showed effectiveness in reversing long-term drug effects expression, inhibiting the reinstatement of Eth-induced behavioral sensitization when administered in the Eth-associated environment. Copyright © 2015 Elsevier Inc. All rights reserved.

Involvement of neuropeptide FF receptors in neuroadaptive responses to acute and chronic opiate treatments

PubMed Central

Elhabazi, K; Trigo, JM; Mollereau, C; Moulédous, L; Zajac, J-M; Bihel, F; Schmitt, M; Bourguignon, JJ; Meziane, H; Petit-demoulière, B; Bockel, F; Maldonado, R; Simonin, F

2012-01-01

BACKGROUND AND PURPOSE Opiates remain the most effective compounds for alleviating severe pain across a wide range of conditions. However, their use is associated with significant side effects. Neuropeptide FF (NPFF) receptors have been implicated in several opiate-induced neuroadaptive changes including the development of tolerance. In this study, we investigated the consequences of NPFF receptor blockade on acute and chronic stimulation of opioid receptors in mice by using RF9, a potent and selective antagonist of NPFF receptors that can be administered systemically. EXPERIMENTAL APPROACH The effects of RF9 were investigated on opioid pharmacological responses including locomotor activity, antinociception, opioid-induced hyperalgesia, rewarding properties and physical dependence. KEY RESULTS RF9 had no effect on morphine-induced horizontal hyperlocomotion and slightly attenuated the decrease induced in vertical activity. Furthermore, RF9 dose-dependently blocked the long-lasting hyperalgesia produced by either acute fentanyl or chronic morphine administration. RF9 also potentiated opiate early analgesic effects and prevented the development of morphine tolerance. Finally, RF9 increased morphine-induced conditioned place preference without producing any rewarding effect by itself and decreased naltrexone-precipitated withdrawal syndrome following chronic morphine treatment. CONCLUSION AND IMPLICATIONS The NPFF system is involved in the development of two major undesirable effects: tolerance and dependence, which are clinically associated with prolonged exposure to opiates. Our findings suggest that NPFF receptors are interesting therapeutic targets to improve the analgesic efficacy of opiates by limiting the development of tolerance, and for the treatment of opioid dependence. PMID:21718302

Involvement of neuropeptide FF receptors in neuroadaptive responses to acute and chronic opiate treatments.

PubMed

Elhabazi, K; Trigo, J M; Mollereau, C; Moulédous, L; Zajac, J-M; Bihel, F; Schmitt, M; Bourguignon, J J; Meziane, H; Petit-demoulière, B; Bockel, F; Maldonado, R; Simonin, F

2012-01-01

BACKGROUND AND PURPOSE Opiates remain the most effective compounds for alleviating severe pain across a wide range of conditions. However, their use is associated with significant side effects. Neuropeptide FF (NPFF) receptors have been implicated in several opiate-induced neuroadaptive changes including the development of tolerance. In this study, we investigated the consequences of NPFF receptor blockade on acute and chronic stimulation of opioid receptors in mice by using RF9, a potent and selective antagonist of NPFF receptors that can be administered systemically. EXPERIMENTAL APPROACH The effects of RF9 were investigated on opioid pharmacological responses including locomotor activity, antinociception, opioid-induced hyperalgesia, rewarding properties and physical dependence. KEY RESULTS RF9 had no effect on morphine-induced horizontal hyperlocomotion and slightly attenuated the decrease induced in vertical activity. Furthermore, RF9 dose-dependently blocked the long-lasting hyperalgesia produced by either acute fentanyl or chronic morphine administration. RF9 also potentiated opiate early analgesic effects and prevented the development of morphine tolerance. Finally, RF9 increased morphine-induced conditioned place preference without producing any rewarding effect by itself and decreased naltrexone-precipitated withdrawal syndrome following chronic morphine treatment. CONCLUSION AND IMPLICATIONS The NPFF system is involved in the development of two major undesirable effects: tolerance and dependence, which are clinically associated with prolonged exposure to opiates. Our findings suggest that NPFF receptors are interesting therapeutic targets to improve the analgesic efficacy of opiates by limiting the development of tolerance, and for the treatment of opioid dependence. © 2011 The Authors. British Journal of Pharmacology © 2011 The British Pharmacological Society.

Suppressive effects of ginsan on the development of allergic reaction in murine asthmatic model.

PubMed

Lim, You-Jin; Na, Hee-Sam; Yun, Yeon-Sook; Choi, Inseon S; Oh, Jong-Suk; Rhee, Joon-Haeng; Cho, Bok-Hee; Lee, Hyun-Chul

2009-01-01

Asthma is a major health problem worldwide, and the morbidity and mortality caused by asthma are on the rise. Corticosteroid therapies for asthma treatment frequently induce many side effects. Therefore, the development of new medicines that have both high efficacy and fewer side effects has been a scientific challenge. Here we tested the effect of ginsan, a polysaccharide derived from Panax ginseng, against allergic reaction in an ovalbumin (OVA)-induced murine asthmatic model in comparison with dexamethasone, and investigated its underlying mechanism. To induce murine asthma, mice were sensitized and challenged with OVA. Ginsan or dexamethasone was administered by injection 3 times a week. Airway hyperresponsiveness, airway inflammation and lung pathology were assessed in order to evaluate the effect of ginsan against asthma. Ginsan treatment reduced airway hyperresponsiveness, remodeling and eosinophilia. These effects of ginsan were equivalent to those of dexamethasone. Ginsan treatment decreased the IL-5 level in the supernatant of cultured splenocytes, while IFN-gamma and serum IgE were not altered. To elucidate the mechanism of ginsan, expression of inflammation-related genes were screened. Interestingly, ginsan treatment upregulated cyclooxygenase (COX)-1 and COX-2 mRNA, and expression of their proteins in the lung were also increased. PGE(2) in the bronchoalveolar lavage fluid was also increased by the ginsan treatment. Lastly, ginsan inhibited the allergic reaction aggravated by COX inhibitor (indomethacin). Ginsan has anti-asthmatic effects, which seem to be partially mediated by enhancing the synthesis of COX gene products. Copyright 2009 S. Karger AG, Basel.

Refractoriness of the gravid rat uterus to tocolytic and biochemical effects of atrial natriuretic peptide.

PubMed Central

Potvin, W.; Varma, D. R.

1990-01-01

1. Effects of atrial natriuretic peptide (ANP) on tension development, particulate guanylate cyclase activity and guanosine 3':5'-cyclic monophosphate (cyclic GMP) concentrations of uteri from oestrogen-treated, progesterone-treated, ovariectomized and pregnant rats were determined in vitro. 2. ANP inhibited the tension development by myometrial tissues from oestrogen-treated virgin rats and the sterile horn of 10 to 14 day pregnant rats but not of the uterus from pregnant and progesterone-treated rats. 3. Inhibition of cyclo-oxygenase and lipoxygenase activities did not restore the tocolytic activity of ANP on gravid uterus. ANP exerted a tocolytic effect on nongravid uterus submaximally stimulated by prostaglandin F2 alpha (PGF2 alpha), oxytocin, vasopressin, angiotensin II or 5-hydroxytryptamine (5-HT). 4. Ovariectomy decreased the tocolytic effects of ANP, which could be restored by oestrogen treatment. 5. The refractoriness to the tocolytic effect of ANP in pregnant rats was not accompanied by a decrease in its relaxant effects on isolated aortic strips. 6. Tocolytic effects of isoprenaline, isobutylmethyl xanthine and hydroxylamine were not influenced by pregnancy or progesterone treatment. Up to a concentration of 3 mM, sodium nitroprusside did not affect myometrial tension development. 7. Pregnancy and progesterone treatment markedly inhibited ANP-induced increases in myometrial particulate guanylate cyclase activity and cyclic GMP concentrations but did not influence the effects of ANP on aortic cyclic GMP concentrations. 8. It is concluded that exposure of the myometrium to circulating and placentally-produced progesterone is responsible for the pregnancy-induced decrease in the effects of ANP on myometrial particulate guanylate cyclase activity and cyclic GMP concentrations and in turn on myometrial tension development. PMID:1974161

FIA BioSum: a tool to evaluate financial costs, opportunities and effectiveness of fuel treatments.

Treesearch

Jeremy Fried; Glenn Christensen

2004-01-01

FIA BioSum, a tool developed by the USDA Forest Services Forest Inventory and Analysis (FIA) Program, generates reliable cost estimates, identifies opportunities and evaluates the effectiveness of fuel treatments in forested landscapes. BioSum is an analytic framework that integrates a suite of widely used computer models with a foundation of attribute-rich,...

Gut hormones: the future of obesity treatment?

PubMed Central

McGavigan, Anne K; Murphy, Kevin G

2012-01-01

Obesity is a major worldwide health problem. The treatment options are severely limited. The development of novel anti-obesity drugs is fraught with efficacy and safety issues. Consequently, several investigational anti-obesity drugs have failed to gain marketing approval in recent years. Anorectic gut hormones offer a potentially safe and viable option for the treatment of obesity. The prospective utility of gut hormones has improved drastically in recent years with the development of longer acting analogues. Additionally, specific combinations of gut hormones have been demonstrated to have additive anorectic effects. This article reviews the current stage of anti-obesity drugs in development, focusing on gut hormone-based therapies. PMID:22452339

Clinical effectiveness and cost-effectiveness of interventions for the treatment of anogenital warts: systematic review and economic evaluation.

