Commencement on a Coral Reef

ERIC Educational Resources Information Center

Webster, Steven K.

1973-01-01

Describes an environmental program in which sixteen students and three biology teachers from Northfield Mount Hermon School in Massachusetts spent two weeks examining the ecology of a Caribbean reef.. (JR)

Gold-Based Medicine: A Paradigm Shift in Anti-Cancer Therapy?

PubMed

Yeo, Chien Ing; Ooi, Kah Kooi; Tiekink, Edward R T

2018-06-11

A new era of metal-based drugs started in the 1960s, heralded by the discovery of potent platinum-based complexes, commencing with cisplatin [(H₃N)₂PtCl₂], which are effective anti-cancer chemotherapeutic drugs. While clinical applications of gold-based drugs largely relate to the treatment of rheumatoid arthritis, attention has turned to the investigation of the efficacy of gold(I) and gold(III) compounds for anti-cancer applications. This review article provides an account of the latest research conducted during the last decade or so on the development of gold compounds and their potential activities against several cancers as well as a summary of possible mechanisms of action/biological targets. The promising activities and increasing knowledge of gold-based drug metabolism ensures that continued efforts will be made to develop gold-based anti-cancer agents.

Nepalese patients’ perceptions of treatment modalities for type 2 diabetes

PubMed Central

Sapkota, Sujata; Brien, Jo-anne E; Aslani, Parisa

2016-01-01

Background Perceptions and beliefs about treatment can influence patients’ adherence to treatment regimens. Perceptions, in turn, are often shaped by patients’ sociocultural context. Nepal and the Nepalese have unique sociocultural traditions and beliefs, and their perceptions of diabetes treatment remain largely unexplored. This study explored Nepalese participants’ perceptions of diabetes treatment, and whether perceptions differed between the Nepalese living in Australia and Nepal. Methods Face-to-face qualitative interviews (n=48) were conducted with Nepalese participants with type 2 diabetes in Sydney and Kathmandu. All interviews were audio-recorded, transcribed verbatim, and thematically analyzed. Results Perceptions of diabetes treatment were similar among Nepalese participants in Australia and Nepal. There was a general reluctance to start oral antidiabetic medications and an even greater reluctance to commence parenteral (insulin) therapy. Participants preferred to try lifestyle modifications and alternative treatments such as herbs and “traditional” medicines, particularly as a first step. Unwillingness to take medications was primarily associated with the belief that, once started, these medications needed to be taken for life, and perceptions of long-term harms caused by such medications. Even when commenced on medication, participants were averse to any type of therapy escalation, for example, moving to insulin therapy. Insulin was perceived as the “last option” available for diabetes treatment. Most participants, however, did not find medication taking challenging once they had commenced treatment. Conclusion Antidiabetic medications were perceived to be harmful and unstoppable once initiated. These perceptions significantly impacted participants’ willingness to commence antidiabetic medications and therefore have the potential to adversely affect their medication-taking behavior. This study therefore highlights the need to explore the impact of these perceptions on participants’ medication-taking behavior, and the need to address patients’ views of “modern” (commonly prescribed) and “traditional” (natural) medications through information and education, to ensure increased understanding of how medications are used for diabetes management. PMID:27695296

Changes in stress and burden in families seeking therapy following traumatic brain injury: a follow-up study.

PubMed

Perlesz, A; O'Loughlan, M

1998-12-01

The current project is a preliminary investigation of changes in levels of distress and burden and family and marital adjustment in families following traumatic brain injury (TBI), replicating measures-used in the earlier Glasgow, TBI outcome research on relatives' stress and burden. Fifteen families (32 individuals) seeking family counselling in a publicly funded family therapy centre were monitored over a two year period: prior to commencing counselling; 12 months following the commencement of counselling; and 24 months following the commencement of counselling. The most significant and sustained changes in psychosocial outcome were a decrease in distress for both individuals with TBI and their carers as well as a reduction in relatives' burden and strain. Family conflict also reduced, just as family cohesion increased and adjustment within the family unit improved from pre-therapy to the time of follow-up 24 months later. However, reported levels of anger, despite significantly reducing during the first 12 months of the study, actually increased back to their original levels at the 24 month follow-up. Marital adjustment also worsened in the latter half of the study, with couples reporting a similar level of marital adjustment to that which they had experienced prior to counselling. These findings are discussed and recommendations made for more rigorous, controlled, longitudinal studies of the effectiveness of family therapy. It was also recommended that marital couples receive longer-term counselling to address their specific needs, and that the issue of anger be further investigated with a view to either reducing family members' anger, or bearing witness to the legitimacy of their anger in the longer-term, and assisting with anger-management programmes.

Evaluation of screening methods for identification of patients with chronic rheumatological disease requiring tuberculosis chemoprophylaxis prior to commencement of TNF-α antagonist therapy.

PubMed

Singanayagam, Aran; Manalan, Kavina; Sridhar, Saranya; Molyneaux, Philip L; Connell, David W; George, Peter M; Kindelerer, Anne; Seneviratne, Suranjith; Lalvani, Ajit; Wickremasinghe, Melissa; Kon, Onn Min

2013-10-01

Patients undergoing tumour necrosis factor (TNF)-α antagonist therapy are at increased risk of latent tuberculosis infection (LTBI) reactivation. The aim of this study was to determine the optimum available screening strategy for identifying patients for tuberculosis (TB) chemoprophylaxis. We conducted a prospective observational study of consecutive adults with chronic rheumatological disease referred for LTBI screening prior to commencement of TNF-α antagonist therapy. All patients included had calculation of TB risk according to age, ethnicity and year of UK entry, as described in the 2005 British Thoracic Society (BTS) guidelines and measurement of tuberculin skin test (TST) and T.Spot.TB. There were 187 patients included in the study, with 157 patients (84%) taking immunosuppressants. 137 patients would require further risk stratification according to the BTS algorithm, with 110 (80.3%) classified as being at low risk of having LTBI. There were 39 patients (35.5%) who were categorised as low risk but were either TST and/or T.Spot positive and would not have received chemoprophylaxis according to the BTS algorithm. Combination of all three methods (risk stratification and/or positive T.Spot and/or positive TST) identified 66 patients out of 137 who would potentially be offered chemoprophylaxis, which was greater than any single test or two-test combination. Performing both a TST and T.Spot in patients on immunosuppressants prior to commencement of TNF-α antagonist therapy gives an additional yield of potential LTBI compared with use of risk stratification tables alone. Our results suggest that use of all three screening modalities gives the highest yield of patients potentially requiring chemoprophylaxis.

Brief coping strategy enhancement for distressing voices: Predictors of engagement and outcome in routine clinical practice.

PubMed

Paulik, Georgie; Jones, Anna-Marie; Hayward, Mark

2018-05-24

Cognitive behaviour therapy is recommended internationally as a treatment for psychosis (targeting symptoms such as auditory hallucinations, or "voices"). Yet mental health services are commonly unable to offer such resource-intensive psychological interventions. Brief, symptom-specific and less resource-intensive therapies are being developed as one initiative to increase access. However, as access increases, so might the risk of offering therapy to clients who are not optimally disposed to engage with and benefit from therapy. Thus, it is important to identify who is most/least likely to engage with and benefit from therapy, and when. In the current study, 225 clients were assessed for suitability for a brief, 4-session, manualized, cognitive behaviour therapy-based intervention for voices (named coping strategy enhancement therapy) and 144 commenced therapy, at a transdiagnostic voices clinic based in Sussex, UK. This article reports on the value of depression, anxiety, stress, insight into the origin of voices, length of voice hearing, and demographics in the prediction of engagement and outcomes. The study found that higher levels of baseline depression, anxiety, and stress were significantly associated with poorer outcomes, especially if clients also had high levels of voice-related distress. The engagement analyses showed that levels of voice-related distress at baseline predicted dropout. These findings highlight the importance of assessing negative affect and voice-related distress prior to commencing therapy for distressing voices, to help determine if the client is suitable or ready for brief-coping strategy enhancement. Copyright © 2018 John Wiley & Sons, Ltd.

Premature ovarian insufficiency in young girls: repercussions on uterine volume and bone mineral density.

PubMed

Bakhsh, Hanadi; Dei, Metella; Bucciantini, Sandra; Balzi, Daniela; Bruni, Vincenzina

2015-01-01

To evaluate biological differences among young subjects with premature ovarian insufficiency (POI) commencing at different stages of life. Retrospective observational study. Careggi University Hospital Participants: One hundred sixty-two females aged between 15 and 29 years with premature ovarian insufficiency. Data were collected as a retrospective chart review of baseline evaluation at diagnosis of premature ovarian insufficiency (POI). About 162 participants were divided into four groups based on gynecological age. Two primary outcome variables (uterine development and bone mineral density (BMD)) were analyzed in terms of differences among groups and in a multivariate logistic regression analysis. Uterine development was clearly jeopardized when estrogen insufficiency started at a very young age. Total body BMD showed significant differences among the four groups studied, clearly corresponding to the duration of ovarian function. Data were discussed in relation to the choice of hormone replacement therapy regimens.

New Prescriptions for Migraine in the Emergency Department

PubMed Central

Lane, Peter L.

1992-01-01

Migraine headache is a common affliction and presenting symptom in the emergency department. Its diagnosis is entirely clinical, and the treating physician should ensure precise diagnosis before commencing therapy. General non-pharmacological measures and oral medications are usually effective in relieving the symptoms. Occasionally, patients with fixed migraines require parenteral therapy. Some medications used for migraine are antiemetic agents, ergot preparations, narcotic agents, phenothiazines (particularly chlorpromazine), and newer selective serotonin agonists. PMID:21221402

Commencement Bay Nearshore/Tideflats Superfund Site, Tacoma, Washington Remedial Investigations. Decisionmaking Framework for Management of Dredged Material: Application to Commencement Bay, Washington. Methods and Sites, and Site Control and Treatment Practices.

DTIC Science & Technology

1985-02-01

impacts in the receiving wator. This r,(-’ y approp-.e: fcan Lo fromI nuwer of’ al--;.3c toxi * to ut u p&ce n- the toxt ?it!; *~<. the reference toxicity...California, Los Angeles; Dr. N. Beyer, US Fish and Wildlife Ser- vice; Dr. F. Bingham, University of California, Riverside; Dr. G. Bryan, Marine Biological...P 77. - 7107 -7 - Y -7 7 ~ ’ -F 7..Yr F7 V. -7 - - LIST OF FIGURES No. Page I Management strategy flowchart ...... ................. ... 20 2 Modified

Adjuvant sunitinib following chemoradiotherapy and surgery for locally advanced esophageal cancer: a phase II trial.

PubMed

Horgan, A M; Darling, G; Wong, R; Guindi, M; Liu, G; Jonker, D J; Lister, J; Xu, W; MacKay, H M; Dinniwell, R; Kim, J; Pierre, A; Shargall, Y; Asmis, T R; Agboola, O; Seely, A J; Ringash, J; Wells, J; Marginean, E C; Haider, M; Knox, J J

2016-11-01

The prognosis for locally advanced esophageal cancer is poor despite the use of trimodality therapy. In this phase II study, we report the feasibility, tolerability and efficacy of adjuvant sunitinib. Included were patients with stage IIa, IIB or III cancer of the thoracic esophagus or gastroesophageal junction. Neoadjuvant therapy involved Irinotecan (65 mg/m 2 ) + Cisplatin (30 mg/m 2 ) on weeks 1 and 2, 4 and 5, 7 and 8 with concurrent radiation (50Gy/25 fractions) on weeks 4-8. Sunitinib was commenced 4-13 weeks after surgery and continued for one year. Sixty-one patients were included in the final analysis, 36 patients commenced adjuvant sunitinib. Fourteen patients discontinued sunitinib due to disease recurrence (39%) within the 12-month period, 12 (33%) discontinued due to toxicity, and 3 (8%) requested cessation of therapy. In the overall population, median survival was 26 months with a 2 and 3-year survival rate of 52% and 35%, respectively. The median survival for the 36 patients treated with sunitinib was 35 months and 2-year survival probability of 68%. In a historical control, a prior phase II study with the same trimodality therapy (n = 43), median survival was 36 months, with a 2-year survival of 67%. Initiation of adjuvant sunitinib is feasible, but poorly tolerated, with no signal of additional benefit over trimodality therapy for locally advanced esophageal cancer. © 2015 International Society for Diseases of the Esophagus.

Does early use of enzyme replacement therapy alter the natural history of mucopolysaccharidosis I? Experience in three siblings.

PubMed

Laraway, Sarah; Breen, Catherine; Mercer, Jean; Jones, Simon; Wraith, James E

2013-07-01

Enzyme replacement therapy is widely used as treatment for mucopolysaccharidosis I (MPS I), and there is evidence that this produces improvement in certain clinical domains. There does appear to be variation in the response of clinical features to treatment once these are established. In a reported sibling pair, when enzyme replacement therapy was commenced pre-symptomatically in the younger child, the natural history of the condition appeared to be affected. We present data from three siblings treated with enzyme replacement therapy at different ages which supports this finding. Copyright © 2013 Elsevier Inc. All rights reserved.

Prospective trial of pelvic floor retraining in patients with fecal incontinence.

PubMed

Rieger, N A; Wattchow, D A; Sarre, R G; Cooper, S J; Rich, C A; Saccone, G T; Schloithe, A C; Toouli, J; McCall, J L

1997-07-01

Our aim was to prospectively evaluate pelvic floor retraining (PFR) in improving symptomatic fecal incontinence. PFR was used to treat 30 patients with fecal incontinence (28 women; age range, 29-85 (median, 68) years). PFR was performed by a physiotherapist in the outpatient department according to a strict protocol and included biofeedback using an anal plug electromyometer. Manometry (24 patients), pudendal nerve terminal motor latency (PNTML, 16 patients), and anal ultrasound (14 patients) were done before commencing therapy. Independent assessment of symptoms was done at the commencement of therapy, at 6 weeks, and at 6 and 12 months posttherapy. Twenty patients (67 percent) had improved incontinence scores, with eight patients (27 percent) being completely or nearly free of symptoms. Of 28 patients followed up longer than six months, 14 achieved a 25 percent or greater improvement at six weeks, which was sustained in all cases. Fourteen had an initial improvement of less than 25 percent, with only four (29 percent) showing later improvement (P < 0.0001). There was no relationship between results of the therapy and patient age, initial severity of symptoms, etiology of incontinence, and results of anal manometry, PNTML, and anal ultrasound. PFR is a physical therapy that should be considered as the initial treatment in patients with fecal incontinence. An improvement can be expected in up to 67 percent of patients. Initial good results can predict overall outcome.

Advances in Radiotherapy Management of Esophageal Cancer.

PubMed

Verma, Vivek; Moreno, Amy C; Lin, Steven H

2016-10-21

Radiation therapy (RT) as part of multidisciplinary oncologic care has been marked by profound advancements over the past decades. As part of multimodality therapy for esophageal cancer (EC), a prime goal of RT is to minimize not only treatment toxicities, but also postoperative complications and hospitalizations. Herein, discussion commences with the historical approaches to treating EC, including seminal trials supporting multimodality therapy. Subsequently, the impact of RT techniques, including three-dimensional conformal RT, intensity-modulated RT, and proton beam therapy, is examined through available data. We further discuss existing data and the potential for further development in the future, with an appraisal of the future outlook of technological advancements of RT for EC.

Advances in Radiotherapy Management of Esophageal Cancer

PubMed Central

Verma, Vivek; Moreno, Amy C.; Lin, Steven H.

2016-01-01

Radiation therapy (RT) as part of multidisciplinary oncologic care has been marked by profound advancements over the past decades. As part of multimodality therapy for esophageal cancer (EC), a prime goal of RT is to minimize not only treatment toxicities, but also postoperative complications and hospitalizations. Herein, discussion commences with the historical approaches to treating EC, including seminal trials supporting multimodality therapy. Subsequently, the impact of RT techniques, including three-dimensional conformal RT, intensity-modulated RT, and proton beam therapy, is examined through available data. We further discuss existing data and the potential for further development in the future, with an appraisal of the future outlook of technological advancements of RT for EC. PMID:27775643

Uveitis associated with juvenile idiopathic arthritis.

PubMed

Sen, Ethan S; Dick, Andrew D; Ramanan, Athimalaipet V

2015-06-01

Uveitis is a potentially sight-threatening complication of juvenile idiopathic arthritis (JIA). JIA-associated uveitis is recognized to have an autoimmune aetiology characterized by activation of CD4(+) T cells, but the underlying mechanisms might overlap with those of autoinflammatory conditions involving activation of innate immunity. As no animal model recapitulates all the features of JIA-associated uveitis, questions remain regarding its pathogenesis. The most common form of JIA-associated uveitis is chronic anterior uveitis, which is usually asymptomatic initially. Effective screening is, therefore, essential to detect early disease and commence treatment before the development of visually disabling complications, such as cataracts, glaucoma, band keratopathy and cystoid macular oedema. Complications can result from uncontrolled intraocular inflammation as well as from its treatment, particularly prolonged use of high-dose topical corticosteroids. Accumulating evidence supports the early introduction of systemic immunosuppressive drugs, such as methotrexate, as steroid-sparing agents. Prospective randomized controlled trials of TNF inhibitors and other biologic therapies are underway or planned. Future research should aim to identify biomarkers to predict which children are at high risk of developing JIA-associated uveitis or have a poor prognosis. Such biomarkers could help to ensure that patients receive earlier interventions and more-potent therapy, with the ultimate aim of reducing loss of vision and ocular morbidity.

Evaluation of Therapy Management and Patient Compliance in Postmenopausal Patients with Hormone Receptor-positive Breast Cancer Receiving Letrozole Treatment: The EvaluateTM Study

PubMed Central

Fasching, P. A.; Fehm, T.; Kellner, S.; de Waal, J.; Rezai, M.; Baier, B.; Baake, G.; Kolberg, H.-C.; Guggenberger, M.; Warm, M.; Harbeck, N.; Würstlein, R.; Deuker, J.-U.; Dall, P.; Richter, B.; Wachsmann, G.; Brucker, C.; Siebers, J. W.; Fersis, N.; Kuhn, T.; Wolf, C.; Vollert, H.-W.; Breitbach, G.-P.; Janni, W.; Landthaler, R.; Kohls, A.; Rezek, D.; Noesslet, T.; Fischer, G.; Henschen, S.; Praetz, T.; Heyl, V.; Kühn, T.; Krauß, T.; Thomssen, C.; Kümmel, S.; Hohn, A.; Tesch, H.; Mundhenke, C.; Hein, A.; Rauh, C.; Bayer, C. M.; Jacob, A.; Schmidt, K.; Belleville, E.; Hadji, P.; Wallwiener, D.; Grischke, E.-M.; Beckmann, M. W.; Brucker, S. Y.

2014-01-01

Introduction: The EvaluateTM study (Evaluation of therapy management and patient compliance in postmenopausal hormone receptor-positive breast cancer patients receiving letrozole treatment) is a prospective, non-interventional study for the assessment of therapy management and compliance in the routine care of postmenopausal women with invasive hormone receptor-positive breast cancer receiving letrozole. The parameters for inclusion in the study are presented and discussed here. Material and Methods: Between January 2008 and December 2009 a total of 5045 patients in 310 study centers were recruited to the EvaluateTM study. Inclusion criteria were hormone receptor-positive breast cancer and adjuvant treatment or metastasis. 373 patients were excluded from the analysis for various reasons. Results: A total of 4420 patients receiving adjuvant treatment and 252 patients with metastasis receiving palliative treatment were included in the study. For 4181 patients receiving adjuvant treatment, treatment with the aromatase inhibitor letrozole commenced immediately after surgery (upfront). Two hundred patients had initially received tamoxifen and started aromatase inhibitor treatment with letrozole at 1–5 years after diagnosis (switch), und 39 patients only commenced letrozole treatment 5–10 years after diagnosis (extended endocrine therapy). Patient and tumor characteristics were within expected ranges, as were comorbidities and concurrent medication. Conclusion: The data from the EvaluateTM study will offer a good overview of therapy management in the routine care of postmenopausal women with hormone receptor-positive breast cancer. Planned analyses will look at therapy compliance and patient satisfaction with how information is conveyed and the contents of the conveyed information. PMID:25568468

Increased risk of SSEs in bone-only metastatic breast cancer patients treated with zoledronic acid.

PubMed

Yanae, Masashi; Fujimoto, Shinichiro; Tane, Kaori; Tanioka, Maki; Fujiwara, Kimiko; Tsubaki, Masanobu; Yamazoe, Yuzuru; Morishima, Yoshiyuki; Chiba, Yasutaka; Takao, Shintaro; Komoike, Yoshifumi; Tsurutani, Junji; Nakagawa, Kazuhiko; Nishida, Shozo

2017-09-01

Bone represents one of the most common sites to which breast cancer cells metastasize. Patients experience skeletal related adverse events (pathological fractures, spinal cord compressions, and irradiation for deteriorated pain on bone) even during treatment with zoledronic acid (ZA). Therefore, we conducted a retrospective cohort study to investigate the predictive factors for symptomatic skeletal events (SSEs) in bone-metastasized breast cancer (b-MBC) patients. We retrospectively collected data on b-MBC patients treated with ZA. Patient characteristics, including age, subtype, the presence of non-bone lesions, the presence of multiple bone metastases at the commencement of ZA therapy, duration of ZA therapy, the time interval between breast cancer diagnosis and the initiation of ZA therapy, and type of systemic therapy, presence of previous SSE were analyzed using multivariable logistic regression analysis. The medical records of 183 patients were reviewed and 176 eligible patients were analyzed. The median age was 59 (range, 30-87) years. Eighty-seven patients were aged ≥60 years and 89 patients were aged < 60 years. The proportions of patients with estrogen receptor, progesterone receptor, and human epidermal growth factor receptor 2-positive disease were 81.8%, 63.1%, and 17.6%, respectively. Fifty-three patients had bone-only MBC at the commencement of ZA therapy. SSEs were observed in 42 patients. In the multivariable logistic regression analysis, bone-only MBC but not a breast cancer subtype was an independent risk factor for an SSE during ZA therapy (odds ratio: 3.878, 95% confidence interval: 1.647-9.481; p = 0.002). Bone-only MBC patients are more likely to experience an SSE even after treatment with ZA.

Student Conceptions about Energy Transformations: Progression from General Chemistry to Biochemistry

ERIC Educational Resources Information Center

Wolfson, Adele J.; Rowland, Susan L.; Lawrie, Gwendolyn A.; Wright, Anthony H.

2014-01-01

Students commencing studies in biochemistry must transfer and build on concepts they learned in chemistry and biology classes. It is well established, however, that students have difficulties in transferring critical concepts from general chemistry courses; one key concept is "energy." Most previous work on students' conception of energy…

Time-lapse cinemicroscopy.

PubMed

Riddle, P N

1990-01-01

Cinematography commenced as a scientific technique used as a system for "slowing down" observed movement. Marey in 1888 (1) constructed, following a number of other ideas, a "Chambre Chronophoto-graphique," which had practically all the elements of the modern cine camera. With this he made serial photographs (not transparencies) of various biological phenomena (2).

A retrospective comparison of infliximab versus adalimumab as induction and maintenance therapy for Crohn disease.

PubMed

Varma, P; Paul, E; Huang, C; Headon, B; Sparrow, M P

2016-07-01

In Australia, infliximab (IFX) and adalimumab (ADA) are available for the treatment of moderate-severe Crohn disease (CD) refractory to conventional therapies, with minimal local data comparing their efficacy. The aim of this study was to compare clinical and biochemical outcomes at 3 and 12 months between patients receiving induction and maintenance therapy with IFX versus ADA. Retrospective single-centre audit of all patients commenced on IFX or ADA as their first anti-tumour necrosis factor agent between July 2007 and May 2012. Clinical and biochemical parameters were compared pre-commencement, 3 and 12 months post-commencement. A total of 81 patients was included in the study; 63 IFX-treated and 18 ADA-treated. Significant Crohn disease activity index (CDAI) reductions were noted within both groups at 3 months (P < 0.001) and 12 months (P < 0.001). Similarly, significant reductions were noted in steroid doses within groups at 3 months (P < 0.05) and 12 months (P < 0.05), with notable reductions in C-reactive protein (CRP) at 3 months within groups (P < 0.05). Adverse events occurred in 14.3% of IFX and 11.1% of ADA patients. Comparing IFX with ADA, no difference was shown between groups in CDAI reductions at 3 months (P = 0.94) and 12 months (P = 0.95), steroid dosing at 3 months (P = 0.23) and 12 months (P = 0.81), and CRP reduction at 3 months (P = 0.33) and 12 months (P = 0.62). Fistula-related admissions were significantly reduced in IFX patients (100% reduction post-IFX vs 66.7% post-ADA) (P = 0.01). Clinical and biochemical outcomes were similar in patients treated with IFX or ADA as induction and maintenance therapy for CD. However, significant reductions were noted in admissions relating to fistulising disease in IFX patients. © 2016 Royal Australasian College of Physicians.

Differences in the Emotional Intelligence between Undergraduate Therapy and Business Students and the Population Norms

ERIC Educational Resources Information Center

Gribble, Nigel; Ladyshewsky, Richard K.; Parsons, Richard

2017-01-01

Students occasionally experience difficulties during work-integrated learning and clinical placements. The authors reasoned that these placement difficulties might be related to the students' emotional intelligence (EI) being underdeveloped before they commence full-time clinical placements. A cross-sectional survey design was used to measure the…

Development of sarcoidosis during adalimumab therapy for chronic plaque psoriasis.

PubMed

Marcella, Stefanie; Welsh, Belinda; Foley, Peter

2011-08-01

A 38-year-old woman developed clinical, biochemical, radiological and histopathological evidence of cutaneous and pulmonary sarcoidosis 5 months after commencing adalimumab for chronic plaque psoriasis. Signs and symptoms resolved within 3 months of cessation of adalimumab. © 2010 The Authors. Australasian Journal of Dermatology © 2010 The Australasian College of Dermatologists.

Severe infusion reactions to fabry enzyme replacement therapy: rechallenge after tracheostomy.

PubMed

Nicholls, K; Bleasel, K; Becker, G

2012-01-01

A 34-year-old male patient with Fabry disease (OMIM 301500) commenced enzyme replacement therapy (ERT) with Agalsidase alfa, with positive clinical response. Infusion reactions, initially mild and easily managed, commenced during his 13th infusion, and continued over the next 3 years. Severity of reactions subsequently increased despite very slow infusion, extended prophylactic medication and attempted desensitisation, requiring regular intensive care unit (ICU) admissions. Facial oedema and flushing, throat tightness, headache and joint pain typically occurred 4-36 h after completion of most infusions, responding rapidly to subcutaneous adrenaline. Low titre specific IgG seroconversion was noted at 12 months, with subsequent reversion to negative after 5 years, despite persistence of infusion reactions. Specific IgE and skin testing was negative. Trial of ERT product switch to Agalsidase-beta resulted in no improvement in reactions. At 5 years, ERT was ceased in the face of recurrent ICU readmissions. In the face of progressive clinical deterioration, he underwent tracheostomy to allow recommencement of ERT. Two years later, he has clinically improved on regular attenuated dose Agalsidase-beta, administered by slow infusion in a local hospital setting.

Urine metabonomic profiling of a female adolescent with PIT-1 mutation before and during growth hormone therapy: insights into the metabolic effects of growth hormone.

PubMed

Abd Rahman, Shaffinaz; Schirra, Horst Joachim; Lichanska, Agnieszka M; Huynh, Tony; Leong, Gary M

2013-01-01

Growth hormone (GH) is a protein hormone with important roles in growth and metabolism. The objective of this study was to investigate the metabolism of a human subject with severe GH deficiency (GHD) due to a PIT-1 gene mutation and the metabolic effects of GH therapy using Nuclear Magnetic Resonance (NMR)-based metabonomics. NMR-based metabonomics is a platform that allows the metabolic profile of biological fluids such as urine to be recorded, and any alterations in the profile modulated by GH can potentially be detected. Urine samples were collected from a female subject with severe GHD before, during and after GH therapy, and from healthy age- and sex-matched controls and analysed with NMR-based metabonomics. The samples were collected at a hospital and the study was performed at a research facility. We studied a 17 year old female adolescent with severe GHD secondary to PIT-1 gene mutation who had reached final adult height and who had ceased GH therapy for over 3 years. The subject was subsequently followed for 5 years with and without GH therapy. Twelve healthy age-matched female subjects acted as control subjects. The GH-deficient subject re-commenced GH therapy at a dose of 1 mg/day to normalise serum IGF-1 levels. Urine metabolic profiles were recorded using NMR spectroscopy and analysed with multivariate statistics to distinguish the profiles at different time points and identify significant metabolites affected by GH therapy. NMR-based metabonomics revealed that the metabolic profile of the GH-deficient subject altered with GH therapy and that her profile was different from healthy controls before, and during withdrawal of GH therapy. This study illustrates the potential use of NMR-based metabonomics for monitoring the effects of GH therapy on metabolism by profiling the urine of GH-deficient subjects. Further controlled studies in larger numbers of GH-deficient subjects are required to determine the clinical benefits of NMR-based metabonomics in subjects receiving GH therapy. Copyright © 2012 Elsevier Ltd. All rights reserved.

Hypopituitarism in the elderly in the presence of elevated thyroid stimulating hormone levels.

PubMed Central

Beringer, T.; McClements, B.; Weir, I.; Gilmore, D.; Kennedy, L.

1988-01-01

Two cases of primary hypothyroidism with hypopituitarism in elderly patients are reported. The elevated levels of thyroid stimulating hormone led to delay in the recognition of accompanying pituitary failure. Elderly patients should not be commenced on thyroxine replacement therapy until the possibility of hypopituitarism and cortisol deficiency has been excluded. PMID:3256811

A Dialogue among Various Cultures and Its Manifestation in Stuttering Therapy

ERIC Educational Resources Information Center

Ezrati-Vinacour, Ruth; Weinstein, Nitza

2011-01-01

This paper presents a historical retrospective of the evolution of the clinical aspects of stuttering, and refers to social, cultural, political, and economic variables that might have exerted an influence on this evolution, particularly in relation to the authors' experience in Israel. The retrospective commences in the early decades of the 20th…

Impact of dual energy characterization of urinary calculus on management.

PubMed

Habashy, David; Xia, Ryan; Ridley, William; Chan, Lewis; Ridley, Lloyd

2016-10-01

Dual energy CT (DECT) is a recent technique that is increasingly being used to differentiate between calcium and uric acid urinary tract calculi. The aim of this study is to determine if urinary calculi composition analysis determined by DECT scanning results in a change of patient management. All patients presenting with symptoms of renal colic, who had not previously undergone DECT scanning underwent DECT KUB. DECT data of all patients between September 2013 and July 2015 were reviewed. Urinary calculi composition based on dual energy characterization was cross-matched with patient management and outcome. A total of 585 DECT KUB were performed. 393/585 (67%) DECT scans revealed urinary tract calculi. After excluding those with isolated bladder or small asymptomatic renal stones, 303 patients were found to have symptomatic stone(s) as an explanation for their presentation. Of these 303 patients, there were 273 (90.1%) calcium calculi, 19 (6.3%) uric acid calculi and 11 (3.4%) mixed calculi. Of those with uric acid calculi, 15 were commenced on dissolution therapy. Twelve of those commenced on dissolution therapy had a successful outcome, avoiding need for surgical intervention (lithotripsy or stone retrieval). Three patients failed dissolution therapy and required operative intervention for definitive management of the stone. Predicting urinary tract calculi composition by DECT plays an important role in identifying patients who may be managed with dissolution therapy. Identification of uric acid stone composition altered management in 15 of 303 (5.0%) patients, and was successful in 12, thereby avoiding surgery and its attendant risks. © 2016 The Royal Australian and New Zealand College of Radiologists.

34 CFR 691.16 - Rigorous secondary school program of study.

Code of Federal Regulations, 2011 CFR

2011-07-01

...: biology, chemistry, and physics. (iv) Three years of social studies. (v) One year of a language other than... 34 Education 4 2011-07-01 2011-07-01 false Rigorous secondary school program of study. 691.16... Procedures § 691.16 Rigorous secondary school program of study. (a)(1) For each award year commencing with...

34 CFR 691.16 - Rigorous secondary school program of study.

Code of Federal Regulations, 2013 CFR

2013-07-01

...: biology, chemistry, and physics. (iv) Three years of social studies. (v) One year of a language other than... 34 Education 4 2013-07-01 2013-07-01 false Rigorous secondary school program of study. 691.16... Procedures § 691.16 Rigorous secondary school program of study. (a)(1) For each award year commencing with...

34 CFR 691.16 - Rigorous secondary school program of study.

Code of Federal Regulations, 2014 CFR

2014-07-01

...: biology, chemistry, and physics. (iv) Three years of social studies. (v) One year of a language other than... 34 Education 4 2014-07-01 2014-07-01 false Rigorous secondary school program of study. 691.16... Procedures § 691.16 Rigorous secondary school program of study. (a)(1) For each award year commencing with...

34 CFR 691.16 - Rigorous secondary school program of study.

Code of Federal Regulations, 2012 CFR

2012-07-01

...: biology, chemistry, and physics. (iv) Three years of social studies. (v) One year of a language other than... 34 Education 4 2012-07-01 2012-07-01 false Rigorous secondary school program of study. 691.16... Procedures § 691.16 Rigorous secondary school program of study. (a)(1) For each award year commencing with...

Regional survey of tuberculosis risk assessment in rheumatology outpatients commencing anti-TNF-alpha treatment in relation to British Thoracic Society guidelines.

PubMed

John, H; Buckley, C; Koh, L; Obrenovic, K; Erb, N; Rowe, I F

2009-06-01

The aim of this study was to analyse tuberculosis (TB) risk assessment for rheumatology patients commencing anti-tumour necrosis factor-alpha (anti-TNF-alpha) therapy using the British Thoracic Society (BTS) guidelines. Data were obtained retrospectively on 856 outpatients regionally receiving anti-TNF-alpha. Prior to commencing treatment, patients had the following assessments documented: respiratory examination, 47.4%; chest X-ray, 84.5%; TB history, 92.9%; and advice about TB risk, 45.8%. Of the 856 patients, 94.3% were on immunosuppressives but 27% had a tuberculin test; 12.6% had > or =1 high-risk factors for TB. In total, 3.4% were referred to a TB specialist and of these, 24.1% had no risk factors for TB. Of patients with > or =1 risk factor, 76.9% were not referred. Only 4/28 patients at high risk for TB due to ethnicity or birthplace received chemoprophylaxis. Marked inter-unit variation was demonstrated and it was evident that patients require improved screening for TB. Greater awareness is necessary of patients with risk factors, particularly ethnicity, to facilitate more appropriate targeting of chemoprophylaxis. Multi-centre audit is a valuable clinical governance tool.

Utilizing 18F-fluoroethyltyrosine (FET) positron emission tomography (PET) to define suspected nonenhancing tumor for radiation therapy planning of glioblastoma.

PubMed

Hayes, Aimee R; Jayamanne, Dasantha; Hsiao, Edward; Schembri, Geoffrey P; Bailey, Dale L; Roach, Paul J; Khasraw, Mustafa; Newey, Allison; Wheeler, Helen R; Back, Michael

2018-01-31

The authors sought to evaluate the impact of 18F-fluoroethyltyrosine (FET) positron emission tomography (PET) on radiation therapy planning for patients diagnosed with glioblastoma (GBM) and the presence of suspected nonenhancing tumors compared with standard magnetic resonance imaging (MRI). Patients with GBM and contrast-enhanced MRI scans showing regions suspicious of nonenhancing tumor underwent postoperative FET-PET before commencing radiation therapy. Two clinical target volumes (CTVs) were created using pre- and postoperative MRI: MRI fluid-attenuated inversion recovery (FLAIR) sequences (CTV FLAIR ) and MRI contrast sequences with an expansion on the surgical cavity (CTV Sx ). FET-PET was used to create biological tumor volumes (BTVs) by encompassing FET-avid regions, forming BTV FLAIR and BTV Sx . Volumetric analyses were conducted between CTVs and respective BTVs using Wilcoxon signed-rank tests. The volume increase with addition of FET was analyzed with respect to BTV FLAIR and BTV Sx . Presence of focal gadolinium contrast enhancement within previously nonenhancing tumor or within the FET-avid region was noted on MRI scans at 1 and 3 months after radiation therapy. Twenty-six patients were identified retrospectively from our database, of whom 24 had demonstrable FET uptake. The median CTV FLAIR , CTV Sx , BTV FLAIR , and BTV Sx were 57.1 mL (range, 1.1-217.4), 83.6 mL (range, 27.2-275.8), 62.8 mL (range, 1.1-307.3), and 94.7 mL (range, 27.2-285.5), respectively. When FET-PET was used, there was a mean increase in volume of 26.8% from CTV FLAIR to BTV FLAIR and 20.6% from CTV Sx to BTV Sx . A statistically significant difference was noted on Wilcoxon signed-rank test when assessing volumetric change between CTV FLAIR and BTV FLAIR (P < .0001) and CTV Sx and BTV Sx (P < .0001). Six of 24 patients (25%) with FET avidity before radiation therapy showed focal gadolinium enhancement within the radiation therapy portal. FET-PET may help improve delineation of GBM in cases with a suspected nonenhancing component. This may result in improved radiation therapy target delineation and reduce the risk of potential geographical miss. We investigated the impact of 18F-fluoroethyltyrosine (FET) positron emission tomography (PET) on radiation therapy planning for patients diagnosed with glioblastoma (GBM) and a suspected nonenhancing tumor compared with standard magnetic resonance imaging. We performed volumetric analyses between clinical target volumes and respective biological target volumes using Wilcoxon signed-rank tests. FET-PET may help improve delineation of GBM in cases with a suspected nonenhancing component and reduce the risk of potential geographical miss. Copyright © 2018 American Society for Radiation Oncology. Published by Elsevier Inc. All rights reserved.

Cerebellar degeneration following neuroleptic malignant syndrome.

PubMed Central

Lal, V.; Sardana, V.; Thussu, A.; Sawhney, I. M.; Prabhakar, S.

1997-01-01

A 55-year-old woman with a history of bipolar affective disorder developed hyperpyrexia, rigidity and depressed consciousness (neuroleptic malignant syndrome) after commencing neuroleptic therapy. On regaining consciousness, she was mute and had signs suggesting pancerebellar involvement. Hyperpyrexia, which is a cardinal feature of neuroleptic malignant syndrome, may have caused cerebellar damage. Neuroleptic malignant syndrome needs both early recognition and prompt treatment to obviate devastating complications. PMID:9519191

Telephone-Delivered Cognitive Behavioral Therapy for Chronic Pain Following Traumatic Brain Injury

DTIC Science & Technology

2013-10-01

ORGANIZATION NAME(S) AND ADDRESS(ES) University of Washington, Seattle, WA 98195 4333 AND ADDRESS(ES) 8 . PERFORMING ORGANIZATION REPORT...Medical Research and Materiel Command (USAMRMC) Office of Research Protections (ORP) Human Research Protections Office (HRPO) on August 8 , 2013... 8 subjects per month with recruitment and enrollment planned to start in Month 14. Study personnel will also commence random assignment of subjects

Treatment and therapeutic monitoring of canine hypothyroidism.