PubMed

Thurgar, Elizabeth; Barton, Samantha; Karner, Charlotta; Edwards, Steven J

2016-03-01

Typically occurring on the external genitalia, anogenital warts (AGWs) are benign epithelial skin lesions caused by human papillomavirus infection. AGWs are usually painless but can be unsightly and physically uncomfortable, and affected people might experience psychological distress. The evidence base on the clinical effectiveness and cost-effectiveness of treatments for AGWs is limited. To systematically review the evidence on the clinical effectiveness of medical and surgical treatments for AGWs and to develop an economic model to estimate the cost-effectiveness of the treatments. Electronic databases (MEDLINE, MEDLINE In-Process & Other Non-Indexed Citations, EMBASE, The Cochrane Library databases and Web of Science) were searched from inception (or January 2000 for Web of Science) to September 2014. Bibliographies of relevant systematic reviews were hand-searched to identify potentially relevant studies. The World Health Organization International Clinical Trials Registry Platform and ClinicalTrials.gov were searched for ongoing and planned studies. A systematic review of the clinical effectiveness literature was carried out according to standard methods and a mixed-treatment comparison (MTC) undertaken. The model implemented for each outcome was that with the lowest deviance information criterion. A de novo economic model was developed to assess cost-effectiveness from the perspective of the UK NHS. The model structure was informed through a systematic review of the economic literature and in consultation with clinical experts. Effectiveness data were obtained from the MTC. Costs were obtained from the literature and standard UK sources. Of 4232 titles and abstracts screened for inclusion in the review of clinical effectiveness, 60 randomised controlled trials (RCTs) evaluating 19 interventions were included. Analysis by MTC indicated that ablative techniques were typically more effective than topical interventions at completely clearing AGWs at the end of treatment. Podophyllotoxin 0.5% solution (Condyline(®), Takeda Pharmaceutical Company Ltd; Warticon(®) solution, Stiefel Laboratories Ltd) was found to be the most effective topical treatment evaluated. Networks for other outcomes included fewer treatments, which restrict conclusions on the comparative effectiveness of interventions. In total, 84 treatment strategies were assessed using the economic model. Podophyllotoxin 0.5% solution first line followed by carbon dioxide (CO2) laser therapy second line if AGWs did not clear was most likely to be considered a cost-effective use of resources at a willingness to pay of £20,000-30,000 per additional quality-adjusted life-year gained. The result was robust to most sensitivity analyses conducted. Limited reporting in identified studies of baseline characteristics for the enrolled population generates uncertainty around the comparability of the study populations and therefore the generalisability of the results to clinical practice. Subgroup analyses were planned based on type, number and size of AGWs, all of which are factors thought to influence treatment effect. Lack of data on clinical effectiveness based on these characteristics precluded analysis of the differential effects of treatments in the subgroups of interest. Despite identification of 60 studies, most comparisons in the MTC are informed by only one RCT. Additionally, lack of head-to-head RCTs comparing key treatments, together with minimal reporting of results in some studies, precluded comprehensive analysis of all treatments for AGWs. The results generated by the MTC are in agreement with consensus opinion that ablative techniques are clinically more effective at completely clearing AGWs after treatment. However, the evidence base informing the MTC is limited. A head-to-head RCT that evaluates the comparative effectiveness of interventions used in clinical practice would help to discern the potential advantages and disadvantages of the individual treatments. The results of the economic analysis suggest that podophyllotoxin 0.5% solution is likely to represent a cost-effective first-line treatment option. More expensive effective treatments, such as CO2 laser therapy or surgery, may represent cost-effective second-line treatment options. No treatment and podophyllin are unlikely to be considered cost-effective treatment options. There is uncertainty around the cost-effectiveness of treatment with imiquimod, trichloroacetic acid and cryotherapy. This study is registered as PROSPERO CRD42013005457. The National Institute for Health Research Health Technology Assessment programme.

Kinase-activating and kinase-impaired cardio-facio-cutaneous syndrome alleles have activity during zebrafish development and are sensitive to small molecule inhibitors.

PubMed

Anastasaki, Corina; Estep, Anne L; Marais, Richard; Rauen, Katherine A; Patton, E Elizabeth

2009-07-15

The Ras/MAPK pathway is critical for human development and plays a central role in the formation and progression of most cancers. Children born with germ-line mutations in BRAF, MEK1 or MEK2 develop cardio-facio-cutaneous (CFC) syndrome, an autosomal dominant syndrome characterized by a distinctive facial appearance, heart defects, skin and hair abnormalities and mental retardation. CFC syndrome mutations in BRAF promote both kinase-activating and kinase-impaired variants. CFC syndrome has a progressive phenotype, and the availability of clinically active inhibitors of the MAPK pathway prompts the important question as to whether such inhibitors might be therapeutically effective in the treatment of CFC syndrome. To study the developmental effects of CFC mutant alleles in vivo, we have expressed a panel of 28 BRAF and MEK alleles in zebrafish embryos to assess the function of human disease alleles and available chemical inhibitors of this pathway. We find that both kinase-activating and kinase-impaired CFC mutant alleles promote the equivalent developmental outcome when expressed during early development and that treatment of CFC-zebrafish embryos with inhibitors of the FGF-MAPK pathway can restore normal early development. Importantly, we find a developmental window in which treatment with a MEK inhibitor can restore the normal early development of the embryo, without the additional, unwanted developmental effects of the drug.

Clinical findings and effect of sodium hydrogen carbonate in patients with glutathione synthetase deficiency.

PubMed

Gündüz, Mehmet; Ünal, Özlem; Kavurt, Sumru; Türk, Emrecan; Mungan, Neslihan Önenli

2016-04-01

Glutathione synthetase (GS) deficiency is a rare inborn error of glutathione (GSH) metabolism manifested by severe metabolic acidosis, hemolytic anemia, neurological problems and massive excretion of pyroglutamic acid (5-oxoproline) in the urine. The disorder has mild, moderate, and severe clinical variants. We aimed to report clinical and laboratory findings of four patients, effect of sodium hydrogen carbonate treatment and long-term follow up of three patients. Urine organic acid analysis was performed with gas chromatography-mass spectrometry. Molecular genetic analysis was performed in three patients, mutation was found in two of them. Enzyme analysis was performed in one patient. Clinical and laboratory findings of four patients were evaluated. One patient died at 4 months old, one patient's growth and development are normal, two patients have developed intellectual disability and seizures in the long term follow up period. Three patients benefited from sodium hydrogen carbonate treatment. The clinical picture varies from patient to patient, so it is difficult to predict the prognosis and the effectiveness of treatment protocols. We reported long term follow up of four patients and demonstrated that sodium hydrogen carbonate is effective for treatment of chronic metabolic acidosis in GS deficieny.

A powerful test for Balaam's design.

PubMed

Mori, Joji; Kano, Yutaka

2015-01-01

The crossover trial design (AB/BA design) is often used to compare the effects of two treatments in medical science because it performs within-subject comparisons, which increase the precision of a treatment effect (i.e., a between-treatment difference). However, the AB/BA design cannot be applied in the presence of carryover effects and/or treatments-by-period interaction. In such cases, Balaam's design is a more suitable choice. Unlike the AB/BA design, Balaam's design inflates the variance of an estimate of the treatment effect, thereby reducing the statistical power of tests. This is a serious drawback of the design. Although the variance of parameter estimators in Balaam's design has been extensively studied, the estimators of the treatment effect to improve the inference have received little attention. If the estimate of the treatment effect is obtained by solving the mixed model equations, the AA and BB sequences are excluded from the estimation process. In this study, we develop a new estimator of the treatment effect and a new test statistic using the estimator. The aim is to improve the statistical inference in Balaam's design. Simulation studies indicate that the type I error of the proposed test is well controlled, and that the test is more powerful and has more suitable characteristics than other existing tests when interactions are substantial. The proposed test is also applied to analyze a real dataset. Copyright © 2015 John Wiley & Sons, Ltd.

Personalized Antidepressant Selection and Pathway to Novel Treatments: Clinical Utility of Targeting Inflammation

PubMed Central

Jha, Manish K.; Trivedi, Madhukar H.

2018-01-01

Major depressive disorder (MDD) is a chronic condition that affects one in six adults in the US during their lifetime. The current practice of antidepressant medication prescription is a trial-and-error process. Additionally, over a third of patients with MDD fail to respond to two or more antidepressant treatments. There are no valid clinical markers to personalize currently available antidepressant medications, all of which have similar mechanisms targeting monoamine neurotransmission. The goal of this review is to summarize the recent findings of immune dysfunction in patients with MDD, the utility of inflammatory markers to personalize treatment selection, and the potential of targeting inflammation to develop novel antidepressant treatments. To personalize antidepressant prescription, a c-reactive protein (CRP)-matched treatment assignment can be rapidly implemented in clinical practice with point-of-care fingerstick tests. With this approach, 4.5 patients need to be treated for 1 additional remission as compared to a CRP-mismatched treatment assignment. Anti-cytokine treatments may be effective as novel antidepressants. Monoclonal antibodies against proinflammatory cytokines, such as interleukin 6, interleukin 17, and tumor necrosis factor α, have demonstrated antidepressant effects in patients with chronic inflammatory conditions who report significant depressive symptoms. Additional novel antidepressant strategies targeting inflammation include pharmaceutical agents that block the effect of systemic inflammation on the central nervous system. In conclusion, inflammatory markers offer the potential not only to personalize antidepressant prescription but also to guide the development of novel mechanistically-guided antidepressant treatments. PMID:29329256

The reality of cancer treatment in a developing country: the effects of delayed TKI treatment on survival, cytogenetic and molecular responses in chronic myeloid leukaemia patients.

PubMed

Kurtovic-Kozaric, Amina; Hasic, Azra; Radich, Jerald P; Bijedic, Vildan; Nefic, Hilada; Eminovic, Izet; Kurtovic, Sabira; Colakovic, Ferida; Kozaric, Mirza; Vranic, Semir; Bovan, Nada S

2016-02-01

Cancer patients in developing and low-income countries have limited access to target therapies. For example, tyrosine kinase inhibitor (TKI) therapy for chronic myeloid leukaemia patients (CML) is often delayed. In Bosnia, 16% of patients received immediate TKI treatment (<3 months of diagnosis), while 66% of patients received therapy after a median 14-month wait period. To assess the effect of delayed treatment on outcome, three patient groups were studied according to the time they received TKI treatment (0-5 months, 6-12 months and >13 months delay). The primary endpoints were complete cytogenetic (CCyR) and major molecular response (MMR) at 12 months. At 12 months of therapy, CCyR and MMR rates on imatinib decreased significantly: CCyR was achieved in 67% of patients in the immediate imatinib treatment group, 18% of patients in 6-12 months group and 15% of patients in >13 months wait group. MMR rates at 12 months occurred in 10% of patients with immediate treatment, 6% of those in 6-12 months group and 0% of patients in >13 months wait group. However, CCyR and MMR rates in patients on nilotinib were not associated with duration of treatment delay. Our data suggests that the deleterious effect of a prolonged TKI therapy delay may be ameliorated by the more active TKI nilotinib. © 2015 John Wiley & Sons Ltd.

Design of a randomized controlled trial examining the efficacy and biological mechanisms of web-prolonged exposure and present-centered therapy for PTSD among active-duty military personnel and veterans.