PubMed

Dixon, R M; Reid, S W J; Mooney, C T

2002-08-01

Thirty-one dogs with spontaneous hypothyroidism were treated with thyroid hormone replacement therapy (THRT) and monitored for approximately three months. Good clinical and laboratory control was ultimately achieved in all cases with a mean L-thyroxine (T4) dose of 0.026 mg/kg administered once daily. There was a significant increase and decrease in circulating total T4 and canine thyroid stimulating hormone (cTSH) concentrations, respectively, after starting THRT. After commencing treatment, 11 cases subsequently required an increase and three cases required a decrease in dose to achieve optimal clinical control. Median (semi interquartile range [SIR]) circulating six-hour post-pill total T4 (53.6 [27.91 nmol/litre) and cTSH (0.03 [0] microg/litre) concentrations were significantly increased and decreased, respectively, in treated dogs that did not require a dose change; corresponding values in treated dogs in which an increase in dose was required were 29.3 (12.7) nmol/litre and 0.15 (0.62) microg/litre, respectively. However, circulating cTSH measurement was of limited value in assessing therapeutic control because, although increased values were associated with inadequate therapy, reference range cTSH values were common in inadequately treated dogs. Lethargy and mental demeanour were typically the first clinical signs to improve, with significant bodyweight reduction occurring within two weeks of commencing THRT. Routine clinicopathological monitoring was of value in confirming a general metabolic response to THRT, but was of limited value in accurately monitoring cases or tailoring therapy in individual cases.

Practical approaches to commencing device-assisted therapies for Parkinson disease in Australia.

PubMed

Williams, David R; Evans, Andrew H; Fung, Victor S C; Hayes, Michael; Iansek, Robert; Kimber, Thomas; O'Sullivan, John D; Sue, Carolyn M

2017-10-01

In Australia 1% of individuals aged over 50 years have Parkinson disease (PD). Guidance for commencing device-assisted therapies (DAT) for PD in Australia was developed based on a review of European recommendations and their relevance to the local clinical setting. An online survey and teleconference discussions were held by a group of eight local movement disorder experts to develop consensus. Referral to a movement disorder specialist and consideration of DAT is appropriate when motor fluctuations cause disability or reduced quality of life, response to treatment is inconsistent or motor fluctuations and dyskinesias require frequent treatment adjustment without apparent benefit and levodopa is required four or more times daily. Three types of DAT are available in Australia for patients with PD: continuous subcutaneous apomorphine; continuous levodopa-carbidopa intestinal gel infusion; and deep brain stimulation. All improve consistency of motor response. The most important aspects when considering which DAT to use are the preferences of the patient and their carers, patient comorbidities, age, cognitive function and neuropsychiatric status. Patients and their families need to be provided with treatment options that are suitable to them, with adequate explanations regarding the recommendations and comparison of potential device-related complications. DAT are best managed, where possible, in a specialist centre with experience in all three types of therapy. Proactive and early management of symptoms during disease progression is essential to maintain optimally motor responses and quality of life in patients with PD. © 2017 Royal Australasian College of Physicians.

The impact of Asian American value systems on palliative care: illustrative cases from the family-focused grief therapy trial.

PubMed

Mondia, Stephen; Hichenberg, Shira; Kerr, Erica; Eisenberg, Megan; Kissane, David W

2012-09-01

Clinicians meet people from different ethnic backgrounds, yet need to respond in culturally sensitive ways. This article focuses on Asian American families. Within a randomized controlled trial of family therapy commenced during palliative care and continued into bereavement, 3 families of Asian American background were examined qualitatively from a cultural perspective by listening to recordings of 26 therapy sessions and reviewing detailed supervision notes compiled by each therapist. A synopsis of each family's therapy narrative is presented. Prominent themes include family closeness, respect for hierarchy within the family, gender-determined roles, intergenerational tensions, preoccupation with shame and limited emotional expressiveness. Family therapists working with culturally diverse families need to pay thoughtful attention to ethnic issues as they strive to support them during palliative care and bereavement.

Management of Gout in a Hospital Setting: A Lost Opportunity.

PubMed

Wright, Sarah; Chapman, Peter T; Frampton, Christopher; O'Donnell, John L; Raja, Rafi; Stamp, Lisa K

2017-10-01

Management of gout is frequently suboptimal. The aim of this study was to determine the proportion of patients presenting to Christchurch Hospital for a gout flare and to determine whether management for both acute flares and urate lowering was in accordance with international recommendations. A retrospective audit was undertaken of all admissions to Christchurch Hospital from June 1, 2013, to May 31, 2014, in which gout was coded as a primary or secondary discharge diagnosis. Information including demographics, comorbidities, concomitant medications, treatment of acute gout, and urate lowering was collected. A total of 235 acute admissions for gout in 216 individuals were identified. Eleven individuals had 2 admissions and 4 individuals had 3 admissions. In 95/235 admissions (40.4%), gout was the primary diagnosis. Gout accounted for 95/77,321 (0.12%) of acute admissions. The treatment of acute gout was prednisone monotherapy in 170/235 (72.3%) of admissions. Serum urate was measured at some point during 123/235 (52.3%) of admissions, with only 19/123 (15.4%) at target urate level (< 0.36 mmol/l). At 60 of the 235 admissions, urate-lowering therapy was already being prescribed. Nine out of 175 patients (5.1%) not treated with urate-lowering therapy at admission commenced allopurinol and 32/174 (18.4%) had commencement of urate-lowering therapy recommended in the discharge plan. Rates of admission for gout are similar to that observed in other studies. Failure to initiate, change, or recommend alterations in urate-lowering therapy to achieve target urate in people with gout admitted to hospital represents a significant lost opportunity to improve longterm gout management.

Experiences from an interprofessional student-assisted chronic disease clinic.

PubMed

Frakes, Kerrie-Anne; Brownie, Sharon; Davies, Lauren; Thomas, Janelle; Miller, Mary-Ellen; Tyack, Zephanie

2014-11-01

Faced with significant health and workforce challenges in the region, the Central Queensland Health Service District (CQHSD) commenced a student-assisted clinical service. The Capricornia Allied Health Partnership (CAHP) is an interprofessional clinical placement program in which pre-entry students from exercise physiology, nutrition and dietetics, occupational therapy, pharmacy, podiatry and social work are embedded in a collaborative chronic disease service delivery model. The model coordinates multiple student clinical placements to: address service delivery gaps for previously underserved people with chronic disease in need of early intervention and management; provide an attractive clinical placement opportunity for students that will potentially lead to future recruitment success, and demonstrate leadership in developing future health workforce trainees to attain appropriate levels of interprofessional capacity. The CAHP clinic commenced student placements and client services in February 2010. This report provides early evaluative information regarding student experiences included self-reported changes in practice.

Does the addition of visceral manipulation improve outcomes for patients with low back pain? Rationale and study protocol.

PubMed

Panagopoulos, John; Hancock, Mark; Ferreira, Paulo

2013-07-01

There has been no randomised controlled trial conducted to investigate the effectiveness of visceral manipulation (VM) for the treatment of low back pain (LBP). The primary aim of this study would be to investigate whether the addition of VM, to a standard physiotherapy treatment regimen, improves pain 6 weeks post treatment commencement in people with LBP. Secondary aims would be to examine the effect of VM on disability and functional outcomes at 2, 6 and 52 weeks post-treatment commencement and pain at 2 and 52 weeks. This paper describes the rationale and design of a randomised controlled trial investigating the addition of VM to a standard physiotherapy treatment algorithm which includes manual therapy, specific exercise and functional exercise prescription. Analysis of data would be carried out by a statistician blinded to group allocation and by intention-to-treat. Copyright © 2013 Elsevier Ltd. All rights reserved.

Physical Activity Patterns of Acute Stroke Patients Managed in a Rehabilitation Focused Stroke Unit

PubMed Central

2013-01-01

Background. Comprehensive stroke unit care, incorporating acute care and rehabilitation, may promote early physical activity after stroke. However, previous information regarding physical activity specific to the acute phase of stroke and the comprehensive stroke unit setting is limited to one stroke unit. This study describes the physical activity undertaken by patients within 14 days after stroke admitted to a comprehensive stroke unit. Methods. This study was a prospective observational study. Behavioural mapping was used to determine the proportion of the day spent in different activities. Therapist reports were used to determine the amount of formal therapy received on the day of observation. The timing of commencement of activity out of bed was obtained from the medical records. Results. On average, patients spent 45% (SD 25) of the day in some form of physical activity and received 58 (SD 34) minutes per day of physiotherapy and occupational therapy combined. Mean time to first mobilisation out of bed was 46 (SD 32) hours post-stroke. Conclusions. This study suggests that commencement of physical activity occurs earlier and physical activity is at a higher level early after stroke in this comprehensive stroke unit, when compared to studies of other acute stroke models of care. PMID:24024192

The Influence of Race and Comorbidity on the Timely Initiation of Antiretroviral Therapy Among Older Persons Living With HIV/AIDS

PubMed Central

Smith, Lerissa; Zhang, Shun; Fairchild, Amanda J.; Heiman, Harry J.; Rust, George

2014-01-01

Objectives. We examined whether the timely initiation of antiretroviral therapy (ART) differed by race and comorbidity among older (≥ 50 years) people living with HIV/AIDS (PLWHA). Methods. We conducted frequency and descriptive statistics analysis to characterize our sample, which we drew from 2005–2007 Medicaid claims data from 14 states. We employed univariate and multivariable Cox regression analyses to evaluate the relationship between race, comorbidity, and timely ART initiation (≤ 90 days post-HIV/AIDS diagnosis). Results. Approximately half of the participants did not commence ART promptly. After we adjusted for covariates, we found that older PLWHA who reported a comorbidity were 40% (95% confidence interval = 0.26, 0.61) as likely to commence ART promptly. We found no racial differences in the timely initiation of ART among older PLWHA. Conclusions. Comorbidities affect timely ART initiation in older PLWHA. Older PLWHA may benefit from integrating and coordinating HIV care with care for other comorbidities and the development of ART treatment guidelines specific to older PLWHA. Consistent Medicaid coverage helps ensure consistent access to HIV treatment and care and may eliminate racial disparities in timely ART initiation among older PLWHA. PMID:25211735

Reducing the cost of dissociative identity disorder: Measuring the effectiveness of specialized treatment by frequency of contacts with mental health services.

PubMed

Lloyd, Mike

2016-01-01

It is important to understand and record the impact of therapy on severe mental health conditions through the use of clinical assessment measures. In this article, I propose to extend outcome evaluation by measuring service use and cost prior to and during the commencement of psychological therapy over a period of 4 years for 2 people diagnosed with dissociative identity disorder. The treatment was provided within an outpatient setting in a U.K. National Health Service hospital trust following therapeutic guidelines set out by the International Society for the Study of Trauma and Dissociation. Results show that service use in both inpatient and out-of-hours crisis services reduced as the 2 people received therapy over the 4-year time period. Based on these 2 cases, it appears to be cost effective to provide specialized therapy for dissociative identity disorder in outpatient settings.

Physical therapy intervention for an adolescent with a knee flexion contracture and diagnosis of multiple pterygium syndrome.

PubMed

Bellamy, Sandra Gail; Gibbs, Karen; Lazaro, Rolando

2007-01-01

The purpose of this case report is to describe a course of physical therapy for a client with a rare genetic condition, multiple pterygium syndrome (MPS). MPS is a rare genetic disorder characterized by connective tissue webbing across multiple joints, dysmorphic facies, and various visceral and skeletal deformities. Before the patient commenced physical therapy, surgical amputation was recommended for the client's knee flexion contracture. The client's treatment plan included stretching, manual therapy, and resisted exercise. Long-term outcomes were decreased back and knee pain and improved range of motion, strength, and ambulation. Therapists using techniques to improve joint range of motion in clients with MPS should be aware that pterygia may include contractile tissue, nerves, and blood vessels and there may be underlying skeletal deformity or weakness in these areas. Children with MPS are at high risk of developing scoliosis and should be appropriately assessed in early childhood.

Biological Testing of Solid Phase and Suspended Phase Dredged Material from Commencement Bay, Tacoma, Washington

DTIC Science & Technology

1983-04-01

BAY, TACOMA, WASHINGTON PREPARED BY: FISHERIES RESEARCH INSTITUTE University of Washington DTIC C. A ELECTE JUL11 1985 DISTRIBUTIONSTATEMENT A...Nakatani 9. PERFORMING ORGANIZATION NAME AND ADDRESS 10. PROGRAM ELEMENT. PROJECT, TASK Fisheries Research Institute AREA & WORK UNIT NUMBERS School of... Fisheries WH-10 University of Washington Seattle, Washington 98195 11. CONTROLLING OFFICE NAME AND ADDRESS 12. REPORT DATE US Army Corps of Engineers

Preclinical Validation of Novel Fluorescently Labeled Compounds to Treat Neurodegenerative Hearing Loss

DTIC Science & Technology

2016-10-01

evaluated using 209, 639, and 1269 magnification. For repre- sentative documentation of the morphology of each specimen, the photographs were taken from the...Holmes SJ, Kaplan SL, Jubelirer DP, Stechenberg BW, Hirsh SK (1984) Prospective evaluation of hearing impairment as a sequela of acute bacterial...enters the field of gene therapy and human studies commence, the question arises whether audiograms e the current gold standard for the evaluation of

Bravemind: Advancing the Virtual Iraq/Afghanistan PTSD Exposure Therapy for MST

DTIC Science & Technology

2015-06-01

threatened death, serious injury or sexual violation. Military Sexual Trauma (MST) has been recognized as a significant risk factor for the...development of PTSD. This has become an issue of grave concern within the military, as reports of sexual violations and assaults have been on the rise over the...far, the system was built and delivered and the RCT has commenced. 15. SUBJECT TERMS PTSD, Virtual Reality, Prolonged Exposure, Military Sexual

Exploring the role of music therapy in cardiac rehabilitation after cardiothoracic surgery: a qualitative study using the Bonny method of guided imagery and music.

PubMed

Short, Alison; Gibb, Heather; Fildes, Jennifer; Holmes, Colin

2013-01-01

Cardiac rehabilitation integrates physical, psychological, and vocational strategies to restore and sustain optimal health. An innovative study using music therapy (Bonny Method of Guided Imagery and Music [BMGIM]) explored the experiences of cardiac rehabilitation participants in an outpatient setting at 2 major metropolitan teaching hospitals. Commencing 6 to 15 weeks after cardiothoracic surgery, 6 study participants were recruited for 6 weekly music therapy (BMGIM) sessions. Qualitative analysis of the patient narrative within a semiotic framework demonstrated that patients used music therapy to spontaneously explore their recovery process. Five grand themes emerged: (1) looking through the frame, (2) feeling the impact, (3) spiralling into the unexpected, (4) sublime plateau, and (5) rehearsing new steps. The themes related to physical changes, adjustment after surgery, and anticipated lifestyle. This study demonstrates that music therapy (BMGIM) may be used to access and understand the internal recovery process of postcardiothoracic surgical patients, providing an additional clinical tool to augment the external rehabilitation process.

The regulatory sciences for stem cell-based medicinal products.

PubMed

Yuan, Bao-Zhu; Wang, Junzhi

2014-06-01

Over the past few years, several new achievements have been made from stem cell studies, many of which have moved up from preclinical stages to early, or from early to middle or late, stages thanks to relatively safe profile and preliminary evidence of effectiveness. Moreover, some stem cell-based products have been approved for marketing by different national regulatory authorities. However, many critical issues associated mainly with incomplete understanding of stem cell biology and the relevant risk factors, and lack of effective regulations still exist and need to be urgently addressed, especially in countries where establishment of appropriate regulatory system just commenced. More relevantly, the stem cell regulatory sciences need to be established or improved to more effectively evaluate quality, safety and efficacy of stem cell products, and for building up the appropriate regulatory framework. In this review, we summarize some new achievements in stem cell studies, especially the preclinical and clinical studies, the existing regulations, and the associated challenges, and we then propose some considerations for improving stem cell regulatory sciences with a goal of promoting the steadfast growth of the well-regulated stem cell therapies abreast of evolvement of stem cell sciences and technologies.

Can exercise ameliorate treatment toxicity during the initial phase of testosterone deprivation in prostate cancer patients? Is this more effective than delayed rehabilitation?

PubMed Central

2012-01-01

Background There has been substantial increase in use of androgen deprivation therapy as adjuvant management of prostate cancer. However, this leads to a range of musculoskeletal toxicities including reduced bone mass and increased skeletal fractures compounded with rapid metabolic alterations, including increased body fat, reduced lean mass, insulin resistance and negative lipoprotein profile, increased incidence of cardiovascular and metabolic morbidity, greater distress and reduced quality of life. Numerous research studies have demonstrated certain exercise prescriptions to be effective at preventing or even reversing these treatment toxicities. However, all interventions to date have been of rehabilitative intent being implemented after a minimum of 3 months since initiation of androgen deprivation, by which time considerable physical and psychological health problems have manifested. The pressing question is whether it is more efficacious to commence exercise therapy at the same time as initiating androgen deprivation, so treatment induced adverse effects can be immediately attenuated or indeed prevented. Methods/design We are proposing a multi-site randomized controlled trial with partial crossover to examine the effects of timing of exercise implementation (immediate or delayed) on preserving long-term skeletal health, reversing short- and long-term metabolic and cardiovascular risk factors, and supporting mental health in men receiving androgen deprivation therapy. 124 men who are about to initiate androgen deprivation for prostate cancer will be randomized to immediate or delayed groups. Immediate will commence a 6-month exercise program within 7–10 days of their first dose. Delayed will receive usual care for 6 months and then commence the exercise program for 6 months (partial cross-over). Immediate will be free to adopt the lifestyle of their choosing following the initial 6-month intervention. Measurements for primary and secondary endpoints will take place at baseline, 6 months and 12 months. Discussion This project is unique as it explores a fundamental question of when exercise implementation will be of most benefit and addresses both physical and psychological consequences of androgen deprivation initiation. The final outcome may be adjunct treatment which will reduce if not prevent the toxicities of androgen deprivation, ultimately resulting in reduced morbidity and mortality for men with prostate cancer. Trial registration ACTRN12612000097842 PMID:23013489

40 CFR 720.102 - Notice of commencement of manufacture or import.

Code of Federal Regulations, 2010 CFR

2010-07-01

... 40 Protection of Environment 30 2010-07-01 2010-07-01 false Notice of commencement of manufacture... (CONTINUED) TOXIC SUBSTANCES CONTROL ACT PREMANUFACTURE NOTIFICATION Commencement of Manufacture or Import § 720.102 Notice of commencement of manufacture or import. (a) Applicability. Any person who commences...

Pollution monitoring of puget sound with honey bees.

PubMed

Bromenshenk, J J; Carlson, S R; Simpson, J C; Thomas, J M

1985-02-08

To show that honey bees are effective biological monitors of environmental contaminants over large geographic areas, beekeepers of Puget Sound, Washington, collected pollen and bees for chemical analysis. From these data, kriging maps of arsenic, cadmium, and fluoride were generated. Results, based on actual concentrations of contaminants in bee tissues, show that the greatest concentrations of contaminants occur close to Commencement Bay and that honey bees are effective as large-scale monitors.

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

Martin, Olga A.; Molecular Radiation Biology Laboratory, Peter MacCallum Cancer Centre, East Melbourne, VIC; The Sir Peter MacCallum Department of Oncology, University of Melbourne, Melbourne, VIC

Purpose: To determine whether radiation therapy (RT) could mobilize viable tumor cells into the circulation of non-small cell lung cancer (NSCLC) patients. Methods and Materials: We enumerated circulating tumor cells (CTCs) by fluorescence microscopy of blood samples immunostained with conventional CTC markers. We measured their DNA damage levels using γ-H2AX, a biomarker for radiation-induced DNA double-strand breaks, either by fluorescence-activated cell sorting or by immunofluorescence microscopy. Results: Twenty-seven RT-treated NSCLC patients had blood samples analyzed by 1 or more methods. We identified increased CTC numbers after commencement of RT in 7 of 9 patients treated with palliative RT, and inmore » 4 of 8 patients treated with curative-intent RT. Circulating tumor cells were also identified, singly and in clumps in large numbers, during RT by cytopathologic examination (in all 5 cases studied). Elevated γ-H2AX signal in post-RT blood samples signified the presence of CTCs derived from irradiated tumors. Blood taken after the commencement of RT contained tumor cells that proliferated extensively in vitro (in all 6 cases studied). Circulating tumor cells formed γ-H2AX foci in response to ex vivo irradiation, providing further evidence of their viability. Conclusions: Our findings provide a rationale for the development of strategies to reduce the concentration of viable CTCs by modulating RT fractionation or by coadministering systemic therapies.« less

A Qualitative Investigation into Why the Motivation of Massage Therapy Students Changes over the Course of Their Professional Education.

PubMed

Finch, Paul

2009-03-19

In previous research, the motivation of massage therapy students was observed to change between commencement of their professional studies and entry into practice. The change involved a decrease in intrinsic motivation (associated with altruism) and an increase in extrinsic motivation (associated with the prospect of external rewards). This paper reports on the influences underlying those changes. The research used a qualitative design in which data were collected during a series of individual in-depth semi-structured interviews with massage therapy graduates, just after completion of a 2-year (2200-hour) full-time program. After informed consent was obtained, interviews were taped, transcribed, and analyzed, resulting in identification of a number of themes and subthemes. Previously noted changes in student motivation involved an increase in the influence of extrinsic rewards and a decrease in motivation related to helping and working with people. The findings of the present study suggest that these changes are explained by two main themes, each with a number of subthemes. The first theme, The Reality of Life in Practice, is associated with two subthemes: Debt Load, and Effectiveness in Achieving Positive Health Outcomes. The second theme, An Evolving Self-Image As a Health Care Professional, is associated with three sub-themes: Rigor/Intensity of the Educational Program, Developing Perspective of Massage Therapy As a Career, and Interaction with Faculty. The data suggest that the change in motivation noted in previous work (increased extrinsic motivation and decreased intrinsic motivation) is influenced in different ways by each identified theme. Although schools must be vigilant in ensuring that their programs support the humanistic mission of health care, the present study indicates that the change in motivation noted in earlier work is not sinister. Rather, it appears to be related to the development of a realistic perspective of life as a health care practitioner, which departs from the more naïve expectations of students when they commence their professional studies.

Outcomes of human immunodeficiency virus-infected children after anti-retroviral therapy in Malaysia.

PubMed

Moy, Fong Siew; Fahey, Paul; Nik Yusoff, Nik K; Razali, Kamarul A; Nallusamy, Revathy

2015-02-01

To describe outcome and examine factors associated with mortality among human immunodeficiency virus (HIV)-infected children in Malaysia after anti-retroviral therapy (ART). Retrospective and prospective data collected through March 2009 from children in four different states in Malaysia enrolled in TREAT Asia's Pediatric HIV Observational Database were analysed. Of 347 children in the cohort, only 278 (80.1%) were commenced on ART. The median CD4 count and median age at baseline prior to ART was 272 cells/μL and 4.2 years (interquartile range (IQR): 1.4, 7.4 years), respectively. The median duration of follow-up was 3.7 years (IQR: 1.8, 6.0) with 32 deaths giving a crude mortality rate of 2.86 per 100 child-years. The mortality rate highest in the first 6 months of ART was 10.62 per 100 child-years and declined to 1.83 per 100 child-years thereafter. On univariate analyses, only baseline median CD4 percentage, weight for age z score, height for age z score and anaemia were significantly associated with mortality. Upon including all four of these predictors into a single multivariate model, only weight for age z score remained statistically significantly predictive of mortality. Children commenced on ART had high mortality in the first 6 months especially in those with low CD4 percentage, wasting and anaemia. Poor nutritional status is an important independent predictor of mortality in this study. Besides initiating ART therapy, nutritional support and intervention must receive the utmost attention. © 2014 The Authors. Journal of Paediatrics and Child Health © 2014 Paediatrics and Child Health Division (Royal Australasian College of Physicians).

Angiotensin-converting enzyme-inhibitor therapy in adolescents with type 1 diabetes in a regional cohort: Auckland, New Zealand from 2006 to 2016.

PubMed

Hornung, Rosalie J; Reed, Peter W; Mouat, Fran; Jefferies, Craig; Gunn, Alistair J; Hofman, Paul L

2018-05-01

To review indications and use of angiotensin-converting enzyme-inhibitor (ACEI) therapy for the treatment of persistent microalbuminuria (MA) and/or hypertension (HTN) in adolescents with type 1 diabetes mellitus (T1DM). Retrospective chart review of adolescent patients with T1DM seen within the paediatric diabetes service in Auckland, New Zealand, from 2006 to 2016. MA, HTN, patient demographic characteristics and ACEI prescribing and monitoring indices were examined. Five hundred adolescents with T1DM were included. There were 26 patients (5%) with MA and/or HTN. MA alone was present in 16, HTN alone in 3 and both HTN and MA in 7. The 5-year MA/HTN-free rate was 98%, and the 10-year MA/HTN-free rate was 93%. Longer disease duration and earlier diagnosis were predictors of MA/HTN. There was no significant difference in standard clinical indices between study patients and others. ACEI was prescribed for 17 of 26 patients for either HTN or MA. Within 6 weeks of ACEI commencement, less than half of the subjects had repeat serum creatinine and MA screens and no record of repeat blood pressure measurement. Despite this, all patients had 3-monthly reviews within outpatient clinics where adjustments of ACEI doses were made. In our regional adolescent population with T1DM, there were low rates of both MA and/or HTN. In those who required treatment with ACEI, clinical monitoring post-commencement of therapy was inconsistent. Local consensus guidelines for the management of persistent MA in children and adolescents with diabetes mellitus were developed in response to this study. © 2017 Paediatrics and Child Health Division (The Royal Australasian College of Physicians).

Mother-to-child transmission of HIV in a community-based antiretroviral clinic in South Africa

PubMed Central

Fitzgerald, Felicity C; Bekker, Linda-Gail; Kaplan, Richard; Myer, Landon; Lawn, Stephen D; Wood, Robin

2014-01-01

Objective To examine the uptake of ART among pregnant women referred to an ART service and the associated rates and risk factors for vertical HIV transmission. Method Retrospective analysis of an observational cohort at a community ART clinic in Cape Town. Results Between 2002 and 2008, 367 treatment-naïve pregnant women accessed the clinic. The median age was 27.5 years, and median gestation at presentation was 28 weeks. The median baseline CD4 count and viral load were 134 cells/µl and 28 282 copies/ml. Two hundred and sixty-five women (72%) commenced ART before giving birth, 73 women (20%) were referred for prevention of mother-to-child transmission therapy (PMTCT), and 29 (8%) received no intervention. Among ART-eligible women, 13% were lost to follow-up. Of those starting ART, median duration of therapy prior to birth was 7.6 weeks (interquartile range (IQR) 4 – 11.9). The HIV transmission rate was 5.1% (95% confidence interval (CI) 2.8 – 9.0%). Factors associated with transmission were advanced maternal WHO disease stage (odds ratio (OR) 9.57, p=0.02), and follow-up viral load above 50 copies/ml (OR 3.64, p=0.03). Each additional week on ART reduced transmission by 20% (p=0.05). There was no HIV transmission among women who received more than 8 weeks’ therapy. Conclusions The rate of HIV transmission in this study was higher than reported in high-income countries. Prevention of vertical transmission with ART was hindered by women presenting late in pregnancy and with advanced stage of HIV disease. Interventions that facilitate earlier ART commencement and improve programmatic retention of pregnant women are required. PMID:21414276

Integration through relatedness in the conversational model: a case study.

PubMed

Haliburn, Joan

2009-02-01

The aim of this paper is to demonstrate the principles of the conversational model in two therapies with a patient, at 16 years of age and again 20 years later. Described is the first therapy of L, which commenced in hospital and continued twice weekly after discharge. L was an acutely disturbed 16-year-old female admitted for 4 months to the psychiatry ward, a dynamically oriented milieu of a University teaching hospital where I was training. This is followed by a brief description of L's second therapy. Supervision was through audiotape of sessions. At the conclusion of the first therapy, L was functioning well. Five years later, she married and had a child. She was referred to me again after she attempted suicide following an acute stressful event which resulted in hospitalization. She is more aware and reflective at present but continues to be vulnerable. Attention to certain aspects of the psychotherapeutic relationship is important as demonstrated in the conversational model.

Pollution monitoring of Puget Sound with honey bees

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

Bromenshenk, J.J.; Carlson, S.R.; Simpson, J.C.

To show that honey bees are effective biological monitors of environmental contaminants over large geographic areas, beekeepers of Puget Sound, Washington, collected pollen and bees for chemical analysis. From these data, kriging maps of arsenic, cadmium, and fluoride were generated. Results, based on actual concentrations of contaminants in bee tissues, show that the greatest concentrations of contaminants occur close to Commencement Bay and that honey bees are effective as large-scale monitors. 27 references, 2 figures.

Dolutegravir-induced liver injury leading to sub-acute liver failure requiring transplantation: a case report and review of literature.

PubMed

Wang, Bo; Abbott, Laura; Childs, Kate; Taylor, Chris; Agarwal, Kosh; Cormack, Ian; Miquel, Rosa; Suddle, Abid

2018-03-01

A patient with human immunodeficiency virus-1 infection presented with sub-acute liver failure, temporally related to commencement of an antiretroviral therapy regimen containing dolutegravir (Triumeq). The patient was not a carrier of HLA-B5701, and abacavir hypersensitivity was unlikely. We believe this is the first report of severe dolutegravir-related hepatotoxicity resulting in sub-acute liver failure and transplantation and highlights a potential need for closer monitoring after drug initiation.

When does atopic dermatitis warrant systemic therapy? Recommendations from an expert panel of the International Eczema Council.

PubMed

Simpson, Eric L; Bruin-Weller, Marjolein; Flohr, Carsten; Ardern-Jones, Michael R; Barbarot, Sebastien; Deleuran, Mette; Bieber, Thomas; Vestergaard, Christian; Brown, Sara J; Cork, Michael J; Drucker, Aaron M; Eichenfield, Lawrence F; Foelster-Holst, Regina; Guttman-Yassky, Emma; Nosbaum, Audrey; Reynolds, Nick J; Silverberg, Jonathan I; Schmitt, Jochen; Seyger, Marieke M B; Spuls, Phyllis I; Stalder, Jean-Francois; Su, John C; Takaoka, Roberto; Traidl-Hoffmann, Claudia; Thyssen, Jacob P; van der Schaft, Jorien; Wollenberg, Andreas; Irvine, Alan D; Paller, Amy S

2017-10-01

Although most patients with atopic dermatitis (AD) are effectively managed with topical medication, a significant minority require systemic therapy. Guidelines for decision making about advancement to systemic therapy are lacking. To guide those considering use of systemic therapy in AD and provide a framework for evaluation before making this therapeutic decision with the patient. A subgroup of the International Eczema Council determined aspects to consider before prescribing systemic therapy. Topics were assigned to expert reviewers who performed a topic-specific literature review, referred to guidelines when available, and provided interpretation and expert opinion. We recommend a systematic and holistic approach to assess patients with severe signs and symptoms of AD and impact on quality of life before systemic therapy. Steps taken before commencing systemic therapy include considering alternate or concomitant diagnoses, avoiding trigger factors, optimizing topical therapy, ensuring adequate patient/caregiver education, treating coexistent infection, assessing the impact on quality of life, and considering phototherapy. Our work is a consensus statement, not a systematic review. The decision to start systemic medication should include assessment of severity and quality of life while considering the individual's general health status, psychologic needs, and personal attitudes toward systemic therapies. Copyright © 2017 American Academy of Dermatology, Inc. All rights reserved.

Combined orthodontic and periodontic treatment in a child with Papillon Lefèvre syndrome.

PubMed

AlSarheed, Maha A; Al-Sehaibany, Fares S

2015-08-01

A 9-year-old girl with Papillon-Lefèvre syndrome (PLS) was treated orthodontically 24 months after the start of mechanical and antibiotic therapy in adjunct with periodontal treatment every 6 weeks. After achieving stable periodontal conditions, orthodontic treatment was commenced to correct the teeth position, facial profile, and maxillary protraction. Following the combination therapy and a failure to detect Actinobacillus actinomycetemcomitans from any site in the oral cavity, orthodontic treatment with a fixed appliance was performed aside from creating space for eruption of permanent teeth. We found that combined periodontal and orthodontic treatment of PLS may be successful with a complex interdisciplinary regimen and close follow up. This is a 2-year follow-up case report of a girl with PLS. Orthodontic and periodontic therapy were offered using combined treatments of orthodontic and periodontal with the benefit of prosthodontic consultation, resulting in a treatment plan.

Combined orthodontic and periodontic treatment in a child with Papillon Lefèvre syndrome

PubMed Central

AlSarheed, Maha A.; Al-Sehaibany, Fares S.

2015-01-01

A 9-year-old girl with Papillon-Lefèvre syndrome (PLS) was treated orthodontically 24 months after the start of mechanical and antibiotic therapy in adjunct with periodontal treatment every 6 weeks. After achieving stable periodontal conditions, orthodontic treatment was commenced to correct the teeth position, facial profile, and maxillary protraction. Following the combination therapy and a failure to detect Actinobacillus actinomycetemcomitans from any site in the oral cavity, orthodontic treatment with a fixed appliance was performed aside from creating space for eruption of permanent teeth. We found that combined periodontal and orthodontic treatment of PLS may be successful with a complex interdisciplinary regimen and close follow up. This is a 2-year follow-up case report of a girl with PLS. Orthodontic and periodontic therapy were offered using combined treatments of orthodontic and periodontal with the benefit of prosthodontic consultation, resulting in a treatment plan. PMID:26219452

Advances in Gene Therapy for Hemophilia.

PubMed

Nathwani, Amit C; Davidoff, Andrew M; Tuddenham, Edward G D

2017-11-01

Gene therapy provides hope for a cure for patients with hemophilia by establishing continuous endogenous expression of factor VIII or factor IX following transfer of a functional gene copy to replace the hemophilic patient's own defective gene. Hemophilia may be considered a "low-hanging fruit" for gene therapy because a small increment in blood factor levels (≥2% of normal) significantly improves the bleeding tendency from severe to moderate, eliminating most spontaneous bleeds. After decades of research, the first trial to provide clear evidence of efficiency after gene transfer in patients with hemophilia B using adeno-associated virus vectors was reported by the authors' group in 2011. This has been followed by unprecedented activity in this area, with the commencement of seven new early-phase trials involving >55 patients with hemophilia A or hemophilia B. These studies have, in large part, generated promising clinical data that lay a strong foundation for gene therapy to move forward rapidly to market authorization. This review discusses the data from the authors' studies and emerging results from other gene therapy trials in both hemophilia A and B.

[Histological effects of short term endocrine therapy on prostatic cancer].

PubMed

Irisawa, C; Yoshimura, Y; Yokota, T; Yamaguchi, O; Kondou, Y; Hamasaki, T; Yamad, Y; Kurosu, S; Chiba, R

1996-07-01

The objective of this study is to investigate the pathological changes which occurred in prostatic cancer shortly after the commencement of endocrine therapy. Fourty-three patients underwent radical prostatectomy immediately after the short term endocrine therapy (treatment period was within one month) and the histological pictures of operative specimens were compared to those obtained from the pretreatment biopsy specimens. Degenerative changes of cancer cells, such as nuclear and cytoplasmic vacuole, collapse of the cytoplasm and the appearance of naked hyperchromatic nucleus were noticed after the short term endocrine therapy. Especially in the cases which were histologically evaluated to be poorly differentiated in the biopsy specimens, not only degenerative changes but also destruction of cancer nests caused by cell death were observed. The histological effects affected by short term endocrine treatment had no relation to the prognosis, but in the cases of stage D2, the pathological grade judged by post-therapeutic specimens were found to be useful for the prediction of prognosis. Endocrine therapy induces remarkable pathological changes in prostatic cancer within a very short time after beginning treatment.

Management of anaemia in haemodialysis and peritoneal dialysis patients (chapter 8).

PubMed

Richardson, Donald; Hodsman, Alex; van Schalkwyk, Dirk; Tomson, Charlie; Warwick, Graham

2007-08-01

Forty-one percent of UK patients commence RRT with an Hb < 10.0 g/dl. The mean Hb at commencement of RRT is 10.3 g/dl. Eighty-five percent of patients on dialysis in the UK have an Hb > or = 10.0 g/dl by 6 months after commencement of RRT. The median Hb on haemodialysis in the UK is 11.8 g/dl with an IQR of 10.7-12.8 g/dl. Eighty-six percent of haemodialysis patients in the UK have a Hb > or = 10.0 g/dl. The median Hb on peritoneal dialysis in the UK is 12.0 g/dl with an IQR of 11.0-12.9 g/dl. Ninety percent of peritoneal dialysis patients in the UK have an Hb > or = 10.0 g/dl. In the UK, 49% of patients on PD and 48% of patients on haemodialysis have an Hb between 10.5-12.5 g/dl. The median ferritin in UK haemodialysis patients is 413 microg/l (IQR 262-623), 95% of UK haemodialysis patients have a ferritin > or =100 microg/l. The median ferritin in UK PD patients is 256 microg/l (IQR 147-421), 86% of UK peritoneal dialysis patients have a ferritin > or = 100 microg/l. A higher proportion of HD patients than PD patients receive ESA therapy (88% vs 76%). The ESA dose is higher for HD than PD patients (9204 vs 6080 IU/week).

The European Renal Association - European Dialysis and Transplant Association Registry Annual Report 2014: a summary.

PubMed

Pippias, Maria; Kramer, Anneke; Noordzij, Marlies; Afentakis, Nikolaos; Alonso de la Torre, Ramón; Ambühl, Patrice M; Aparicio Madre, Manuel I; Arribas Monzón, Felipe; Åsberg, Anders; Bonthuis, Marjolein; Bouzas Caamaño, Encarnación; Bubic, Ivan; Caskey, Fergus J; Castro de la Nuez, Pablo; Cernevskis, Harijs; de Los Ángeles Garcia Bazaga, Maria; des Grottes, Jean-Marin; Fernández González, Raquel; Ferrer-Alamar, Manuel; Finne, Patrik; Garneata, Liliana; Golan, Eliezer; Heaf, James G; Hemmelder, Marc H; Idrizi, Alma; Ioannou, Kyriakos; Jarraya, Faical; Kantaria, Nino; Kolesnyk, Mykola; Kramar, Reinhard; Lassalle, Mathilde; Lezaic, Visnja V; Lopot, Frantisek; Macario, Fernando; Magaz, Ángela; Martín de Francisco, Angel L; Martín Escobar, Eduardo; Martínez Castelao, Alberto; Metcalfe, Wendy; Moreno Alia, Inmaculada; Nordio, Maurizio; Ots-Rosenberg, Mai; Palsson, Runolfur; Ratkovic, Marina; Resic, Halima; Rutkowski, Boleslaw; Santiuste de Pablos, Carmen; Seyahi, Nurhan; Fernanda Slon Roblero, María; Spustova, Viera; Stas, Koenraad J F; Stendahl, María E; Stojceva-Taneva, Olivera; Vazelov, Evgueniy; Ziginskiene, Edita; Massy, Ziad; Jager, Kitty J; Stel, Vianda S

2017-04-01

Background: This article summarizes the European Renal Association - European Dialysis and Transplant Association Registry's 2014 annual report. It describes the epidemiology of renal replacement therapy (RRT) for end-stage renal disease (ESRD) in 2014 within 35 countries. Methods: In 2016, the ERA-EDTA Registry received data on patients who in 2014 where undergoing RRT for ESRD, from 51 national or regional renal registries. Thirty-two registries provided individual patient level data and 19 provided aggregated patient level data. The incidence, prevalence and survival probabilities of these patients were determined. Results: In 2014, 70 953 individuals commenced RRT for ESRD, equating to an overall unadjusted incidence rate of 133 per million population (pmp). The incidence ranged by 10-fold; from 23 pmp in the Ukraine to 237 pmp in Portugal. Of the patients commencing RRT, almost two-thirds were men, over half were aged ≥65 years and a quarter had diabetes mellitus as their primary renal diagnosis. By day 91 of commencing RRT, 81% of patients were receiving haemodialysis. On 31 December 2014, 490 743 individuals were receiving RRT for ESRD, equating to an unadjusted prevalence of 924 pmp. This ranged throughout Europe by more than 10-fold, from 157 pmp in the Ukraine to 1794 pmp in Portugal. In 2014, 19 406 kidney transplantations were performed, equating to an overall unadjusted transplant rate of 36 pmp. Again this varied considerably throughout Europe. For patients commencing RRT during 2005-09, the 5-year-adjusted patient survival probabilities on all RRT modalities was 63.3% (95% confidence interval 63.0-63.6). The expected remaining lifetime of a 20- to 24-year-old patient with ESRD receiving dialysis or living with a kidney transplant was 21.9 and 44.0 years, respectively. This was substantially lower than the 61.8 years of expected remaining lifetime of a 20-year-old patient without ESRD.