PubMed

McLean, Carmen P; Rauch, Sheila A M; Foa, Edna B; Sripada, Rebecca K; Tannahill, Hallie S; Mintz, Jim; Yarvis, Jeffrey; Young-McCaughan, Stacey; Dondanville, Katherine A; Hall-Clark, Brittany N; Fina, Brooke A; Keane, Terence M; Peterson, Alan L

2018-01-01

Improved accessibility of effective and efficient evidence-based treatments (EBTs) for military personnel suffering with posttraumatic stress disorder (PTSD) is an urgent need to meet the growing demand for timely care. In addition, a better understanding of the mechanism of action of behavioral therapy can inform the delivery of care to meet accessibility demands. Effective EBTs for PTSD are available, but logistical and stigma-related barriers to accessing behavioral healthcare can deter military personnel from receiving these treatments. Web-based treatments represent an innovative way to overcome these barriers. The efficacy of previously developed web-based treatments for PTSD appears promising; however, they were not developed based on treatment protocols with strong empirical support for their efficacy. No study to date has examined web-based treatment of PTSD using a well-established evidence-based treatment, nor delineated the biological mechanisms through which a web-based treatment exerts its effects. This paper describes the rationale and methods of a randomized controlled trial comparing the efficacy and potential biological mediators of 10 sessions of a web-version of Prolonged Exposure (PE), "Web-PE," delivered over 8weeks compared to 10 sessions of in-person Present-Centered Therapy (PCT) delivered over 8weeks by a therapist in 120 active duty military personnel and veterans with PTSD. Copyright © 2017 Elsevier Inc. All rights reserved.

Steroid oestrogens in the environment: an Australian perspective.

PubMed

Sutcliffe, Sarah; Clarke, Bradley O; Jones, Oliver A H

2013-01-01

Endocrine disrupting compounds (EDCs) have been in the scientific spotlight since the 1980s. However, there has been much less research reported in Australia than in other developed countries and little information is known about how these compounds interact with native Australian species compared to European and North American fauna. This is of concern because Australia has distinct wildlife and environments that face increasing intensity and frequency of extreme, climatic events compared to northern hemisphere countries. Since oestrogenic compounds cannot be prevented from entering wastewater their management and removal must occur at wastewater treatment plants. Biological treatment is the most effective tool in this regard; however the financial and environmental costs must be balanced with the environmental benefit to effectively plan treatment options. Since standard risk assessment models and procedures developed internationally are unlikely to translate well to Australian ecosystems, new, novel and localised research on both the monitoring and assessment of EDCs in Australian wastewater and receiving aquatic environments is recommended. This includes the development of relevant bioassays and application of treatment technologies that reflect the local community and climate.

Acute immunosuppression and syngeneic bone marrow transplantation in ocular autoimmunity abort disease, but do not result in induction of long-term protection.

PubMed

Savion, S; Silver, P B; Chan, C C; Caspi, R R

1998-09-01

Acute immunosuppression induced by total body irradiation (TBI) or cyclophosphamide (Cy) treatment, followed by syngeneic bone marrow transplantation (SBMT), was reported to be effective in inducing long-term tolerance in some autoimmune disease models. We examined the efficacy of this approach in the mouse model of experimental autoimmune uveoretinitis (EAU). Development of EAU induced by the interphotoreceptor retinoid binding protein (IRBP) was abolished almost completely by either TBI or Cy treatment, followed by SBMT, instituted one week after priming. In parallel, IRBP-specific delayed-type hypersensitivity (DTH) responses and lymph node cell proliferation were strongly suppressed or abolished. However, when these IRBP-immunized, lymphoablated and BM reconstituted mice were rechallenged with the immunizing antigen seven weeks after the primary immunization, they were not protected from developing disease, despite the fact that DTH and lymph node cell proliferation to the antigen were suppressed relative to controls. TBI treatment appeared somewhat more effective than Cy treatment as judged by its more profound effect on immunological responses. These results demonstrate the ability of acute immunosuppression followed by reconstitution of the immune system to inhibit the development of EAU, although long-term protection from disease was not achieved.

Treatment of Obesity-Related Complications with Novel Classes of Naturally Occurring PPAR Agonists.

PubMed

Bassaganya-Riera, Josep; Guri, Amir J; Hontecillas, Raquel

2011-01-01

The prevalence of obesity and its associated comorbidities has grown to epidemic proportions in the US and worldwide. Thus, developing safe and effective therapeutic approaches against these widespread and debilitating diseases is important and timely. Activation of peroxisome proliferator-activated receptors (PPARs) α, γ, and δ through several classes of pharmaceuticals can prevent or treat a variety of metabolic and inflammatory diseases, including type II diabetes (T2D). Thus, PPARs represent important molecular targets for developing novel and better treatments for a wide range of debilitating and widespread obesity-related diseases and disorders. However, available PPAR γ agonistic drugs such as Avandia have significant adverse side effects, including weight gain, fluid retention, hepatotoxicity, and congestive heart failure. An alternative to synthetic agonists of PPAR γ is the discovery and development of naturally occurring and safer nutraceuticals that may be dual or pan PPAR agonists. The purpose of this paper is to summarize the health effects of three plant-derived PPAR agonists: abscisic acid (ABA), punicic acid (PUA), and catalpic acid (CAA) in the prevention and treatment of chronic inflammatory and metabolic diseases and disorders.

Development and validation of a questionnaire to evaluate how a cosmetic product for oily skin is able to improve well-being in women.

PubMed

Segot-Chicq, E; Compan-Zaouati, D; Wolkenstein, P; Consoli, S; Rodary, C; Delvigne, V; Guillou, V; Poli, F

2007-10-01

Skin diseases are known to negatively affect self-image and to have detrimental psychosocial effects. Oily skin is a cosmetic skin problem that women often describe as 'invalidating'. To develop and validate a questionnaire to assess the psychological and psychosocial effects of oily skin condition in women and the outcome of a targeted cosmetic skincare treatment. We developed and validated a concise 18-item questionnaire [oily skin self-image questionnaire (OSSIQ)] to assess perception, behavioural, and emotional consequences associated with oily skin condition. The questionnaire was then used to assess the effects of a skincare treatment for oily skin and compare them with sebum level measurements. The 18-item questionnaire clearly distinguished the oily skin group from the control group. Responsiveness, reliability, and construct validity showed satisfactory performance. The questionnaire provided a relevant assessment of the psychological benefits associated with the skincare programme. The OSSIQ is a valid tool that can be used to monitor the benefits of cosmetic skincare treatments.

Consensus Treatment Plans for Chronic Nonbacterial Osteomyelitis Refractory to Nonsteroidal Anti-Inflammatory Drugs and/or with Active Spinal Lesions.

PubMed

Zhao, Yongdong; Wu, Eveline Y; Oliver, Melissa S; Cooper, Ashley M; Basiaga, Matthew L; Vora, Sheetal S; Lee, Tzielan C; Fox, Emily; Amarilyo, Gil; Stern, Sara M; Dvergsten, Jeffrey A; Haines, Kathleen A; Rouster-Stevens, Kelly A; Onel, Karen B; Cherian, Julie; Hausmann, Jonathan S; Miettunen, Paivi; Cellucci, Tania; Nuruzzaman, Farzana; Taneja, Angela; Barron, Karyl S; Hollander, Matthew C; Lapidus, Sivia K; Li, Suzanne C; Ozen, Seza; Girschick, Hermann; Laxer, Ronald M; Dedeoglu, Fatma; Hedrich, Christian M; Ferguson, Polly J

2017-11-07

To develop standardized treatment regimens for chronic nonbacterial osteomyelitis (CNO), also known as chronic recurrent multifocal osteomyelitis (CRMO) to enable comparative effectiveness treatment studies. Virtual and face-to-face discussions and meetings were held within the CNO subgroup of the Childhood Arthritis and Rheumatology Research Alliance (CARRA). A literature search was conducted, and CARRA membership was surveyed to evaluate available treatment data and identify current treatment practices. Nominal group technique was used to achieve consensus on treatment plans for CNO refractory to non-steroidal anti-inflammatory drug (NSAID) monotherapy and/or with active spinal lesions. Three consensus treatment plans (CTPs) were developed for the first 12 months of therapy for CNO patients refractory to NSAID monotherapy and/or with active spinal lesions. The three CTPs are: (1) methotrexate or sulfasalazine, (2) tumor necrosis factor (TNF)-alpha inhibitors with optional use of methotrexate, and (3) bisphosphonates. Short courses of glucocorticoids and continuation of NSAIDs are permitted for all regimens. Consensus was achieved on these CTPs among CARRA members. Consensus was also reached on subject eligibility criteria, initial evaluations that should be conducted prior to the initiation of CTPs, and data items to collect to assess treatment response. Three consensus treatment plans were developed for pediatric patients with CNO refractory to NSAIDs and/or with active spinal lesions. Use of these CTPs will provide additional information on efficacy and will generate meaningful data for comparative effectiveness research in CNO. This article is protected by copyright. All rights reserved. This article is protected by copyright. All rights reserved.

Patient-reported outcomes in drug development for hematology.

PubMed

Acquadro, Catherine; Regnault, Antoine

2015-01-01

Patient-reported outcomes (PROs) are any outcome evaluated directly by the patient himself and based on the patient's perception of a disease and its treatment(s). PROs are direct outcome measures that can be used as clinical meaningful endpoints to characterize treatment benefit. They provide unique and important information about the effect of treatment from a patient's view. However, PROs will only be considered adequate if the assessment is well-defined and reliable. In 2009, the FDA has issued a guidance, which defines good measurement principles to consider for PRO measures intended to give evidence of treatment benefit in drug development. In hematologic clinical trials, when applied rigorously, they may be used to evaluate overall treatment effectiveness, treatment toxicity, and quality of patient's well-being at short-term and long-term after treatment from a patient's perspective. In situations in which multiple treatment options exist with similar survival outcome or if a new therapeutic strategy needs to be evaluated, the inclusion of PROs as an endpoint can provide additional data and help in clinical decision making. Given the diversity of the hematological field, the approach to measurement needs to be tailored for each specific situation. The importance of PROs in hematologic diseases has been highlighted in a number of international recommendations. In addition, new perspectives in the regulatory field will enhance the inclusion of PRO endpoints in clinical trials in hematology, allowing the voice of the patients with hematologic diseases to be taken into greater consideration in the development of new drugs. © 2015 by The American Society of Hematology. All rights reserved.

RARE EARTH ELEMENT IMPACTS ON BIOLOGICAL WASTEWATER TREATMENT

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

Fujita, Y.; Barnes, J.; Fox, S.