The European Renal Association – European Dialysis and Transplant Association (ERA-EDTA) Registry Annual Report 2015: a summary

PubMed Central

Pippias, Maria; Noordzij, Marlies; Stel, Vianda S; Afentakis, Nikolaos; Ambühl, Patrice M; Andrusev, Anton M; Fuster, Emma Arcos; Arribas Monzón, Federico E; Åsberg, Anders; Barbullushi, Myftar; Bonthuis, Marjolein; Caskey, Fergus J; Castro de la Nuez, Pablo; Cernevskis, Harijs; des Grottes, Jean-Marin; Garneata, Liliana; Golan, Eliezer; Hemmelder, Marc H; Ioannou, Kyriakos; Jarraya, Faical; Kolesnyk, Mykola; Komissarov, Kirill; Lassalle, Mathilde; Macario, Fernando; Mahillo-Duran, Beatriz; Martín de Francisco, Angel L; Palsson, Runolfur; Pechter, Ülle; Resic, Halima; Rutkowski, Boleslaw; Santiuste de Pablos, Carmen; Seyahi, Nurhan; Simic Ogrizovic, Sanja; Slon Roblero, María F; Spustova, Viera; Stojceva-Taneva, Olivera; Massy, Ziad A; Jager, Kitty J

2018-01-01

Abstract Background This article summarizes the European Renal Association – European Dialysis and Transplant Association (ERA-EDTA) Registry’s 2015 Annual Report. It describes the epidemiology of renal replacement therapy (RRT) for end-stage renal disease (ESRD) in 2015 within 36 countries. Methods In 2016 and 2017, the ERA-EDTA Registry received data on patients who were undergoing RRT for ESRD in 2015, from 52 national or regional renal registries. Thirty-two registries provided individual patient-level data and 20 provided aggregated-level data. The incidence, prevalence and survival probabilities of these patients were determined. Results In 2015, 81 373 individuals commenced RRT for ESRD, equating to an overall unadjusted incidence rate of 119 per million population (pmp). The incidence ranged by 10-fold, from 24 pmp in Ukraine to 232 pmp in the Czech Republic. Of the patients commencing RRT, almost two-thirds were men, over half were aged ≥65 years and a quarter had diabetes mellitus as their primary renal diagnosis. Treatment modality at the start of RRT was haemodialysis for 85% of the patients, peritoneal dialysis for 11% and a kidney transplant for 4%. By Day 91 of commencing RRT, 82% of patients were receiving haemodialysis, 13% peritoneal dialysis and 5% had a kidney transplant. On 31 December 2015, 546 783 individuals were receiving RRT for ESRD, corresponding to an unadjusted prevalence of 801 pmp. This ranged throughout Europe by more than 10-fold, from 178 pmp in Ukraine to 1824 pmp in Portugal. In 2015, 21 056 kidney transplantations were performed, equating to an overall unadjusted transplant rate of 31 pmp. This varied from 2 pmp in Ukraine to 94 pmp in the Spanish region of Cantabria. For patients commencing RRT during 2006–10, the 5-year unadjusted patient survival probabilities on all RRT modalities combined was 50.0% (95% confidence interval 49.9–50.1). PMID:29423210

Outcomes in patients with chronic kidney disease not on dialysis receiving extended dosing regimens of darbepoetin alfa: long-term results of the EXTEND observational cohort study

PubMed Central

Galle, Jan-Christoph; Addison, Janet; Suranyi, Michael G.; Claes, Kathleen; Di Giulio, Salvatore; Guerin, Alain; Herlitz, Hans; Kiss, István; Farouk, Mourad; Manamley, Nick; Wirnsberger, Gerhard; Winearls, Christopher

2016-01-01

Background Extended dosing of the erythropoiesis-stimulating agent (ESA) darbepoetin alfa (DA) once biweekly or monthly reduces anaemia treatment burden. This observational study assessed outcomes and dosing patterns in patients with chronic kidney disease not on dialysis (CKD-NoD) commencing extended dosing of DA. Methods Adult CKD-NoD patients starting extended dosing of DA in Europe or Australia in June 2006 or later were followed up until December 2012. Outcomes included haemoglobin (Hb) concentration, ESA dosing, mortality rates and receipt of dialysis and renal transplantation. Subgroup analyses were conducted for selected outcomes. Results Of 6035 enrolled subjects, 5723 (94.8%) met analysis criteria; 1795 (29.7%) received dialysis and 238 (3.9%) underwent renal transplantation. Mean (standard deviation) Hb concentration at commencement of extended dosing was 11.0 (1.5) g/dL. Mean [95% confidence interval (CI)] Hb 12 months after commencement of extended dosing (primary outcome) was 11.6 g/dL (11.5, 11.6) overall and was similar across countries, with no differences between subjects previously treated with an ESA versus ESA-naïve subjects, subjects with versus without prior renal transplant or diabetics versus non-diabetics. Weekly ESA dose gradually decreased following commencement of extended DA dosing and was similar across subgroups. The decrease in weekly DA dose was accompanied by an increase in the proportion of patients receiving iron therapy. Hb concentrations declined following changes in ESA labels and treatment guidelines. The mortality rate (95% CI) was 7.06 (6.68, 7.46) deaths per 100 years of follow-up. Subjects alive at study end had stable Hb concentrations in the preceding year, while those who died had lower and declining Hb concentrations in their last year. Conclusions Long-term, extended dosing of DA maintained Hb concentrations in patients already treated with an ESA and corrected and maintained Hb in ESA-naïve patients. PMID:27190334

The European Renal Association – European Dialysis and Transplant Association Registry Annual Report 2014: a summary

PubMed Central

Kramer, Anneke; Noordzij, Marlies; Afentakis, Nikolaos; Alonso de la Torre, Ramón; Ambühl, Patrice M.; Aparicio Madre, Manuel I.; Arribas Monzón, Felipe; Åsberg, Anders; Bonthuis, Marjolein; Bouzas Caamaño, Encarnación; Bubic, Ivan; Caskey, Fergus J.; Castro de la Nuez, Pablo; Cernevskis, Harijs; de los Ángeles Garcia Bazaga, Maria; des Grottes, Jean-Marin; Fernández González, Raquel; Ferrer-Alamar, Manuel; Finne, Patrik; Garneata, Liliana; Golan, Eliezer; Heaf, James G.; Hemmelder, Marc H.; Idrizi, Alma; Ioannou, Kyriakos; Jarraya, Faical; Kantaria, Nino; Kolesnyk, Mykola; Kramar, Reinhard; Lassalle, Mathilde; Lezaic, Visnja V.; Lopot, Frantisek; Macario, Fernando; Magaz, Ángela; Martín de Francisco, Angel L.; Martín Escobar, Eduardo; Martínez Castelao, Alberto; Metcalfe, Wendy; Moreno Alia, Inmaculada; Nordio, Maurizio; Ots-Rosenberg, Mai; Palsson, Runolfur; Ratkovic, Marina; Resic, Halima; Rutkowski, Boleslaw; Santiuste de Pablos, Carmen; Seyahi, Nurhan; Fernanda Slon Roblero, María; Spustova, Viera; Stas, Koenraad J.F.; Stendahl, María E.; Stojceva-Taneva, Olivera; Vazelov, Evgueniy; Ziginskiene, Edita; Massy, Ziad; Jager, Kitty J.; Stel, Vianda S.

2017-01-01

Abstract Background: This article summarizes the European Renal Association – European Dialysis and Transplant Association Registry’s 2014 annual report. It describes the epidemiology of renal replacement therapy (RRT) for end-stage renal disease (ESRD) in 2014 within 35 countries. Methods: In 2016, the ERA-EDTA Registry received data on patients who in 2014 where undergoing RRT for ESRD, from 51 national or regional renal registries. Thirty-two registries provided individual patient level data and 19 provided aggregated patient level data. The incidence, prevalence and survival probabilities of these patients were determined. Results: In 2014, 70 953 individuals commenced RRT for ESRD, equating to an overall unadjusted incidence rate of 133 per million population (pmp). The incidence ranged by 10-fold; from 23 pmp in the Ukraine to 237 pmp in Portugal. Of the patients commencing RRT, almost two-thirds were men, over half were aged ≥65 years and a quarter had diabetes mellitus as their primary renal diagnosis. By day 91 of commencing RRT, 81% of patients were receiving haemodialysis. On 31 December 2014, 490 743 individuals were receiving RRT for ESRD, equating to an unadjusted prevalence of 924 pmp. This ranged throughout Europe by more than 10-fold, from 157 pmp in the Ukraine to 1794 pmp in Portugal. In 2014, 19 406 kidney transplantations were performed, equating to an overall unadjusted transplant rate of 36 pmp. Again this varied considerably throughout Europe. For patients commencing RRT during 2005–09, the 5-year-adjusted patient survival probabilities on all RRT modalities was 63.3% (95% confidence interval 63.0–63.6). The expected remaining lifetime of a 20- to 24-year-old patient with ESRD receiving dialysis or living with a kidney transplant was 21.9 and 44.0 years, respectively. This was substantially lower than the 61.8 years of expected remaining lifetime of a 20-year-old patient without ESRD. PMID:28584624

Differences in the direction of change of cerebral function parameters are evident over three years in HIV-infected individuals electively commencing initial cART.

PubMed

Winston, Alan; Puls, Rebekah; Kerr, Stephen J; Duncombe, Chris; Li, Patrick; Gill, John M; Ramautarsing, Reshmie; Taylor-Robinson, Simon D; Emery, Sean; Cooper, David A

2015-01-01

Changes in cerebral metabolite ratios (CMR) measured on 1H-MRS and changes in cognitive function (CF) are described in subjects commencing combination antiretroviral therapy (cART), although the dynamics of such changes are poorly understood. Neuroasymptomatic, HIV-infected subjects electively commencing cART were eligible. CMR were assessed in three anatomical voxels and CF assessed at baseline, week 48 and week 144. Overall differences in absolute change in CMRs and CF parameters between 0-48 and 48-144 weeks were assessed. Twenty-two subjects completed study procedures. Plasma HIV-RNA was <50 copies/mL in all at week 48 and in all, but two subjects at week 144. In general, between weeks 0-48 a rise in N-acetyl-aspartate(NAA)/Creatine(Cr) ratio and a decline in myo-Inositol(mI)/Cr ratio were observed. Between weeks 48-144, small rises in NAA/Cr ratio were observed in two anatomical voxels, whereas a rise in mI/Cr ratio was observed in all anatomical locations (0.31 (0.66) and -0.27 (1.35) between weeks 0-48 and 0.13 (0.91) and 1.13 (1.71) between weeks 48-144 for absolute changes in NAA/Cr and mI/Cr (SD) in frontal-grey voxel, respectively). Global CF score improved between weeks 0-48 and then declined between weeks 48-144 (0.63 (1.16) and -0.63 (0.1.41) for mean absolute change (SD) between weeks 0-48 and weeks 48-144, respectively). The direction of change of cerebral function parameters differs over time in HIV-infected subjects commencing cART, highlighting the need for long-term follow-up in such studies. The changes we have observed between weeks 48-144 may represent the initial development of cerebral toxicities from cART.

45 CFR 2400.44 - Commencement of graduate study.

Code of Federal Regulations, 2011 CFR

2011-10-01

... 45 Public Welfare 4 2011-10-01 2011-10-01 false Commencement of graduate study. 2400.44 Section... FELLOWSHIP FOUNDATION FELLOWSHIP PROGRAM REQUIREMENTS Graduate Study § 2400.44 Commencement of graduate study. (a) Fellows may commence study under their fellowships as early as the summer following the...

45 CFR 2400.44 - Commencement of graduate study.

Code of Federal Regulations, 2010 CFR

2010-10-01

... 45 Public Welfare 4 2010-10-01 2010-10-01 false Commencement of graduate study. 2400.44 Section... FELLOWSHIP FOUNDATION FELLOWSHIP PROGRAM REQUIREMENTS Graduate Study § 2400.44 Commencement of graduate study. (a) Fellows may commence study under their fellowships as early as the summer following the...

40 CFR 725.190 - Notice of commencement of manufacture or import.

Code of Federal Regulations, 2010 CFR

2010-07-01

... 40 Protection of Environment 30 2010-07-01 2010-07-01 false Notice of commencement of manufacture... Microbial Commercial Activities Notification Requirements § 725.190 Notice of commencement of manufacture or import. (a) Applicability. Any person who commences the manufacture or import of a new microorganism for...

24 CFR 242.45 - Early commencement of work.

Code of Federal Regulations, 2013 CFR

2013-04-01

... 24 Housing and Urban Development 2 2013-04-01 2013-04-01 false Early commencement of work. 242.45... MORTGAGE INSURANCE FOR HOSPITALS Construction § 242.45 Early commencement of work. (a) Site preparation... commencement of certain limited site preparation for the project within legal guidelines and state law. Such...

24 CFR 242.45 - Early commencement of work.

Code of Federal Regulations, 2012 CFR

2012-04-01

... 24 Housing and Urban Development 2 2012-04-01 2012-04-01 false Early commencement of work. 242.45... MORTGAGE INSURANCE FOR HOSPITALS Construction § 242.45 Early commencement of work. (a) Site preparation... commencement of certain limited site preparation for the project within legal guidelines and state law. Such...

24 CFR 242.45 - Early commencement of work.

Code of Federal Regulations, 2014 CFR

2014-04-01

... 24 Housing and Urban Development 2 2014-04-01 2014-04-01 false Early commencement of work. 242.45... MORTGAGE INSURANCE FOR HOSPITALS Construction § 242.45 Early commencement of work. (a) Site preparation... commencement of certain limited site preparation for the project within legal guidelines and state law. Such...

24 CFR 242.45 - Early commencement of work.

Code of Federal Regulations, 2010 CFR

2010-04-01

... 24 Housing and Urban Development 2 2010-04-01 2010-04-01 false Early commencement of work. 242.45... MORTGAGE INSURANCE FOR HOSPITALS Construction § 242.45 Early commencement of work. (a) Site preparation... work can commence only after the review of the work and concurrence by HUD, including the environmental...

24 CFR 242.45 - Early commencement of work.

Code of Federal Regulations, 2011 CFR

2011-04-01

... 24 Housing and Urban Development 2 2011-04-01 2011-04-01 false Early commencement of work. 242.45... MORTGAGE INSURANCE FOR HOSPITALS Construction § 242.45 Early commencement of work. (a) Site preparation... the commencement of certain necessary early site work and limited construction activity in connection...

Economic benefits of optimizing anchor therapy for rheumatoid arthritis.

PubMed

Fautrel, Bruno

2012-06-01

The total cost of RA is substantial, particularly in patients with high levels of disability. There are considerable differences in cost between countries, driven in part by differences in the use of biologic therapies. Economic evaluations are needed to assess the extra cost of using these treatments and the benefits obtained, to ensure appropriate allocation of limited health care resources. The BeSt trial, evaluating four treatment strategies, found comparable medium-term efficacy but substantially higher costs with early biologic therapy. A systematic review of such cost-effectiveness analyses concluded that biologic therapy should be used after therapy has failed with less costly alternatives such as synthetic DMARDs and glucocorticoids. Optimizing such relatively low-cost therapy to improve outcomes may delay the need for biologic therapy, thereby saving costs. A simple model has confirmed the value of this approach. The addition of modified-release prednisone 5 mg/day to existing synthetic DMARD therapy in patients with active disease resulted in improvement in DAS-28 to below the threshold level for initiation of reimbursed biologic therapy in 28-34% of patients. On a conservative estimate (i.e. assuming no further benefits beyond the 12 weeks of the study and a 12-week wait-and-see approach to starting biologic therapy), cost savings amounted to nearly € 400 per patient. While treatment decisions should never be based only on cost considerations, prolonging disease control by optimizing the use of non-biologic treatments may bring benefits to patients and also economic benefits by delaying the need for biologic treatments.

Inhalation delivery of protein therapeutics.

PubMed

Kane, Colleen; O'Neil, Karyn; Conk, Michelle; Picha, Kristen

2013-04-01

Inhaled therapeutics are used routinely to treat a variety of pulmonary diseases including asthma, COPD and cystic fibrosis. In addition, biological therapies represent the fastest growing segment of approved pharmaceuticals. However, despite the increased availability of biological therapies, nearly all inhaled therapeutics are small molecule drugs with only a single inhaled protein therapeutic approved. There remains a significant unmet need for therapeutics in pulmonary diseases, and biological therapies with potential to alter disease progression represent a significant opportunity to treat these challenging diseases. This review provides a background into efforts to develop inhaled biological therapies and highlights some of the associated challenges. In addition, we speculate on the ideal properties of a biologic therapy for inhaled delivery.

Sexual health and relationships after age 60.

PubMed

Minkin, Mary Jane

2016-01-01

A commonly used phrase describing aging is "60 is the new 40". Although in many aspects of life this may be correct, in discussing sexual health, challenges to maintaining excellent sexual health become more common around age 60. Biological aging challenges physical sexual activity and responsiveness. We commence by briefly surveying the extensive coverage of 'normal' physiological aging. We primarily focus on issues that arise in distinct disease and or pathophysiological states, including gynecological and breast cancer, as well as those associated with partners of men who are either prostate cancer survivors or who have taken therapy for erectile dysfunction (ED). Regrettably, there is a very modest literature on sexual health and associated possible interventions in older patients in these cohorts. We discuss a variety of interventions and approaches, including those that we have developed and applied in a clinic at our host university, which have generally produced successful outcomes. The extended focus to sexual relationship dynamics in partners of men with either prostate cancer or ED in particular is virtually unexplored, yet is especially timely given the large numbers of women who encounter this situation. Finally, we briefly discuss cross-cultural distinctions in older couples' expectations, which exhibit remarkable variation. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

Travel and biologic therapy: travel-related infection risk, vaccine response and recommendations.

PubMed

Hall, Victoria; Johnson, Douglas; Torresi, Joseph

2018-01-01

Biologic therapy has revolutionized the management of refractory chronic autoimmune and auto-inflammatory disease, as well as several malignancies, providing rapid symptomatic relief and/or disease remission. Patients receiving biologic therapies have an improved quality of life, facilitating travel to exotic destinations and potentially placing them at risk of a range of infections. For each biologic agent, we review associated travel-related infection risk and expected travel vaccine response and effectiveness. A PUBMED search [vaccination OR vaccine] AND/OR ['specific vaccine'] AND/OR [immunology OR immune response OR response] AND [biologic OR biological OR biologic agent] was performed. A review of the literature was performed in order to develop recommendations on vaccination for patients in receipt of biologic therapy travelling to high-risk travel destinations. There is a paucity of literature in this area, however, it is apparent that travel-related infection risk is increased in patients on biologic therapy and when illness occurs they are at a higher risk of complication and hospitalization. Patients in receipt of biologic agents are deemed as having a high level of immunosuppression-live vaccines, including the yellow fever vaccine, are contraindicated. Inactivated vaccines are considered safe; however, vaccine response can be attenuated by the patient's biologic therapy, thereby resulting in reduced vaccine effectiveness and protection. Best practice requires a collaborative approach between the patient's primary healthcare physician, relevant specialist and travel medicine expert, who should all be familiar with the immunosuppressive and immunomodulatory effects resulting from the biologic therapies. Timing of vaccines should be carefully planned, and if possible, vaccination provided well before established immunosuppression.

12 CFR 1272.4 - Commencement of new business activities.

Code of Federal Regulations, 2013 CFR

2013-01-01

... 12 Banks and Banking 9 2013-01-01 2013-01-01 false Commencement of new business activities. 1272.4 Section 1272.4 Banks and Banking FEDERAL HOUSING FINANCE AGENCY FEDERAL HOME LOAN BANKS NEW BUSINESS ACTIVITIES § 1272.4 Commencement of new business activities. A Bank may commence a new business activity: (a...

12 CFR 1272.4 - Commencement of new business activities.

Code of Federal Regulations, 2012 CFR

2012-01-01

... 12 Banks and Banking 9 2012-01-01 2012-01-01 false Commencement of new business activities. 1272.4 Section 1272.4 Banks and Banking FEDERAL HOUSING FINANCE AGENCY FEDERAL HOME LOAN BANKS NEW BUSINESS ACTIVITIES § 1272.4 Commencement of new business activities. A Bank may commence a new business activity: (a...

12 CFR 1272.4 - Commencement of new business activities.

Code of Federal Regulations, 2014 CFR

2014-01-01

... 12 Banks and Banking 10 2014-01-01 2014-01-01 false Commencement of new business activities. 1272.4 Section 1272.4 Banks and Banking FEDERAL HOUSING FINANCE AGENCY FEDERAL HOME LOAN BANKS NEW BUSINESS ACTIVITIES § 1272.4 Commencement of new business activities. A Bank may commence a new business...

24 CFR 26.38 - Commencement of action.

Code of Federal Regulations, 2011 CFR

2011-04-01

... 24 Housing and Urban Development 1 2011-04-01 2011-04-01 false Commencement of action. 26.38... § 26.38 Commencement of action. Proceedings under subpart B of this part shall commence with the... response to the Docket Clerk, then the Government may file a motion for a default judgment in accordance...

Adherence to Anti Retroviral Therapy (ART) During Muslim Ramadan Fasting

PubMed Central

Habib, A. G.; Shepherd, J. C.; Eng, M. K. L.; Babashani, M.; Jumare, J.; Yakubu, U.; Gebi, U. I.; Saad, M.; Ibrahim, H.; Blattner, W. A.

2010-01-01

Annual fasting during the month of Ramadan is observed in Muslim countries, some of which have widespread HIV infection. We studied treatment adherence and customary practices among 142 fasting `FT' and 101 non-fasting `NFT' patients on anti-retroviral therapy (ART) in Nigeria. Adherence on ART among FT and NFT patients was similar during Ramadan, 96% and 98%, and ever since commencement of ART, 80% and 88%, respectively. FT patients altered their typical daily behaviors by advancing morning and delaying evening doses thereby prolonging dosing intervals, eating heavier meals pre-dawn and on breakfast at sunset (78%), and changing or reducing their sleeping and waking times (40%). This preliminary study suggests that adherence and drug taking frequency appear uncompromised in FT HIV infected patients on ARVs. PMID:18521736

Lenalidomide-induced myelosuppression is associated with renal dysfunction: adverse events evaluation of treatment-naïve patients undergoing front-line lenalidomide and dexamethasone therapy.

PubMed

Niesvizky, Ruben; Naib, Tara; Christos, Paul J; Jayabalan, David; Furst, Jessica R; Jalbrzikowski, Jessica; Zafar, Faiza; Mark, Tomer; Lent, Richard; Pearse, Roger N; Ely, Scott; Leonard, John P; Mazumdar, Madhu; Chen-Kiang, Selina; Coleman, Morton

2007-09-01

Data on 72 patients receiving lenalidomide/dexamethasone for multiple myeloma (MM) was used to determine the factors that are associated with lenalidomide-induced myelosuppression. Eight of 14 patients with grade > or =3 myelosuppression had baseline creatinine clearance (CrCl) < or =0.67 ml/s. Kaplan-Meier analysis by log-rank test demonstrated a significant association (P < 0.0001) between renal insufficiency and time to myelosuppression (hazard ratio = 8.4; 95% confidence interval 2.9-24.7, P = 0.0001). Therefore, CrCl is inversely associated with significant myelosuppression. Caution should be exercised when lenalidomide therapy is commenced and CrCl should be incorporated as a determinant of the initial dosing of lenalidomide in MM patients.

[A case of infectious mononucleosis with splenic infarction].

PubMed

Kobe, Daisuke; Nakatani, Toshiya; Fujinaga, Yukihisa; Seki, Kenichiro; Saikawa, Soichiro; Sawada, Yasuhiko; Sato, Yoshiki; Nagamatsu, Shinsaku; Matsuo, Hideki; Kikuchi, Eiryo

2013-08-01

A 22-year-old man complaining of persisting high fever and right hypochondralgia was admitted to our hospital for infectious mononucleosis with splenic infarction detected by computed tomography. The splenic infarction deteriorated with a marked elevation of inflammatory parameters. This necessitated the commencement of methylprednisolone pulse therapy, resulting in prompt amelioration of inflammation and a reduction in cytokine levels. Including our case, only 9 cases of mononucleosis with splenic infarction have been reported to date; however, splenic infarction should be considered because it is a significant complication of infectious mononucleosis.

Chronic peritoneal dialysis in children

PubMed Central

Fraser, Nia; Hussain, Farida K; Connell, Roy; Shenoy, Manoj U

2015-01-01

The incidence of end-stage renal disease in children is increasing. Peritoneal dialysis (PD) is the modality of choice in many European countries and is increasingly applied worldwide. PD enables children of all ages to be successfully treated while awaiting the ultimate goal of renal transplantation. The advantages of PD over other forms of renal replacement therapy are numerous, in particular the potential for the child to lead a relatively normal life. Indications for commencing PD, the rationale, preparation of family, technical aspects, and management of complications are discussed. PMID:26504404

Cost-Effectiveness Analysis of Abatacept Compared with Adalimumab on Background Methotrexate in Biologic-Naive Adult Patients with Rheumatoid Arthritis and Poor Prognosis.

PubMed

Alemao, Evo; Johal, Sukhvinder; Al, Maiwenn J; Rutten-van Mölken, Maureen

2018-02-01

To assess cost effectiveness of abatacept versus adalimumab, each administered with methotrexate, in treating patients with rheumatoid arthritis (RA) stratified according to baseline anticitrullinated protein antibody (ACPA) levels (marker of poor prognosis in RA). A payer-perspective cost-effectiveness model simulated disease progression in patients with RA who had previously failed conventional disease-modifying antirheumatic drugs and were starting biologic therapy. Patients commenced treatment with abatacept or adalimumab plus methotrexate and were evaluated after 6 months. Therapy continuation was based on the European League Against Rheumatism treatment response; disease progression was based on the Health Assessment Questionnaire Disability Index score. These score changes were used to estimate health state utilities and direct medical costs. Quality-adjusted life-years (QALYs) and incremental cost per QALY gained were calculated by baseline ACPA groups (Q1, 28-234 AU/ml; Q2, 235-609 AU/ml; Q3, 613-1045 AU/ml; and Q4, 1060-4894 AU/ml). Scenario analysis and one-way and probabilistic sensitivity analyses were used to evaluate robustness of model assumptions. Abatacept resulted in QALY gain versus adalimumab in ACPA Q1, Q3, and Q4; between-treatment difference (difference: Q1, -0.115 Q2, -0.009 Q3, 0.045; and Q4, 0.279). Total lifetime discounted cost was higher for abatacept versus adalimumab in most quartiles (Q2, £77,612 vs. £77,546; Q3, £74,441 vs. £73,263; and Q4, £78,428 vs. £76,696) because of longer time on treatment. Incremental cost per QALY for abatacept (vs. adalimumab) was the lowest in the high ACPA titer group (Q4, £6200/QALY), followed by the next lowest titer group (Q3, £26,272/QALY). Abatacept is a cost effective alternative to adalimumab in patients with RA with high ACPA levels. Copyright © 2018 International Society for Pharmacoeconomics and Outcomes Research (ISPOR). Published by Elsevier Inc. All rights reserved.

[Biological therapies in systemic lupus erythematosus].

PubMed

Cairoli, Ernesto; Espinosa, Gerard; Cervera, Ricard

2010-07-01

The immunosuppressive agents used in patients with systemic lupus erythematosus (SLE) have significantly improved prognosis. However, it is necessary to develop more specific immunosuppressive treatments with less toxicity. Better understanding of the mechanisms involved in the loss of tolerance in autoimmune diseases has contributed to the development of potential new treatments called biologic therapies. The targets of these biological therapies are directed toward the B cell depletion, interference in the co-stimulation signals and the blockade of cytokines. Therapies using anti-CD20 monoclonal antibodies have shown satisfactory results especially in patients with SLE refractory to conventional treatment. The biological therapies provide encouraging results that represent a possible option in the treatment of refractory patients as well as a potential therapy in the future management of SLE.

Differential Drug Survival of Second-Line Biologic Therapies in Patients with Psoriasis: Observational Cohort Study from the British Association of Dermatologists Biologic Interventions Register (BADBIR).

PubMed

Iskandar, Ireny Y K; Warren, Richard B; Lunt, Mark; Mason, Kayleigh J; Evans, Ian; McElhone, Kathleen; Smith, Catherine H; Reynolds, Nick J; Ashcroft, Darren M; Griffiths, Christopher E M

2018-04-01

Little is known about the drug survival of second-line biologic therapies for psoriasis in routine clinical practice. We assessed drug survival of second-line biologic therapies and estimated the risk of recurrent discontinuation due to adverse events or ineffectiveness in patients with psoriasis who had failed a first biologic therapy and switched to a second in a large, multicenter pharmacovigilance registry (n = 1,239; adalimumab, n = 538; etanercept, n = 104; ustekinumab, n = 597). The overall drug survival rate in the first year after switching was 77% (95% confidence interval = 74-79%), falling to 58% (55-61%) in the third year. Female sex, multiple comorbidities, concomitant therapy with cyclosporine, and a high Psoriasis Area and Severity Index at switching to the second-line biologic therapy were predictors of overall discontinuation (multivariable Cox proportional hazard model). Compared to adalimumab, patients receiving etanercept were more likely to discontinue therapy (hazard ratio = 1.87, 95% confidence interval = 1.24-2.83), whereas patients receiving ustekinumab were more likely to persist (hazard ratio = 0.46; 95% confidence interval = 0.33-0.64). Discontinuation of the first biologic therapy because of adverse events was associated with an increased rate of second drug discontinuation because of adverse events (hazard ratio = 2.55; 95% confidence interval = 1.50-4.32). In conclusion, drug survival rates differed among biologic therapies and decreased over time; second-line discontinuation because of adverse events was more common among those who discontinued first-line treatment for this reason. The results of this study should support clinical decision making when choosing second-line biologic therapy for patients with psoriasis. Copyright © 2017 The Authors. Published by Elsevier Inc. All rights reserved.

Pneumocystis jirovecii pneumonia associated with gemcitabine chemotherapy: experience at an Australian center and recommendations for targeted prophylaxis.

PubMed

Lingaratnam, Senthil M; Slavin, Monica A; Thursky, Karin A; Teh, Benjamin W; Haeusler, Gabrielle M; Seymour, John F; Rischin, Danny; Worth, Leon J

2015-01-01

Pneumocystis jirovecii pneumonia (PJP) is seen increasingly in non-human immunodeficiency virus (HIV) infected immunocompromised populations, but few cases have previously been reported in association with gemcitabine therapy. We identified all patients administered gemcitabine between March 2009 and December 2012 at the Peter MacCallum Cancer Centre. Cases of PJP were identified using accepted definitions. Overall, 288 gemcitabine-treated patients were identified. Nine cases of PJP were detected, corresponding to an overall rate of 3.1% (95% confidence interval [CI] 1.5-5.7%). PJP was diagnosed during gemcitabine therapy in seven patients, a median of 67 (range 31-109) days from commencement. Among patients with lymphoma, 4/22 developed PJP, corresponding to a rate of 18.2% (95% CI 6.1-38.2%). Fewer infections were associated with breast, lung and gastrointestinal malignancies (1/24 [4.2%], 3/118 [2.5%] and 1/61 [1.6%], respectively). A risk-based tool incorporating concomitant steroid therapy can be applied to target high-risk populations who would benefit from PJP prophylaxis during gemcitabine therapy.

DRESS syndrome due to antibiotic therapy of osteoarticular infections in children: two case reports.

PubMed

Ramírez, A; Abril, J C; Cano, J

2015-01-01

Osteoarticular infection in children frequently occurs before 10 years of age. Surgical drainage is sometimes required, whereas acute osteomyelitis can be treated with antibiotic therapy alone. The duration of antibiotic therapy varies, 2 weeks is sufficient for septic arthritis, whereas 6 weeks is often required for complicated cases. Some of these antibiotic drugs present direct complications with low clinical impact in certain individuals. Hypersensitivity to these drugs causes different reactions in children. DRESS syndrome (Drug Reaction with Eosinophilia and Systemic Symptoms) is a severe and potentially life-threatening drug reaction. It is characterised by high fever, malaise, lymphadenopathy and skin rash. From a clinical perspective, these symptoms can lead to an exacerbation of the initial infectious process for which treatment was commenced. The liver is the organ most often affected in DRESS syndrome associated with haematological changes, potentially similar to sepsis. We present two cases of children with osteoarticular infections who developed DRESS syndrome after antibiotic therapy. Both patients made a complete recovery after cessation of the antibiotic drugs used. Copyright © 2014 SECOT. Published by Elsevier Espana. All rights reserved.

Palmoplantar peeling secondary to sirolimus therapy.

PubMed

Liu, L S; McNiff, J M; Colegio, O R

2014-01-01

Sirolimus (rapamycin) is an immunosuppressive agent commonly used in transplant recipients. Although sirolimus has less renal toxicity than calcineurin inhibitors, its use has been limited by its side effects. The most common cutaneous pathologies associated with sirolimus are inflammatory acneiform eruptions, lymphedema and aphthous ulcers. We present a novel cutaneous manifestation of sirolimus therapy that limited its use in at least one transplant recipient. Upon commencing sirolimus therapy, four solid organ transplant recipients developed tender, nonpruritic palmoplantar peeling within the first month of therapy. The peeling clinically resembled a mild form of hand-foot syndrome, yet none of the patients had been treated with chemotherapeutics. Desquamation presented on the palms and soles with dry vesicles and minor peeling extending to the dorsal aspects of the hands and feet. Histologically, the lesions were noninflammatory; the epidermis showed subtle separation between keratinocytes, suggesting either spongiosis or a defect in intercellular adhesion. One patient opted to discontinue treatment because of the tenderness associated with the palmoplantar peeling, which resulted in complete resolution within 2 weeks. © Copyright 2013 The American Society of Transplantation and the American Society of Transplant Surgeons.

Cognitive-behavioral therapy for eating disorders in primary care settings: Does it work, and does a greater dose make it more effective?

PubMed

Rose, Charlotte; Waller, Glenn

2017-12-01

This study aimed to determine whether cognitive-behavioral therapy (CBT) for eating disorders can be effective in a routine, primary care clinical setting, and to assess dose response. The participants were 47 patients who commenced treatment with a publicly-funded primary care eating disorder service. They attended 7-33 sessions of individual CBT (mean = 17), using an evidence-based approach. Routine measures were collected pre- and post-therapy. Three-quarters of the patients completed treatment. Using intention to treat analysis (multiple imputation), the patients showed substantial improvements in eating attitudes, bulimic behaviors, and depression. However, there was no association between the level of improvement and the length of therapy past the 8th to 12th session. The level of effectiveness shown here is comparable to that previously demonstrated by more specialist services in secondary and tertiary care. The nonlinear association between number of sessions and recovery highlights the importance of early change, across the eating disorders. © 2017 Wiley Periodicals, Inc.

Delay in estrogen commencement is associated with lower bone mineral density in Turner syndrome.

PubMed

Nguyen, H H; Wong, P; Strauss, B J; Jones, G; Ebeling, P R; Milat, F; Vincent, A

2017-10-01

Turner syndrome (TS) is associated with hypogonadism, osteoporosis and fractures. We investigated the prevalence and risk factors for low bone density and fractures in a TS cohort. We included 76 TS patients (median age 28.5 years) attending a tertiary hospital between 1998 and 2015 who underwent dual-energy X-ray absorptiometry. Spine and femoral neck (FN) areal bone mineral density (aBMD) were compared with those of a control group. To adjust for smaller bone size, bone mineral apparent density (BMAD) was calculated. Primary amenorrhea was common (83%) in the TS cohort; the median age of pubertal induction was 15 years (range 11-30 years), and non-continuous estrogen therapy (ET) recorded in 40%. Almost one-third of TS patients reported fractures. TS patients had lower median spinal aBMD (1.026 g/cm 2 vs. 1.221 g/cm 2 ) and BMAD (0.156 g/cm 3 vs. 0.161 g/cm 3 ) than controls, and lower median FN aBMD (0.850 g/cm 2 vs. 1.026 g/cm 2 ) (all p < 0.01). More women with TS had spinal Z-score < -2.0 compared to controls (26.0% vs. 3.6%, p = 0.001). Spine and FN aBMD, BMAD and Z-scores were inversely associated with age commencing ET or years of estrogen deficiency. Delay in ET commencement was an independent risk factor for the lower bone density observed in women with TS. Early pubertal induction and ET compliance are important targets to optimize aBMD.

40 CFR Table 6 to Subpart Cccc of... - Emission Limitations for Energy Recovery Units That Commenced Construction After June 4, 2010, or...

Code of Federal Regulations, 2014 CFR

2014-07-01

... Recovery Units That Commenced Construction After June 4, 2010, or That Commenced Reconstruction or... Standards of Performance for Commercial and Industrial Solid Waste Incineration Units Pt. 60, Subpt. CCCC, Table 6 Table 6 to Subpart CCCC of Part 60—Emission Limitations for Energy Recovery Units That Commenced...

Changes in body composition after spasticity treatment with intrathecal baclofen.

PubMed

Skogberg, Olle; Samuelsson, Kersti; Ertzgaard, Per; Levi, Richard

2017-01-19

To assess changes in body composition, body weight and resting metabolic rate in patients who received intrathecal baclofen therapy for spasticity. Prospective, longitudinal, quasi-experimental, with a pre/post design. Twelve patients with spasticity, fulfilling study criteria, and due for pump implantation for intrathecal baclofen therapy, completed the study. Data were obtained before, 6 months and 12 months after commencement of intrathecal baclofen therapy as regards body composition (by skinfold calliper), body weight, and resting metabolic rate (by resting oxygen consumption). Spasticity was assessed according to the Modified Ashworth Scale (MAS) and Penn Spasm Frequency Scale (PSFS). A reduction in spasticity according to MAS occurred. Mean fat body mass increased and mean lean body mass decreased. Mean body weight showed a non-significant increase and resting metabolic rate a non-significant decrease. This explorative study indicates that unfavourable changes in body composition might occur after intrathecal baclofen therapy. Since obesity and increased fat body mass contribute to an increased cardiovascular risk, these findings may indicate a need for initiation of countermeasures, e.g. increased physical activity and/or dietary measures, in conjunction with intrathecal baclofen therapy. Further studies, including larger study samples and control groups, are needed to corroborate these findings.

The outcome of clinical parameters in adults with severe Type I Gaucher disease using very low dose enzyme replacement therapy.

PubMed

Wilson, Callum; Spearing, Ruth; Teague, Lochie; Robertson, Patsy; Blacklock, Hilary

2007-01-01

Enzyme replacement therapy is now well established as the treatment of choice in Type I Gaucher disease. Historically higher dosage regimens have been used in preference to lower doses despite the little clinical evidence in the way of large controlled clinical trials to support this. Moreover, the extraordinary cost of therapy means that not all eligible patients are able to be treated at the higher dose. Twelve type I adult patients with relatively severe disease were commenced on a very low dose of 7.5U of alglucerase/imiglucerase per kg every two weeks (initially given thrice weekly and later weekly). Follow-up 5 year data reveal a good visceral and haematological response with outcomes consistent with recently published treatment guidelines. Satisfactory clinical and radiological skeletal improvement was also demonstrated in most patients. Three patients had an inadequate overall skeletal response to therapy. Biomarkers also steadily improved although perhaps not quite at the same rate as that seen in higher doses. Very low dose enzyme replacement therapy may be appropriate for adult type I Gaucher patients with mild-moderate skeletal disease.

Deliverability and efficacy of R-CHOP chemotherapy in very elderly patients with diffuse large B-cell lymphoma: an Australian retrospective analysis.

PubMed

Millar, A; Ellis, M; Mollee, P; Cochrane, T; Fletcher, J; Caudron, A; Webster, B; Trotman, J

2015-11-01

Elderly patients with diffuse large B-cell lymphoma (DLBCL) have an inferior prognosis, due in part to advanced age and pre-existing comorbidities, with reduced tolerability and deliverability of standard R-CHOP chemotherapy. To examine the deliverability, toxicity and efficacy of R-CHOP and the prevalence of the germinal and non-germinal phenotype DLBCL in an elderly Australian cohort. This retrospective analysis included patients ≥75 years diagnosed with DLBCL. Comprehensive chemotherapy and toxicity data were collected for patients treated with R-CHOP. Baseline demographics and chemotherapy characteristics were compared with progression-free (PFS) and overall survival (OS). Immunohistochemical staining identified the prevalence of the non-germinal centre (non-GCB) phenotype. Of the 111 patients, 92 (83%) commenced R-CHOP with 26/92 (28%) receiving ≤4 cycles. Median average relative dose (ARD) was 0.80 (0.07-1.17). Median average relative dose intensity (ARDI) was 0.89 (0.33-1.18). Serious adverse events occurred in 77% of patients with ≥Gd3 adverse events in 74%. Overall response rate was 85%. Two-year PFS was 63% and OS 74%. ARD and performance status ≥2 were significant prognostic factors for PFS and OS but not ARDI. Non-GCB-phenotype was identified in 44/72 (61%) of patients with immunohistochemical data. Despite high response rates and respectable survival estimates, the absence of standard therapy in 17% of patients, and dose reductions and serious toxicity of R-CHOP in this Australian cohort highlights the need for the development of less toxic yet efficacious treatments for very elderly patients with DLBCL. The high prevalence of the non-GCB phenotype highlights the potential value of targeted biological therapy for this demographic. © 2015 Royal Australasian College of Physicians.

Occupational therapy students' perceptions of occupational therapy.

PubMed

Turpin, Merrill June; Rodger, Sylvia; Hall, Anna R

2012-10-01

An understanding of students' perceptions of occupational therapy on entry is required to recognise how professional socialisation occurs through curriculum. Findings pertain to a qualitative study investigating students' perceptions of occupational therapy upon entry to two occupational therapy programmes in Australia. Students commencing Bachelor of Occupational Therapy and Masters of Occupational Therapy Studies programmes participated in the study (n = 462). A purpose-designed questionnaire was distributed to students in the first lecture of each programme. Preliminary analysis comprised identification of keywords/phrases and coding categories were generated from patterns of keywords. Frequency counts and percentages of keywords/phrases within categories were completed. Students' responses were categorised as 'what' occupational therapists do; 'how' they do it; 'why' they do it; and 'who' they work with. In 'what' occupational therapists do students frequently described 'helping' people. Both undergraduate and graduate entry masters students used the term 'rehabilitation' to describe how occupational therapy is done, with graduate entry students occasionally responding with 'through occupation' and 'modifying the environment'. Students perceived the 'why' of occupational therapy as getting back to 'everyday activities', with some students emphasising returning to 'normal' activities or life. Regarding the 'who' category, students also thought occupational therapists worked with people with an 'injury' or 'disability'. Students entered their occupational therapy programmes with perceptions consistent with the general public's views of occupational therapy. However, graduate entry students exposed to a pre-reading package prior to entry had more advanced occupational therapy concepts than undergraduate students. © 2011 The Authors. Australian Occupational Therapy Journal © 2011 Occupational Therapy Australia.

A Qualitative Investigation into Why the Motivation of Massage Therapy Students Changes over the Course of Their Professional Education

PubMed Central

Finch, Paul

2009-01-01

Purpose: In previous research, the motivation of massage therapy students was observed to change between commencement of their professional studies and entry into practice. The change involved a decrease in intrinsic motivation (associated with altruism) and an increase in extrinsic motivation (associated with the prospect of external rewards). This paper reports on the influences underlying those changes. Methods: The research used a qualitative design in which data were collected during a series of individual in-depth semi-structured interviews with massage therapy graduates, just after completion of a 2-year (2200-hour) full-time program. After informed consent was obtained, interviews were taped, transcribed, and analyzed, resulting in identification of a number of themes and subthemes. Results: Previously noted changes in student motivation involved an increase in the influence of extrinsic rewards and a decrease in motivation related to helping and working with people. The findings of the present study suggest that these changes are explained by two main themes, each with a number of subthemes. The first theme, The Reality of Life in Practice, is associated with two subthemes: Debt Load, and Effectiveness in Achieving Positive Health Outcomes. The second theme, An Evolving Self-Image As a Health Care Professional, is associated with three sub-themes: Rigor/Intensity of the Educational Program, Developing Perspective of Massage Therapy As a Career, and Interaction with Faculty. Conclusions: The data suggest that the change in motivation noted in previous work (increased extrinsic motivation and decreased intrinsic motivation) is influenced in different ways by each identified theme. Although schools must be vigilant in ensuring that their programs support the humanistic mission of health care, the present study indicates that the change in motivation noted in earlier work is not sinister. Rather, it appears to be related to the development of a realistic perspective of life as a health care practitioner, which departs from the more naïve expectations of students when they commence their professional studies. PMID:21589720

Biological Gene Delivery Vehicles: Beyond Viral Vectors

PubMed Central

Seow, Yiqi; Wood, Matthew J

2009-01-01

Gene therapy covers a broad spectrum of applications, from gene replacement and knockdown for genetic or acquired diseases such as cancer, to vaccination, each with different requirements for gene delivery. Viral vectors and synthetic liposomes have emerged as the vehicles of choice for many applications today, but both have limitations and risks, including complexity of production, limited packaging capacity, and unfavorable immunological features, which restrict gene therapy applications and hold back the potential for preventive gene therapy. While continuing to improve these vectors, it is important to investigate other options, particularly nonviral biological agents which include bacteria, bacteriophage, virus-like particles (VLPs), erythrocyte ghosts, and exosomes. Exploiting the natural properties of these biological entities for specific gene delivery applications will expand the repertoire of gene therapy vectors available for clinical use. Here, we review the prospects for nonviral biological delivery vehicles as gene therapy agents with focus on their unique evolved biological properties and respective limitations and potential applications. The potential of these nonviral biological entities to act as clinical gene therapy delivery vehicles has already been shown in clinical trials using bacteria-mediated gene transfer and with sufficient development, these entities will complement the established delivery techniques for gene therapy applications. PMID:19277019

Biological gene delivery vehicles: beyond viral vectors.

PubMed

Seow, Yiqi; Wood, Matthew J

2009-05-01

Gene therapy covers a broad spectrum of applications, from gene replacement and knockdown for genetic or acquired diseases such as cancer, to vaccination, each with different requirements for gene delivery. Viral vectors and synthetic liposomes have emerged as the vehicles of choice for many applications today, but both have limitations and risks, including complexity of production, limited packaging capacity, and unfavorable immunological features, which restrict gene therapy applications and hold back the potential for preventive gene therapy. While continuing to improve these vectors, it is important to investigate other options, particularly nonviral biological agents which include bacteria, bacteriophage, virus-like particles (VLPs), erythrocyte ghosts, and exosomes. Exploiting the natural properties of these biological entities for specific gene delivery applications will expand the repertoire of gene therapy vectors available for clinical use. Here, we review the prospects for nonviral biological delivery vehicles as gene therapy agents with focus on their unique evolved biological properties and respective limitations and potential applications. The potential of these nonviral biological entities to act as clinical gene therapy delivery vehicles has already been shown in clinical trials using bacteria-mediated gene transfer and with sufficient development, these entities will complement the established delivery techniques for gene therapy applications.

A report on the first case of vancomycin-intermediate Staphylococcus aureus (VISA) in Hawai'i.

PubMed

Chaiwongkarjohn, Suttirak; Pramyothin, Pornpoj; Suwantarat, Nuntra; Bankowski, Matthew J; Koyamatsu, Terrie; Seifried, Steven E; Bello, Erlaine F

2011-11-01

The state of Hawai'i has the highest prevalence of methicillin-resistant Staphylococcus aureus (MRSA) infection in the United States. Since vancomycin is the most frequently-prescribed antibiotic for healthcare-associated MRSA infection, there is concern for development of vancomycin resistance. We report on a 61 year-old woman with history of previous successful treatments of MRSA bacteremia with vancomycin. She was later hospitalized for catheter-related MRSA bacteremia that persisted despite vancomycin treatment. The vancomycin minimal inhibitory concentration (MIC) was initially 1-2 µg/ml, suggesting susceptibility, but changed to 4 µg/ml. At this level, the organism was classified as a vancomycin-intermediate Staphylococcus aureus (VISA). Therapy was changed from vancomycin to daptomycin, and the patient's blood cultures were sterilized. High suspicion of VISA should be raised in MRSA-infected patients who fail or have a history of vancomycin therapy so that additional susceptibility testing and appropriate antibiotic therapy can be promptly commenced to reduce the morbidity associated with VISA infection.

Annually recurring parthenogenesis in a zebra shark Stegostoma fasciatum.

PubMed

Robinson, D P; Baverstock, W; Al-Jaru, A; Hyland, K; Khazanehdari, K A

2011-11-01

A zebra shark, Stegostoma fasciatum, held in captivity at the Burj Al Arab aquarium, produced embryos and pups in the absence of a male. A total of 15 pups were produced from eggs laid within the aquarium over a period of four consecutive years commencing 2007. Parthenogenesis was confirmed through DNA analysis for three pups sampled during the first two consecutive egg cycles and is presumed to be the method of reproduction responsible thereafter. © 2011 The Authors. Journal of Fish Biology © 2011 The Fisheries Society of the British Isles.

Ketogenic Diet Therapy in Infants: Efficacy and Tolerability.

PubMed

Wirrell, Elaine; Eckert, Susan; Wong-Kisiel, Lily; Payne, Eric; Nickels, Katherine

2018-05-01

This study evaluated tolerability and efficacy of the ketogenic diet in infants less than 12 months of age. Infants less than 12 months of age, commencing the ketogenic diet between September 2007 and July 2016 were identified. Records were reviewed for epilepsy details, diet initiation details, efficacy and tolerability. Twenty-seven infants commenced the ketogenic diet (56% male, median age seven months). Median age at seizure onset was 1.9 months and 92% had daily seizures. An epilepsy syndrome was noted in 19 (West-11, epilepsy in infancy with migrating focal seizures-5, early myoclonic encephalopathy-1, Ohtahara-1, Dravet-1). Infants were on a median of two and had failed a median of one medications for lack of efficacy. All initiated a traditional ketogenic diet at full calories without fasting, and all but one started the diet in hospital. Significant hypoglycemia during initiation was seen in two - both had emesis +/- decreased oral intake. Eighty-eight percent developed urinary ketosis by 48 hours and all were successfully discharged on the diet (median ratio 3:1). Of those continuing dietary therapy, responder rates at one, six and 12 months were 68%, 82% and 91%, with 20%, 29% and 27% achieving seizure freedom. By 12 months, two stopped the diet for serious adverse effects, five discontinued for lack of efficacy, six were lost to follow-up and two died of unrelated causes. The ketogenic diet is an effective and well-tolerated treatment for infants with intractable epilepsy. In-hospital initiation is strongly recommended due to risk of hypoglycemia with emesis or reduced intake. Copyright © 2018 Elsevier Inc. All rights reserved.

Insulin oedema and treatment-induced neuropathy occurring in a 20-year-old patient with Type 1 diabetes commenced on an insulin pump.

PubMed

Rothacker, K M; Kaye, J

2014-01-01

Oedema may occur following initiation or intensification of insulin therapy in patients with Type 1 and Type 2 diabetes. Mild oedema is thought to be not uncommon, but under-reported, whilst generalized oedema with involvement of serous cavities has rarely been described. Multiple pathogenic mechanisms have been proposed, including insulin-induced sodium and water retention. Patients at greater risk for insulin oedema include those with poor glycaemic control. Dramatic improvement in glycaemic control is also associated with sensory and autonomic neuropathy. We describe a case of generalized oedema occurring in a 20-year-old, low body weight patient with Type 1 diabetes with poor glycaemic control 3 days following commencement of an insulin pump; blood sugars had dramatically improved with this treatment. Alternative causes for oedema were excluded. Oedema slowly improved with insulin dose reduction with higher blood sugar targets plus frusemide treatment. Subsequent to oedema resolution, the patient unfortunately developed generalized neuropathic pain, thought to be another manifestation of rapid improvement in glycaemic control. Caution should be taken when a patient with diabetes that is poorly controlled has an escalation in therapy that may dramatically improve their blood sugar levels; this includes the initiation of an insulin pump. Clinicians and patients should be aware of the potential risk of insulin oedema, treatment-induced neuropathy and worsening of diabetic retinopathy in the setting of rapid improvement in glycaemic control. © 2013 The Authors. Diabetic Medicine © 2013 Diabetes UK.

Antiretroviral therapy CNS penetration and HIV-1-associated CNS disease.

PubMed

Garvey, L; Winston, A; Walsh, J; Post, F; Porter, K; Gazzard, B; Fisher, M; Leen, C; Pillay, D; Hill, T; Johnson, M; Gilson, R; Anderson, J; Easterbrook, P; Bansi, L; Orkin, C; Ainsworth, J; Palfreeman, A; Gompels, M; Phillips, A N; Sabin, C A

2011-02-22

The impact of different antiretroviral agents on the risk of developing or surviving CNS disease remains unknown. The aim of this study was to investigate whether using antiretroviral regimens with higher CNS penetration effectiveness (CPE) scores was associated with reduced incidence of CNS disease and improved survival in the UK Collaborative HIV Cohort (CHIC) Study. Adults without previous CNS disease, who commenced combination antiretroviral therapy (cART) between 1996 and 2008, were included (n = 22,356). Initial and most recent cART CPE scores were calculated. CNS diseases were HIV encephalopathy (HIVe), progressive multifocal leukoencephalopathy (PML), cerebral toxoplasmosis (TOXO), and cryptococcal meningitis (CRYPTO). Incidence rates and overall survival were stratified by CPE score. A multivariable Poisson regression model was used to identify independent associations. The median (interquartile range) CPE score for initial cART regimen increased from 7 (5-8) in 1996-1997 to 9 (8-10) in 2000-2001 and subsequently declined to 6 (7-8) in 2006-2008. Differences in gender, HIV acquisition risk group, and ethnicity existed between CPE score strata. A total of 251 subjects were diagnosed with a CNS disease (HIVe 80; TOXO 59; CRYPTO 56; PML 54). CNS diseases occurred more frequently in subjects prescribed regimens with CPE scores ≤ 4, and less frequently in those with scores ≥ 10; however, these differences were nonsignificant. Initial and most recent cART CPE scores ≤ 4 were independently associated with increased risk of death. Clinical status at time of commencing cART influences antiretroviral selection and CPE score. This information should be considered when utilizing CPE scores for retrospective analyses.

CD4 cell responses to combination antiretroviral therapy in patients starting therapy at high CD4 cell counts.

PubMed

Wright, Stephen T; Carr, Andrew; Woolley, Ian; Giles, Michelle; Hoy, Jennifer; Cooper, David A; Law, Matthew G

2011-09-01

To examine CD4 cell responses to combination antiretroviral therapy (cART) in patients enrolled in the Australian HIV Observational Database who commenced cART at CD4 cell counts >350 cells per microliter. CD4 cell counts were modelled using random effects, repeated measurement models in 432 HIV-infected adults from Australian HIV Observational Database who commenced their first cART regimen and had a baseline CD4 count >350 cells per microliter. Using published AIDS and/or death incidence rates combined with the data summarized by time and predicted CD4 cell count, we calculated the expected reduction in risk of an event for different starting baseline CD4 strata. Mean CD4 counts increased above 500 cells per microliter in all baseline CD4 strata by 12 months (means of 596, 717, and 881 cells/μL in baseline CD4 strata 351-500, 501-650, and >650 cells/μL, respectively) and after 72 months since initiating cART, mean CD4 cell counts (by increasing baseline CD4 strata) were 689, 746, 742 cells per microliter. The expected reduction in risk of mortality for baseline CD4 counts >650 cells per microliter relative to 351-500 cells per microliter was approximately 8%, an absolute risk reduction 0.33 per 1000 treated patient-years. Patients starting cART at high CD4 cell counts (>650 cells/μL) tend to maintain this immunological level over 6 years of follow-up. Patients starting from 351 to 500 CD4 cells per microliter achieve levels of >650 cells per microliter after approximately 3 years of cART. Initiating cART with a baseline CD4 count 501-650 or >650 cells per microliter relative to 351-500 cells per microliter indicated a minimal reduction in risk of AIDS incidence and/or death.

Experiences of mobility for people living with rheumatoid arthritis who are receiving biologic drug therapy: implications for podiatry services.

PubMed

Sanders, Lucy; Donovan-Hall, Margaret; Borthwick, Alan; Bowen, Catherine J

2017-01-01

Despite significant advancements in new treatment modalities for rheumatoid arthritis with biological therapies, foot complications remain a disabling and common feature of the disease . In this study the aim was to explore and describe the personal experiences of people with rheumatoid arthritis in receipt of biologic treatments in a bid to understand the impact of this form of medication on their mobility. An interpretative phenomenological analysis (IPA) was undertaken to explore in depth the individual experience of rheumatoid disease through personal accounts of the patient journey spanning both 'before' and 'after' the instigation of biologic therapy. A purposive sampling strategy was adopted and in-depth semi structured interviews used to facilitate rich, detailed interview data exploring the lived experiences of individuals undertaking biological therapy and the changes to mobility experienced as a result. Thematic analysis was employed with an IPA framework to identify key meanings, and report patterns within the data. Five people with rheumatoid arthritis participated in the study. The mean disease duration was 20.2 years (range: 6 -32) and all were being treated with biologic therapies. Four key themes emerged from the data: 1) Life before biologic treatment, depicted in accounts as a negative experience characterised by painful and disabling symptoms and feelings of hopelessness. 2) Life with biologic treatment, often experienced as a life changing transition, restoring function and mobility and offering renewed hope. 3) Sense of self, in which the impact of rheumatoid disease and the subsequent changes arising from biologic therapy reveal a profound impact on feelings of personal identity both pre and post biologic therapy; an effect of footwear on self-image emerges as a dominant sub theme; 4) Unmet footcare needs were evident in the patient narrative, where the unrelenting if diminished impact of foot pain on mobility was viewed in the context of problematic access to foot health services. Whilst the findings from this study mirror those within the existing literature, which report improvements in physical function related to biological therapy, foot problems clearly remained an unremitting feature of life for patients with rheumatoid disease, even when in receipt of biologics.

Aromatherapy in midwifery practice.

PubMed

Einion, Alys

2016-05-01

Aromatherapy is a complementary therapy that uses essential oils of plants to achieve therapeutic effects. Midwives can offer complementary therapies to women if they have been trained in their use and follow the required professional frameworks for regulation, permissions, monitoring and insurance. This article explores the use of aromatherapy to ease a common condition of pregnancy: that of lower back pain. This may be due to the lordosis of pregnancy, caused by the hormone relaxin--which increases in pregnancy and causes greater flexibility of joints and connective tissue--and by changes in body mass and centre of gravity; but it could also be caused by something else, such as strain or repeated movement. Any midwife offering aromatherapy should ensure that all other potential conditions and contraindications have been considered before commencing treatment, and would carry out a full assessment including taking adetailed history.

Is the Nintendo Wii Fit really acceptable to older people?: a discrete choice experiment

PubMed Central

2011-01-01

Background Interactive video games such as the Nintendo Wii Fit are increasingly used as a therapeutic tool in health and aged care settings however, their acceptability to older people is unclear. The aim of this study was to determine the acceptability of the Nintendo Wii Fit as a therapy tool for hospitalised older people using a discrete choice experiment (DCE) before and after exposure to the intervention. Methods A DCE was administered to 21 participants in an interview style format prior to, and following several sessions of using the Wii Fit in physiotherapy. The physiotherapist prescribed the Wii Fit activities, supervised and supported the patient during the therapy sessions. Attributes included in the DCE were: mode of therapy (traditional or using the Wii Fit), amount of therapy, cost of therapy program and percentage of recovery made. Data was analysed using conditional (fixed-effects) logistic regression. Results Prior to commencing the therapy program participants were most concerned about therapy time (avoiding programs that were too intensive), and the amount of recovery they would make. Following the therapy program, participants were more concerned with the mode of therapy and preferred traditional therapy programs over programs using the Wii Fit. Conclusions The usefulness of the Wii Fit as a therapy tool with hospitalised older people is limited not only by the small proportion of older people who are able to use it, but by older people's preferences for traditional approaches to therapy. Mainstream media portrayals of the popularity of the Wii Fit with older people may not reflect the true acceptability in the older hospitalised population. PMID:22011360

Switching of biologics in psoriasis: Reasons and results.

PubMed

Honda, Hiromi; Umezawa, Yoshinori; Kikuchi, Sota; Yanaba, Koichi; Fukuchi, Osamu; Ito, Toshihiro; Nobeyama, Yoshimasa; Asahina, Akihiko; Nakagawa, Hidemi

2017-09-01

Efficacy and safety profiles of biologics have been established for moderate to severe psoriasis. However, inefficacy or adverse events sometimes require changing the treatment to other biologics. Here, we examine the effectiveness of this strategy. We retrospectively investigated cases requiring switching biologics. We enrolled 275 psoriatic patients treated with biologics between January 2010 and December 2014 in our hospital. Of these, 51 required a switch to another biologic. First-line therapies were infliximab (IFX, n = 26), adalimumab (ADA, n = 18) and ustekinumab (UST, n = 7), and second-line therapies were IFX (n = 5), ADA (n = 21) and UST (n = 25). Reasons for switching were inefficacy (n = 38), adverse events (n = 11) and others (n = 2). The details were primary failure (n = 15), secondary failure (n = 23) and infusion reactions (n = 8). In 49 patients who switched biologics due to inefficacy and adverse events, the mean Psoriasis Area and Severity Index (PASI) score at week 16 was 4.3 for first-line therapies and 2.9 for second-line therapies (P < 0.05). Switching to a second biologic therapy to address the first's inefficacy or adverse events often results in significant improvement in moderate to severe psoriasis. © 2017 Japanese Dermatological Association.

Effects of background statin therapy on glycemic response and cardiovascular events following initiation of insulin therapy in type 2 diabetes: a large UK cohort study.

PubMed

Anyanwagu, Uchenna; Mamza, Jil; Donnelly, Richard; Idris, Iskandar

2017-08-22

Statins may increase the risk of new-onset diabetes and adversely affect glycaemic control, but their effects on the glycemic response and mortality outcomes following commencement of insulin therapy in patients with Type 2 Diabetes (T2D) are unclear. A retrospective cohort study was conducted in 12,725 insulin initiators with T2D using The Health Improvement Network (THIN) UK database. Changes in HbA1c at 6, 12, 24 and 36 months, and the 5-year risk of mortality and (3-point) major adverse cardiovascular events (MACE), were compared between prior users (n = 10,682) and non-users (n = 2043) of statin therapy who were newly commenced on insulin treatment. Cox proportional hazard models were used to estimate the hazard ratios of the different outcomes. Mean age of the cohort was 58.7 ± 14.0 years (51% male) and mean baseline HbA1c was 8.7 ± 1.8%. A greater initial reduction in HbA1c was observed following insulin initiation in the non-users of statins compared with the users, which was significant in the short term (-0.34% vs -0.26% at 6 months; mean diff = -0.09%, p = 0.004) but not in the long term: -0.31% versus -0.35% at 3 years (mean diff = 0.05%, p = 0.344). CV events (3-point MACE) were 878 versus 217 in statin users versus non-users (20.7 vs 30.9 per 1000 person-years; adjusted Hazard Ratio (aHR) 1.36 (95% CI 1.15-1.62; p < 0.0001). In a subgroup analysis of individual statins, HbA1c was higher throughout the study duration with all statins relative to non-users of statin therapy (p < 0.05). The aHRs for 3-point MACE for atorvastatin, simvastatin, rosuvastatin and pravastatin were 0.82 (95% CI 0.68-0.98), 0.67 (0.55-0.82), 0.56 (0.39-0.81) and 0.78 (0.60-1.01), respectively. Following initiation of insulin therapy in patients with T2D in routine care, concurrent use of a statin was associated with less good glycaemic control in the short-term but a much lower risk of major adverse CV events.

Outcomes in patients with chronic kidney disease not on dialysis receiving extended dosing regimens of darbepoetin alfa: long-term results of the EXTEND observational cohort study.

PubMed

Galle, Jan-Christoph; Addison, Janet; Suranyi, Michael G; Claes, Kathleen; Di Giulio, Salvatore; Guerin, Alain; Herlitz, Hans; Kiss, István; Farouk, Mourad; Manamley, Nick; Wirnsberger, Gerhard; Winearls, Christopher

2016-12-01

Extended dosing of the erythropoiesis-stimulating agent (ESA) darbepoetin alfa (DA) once biweekly or monthly reduces anaemia treatment burden. This observational study assessed outcomes and dosing patterns in patients with chronic kidney disease not on dialysis (CKD-NoD) commencing extended dosing of DA. Adult CKD-NoD patients starting extended dosing of DA in Europe or Australia in June 2006 or later were followed up until December 2012. Outcomes included haemoglobin (Hb) concentration, ESA dosing, mortality rates and receipt of dialysis and renal transplantation. Subgroup analyses were conducted for selected outcomes. Of 6035 enrolled subjects, 5723 (94.8%) met analysis criteria; 1795 (29.7%) received dialysis and 238 (3.9%) underwent renal transplantation. Mean (standard deviation) Hb concentration at commencement of extended dosing was 11.0 (1.5) g/dL. Mean [95% confidence interval (CI)] Hb 12 months after commencement of extended dosing (primary outcome) was 11.6 g/dL (11.5, 11.6) overall and was similar across countries, with no differences between subjects previously treated with an ESA versus ESA-naïve subjects, subjects with versus without prior renal transplant or diabetics versus non-diabetics. Weekly ESA dose gradually decreased following commencement of extended DA dosing and was similar across subgroups. The decrease in weekly DA dose was accompanied by an increase in the proportion of patients receiving iron therapy. Hb concentrations declined following changes in ESA labels and treatment guidelines. The mortality rate (95% CI) was 7.06 (6.68, 7.46) deaths per 100 years of follow-up. Subjects alive at study end had stable Hb concentrations in the preceding year, while those who died had lower and declining Hb concentrations in their last year. Long-term, extended dosing of DA maintained Hb concentrations in patients already treated with an ESA and corrected and maintained Hb in ESA-naïve patients. © The Author 2016. Published by Oxford University Press on behalf of ERA-EDTA.

Value of biologic therapy: a forecasting model in three disease areas.

PubMed

Paramore, L Clark; Hunter, Craig A; Luce, Bryan R; Nordyke, Robert J; Halbert, R J

2010-01-01

Forecast the return on investment (ROI) for advances in biologic therapies in years 2015 and 2030, based upon impact on disease prevalence, morbidity, and mortality for asthma, diabetes, and colorectal cancer. A deterministic, spreadsheet-based, forecasting model was developed based on trends in demographics and disease epidemiology. 'Return' was defined as reductions in disease burden (prevalence, morbidity, mortality) translated into monetary terms; 'investment' was defined as the incremental costs of biologic therapy advances. Data on disease prevalence, morbidity, mortality, and associated costs were obtained from government survey statistics or published literature. Expected impact of advances in biologic therapies was based on expert opinion. Gains in quality-adjusted life years (QALYs) were valued at $100,000 per QALY. The base case analysis, in which reductions in disease prevalence and mortality predicted by the expert panel are not considered, shows the resulting ROIs remain positive for asthma and diabetes but fall below $1 for colorectal cancer. Analysis involving expert panel predictions indicated positive ROI results for all three diseases at both time points, ranging from $207 for each incremental dollar spent on biologic therapies to treat asthma in 2030, to $4 for each incremental dollar spent on biologic therapies to treat colorectal cancer in 2015. If QALYs are not considered, the resulting ROIs remain positive for all three diseases at both time points. Society may expect substantial returns from investments in innovative biologic therapies. These benefits are most likely to be realized in an environment of appropriate use of new molecules. The potential variance between forecasted (from expert opinion) and actual future health outcomes could be significant. Similarly, the forecasted growth in use of biologic therapies relied upon unvalidated market forecasts.

Ethnographic Observational Study of the Biologic Initiation Conversation Between Rheumatologists and Biologic-Naive Rheumatoid Arthritis Patients.

PubMed

Kottak, Nicholas; Tesser, John; Leibowitz, Evan; Rosenberg, Melissa; Parenti, Dennis; DeHoratius, Raphael

2018-01-30

This ethnographic market research study investigated the biologic initiation conversation between rheumatologists and biologic-naive patients with rheumatoid arthritis to assess how therapy options, particularly mode of administration, were discussed. Consenting rheumatologists (n = 16) and patients (n = 48) were videotaped during medical visits and interviewed by a trained ethnographer. The content, structure, and timing of conversations regarding biologic initiation were analyzed. The mean duration of physician-patient visits was approximately 15 minutes; biologic therapies were discussed for a mean of 5.6 minutes. Subcutaneous (SC) and intravenous (IV) therapy options were mentioned in 45 and 35 visits, respectively, out of a total of 48 visits. All patients had some familiarity with SC administration, but nearly half of patients (22 of 48) were unfamiliar with IV therapy going into the visit. IV administration was not defined or described by rheumatologists in 77% of visits (27 of 35) mentioning IV therapy. Thus, 19 of 22 patients who were initially unfamiliar with IV therapy remained unfamiliar after the visit. Disparities in physician-patient perceptions were revealed, as all rheumatologists (16 of 16) believed IV therapy would be less convenient than SC therapy for patients, while 46% of patients (22 of 48) felt this way. In post-visit interviews, some patients seemed confused and overwhelmed, particularly when presented with many treatment choices in a visit. Some patients stated they would benefit from visual aids or summary sheets of key points. This study revealed significant educational opportunities to improve the biologic initiation conversation and indicated a disparity between patients' and rheumatologists' perception of IV therapy. © 2018 The Authors. Arthritis Care & Research published by Wiley Periodicals, Inc. on behalf of American College of Rheumatology.

5 CFR 844.301 - Commencing date of disability annuity.

Code of Federal Regulations, 2010 CFR

2010-01-01

... 5 Administrative Personnel 2 2010-01-01 2010-01-01 false Commencing date of disability annuity... Disability Annuity § 844.301 Commencing date of disability annuity. A disability annuity under this part... requirements for title to an annuity. ...

Cancer Immunotherapy

MedlinePlus

Immunotherapy is a cancer treatment that helps your immune system fight cancer. It is a type of biological therapy. Biological therapy uses substances ... t yet use immunotherapy as often as other cancer treatments, such as surgery, chemotherapy, and radiation therapy. ...

Prophylactic non-absorbable antibiotics in leukaemic patients.

PubMed Central

King, K.

1980-01-01

A regimen of oral non-absorbable prophylactic antibiotics (kanamycin-vancomycin-nystatin) was given to nine severely neutropaenic leukaemic patients on cytotoxic therapy (11 courses), in conjunction with isolation procedures. An appreciable decrease in faecal organisms, especially anaerobes, was apparent after 48 h of commencing the course, and most bacteria had disappeared from the stool after five days. There were three episodes of septicaemia, all with enteric organisms, whilst on these antibiotics; one proved fatal. The emergence of resistance to aminoglycosides in faecal flora, notably Klebsiella, in 6/11 courses constituted a major problem in the use of such prophylaxis. PMID:7052229

Prophylactic non-absorbable antibiotics in leukaemic patients.

PubMed

King, K

1980-08-01

A regimen of oral non-absorbable prophylactic antibiotics (kanamycin-vancomycin-nystatin) was given to nine severely neutropaenic leukaemic patients on cytotoxic therapy (11 courses), in conjunction with isolation procedures. An appreciable decrease in faecal organisms, especially anaerobes, was apparent after 48 h of commencing the course, and most bacteria had disappeared from the stool after five days. There were three episodes of septicaemia, all with enteric organisms, whilst on these antibiotics; one proved fatal. The emergence of resistance to aminoglycosides in faecal flora, notably Klebsiella, in 6/11 courses constituted a major problem in the use of such prophylaxis.

38 CFR 21.4131 - Commencing dates.

Code of Federal Regulations, 2010 CFR

2010-07-01

...) VOCATIONAL REHABILITATION AND EDUCATION Administration of Educational Assistance Programs Payments; Educational Assistance Allowance § 21.4131 Commencing dates. VA will determine under this section the commencing date of an award or increased award of educational assistance provided pursuant to subpart C or G...

38 CFR 21.4131 - Commencing dates.

Code of Federal Regulations, 2011 CFR

2011-07-01

...) VOCATIONAL REHABILITATION AND EDUCATION Administration of Educational Assistance Programs Payments; Educational Assistance Allowance § 21.4131 Commencing dates. VA will determine under this section the commencing date of an award or increased award of educational assistance provided pursuant to subpart C or G...

42 CFR 419.64 - Transitional pass-through payments: Drugs and biologicals.

Code of Federal Regulations, 2014 CFR

2014-10-01

..., 2000. (2) Cancer therapy drugs and biologicals. A drug or biological that is used in cancer therapy... 42 Public Health 3 2014-10-01 2014-10-01 false Transitional pass-through payments: Drugs and...-through payments: Drugs and biologicals. (a) Eligibility for pass-through payment. CMS makes a...

42 CFR 419.64 - Transitional pass-through payments: Drugs and biologicals.

Code of Federal Regulations, 2012 CFR

2012-10-01

..., 2000. (2) Cancer therapy drugs and biologicals. A drug or biological that is used in cancer therapy... 42 Public Health 3 2012-10-01 2012-10-01 false Transitional pass-through payments: Drugs and...-through payments: Drugs and biologicals. (a) Eligibility for pass-through payment. CMS makes a...

42 CFR 419.64 - Transitional pass-through payments: Drugs and biologicals.

Code of Federal Regulations, 2013 CFR

2013-10-01

..., 2000. (2) Cancer therapy drugs and biologicals. A drug or biological that is used in cancer therapy... 42 Public Health 3 2013-10-01 2013-10-01 false Transitional pass-through payments: Drugs and...-through payments: Drugs and biologicals. (a) Eligibility for pass-through payment. CMS makes a...

Comparative study of the efficacy of topical steroid and antibiotic combination therapy versus oral antibiotic alone when treating acute rhinosinusitis.

PubMed

El-Hennawi, D M; Ahmed, M R; Farid, A M; Al Murtadah, A M

2015-05-01

Acute rhinosinusitis arises as a consequence of viral rhinitis, and bacterial infection can subsequently occur. Intranasal antibiotics as an adjunct to corticosteroids usually demonstrate the greatest symptom relief. We wanted to clinically evaluate the effects of a topical antibiotic and steroid combination administered intranasally, versus an oral antibiotic alone when treating acute rhinosinusitis. Forty patients with acute bacterial rhinosinusitis were divided into two groups. Group A received an antibiotic and steroid combination (ofloxacin 0.26 per cent and dexamethasone 0.053 per cent nasal drops) for 10 days, administered intranasally (5 drops in each nostril/8 hours). Group B, the control group, received an oral antibiotic alone (amoxicillin 90 mg/kg). Eight hours after commencing treatment, facial pain was more severe in group B and nasal obstruction was reduced in both groups. Ten days after commencing treatment, anterior nasal discharge was 0.15 per cent in group A and absent in group B. The application of a topical antibiotic and steroid combination into the nasal cavity is an effective way of treating uncomplicated, acute bacterial rhinosinusitis with the theoretical advantages of easy administration, high local drug concentration and minimal systemic adverse effects.

Economics of non-adherence to biologic therapies in rheumatoid arthritis.

PubMed

De Vera, Mary A; Mailman, Jonathan; Galo, Jessica S

2014-11-01

Adherence to biologic therapies among patients with rheumatoid arthritis is sub-optimal, with the proportion of adherent patients reported to be as low as 11 %. We found few studies evaluating economic outcomes, including health care costs, associated with non-adherence with biologic therapies. Findings suggest that while higher pharmacy costs drive total health care costs among adherent patients, non-adherent patients incur greater health care utilization including inpatient, outpatient, and laboratory services. Finally, economic factors are important determinants of adherence to biologics in patients with rheumatoid arthritis. Evidence to date has shown that higher out-of-pocket payments have a negative association with adherence to biologics. Furthermore, cost-related non-adherence is a highly prevalent problem in rheumatoid arthritis. Given the high costs of biologics and continued expansion of use in rheumatoid arthritis, there is need for more research to understand the economic implications of adherence to these therapies.

19 CFR 210.8 - Commencement of preinstitution proceedings.

Code of Federal Regulations, 2010 CFR

2010-04-01

... 19 Customs Duties 3 2010-04-01 2010-04-01 false Commencement of preinstitution proceedings. 210.8 Section 210.8 Customs Duties UNITED STATES INTERNATIONAL TRADE COMMISSION INVESTIGATIONS OF UNFAIR PRACTICES IN IMPORT TRADE ADJUDICATION AND ENFORCEMENT Commencement of Preinstitution Proceedings and...

SER consensus statement on the use of biologic therapy for systemic lupus erythematosus.

PubMed

Calvo-Alén, Jaime; Silva-Fernández, Lucía; Úcar-Angulo, Eduardo; Pego-Reigosa, José María; Olivé, Alejandro; Martínez-Fernández, Carmen; Martínez-Taboada, Víctor; Luis Marenco, José; Loza, Estíbaliz; López-Longo, Javier; Gómez-Reino, Juan Jesús; Galindo-Izquierdo, María; Fernández-Nebro, Antonio; Cuadrado, María José; Aguirre-Zamorano, María Ángeles; Zea-Mendoza, Antonio; Rúa-Figueroa, Iñigo

2013-01-01

To provide a reference to rheumatologists and other physicians involved in the treatment of systemic lupus erythematosus (SLE) who are using, or about to use biologic therapies. Recommendations were developed following a nominal group methodology and based on systematic reviews. The level of evidence and degree of recommendation were classified according to a model proposed by the Center for Evidence Based Medicine at Oxford. The level of agreement was established through a Delphi technique. We have produced recommendations on the use of belimumab, the only biological agent with approved indications for SLE, and other biological agents without an indication for SLE. The objective of treatment is to achieve a complete clinical response, taken as the absence of perceived or evident disease activity. Nuances regarding the use of biologic therapies in SLE were reviewed as well, such as the evaluation that should be performed prior to administration and the follow up of patients undergoing these therapies. We present the SER recommendations for the use of biological therapies in patients with SLE. Copyright © 2013 Elsevier España, S.L. All rights reserved.