Increasing demand for rare earth elements (REE) is expected to lead to new development and expansion in industries processing and or recycling REE. For some industrial operators, sending aqueous waste streams to a municipal wastewater treatment plant, or publicly owned treatment works (POTW), may be a cost effective disposal option. However, wastewaters that adversely affect the performance of biological wastewater treatment at the POTW will not be accepted. The objective of our research is to assess the effects of wastewaters that might be generated by new rare earth element (REE) beneficiation or recycling processes on biological wastewater treatment systems. Wemore » have been investigating the impact of yttrium and europium on the biological activity of activated sludge collected from an operating municipal wastewater treatment plant. We have also examined the effect of an organic complexant that is commonly used in REE extraction and separations; similar compounds may be a component of newly developed REE recycling processes. Our preliminary results indicate that in the presence of Eu, respiration rates for the activated sludge decrease relative to the no-Eu controls, at Eu concentrations ranging from <10 to 660 µM. Yttrium appears to inhibit respiration as well, although negative impacts have been observed only at the highest Y amendment level tested (660 µM). The organic complexant appears to have a negative impact on activated sludge activity as well, although results are variable. Ultimately the intent of this research is to help REE industries to develop environmentally friendly and economically sustainable beneficiation and recycling processes.« less

Affective Biases in Humans and Animals.

PubMed

Robinson, E S J; Roiser, J P

Depression is one of the most common but poorly understood psychiatric conditions. Although drug treatments and psychological therapies are effective in some patients, many do not achieve full remission and some patients receive no apparent benefit. Developing new improved treatments requires a better understanding of the aetiology of symptoms and evaluation of novel therapeutic targets in pre-clinical studies. Recent developments in our understanding of the basic cognitive processes that may contribute to the development of depression and its treatment offer new opportunities for both clinical and pre-clinical research. This chapter discusses the clinical evidence supporting a cognitive neuropsychological model of depression and antidepressant efficacy, and how this information may be usefully translated to pre-clinical investigation. Studies using neuropsychological tests in depressed patients and at risk populations have revealed basic negative emotional biases and disrupted reward and punishment processing, which may also impact on non-affective cognition. These affective biases are sensitive to antidepressant treatments with early onset effects observed, suggesting an important role in recovery. This clinical work into affective biases has also facilitated back-translation to animals and the development of assays to study affective biases in rodents. These animal studies suggest that, similar to humans, rodents in putative negative affective states exhibit negative affective biases on decision-making and memory tasks. Antidepressant treatments also induce positive biases in these rodent tasks, supporting the translational validity of this approach. Although still in the early stages of development and validation, affective biases in depression have the potential to offer new insights into the clinical condition, as well as facilitating the development of more translational approaches for pre-clinical studies.

Designs and adaptive analysis plans for pivotal clinical trials of therapeutics and companion diagnostics.

PubMed

Simon, Richard

2008-06-01

Developments in genomics and biotechnology provide unprecedented opportunities for the development of effective therapeutics and companion diagnostics for matching the right drug to the right patient. Effective co-development involves many new challenges with increased opportunity for success as well as delay and failure. Clinical trial designs and adaptive analysis plans for the prospective design of pivotal trials of new therapeutics and companion diagnostics are reviewed. Effective co-development requires careful prospective planning of the design and analysis strategy for pivotal clinical trials. Randomized clinical trials continue to be important for evaluating the effectiveness of new treatments, but the target populations for analysis should be prospectively specified based on the companion diagnostic. Post hoc analyses of traditionally designed randomized clinical trials are often deeply problematic. Clear separation is generally required of the data used for developing the diagnostic test, including their threshold of positivity, from the data used for evaluating treatment effectiveness in subsets determined by the test. Adaptive analysis can be used to provide flexibility to the analysis but the use of such methods requires careful planning and prospective definition in order to assure that the pivotal trial adequately limits the chance of erroneous conclusions.

Generic radiation quarantine treatments: the next steps.

PubMed

Follett, Peter A

2009-08-01

In 2006, U.S. Department of Agriculture-Animal and Plant Health Inspection Service published a landmark rule providing generic radiation quarantine treatments. The rule approved radiation doses of 150 Gy for any tephritid fruit fly and 400 Gy for all other insects except the pupa and adult stages of Lepidoptera. The generic radiation treatments apply to all fresh horticultural commodities. Therefore, if a pest risk assessment demonstrates that no pupae or adult Lepidoptera are associated with a commodity, export approval can be forthcoming with no further research. Generic treatments are the culmination of decades of research but not an end point. Future research on quarantine and phytosanitary uses of radiation should focus on 1) development of specific doses for quarantine Lepidoptera not covered by the generic treatments, 2) reduction of dose levels for specific pests and commodities to shorten treatment time and minimize any deleterious effects of radiation treatment on commodity quality, 3) development of generic doses below 400 Gy for important groups of quarantine arthropods other than fruit flies, and 4) development of information on commodity tolerance and development of value-added irradiated fresh products that use generic radiation treatments. Generic treatments will facilitate safe trade between countries that have approved phytosanitary uses of radiation for fresh agricultural commodities.

Study on bubble column humidification and dehumidification system for coal mine wastewater treatment.

PubMed

Gao, Penghui; Zhang, Meng; Du, Yuji; Cheng, Bo; Zhang, Donghai

2018-04-01

Water is important resource for human survival and development. Coal mine wastewater (CMW) is a byproduct of the process of coal mining, which is about 7.0 × 10 10 m 3 in China in 2016. Considering coal mine wastewater includes different ingredients, a new bubble column humidification and dehumidification system is proposed for CMW treatment. The system is mainly composed of a bubble column humidification and dehumidification unit, solar collector, fan and water tank, in which air is used as a circulating medium. The system can avoid water treatment component blocking for reverse osmosis (RO) and multi effect distillation (MED) dealing with CMW, and produce water greenly. By analysis of heat and mass transfer, the effects of solar radiation, air bubble velocity and mine water temperature on water treatment production characteristics are studied. Compared with other methods, thermal energy consumption (TEC) of bubble column humidification and dehumidification (BCHD) is moderate, which is about 700 kJ/kg (powered by solar energy). The results would provide a new method for CMW treatment and insights into the efficient coal wastewater treatment, besides, it helps to identify the parameters for the technology development in mine water treatment.

Regulatory T cells and other lymphocyte subpopulations in patients with melanoma developing interferon-induced thyroiditis during high-dose interferon-α2b treatment.

PubMed

Soldevila, Berta; Alonso, Núria; Martínez-Arconada, Maria J; Granada, Maria L; Boada, Aram; Vallejos, Virginia; Fraile, Manuel; Fernández-Sanmartín, Marco A; Pujol-Borrell, Ricardo; Puig-Domingo, Manel; Sanmartí, Anna; Martínez-Cáceres, Eva M

2013-04-01

One of the side effects of interferon-alpha therapy is interferon-induced thyroiditis (IIT). The role of lymphocyte subpopulations in IIT melanoma patients remains to be defined. Our objective was to assess different peripheral blood lymphocyte subpopulations, mainly regulatory T cells (Tregs), in melanoma patients who developed IIT. From 30 melanoma patients receiving high-dose interferon (HDI)-alpha 2b (IFN-α2b) treatment, those who developed IIT (IIT patients) were selected and compared with patients who did not develop IIT (Co-MM) and healthy controls (Co-H). Peripheral blood mononuclear cells were obtained before treatment (BT), mid-treatment (MT), end of treatment (ET), 24 weeks post-treatment and at appearance of IIT (TT). Nine patients developed IIT (30%): four Hashimoto's thyroiditis and five destructive thyroiditis. An increase in Tregs was observed in both melanoma groups during HDI treatment. A decrease in CD3(+) , NKT lymphocyte subpopulations and Bcl2 expression on B cells was also observed in both groups. However, no changes were observed in the percentage of CD4(+) , CD8(+) , CD3(+) γδ(+) , CD19(+) , transitional B cells (CD24(high) CD38(high) CD19(+) CD27(-) ), natural killer (NK), invariant NKT (iNKT) lymphocytes and Th1/Th2 balance when BT was compared with ET. At TT, IIT patients had a higher Tregs percentage than Co-MM (P = 0·012) and Co-H (P = 0·004), a higher iNKT percentage than Co-MM (P = 0·011), a higher transitional B cells percentage than Co-H (P = 0·015), a lower CD3(+) percentage than Co-H (P = 0·001) and a lower Bcl2 expression on B cells than Co-H (P < 0·001). Our results point to the immunomodulatory effects of IFN-α on different lymphocyte subpopulations and a possible role of Tregs in melanoma patients who developed IIT. © 2012 Blackwell Publishing Ltd.

Effects of peripubertal gonadotropin-releasing hormone agonist on brain development in sheep--a magnetic resonance imaging study.

PubMed

Nuruddin, Syed; Bruchhage, Muriel; Ropstad, Erik; Krogenæs, Anette; Evans, Neil P; Robinson, Jane E; Endestad, Tor; Westlye, Lars T; Madison, Cindee; Haraldsen, Ira Ronit Hebold

2013-10-01

In many species sexual dimorphisms in brain structures and functions have been documented. In ovine model, we have previously demonstrated that peri-pubertal pharmacological blockade of gonadotropin releasing hormone (GnRH) action increased sex-differences of executive emotional behavior. The structural substrate of this behavioral alteration however is unknown. In this magnetic resonance image (MRI) study on the same animals, we investigated the effects of GnRH agonist (GnRHa) treatment on the volume of total brain, hippocampus and amygdala. In total 41 brains (17 treated; 10 females and 7 males, and 24 controls; 11 females and 13 males) were included in the MRI study. Image acquisition was performed with 3-T MRI scanner. Segmentation of the amygdala and the hippocampus was done by manual tracing and total gray and white matter volumes were estimated by means of automated brain volume segmentation of the individual T2-weighted MRI volumes. Statistical comparisons were performed with general linear models. Highly significant GnRHa treatment effects were found on the volume of left and right amygdala, indicating larger amygdalae in treated animals. Significant sex differences were found for total gray matter and right amygdala, indicating larger volumes in male compared to female animals. Additionally, we observed a significant interaction between sex and treatment on left amygdala volume, indicating stronger effects of treatment in female compared to male animals. The effects of GnRHa treatment on amygdala volumes indicate that increasing GnRH concentration during puberty may have an important impact on normal brain development in mammals. These novel findings substantiate the need for further studies investigating potential neurobiological side effects of GnRHa treatment on the brains of young animals and humans. Copyright © 2013 Elsevier Ltd. All rights reserved.

The development of a stochastic mathematical model of Alzheimer’s disease to help improve the design of clinical trials of potential treatments

PubMed Central

Ower, Alison K.; de Wolf, Frank; Anderson, Roy M.