Frequency and prognostic role of mucosal healing in patients with Crohn’s disease and ulcerative colitis after one-year of biological therapy

PubMed Central

Farkas, Klaudia; Lakatos, Péter László; Szűcs, Mónika; Pallagi-Kunstár, Éva; Bálint, Anita; Nagy, Ferenc; Szepes, Zoltán; Vass, Noémi; Kiss, Lajos S; Wittmann, Tibor; Molnár, Tamás

2014-01-01

AIM: To assess the endoscopic activity before and after a one-year period of biological therapy and to evaluate the frequency of relapses and need for retreatment after stopping the biologicals in patients with Crohn’s disease (CD) and ulcerative colitis (UC). METHODS: The data from 41 patients with CD and 22 patients with UC were assessed. Twenty-four CD patients received infliximab, and 17 received adalimumab. The endoscopic severity of CD was quantified with the simplified endoscopic activity score for Crohn’s disease in CD and with the Mayo endoscopic subscore in UC. RESULTS: Mucosal healing was achieved in 23 CD and 7 UC patients. Biological therapy had to be restarted in 78% of patients achieving complete mucosal healing with CD and in 100% of patients with UC. Neither clinical remission nor mucosal healing was associated with the time to restarting the biological therapy in either CD or UC. CONCLUSION: Mucosal healing did not predict sustained clinical remission in patients in whom the biological therapies had been stopped. PMID:24659890

Sex Differences in Dose Escalation and Overdose Death during Chronic Opioid Therapy: A Population-Based Cohort Study

PubMed Central

Kaplovitch, Eric; Gomes, Tara; Camacho, Ximena; Dhalla, Irfan A.; Mamdani, Muhammad M.; Juurlink, David N.

2015-01-01

Background The use of opioids for noncancer pain is widespread, and more than 16,000 die of opioid-related causes in the United States annually. The patients at greatest risk of death are those receiving high doses of opioids. Whether sex influences the risk of dose escalation or opioid-related mortality is unknown. Methods and Findings We conducted a cohort study using healthcare records of 32,499 individuals aged 15 to 64 who commenced chronic opioid therapy for noncancer pain between April 1, 1997 and December 31, 2010 in Ontario, Canada. Patients were followed from their first opioid prescription until discontinuation of therapy, death from any cause or the end of the study period. Among patients receiving chronic opioid therapy, 589 (1.8%) escalated to high dose therapy and n = 59 (0.2%) died of opioid-related causes while on treatment. After multivariable adjustment, men were more likely than women to escalate to high-dose opioid therapy (adjusted hazard ratio 1.44; 95% confidence interval 1.21 to 1.70) and twice as likely to die of opioid-related causes (adjusted hazard ratio 2.04; 95% confidence interval 1.18 to 3.53). These associations were maintained in a secondary analysis of 285,520 individuals receiving any opioid regardless of the duration of therapy. Conclusions Men are at higher risk than women for escalation to high-dose opioid therapy and death from opioid-related causes. Both outcomes were more common than anticipated. PMID:26291716

Description of Patients Treated with Biologic Drugs as First-Line Systemic Therapy in the BIOBADADERM Registry Between 2008 and 2016.

PubMed

Carretero Hernández, G; Ferrándiz, C; Rivera Díaz, R; Daudén Tello, E; de la Cueva-Dobao, P; Gómez-García, F J; Herrera-Ceballos, E; Belinchón Romero, I; López-Estebaranz, J L; Alsina Gibert, M; Sánchez-Carazo, J L; Ferrán Farrés, M; González Quesada, A; Carrascosa Carrillo, J M; Llamas-Velasco, M; Mendiola Fernández, M V; Ruiz Genao, D; Muñoz Santos, C; García-Doval, I; Descalzo, M A

2018-06-07

Biologic drugs are usually prescribed as second-line treatment for psoriasis, that is, after the patient has first been treated with a conventional psoriasis drug. There are, however, cases where, depending on the characteristics of the patient or the judgement of the physician, biologics may be chosen as first-line therapy. No studies to date have analyzed the demographics or clinical characteristics of patients in this setting or the safety profile of the agents used. The main aim of this study was to characterize these aspects of first-line biologic therapy and compare them to those observed for patients receiving biologics as second-line therapy. We conducted an observational study of 181 patients treated in various centers with a systemic biologic drug as first-line treatment for moderate to severe psoriasis between January 2008 and November 2016. All the patients were registered in the Spanish Registry of Adverse Events Associated with Biologic Drugs in Dermatology. The characteristics of the first- and second-line groups were very similar, although the patients receiving a biologic as first-line treatment for their psoriasis were older. No differences were observed for disease severity (assessed using the PASI) or time to diagnosis. Hypertension, diabetes, and liver disease were all more common in the first-line group. There were no differences between the groups in terms of reasons for drug withdrawal or occurrence of adverse effects. No major differences were found between patients with psoriasis receiving biologic drugs as first- or second-line therapy, a finding that provides further evidence of the safety of biologic therapy in patients with psoriasis. Publicado por Elsevier España, S.L.U.

6 CFR 27.310 - Commencement of adjudication proceedings.

Code of Federal Regulations, 2014 CFR

2014-01-01

... 6 Domestic Security 1 2014-01-01 2014-01-01 false Commencement of adjudication proceedings. 27.310 Section 27.310 Domestic Security DEPARTMENT OF HOMELAND SECURITY, OFFICE OF THE SECRETARY CHEMICAL FACILITY ANTI-TERRORISM STANDARDS Orders and Adjudications § 27.310 Commencement of adjudication...

6 CFR 27.310 - Commencement of adjudication proceedings.

Code of Federal Regulations, 2013 CFR

2013-01-01

... 6 Domestic Security 1 2013-01-01 2013-01-01 false Commencement of adjudication proceedings. 27.310 Section 27.310 Domestic Security DEPARTMENT OF HOMELAND SECURITY, OFFICE OF THE SECRETARY CHEMICAL FACILITY ANTI-TERRORISM STANDARDS Orders and Adjudications § 27.310 Commencement of adjudication...

6 CFR 27.310 - Commencement of adjudication proceedings.

Code of Federal Regulations, 2012 CFR

2012-01-01

... 6 Domestic Security 1 2012-01-01 2012-01-01 false Commencement of adjudication proceedings. 27.310 Section 27.310 Domestic Security DEPARTMENT OF HOMELAND SECURITY, OFFICE OF THE SECRETARY CHEMICAL FACILITY ANTI-TERRORISM STANDARDS Orders and Adjudications § 27.310 Commencement of adjudication...

6 CFR 27.310 - Commencement of adjudication proceedings.

Code of Federal Regulations, 2010 CFR

2010-01-01

... 6 Domestic Security 1 2010-01-01 2010-01-01 false Commencement of adjudication proceedings. 27.310 Section 27.310 Domestic Security DEPARTMENT OF HOMELAND SECURITY, OFFICE OF THE SECRETARY CHEMICAL FACILITY ANTI-TERRORISM STANDARDS Orders and Adjudications § 27.310 Commencement of adjudication...

6 CFR 27.310 - Commencement of adjudication proceedings.

Code of Federal Regulations, 2011 CFR

2011-01-01

... 6 Domestic Security 1 2011-01-01 2011-01-01 false Commencement of adjudication proceedings. 27.310 Section 27.310 Domestic Security DEPARTMENT OF HOMELAND SECURITY, OFFICE OF THE SECRETARY CHEMICAL FACILITY ANTI-TERRORISM STANDARDS Orders and Adjudications § 27.310 Commencement of adjudication...

45 CFR 2400.44 - Commencement of graduate study.

Code of Federal Regulations, 2013 CFR

2013-10-01

... 45 Public Welfare 4 2013-10-01 2013-10-01 false Commencement of graduate study. 2400.44 Section 2400.44 Public Welfare Regulations Relating to Public Welfare (Continued) JAMES MADISON MEMORIAL FELLOWSHIP FOUNDATION FELLOWSHIP PROGRAM REQUIREMENTS Graduate Study § 2400.44 Commencement of graduate study...

45 CFR 2400.44 - Commencement of graduate study.

Code of Federal Regulations, 2014 CFR

2014-10-01

... 45 Public Welfare 4 2014-10-01 2014-10-01 false Commencement of graduate study. 2400.44 Section 2400.44 Public Welfare Regulations Relating to Public Welfare (Continued) JAMES MADISON MEMORIAL FELLOWSHIP FOUNDATION FELLOWSHIP PROGRAM REQUIREMENTS Graduate Study § 2400.44 Commencement of graduate study...

45 CFR 2400.44 - Commencement of graduate study.

Code of Federal Regulations, 2012 CFR

2012-10-01

... 45 Public Welfare 4 2012-10-01 2012-10-01 false Commencement of graduate study. 2400.44 Section 2400.44 Public Welfare Regulations Relating to Public Welfare (Continued) JAMES MADISON MEMORIAL FELLOWSHIP FOUNDATION FELLOWSHIP PROGRAM REQUIREMENTS Graduate Study § 2400.44 Commencement of graduate study...

10 CFR 501.165 - Commencement of enforcement proceedings.

Code of Federal Regulations, 2010 CFR

2010-01-01

... 10 Energy 4 2010-01-01 2010-01-01 false Commencement of enforcement proceedings. 501.165 Section 501.165 Energy DEPARTMENT OF ENERGY (CONTINUED) ALTERNATE FUELS ADMINISTRATIVE PROCEDURES AND SANCTIONS Enforcement § 501.165 Commencement of enforcement proceedings. (a) Whenever, on the basis of any...

Neural reorganization accompanying upper limb motor rehabilitation from stroke with virtual reality-based gesture therapy.

PubMed

Orihuela-Espina, Felipe; Fernández del Castillo, Isabel; Palafox, Lorena; Pasaye, Erick; Sánchez-Villavicencio, Israel; Leder, Ronald; Franco, Jorge Hernández; Sucar, Luis Enrique

2013-01-01

Gesture Therapy is an upper limb virtual reality rehabilitation-based therapy for stroke survivors. It promotes motor rehabilitation by challenging patients with simple computer games representative of daily activities for self-support. This therapy has demonstrated clinical value, but the underlying functional neural reorganization changes associated with this therapy that are responsible for the behavioral improvements are not yet known. We sought to quantify the occurrence of neural reorganization strategies that underlie motor improvements as they occur during the practice of Gesture Therapy and to identify those strategies linked to a better prognosis. Functional magnetic resonance imaging (fMRI) neuroscans were longitudinally collected at 4 time points during Gesture Therapy administration to 8 patients. Behavioral improvements were monitored using the Fugl-Meyer scale and Motricity Index. Activation loci were anatomically labelled and translated to reorganization strategies. Strategies are quantified by counting the number of active clusters in brain regions tied to them. All patients demonstrated significant behavioral improvements (P < .05). Contralesional activation of the unaffected motor cortex, cerebellar recruitment, and compensatory prefrontal cortex activation were the most prominent strategies evoked. A strong and significant correlation between motor dexterity upon commencing therapy and total recruited activity was found (r2 = 0.80; P < .05), and overall brain activity during therapy was inversely related to normalized behavioral improvements (r2 = 0.64; P < .05). Prefrontal cortex and cerebellar activity are the driving forces of the recovery associated with Gesture Therapy. The relation between behavioral and brain changes suggests that those with stronger impairment benefit the most from this paradigm.

The effect of oral immunomodulatory therapy on treatment uptake and persistence in multiple sclerosis.

PubMed

Warrender-Sparkes, Matthew; Spelman, Tim; Izquierdo, Guillermo; Trojano, Maria; Lugaresi, Alessandra; Grand'Maison, François; Havrdova, Eva; Horakova, Dana; Boz, Cavit; Oreja-Guevara, Celia; Alroughani, Raed; Iuliano, Gerardo; Duquette, Pierre; Girard, Marc; Terzi, Murat; Hupperts, Raymond; Grammond, Pierre; Petersen, Thor; Fernandez-Bolaños, Ricardo; Fiol, Marcela; Pucci, Eugenio; Lechner-Scott, Jeannette; Verheul, Freek; Cristiano, Edgardo; Van Pesch, Vincent; Petkovska-Boskova, Tatjana; Moore, Fraser; Kister, Ilya; Bergamaschi, Roberto; Saladino, Maria Laura; Slee, Mark; Barnett, Michael; Amato, Maria Pia; Shaw, Cameron; Shuey, Neil; Young, Carolyn; Gray, Orla; Kappos, Ludwig; Butzkueven, Helmut; Kalincik, Tomas; Jokubaitis, Vilija

2016-04-01

We aimed to analyse the effect of the introduction of fingolimod, the first oral disease-modifying therapy, on treatment utilisation and persistence in an international cohort of patients with multiple sclerosis (MS). MSBASIS, a prospective, observational sub-study of the MSBase registry, collects demographic, clinical and paraclinical data on patients followed from MS onset (n=4718). We conducted a multivariable conditional risk set survival analysis to identify predictors of treatment discontinuation, and to assess if the introduction of fingolimod has altered treatment persistence. A total of 2640 patients commenced immunomodulatory therapy. Following the introduction of fingolimod, patients were more likely to discontinue all other treatments (hazard ratio 1.64, p<0.001) while more patients switched to fingolimod than any other therapy (42.3% of switches). Patients switched to fingolimod due to convenience. Patients treated with fingolimod were less likely to discontinue treatment compared with other therapies (p<0.001). Female sex, country of residence, younger age, a high Expanded Disability Status Scale score and relapse activity were all independently associated with higher rates of treatment discontinuation. Following the availability of fingolimod, patients were more likely to discontinue injectable treatments. Those who switched to fingolimod were more likely to do so for convenience. Persistence was improved on fingolimod compared to other medications. © The Author(s), 2015.

Manuka honey as an effective treatment for chronic pilonidal sinus wounds.

PubMed

Thomas, M; Hamdan, M; Hailes, S; Walker, M

2011-11-01

A retrospective study to investigate the effectiveness of topical manuka honey in the treatment of chronic or recurrent pilonidal sinus disease (PSD), assessing the ability of this simple dressing technique to achieve complete wound healing, the time taken to achieve healing and the recurrence rate. All patients who received manuka honey dressing therapy following surgical intervention for chronic or recurrent PSD were identified over a 4-year period. In a retrospective review of case notes, data were collected on patient sex, age, nature of surgical procedures performed, time to achieve complete wound healing, and recurrences after completion of honey therapy. Seventeen patients were eligible for inclusion in the study. Mean time to commence honey therapy post-surgery was 93 days (5-517 days; median 33 days); 15 patients achieved complete wound healing, in a mean time of 65 days (14-264 days; median 49 days). Honey was discontinued in one patient due to an adverse event, and two patients experienced recurrence several months after completing honey therapy. Manuka honey dressing therapy provides an effective topical treatment for chronic/recurrent PSD. Further research is necessary to determine the optimum dressing protocol. The authors have no conflicts of interest to declare. There were no external sources of funding for this study.

Appropriateness and long-term discontinuation rate of biological therapies in ulcerative colitis.

PubMed

Maillard, Michel H; Bortolotti, Murielle; Vader, John-Paul; Mottet, Christian; Schoepfer, Alain; Gonvers, Jean-Jacques; Burnand, Bernard; Froehlich, Florian; Michetti, Pierre; Pittet, Valérie

2014-08-01

Anti-TNFα agents are commonly used for ulcerative colitis (UC) therapy in the event of non-response to conventional strategies or as colon-salvaging therapy. The objectives were to assess the appropriateness of biological therapies for UC patients and to study treatment discontinuation over time, according to appropriateness of treatment, as a measure of outcome. We selected adult ulcerative colitis patients from the Swiss IBD cohort who had been treated with anti-TNFα agents. Appropriateness of the first-line anti-TNFα treatment was assessed using detailed criteria developed during the European Panel on the Appropriateness of Therapy for UC. Treatment discontinuation as an outcome was assessed for categories of appropriateness. Appropriateness of the first-line biological treatment was determined in 186 UC patients. For 64% of them, this treatment was considered appropriate. During follow-up, 37% of all patients discontinued biological treatment, 17% specifically because of failure. Time-to-failure of treatment was significantly different among patients on an appropriate biological treatment compared to those for whom the treatment was considered not appropriate (p=0.0007). Discontinuation rate after 2years was 26% compared to 54% between those two groups. Patients on inappropriate biological treatment were more likely to have severe disease, concomitant steroids and/or immunomodulators. They were also consistently more likely to suffer a failure of efficacy and to stop therapy during follow-up. Appropriateness of first-line anti-TNFα therapy results in a greater likelihood of continuing with the therapy. In situations where biological treatment is uncertain or inappropriate, physicians should consider other options instead of prescribing anti-TNFα agents. Copyright © 2014 European Crohn's and Colitis Organisation. Published by Elsevier B.V. All rights reserved.

Therapeutic administration of atomoxetine combined with rTMS and occupational therapy for upper limb hemiparesis after stroke: a case series study of three patients.

PubMed

Kinoshita, Shoji; Kakuda, Wataru; Yamada, Naoki; Momosaki, Ryo; Okuma, Ryo; Watanabe, Shu; Abo, Masahiro

2016-03-01

Atomoxetine, a selective noradrenaline reuptake inhibitor, has been reported to enhance brain plasticity, but has not yet been used in stroke patients. We reported the feasibility and clinical benefits on motor functional recovery of the combination of repetitive transcranial magnetic stimulation (rTMS) and intensive occupational therapy (OT) in stroke patients. This pilot study was designed to evaluate the additive effects of oral atomoxetine to rTMS/OT in post-stroke hemiparetic patients. The study included three post-stroke patients with upper limb hemiparesis. Treatment with 40 mg/day atomoxetine commenced 2 weeks before admission. After confirming tolerance, the dose was increased to 120 mg/day. Low-frequency rTMS/OT was provided daily for 15 days during continued atomoxetine therapy. Motor function of the affected upper limb was evaluated with the Fugl-Meyer Assessment and Wolf Motor Function test. All patients completed the protocol and showed motor improvement up to 4 weeks after the treatment. No atomoxetine-related side effects were noted. Our protocol of triple therapy of atomoxetine, low-frequency rTMS, and OT is safe and feasible intervention for upper limb hemiparesis after stroke.

[Biologic therapy in idiopathic inflammatory myopathy].

PubMed

Selva-O'Callaghan, Albert; Ramos Casals, Manel; Grau Junyent, Josep M

2014-09-15

The aim of this article is to study the evidence-based knowledge related to the use of biological therapies in patients diagnosed with idiopathic inflammatory myopathy (dermatomyositis, polymyositis and inclusion body myositis). In this review the leading published studies related to the use of biological therapy in patients with myositis are analysed; mainly those with high methodological standards, that means randomized and controlled studies. Methodological drawbacks due to the rarity and heterogeneity of these complex diseases are also addressed. Up to now is not possible to ascertain the biologics as a recommended therapy in patients with myositis, at least based in the current evidence-based knowledge, although it can not be neglected as a therapeutic option in some clinical situations, taking into account the scarce of effective treatments in those patients, especially in refractory myositis. Future studies probably will help to better define the role of biological therapies in patients with idiopathic inflammatory myopathy. Copyright © 2013 Elsevier España, S.L.U. All rights reserved.

Surfer’s myelopathy: a rare presentation in a non-surfing setting and review of the literature

PubMed Central

Phan, Kevin; Hariswamy, Soumya; Rao, Prashanth J.

2016-01-01

Background Surfers myelopathy can be a rapidly devastating disease and little is known surrounding the pathophysiology of the condition. Although the classical pattern of illness has been well reported, it has never been observed in a non-surfing setting. Methods A 51-year-old demolition worker presented with acute non-traumatic myelopathy. Clinical examination revealed sensory loss to the level of L2. T2-MRI and MRI-DWI revealed a hyperintense signal suggestive of an ischaemic event. A diagnosis of surfer’s myelopathy was made and he was commenced on steroid therapy. Results Following steroid therapy and fluid management the patient was discharged after 6 days with minor anaethesia but significant overall neurological improvement. Conclusions Diagnosis of SM requires a thorough history, clinical examination and imaging (MRI, MRI-DWI). The patient should be admitted early and investigated. The use of rehabilitation services may be useful if available. PMID:27757436

Surfer's myelopathy: a rare presentation in a non-surfing setting and review of the literature.

PubMed

Maharaj, Monish M; Phan, Kevin; Hariswamy, Soumya; Rao, Prashanth J

2016-09-01

Surfers myelopathy can be a rapidly devastating disease and little is known surrounding the pathophysiology of the condition. Although the classical pattern of illness has been well reported, it has never been observed in a non-surfing setting. A 51-year-old demolition worker presented with acute non-traumatic myelopathy. Clinical examination revealed sensory loss to the level of L2. T2-MRI and MRI-DWI revealed a hyperintense signal suggestive of an ischaemic event. A diagnosis of surfer's myelopathy was made and he was commenced on steroid therapy. Following steroid therapy and fluid management the patient was discharged after 6 days with minor anaethesia but significant overall neurological improvement. Diagnosis of SM requires a thorough history, clinical examination and imaging (MRI, MRI-DWI). The patient should be admitted early and investigated. The use of rehabilitation services may be useful if available.

[Hypoplastic acute promyelocytic leukemia with continuous hypocellular bone marrow after remission].

PubMed

Nakamura, Toshiki; Makiyama, Junya; Matsuura, Ayumi; Kurohama, Hirokazu; Kitanosono, Hideaki; Ito, Masahiro; Yoshida, Shinichiro; Miyazaki, Yasushi

2018-01-01

An 87-year old female presented with unsteady gait and occasional subcutaneous hematomas. Blood examination findings revealed pancytopenia and mild coagulopathy. Both the histopathological evaluation of bone marrow smears and bone marrow biopsy revealed a hypocellular bone marrow. However, APL cells were observed and PML-RARA fusion gene was detected. On the basis of these findings, the patient was diagnosed with hypoplastic acute promyelocytic leukemia. She received ATRA treatment and achieved complete remission (CR) 29 days from the commencement of therapy. After the first CR, she received two courses of ATO as a consolidation therapy. Following the latter treatments, she maintained CR, but a hypoplastic bone marrow was still observed. Hypoplastic AML is defined as AML with a low bone marrow cellularity. It is clinically important to distinguish it from aplastic anemia and hypoplastic MDS. It has been suggested that both cytogenetic and morphological diagnosis are imperative to the differential diagnosis of hypocellular bone marrow.

Positron emission tomography as an aid in the diagnosis and follow-up of Riedel's thyroiditis.

PubMed

Kotilainen, Pirkko; Airas, Laura; Kojo, Tiina; Kurki, Timo; Kataja, Kaisa; Minn, Heikki; Nuutila, Pirjo

2004-06-01

We describe the usage of positron emission tomography (PET) as an aid in the initial diagnosis and follow-up of Riedel's thyroiditis. A 41-year-old patient was admitted for an enlarged and tender thyroid gland in association with severe systemic symptoms of inflammation. Imaging with fluorine-18 fluorodeoxyglucose (FDG) and PET demonstrated an intensive uptake of FDG in both lobes of the thyroid gland as an indication of severe inflammation. The diagnosis of Riedel's thyroiditis was confirmed by the histological findings of biopsy specimens taken during a palliative thyroid resection. The inflammatory symptoms and local pain dramatically disappeared after commencement of high-dose corticosteroid therapy. A follow-up PET scan after 2 weeks of corticosteroid treatment showed a 60% decrease in the uptake of FDG in the thyroid. This indicates that FDG metabolic activity can also be used to assess a patient's response to therapy in Riedel's thyroiditis.

The effects of oxcarbazepine and valproate therapies on growth in children with epilepsy.

PubMed

Cansu, Ali; Yesilkaya, Ediz; Serdaroglu, Ayse; Camurdan, Orhun; Hirfanoglu, Tugba Luleci; Karaoglu, Abdulbaki; Bideci, Aysun; Cinaz, Peyami

2012-01-01

This study aimed to evaluate the effects of monotherapy with valproate or oxcarbazepine on the linear growth of children with idiopathic epilepsy. Antiepileptic treatment with valproate or oxcarbazepine was initiated in 76 patients. These were evaluated at baseline and at 6 and 18 months after commencement of therapy to determine height standard deviations (height z-scores). Serum ghrelin, insulin-like growth factor-1, and insulin-like growth factor-binding protein-3 levels were measured. In prepubertal patients receiving oxcarbazepine, height z-scores were elevated after 6 and 18 months of therapy (p = 0.008 and p = 0.001, respectively); in pubertal patients, a significant increase was noted at the 18th month of therapy (p = 0.004). In prepubertal patients receiving oxcarbazepine, serum standardized insulin-like growth factor-1 and insulin-like growth factor-binding protein-3 levels were significantly higher at the 18th month of therapy compared with baseline (p = 0.005 and p = 0.004, respectively). In puber-tal patients receiving valproate, serum ghrelin levels were significantly decreased at the 18th month of therapy compared with baseline (p = 0.006). Exposure to oxcarbazepine stimulated linear growth in epileptic patients through mechanisms involving the release of insulin-like growth factor-1 and insulin-like growth factor-binding protein-3. In contrast, expo-sure to valproate did not affect linear growth, but did lead to a decrease in serum ghrelin levels.

Treatment of premature infants with pulmonary hypertension and right ventricular dysfunction with milrinone: a case series.

PubMed

James, A T; Bee, C; Corcoran, J D; McNamara, P J; Franklin, O; El-Khuffash, A F

2015-04-01

Milrinone has been proposed as an effective treatment for pulmonary hypertension (PH) and right ventricular (RV) dysfunction. We aimed to determine the effect of milrinone therapy on clinical and echocardiography parameters of PH in preterm infants with elevated pulmonary pressures. A retrospective case review was conducted on infants <32 weeks gestation who received milrinone for the treatment of PH and reduced RV function. Echocardiographic data were collected before and after treatment with milrinone, and serial clinical parameters were recorded over a 72h  period. Seven infants met the inclusion criteria with a median gestation and birth weight of 27.3 weeks and 1140 g, respectively. Four infants had a diagnosis of pulmonary hypoplasia with PH, and three infants were recipients in twin-to-twin transfusion syndrome who also developed PH. Nitric oxide was used in six infants before commencement of milrinone. Milrinone was commenced at a dose of 0.33 μg kg(-1) min(-1) to 0.5 μg kg(-1) min(-1) and continued for a median duration of 70 h. Use of milrinone was associated with a fall in oxygenation index and inhaled nitric oxide dose. Following an initial fall in blood pressure over the first 6 h, there was an increase in blood pressure over the subsequent 72 h. Echocardiographic data demonstrated an increase in indicators of myocardial performance and PH. One infant died before discharge. This case series suggests that milrinone may be a useful therapy for premature infants with echocardiography findings of PH and/or RH dysfunction. This data support the need for a randomised control trial to confirm its efficacy.

Antiretroviral therapy CNS penetration and HIV-1–associated CNS disease

PubMed Central

Winston, A.; Walsh, J.; Post, F.; Porter, K.; Gazzard, B.; Fisher, M.; Leen, C.; Pillay, D.; Hill, T.; Johnson, M.; Gilson, R.; Anderson, J.; Easterbrook, P.; Bansi, L.; Orkin, C.; Ainsworth, J.; Palfreeman, A.; Gompels, M.; Phillips, A.N.; Sabin, C.A.

2011-01-01

Objective: The impact of different antiretroviral agents on the risk of developing or surviving CNS disease remains unknown. The aim of this study was to investigate whether using antiretroviral regimens with higher CNS penetration effectiveness (CPE) scores was associated with reduced incidence of CNS disease and improved survival in the UK Collaborative HIV Cohort (CHIC) Study. Methods: Adults without previous CNS disease, who commenced combination antiretroviral therapy (cART) between 1996 and 2008, were included (n = 22,356). Initial and most recent cART CPE scores were calculated. CNS diseases were HIV encephalopathy (HIVe), progressive multifocal leukoencephalopathy (PML), cerebral toxoplasmosis (TOXO), and cryptococcal meningitis (CRYPTO). Incidence rates and overall survival were stratified by CPE score. A multivariable Poisson regression model was used to identify independent associations. Results: The median (interquartile range) CPE score for initial cART regimen increased from 7 (5–8) in 1996–1997 to 9 (8–10) in 2000–2001 and subsequently declined to 6 (7–8) in 2006–2008. Differences in gender, HIV acquisition risk group, and ethnicity existed between CPE score strata. A total of 251 subjects were diagnosed with a CNS disease (HIVe 80; TOXO 59; CRYPTO 56; PML 54). CNS diseases occurred more frequently in subjects prescribed regimens with CPE scores ≤4, and less frequently in those with scores ≥10; however, these differences were nonsignificant. Initial and most recent cART CPE scores ≤4 were independently associated with increased risk of death. Conclusion: Clinical status at time of commencing cART influences antiretroviral selection and CPE score. This information should be considered when utilizing CPE scores for retrospective analyses. PMID:21339496

Optimal initiation of Helicobacter pylori eradication in patients with peptic ulcer bleeding.

PubMed

Yoon, Hyuk; Lee, Dong Ho; Jang, Eun Sun; Kim, Jaihwan; Shin, Cheol Min; Park, Young Soo; Hwang, Jin-Hyeok; Kim, Jin-Wook; Jeong, Sook-Hayng; Kim, Nayoung

2015-02-28

To evaluate when Helicobacter pylori (H. pylori) eradication therapy (ET) should be started in patients with peptic ulcer bleeding (PUB). Clinical data concerning adults hospitalized with PUB were retrospectively collected and analyzed. Age, sex, type and stage of peptic ulcer, whether endoscopic therapy was performed or not, methods of H. pylori detection, duration of hospitalization, and specialty of the attending physician were investigated. Factors influencing the confirmation of H. pylori infection prior to discharge were determined using multiple logistic regression analysis. The H. pylori eradication rates of patients who received ET during hospitalization and those who commenced ET as outpatients were compared. A total of 232 patients with PUB were evaluated for H. pylori infection by histology and/or rapid urease testing. Of these patients, 53.7% (127/232) had confirmed results of H. pylori infection prior to discharge. In multivariate analysis, duration of hospitalization and ulcer stage were factors independently influencing whether H. pylori infection was confirmed before or after discharge. Among the patients discharged before confirmation of H. pylori infection, 13.3% (14/105) were lost to follow-up. Among the patients found to be H. pylori-positive after discharge, 41.4% (12/29) did not receive ET. There was no significant difference in the H. pylori eradication rate between patients who received ET during hospitalization and those who commenced ET as outpatients [intention-to-treat: 68.8% (53/77) vs 60% (12/20), P=0.594; per-protocol: 82.8% (53/64) vs 80% (12/15), P=0.723]. Because many patients with PUB who were discharged before H. pylori infection status was confirmed lost an opportunity to receive ET, we should confirm H. pylori infection and start ET prior to discharge.

Changes in Body Fat Distribution on Dual-Energy X-Ray Absorptiometry in Black South Africans Starting First-Line Antiretroviral Therapy.

PubMed

Abrahams, Zulfa; Levitt, Naomi; Lesosky, Maia; Maartens, Gary; Dave, Joel

2016-10-01

Long-term use of antiretroviral therapy (ART) increases the risk of developing lipodystrophy. Few studies from Africa have used longitudinal data to assess the development of lipoatrophy and lipohypertrophy. We use clinical anthropometry and dual-energy X-ray absorptiometry (DEXA) to describe changes in body fat distribution over a 24-month period in individuals initiated on ART. A convenience sample of black South Africans (55 men and 132 women) were recruited and followed for 24 months after commencing ART. Body fat distribution was assessed using anthropometric measurements and DEXA scans at baseline and then at 3, 6, 12, 18, and 24 months after commencing ART. DEXA was also used to estimate abdominal visceral adipose tissue (VAT) and subcutaneous adipose tissue (SAT). Women gained more overall weight and more regional fat in all areas analyzed on DEXA scans. Women, not men, experienced a significant increasing trend in trunk fat and a significant decreasing trend in limb fat, when expressed as a percentage of total body fat. In men, the risk of developing lipoatrophy was more than two times greater than that of women, after adjusting for age, baseline body mass index, and ART regimen. Lipohypertrophy occurred similarly in men and women. VAT and SAT increased significantly in men and women, with women gaining considerably more than men. These findings are of great concern as an increased waist circumference is associated with increased mortality in HIV-infected populations. Further investigation is required to understand the mechanisms underlying the sex differences in changes in body fat distribution and its effects on cardiovascular risk.

Effect of contrast water therapy duration on recovery of cycling performance: a dose-response study.

PubMed

Versey, Nathan; Halson, Shona; Dawson, Brian

2011-01-01

This study investigated whether contrast water therapy (CWT) has a dose-response effect on recovery from high-intensity cycling. Eleven trained male cyclists completed four trials, each commencing with a 75-min cycling protocol containing six sets of five 15-s sprints and three 5-min time-trials in thermoneutral conditions. Ten minutes post-exercise, participants performed one of four recovery protocols: CWT for 6 min (CWT6), 12 min (CWT12), or 18 min (CWT18) duration, or a seated rest control trial. The CWT commenced in hot water (38.4 ± 0.6°C) and alternated between hot and cold water (14.6 ± 0.3°C) every minute with a 5-s changeover. The cycling protocol was repeated 2 h after completion of exercise bout one. Prior to exercise bout two, core temperature was lower in CWT12 (-0.19 ± 0.14°C, mean ± 90% CL) and CWT18 (-0.21 ± 0.10°C) than control. Compared with control, CWT6 substantially improved time-trial (1.5 ± 2.1%) and sprint performance (3.0 ± 3.1%), and CWT12 substantially improved sprint total work (4.3 ± 3.4%) and peak power (2.7 ± 3.8%) in exercise bout two. All CWT conditions generally improved thermal sensation, whole body fatigue and muscle soreness compared with control, but no differences existed between conditions in heart rate or rating of perceived exertion. In conclusion, CWT duration did not have a dose-response effect on recovery from high-intensity cycling; however, CWT for up to 12 min assisted recovery of cycling performance.

77 FR 48924 - Perfluoroalkyl Sulfonates and Long-Chain Perfluoroalkyl Carboxylate Chemical Substances; Proposed...

Federal Register 2010, 2011, 2012, 2013, 2014

2012-08-15

... have not yet commenced production or import. Any person who commences the manufacture or import of a... new chemical review process but have not yet commenced production or import, and to designate (for all... long-chain perfluoroalkyl carboxylate (LCPFAC) chemical substances that would designate manufacturing...

DefenseLink Feature: Service & Military Academies 2008 Graduations

Science.gov Websites

-Marine Corps Memorial Stadium in Annapolis, Md., during their commencement ceremony, May 23, 2008. U.S States Naval Academy commencement ceremony at the Navy-Marine Corps Memorial Stadium, May 23, 2008 Academy commencement ceremony at Navy-Marine Corps Memorial Stadium, May 23, 2008, Annapolis, Md

50 CFR 11.21 - Commencement of hearing procedures.

Code of Federal Regulations, 2010 CFR

2010-10-01

... PLANTS CIVIL PROCEDURES Hearing and Appeal Procedures § 11.21 Commencement of hearing procedures... 50 Wildlife and Fisheries 1 2010-10-01 2010-10-01 false Commencement of hearing procedures. 11.21 Section 11.21 Wildlife and Fisheries UNITED STATES FISH AND WILDLIFE SERVICE, DEPARTMENT OF THE INTERIOR...

50 CFR 11.21 - Commencement of hearing procedures.

Code of Federal Regulations, 2011 CFR

2011-10-01

... PLANTS CIVIL PROCEDURES Hearing and Appeal Procedures § 11.21 Commencement of hearing procedures... 50 Wildlife and Fisheries 1 2011-10-01 2011-10-01 false Commencement of hearing procedures. 11.21 Section 11.21 Wildlife and Fisheries UNITED STATES FISH AND WILDLIFE SERVICE, DEPARTMENT OF THE INTERIOR...

38 CFR 21.7131 - Commencing dates.

Code of Federal Regulations, 2010 CFR

2010-07-01

... standard college degree. (1) When the student enrolls in a course offered by independent study, the commencing date of the award or increased award of educational assistance will be the date the student began...) When a student enrolls in a resident course or subject, the commencing date of the award or increased...

Prayer and University Commencement: Application of "Lee v. Weisman."

ERIC Educational Resources Information Center

Colwell, W. Bradley; Thurston, Paul W.

1995-01-01

Discusses reasons why the "Lee v. Weisman" Supreme Court decision that held unconstitutional a Rhode Island school policy for prayer at a junior high school commencement does not extend to the university level. Concludes that an appropriately worded commencement prayer could pass the three-part "Lemon" threshold and not violate…

40 CFR 60.32e - Designated facilities.

Code of Federal Regulations, 2010 CFR

2010-07-01

... modification was commenced on or before March 16, 1998. (2) For which construction was commenced after June 20, 1996 but no later than December 1, 2008, or for which modification is commenced after March 16, 1998... only pathological waste, low-level radioactive waste, and/or chemotherapeutic waste (all defined in...

40 CFR 60.1050 - Who must submit a materials separation plan?

Code of Federal Regulations, 2014 CFR

2014-07-01

... Municipal Waste Combustion Units for Which Construction is Commenced After August 30, 1999 or for Which... separation plan for your municipal waste combustion unit if you commence construction of a new small municipal waste combustion unit after December 6, 2000. (b) If you commence construction of your municipal...

40 CFR 60.1050 - Who must submit a materials separation plan?

Code of Federal Regulations, 2012 CFR

2012-07-01

... Municipal Waste Combustion Units for Which Construction is Commenced After August 30, 1999 or for Which... separation plan for your municipal waste combustion unit if you commence construction of a new small municipal waste combustion unit after December 6, 2000. (b) If you commence construction of your municipal...

The London Position Statement of the World Congress of Gastroenterology on Biological Therapy for IBD with the European Crohn's and Colitis Organization: when to start, when to stop, which drug to choose, and how to predict response?

PubMed

D'Haens, Geert R; Panaccione, Remo; Higgins, Peter D R; Vermeire, Severine; Gassull, Miquel; Chowers, Yehuda; Hanauer, Stephen B; Herfarth, Hans; Hommes, Daan W; Kamm, Michael; Löfberg, Robert; Quary, A; Sands, Bruce; Sood, A; Watermeyer, G; Watermayer, G; Lashner, Bret; Lémann, Marc; Plevy, Scott; Reinisch, Walter; Schreiber, Stefan; Siegel, Corey; Targan, Stephen; Watanabe, M; Feagan, Brian; Sandborn, William J; Colombel, Jean Frédéric; Travis, Simon

2011-02-01

The advent of biological therapy has revolutionized inflammatory bowel disease (IBD) care. Nonetheless, not all patients require biological therapy. Selection of patients depends on clinical characteristics, previous response to other medical therapy, and comorbid conditions. Availability, reimbursement guidelines, and patient preferences guide the choice of first-line biological therapy for luminal Crohn's disease (CD). Infliximab (IFX) has the most extensive clinical trial data, but other biological agents (adalimumab (ADA), certolizumab pegol (CZP), and natalizumab (NAT)) appear to have similar benefits in CD. Steroid-refractory, steroid-dependent, or complex fistulizing CD are indications for starting biological therapy, after surgical drainage of any sepsis. For fistulizing CD, the efficacy of IFX for inducing fistula closure is best documented. Unique risks of NAT account for its labeling as a second-line biological agent in some countries. Patients who respond to induction therapy benefit from systematic re-treatment. The combination of IFX with azathioprine is better than monotherapy for induction of remission and mucosal healing up to 1 year in patients who are naïve to both agents. Whether this applies to other agents remains unknown. IFX is also effective for treatment-refractory, moderate, or severely active ulcerative colitis. Patients who have a diminished or loss of response to anti-tumor necrosis factor (TNF) therapy may respond to dose adjustment of the same agent or switching to another agent. Careful consideration should be given to the reasons for loss of response. There are insufficient data to make recommendations on when to stop anti-TNF therapy. Preliminary evidence suggests that a substantial proportion of patients in clinical remission for >1 year, without signs of active inflammation can remain in remission after stopping treatment.

Patients with knee osteoarthritis demonstrate improved gait pattern and reduced pain following a non-invasive biomechanical therapy: a prospective multi-centre study on Singaporean population.

PubMed

Elbaz, Avi; Mor, Amit; Segal, Ganit; Aloni, Yoav; Teo, Yee Hong; Teo, Yee Sze; Das-De, Shamal; Yeo, Seng Jin

2014-01-02

Previous studies have shown the effect of a unique therapy with a non-invasive biomechanical foot-worn device (AposTherapy) on Caucasian western population suffering from knee osteoarthritis. The purpose of the current study was to evaluate the effect of this therapy on the level of symptoms and gait patterns in a multi-ethnic Singaporean population suffering from knee osteoarthritis. Fifty-eight patients with bilateral medial compartment knee osteoarthritis participated in the study. All patients underwent a computerized gait test and completed two self-assessment questionnaires (WOMAC and SF-36). The biomechanical device was calibrated to each patient, and therapy commenced. Changes in gait patterns and self-assessment questionnaires were reassessed after 3 and 6 months of therapy. A significant improvement was seen in all of the gait parameters following 6 months of therapy. Specifically, gait velocity increased by 15.9%, step length increased by 10.3%, stance phase decreased by 5.9% and single limb support phase increased by 2.7%. In addition, pain, stiffness and functional limitation significantly decreased by 68.3%, 66.7% and 75.6%, respectively. SF-36 physical score and mental score also increased significantly following 6 months of therapy (46.1% and 22.4%, respectively) (P < 0.05 for all parameters). Singaporean population with medial compartment knee osteoarthritis demonstrated improved gait patterns, reported alleviation in symptoms and improved function and quality of life following 6 months of therapy with a unique biomechanical device. Registration number NCT01562652.

Novel antipsychotics and severe hyperlipidemia.

PubMed

Meyer, J M

2001-08-01

Newer atypical antipsychotics demonstrate superior effectiveness, with a diminished incidence of extrapyramidal side effects compared with older typical antipsychotics, but they have been associated with the development of obesity and new-onset diabetes. A small number of reports documenting modest hypertriglyceridemia related to newer antipsychotics have implicated fluperlapine, clozapine, and, most recently, olanzapine. This study summarizes the results of 14 cases of severe hypertriglyceridemia (>600 mg/dL) associated with olanzapine and quetiapine therapy occurring among inpatients at Oregon State Hospital, including 7 patients whose serum triglyceride levels exceeded 1,000 mg/ dL. Four of these patients also developed new-onset diabetes. Nine cases occurred during the first 8 months of treatment, with three cases identified within 3 months of commencing olanzapine or quetiapine therapy. Weight gain in olanzapine and quetiapine groups was modest (12.3 lb and 8.5 lb, respectively) and did not correlate with the severity of hypertriglyceridemia. Biochemical causes for severe hypertriglyceridemia associated with novel antipsychotics are unclear, but clinical monitoring of serum lipids must be added to the concerns about the metabolic consequences of therapy with certain newer antipsychotic agents.

26 CFR 25.2702-5 - Personal residence trusts.

Code of Federal Regulations, 2012 CFR

2012-04-01

... that the reformation has been commenced or will be commenced within the 90-day period. In the case of a... judicial reformation (or nonjudicial reformation if effective under state law), to comply with the requirements. In the case of a trust created after December 31, 1996, the reformation must be commenced within...

26 CFR 25.2702-5 - Personal residence trusts.

Code of Federal Regulations, 2011 CFR

2011-04-01

... that the reformation has been commenced or will be commenced within the 90-day period. In the case of a... judicial reformation (or nonjudicial reformation if effective under state law), to comply with the requirements. In the case of a trust created after December 31, 1996, the reformation must be commenced within...

26 CFR 25.2702-5 - Personal residence trusts.

Code of Federal Regulations, 2013 CFR

2013-04-01

... that the reformation has been commenced or will be commenced within the 90-day period. In the case of a... judicial reformation (or nonjudicial reformation if effective under state law), to comply with the requirements. In the case of a trust created after December 31, 1996, the reformation must be commenced within...

26 CFR 25.2702-5 - Personal residence trusts.

Code of Federal Regulations, 2014 CFR

2014-04-01

... that the reformation has been commenced or will be commenced within the 90-day period. In the case of a... judicial reformation (or nonjudicial reformation if effective under state law), to comply with the requirements. In the case of a trust created after December 31, 1996, the reformation must be commenced within...

26 CFR 301.9100-14T - Individual's election to terminate taxable year when case commences.

Code of Federal Regulations, 2010 CFR

2010-04-01

... when case commences. 301.9100-14T Section 301.9100-14T Internal Revenue INTERNAL REVENUE SERVICE... Rules Application of Internal Revenue Laws § 301.9100-14T Individual's election to terminate taxable year when case commences. (a) Scope. The regulations prescribed in this section provide rules for...

40 CFR 60.32e - Designated facilities.

Code of Federal Regulations, 2014 CFR

2014-07-01

... individual HMIWI: (1) For which construction was commenced on or before June 20, 1996, or for which modification was commenced on or before March 16, 1998. (2) For which construction was commenced after June 20... an exemption claim; and (2) Keeps records on a calendar quarter basis of the periods of time when...

40 CFR 60.32e - Designated facilities.

Code of Federal Regulations, 2013 CFR

2013-07-01

... individual HMIWI: (1) For which construction was commenced on or before June 20, 1996, or for which modification was commenced on or before March 16, 1998. (2) For which construction was commenced after June 20... an exemption claim; and (2) Keeps records on a calendar quarter basis of the periods of time when...

12 CFR 611.1210 - Advance notices-commencement resolution and notice to equity holders.

Code of Federal Regulations, 2010 CFR

2010-01-01

... 12 Banks and Banking 6 2010-01-01 2010-01-01 false Advance notices-commencement resolution and notice to equity holders. 611.1210 Section 611.1210 Banks and Banking FARM CREDIT ADMINISTRATION FARM..., within 10 days of adopting the commencement resolution, your bank and the other Farm Credit banks must...

40 CFR 60.50c - Applicability and delegation of authority.

Code of Federal Regulations, 2012 CFR

2012-07-01

... Hospital/Medical/Infectious Waste Incinerators for Which Construction is Commenced After June 20, 1996 § 60.../infectious waste incinerator (HMIWI): (1) For which construction is commenced after June 20, 1996 but no... later than April 6, 2010. (3) For which construction is commenced after December 1, 2008; or (4) For...

The indirect and direct pathways between physical fitness and academic achievement on commencement in post-compulsory education in a historical cohort of Danish school youth.

PubMed

Andersen, Mikkel Porsborg; Starkopf, Liis; Sessa, Maurizio; Mortensen, Rikke Nørmark; Vardinghus-Nielsen, Henrik; Bøggild, Henrik; Lange, Theis; Torp-Pedersen, Christian

2017-09-11

Some studies have found positive associations between physical fitness and academic achievements. Pupils' academic achievements should indicate scholastic abilities to commence a post-compulsory education. However, the effect magnitude of physical fitness and academic achievements on commencement in post-compulsory education is unknown. We examined the pathways between physical fitness and academic achievement on pupils' commencement in post-compulsory education. This historical cohort study followed 530 girls and 554 boys from the Danish municipality of Aalborg in the period 2008-2014, 13 to 15 years old in 2010. Physical fitness was assessed through a watt-max cycle ergometer test represented as VO 2 max (mL·kg -1 ·min -1 ). Academic achievement, commencement status and information on covariates were obtained from Danish nationwide registers. Causal inference based mediation analysis was used to investigate the indirect and direct pathways by separating the total effect of physical fitness on post-compulsory education commencement. Adjusting for sex, age, ethnicity and socioeconomic status, the overall mediation analysis showed an odds ratio (OR) of 1.87 (95% confidence interval (CI): 1.30; 2.73) for the total effect, corresponding to an increase in odds of post-compulsory education commencement when the physical fitness was increased by 10 units of VO 2 max. The separated total effect showed a natural direct OR of 1.36 (95% CI: 0.93; 1.98) and a natural indirect (i.e., through academic achievement) OR of 1.37 (95% CI: 1.20; 1.57). Thus, 51% (95% CI: 27%; 122%) of the effect of physical fitness on post-compulsory education commencement was mediated through academic achievement. Physical fitness had a positive effect on post-compulsory education commencement. A substantial part of this effect was mediated through academic achievement.

Opportunistic Infections in Biological Therapy, Risk and Prevention.

PubMed

Bryant, Paul A; Baddley, John W

2017-02-01

Patients being treated with biological therapies are at increased risk for serious infections, including opportunistic infections. Although more is known about opportunistic infection risk with older biologics, such as antitumor necrosis factor drugs, there is less knowledge of opportunistic infection risk with newer biological therapies. The incidence of certain opportunistic infections (tuberculosis, herpes zoster, pneumocystosis) has been rigorously evaluated in large observational studies. However, data are more limited for other infections (histoplasmosis, nontuberculous mycobacteria). Infectious morbidity and mortality may be preventable with screening and prophylaxis in select populations. Copyright © 2016 Elsevier Inc. All rights reserved.

The implications of biologic therapy for elective foot and ankle surgery in patients with rheumatoid arthritis.

PubMed

Diaper, Ross; Wong, Ernest; Metcalfe, Stuart A

2017-03-01

Rheumatoid arthritis (RA) is one of a number of inflammatory arthropathies resulting in foot pain and deformity. Patients with this disease may require surgical intervention as part of their management. Many of these patients are now taking biologic agents which pose several risks to patients in the perioperative phase. The surgical team therefore need to be aware of these associated complications and how to manage these cases. This paper aims to review the current literature about perioperative needs (foot and ankle surgery) associated with patients with rheumatoid arthritis receiving biologic therapy. The majority of the literature discusses the perioperative complications associated with patients on anti-TNFα therapy with few studies investigating the other biologics in common use. There is conflicting evidence as to the safety of continuing or stopping biologic drug therapy prior to orthopaedic procedures. The British Society for Rheumatology (BSR) have produced guidelines for the management of patients on anti-TNFα therapy or the biologic agent Tocilizumab. These recommendations suggest the risks of post-operative infection need to be balanced against the risk of a post-operative disease flare. In essence, it is suggested anti-TNFα therapy is stopped 3-5 times the half-life of the drug whilst Tocilizumab is stopped 4 weeks prior to surgery. Good communication is needed between the surgical team and the local Rheumatology department managing the patient's disease in order to optimise perioperative care. Local pathways may vary from the BSR recommendations to determine the most suitable course of action with regards to continuing or stopping biologic therapy prior to foot and ankle surgery. Copyright © 2017 Elsevier Ltd. All rights reserved.

[Side effects of biologic therapies in psoriasis].

PubMed

Altenburg, A; Augustin, M; Zouboulis, C C

2018-04-01

The introduction of biologics has revolutionized the treatment of moderate to severe plaque psoriasis. Due to the continuous expansion of biological therapies for psoriasis, it is particularly important to acknowledge efficacy and safety of the compounds not only in clinical trials but also in long-term registry-based observational studies. Typical side effects and significant risks of antipsoriatic biologic therapies considering psoriatic control groups are presented. A selective literature search was conducted in PubMed and long-term safety studies of the psoriasis registries PsoBest, PSOLAR and BADBIR were evaluated. To assess the long-term safety of biologics, the evaluation of the course of large patient cohorts in long-term registries is of particular medical importance. Newer biologic drugs seem to exhibit a better safety profile than older ones.

Venetoclax plus rituximab in relapsed or refractory chronic lymphocytic leukaemia: a phase 1b study.

PubMed

Seymour, John F; Ma, Shuo; Brander, Danielle M; Choi, Michael Y; Barrientos, Jacqueline; Davids, Matthew S; Anderson, Mary Ann; Beaven, Anne W; Rosen, Steven T; Tam, Constantine S; Prine, Betty; Agarwal, Suresh K; Munasinghe, Wijith; Zhu, Ming; Lash, L Leanne; Desai, Monali; Cerri, Elisa; Verdugo, Maria; Kim, Su Young; Humerickhouse, Rod A; Gordon, Gary B; Kipps, Thomas J; Roberts, Andrew W

2017-02-01

Selective BCL2 inhibition with venetoclax has substantial activity in patients with relapsed or refractory chronic lymphocytic leukaemia. Combination therapy with rituximab enhanced activity in preclinical models. The aim of this study was to assess the safety, pharmacokinetics, and activity of venetoclax in combination with rituximab. Adult patients with relapsed or refractory chronic lymphocytic leukaemia (according to the 2008 Modified International Workshop on CLL guidelines) or small lymphocytic lymphoma were eligible for this phase 1b, dose-escalation trial. The primary outcomes were to assess the safety profile, to determine the maximum tolerated dose, and to establish the recommended phase 2 dose of venetoclax when given in combination with rituximab. Secondary outcomes were to assess the pharmacokinetic profile and analyse efficacy, including overall response, duration of response, and time to tumour progression. Minimal residual disease was a protocol-specified exploratory objective. Central review of the endpoints was not done. Venetoclax was dosed daily using a stepwise escalation to target doses (200-600 mg) and then monthly rituximab commenced (375 mg/m 2 in month 1 and 500 mg/m 2 in months 2-6). Adverse events were graded according to the National Cancer Institute Common Terminology Criteria for adverse events version 4.0. Protocol-guided drug cessation was allowed for patients who achieved complete response (including complete response with incomplete marrow recovery) or negative bone marrow minimal residual disease. Analyses were done per protocol for all patients who commenced drug and included all patients who received at least one dose of venetoclax. Data were pooled across dose cohorts. Patients are still receiving therapy and follow-up is ongoing. The trial is registered at ClinicalTrials.gov, number NCT01682616. Between Aug 6, 2012, and May 28, 2014, we enrolled 49 patients. Common grade 1-2 toxicities included upper respiratory tract infections (in 28 [57%] of 49 patients), diarrhoea (27 [55%]), and nausea (25 [51%]). Grade 3-4 adverse events occurred in 37 (76%) of 49 patients; most common were neutropenia (26 [53%]), thrombocytopenia (eight [16%]), anaemia (seven [14%]), febrile neutropenia (six [12%]), and leucopenia (six [12%]). The most common serious adverse events were pyrexia (six [12%]), febrile neutropenia (five [10%]), lower respiratory tract infection, and pneumonia (each three [6%]). Clinical tumour lysis syndrome occurred in two patients (resulting in one death) who initiated venetoclax at 50 mg. After enhancing tumour lysis syndrome prophylaxis measures and commencing venetoclax at 20 mg, clinical tumour lysis syndrome did not occur. The maximum tolerated dose was not identified; the recommended phase 2 dose of venetoclax in combination with rituximab was 400 mg. Overall, 42 (86%) of 49 patients achieved a response, including a complete response in 25 (51%) of 49 patients. 2 year estimates for progression-free survival and ongoing response were 82% (95% CI 66-91) and 89% (95% CI 72-96), respectively. Negative marrow minimal residual disease was attained in 20 (80%) of 25 complete responders and 28 (57%) of 49 patients overall. 13 responders ceased all therapy; among these all 11 minimal residual disease-negative responders remain progression-free off therapy. Two with minimal residual disease-positive complete response progressed after 24 months off therapy and re-attained response after re-initiation of venetoclax. A substantial proportion of patients achieved an overall response with the combination of venetoclax and rituximab including 25 (51%) of 49 patients who achieved a complete response and 28 (57%) of 49 patients who achieved negative marrow minimal residual disease with acceptable safety. The depth and durability of responses observed with the combination offers an attractive potential treatment option for patients with relapsed or refractory chronic lymphocytic leukaemia and could allow some patients to maintain response after discontinuing therapy, a strategy that warrants further investigation in randomised studies. AbbVie Inc and Genentech Inc. Copyright © 2017 Elsevier Ltd. All rights reserved.

Venetoclax plus rituximab in relapsed or refractory chronic lymphocytic leukaemia: a phase 1b study

PubMed Central

Seymour, John F; Ma, Shuo; Brander, Danielle M; Choi, Michael Y; Barrientos, Jacqueline; Davids, Matthew S; Anderson, Mary Ann; Beaven, Anne W; Rosen, Steven T; Tam, Constantine S; Prine, Betty; Agarwal, Suresh K; Munasinghe, Wijith; Zhu, Ming; Lash, L Leanne; Desai, Monali; Cerri, Elisa; Verdugo, Maria; Kim, Su Young; Humerickhouse, Rod A; Gordon, Gary B; Kipps, Thomas J; Roberts, Andrew W

2017-01-01

Summary Background Selective BCL2 inhibition with venetoclax has substantial activity in patients with relapsed or refractory chronic lymphocytic leukaemia. Combination therapy with rituximab enhanced activity in preclinical models. The aim of this study was to assess the safety, pharmacokinetics, and activity of venetoclax in combination with rituximab. Methods Adult patients with relapsed or refractory chronic lymphocytic leukaemia (according to the 2008 Modified International Workshop on CLL guidelines) or small lymphocytic lymphoma were eligible for this phase 1b, dose-escalation trial. The primary outcomes were to assess the safety profile, to determine the maximum tolerated dose, and to establish the recommended phase 2 dose of venetoclax when given in combination with rituximab. Secondary outcomes were to assess the pharmacokinetic profile and analyse efficacy, including overall response, duration of response, and time to tumour progression. Minimal residual disease was a protocol-specified exploratory objective. Central review of the endpoints was not done. Venetoclax was dosed daily using a stepwise escalation to target doses (200–600 mg) and then monthly rituximab commenced (375 mg/m2 in month 1 and 500 mg/m2 in months 2–6). Adverse events were graded according to the National Cancer Institute Common Terminology Criteria for adverse events version 4.0. Protocol-guided drug cessation was allowed for patients who achieved complete response (including complete response with incomplete marrow recovery) or negative bone marrow minimal residual disease. Analyses were done per protocol for all patients who commenced drug and included all patients who received at least one dose of venetoclax. Data were pooled across dose cohorts. Patients are still receiving therapy and follow-up is ongoing. The trial is registered at ClinicalTrials.gov, number NCT01682616. Findings Between Aug 6, 2012, and May 28, 2014, we enrolled 49 patients. Common grade 1–2 toxicities included upper respiratory tract infections (in 28 [57%] of 49 patients), diarrhoea (27 [55%]), and nausea (25 [51%]). Grade 3–4 adverse events occurred in 37 (76%) of 49 patients; most common were neutropenia (26 [53%]), thrombocytopenia (eight [16%]), anaemia (seven [14%]), febrile neutropenia (six [12%]), and leucopenia (six [12%]). The most common serious adverse events were pyrexia (six [12%]), febrile neutropenia (five [10%]), lower respiratory tract infection, and pneumonia (each three [6%]). Clinical tumour lysis syndrome occurred in two patients (resulting in one death) who initiated venetoclax at 50 mg. After enhancing tumour lysis syndrome prophylaxis measures and commencing venetoclax at 20 mg, clinical tumour lysis syndrome did not occur. The maximum tolerated dose was not identified; the recommended phase 2 dose of venetoclax in combination with rituximab was 400 mg. Overall, 42 (86%) of 49 patients achieved a response, including a complete response in 25 (51%) of 49 patients. 2 year estimates for progression-free survival and ongoing response were 82% (95% CI 66–91) and 89% (95% CI 72–96), respectively. Negative marrow minimal residual disease was attained in 20 (80%) of 25 complete responders and 28 (57%) of 49 patients overall. 13 responders ceased all therapy; among these all 11 minimal residual disease-negative responders remain progression-free off therapy. Two with minimal residual disease-positive complete response progressed after 24 months off therapy and re-attained response after re-initiation of venetoclax. Interpretation A substantial proportion of patients achieved an overall response with the combination of venetoclax and rituximab including 25 (51%) of 49 patients who achieved a complete response and 28 (57%) of 49 patients who achieved negative marrow minimal residual disease with acceptable safety. The depth and durability of responses observed with the combination offers an attractive potential treatment option for patients with relapsed or refractory chronic lymphocytic leukaemia and could allow some patients to maintain response after discontinuing therapy, a strategy that warrants further investigation in randomised studies. PMID:28089635

Developmental Biology and Regenerative Medicine: Addressing the Vexing Problem of Persistent Muscle Atrophy in the Chronically Torn Human Rotator Cuff.

PubMed

Meyer, Gretchen A; Ward, Samuel R

2016-05-01

Persistent muscle atrophy in the chronically torn rotator cuff is a significant obstacle for treatment and recovery. Large atrophic changes are predictive of poor surgical and nonsurgical outcomes and frequently fail to resolve even following functional restoration of loading and rehabilitation. New insights into the processes of muscle atrophy and recovery gained through studies in developmental biology combined with the novel tools and strategies emerging in regenerative medicine provide new avenues to combat the vexing problem of muscle atrophy in the rotator cuff. Moving these treatment strategies forward likely will involve the combination of surgery, biologic/cellular agents, and physical interventions, as increasing experimental evidence points to the beneficial interaction between biologic therapies and physiologic stresses. Thus, the physical therapy profession is poised to play a significant role in defining the success of these combinatorial therapies. This perspective article will provide an overview of the developmental biology and regenerative medicine strategies currently under investigation to combat muscle atrophy and how they may integrate into the current and future practice of physical therapy. © 2016 American Physical Therapy Association.

77 FR 19044 - Self-Regulatory Organizations; the NASDAQ Stock Market LLC; Notice of Filing and Immediate...

Federal Register 2010, 2011, 2012, 2013, 2014

2012-03-29

... that the quality of its process for commencing IPO trading would be enhanced by allowing market... orders being entered prior to commencement of trading, resulting in a higher level of order interaction... commencement of trading of IPO securities, resulting in a higher level of order interaction at the open. Thus...

13 CFR 134.304 - Commencement of appeals from size determinations and NAICS code designations.

Code of Federal Regulations, 2010 CFR

2010-01-01

... 13 Business Credit and Assistance 1 2010-01-01 2010-01-01 false Commencement of appeals from size determinations and NAICS code designations. 134.304 Section 134.304 Business Credit and Assistance SMALL BUSINESS... Appeals From Size Determinations and NAICS Code Designations § 134.304 Commencement of appeals from size...

46 CFR 201.85 - Commencement of functions of Department of Transportation Office of Hearings.

Code of Federal Regulations, 2010 CFR

2010-10-01

... 46 Shipping 8 2010-10-01 2010-10-01 false Commencement of functions of Department of Transportation Office of Hearings. 201.85 Section 201.85 Shipping MARITIME ADMINISTRATION, DEPARTMENT OF TRANSPORTATION POLICY, PRACTICE AND PROCEDURE RULES OF PRACTICE AND PROCEDURE Responsibilities and Duties of Presiding Officer (Rule 8) § 201.85 Commencement...

A phase I study of recombinant human leukemia inhibitory factor in patients with advanced cancer.

PubMed

Gunawardana, Dishan H; Basser, Russell L; Davis, Ian D; Cebon, Jonathan; Mitchell, Paul; Underhill, Craig; Kilpatrick, Trevor J; Reardon, Katrina; Green, Michael D; Bardy, Peter; Amor, Pene; Crump, David; Ng, Siobhan; Nation, Roger L; Begley, C Glenn

2003-06-01

Leukemia inhibitory factor (LIF) is a pleiotropic molecule of the interleukin 6 family of cytokines. We aimed to examine the safety, pharmacokinetics, and biological effects of recombinant human LIF (rhLIF, emfilermin) in patients with advanced cancer. In stage 1 of the study, 34 patients received rhLIF or placebo (3:1 ratio) at doses of 0.25-16.0 micro g/kg/day or 4.0 micro g/kg three times daily for 7 days. In stage 2, 40 patients received rhLIF or placebo, either once daily for 14 days commencing the day after chemotherapy (0.25-8.0 micro g/kg/day) or for 7 days commencing the day before chemotherapy (4.0 micro g/kg three times daily). The chemotherapy was cisplatin 75 mg/m(2) and paclitaxel 135 mg/m(2). In stage 1, platelet counts increased in most patients, including those who received placebo. Blood progenitor cells increased in response to rhLIF. In stage 2, platelet recovery to baseline levels was earlier for patients receiving higher doses of rhLIF (>/=4.0 micro g/kg/day; P = 0.02). The neutrophil nadir after chemotherapy was less severe in patients receiving >/=4.0 micro g/kg/day of rhLIF. In stages 1 and 2, increases in C reactive protein were seen at higher doses. Several patients developed evidence of autonomic dysfunction, in particular impotence and episodic hypotension. The dose-limiting toxicities were hypotension and rigors. Pharmacokinetic studies demonstrated a short half-life (1-5 h) independent of dose. We demonstrated a biological effect of rhLIF on blood progenitor cells, C reactive protein levels, and hemopoietic recovery after chemotherapy.

Impact of pay for performance on access at first dialysis in Queensland.

PubMed

Haarsager, Jennie; Krishnasamy, Rathika; Gray, Nicholas A

2018-05-01

Commencement of haemodialysis with an arteriovenous fistula (AVF) or arteriovenous graft (AVG) is associated with improved survival compared with commencement with a central venous catheter. In 2011-2012, Queensland Health made incentive payments to renal units for early referred patients who commenced peritoneal dialysis (PD), or haemodialysis with an AVF/AVG. The aim of this study was to determine if pay for performance improved clinical care. All patients who commenced dialysis in Australia between 2009 and 2014 and were registered with the Australia and New Zealand Dialysis and Transplant Registry (ANZDATA) were included. A multivariable regression model was used to compare rates of commencing dialysis with a PD catheter or permanent AVF/AVG during the pay-for-performance period (2011-2012) with periods prior (2009-2010) and after (2013-2014). A total of 10 858 early referred patients commenced dialysis during the study period, including 2058 in Queensland. In Queensland, PD as first modality increased with time (P < 0.001) but there was no change in AVF/AVG rate at first haemodialysis (P = 0.5). In a multivariate model using the pay-for-performance period as reference, the odds ratio for commencement with PD or haemodialysis with an AVF/AVG in Queensland was 1.02 (95% CI 0.81-1.29) in 2009-2010 and 1.28 (95% CI 1.01-1.61) in 2013-2014. There was no change for the rest of Australia (0.97 95% CI 0.87-1.09 in 2009-2010 and 1.00 95% CI 0.90-1.11 in 2013-14). Pay for performance did not improve rates of commencement of dialysis with PD or an AVF/AVG during the payment period. A lag effect on clinical care may explain the improvement in later years. © 2017 Asian Pacific Society of Nephrology.

Fungal Infections and New Biologic Therapies.

PubMed

Vallabhaneni, Snigdha; Chiller, Tom M

2016-05-01

The development of biologic therapies targeting proinflammatory mediators has led to significant advances in the treatment of immune-mediated inflammatory diseases (IMIDs). Blocking undesired inflammatory effects also has the potential to disrupt the body's immune response and increase the risk for infections, including fungal infections. This review summarizes the published data on the frequency and risk for fungal infections among patients treated with biologics, with a focus on the newer therapies approved for use with IMIDs in the last 10 years. The use of biologics is associated with a small but important risk of fungal infections. Pneumocystis jirovecii pneumonia, histoplasmosis, and candidiasis are some of the most common fungal infections associated with biologics. Providers should be vigilant for fungal infection among patients taking biologics, be aware that biologic agents may alter the typical presentation of fungal infections, and take timely steps to diagnose and treat fungal infection to reduce resultant morbidity and mortality.

Listeriosis in patients receiving biologic therapies.

PubMed

Bodro, M; Paterson, D L

2013-09-01

The evolution of inflammatory diseases has radically changed since the introduction of biologic therapies, such as tumour necrosis factor alpha inhibitors (anti-TNFα). They, therefore, represent a widely used therapeutic modality. Nevertheless, post-marketing studies reveal an increased risk of infection in patients taking these drugs, especially granulomatous infections such as listeriosis. We aimed to evaluate the reported cases of listeriosis in patients treated with biologic treatments. We used the United States Food and Drug Administration (FDA) Adverse Event Reporting System (AERS) from 2004 to 2011. We also perform a literature review of previously reported cases of listeriosis in patients taking biologic therapies. We identified 266 cases of Listeria monocytogenes infection associated with biologic therapies. The majority of patients were receiving infliximab (77.1 %), followed by etanercept (11.7 %), adalimumab (9.8 %), rituximab (4.1 %), abatacept (0.4 %) and golimumab (0.4 %). Indications for the use of biologics were as follows: 47.7 % for rheumatologic diseases, 38 % for inflammatory bowel diseases, 3.4 % for haematological diseases and 10.5 % for other indications. Seventy-three percent of the patients were receiving concomitant immunosuppressant drugs, especially steroids (56 %) and methotrexate (31.6 %). The median time to the onset of infection was 184 days. Mortality rates range from 11.1 % in adalimumab-treated patients to 27.3 % in rituximab-treated patients (p = 0.7). Listeriosis is common in biologics-treated patients, especially related to infliximab use given concomitantly with other immunosuppressive therapies. Infections after treatment with biologics mostly occurred in the first year after initiating treatment.

A 21st-century approach to age-old problems: the ascension of biologics in clinical therapeutics.

PubMed

Espiritu, Michael J; Collier, Abby C; Bingham, Jon-Paul

2014-08-01

Small organic molecules have been the pharmaceutical mainstay of the developed world for some time. However, in recent years, advances within the fields of genomics and proteomics have strengthened and given rise to new biologic therapies. Protein therapies, such as monoclonal antibodies and peptide drugs, have provided patients with pharmaceuticals that offer a higher level of selectivity and effectiveness that would be otherwise undeliverable within the realm of small organics. In addition to protein therapies, DNA-based therapy, such as RNA interference (RNAi) and gene therapy, have gained renewed interest within modern medicine and are potentially poised for a comeback within the biotechnology industry. As we discuss here, the advantages of such therapies continue to accumulate and have kept the biologic market strong. Copyright © 2014 Elsevier Ltd. All rights reserved.

Cytomegalovirus retinitis and HIV: Case reviews from KwaZulu-Natal Province, South Africa.

PubMed

Hassan-Moosa, R; Chinappa, T; Jeena, L; Visser, L; Naidoo, K

2017-09-22

Retinal cytomegalovirus (CMV) infection is a common opportunistic infection and remains a significant contributor to visual loss in patients with AIDS. We highlight the poor outcomes of CMV retinitis in three HIV-infected patients who were initiated on antiretroviral therapy (ART). We conducted a retrospective chart review of advanced stage HIV-infected patients with known CMV retinitis.Case 1. A 37-year-old man, with a CD4+ cell count of 35 cells/µL, presented for ART initiation with a 5-month history of visual loss in his left eye. Fundoscopy showed left eye CMV retinitis and right eye HIV retinopathy. ART and 5 months of weekly intravitreal ganciclovir injections (left eye) were commenced. Six-month outcomes included virological suppression, and visual acuity in the right eye of 6/6 and in the left eye of 3/60.Case 2. A 31-year-old woman, with a CD4+ cell count of 39 cells/µL and on tuberculosis therapy, presented for ART initiation. She presented with a 2-month history of decreased visual acuity. Fundoscopy showed bilateral CMV retinitis, which was more pronounced in the left eye. ART and 8 months of intravitreal ganciclovir injections were commenced. Six-month outcomes included virological suppression and visual acuity in the right eye of 6/9, and in the left eye of 6/24.Case 3. A 29-year-old woman, with a CD4+ cell count of 24 cells/µL, who was on tuberculosis therapy and ART, complained of blurred vision at her 2-month ART follow-up visit. Fundoscopy showed bilateral retinal detachment secondary to CMV retinitis. While silicone oil tamponade and subsequent retinectomy successfully repaired the right eye, extensive damage rendered the left eye irreparable. Six-month outcomes included virological suppression, with 6/120 visual acuity in the right eye and complete blindness in the left eye. CMV retinitis causes debilitating, permanent sequelae, which is preventable by ART initiation at higher CD4+ cell counts. Despite achieving virological suppression, vision could not be completely restored in these patients, irrespective of the severity of CMV retinitis.

Pre-emptive therapy for severe nausea and vomiting of pregnancy and hyperemesis gravidarum.

PubMed

Koren, G; Maltepe, Caroline

2004-08-01

Nausea and vomiting of pregnancy (NVP) affects 80% of pregnancies. Its severe form, hyperemesis gravidarum (HG), results in dehydration, electrolyte imbalance, the need for hospitalisation and can, rarely, be fatal. This was a prospective, open-labelled, controlled, interventional study to evaluate the effectiveness of pre-emptive treatment of NVP symptoms in women who experienced severe NVP or HG in their previous pregnancy. Twenty-five women who reported severe symptoms of NVP with or without HG in their previous pregnancy were recruited and counselled to commence the use of antiemetics as soon as they became aware of the present pregnancy, and no later than the beginning of symptoms. They were followed-up prospectively through the index pregnancy for symptoms of NVP, and were counselled continuously as to how to modify antiemetic doses based on symptoms. A comparison group consisted of randomly selected women also counselled by us for NVP, who had also had severe NVP in the previous pregnancy, but who did not call before a planned pregnancy and thus could not be offered pre-emptive therapy. The recruited women commenced pre-emptive drug therapy for NVP before conception or up to 7 weeks' gestation, before the appearance of NVP symptoms in all cases. In comparison to the previous pregnancy, only eight of these 18 women experienced a HG again in the index pregnancy (P = 0.01). The majority of study the women had an improvement in severity of NVP symptoms compared to the previous pregnancy. In the comparison group (n = 35), symptoms in the index pregnancy remained severe in 28 cases (80%), decreased to moderate in six (16.6%) and decreased to mild in five cases (13.9%). There were five cases of HG in the previous pregnancy and three in the index pregnancy. The pre-emptive group was improved significantly compared to the control group (P = 0.01). Pre-emptive symptom management appears to be effective in preventing severe NVP in general, and HG in particular. Women who have experienced severe NVP in a previous pregnancy may benefit from taking antiemetics before, or immediately at the start of symptoms in a subsequent pregnancy.

Perception of peer physical examination in two Australian osteopathy programs.

PubMed

Vaughan, Brett; Grace, Sandra

2016-01-01

Peer physical examination (PPE) is an efficient and practical educational approach whereby students can practise their examination skills on each other before commencing clinical practice with actual patients. Little is known about the use of PPE in osteopathy education. Students in Year 1 of the osteopathy programs at Victoria University (Melbourne, Australia) and Southern Cross University (Lismore, Australia) completed the Examining Fellow Students and the Peer Physical Examination questionnaires prior to, and at the completion of, their first 12-week teaching session. Descriptive statistics were generated for each questionnaire. The McNemar and sign tests were used to evaluate differences between each questionnaire administration. Logistic regression was used to evaluate the influence of demographics on responses to both questionnaires. Results showed that students in both programs were generally willing to examine non-sensitive areas both before and after the 12-week teaching session. Students' were less apprehensive about PPE at the end of the teaching session, and this was reinforced by results for previous exposure to PPE in other courses. Consistent with previous studies, unwillingness to participate in PPE was associated with being female, being born outside Australia, holding religious beliefs, and being older. This is the first study to explore students' perceptions of PPE in this cohort and provides a basis for further work, including evaluating longer term changes in student perception of PPE, and whether these perceptions extend to practising manual therapy techniques. This study demonstrates that perceptions about PPE reported in medicine and other disciplines, namely that unwillingness to participate in PPE is associated with being female, being born outside Australia, holding religious beliefs, and being older, also apply to osteopathy. These findings are significant for all manual therapy students who spend a substantial portion of their course developing skills in PPE and practising manual therapy techniques. They highlight the need for curriculum development that acknowledges the importance of good practice in PPE, including discussions about body image, feedback skills training for educators, and providing detailed information to students about what to expect in practical skills classes before they commence their course.

Efficacy and tolerability of high-dose phenobarbital in children with focal seizures.

PubMed

Okumura, Akihisa; Nakahara, Eri; Ikeno, Mitsuru; Abe, Shinpei; Igarashi, Ayuko; Nakazawa, Mika; Takasu, Michihiko; Shimizu, Toshiaki

2016-04-01

We retrospectively reviewed the outcomes of children with focal epilepsy treated with oral high-dose phenobarbital. We reviewed data on children (aged<15 years) with focal seizures treated with high-dose phenobarbital (>5 mg/kg/day to maintain a target serum level >40 μg/mL) for at least 6 months. Seizure frequency was evaluated after phenobarbital titration, and 1 and 2 years after high-dose phenobarbital treatment commenced. Treatment was judged effective when seizure frequencies fell by ⩾75%. Seven boys and eight girls were treated. The median age at commencement of high-dose phenobarbital therapy was 30 months. The maximal serum phenobarbital level ranged from 36.5 to 62.9 μg/mL. High-dose PB was effective in seven. In two patients, treatment was transiently effective, but seizure frequency later returned to the baseline. High-dose PB was ineffective in six. No significant association between effectiveness and any clinical variable was evident. Drowsiness was recorded in nine patients, but no patient developed a behavioral problem or hypersensitivity. Oral high-dose phenobarbital was effective in 7 of 15 patients with focal epilepsy and well tolerated. High-dose PB may be useful when surgical treatment is difficult. Copyright © 2015 The Japanese Society of Child Neurology. Published by Elsevier B.V. All rights reserved.

5 CFR Appendix A to Subpart C of... - Present Value Conversion Factors for Earlier Commencing Date of Annuities of Current and Former...

Code of Federal Regulations, 2010 CFR

2010-01-01

... 5 Administrative Personnel 2 2010-01-01 2010-01-01 false Present Value Conversion Factors for Earlier Commencing Date of Annuities of Current and Former Spouses of Deceased Separated Employees A...—Present Value Conversion Factors for Earlier Commencing Date of Annuities of Current and Former Spouses of...

75 FR 81604 - Price Dam Partnership, Limited; Notice of Request for Extension of Time to Commence and Complete...

Federal Register 2010, 2011, 2012, 2013, 2014

2010-12-28

... Partnership, Limited; Notice of Request for Extension of Time to Commence and Complete Construction and.... Application Type: Request for Extension of Time. b. Project No.: 12187-016. c. Date Filed: December 8, 2010. d...-year extension of time from the existing deadline of July 28, 2011 to July 28, 2013 to commence project...

26 CFR 1.401(a)-14 - Commencement of benefits under qualified trusts.

Code of Federal Regulations, 2010 CFR

2010-04-01

... 26 Internal Revenue 5 2010-04-01 2010-04-01 false Commencement of benefits under qualified trusts.... § 1.401(a)-14 Commencement of benefits under qualified trusts. (a) In general. Under section 401(a)(14... section 401 unless the plan of which such trust is a part provides that the payment of benefits under the...

40 CFR Table 7 to Subpart Cccc of... - Emission Limitations for Waste-Burning Kilns That Commenced Construction After June 4, 2010, or...