2018-01-01

Alzheimer’s disease (AD) is a neurodegenerative disorder characterised by a slow progressive deterioration of cognitive capacity. Drugs are urgently needed for the treatment of AD and unfortunately almost all clinical trials of AD drug candidates have failed or been discontinued to date. Mathematical, computational and statistical tools can be employed in the construction of clinical trial simulators to assist in the improvement of trial design and enhance the chances of success of potential new therapies. Based on the analysis of a set of clinical data provided by the Alzheimer's Disease Neuroimaging Initiative (ADNI) we developed a simple stochastic mathematical model to simulate the development and progression of Alzheimer’s in a longitudinal cohort study. We show how this modelling framework could be used to assess the effect and the chances of success of hypothetical treatments that are administered at different stages and delay disease development. We demonstrate that the detection of the true efficacy of an AD treatment can be very challenging, even if the treatment is highly effective. An important reason behind the inability to detect signals of efficacy in a clinical trial in this therapy area could be the high between- and within-individual variability in the measurement of diagnostic markers and endpoints, which consequently results in the misdiagnosis of an individual’s disease state. PMID:29377891

The development of a stochastic mathematical model of Alzheimer's disease to help improve the design of clinical trials of potential treatments.

PubMed

Hadjichrysanthou, Christoforos; Ower, Alison K; de Wolf, Frank; Anderson, Roy M

2018-01-01

Alzheimer's disease (AD) is a neurodegenerative disorder characterised by a slow progressive deterioration of cognitive capacity. Drugs are urgently needed for the treatment of AD and unfortunately almost all clinical trials of AD drug candidates have failed or been discontinued to date. Mathematical, computational and statistical tools can be employed in the construction of clinical trial simulators to assist in the improvement of trial design and enhance the chances of success of potential new therapies. Based on the analysis of a set of clinical data provided by the Alzheimer's Disease Neuroimaging Initiative (ADNI) we developed a simple stochastic mathematical model to simulate the development and progression of Alzheimer's in a longitudinal cohort study. We show how this modelling framework could be used to assess the effect and the chances of success of hypothetical treatments that are administered at different stages and delay disease development. We demonstrate that the detection of the true efficacy of an AD treatment can be very challenging, even if the treatment is highly effective. An important reason behind the inability to detect signals of efficacy in a clinical trial in this therapy area could be the high between- and within-individual variability in the measurement of diagnostic markers and endpoints, which consequently results in the misdiagnosis of an individual's disease state.

Emerging nanotechnology approaches for HIV/AIDS treatment and prevention

PubMed Central

Mamo, Tewodros; Moseman, E Ashley; Kolishetti, Nagesh; Salvador-Morales, Carolina; Shi, Jinjun; Kuritzkes, Daniel R; Langer, Robert; von Andrian, Ulrich

2010-01-01

Currently, there is no cure and no preventive vaccine for HIV/AIDS. Combination antiretroviral therapy has dramatically improved treatment, but it has to be taken for a lifetime, has major side effects and is ineffective in patients in whom the virus develops resistance. Nanotechnology is an emerging multidisciplinary field that is revolutionizing medicine in the 21st century. It has a vast potential to radically advance the treatment and prevention of HIV/AIDS. In this review, we discuss the challenges with the current treatment of the disease and shed light on the remarkable potential of nanotechnology to provide more effective treatment and prevention for HIV/AIDS by advancing antiretroviral therapy, gene therapy, immunotherapy, vaccinology and microbicides. PMID:20148638

Treatment Principles for the Management of Mold Infections

PubMed Central

Kontoyiannis, Dimitrios P.; Lewis, Russell E.

2015-01-01

Survival rates among immunocompromised patients with invasive mold infections have markedly improved over the last decade with earlier diagnosis and new antifungal treatment options. Yet, increasing antifungal resistance, breakthrough infections with intrinsically resistant fungi, and potentially life-threatening adverse effects and drug interactions are becoming more problematic, especially with prolonged therapy. Evidence-based recommendations for treating invasive aspergillosis and mucormycosis provide excellent guidance on the initial workup and treatment of these molds, but they cannot address all of the key management issues. Herein, we discuss 10 general treatment principles in the management of invasive mold disease in immunocompromised patients and discuss how these principles can be integrated to develop an effective, individualized treatment plan. PMID:25377139

Developing Alternative Methods/Techniques for Plant Establishment Under Reduced Irrigation

DOT National Transportation Integrated Search

2009-06-10

The purpose of the study was to evaluate soil treatments for their effect on establishment of wild-land : shrubs without supplemental irrigation. The treatments that significantly improved growth over irrigation : alone at a central California fill s...

Selected National Cancer Institute Breast Cancer Research Topics | NIH MedlinePlus the Magazine

MedlinePlus

... effective treatments for these women. The Integrative Cancer Biology Program combines experimental and clinical research with mathematical modeling to gain new insights into cancer biology, prevention, diagnostics, and treatments. Multiple centers are developing ...

Agoraphobia: an outreach treatment programme.

PubMed

Croft, Alison; Hackmann, Ann

2013-05-01

Agoraphobia is disabling and clients find it hard to access effective treatment. This paper describes the development of an inexpensive service, delivered by trained volunteers in or near the client's own home. We describe the development of the service, including selection, training and supervision. Outcomes were evaluated over 5 years, and compared with those available from the local psychology service. Effect sizes on all measures were high. Benchmarking indicated that results on comparable measures were not significantly different from the local psychology service. As in many previous studies drop-out rate was fairly high. This model worked well, and was inexpensive and effective. Further research on long term outcome and methods of enhancing engagement is needed.

Antimicrobial stewardship in long term care facilities: what is effective?

PubMed

Nicolle, Lindsay E

2014-02-12

Intense antimicrobial use in long term care facilities promotes the emergence and persistence of antimicrobial resistant organisms and leads to adverse effects such as C. difficile colitis. Guidelines recommend development of antimicrobial stewardship programs for these facilities to promote optimal antimicrobial use. However, the effectiveness of these programs or the contribution of any specific program component is not known. For this review, publications describing evaluation of antimicrobial stewardship programs for long term care facilities were identified through a systematic literature search. Interventions included education, guidelines development, feedback to practitioners, and infectious disease consultation. The studies reviewed varied in types of facilities, interventions used, implementation, and evaluation. Comprehensive programs addressing all infections were reported to have improved antimicrobial use for at least some outcomes. Targeted programs for treatment of pneumonia were minimally effective, and only for indicators of uncertain relevance for stewardship. Programs focusing on specific aspects of treatment of urinary infection - limiting treatment of asymptomatic bacteriuria or prophylaxis of urinary infection - were reported to be effective. There were no reports of cost-effectiveness, and the sustainability of most of the programs is unclear. There is a need for further evaluation to characterize effective antimicrobial stewardship for long term care facilities.

Cost-effectiveness analysis for joint pain treatment in patients with osteoarthritis treated at the Instituto Mexicano del Seguro Social (IMSS): Comparison of nonsteroidal anti-inflammatory drugs (NSAIDs) vs. cyclooxygenase-2 selective inhibitors.

PubMed

Contreras-Hernández, Iris; Mould-Quevedo, Joaquín F; Torres-González, Rubén; Goycochea-Robles, María Victoria; Pacheco-Domínguez, Reyna Lizette; Sánchez-García, Sergio; Mejía-Aranguré, Juan Manuel; Garduño-Espinosa, Juan

2008-11-12

Osteoarthritis (OA) is one of the main causes of disability worldwide, especially in persons >55 years of age. Currently, controversy remains about the best therapeutic alternative for this disease when evaluated from a cost-effectiveness viewpoint. For Social Security Institutions in developing countries, it is very important to assess what drugs may decrease the subsequent use of medical care resources, considering their adverse events that are known to have a significant increase in medical care costs of patients with OA. Three treatment alternatives were compared: celecoxib (200 mg twice daily), non-selective NSAIDs (naproxen, 500 mg twice daily; diclofenac, 100 mg twice daily; and piroxicam, 20 mg/day) and acetaminophen, 1000 mg twice daily. The aim of this study was to identify the most cost-effective first-choice pharmacological treatment for the control of joint pain secondary to OA in patients treated at the Instituto Mexicano del Seguro Social (IMSS). A cost-effectiveness assessment was carried out. A systematic review of the literature was performed to obtain transition probabilities. In order to evaluate analysis robustness, one-way and probabilistic sensitivity analyses were conducted. Estimations were done for a 6-month period. Treatment demonstrating the best cost-effectiveness results [lowest cost-effectiveness ratio $17.5 pesos/patient ($1.75 USD)] was celecoxib. According to the one-way sensitivity analysis, celecoxib would need to markedly decrease its effectiveness in order for it to not be the optimal treatment option. In the probabilistic analysis, both in the construction of the acceptability curves and in the estimation of net economic benefits, the most cost-effective option was celecoxib. From a Mexican institutional perspective and probably in other Social Security Institutions in similar developing countries, the most cost-effective option for treatment of knee and/or hip OA would be celecoxib.

Cost-effectiveness analysis for joint pain treatment in patients with osteoarthritis treated at the Instituto Mexicano del Seguro Social (IMSS): Comparison of nonsteroidal anti-inflammatory drugs (NSAIDs) vs. cyclooxygenase-2 selective inhibitors

PubMed Central

Contreras-Hernández, Iris; Mould-Quevedo, Joaquín F; Torres-González, Rubén; Goycochea-Robles, María Victoria; Pacheco-Domínguez, Reyna Lizette; Sánchez-García, Sergio; Mejía-Aranguré, Juan Manuel; Garduño-Espinosa, Juan

2008-01-01

Background Osteoarthritis (OA) is one of the main causes of disability worldwide, especially in persons >55 years of age. Currently, controversy remains about the best therapeutic alternative for this disease when evaluated from a cost-effectiveness viewpoint. For Social Security Institutions in developing countries, it is very important to assess what drugs may decrease the subsequent use of medical care resources, considering their adverse events that are known to have a significant increase in medical care costs of patients with OA. Three treatment alternatives were compared: celecoxib (200 mg twice daily), non-selective NSAIDs (naproxen, 500 mg twice daily; diclofenac, 100 mg twice daily; and piroxicam, 20 mg/day) and acetaminophen, 1000 mg twice daily. The aim of this study was to identify the most cost-effective first-choice pharmacological treatment for the control of joint pain secondary to OA in patients treated at the Instituto Mexicano del Seguro Social (IMSS). Methods A cost-effectiveness assessment was carried out. A systematic review of the literature was performed to obtain transition probabilities. In order to evaluate analysis robustness, one-way and probabilistic sensitivity analyses were conducted. Estimations were done for a 6-month period. Results Treatment demonstrating the best cost-effectiveness results [lowest cost-effectiveness ratio $17.5 pesos/patient ($1.75 USD)] was celecoxib. According to the one-way sensitivity analysis, celecoxib would need to markedly decrease its effectiveness in order for it to not be the optimal treatment option. In the probabilistic analysis, both in the construction of the acceptability curves and in the estimation of net economic benefits, the most cost-effective option was celecoxib. Conclusion From a Mexican institutional perspective and probably in other Social Security Institutions in similar developing countries, the most cost-effective option for treatment of knee and/or hip OA would be celecoxib. PMID:19014495