Code of Federal Regulations, 2012 CFR

2012-07-01

... 40 Protection of Environment 7 2012-07-01 2012-07-01 false Emission Limitations for Waste-Burning... Waste-Burning Kilns That Commenced Construction After June 4, 2010, or Reconstruction or Modification... indefinitely. Table 7 to Subpart CCCC of Part 60—Emission Limitations for Waste-Burning Kilns That Commenced...

40 CFR Table 7 to Subpart Cccc of... - Emission Limitations for Waste-Burning Kilns That Commenced Construction After June 4, 2010, or...

Code of Federal Regulations, 2011 CFR

2011-07-01

... 40 Protection of Environment 6 2011-07-01 2011-07-01 false Emission Limitations for Waste-Burning... Waste-Burning Kilns That Commenced Construction After June 4, 2010, or Reconstruction or Modification... indefinitely. Table 7 to Subpart CCCC of Part 60—Emission Limitations for Waste-Burning Kilns That Commenced...

40 CFR Table 7 to Subpart Cccc of... - Emission Limitations for Waste-burning Kilns That Commenced Construction After June 4, 2010, or...

Code of Federal Regulations, 2014 CFR

2014-07-01

... 40 Protection of Environment 7 2014-07-01 2014-07-01 false Emission Limitations for Waste-burning Kilns That Commenced Construction After June 4, 2010, or Reconstruction or Modification After August 7... to Subpart CCCC of Part 60—Emission Limitations for Waste-burning Kilns That Commenced Construction...

WE-FG-BRB-00: The Challenges of Predicting RBE Effects in Particle Therapy and Opportunities for Improving Cancer Therapy

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

NONE

The physical pattern of energy deposition and the enhanced relative biological effectiveness (RBE) of protons and carbon ions compared to photons offer unique and not fully understood or exploited opportunities to improve the efficacy of radiation therapy. Variations in RBE within a pristine or spread out Bragg peak and between particle types may be exploited to enhance cell killing in target regions without a corresponding increase in damage to normal tissue structures. In addition, the decreased sensitivity of hypoxic tumors to photon-based therapies may be partially overcome through the use of more densely ionizing radiations. These and other differences betweenmore » particle and photon beams may be used to generate biologically optimized treatments that reduce normal tissue complications. In this symposium, speakers will examine the impact of the RBE of charged particles on measurable biological endpoints, treatment plan optimization, and the prediction or retrospective assessment of treatment outcomes. In particular, an AAPM task group was formed to critically examine the evidence for a spatially-variant RBE in proton therapy. Current knowledge of proton RBE variation with respect to dose, biological endpoint, and physics parameters will be reviewed. Further, the clinical relevance of these variations will be discussed. Recent work focused on improving simulations of radiation physics and biological response in proton and carbon ion therapy will also be presented. Finally, relevant biology research and areas of research needs will be highlighted, including the dependence of RBE on genetic factors including status of DNA repair pathways, the sensitivity of cancer stem-like cells to charged particles, the role of charged particles in hypoxic tumors, and the importance of fractionation effects. In addition to the physical advantages of protons and more massive ions over photons, the future application of biologically optimized treatment plans and their potential to provide higher levels of local tumor control and improved normal tissue sparing will be discussed. Learning Objectives: To assess whether the current practice of a constant RBE of 1.1 should be revised or maintained in proton therapy and to evaluate the potential clinical consequences of delivering RBE-weighted dose distributions based on variable RBE To review current research on biological models used to predict the increased biological effectiveness of proton and carbon ions to help move towards a practical understanding and implementation of biological optimization in particle therapy To discuss potential differences in biological mechanisms between photons and charged particles (light and heavy ions) that could impact clinical cancer therapy H. Paganetti, NCI U19 CA21239D. Grosshans, Our research is supported by the NCIK. Held, Funding Support: National Cancer Institute of the National Institutes of Health, USA, under Award Number R21CA182259 and Federal Share of Program Income Earned by Massachusetts General Hospital on C06CA059267, Proton Therapy Research and Treatment Center.« less

Treatment with biologic agents improves the prognosis of patients with rheumatoid arthritis and amyloidosis.

PubMed

Kuroda, Takeshi; Tanabe, Naohito; Kobayashi, Daisuke; Sato, Hiroe; Wada, Yoko; Murakami, Shuichi; Saeki, Takako; Nakano, Masaaki; Narita, Ichiei

2012-07-01

Reactive amyloid A (AA) amyloidosis is a serious and life-threatening systemic complication of rheumatoid arthritis (RA). We evaluated the safety of therapy with anti-tumor necrosis factor and anti-interleukin 6 biologic agents in RA patients with reactive AA amyloidosis, together with prognosis and hemodialysis (HD)-free survival, in comparison with patients with AA amyloidosis without such therapy. One hundred thirty-three patients with an established diagnosis of reactive AA amyloidosis participated in the study. Clinical data were assessed from patient records at the time of amyloid detection and administration of biologics. Survival was calculated from the date when amyloid was first demonstrated histologically or the date when biologic therapy was started until the time of death or to the end of 2010 for surviving patients. Patients who had started HD were selected for inclusion only after the presence of amyloid was demonstrated. Fifty-three patients were treated with biologic agents (biologic group) and 80 were not (nonbiologic group). Survival rate was significantly higher in the biologic group than in the nonbiologic group. Nine patients in the biologics group and 33 in the nonbiologic group started HD. Biologic therapy had a tendency for reduced risk of initiation of HD without any statistical significance. Patients with amyloidosis have a higher mortality rate, but the use of biologic agents can reduce risk of death. The use of biologics may not significantly influence the HD-free survival rate.

Cost Sharing, Family Health Care Burden, and the Use of Specialty Drugs for Rheumatoid Arthritis

PubMed Central

Karaca-Mandic, Pinar; Joyce, Geoffrey F; Goldman, Dana P; Laouri, Marianne

2010-01-01

Objectives To examine the impact of benefit generosity and household health care financial burden on the demand for specialty drugs in the treatment of rheumatoid arthritis (RA). Data Sources/Study Setting Enrollment, claims, and benefit design information for 35 large private employers during 2000–2005. Study Design We estimated multivariate models of the effects of benefit generosity and household financial burden on initiation and continuation of biologic therapies. Data Extraction Methods We defined initiation of biologic therapy as first-time use of etanercept, adalimumab, or infliximab, and we constructed an index of plan generosity based on coverage of biologic therapies in each plan. We estimated the household's burden by summing up the annual out-of-pocket (OOP) expenses of other family members. Principal Findings Benefit generosity affected both the likelihood of initiating a biologic and continuing drug therapy, although the effects were stronger for initiation. Initiation of a biologic was lower in households where other family members incurred high OOP expenses. Conclusions The use of biologic therapy for RA is sensitive to benefit generosity and household financial burden. The increasing use of coinsurance rates for specialty drugs (as under Medicare Part D) raises concern about adverse health consequences. PMID:20831715

Method for photo-altering a biological system to improve biological effect

DOEpatents

Hill, Richard A.; Doiron, Daniel R.; Crean, David H.

2000-08-01

Photodynamic therapy is a new adjunctive therapy for filtration surgery that does not use chemotherapy agents or radiation, but uses pharmacologically-active sensitizing compounds to produce a titratable, localized, transient, post operative avascular conjunctiva. A photosensitizing agent in a biological system is selectively activated by delivering the photosensitive agent to the biological system and laser activating only a spatially selected portion of the delivered photosensitive agent. The activated portion of the photosensitive agent reacts with the biological system to obtain a predetermined biological effect. As a result, an improved spatial disposition and effectuation of the biological effect by the photosensitive agent in the biological system is achieved.

Effects of balneotherapy and spa therapy on levels of cortisol as a stress biomarker: a systematic review

NASA Astrophysics Data System (ADS)

Antonelli, Michele; Donelli, Davide

2018-06-01

Balneotherapy and spa therapy are well-known practices, even though limited evidence has been produced about their biological effects. This systematic review primarily aims at assessing if balneotherapy, mud/peloid therapy, and spa therapy may influence cortisol levels. Secondarily, it aims at understanding if these interventions may improve stress resilience. PubMed/Medline, Embase, and Cochrane Library were searched for relevant articles in English or Italian about studies involving healthy and sub-healthy subjects or patients with a diagnosed disease about effects of balneotherapy, mud/peloid therapy, and spa therapy on serum and salivary cortisol levels. Fifteen studies involving 684 subjects were included. Five studies investigated biological effects of balneotherapy alone. Two of them reported significant changes of cortisol levels in healthy participants. The other three studies reported no significant variations in patients with rheumatic conditions. No studies investigated biological effects of mud/peloid therapy alone. Ten studies investigated biological effects of spa therapy with or without included mud/peloid therapy, and in all but two studies, significant variations of cortisol levels were reported. Our main findings suggest that balneotherapy may have the potential to influence cortisol levels in healthy subjects, in such a way as to improve stress resilience. Spa therapy with or without included mud/peloid therapy demonstrated the same potential to influence cortisol levels also in sub-healthy subjects and in patients with a diagnosed disease. Therefore, balneotherapy and spa therapy may be considered as useful interventions for the management of stress conditions. Further investigation is needed because of limited available data.

Effects of balneotherapy and spa therapy on levels of cortisol as a stress biomarker: a systematic review.

PubMed

Antonelli, Michele; Donelli, Davide

2018-02-18

Balneotherapy and spa therapy are well-known practices, even though limited evidence has been produced about their biological effects. This systematic review primarily aims at assessing if balneotherapy, mud/peloid therapy, and spa therapy may influence cortisol levels. Secondarily, it aims at understanding if these interventions may improve stress resilience. PubMed/Medline, Embase, and Cochrane Library were searched for relevant articles in English or Italian about studies involving healthy and sub-healthy subjects or patients with a diagnosed disease about effects of balneotherapy, mud/peloid therapy, and spa therapy on serum and salivary cortisol levels. Fifteen studies involving 684 subjects were included. Five studies investigated biological effects of balneotherapy alone. Two of them reported significant changes of cortisol levels in healthy participants. The other three studies reported no significant variations in patients with rheumatic conditions. No studies investigated biological effects of mud/peloid therapy alone. Ten studies investigated biological effects of spa therapy with or without included mud/peloid therapy, and in all but two studies, significant variations of cortisol levels were reported. Our main findings suggest that balneotherapy may have the potential to influence cortisol levels in healthy subjects, in such a way as to improve stress resilience. Spa therapy with or without included mud/peloid therapy demonstrated the same potential to influence cortisol levels also in sub-healthy subjects and in patients with a diagnosed disease. Therefore, balneotherapy and spa therapy may be considered as useful interventions for the management of stress conditions. Further investigation is needed because of limited available data.

Effects of balneotherapy and spa therapy on levels of cortisol as a stress biomarker: a systematic review

NASA Astrophysics Data System (ADS)

Antonelli, Michele; Donelli, Davide

2018-02-01

Balneotherapy and spa therapy are well-known practices, even though limited evidence has been produced about their biological effects. This systematic review primarily aims at assessing if balneotherapy, mud/peloid therapy, and spa therapy may influence cortisol levels. Secondarily, it aims at understanding if these interventions may improve stress resilience. PubMed/Medline, Embase, and Cochrane Library were searched for relevant articles in English or Italian about studies involving healthy and sub-healthy subjects or patients with a diagnosed disease about effects of balneotherapy, mud/peloid therapy, and spa therapy on serum and salivary cortisol levels. Fifteen studies involving 684 subjects were included. Five studies investigated biological effects of balneotherapy alone. Two of them reported significant changes of cortisol levels in healthy participants. The other three studies reported no significant variations in patients with rheumatic conditions. No studies investigated biological effects of mud/peloid therapy alone. Ten studies investigated biological effects of spa therapy with or without included mud/peloid therapy, and in all but two studies, significant variations of cortisol levels were reported. Our main findings suggest that balneotherapy may have the potential to influence cortisol levels in healthy subjects, in such a way as to improve stress resilience. Spa therapy with or without included mud/peloid therapy demonstrated the same potential to influence cortisol levels also in sub-healthy subjects and in patients with a diagnosed disease. Therefore, balneotherapy and spa therapy may be considered as useful interventions for the management of stress conditions. Further investigation is needed because of limited available data.

Biologic agents therapy for Saudi children with rheumatic diseases: indications and safety.

PubMed

Al-Mayouf, Sulaiman M; Alenazi, Abdullatif; AlJasser, Hind

2016-06-01

To report the indications and safety of biologic agents in childhood rheumatic diseases at a tertiary hospital. Children with rheumatic diseases treated with biologic agents at King Faisal Specialist Hospital and Research Center, Riyadh, Saudi Arabia, from January 2001 to December 2011 were included. All patients were reviewed for: demographic characteristics, diagnosis, concomitant treatment and indications of using biologic agents, age at start of therapy and side effects during the treatment period. In all, 134 children (89 female) with various rheumatic diseases were treated with biologic agents. Mean age at starting biologic treatment was 9.3 (4.25-14) years and mean therapy duration was 14.7 (3-88) months. Juvenile idiopathic arthritis (JIA) was the most frequent diagnosis (70.1%) followed by systemic lupus erythematosus (12.7%) and vasculitis (4.5%). All patients received concomitant therapy (corticosteroids and disease-modifying antirheumatic drugs). In total, 273 treatments with biologic agents were used, (95 etanercept, 52 rituximab, 47 adalimumab, 37 infliximab, 23 anakinra, 10 tocilizumab and nine abatacept). Therapy was switched to another agent in 57 (42.5%) patients, mainly because of inefficacy (89.4%) or adverse event (10.6%). A total of 95 (34.8%) adverse events were notified; of these, the most frequent were infusion-related reactions (33.7%) followed by infections (24.2%) and autoantibody positivity (10.6%). One patient developed macrophage activation syndrome. Biologic agents were used in children with a range of rheumatic diseases. Of these, the most frequent was JIA. Off-label use of biologic agents in our cohort is common. These agents seem safe. However, they may associated with various adverse events. Sequential therapy seems well tolerated. However, this should be carefully balanced and considered on an individual basis. © 2014 Asia Pacific League of Associations for Rheumatology and Wiley Publishing Asia Pty Ltd.

Cardiovascular safety of biologic therapies for the treatment of RA.

PubMed

Greenberg, Jeffrey D; Furer, Victoria; Farkouh, Michael E

2011-11-15

Cardiovascular disease represents a major source of extra-articular comorbidity in patients with rheumatoid arthritis (RA). A combination of traditional cardiovascular risk factors and RA-related factors accounts for the excess risk in RA. Among RA-related factors, chronic systemic inflammation has been implicated in the pathogenesis and progression of atherosclerosis. A growing body of evidence--mainly derived from observational databases and registries--suggests that specific RA therapies, including methotrexate and anti-TNF biologic agents, can reduce the risk of future cardiovascular events in patients with RA. The cardiovascular profile of other biologic therapies for the treatment of RA has not been adequately studied, including of investigational drugs that improve systemic inflammation but alter traditional cardiovascular risk factors. In the absence of large clinical trials adequately powered to detect differences in cardiovascular events between biologic drugs in RA, deriving firm conclusions on cardiovascular safety is challenging. Nevertheless, observational research using large registries has emerged as a promising approach to study the cardiovascular risk of emerging RA biologic therapies.

Initiation of insulin for type 2 diabetes mellitus patients: what are the issues? A qualitative study.

PubMed

Tan, A M; Muthusamy, L; Ng, C C; Phoon, K Y; Ow, J H; Tan, N C

2011-11-01

Type 2 diabetes mellitus is a progressive condition in which the pancreatic beta-cell function deteriorates with increasing duration of the disease. When good glycaemic control is not achieved despite adherence to oral hypoglycaemic drugs, healthy diet and lifestyle, insulin should be initiated. However, this is often delayed due to various reasons. We aimed to determine the issues relating to insulin initiation for diabetic patients managed in primary care polyclinics in Singapore. Qualitative data was obtained during four focus group discussions, with participation from healthcare professionals (HCPs), including physicians and nurses, and type 2 diabetes mellitus patients. The data was transcribed into text, coded and grouped into themes. Launching the topic and doctor-patient communication on insulin therapy were key issues in insulin initiation. Patient barriers to insulin commencement included: refusal to acknowledge the need for insulin therapy; its perception as a social stigma, an inconvenient mode of treatment or punishment for failure; and fear of needles, side-effects and complications. The HCP's attitude and experience with insulin therapy were also possible barriers. Our findings highlight that insulin initiation is affected by the complex interaction between the patients and HCPs, and other system factors. Patients may harbour misconceptions about insulin due to the late introduction of insulin therapy by HCPs or the way the therapy is being communicated to them. The key issues to address are the disparity in perceptions of diabetic control between HCPs and patients, and education regarding the need for insulin therapy.

Preservative-free tafluprost/timolol fixed combination: a new opportunity in the treatment of glaucoma.

PubMed

Konstas, Anastasios G P; Holló, Gabor

2016-06-01

Medical therapy of glaucoma aims to maintain the patient's visual function and quality of life. This generally commences with monotherapy, but it is often difficult to reach the predetermined target pressure with this approach. Fixed combinations (FCs) are therefore selected as the next step of the medical therapy algorithm. By employing a prostaglandin/timolol fixed combination (PTFC) the desired target 24-hour intraocular pressure can be reached in many glaucoma patients with the convenience of once-a-day administration and the associated high rate of adherence. The current role and value of FCs in the medical therapy of glaucoma is critically appraised. Special attention is paid to the PTFCs and the emerging role of preservative-free PTFCs. This review summarizes existing information on the efficacy and tolerability of the new preservative-free tafluprost/timolol FC (Taptiqom®). The preservative-free tafluprost/timolol FC represents a promising stepwise treatment option for those patients whose intraocular pressure is insufficiently controlled with available monotherapy options. This novel FC has the potential to substantially improve glaucoma management and through evolution of the current glaucoma treatment paradigm, to become a core therapeutic option in the future. Nonetheless, future research is needed to better delineate the therapeutic role of current and future preservative-free FCs in glaucoma therapy.

Retrospective clinical evaluation of gauze-based negative pressure wound therapy.

PubMed

Campbell, Penny E; Smith, Gary S; Smith, Jennifer M

2008-06-01

Negative pressure wound therapy (NPWT) is an established modality in the treatment of challenging wounds. However, most existing clinical evidence is derived from the use of open-cell polyurethane foam at -125 mmHg. Alternative negative pressure systems are becoming available, which use gauze at a pressure of -80 mmHg. This study describes clinical results from a retrospective non comparative analysis of 30 patients treated with Chariker-Jeter gauze-based negative pressure systems (V1STA, Versatile-1 and EZ-Care; Smith & Nephew, Inc.) in a long-term care setting. The mean age of the patients was 72 years. The wounds consisted of chronic (n = 11), surgical dehiscence (n = 11) and surgical incision (n = 8). Wound volume and area were recorded at commencement and at the cessation of therapy. Discontinuation of therapy was instigated upon closure through secondary intention or when size and exudate were sufficiently reduced that the wounds could be managed by conventional wound dressing (median 41 days). An overall median reduction in wound volume of 88.0% (P < 0.001) and a 68.0% reduction in area (P < 0.001) compared with baseline were observed over the course of NPWT. The overall rate of volume reduction (15.1% per week) compares favourably with published data from foam-based systems.

Spontaneous abortion and the prophylactic effect of folic acid supplementation in epileptic women undergoing antiepileptic therapy.

PubMed

Pittschieler, Sabine; Brezinka, Christoph; Jahn, Beate; Trinka, Eugen; Unterberger, Iris; Dobesberger, Judith; Walser, Gerald; Auckenthaler, Andrea; Embacher, Norbert; Bauer, Gerhard; Luef, Gerhard

2008-12-01

Antiepileptic drugs (AEDs) like phenytoin (PHE), carbamazepine (CBZ), barbiturates and valproic acid (VPA) interfere with folic acid absorption and metabolism, which in turn can be the cause of adverse pregnancy outcome. To study the prophylactic effect of folic acid supplementation with regard to spontaneous abortion and preterm delivery (fetal demise after week 20 of gestational age) in pregnant women receiving AED therapy, as well as benefits of most common dosage and preconceptional commencement. Prospective examination of 104 patients, registered in EURAP from 1999-2004 at a single center and a retrospective analysis of data from our epilepsy databank completed with medical records and patients interviews of the Department of Neurology of Innsbruck University Hospital from 1971 to 1999. 388 pregnancies in 244 patients were analyzed. Pregnancies with folic acid supplementation showed significant reduction of spontaneous abortion. With regard to monotherapies, in the group of women taking VPA, supplementation of folic acid had significant benefit. Other examined monotherapies (CBZ, PHE, and PB) known to interfere with folic acid showed no significant results. This study confirms the prophylactic effect of folic acid supplementation on spontaneous abortion. For AED therapy, folic acid supplementation should be part of the therapy of every pregnant epileptic woman, especially for those treated with VPA.

The changing motivation of massage therapy students.

PubMed

Finch, P

2007-05-01

The study was conducted in order to determine whether the level of motivation related to intrinsic (people-oriented) and extrinsic (external reward) value complexes in a class of massage therapy students changed during their professional education. The research was a quasi-experimental within-subject design, in which survey data was collected from students on their first day in the massage therapy program and again towards the end of their final term. The data were collated and summarized, and the differences in motivation scores were assessed using Fisher's Least Significant Difference procedure. The results support the hypothesis that massage therapy students are motivated more strongly by intrinsic than extrinsic rewards both at the commencement of their studies and as they approach entry to practice. Also evident from the data is the fact that the students' motivation changed during their professional studies. This change involved a significant decrease in the level of intrinsic motivation and significant increase in the level of extrinsic motivation. Thus, although intrinsic motivation reduced while extrinsic motivation increased, the former remained the more powerful influence. Professional programs should consider the balance between intrinsic and extrinsic student motivation and attempt to control influences that might shift this such that the humanistic / altruistic mission of health care is undermined.

Graph Theory

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

Sanfilippo, Antonio P.

2005-12-27

Graph theory is a branch of discrete combinatorial mathematics that studies the properties of graphs. The theory was pioneered by the Swiss mathematician Leonhard Euler in the 18th century, commenced its formal development during the second half of the 19th century, and has witnessed substantial growth during the last seventy years, with applications in areas as diverse as engineering, computer science, physics, sociology, chemistry and biology. Graph theory has also had a strong impact in computational linguistics by providing the foundations for the theory of features structures that has emerged as one of the most widely used frameworks for themore » representation of grammar formalisms.« less

40 CFR Table 5 to Subpart Cccc of... - Emission Limitations for Incinerators That Commenced Construction After June 4, 2010, or That...

Code of Federal Regulations, 2011 CFR

2011-07-01

... 40 Protection of Environment 6 2011-07-01 2011-07-01 false Emission Limitations for Incinerators That Commenced Construction After June 4, 2010, or That Commenced Reconstruction or Modification After September 21, 2011 5 Table 5 to Subpart CCCC of Part 60 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED) AIR PROGRAMS ...

40 CFR Table 5 to Subpart Cccc of... - Emission Limitations for Incinerators That Commenced Construction After June 4, 2010, or That...

Code of Federal Regulations, 2014 CFR

2014-07-01

... 40 Protection of Environment 7 2014-07-01 2014-07-01 false Emission Limitations for Incinerators That Commenced Construction After June 4, 2010, or That Commenced Reconstruction or Modification After August 7, 2013 5 Table 5 to Subpart CCCC of Part 60 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED) AIR PROGRAMS (CONTINUED)...

40 CFR Table 5 to Subpart Cccc of... - Emission Limitations for Incinerators That Commenced Construction After June 4, 2010, or That...

Code of Federal Regulations, 2013 CFR

2013-07-01

... 40 Protection of Environment 7 2013-07-01 2013-07-01 false Emission Limitations for Incinerators That Commenced Construction After June 4, 2010, or That Commenced Reconstruction or Modification After September 21, 2011 5 Table 5 to Subpart CCCC of Part 60 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED) AIR PROGRAMS ...

40 CFR Table 5 to Subpart Cccc of... - Emission Limitations for Incinerators That Commenced Construction After June 4, 2010, or That...

Code of Federal Regulations, 2012 CFR

2012-07-01

... 40 Protection of Environment 7 2012-07-01 2012-07-01 false Emission Limitations for Incinerators That Commenced Construction After June 4, 2010, or That Commenced Reconstruction or Modification After September 21, 2011 5 Table 5 to Subpart CCCC of Part 60 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED) AIR PROGRAMS ...

Severe and acute complications of biologics in psoriasis.

PubMed

Oussedik, Elias; Patel, Nupur U; Cash, Devin R; Gupta, Angela S; Feldman, Steven R

2017-12-01

Biologic therapies have revolutionized the approach to immune-mediated diseases such as psoriasis. Due to their favorable safety profiles and excellent efficacy, biologic agents are considered the gold standard for moderate-to-severe psoriasis. The aim of this paper is to saliently review the severe and acute complications of the Food and Drug Administration (FDA) approved biologic agents for psoriasis. Reviewed agents include tumor necrosis factor alpha inhibitors (etanercept, infliximab, and adalimumab), interleukin 12/23 inhibitors (ustekinumab), and interleukin 17 (IL-17) inhibitors (secukinumab and ixekizumab). While malignancies, serious infections, and major adverse cardiovascular events have been reported, their association with biologic therapy are not hypothesized as causal. However, IL-17 inhibitors appear to cause exacerbations and new cases of inflammatory bowel disease. While more long-term studies are warranted in understanding the biologic's long-term side effect profile, short-term studies have confirmed that the biologics are some of the safest treatment options for psoriasis. Nevertheless, certain populations yield higher risk to acute complications with the biologics than others - physicians must use their judgement and vigilance when monitoring and treating patients undergoing therapy with biological agents.

Cancer Systems Biology: a peak into the future of patient care?

PubMed Central

Werner, Henrica M. J.; Mills, Gordon B.; Ram, Prahlad T.

2015-01-01

Traditionally, scientific research has focused on studying individual events, such as single mutations, gene function or the effect of the manipulation of one protein on a biological phenotype. A range of technologies, combined with the ability to develop robust and predictive mathematical models, is beginning to provide information that will enable a holistic view of how the genomic and epigenetic aberrations in cancer cells can alter the homeostasis of signalling networks within these cells, between cancer cells and the local microenvironment, at the organ and organism level. This systems biology process needs to be integrated with an iterative approach wherein hypotheses and predictions that arise from modelling are refined and constrained by experimental evaluation. Systems biology approaches will be vital for developing and implementing effective strategies to deliver personalized cancer therapy. Specifically, these approaches will be important to select those patients most likely to benefit from targeted therapies as well as for the development and implementation of rational combinatorial therapies. Systems biology can help to increase therapy efficacy or bypass the emergence of resistance, thus converting the current (often short term) effects of targeted therapies into durable responses, ultimately to improve quality of life and provide a cure. PMID:24492837

Preoperative biological therapy and short-term outcomes of abdominal surgery in patients with inflammatory bowel disease.

PubMed

Waterman, Matti; Xu, Wei; Dinani, Amreen; Steinhart, A Hillary; Croitoru, Kenneth; Nguyen, Geoffrey C; McLeod, Robin S; Greenberg, Gordon R; Cohen, Zane; Silverberg, Mark S

2013-03-01

Previous investigations of short-term outcomes after preoperative exposure to biological therapy in inflammatory bowel disease (IBD) were conflicting. The authors aimed to assess postoperative outcomes in patients who underwent abdominal surgery with recent exposure to anti-tumour necrosis factor therapy. A retrospective case-control study with detailed matching was performed for subjects with IBD with and without exposure to biologics within 180 days of abdominal surgery. Postoperative outcomes were compared between the groups. 473 procedures were reviewed consisting of 195 patients with exposure to biologics and 278 matched controls. There were no significant differences in most postoperative outcomes such as: length of stay, fever (≥ 38.5°C), urinary tract infection, pneumonia, bacteraemia, readmission, reoperations and mortality. On univariate analysis, procedures on biologics had more wound infections compared with controls (19% vs 11%; p=0.008), but this was not significant in multivariate analysis. Concomitant therapy with biologics and thiopurines was associated with increased frequencies of urinary tract infections (p=0.0007) and wound infections (p=0.0045). Operations performed ≤ 14 days from last biologic dose had similar rates of infections and other outcomes when compared with those performed within 15-30 days or 31-180 days. Patients with detectable preoperative infliximab levels had similar rates of wound infection compared with those with undetectable levels (3/10 vs 0/9; p=0.21). Preoperative treatment with TNF-α antagonists in patients with IBD is not associated with most early postoperative complications. A shorter time interval from last biological dose is not associated with increased postoperative complications. In most cases, surgery should not be delayed, and appropriate biological therapy may be continued perioperatively.

Age-dependent differences in nicotine reward and withdrawal in female mice.

PubMed

Kota, D; Martin, B R; Damaj, M I

2008-06-01

Adolescent smoking is an increasing epidemic in the US. Research has shown that the commencement of smoking at a young age increases addiction and decreases the probability of successful cessation; however, limited work has focused on nicotine dependence in the female. The goal of the present study was to identify the biological and behavioral factors that may contribute to nicotine's increased abuse liability in female adolescents using animal models of nicotine dependence. Early adolescent (PND 28) and adult (PND 70) female mice were compared in various aspects of nicotine dependence using reward and withdrawal models following sub-chronic nicotine exposure. Furthermore, in vivo acute sensitivity and tolerance to nicotine were examined. In the conditioned place preference model, adolescents demonstrated a significant preference at 0.5 mg/kg nicotine, an inactive dose in adults. Adults found higher doses (0.7 and 1.0 mg/kg) of nicotine to elicit rewarding effects. Furthermore, adolescents displayed increased physical, but not affective, withdrawal signs in three models. Upon acute exposure to nicotine, adolescent mice showed increased sensitivity in an analgesic measure as well as hypothermia. After chronic nicotine exposure, both adults and adolescents displayed tolerance to nicotine with adolescents having a lower degree of tolerance to changes in body temperature. These data indicate that differences in nicotine's rewarding and aversive effects may contribute to variations in certain components of nicotine dependence between adult and adolescent female mice. Furthermore, this implies that smoking cessation therapies may not be equally effective across all ages.

TOOTH (The Open study Of dental pulp stem cell Therapy in Humans): Study protocol for evaluating safety and feasibility of autologous human adult dental pulp stem cell therapy in patients with chronic disability after stroke.

PubMed

Nagpal, Anjali; Kremer, Karlea L; Hamilton-Bruce, Monica A; Kaidonis, Xenia; Milton, Austin G; Levi, Christopher; Shi, Songtao; Carey, Leeanne; Hillier, Susan; Rose, Miranda; Zacest, Andrew; Takhar, Parabjit; Koblar, Simon A

2016-07-01

Stroke represents a significant global disease burden. As of 2015, there is no chemical or biological therapy proven to actively enhance neurological recovery during the chronic phase post-stroke. Globally, cell-based therapy in stroke is at the stage of clinical translation and may improve neurological function through various mechanisms such as neural replacement, neuroprotection, angiogenesis, immuno-modulation, and neuroplasticity. Preclinical evidence in a rodent model of middle cerebral artery ischemic stroke as reported in four independent studies indicates improvement in neurobehavioral function with adult human dental pulp stem cell therapy. Human adult dental pulp stem cells present an exciting potential therapeutic option for improving post-stroke disability. TOOTH (The Open study Of dental pulp stem cell Therapy in Humans) will investigate the use of autologous stem cell therapy for stroke survivors with chronic disability, with the following objectives: (a) determine the maximum tolerable dose of autologous dental pulp stem cell therapy; (b) define that dental pulp stem cell therapy at the maximum tolerable dose is safe and feasible in chronic stroke; and (c) estimate the parameters of efficacy required to design a future Phase 2/3 clinical trial. TOOTH is a Phase 1, open-label, single-blinded clinical trial with a pragmatic design that comprises three stages: Stage 1 will involve the selection of 27 participants with middle cerebral artery ischemic stroke and the commencement of autologous dental pulp stem cell isolation, growth, and testing in sequential cohorts (n = 3). Stage 2 will involve the transplantation of dental pulp stem cell in each cohort of participants with an ascending dose and subsequent observation for a 6-month period for any dental pulp stem cell-related adverse events. Stage 3 will investigate the neurosurgical intervention of the maximum tolerable dose of autologous dental pulp stem cell followed by 9 weeks of intensive task-specific rehabilitation. Advanced magnetic resonance and positron emission tomography neuro-imaging, and clinical assessment will be employed to probe any change afforded by stem cell therapy in combination with rehabilitation. Nine participants will step-wise progress in Stage 2 to a dose of up to 10 million dental pulp stem cell, employing a cumulative 3 + 3 statistical design with low starting stem cell dose and subsequent dose escalation, assuming that an acceptable probability of dose-limiting complications is between 1 in 6 (17%) and 1 in 3 (33%) of patients. In Stage 3, another 18 participants will receive an intracranial injection with the maximum tolerable dose of dental pulp stem cell. The primary outcomes to be measured are safety and feasibility of intracranial administration of autologous human adult DPSC in patients with chronic stroke and determination of the maximum tolerable dose in human subjects. Secondary outcomes include estimation of the measures of effectiveness required to design a future Phase 2/3 clinical trial. © 2016 World Stroke Organization.

Stem cells rejuvenate radiation-impaired vasculogenesis in murine distraction osteogenesis.

PubMed

Deshpande, Sagar S; Gallagher, Kathleen K; Donneys, Alexis; Nelson, Noah S; Guys, Nicholas P; Felice, Peter A; Page, Erin E; Sun, Hongli; Krebsbach, Paul H; Buchman, Steven R

2015-03-01

Radiotherapy is known to be detrimental to bone and soft-tissue repair. Bone marrow stromal cells have been shown to enhance bone regeneration during distraction osteogenesis following radiation therapy. The authors posit that transplanted bone marrow stromal cells will significantly augment the mandibular vascularity devastated by radiation therapy. Nineteen male Lewis rats were split randomly into three groups: distraction osteogenesis only (n = 5), radiation therapy plus distraction osteogenesis (n = 7), and radiation therapy plus distraction osteogenesis with intraoperative placement of 2 million bone marrow stromal cells (n = 7). A mandibular osteotomy was performed, and an external fixator device was installed. From postoperative days 4 through 12, rats underwent a gradual 5.1-mm distraction followed by a 28-day consolidation period. On postoperative day 40, Microfil was perfused into the vasculature and imaging commenced. Vascular radiomorphometric values were calculated for regions of interest. An analysis of variance with post hoc Tukey or Games-Howell tests was used, dependent on data homogeneity. Stereologic analysis indicated significant remediation in vasculature in the bone marrow stromal cell group compared with the radiation therapy/distraction osteogenesis group. Each of five metrics idicated significant improvements from radiation therapy/distraction osteogenesis to the bone marrow stromal cell group, with no difference between the bone marrow stromal cell group and the distraction osteogenesis group. Bone marrow stromal cells used together with distraction osteogenesis can rejuvenate radiation-impaired vasculogenesis in the mandible, reversing radiation therapy-induced isotropy and creating a robust vascular network. Bone marrow stromal cells may offer clinicians an alternative reconstructive modality that could improve the lifestyle of patients with hypovascular bone.

Toroidal standing waves excited by a storm sudden commencement - DE 1 observations

NASA Technical Reports Server (NTRS)

Cahill, L. J., Jr.; Lin, N. G.; Engebretson, M. J.; Waite, J. H.; Sugiura, M.

1990-01-01

A 74-nT sudden commencement on July 13, 1982, was observed in the magnetosphere, with instruments on the Dynamics Explorer 1 satellite. Inbound, near L = 4.5, the satellite was located at 1524 magnetic local time and 20 deg magnetic latitude. The sudden commmencement established a strong, east-west oscillation, with 100-s period, which was observed in the magnetic field, the electric field, and the plasma flow velocity records. There was also a compressional component of this 100-s oscillation and a rapidly damped 300-s compressional pulsation. The compressional oscillations may be an evidence of cavity resonances, excited by the sudden commencement. The cavity waves may, in turn, couple to toroidal waves in field line resonance at the satellite location. In addition, the sudden commencement caused the onset of waves with frequencies from 0.1 up to at least 0.5 Hz. The observations are compared with similar reports from earlier pulsations related to sudden commencements.

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

Bookman, M.A.; Bast, R.C. Jr.

Small volume residual peritoneal disease in patients undergoing therapy for ovarian carcinoma remains an attractive, but elusive, target for immunobiological therapy. Hypothetical advantages and disadvantages of regional peritoneal therapy are being better defined through increased clinical experience and more sophisticated animal models. Developments in cytokine biology, adoptive cellular therapy, monoclonal antibody conjugation, and molecular biology continue to provide an exciting, and nearly overwhelming, array of reagents for clinical evaluation. Ongoing and anticipated investigational trials should provide intriguing data in years to follow.198 references.

Vedolizumab is an effective alternative in inflammatory bowel disease patients with anti-TNF-alpha therapy-induced dermatological side effects.

PubMed

Pijls, Philippe A R R; Gilissen, Lennard P L

2016-11-01

The treatment of patients with inflammatory bowel diseases has been revolutionized by the introduction of biological therapy with TNF-alpha blockers. However, TNF-alpha blockers are also associated with a wide variety of dermatological side effects, such as local skin infections, psoriasis and eczema. A new biological therapy, targeting the gut-specific adhesion molecule alpha4beta7 integrin, is the humanized monoclonal IgG1 antibody vedolizumab. Vedolizumab prevents leukocyte migration to the gastrointestinal tract, thereby reducing inflammation. This gut-specific therapy has the potential to reduce systemic side effects, including dermatological ones. We describe 3 inflammatory bowel disease patients who experience anti-TNF-alpha therapy-induced dermatological side effects, consisting of hidradenitis suppurativa, a folliculitis, scalp psoriasis and a dissecting folliculitis. In all patients, anti-TNF-alpha therapy-induced dermatological side effects diminished after switching to vedolizumab. Vedolizumab may be a viable alternative biological therapy in inflammatory bowel disease patients who experience anti-TNF-alpha therapy-induced dermatological side effects. Copyright © 2016 Editrice Gastroenterologica Italiana S.r.l. Published by Elsevier Ltd. All rights reserved.

WE-FG-BRB-04: RBEs for Human Lung Cancer Cells Exposed to Protons and Heavier Ions: Implications for Clinical Use of Charged Particles in Cancer Therapy

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

Held, K.

The physical pattern of energy deposition and the enhanced relative biological effectiveness (RBE) of protons and carbon ions compared to photons offer unique and not fully understood or exploited opportunities to improve the efficacy of radiation therapy. Variations in RBE within a pristine or spread out Bragg peak and between particle types may be exploited to enhance cell killing in target regions without a corresponding increase in damage to normal tissue structures. In addition, the decreased sensitivity of hypoxic tumors to photon-based therapies may be partially overcome through the use of more densely ionizing radiations. These and other differences betweenmore » particle and photon beams may be used to generate biologically optimized treatments that reduce normal tissue complications. In this symposium, speakers will examine the impact of the RBE of charged particles on measurable biological endpoints, treatment plan optimization, and the prediction or retrospective assessment of treatment outcomes. In particular, an AAPM task group was formed to critically examine the evidence for a spatially-variant RBE in proton therapy. Current knowledge of proton RBE variation with respect to dose, biological endpoint, and physics parameters will be reviewed. Further, the clinical relevance of these variations will be discussed. Recent work focused on improving simulations of radiation physics and biological response in proton and carbon ion therapy will also be presented. Finally, relevant biology research and areas of research needs will be highlighted, including the dependence of RBE on genetic factors including status of DNA repair pathways, the sensitivity of cancer stem-like cells to charged particles, the role of charged particles in hypoxic tumors, and the importance of fractionation effects. In addition to the physical advantages of protons and more massive ions over photons, the future application of biologically optimized treatment plans and their potential to provide higher levels of local tumor control and improved normal tissue sparing will be discussed. Learning Objectives: To assess whether the current practice of a constant RBE of 1.1 should be revised or maintained in proton therapy and to evaluate the potential clinical consequences of delivering RBE-weighted dose distributions based on variable RBE To review current research on biological models used to predict the increased biological effectiveness of proton and carbon ions to help move towards a practical understanding and implementation of biological optimization in particle therapy To discuss potential differences in biological mechanisms between photons and charged particles (light and heavy ions) that could impact clinical cancer therapy H. Paganetti, NCI U19 CA21239D. Grosshans, Our research is supported by the NCIK. Held, Funding Support: National Cancer Institute of the National Institutes of Health, USA, under Award Number R21CA182259 and Federal Share of Program Income Earned by Massachusetts General Hospital on C06CA059267, Proton Therapy Research and Treatment Center.« less

WE-FG-BRB-01: Clinical Significance of RBE Variations in Proton Therapy

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

Paganetti, H.