Predicting Nonauditory Adverse Radiation Effects Following Radiosurgery for Vestibular Schwannoma: A Volume and Dosimetric Analysis

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

Hayhurst, Caroline; Monsalves, Eric; Bernstein, Mark

2012-04-01

Purpose: To define clinical and dosimetric predictors of nonauditory adverse radiation effects after radiosurgery for vestibular schwannoma treated with a 12 Gy prescription dose. Methods: We retrospectively reviewed our experience of vestibular schwannoma patients treated between September 2005 and December 2009. Two hundred patients were treated at a 12 Gy prescription dose; 80 had complete clinical and radiological follow-up for at least 24 months (median, 28.5 months). All treatment plans were reviewed for target volume and dosimetry characteristics; gradient index; homogeneity index, defined as the maximum dose in the treatment volume divided by the prescription dose; conformity index; brainstem; andmore » trigeminal nerve dose. All adverse radiation effects (ARE) were recorded. Because the intent of our study was to focus on the nonauditory adverse effects, hearing outcome was not evaluated in this study. Results: Twenty-seven (33.8%) patients developed ARE, 5 (6%) developed hydrocephalus, 10 (12.5%) reported new ataxia, 17 (21%) developed trigeminal dysfunction, 3 (3.75%) had facial weakness, and 1 patient developed hemifacial spasm. The development of edema within the pons was significantly associated with ARE (p = 0.001). On multivariate analysis, only target volume is a significant predictor of ARE (p = 0.001). There is a target volume threshold of 5 cm3, above which ARE are more likely. The treatment plan dosimetric characteristics are not associated with ARE, although the maximum dose to the 5th nerve is a significant predictor of trigeminal dysfunction, with a threshold of 9 Gy. The overall 2-year tumor control rate was 96%. Conclusions: Target volume is the most important predictor of adverse radiation effects, and we identified the significant treatment volume threshold to be 5 cm3. We also established through our series that the maximum tolerable dose to the 5th nerve is 9 Gy.« less

Interventions for Tobacco Smoking

PubMed Central

Schlam, Tanya R.; Baker, Timothy B.

2017-01-01

Around 19% of U.S. adults smoke cigarettes, and smoking remains the leading avoidable cause of death in this country. Without treatment only ~5% of smokers who try to quit achieve long-term abstinence, but evidence-based cessation treatment increases this figure to 10-30%. The process of smoking cessation comprises different pragmatically defined phases, and these can help guide smoking treatment development and evaluation. This review evaluates the effectiveness of smoking interventions for smokers who are unwilling to make a quit attempt (Motivation Phase), who are willing to make a quit attempt (Cessation Phase), who have recently quit (Maintenance Phase), and who have recently relapsed (Relapse Recovery Phase). Multiple effective treatments exist for some phases (Cessation), but not others (Relapse Recovery). A chronic care approach to treating smoking requires effective interventions for every phase, especially interventions that exert complementary effects both within and across phases, and that can be disseminated broadly and cost-effectively. PMID:23297788

Anti-Obesity Drugs: A Review about Their Effects and Safety

PubMed Central

Kang, Jun Goo

2012-01-01

The current recommendations for the treatment of obese people include increased physical activity and reduced calories intake. When the behavioral approach is not sufficient, a pharmacologic treatment is recommended. In past years, numerous drugs have been approved for the treatment of obesity; however, most of them have been withdrawn from the market because of their adverse effects. In fact, amphetamine, rimonabant and sibutramine licenses have been withdrawn due to an increased risk of psychiatric disorders and non-fatal myocardial infarction or stroke. Even if orlistat is not as effective as other drugs in reducing body weight, orlistat is presently the only available choice for the treatment of obesity because of its safety for cardiovascular events and positive effects on diabetic control. Hopefully, more effective and better tolerated anti-obesity drugs will be developed through an improved understanding of the multiple mechanisms and complex physiological systems targeting appetite. PMID:22363917

Practical tips for sexual counseling and psychotherapy in premature ejaculation.

PubMed

Rowland, David; Cooper, Stewart

2011-10-01

A number of milestones in the treatment of premature ejaculation (PE) have occurred over the past five decades, including the development of various behavioral and cognitive techniques as well as pharmacotherapies that modify neurophysiological processes involved in ejaculation. Nevertheless, the notion that sexual responses such as PE are influenced by physiological, psychobehavioral, cultural, and relationship factors is as valid now as it was 50 years ago, and therefore, interventions should consider all such domains in the development of effective treatment strategies. Provide an overview of which patients with PE are suitable to receive psychosexual treatment and the psychological approaches for managing this disorder. Review of the literature. Psychosexual treatments that integrate behavioral, psychological, and relationship functioning. PE is typically a couple's problem and, therefore, psychotherapy is best when the partner is involved. Before embarking on psychotherapy, the clinician should obtain a medical history pertaining to sexual-, psychological-, and relationship-related factors, so that the treatment strategy can be tailored to the needs of the individual. General strategies underpinning integrative, "process-oriented" elements of psychotherapy most relevant to PE are: developing the therapist-patient relationship; expressing empathy, genuineness, and positive regard; motivational interviewing, i.e., developing motivation to change; developing discrepancy; working through resistance; identifying PE-related affect, cognitions, and behaviors (including interaction with partners); and supporting self-efficacy. The four main domains that encompass psychotherapy techniques specific to the treatment of PE are: behavioral; cognitive; affective; and relational. Sustained positive outcomes in PE may be obtained using a combination treatment strategy that addresses all elements of PE, including psychological and biological factors. Psychosexual treatments may help the patient with PE and his partner to address their sexual problems and improve their overall relationship. The effects of psychosexual therapy may be augmented by combining this intervention with pharmacotherapy. 2011 International Society for Sexual Medicine.

The effect of low-density diets on broiler breeder performance during the laying period and on embryonic development of their offspring.

PubMed

Enting, H; Kruip, T A M; Verstegen, M W A; van der Aar, P J

2007-05-01

The effect of low-density diets on bird performance, egg composition, and embryonic development was studied with 2,100 female and 210 male Cobb broiler breeders from 25 to 60 wk of age. The experiment included 5 treatments. These included a control group with a normal density diet (ND, 2,800 kcal of AME/kg). Treatments 2 (LD11) and 3 (LD21) had a 11 and 21% lower nutrient density. Treatment 4 (LD11(OP)) had a 11% less dense diet, which was obtained by inclusion of other feed ingredients. In these 4 treatments similar diets were given during the rearing and the laying period. Treatment 5 combined LD12 in the rearing period and ND diets during the laying period (LD12-ND). Egg composition and embryonic development were measured in eggs of ND and LD21 birds at 29 and 41 wk of age. During the laying period from wk 25 to 60, live weights did not differ among treatments, except that birds fed LD11(OP) had lower live weights. A significantly higher rate of lay was provided by LD11 compared with ND. Egg weights were significantly higher when low-density diets were fed, particularly in LD11(OP). Percentage of fertile eggs did not differ among treatments. Compared with the other treatments, LD11(OP) provided a significantly lower hatchability. We found that LD21 resulted in a better development of the area vitellina externa and heart and embryo weight at 29 wk of age. It was concluded that this was related to a higher egg weight and egg white proportion. This suggests that the amount of egg white in eggs of hens fed ND was limiting for embryonic development, particularly in eggs of young broiler breeders.

"There is a chain of connections": using syndemics theory to understand HIV treatment side effects.

PubMed

Gagnon, Marilou

2018-03-12

Side effects are central to the experience of living longer with HIV but rarely have they been studied alone. Unlike other aspects of that experience, like quality of life, treatment adherence, chronicity, episodic disability, aging, health, and viral load suppression, side effects have not benefited from the same level of empirical and theoretical engagement from qualitative researchers. In this paper, we draw on syndemics theory and 50 qualitative interviews to better understand the experience of HIV treatment side effects. Two main categories were identified in the data: side effects as a product and side effects as a risk factor. The first category suggests that side effects are not just the product of taking antiretroviral drugs. They are also the product of particular conditions and tend to cluster with other health problems. The second category puts forward the idea that side effects can act as a syndemic risk factor by exposing PLWH to a greater risk of developing health problems and creating conditions in which psychosocial issues are more likely to emerge. The paper concludes by calling for more research on the complex nature of side effects and for the development of comprehensive approaches for the assessment and management of side effects.

Developing statistical wildlife habitat relationships for assessing cumulative effects of fuels treatments: Final Report for Joint Fire Science Program Project

Treesearch

Samuel A. Cushman; Kevin S. McKelvey

2006-01-01

The primary weakness in our current ability to evaluate future landscapes in terms of wildlife lies in the lack of quantitative models linking wildlife to forest stand conditions, including fuels treatments. This project focuses on 1) developing statistical wildlife habitat relationships models (WHR) utilizing Forest Inventory and Analysis (FIA) and National Vegetation...

Nanotechnology in the management of cervical cancer.

PubMed

Chen, Jiezhong; Gu, Wenyi; Yang, Lei; Chen, Chen; Shao, Renfu; Xu, Kewei; Xu, Zhi Ping

2015-03-01

Cervical cancer is a major disease with high mortality. All cervical cancers are caused by infection with human papillomaviruses (HPV). Although preventive vaccines for cervical cancer are successful, treatment of cervical cancer is far less satisfactory because of multidrug resistance and side effects. In this review, we summarize the recent application of nanotechnology to the diagnosis and treatment of cervical cancer as well as the development of HPV vaccines. Early detection of cervical cancer enables tumours to be efficiently removed by surgical procedures, leading to increased survival rate. The current method of detecting cervical cancer by Pap smear can only achieve 50% sensitivity, whereas nanotechnology has been used to detect HPVs with greatly improved sensitivity. In cervical cancer treatment, nanotechnology has been used for the delivery of anticancer drugs to increase treatment efficacy and decrease side effects. Nanodelivery of HPV preventive and therapeutic vaccines has also been investigated to increase vaccine efficacy. Overall, these developments suggest that nanoparticle-based vaccine may become the most effective way to prevent and treat cervical cancer, assisted or combined with some other nanotechnology-based therapy. Copyright © 2015 John Wiley & Sons, Ltd.

Simulations of Precipitate Microstructure Evolution during Heat Treatment

NASA Astrophysics Data System (ADS)

Wu, Kaisheng; Sterner, Gustaf; Chen, Qing; Jou, Herng-Jeng; Jeppsson, Johan; Bratberg, Johan; Engström, Anders; Mason, Paul

Precipitation, a major solid state phase transformation during heat treatment processes, has for more than one century been intensively employed to improve the strength and toughness of various high performance alloys. Recently, sophisticated precipitation reaction models, in assistance with well-developed CALPHAD databases, provide an efficient and cost-effective way to tailor precipitate microstructures that maximize the strengthening effect via the optimization of alloy chemistries and heat treatment schedules. In this presentation, we focus on simulating precipitate microstructure evolution in Nickel-base superalloys under arbitrary heat treatment conditions. The newly-developed TC-PRISMA program has been used for these simulations, with models refined especially for non-isothermal conditions. The effect of different cooling profiles on the formation of multimodal microstructures has been thoroughly examined in order to understand the underlying thermodynamics and kinetics. Meanwhile, validations against several experimental results have been carried out. Practical issues that are critical to the accuracy and applicability of the current simulations, such as modifications that overcome mean-field approximations, compatibility between CALPHAD databases, selection of key parameters (particularly interfacial energy and nucleation site densities), etc., are also addressed.

Diagnostic criteria, severity classification and guidelines of systemic sclerosis.

PubMed

Asano, Yoshihide; Jinnin, Masatoshi; Kawaguchi, Yasushi; Kuwana, Masataka; Goto, Daisuke; Sato, Shinichi; Takehara, Kazuhiko; Hatano, Masaru; Fujimoto, Manabu; Mugii, Naoki; Ihn, Hironobu

2018-06-01

Several effective drugs have been identified for the treatment of systemic sclerosis (SSc). However, in advanced cases, not only their effectiveness is reduced but they may be also harmful due to their side-effects. Therefore, early diagnosis and early treatment is most important for the treatment of SSc. We established diagnostic criteria for SSc in 2003 and early diagnostic criteria for SSc in 2011, for the purpose of developing evaluation of each organ in SSc. Moreover, in November 2013, the American College of Rheumatology and the European Rheumatology Association jointly developed new diagnostic criteria for increasing their sensitivity and specificity, so we revised our diagnostic criteria and severity classification of SSc. Furthermore, we have revised the clinical guideline based on the newest evidence. In particular, the clinical guideline was established by clinical questions based on evidence-based medicine according to the New Minds Clinical Practice Guideline Creation Manual (version 1.0). We aimed to make the guideline easy to use and reliable based on the newest evidence, and to present guidance as specific as possible for various clinical problems in treatment of SSc. © 2018 Japanese Dermatological Association.

Lipid-Based Drug Delivery Systems in Cancer Therapy: What Is Available and What Is Yet to Come

PubMed Central

Yingchoncharoen, Phatsapong; Kalinowski, Danuta S.

2016-01-01

Cancer is a leading cause of death in many countries around the world. However, the efficacy of current standard treatments for a variety of cancers is suboptimal. First, most cancer treatments lack specificity, meaning that these treatments affect both cancer cells and their normal counterparts. Second, many anticancer agents are highly toxic, and thus, limit their use in treatment. Third, a number of cytotoxic chemotherapeutics are highly hydrophobic, which limits their utility in cancer therapy. Finally, many chemotherapeutic agents exhibit short half-lives that curtail their efficacy. As a result of these deficiencies, many current treatments lead to side effects, noncompliance, and patient inconvenience due to difficulties in administration. However, the application of nanotechnology has led to the development of effective nanosized drug delivery systems known commonly as nanoparticles. Among these delivery systems, lipid-based nanoparticles, particularly liposomes, have shown to be quite effective at exhibiting the ability to: 1) improve the selectivity of cancer chemotherapeutic agents; 2) lower the cytotoxicity of anticancer drugs to normal tissues, and thus, reduce their toxic side effects; 3) increase the solubility of hydrophobic drugs; and 4) offer a prolonged and controlled release of agents. This review will discuss the current state of lipid-based nanoparticle research, including the development of liposomes for cancer therapy, different strategies for tumor targeting, liposomal formulation of various anticancer drugs that are commercially available, recent progress in liposome technology for the treatment of cancer, and the next generation of lipid-based nanoparticles. PMID:27363439

Effective physical treatment for chronic low back pain.

PubMed

Maher, C G

2004-01-01

It is now feasible to adopt an evidence-based approach when providing physical treatment for patients with chronic LBP. A summary of the efficacy of a range of physical treatments is provided in Table 1. The evidence-based primary care options are exercise, laser, massage, and spinal manipulation; however, the latter three have small or transient effects that limit their value as therapies for chronic LBP. In contrast, exercise produces large reductions in pain and disability, a feature that suggests that exercise should play a major role in the management of chronic LBP. Physical treatments, such as acupuncture, backschool, hydrotherapy, lumbar supports, magnets, TENS, traction, ultrasound, Pilates therapy, Feldenkrais therapy, Alexander technique, and craniosacral therapy are either of unknown value or ineffective and so should not be considered. Outside of primary care, multidisciplinary treatment or functional restoration is effective; however, the high cost probably means that these programs should be reserved for patients who do not respond to cheaper treatment options for chronic LBP. Although there are now effective treatment options for chronic LBP, it needs to be acknowledged that the problem of chronic LBP is far from solved. Though treatments can provide marked improvements in the patient's condition, the available evidence suggests that the typical chronic LBP patient is left with some residual pain and disability. Developing new, more powerful treatments and refining the current group of known effective treatments is the challenge for the future.

Effects of Individual Development Accounts (IDAs) on Household Wealth and Saving Taste

ERIC Educational Resources Information Center

Huang, Jin

2010-01-01

This study examines effects of individual development accounts (IDAs) on household wealth of low-income participants. Methods: This study uses longitudinal survey data from the American Dream Demonstration (ADD) involving experimental design (treatment group = 537, control group = 566). Results: Results from quantile regression analysis indicate…

HIV Infection: Transmission, Effects on Early Development, and Interventions.

ERIC Educational Resources Information Center

Lowenthal, Barbara

1997-01-01

Describes the modes of transmission of HIV and the course of the disease in infants and toddlers. Information is provided on its effects on early development, medical screening and treatments, therapies, psychosocial assistance, and interventions, including nutritional therapy, occupational and physical therapies, and speech and language therapy.…

Social environment alters opioid-induced hyperalgesia and antinociceptive tolerance in adolescent mice.

PubMed

Bates, M L S; Emery, M A; Wellman, P J; Eitan, S

2016-07-01

Chronic opioid treatment is complicated by the development of tolerance and hyperalgesia. Social environment alters both opioid-induced behaviours and nociceptive mechanisms. Our previous studies demonstrated that, in adolescent rodents, the susceptibility to acquire opioid dependence and reward is dependent on the nature of social housing conditions. Specifically, our previous studies demonstrate that housing morphine-treated mice with drug-naïve animals mitigates the abuse liability of opioids. Thus, this study tested the effect of social housing conditions on the development of adaptive processes to morphine antinociception. Adolescent males were group-housed in different conditions. In the mixed treatment condition, mice treated with 20 mg/kg morphine (i.e. 'morphine cage-mates') and saline (i.e. 'saline cage-mates') were housed together. In the separated treatment conditions, all mice in the cage received morphine (i.e. 'morphine only') or saline (i.e. 'saline only'). All animals were tested for baseline pain sensitivity and for the response to morphine in the tail withdrawal, hot plate, acetone and von Frey filament tests, during and after discontinuation of opioid treatment. Both morphine cage-mate and morphine only animals developed antinociceptive tolerance. However, this effect was more robust and persistent in the morphine only group. Notably, morphine only animals, but not morphine cage-mates, developed opioid-induced hyperalgesia. This study demonstrates that housing morphine-treated mice with drug-naïve animals mitigates the development of opioid-induced hyperalgesia and antinociceptive tolerance. Thus, this study indicates that social environment influences the effectiveness of opioid pain management. © 2016 European Pain Federation - EFIC®

The gut-brain interaction in opioid tolerance.

PubMed

Akbarali, Hamid I; Dewey, William L

2017-12-01

The prevailing opioid crisis has necessitated the need to understand mechanisms leading to addiction and tolerance, the major contributors to overdose and death and to develop strategies for developing drugs for pain treatment that lack abuse liability and side-effects. Opioids are commonly used for treatment of pain and symptoms of inflammatory bowel disease. The significant effect of opioids in the gut, both acute and chronic, includes persistent constipation and paradoxically may also worsen pain symptoms. Recent work has suggested a significant role of the gastrointestinal microbiome in behavioral responses to opioids, including the development of tolerance to its pain-relieving effects. In this review, we present current concepts of gut-brain interaction in analgesic tolerance to opioids and suggest that peripheral mechanisms emanating from the gut can profoundly affect central control of opioid function. Copyright © 2017 Elsevier Ltd. All rights reserved.

Advances in the medical treatment of juvenile rheumatoid arthritis.

PubMed

Onel, K B

2000-02-01

Juvenile rheumatoid arthritis (JRA) remains a challenge for clinicians. Nonsteroidal anti-inflammatory drugs and corticosteroids remain the mainstays of therapy, but concerns persist about side effects and the ability of these agents to prevent progression of bony disease. In recent years, novel treatments have been developed and quickly discarded because of unexpected toxicities or lack of efficacy. However, recent studies have shown that methotrexate and sulfasalazine are relatively safe and effective for JRA. Newly developed drugs, such as selective cyclooxygenase-2 inhibitors and soluble tumor necrosis factor receptor, whose development has stemmed from a more basic understanding of pathophysiology, may provide better disease control with fewer side effects. Finally, novel therapies, such as stem cell transplantation, may offer hope for children with JRA, especially systemic-onset JRA, whose disease has been refractory to conventional therapy.

Prolonged Exposure Therapy for Combat-Related Posttraumatic Stress Disorder: Comparing Outcomes for Veterans of Different Wars

PubMed Central

Yoder, Matthew; Tuerk, Peter W.; Price, Matthew; Grubaugh, Anouk L.; Strachan, Martha; Myrick, Hugh; Acierno, Ron

2012-01-01

There is significant support for exposure therapy as an effective treatment for posttraumatic stress disorder (PTSD) across a variety of populations, including veterans; however, there is little empirical information regarding how veterans of different war theaters respond to exposure therapy. Accordingly, questions remain regarding therapy effectiveness for treatment of PTSD for veterans of different eras. Such questions have important implications for the dissemination of evidence based treatments, treatment development, and policy. The current study compared treatment outcomes across 112 veterans of the Vietnam War, the first Persian Gulf War, and the wars in Afghanistan and Iraq. All subjects were diagnosed with PTSD and enrolled in Prolonged Exposure (PE) treatment. Veterans from all three groups showed significant improvement in PTSD symptoms, with veterans from Vietnam and Afghanistan/Iraq responding similarly to treatment. Persian Gulf veterans did not respond to treatment at the same rate or to the same degree as veterans from the other two eras. Questions and issues regarding the effectiveness of evidence based treatment for veterans from different eras are discussed. PMID:22449084

Prolonged exposure therapy for combat-related posttraumatic stress disorder: comparing outcomes for veterans of different wars.

PubMed

Yoder, Matthew; Tuerk, Peter W; Price, Matthew; Grubaugh, Anouk L; Strachan, Martha; Myrick, Hugh; Acierno, Ron

2012-02-01

There is significant support for exposure therapy as an effective treatment for posttraumatic stress disorder (PTSD) across a variety of populations, including veterans; however, there is little empirical information regarding how veterans of different war theaters respond to exposure therapy. Accordingly, questions remain regarding therapy effectiveness for treatment of PTSD for veterans of different eras. Such questions have important implications for the dissemination of evidence based treatments, treatment development, and policy. The current study compared treatment outcomes across 112 veterans of the Vietnam War, the first Persian Gulf War, and the wars in Afghanistan and Iraq. All subjects were diagnosed with PTSD and enrolled in prolonged exposure (PE) treatment. Veterans from all three groups showed significant improvement in PTSD symptoms, with veterans from Vietnam and Afghanistan/Iraq responding similarly to treatment. Persian Gulf veterans did not respond to treatment at the same rate or to the same degree as veterans from the other two eras. Questions and issues regarding the effectiveness of evidence based treatment for veterans from different eras are discussed.

Protocol for a prospective observational study of conventional treatment and traditional Korean medicine combination treatment for children with cerebral palsy.

PubMed

Yoo, Jeong-Eun; Yun, Young-Ju; Shin, Yong-Beom; Kim, Nam-Kwen; Kim, Soo-Yeon; Shin, Myung-Jun; Yu, Sun-Ae

2016-06-08

Cerebral palsy leads to many complications as well as delayed motor development, and early intensive rehabilitation in infancy, which is based on the theory of brain plasticity, is emphasized. In addition to conventional treatment, including physical, occupational, or speech-language therapies, children also have a demand for traditional Korean medicine interventions such as acupuncture or herbal medicine; however, a lack of evidence has made traditional Korean medicine difficult to implement in practice. We planned a multicentre, prospective, observational study to assess the effectiveness, safety and cost-effectiveness of conventional treatment and traditional Korean medicine combination treatment for children with cerebral palsy. Three hundred children with cerebral palsy aged 6 to 78 months will be recruited from six institutions. Data from each child are collected every month for a one-year period, during which time treatment might be changed or discontinued. A qualified investigator visits the sites to measure effectiveness variables, including Gross Motor Function Measure and Paediatric Evaluation of Disability Inventory. Adverse events and cost-effectiveness variables are collected using surveys conducted at baseline, mid-study, and end of study, as well as monthly tracking surveys. In the analyses, participants will be classified into two groups: group A children will be the conventional treatment group with physical, occupational, speech-language or other conventional rehabilitation therapies, whereas group B children will be the combination treatment group with traditional Korean medicine interventions, that is, herbal medicine, chuna, moxibustion and acupuncture, in addition to conventional treatment. Only a few clinical case reports have evaluated the effectiveness and safety of traditional Korean medicine; therefore, more data are required to provide optimal information to children with cerebral palsy and their guardians. We hypothesized that traditional Korean medicine combination treatment for children with cerebral palsy would have benefits compared with conventional therapy alone. The findings of this study might provide informative data for conducting economic evaluations and developing clinical research on combination treatment for cerebral palsy in South Korea. NCT02223741.

Metabolic interrogation as a tool to optimize chemotherapeutic regimens.

PubMed

Sandulache, Vlad C; Chen, Yunyun; Feng, Lei; William, William N; Skinner, Heath D; Myers, Jeffrey N; Meyn, Raymond E; Li, Jinzhong; Mijiti, Ainiwaer; Bankson, James A; Fuller, Clifton D; Konopleva, Marina Y; Lai, Stephen Y

2017-03-14

Platinum-based (Pt) chemotherapy is broadly utilized in the treatment of cancer. Development of more effective, personalized treatment strategies require identification of novel biomarkers of treatment response. Since Pt compounds are inactivated through cellular metabolic activity, we hypothesized that metabolic interrogation can predict the effectiveness of Pt chemotherapy in a pre-clinical model of head and neck squamous cell carcinoma (HNSCC).We tested the effects of cisplatin (CDDP) and carboplatin (CBP) on DNA damage, activation of cellular death cascades and tumor cell metabolism, specifically lactate production. Pt compounds induced an acute dose-dependent, transient drop in lactate generation in vitro, which correlated with effects on DNA damage and cell death. Neutralization of free radical stress abrogated these effects. The magnitude of this effect on lactate production correlated with the differential sensitivity of HNSCC cells to Pt compounds (CDDP vs CBP) and p53-driven Pt chemotherapy resistance. Using dual flank xenograft tumors, we demonstrated that Pt-driven effects on lactate levels correlate with effects on tumor growth delay in a dose-dependent manner and that lactate levels can define the temporal profile of Pt chemotherapy-induced metabolic stress. Lactate interrogation also predicted doxorubicin effects on cell death in both solid tumor (HNSCC) and acute myelogenous leukemia (AML) cell lines.Real-time metabolic interrogation of acute changes in cell and tumor lactate levels reflects chemotherapy effects on DNA damage, cell death and tumor growth delay. We have identified a real-time biomarker of chemotherapy effectiveness which can be used to develop adaptive, iterative and personalized treatment regimens against a variety of solid and hematopoietic malignancies.

Metabolic interrogation as a tool to optimize chemotherapeutic regimens

PubMed Central

Feng, Lei; William, William N.; Skinner, Heath D.; Myers, Jeffrey N.; Meyn, Raymond E.; Li, Jinzhong; Mijiti, Ainiwaer; Bankson, James A.; Fuller, Clifton D.; Konopleva, Marina Y.; Lai, Stephen Y.

2017-01-01

Platinum-based (Pt) chemotherapy is broadly utilized in the treatment of cancer. Development of more effective, personalized treatment strategies require identification of novel biomarkers of treatment response. Since Pt compounds are inactivated through cellular metabolic activity, we hypothesized that metabolic interrogation can predict the effectiveness of Pt chemotherapy in a pre-clinical model of head and neck squamous cell carcinoma (HNSCC). We tested the effects of cisplatin (CDDP) and carboplatin (CBP) on DNA damage, activation of cellular death cascades and tumor cell metabolism, specifically lactate production. Pt compounds induced an acute dose-dependent, transient drop in lactate generation in vitro, which correlated with effects on DNA damage and cell death. Neutralization of free radical stress abrogated these effects. The magnitude of this effect on lactate production correlated with the differential sensitivity of HNSCC cells to Pt compounds (CDDP vs CBP) and p53-driven Pt chemotherapy resistance. Using dual flank xenograft tumors, we demonstrated that Pt-driven effects on lactate levels correlate with effects on tumor growth delay in a dose-dependent manner and that lactate levels can define the temporal profile of Pt chemotherapy-induced metabolic stress. Lactate interrogation also predicted doxorubicin effects on cell death in both solid tumor (HNSCC) and acute myelogenous leukemia (AML) cell lines. Real-time metabolic interrogation of acute changes in cell and tumor lactate levels reflects chemotherapy effects on DNA damage, cell death and tumor growth delay. We have identified a real-time biomarker of chemotherapy effectiveness which can be used to develop adaptive, iterative and personalized treatment regimens against a variety of solid and hematopoietic malignancies. PMID:28184025

Osteoporosis treatment: recent developments and ongoing challenges

PubMed Central

Khosla, Sundeep; Hofbauer, Lorenz C

2018-01-01

Osteoporosis is an enormous and growing public health problem. Once considered an inevitable consequence of ageing, it is now eminently preventable and treatable. Ironically, despite tremendous therapeutic advances, there is an increasing treatment gap for patients at high fracture risk. In this Series paper, we trace the evolution of drug therapy for osteoporosis, which began in the 1940s with the demonstration by Fuller Albright that treatment with oestrogen could reverse the negative calcium balance that developed in women after menopause or oophorectomy. We note a watershed in osteoporosis drug discovery around the year 2000, when the approach to developing novel therapeutics shifted from one driven by discoveries in animal studies and clinical observations (eg, oestrogen, calcitonin, and teriparatide) or opportunistic repurposing of existing compounds (eg, bisphosphonates) to one driven by advances in fundamental bone biology (eg, denosumab) coupled with clues from patients with rare bone diseases (eg, romosozumab, odanacatib). Despite these remarkable advances, concerns about rare side-effects of anti-resorptive drugs, particularly bisphosphonates, and the absence of clear evidence in support of their long-term efficacy is leading many patients who could benefit from drug therapy to not take these drugs. As such, there remains an important clinical need to develop ways to enhance patient acceptance and compliance with these effective drugs, and to continue to develop new drugs that do not cause these side-effects and have prolonged anabolic effects on bone. Such changes could lead to a true reversal of this potentially devastating disease of ageing. PMID:28689769

Sarcomatoid renal cell carcinoma: Biology and treatment advances.

PubMed

Mouallem, Nemer El; Smith, Steven C; Paul, Asit K

2018-06-01

Sarcomatoid transformation in renal cell carcinoma, so called sacromatoid RCC (sRCC), is associated with an aggressive behavior and a poor prognosis. Current therapeutic approaches are largely ineffective. Recent studies looking into the genomic and molecular characterization of sRCCs have provided insights into the biology and pathogenesis of this entity. These advances in molecular signatures may help development of effective treatment strategies. We herein present a review of recent developments in the pathology, biology, and treatment modalities in sRCC. Copyright © 2017 Elsevier Inc. All rights reserved.