2016-06-15

The physical pattern of energy deposition and the enhanced relative biological effectiveness (RBE) of protons and carbon ions compared to photons offer unique and not fully understood or exploited opportunities to improve the efficacy of radiation therapy. Variations in RBE within a pristine or spread out Bragg peak and between particle types may be exploited to enhance cell killing in target regions without a corresponding increase in damage to normal tissue structures. In addition, the decreased sensitivity of hypoxic tumors to photon-based therapies may be partially overcome through the use of more densely ionizing radiations. These and other differences betweenmore » particle and photon beams may be used to generate biologically optimized treatments that reduce normal tissue complications. In this symposium, speakers will examine the impact of the RBE of charged particles on measurable biological endpoints, treatment plan optimization, and the prediction or retrospective assessment of treatment outcomes. In particular, an AAPM task group was formed to critically examine the evidence for a spatially-variant RBE in proton therapy. Current knowledge of proton RBE variation with respect to dose, biological endpoint, and physics parameters will be reviewed. Further, the clinical relevance of these variations will be discussed. Recent work focused on improving simulations of radiation physics and biological response in proton and carbon ion therapy will also be presented. Finally, relevant biology research and areas of research needs will be highlighted, including the dependence of RBE on genetic factors including status of DNA repair pathways, the sensitivity of cancer stem-like cells to charged particles, the role of charged particles in hypoxic tumors, and the importance of fractionation effects. In addition to the physical advantages of protons and more massive ions over photons, the future application of biologically optimized treatment plans and their potential to provide higher levels of local tumor control and improved normal tissue sparing will be discussed. Learning Objectives: To assess whether the current practice of a constant RBE of 1.1 should be revised or maintained in proton therapy and to evaluate the potential clinical consequences of delivering RBE-weighted dose distributions based on variable RBE To review current research on biological models used to predict the increased biological effectiveness of proton and carbon ions to help move towards a practical understanding and implementation of biological optimization in particle therapy To discuss potential differences in biological mechanisms between photons and charged particles (light and heavy ions) that could impact clinical cancer therapy H. Paganetti, NCI U19 CA21239D. Grosshans, Our research is supported by the NCIK. Held, Funding Support: National Cancer Institute of the National Institutes of Health, USA, under Award Number R21CA182259 and Federal Share of Program Income Earned by Massachusetts General Hospital on C06CA059267, Proton Therapy Research and Treatment Center.« less

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

Carlson, D.

The physical pattern of energy deposition and the enhanced relative biological effectiveness (RBE) of protons and carbon ions compared to photons offer unique and not fully understood or exploited opportunities to improve the efficacy of radiation therapy. Variations in RBE within a pristine or spread out Bragg peak and between particle types may be exploited to enhance cell killing in target regions without a corresponding increase in damage to normal tissue structures. In addition, the decreased sensitivity of hypoxic tumors to photon-based therapies may be partially overcome through the use of more densely ionizing radiations. These and other differences betweenmore » particle and photon beams may be used to generate biologically optimized treatments that reduce normal tissue complications. In this symposium, speakers will examine the impact of the RBE of charged particles on measurable biological endpoints, treatment plan optimization, and the prediction or retrospective assessment of treatment outcomes. In particular, an AAPM task group was formed to critically examine the evidence for a spatially-variant RBE in proton therapy. Current knowledge of proton RBE variation with respect to dose, biological endpoint, and physics parameters will be reviewed. Further, the clinical relevance of these variations will be discussed. Recent work focused on improving simulations of radiation physics and biological response in proton and carbon ion therapy will also be presented. Finally, relevant biology research and areas of research needs will be highlighted, including the dependence of RBE on genetic factors including status of DNA repair pathways, the sensitivity of cancer stem-like cells to charged particles, the role of charged particles in hypoxic tumors, and the importance of fractionation effects. In addition to the physical advantages of protons and more massive ions over photons, the future application of biologically optimized treatment plans and their potential to provide higher levels of local tumor control and improved normal tissue sparing will be discussed. Learning Objectives: To assess whether the current practice of a constant RBE of 1.1 should be revised or maintained in proton therapy and to evaluate the potential clinical consequences of delivering RBE-weighted dose distributions based on variable RBE To review current research on biological models used to predict the increased biological effectiveness of proton and carbon ions to help move towards a practical understanding and implementation of biological optimization in particle therapy To discuss potential differences in biological mechanisms between photons and charged particles (light and heavy ions) that could impact clinical cancer therapy H. Paganetti, NCI U19 CA21239D. Grosshans, Our research is supported by the NCIK. Held, Funding Support: National Cancer Institute of the National Institutes of Health, USA, under Award Number R21CA182259 and Federal Share of Program Income Earned by Massachusetts General Hospital on C06CA059267, Proton Therapy Research and Treatment Center.« less

Risk of death among those awaiting treatment for HIV infection in Zimbabwe: adolescents are at particular risk

PubMed Central

Shroufi, Amir; Ndebele, Wedu; Nyathi, Mary; Gunguwo, Hilary; Dixon, Mark; Saint-Sauveur, Jean F; Taziwa, Fabian; Viñoles, Mari C; Ferrand, Rashida A

2015-01-01

Introduction Mortality among HIV-positive adults awaiting antiretroviral therapy (ART) has previously been found to be high. Here, we compare adolescent pre-ART mortality to that of adults in a public sector HIV care programme in Bulawayo, Zimbabwe. Methods In this retrospective cohort study, we compared adolescent pre-ART outcomes with those of adults enrolled for HIV care in the same clinic. Adolescents were defined as those aged 10–19 at the time of registration. Comparisons of means and proportions were carried out using two-tailed sample t-tests and chi-square tests respectively, for normally distributed data, and the Mann–Whitney U-tests for non-normally distributed data. Loss to follow-up (LTFU) was defined as missing a scheduled appointment by three or more months. Results Between 2004 and 2010, 1382 of 1628 adolescents and 7557 of 11,106 adults who registered for HIV care met the eligibility criteria for ART. Adolescents registered at a more advanced disease stage than did adults (83% vs. 73% WHO stage III/IV, respectively, p<0.001), and the median time to ART initiation was longer for adolescents than for adults [21 (10–55) days vs. 15 (7–42) days, p<0.001]. Among the 138 adolescents and 942 adults who never commenced ART, 39 (28%) of adolescents and 135 (14%) of adults died, the remainder being LTFU. Mortality among treatment-eligible adolescents awaiting ART was significantly higher than among adults (3% vs. 1.8%, respectively, p=0.004). Conclusions Adolescents present to ART services at a later clinical stage than adults and are at an increased risk of death prior to commencing ART. Improved and innovative HIV case-finding approaches and emphasis on prompt ART initiation in adolescents are urgently needed. Following registration, defaulter tracing should be used, whether or not ART has been commenced. PMID:25712590

Long-term patterns in CD4 response are determined by an interaction between baseline CD4 cell count, viral load, and time: The Asia Pacific HIV Observational Database (APHOD).

PubMed

Egger, Sam; Petoumenos, Kathy; Kamarulzaman, Adeeba; Hoy, Jennifer; Sungkanuparph, Somnuek; Chuah, John; Falster, Kathleen; Zhou, Jialun; Law, Matthew G

2009-04-15

Random effects models were used to explore how the shape of CD4 cell count responses after commencing combination antiretroviral therapy (cART) develop over time and, in particular, the role of baseline and follow-up covariates. Patients in Asia Pacific HIV Observational Database who first commenced cART after January 1, 1997, and who had a baseline CD4 cell count and viral load measure and at least 1 follow-up measure between 6 and 24 months, were included. CD4 cell counts were determined at every 6-month period after the commencement of cART for up to 6 years. A total of 1638 patients fulfilled the inclusion criteria with a median follow-up time of 58 months. Lower post-cART mean CD4 cell counts were found to be associated with increasing age (P < 0.001), pre-cART hepatitis C coinfection (P = 0.038), prior AIDS (P = 0.019), baseline viral load < or equal to 100,000 copies per milliliter (P < 0.001), and the Asia Pacific region compared with Australia (P = 0.005). A highly significant 3-way interaction between the effects of time, baseline CD4 cell count, and post-cART viral burden (P < 0.0001) was demonstrated. Higher long-term mean CD4 cell counts were associated with lower baseline CD4 cell count and consistently undetectable viral loads. Among patients with consistently detectable viral load, CD4 cell counts seemed to converge for all baseline CD4 levels. Our analysis suggest that the long-term shape of post-cART CD4 cell count changes depends only on a 3-way interaction between baseline CD4 cell count, viral load response, and time.

Patient Understanding of the Risks and Benefits of Biologic Therapies in Inflammatory Bowel Disease: Insights from a Large-scale Analysis of Social Media Platforms.

PubMed

Martinez, Bibiana; Dailey, Francis; Almario, Christopher V; Keller, Michelle S; Desai, Mansee; Dupuy, Taylor; Mosadeghi, Sasan; Whitman, Cynthia; Lasch, Karen; Ursos, Lyann; Spiegel, Brennan M R

2017-07-01

Few studies have examined inflammatory bowel disease (IBD) patients' knowledge and understanding of biologic therapies outside traditional surveys. Here, we used social media data to examine IBD patients' understanding of the risks and benefits associated with biologic therapies and how this affects decision-making. We collected posts from Twitter and e-forum discussions from >3000 social media sites posted between June 27, 2012 and June 27, 2015. Guided by natural language processing, we identified posts with specific IBD keywords that discussed the risks and/or benefits of biologics. We then manually coded the resulting posts and performed qualitative analysis using ATLAS.ti software. A hierarchical coding structure was developed based on the keyword list and relevant themes were identified through manual coding. We examined 1598 IBD-related posts, of which 452 (28.3%) centered on the risks and/or benefits of biologics. There were 5 main themes: negative experiences and concerns with biologics (n = 247; 54.6%), decision-making surrounding biologic use (n = 169; 37.4%), positive experiences with biologics (n = 168; 37.2%), information seeking from peers (n = 125; 27.7%), and cost (n = 38; 8.4%). Posts describing negative experiences primarily commented on side effects from biologics, concerns about potential side effects and increased cancer risk, and pregnancy safety concerns. Posts on decision-making focused on nonbiologic treatment options, hesitation to initiate biologics, and concerns about changing or discontinuing regimens. Social media reveals a wide range of themes governing patients' experience and choice with IBD biologics. The complexity of navigating their risk-benefit profiles suggests merit in creating online tailored decision tools to support IBD patients' decision-making with biologic therapies.

A Cocaine Hydrolase Engineered from Human Butyrylcholinesterase Selectively Blocks Cocaine Toxicity and Reinstatement of Drug Seeking in Rats

PubMed Central

Brimijoin, Stephen; Gao, Yang; Anker, Justin J; Gliddon, Luke A; LaFleur, David; Shah, R; Zhao, Qinghai; Singh, M; Carroll, Marilyn E

2008-01-01

Successive rational mutations of human butyrylcholinesterase (BChE) followed by fusion to human serum albumin have yielded an efficient hydrolase that offers realistic options for therapy of cocaine overdose and abuse. This albumin-BChE prevented seizures in rats given a normally lethal cocaine injection (100 mg/kg, i.p.), lowered brain cocaine levels even when administered after the drug, and provided rescue after convulsions commenced. Moreover, it selectively blocked cocaine-induced reinstatement of drug seeking in rats that had previously self-administered cocaine. The enzyme treatment was well tolerated and may be worth exploring for clinical application in humans. PMID:18199998

The ViewRay system: magnetic resonance-guided and controlled radiotherapy.

PubMed

Mutic, Sasa; Dempsey, James F

2014-07-01

A description of the first commercially available magnetic resonance imaging (MRI)-guided radiation therapy (RT) system is provided. The system consists of a split 0.35-T MR scanner straddling 3 (60)Co heads mounted on a ring gantry, each head equipped with independent doubly focused multileaf collimators. The MR and RT systems share a common isocenter, enabling simultaneous and continuous MRI during RT delivery. An on-couch adaptive RT treatment-planning system and integrated MRI-guided RT control system allow for rapid adaptive planning and beam delivery control based on the visualization of soft tissues. Treatment of patients with this system commenced at Washington University in January 2014. Copyright © 2014 Elsevier Inc. All rights reserved.

Hormone therapy for radiorecurrent prostate cancer.

PubMed

Payne, H; Khan, A; Chowdhury, S; Davda, R

2013-12-01

The management of patients who relapse after radical radiotherapy is a challenging problem for the multidisciplinary team. This group of men may have been considered ineligible or chosen not to be treated with an initial surgical approach as a result of high-risk features or significant comorbid conditions. It is important not to miss the opportunity for definitive local salvage therapies at this stage, and eligible patients should undergo careful restaging to determine their suitability for these approaches. For those men not suitable for local treatment, androgen deprivation therapy (ADT) remains an option. Literature review of the evidence relating to the management of hormone therapy for radiorecurrent prostate cancer. Results from retrospective studies have shown that not all men with biochemical relapse will experience distant metastasis or a reduction in survival due to prostate cancer progression. Therefore, the timing of ADT commencement remains controversial. However, it would seem appropriate to offer immediate therapy to men with advanced disease or unfavourable prostate-specific antigen (PSA) kinetics at relapse. Patients with more favourable risk factors and PSA kinetics may be considered for watchful waiting and deferred ADT to avoid or delay the associated toxicities. Patients with non-metastatic disease can be given the option of castration-based therapy or an antiandrogen such as bicalutamide which may have potential advantages in maintenance of sexual function, physical capacity and bone mineral density but at the expense of an increase in gynaecomastia and mastalgia. Recent data suggest the burden of toxicity from ADT may be reduced by the use of intermittent hormone therapy without compromising survival in this group of patients with radiorecurrence. Hormone therapy remains an option for men with radiorecurrent prostate cancer.

Group schema therapy for eating disorders: study protocol.

PubMed

Calvert, Fiona; Smith, Evelyn; Brockman, Rob; Simpson, Susan

2018-01-01

The treatment of eating disorders is a difficult endeavor, with only a relatively small proportion of clients responding to and completing standard cognitive behavioural therapy (CBT). Given the prevalence of co-morbidity and complex personality traits in this population, Schema Therapy has been identified as a potentially viable treatment option. A case series of Group Schema Therapy for Eating Disorders (ST-E-g) yielded positive findings and the study protocol outlined in this article aims to extend upon these preliminary findings to evaluate group Schema Therapy for eating disorders in a larger sample ( n  = 40). Participants undergo a two-hour assessment where they complete a number of standard questionnaires and their diagnostic status is ascertained using the Eating Disorder Examination. Participants then commence treatment, which consists of 25 weekly group sessions lasting for 1.5 h and four individual sessions. Each group consists of five to eight participants and is facilitated by two therapists, at least one of who is a registered psychologist trained on schema therapy. The primary outcome in this study is eating disorder symptom severity. Secondary outcomes include: cognitive schemas, self-objectification, general quality of life, self-compassion, schema mode presentations, and Personality Disorder features. Participants complete psychological measures and questionnaires at pre, post, six-month and 1-year follow-up. This study will expand upon preliminary research into the efficacy of group Schema Therapy for individuals with eating disorders. If group Schema Therapy is shown to reduce eating disorder symptoms, it will hold considerable promise as an intervention option for a group of disorders that is typically difficult to treat. ACTRN12615001323516. Registered: 2/12/2015 (retrospectively registered, still recruiting).

Disclosure amongst adult HIV patients on antiretroviral therapy in Port Harcourt, Nigeria.

PubMed

Omunakwe, Hannah E; Okoye, Helen; Efobi, Chilota; Onodingene, Maryanne; Chinenye, Sunny; Nwauche, Chijioke A

2015-09-01

HIV transmission is still a public health concern in sub-Saharan Africa; disclosure is an effective tool for its prevention, contact tracing and treatment. We aimed to evaluate the disclosure behaviours of adult HIV-positive patients receiving antiretroviral therapy (ART) in University of Port Harcourt Teaching Hospital, and identify major challenges to disclosure in a bid to develop ways to improve this practice in the environment. Patients receiving ART in this centre were interviewed using an interviewer-administered questionnaire. A total of 250 clients were interviewed over three months. A majority of the patients were tested on account of ill health 143 (57.2%). They commenced ART within 8 ± 15.4 SD months of presentation. The mean period before disclosure was 4.75 ± 12.8 SD months of diagnosis. Thirty-six (14.4%) of the respondents had not disclosed their HIV status; the major barrier to disclosure was stigmatisation in 19 (36%). © The Author(s) 2014.

Diabetic Cardiomyopathy and Metabolic Remodeling of the Heart

PubMed Central

Battiprolu, Pavan K.; Lopez-Crisosto, Camila; Wang, Zhao V.; Nemchenko, Andriy; Lavandero, Sergio; Hill, Joseph A.

2012-01-01

The incidence and prevalence of diabetes mellitus are each increasing rapidly in societies around the globe. The majority of patients with diabetes succumb ultimately to heart disease, much of which stems from atherosclerotic disease and hypertension. However, the diabetic milieu is itself intrinsically noxious to the heart, and cardiomyopathy can develop independent of elevated blood pressure or coronary artery disease. This process, termed diabetic cardiomyopathy, is characterized by significant changes in the physiology, structure, and mechanical function of the heart. Presently, therapy for patients with diabetes focuses largely on glucose control, and attention to the heart commences with the onset of symptoms. When the latter develops, standard therapy for heart failure is applied. However, recent studies highlight that specific elements of the pathogenesis of diabetic heart disease are unique, raising the prospect of diabetes-specific therapeutic intervention. Here, we review recently unveiled insights into the pathogenesis of diabetic cardiomyopathy and associated metabolic remodeling with an eye toward identifying novel targets with therapeutic potential. PMID:23123443

Lithium suppression of tau induces brain iron accumulation and neurodegeneration.

PubMed

Lei, P; Ayton, S; Appukuttan, A T; Moon, S; Duce, J A; Volitakis, I; Cherny, R; Wood, S J; Greenough, M; Berger, G; Pantelis, C; McGorry, P; Yung, A; Finkelstein, D I; Bush, A I

2017-03-01

Lithium is a first-line therapy for bipolar affective disorder. However, various adverse effects, including a Parkinson-like hand tremor, often limit its use. The understanding of the neurobiological basis of these side effects is still very limited. Nigral iron elevation is also a feature of Parkinsonian degeneration that may be related to soluble tau reduction. We found that magnetic resonance imaging T 2 relaxation time changes in subjects commenced on lithium therapy were consistent with iron elevation. In mice, lithium treatment lowers brain tau levels and increases nigral and cortical iron elevation that is closely associated with neurodegeneration, cognitive loss and parkinsonian features. In neuronal cultures lithium attenuates iron efflux by lowering tau protein that traffics amyloid precursor protein to facilitate iron efflux. Thus, tau- and amyloid protein precursor-knockout mice were protected against lithium-induced iron elevation and neurotoxicity. These findings challenge the appropriateness of lithium as a potential treatment for disorders where brain iron is elevated (for example, Alzheimer's disease), and may explain lithium-associated motor symptoms in susceptible patients.

Parents' Perspectives About Factors Influencing Adherence to Pharmacotherapy for ADHD.

PubMed

Ahmed, Rana; Borst, Jacqueline; Wei, Yong C; Aslani, Parisa

2017-01-01

The aim of the present study was to explore factors influencing parents' decisions to adhere and persist with ADHD pharmacotherapy in children. Focus groups ( n = 3) were conducted with 16 parents recruited from metropolitan Sydney. Group discussions explored factors impacting on treatment initiation, continuation, and cessation. Focus groups were audio-recorded, transcribed verbatim, and thematically content analyzed. Parents commenced and continued pharmacotherapy due to its positive impact on their child's behavior. Improvements in the child's academic performance and social interactions encouraged persistence with therapy. Parents elected to cease therapy after their children experienced side effects including appetite suppression, weight loss, and sleep disturbances. Concerns about long-term effects of ADHD medication use including potential for addiction and growth stunting, in addition to the stigma surrounding ADHD also contributed to parents ceasing treatment. The findings highlight a need for the provision of accurate information about ADHD and its treatments to parents to empower their treatment decisions and promote adherence.

Acral keratoses and leucocytoclastic vasculitis occurring during treatment of essential thrombocythaemia with hydroxyurea.

PubMed

Worley, B; Glassman, S J

2016-03-01

Hydroxyurea is used in essential thrombocythaemia to lower thromboembolic risk. Cutaneous adverse effects from hydroxyurea are diverse. Small vessel vasculitis has been rarely reported, and the coexistence of several different morphologies has not been described. We report a case of acral keratoses, psoriasiform plaques and leucocytoclastic vasculitis (LCV) in a patient with essential thrombocythaemia. A 69-year-old woman developed a confusing array of skin lesions including keratotic papules, psoriasiform plaques and keratoderma 4 years after commencing hydroxyurea therapy. The initial diagnosis was hand and foot psoriasis, but lesions were resistant to therapy. With an increase in the dose of hydroxyurea, the lesions ulcerated. Skin biopsies taken from different sites indicated different diagnoses, including LCV. Discontinuation of hydroxyurea yielded rapid improvement. Although the most commonly reported cutaneous adverse effect from hydroxyurea is leg ulceration, this can be preceded or accompanied by less dramatic skin lesions. Unless recognized, delayed diagnosis and lesion progression can occur. © 2015 British Association of Dermatologists.

Antiphospholipid antibody-associated non-infective mitral valve endocarditis successfully treated with medical therapy.

PubMed

Contractor, Tahmeed; Bell, Adrian; Khasnis, Atul; Silverberg, Bruce J; Martinez, Matthew W

2013-01-01

Non-bacterial endocarditis lesions associated with antiphospholipid antibodies (aPLs) in the absence of other criteria for antiphospholipid syndrome or systemic lupus erythematosus is termed an aPL-associated cardiac valve disease. Evidence regarding the management of this condition is sparse. A rare case is described of a 20-year-old female who presented with an incidental finding of 'vegetations on a heart valve'. Echocardiography revealed mitral valve leaflet thickening and echodensities with moderate mitral regurgitation. She had an elevated partial thromboplastin time that did not correct with a mixing study, and elevated levels of antiocardiolipin antibodies. Hence, a diagnosis of aPL-associated cardiac valve disease was made, and the patient commenced on warfarin, hydroxychloroquine, and a short course of oral prednisone. At one year after diagnosis the patient remained symptom-free, and follow up echocardiography revealed resolution of the vegetations with minimal mitral regurgitation. Further evidence is needed to guide the therapy of this rare condition.

A prospective study of the effects of radioiodine therapy for hyperthyroidism in patients with minimally active graves' ophthalmopathy.

PubMed

Perros, Petros; Kendall-Taylor, Pat; Neoh, Chris; Frewin, Sarah; Dickinson, Jane

2005-09-01

Radioiodine is an effective and safe treatment for hyperthyroidism but has been implicated as a risk factor for deterioration or new presentation of Graves' ophthalmopathy (GO). Prophylactic glucocorticoids appear to prevent this effect. The objective of this study was to document the course of GO after radioiodine therapy. This was a prospective observational study. Patients were assessed at baseline and 2, 4, 6, and 12 months after radioiodine therapy. The study was conducted at a tertiary referral center. Seventy-two GO patients with minimally active eye disease participated in the study. A fixed dose of radioiodine was administered. T(4) was commenced 2 wk later to prevent hypothyroidism. Change in activity and severity of GO were analyzed. Exophthalmometer readings, the width of the palpebral aperture, diplopia scores, and the clinical activity score improved significantly. By clinically significant criteria, the eye disease improved in four patients (transiently in three of the four cases), most likely attributable to the natural course of the disease. No patient's eyes deteriorated. Radioiodine is not associated with deterioration of GO in patients with minimally active eye disease when postradioiodine hypothyroidism is prevented.

Evolution of magnetic therapy from alternative to traditional medicine.

PubMed

Vallbona, C; Richards, T

1999-08-01

Static or electromagnetic fields have been used for centuries to control pain and other biologic problems, but scientific evidence of their effect had not been gathered until recently. This article explores the value of magnetic therapy in rehabilitation medicine in terms of static magnetic fields and time varying magnetic fields (electromagnetic). A historical review is given and the discussion covers the areas of scientific criteria, modalities of magnetic therapy, mechanisms of the biologic effects of magnetic fields, and perspectives on the future of magnetic therapy.

Surgical treatment of ulcerative colitis in the biologic therapy era

PubMed Central

Biondi, Alberto; Zoccali, Marco; Costa, Stefano; Troci, Albert; Contessini-Avesani, Ettore; Fichera, Alessandro

2012-01-01

Recently introduced in the treatment algorithms and guidelines for the treatment of ulcerative colitis, biological therapy is an effective treatment option for patients with an acute severe flare not responsive to conventional treatments and for patients with steroid dependent disease. The reduction in hospitalization and surgical intervention for patients affected by ulcerative colitis after the introduction of biologic treatment remains to be proven. Furthermore, these agents seem to be associated with increase in cost of treatment and risk for serious postoperative complications. Restorative proctocolectomy with ileal pouch-anal anastomosis is the surgical treatment of choice in ulcerative colitis patients. Surgery is traditionally recommended as salvage therapy when medical management fails, and, despite advances in medical therapy, colectomy rates remain unchanged between 20% and 30%. To overcome the reported increase in postoperative complications in patients on biologic therapies, several surgical strategies have been developed to maintain long-term pouch failure rate around 10%, as previously reported. Surgical staging along with the development of minimally invasive surgery are among the most promising advances in this field. PMID:22563165

Telomerase and the search for the end of cancer.

PubMed

Mocellin, Simone; Pooley, Karen A; Nitti, Donato

2013-02-01

Many of the fundamental molecular mechanisms underlying tumor biology remain elusive and, thus, developing specific anticancer therapies remains a challenge. The recently discovered relationships identified among telomeres, telomerase, aging, and cancer have opened a new avenue in tumor biology research that may revolutionize anticancer therapy. This review summarizes the critical aspects of telomerase biology that underpin the development of novel telomerase-targeting therapies for malignant diseases, and special regard is given to the aspects of telomerase that make it such an appealing target, such as the widespread expression of telomerase in cancers. Despite significant progress, issues remain to be addressed before telomerase-based therapies are truly effective and we include critical discussion of the results obtained thus far. Copyright © 2012 Elsevier Ltd. All rights reserved.

Biologic Modulators in Allergic and Autoinflammatory Diseases

PubMed Central

Broderick, Lori; Tourangeau, Louanne M.; Kavanaugh, Arthur; Wasserman, Stephen I.

2011-01-01

Purpose of review The advent of molecular techniques has resulted in the ability to tailor medications to specific protein targets. This review will emphasize several biological therapies, specifically directed toward cytokine receptors and inhibitors, and their role in the treatment of atopic and autoinflammatory diseases. Recent findings Translational research and the identification of the molecular pathophysiology of diseases have led to more targeted treatment approaches. The biologic modulators, encompassing monoclonal antibodies as cytokine inhibitors, receptor blocking antibodies and new fusion receptors are now being applied to diseases beyond their original application. Summary The expanded use of biological therapies has experienced success in the treatment of numerous disorders, especially in subsets of patients with disease that has been refractory to conventional therapies. PMID:21659854

Aggressive treatment of early rheumatoid arthritis: recognizing the window of opportunity and treating to target goals.

PubMed

Resman-Targoff, Beth H; Cicero, Marco P

2010-11-01

Evidence supports the use of aggressive therapy for patients with early rheumatoid arthritis (RA). Clinical outcomes in patients with early RA can improve with a treat-to-target approach that sets the goal at disease remission. The current selection of antirheumatic therapies, including conventional and biologic disease-modifying antirheumatic drugs (DMARDs), has made disease remission a realistic target for patients with early RA. The challenge is selecting the optimal antirheumatic drug or combination of drugs for initial and subsequent therapy to balance the clinical benefits, risks, and economic considerations. In some cases, the use of biologic agents as part of the treatment regimen has shown superior results compared with conventional DMARDs alone in halting the progression of disease, especially in reducing radiographic damage. However, the use of biologic agents as initial therapy is challenged by cost-effectiveness analyses, which favor the use of conventional DMARDs. The use of biologic agents may be justified in certain patients with poor prognostic factors or those who experience an inadequate response to conventional DMARDs as a means to slow or halt disease progression and its associated disability. In these cases, the higher cost of treatment with biologic agents may be offset by decreased societal costs, such as lost work productivity, and increased health-related quality of life. Further research is needed to understand optimal strategies for balancing costs, benefits, and risks of antirheumatic drugs. Some key questions are (1) when biologic agents are appropriate for initial therapy, and (2) when to conclude that response to conventional DMARDs is inadequate and biologic agents should be initiated.

Safety and Effectiveness of Highly Active Antiretroviral Therapy in Treatment-Naïve HIV Patients: Preliminary Findings of a Cohort Event Monitoring Study in Belarus.

PubMed

Setkina, Svetlana; Dotsenko, Marina; Bondar, Sviatlana; Charnysh, Iryna; Kuchko, Alla; Kaznacheeva, Alena; Kozorez, Elena; Dodaleva, Alena; Rossa, Natalia

2015-04-01

Antiretroviral drugs have well-documented evidence-based favorable benefit-risk ratios. Although various studies have investigated and characterized the safety profile of antiretroviral medicines, there are a limited number of studies evaluating the safety of first-line antiretroviral therapy (ART) in patients with a specific co-morbidity. A cohort event monitoring (CEM) study of the safety and effectiveness of antiretroviral medicines in a target population that has a significant level of co-morbidities (chronic infectious diseases, peripheral blood cytopenias) was implemented. The aim was to evaluate the safety profile of the highly active ART (HAART) in the target population and subpopulations with risk factors, to optimize the monitoring and decision-making procedure for subgroups of patients with specific types of co-morbidity, and to implement a more vigilant approach to therapy management in risk groups of patients. Prospective observational CEM was implemented among HAART-naïve HIV-positive patients at four clinical sites from December 2012. Eligible patients were those starting first-line HAART. Close medical supervision of all enrolled patients, with regular clinical and laboratory monitoring, was provided by healthcare professionals within 1 year after commencement of therapy. Standardized forms were used for data collection on initial and subsequent visits. All objective or subjective deviations in condition (events) were assessed for a causal relationship with ART, and for severity, seriousness, reversibility, preventability, and pre-existing risk factors in the case of adverse drug reactions (ADRs). A total of 518 HAART-naïve HIV-positive patients were enrolled in the CEM study. Of these patients, 65% (337) experienced one or several ADRs related to one or more components of HAART. Most of the ADRs reported were non-serious, expected, common (very common), transient (correctable), or reversible. The most common were hematotoxic, hepatotoxic, and neurotoxic adverse reactions. In several cases, some types of toxicities, associated with zidovudine, efavirenz, and nevirapine, had a high level of severity, necessitating hospitalization and drug regimen or single-agent substitution. Severe cases of hematological, hepatobiliary, and psychiatric toxicities were associated with pre-existing risk factors. CEM is an effective tool for safety and effectiveness monitoring and could be successfully implemented for intensive study of important safety issues and for overcoming knowledge gaps regarding safety. In order to achieve a favorable benefit-risk ratio for HAART in the specific sections of the population with pre-existing risk factors for development of ART toxicities, more vigilant consideration and careful assessment before therapy is commenced and further regular monitoring of key laboratory parameters is required.

Development and Translation of a Tissue-Engineered Disc in a Preclinical Rodent Model

DTIC Science & Technology

2012-10-01

DAPS AF constructs, fabricated complete DAPS comprised of a PCL nanofiber AF and a hyaluronic acid hydrogel NP, and designed and commencement of...of a PCL nanofiber AF and a hyaluronic acid hydrogel NP, and design and commencement of construction of a novel multi-axis bioreactor that will be... nanofiber AF and a hyaluronic acid hydrogel NP We have commenced fabrication and in vitro pre-culture of composite DAPS constructs. An AF region

Molecular Biology in Pediatric High-Grade Glioma: Impact on Prognosis and Treatment.

PubMed

Rizzo, Daniela; Ruggiero, Antonio; Martini, Maurizio; Rizzo, Valentina; Maurizi, Palma; Riccardi, Riccardo

2015-01-01

High-grade gliomas are the main cause of death in children with brain tumours. Despite recent advances in cancer therapy, their prognosis remains poor and the treatment is still challenging. To date, surgery followed by radiotherapy and temozolomide is the standard therapy. However, increasing knowledge of glioma biology is starting to impact drug development towards targeted therapies. The identification of agents directed against molecular targets aims at going beyond the traditional therapeutic approach in order to develop a personalized therapy and improve the outcome of pediatric high-grade gliomas. In this paper, we critically review the literature regarding the genetic abnormalities implicated in the pathogenesis of pediatric malignant gliomas and the current development of molecularly targeted therapies. In particular, we analyse the impact of molecular biology on the prognosis and treatment of pediatric high-grade glioma, comparing it to that of adult gliomas.

Molecular Biology in Pediatric High-Grade Glioma: Impact on Prognosis and Treatment

PubMed Central

Rizzo, Daniela; Ruggiero, Antonio; Martini, Maurizio; Rizzo, Valentina; Maurizi, Palma; Riccardi, Riccardo

2015-01-01

High-grade gliomas are the main cause of death in children with brain tumours. Despite recent advances in cancer therapy, their prognosis remains poor and the treatment is still challenging. To date, surgery followed by radiotherapy and temozolomide is the standard therapy. However, increasing knowledge of glioma biology is starting to impact drug development towards targeted therapies. The identification of agents directed against molecular targets aims at going beyond the traditional therapeutic approach in order to develop a personalized therapy and improve the outcome of pediatric high-grade gliomas. In this paper, we critically review the literature regarding the genetic abnormalities implicated in the pathogenesis of pediatric malignant gliomas and the current development of molecularly targeted therapies. In particular, we analyse the impact of molecular biology on the prognosis and treatment of pediatric high-grade glioma, comparing it to that of adult gliomas. PMID:26448930

EUD-based biological optimization for carbon ion therapy

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

Brüningk, Sarah C., E-mail: sarah.brueningk@icr.ac.uk; Kamp, Florian; Wilkens, Jan J.

2015-11-15

Purpose: Treatment planning for carbon ion therapy requires an accurate modeling of the biological response of each tissue to estimate the clinical outcome of a treatment. The relative biological effectiveness (RBE) accounts for this biological response on a cellular level but does not refer to the actual impact on the organ as a whole. For photon therapy, the concept of equivalent uniform dose (EUD) represents a simple model to take the organ response into account, yet so far no formulation of EUD has been reported that is suitable to carbon ion therapy. The authors introduce the concept of an equivalentmore » uniform effect (EUE) that is directly applicable to both ion and photon therapies and exemplarily implemented it as a basis for biological treatment plan optimization for carbon ion therapy. Methods: In addition to a classical EUD concept, which calculates a generalized mean over the RBE-weighted dose distribution, the authors propose the EUE to simplify the optimization process of carbon ion therapy plans. The EUE is defined as the biologically equivalent uniform effect that yields the same probability of injury as the inhomogeneous effect distribution in an organ. Its mathematical formulation is based on the generalized mean effect using an effect-volume parameter to account for different organ architectures and is thus independent of a reference radiation. For both EUD concepts, quadratic and logistic objective functions are implemented into a research treatment planning system. A flexible implementation allows choosing for each structure between biological effect constraints per voxel and EUD constraints per structure. Exemplary treatment plans are calculated for a head-and-neck patient for multiple combinations of objective functions and optimization parameters. Results: Treatment plans optimized using an EUE-based objective function were comparable to those optimized with an RBE-weighted EUD-based approach. In agreement with previous results from photon therapy, the optimization by biological objective functions resulted in slightly superior treatment plans in terms of final EUD for the organs at risk (OARs) compared to voxel-based optimization approaches. This observation was made independent of the underlying objective function metric. An absolute gain in OAR sparing was observed for quadratic objective functions, whereas intersecting DVHs were found for logistic approaches. Even for considerable under- or overestimations of the used effect- or dose–volume parameters during the optimization, treatment plans were obtained that were of similar quality as the results of a voxel-based optimization. Conclusions: EUD-based optimization with either of the presented concepts can successfully be applied to treatment plan optimization. This makes EUE-based optimization for carbon ion therapy a useful tool to optimize more specifically in the sense of biological outcome while voxel-to-voxel variations of the biological effectiveness are still properly accounted for. This may be advantageous in terms of computational cost during treatment plan optimization but also enables a straight forward comparison of different fractionation schemes or treatment modalities.« less

Dual delivery of biological therapeutics for multimodal and synergistic cancer therapies.

PubMed

Jang, Bora; Kwon, Hyokyoung; Katila, Pramila; Lee, Seung Jin; Lee, Hyukjin

2016-03-01

Cancer causes >8.2 million deaths annually worldwide; thus, various cancer treatments have been investigated over the past decades. Among them, combination drug therapy has become extremely popular, and treatment with more than one drug is often necessary to achieve appropriate anticancer efficacy. With the development of nanoformulations and nanoparticulate-based drug delivery, researchers have explored the feasibility of dual delivery of biological therapeutics to overcome the current drawbacks of cancer therapy. Compared with the conventional single drug therapy, dual delivery of therapeutics has provided various synergistic effects in addition to offering multimodality to cancer treatment. In this review, we highlight and summarize three aspects of dual-delivery systems for cancer therapy. These include (1) overcoming drug resistance by the dual delivery of chemical drugs with biological therapeutics for synergistic therapy, (2) targeted and controlled drug release by the dual delivery of drugs with stimuli-responsive nanomaterials, and (3) multimodal theranostics by the dual delivery of drugs and molecular imaging probes. Furthermore, recent developments, perspectives, and new challenges regarding dual-delivery systems for cancer therapy are discussed. Copyright © 2015 Elsevier B.V. All rights reserved.

Biologic agents in the management of Hodgkin lymphoma.

PubMed

Rashidi, Armin; Bartlett, Nancy L

2015-05-01

The advent of biologic approaches for the treatment of solid tumors and hematologic malignancies has been a major accomplishment in oncology and a rapidly growing field of clinical and translational research in cancer therapeutics. Classical Hodgkin lymphoma (HL) is no exception. Although the investigation of biologic therapies in HL started decades ago, it has only recently flourished, largely because of the development of new monoclonal antibody drug conjugates and checkpoint inhibitors. Biologic therapies represent a potent treatment option that have produced durable remissions even in patients who have had multiple relapses or with refractory disease. This article reviews 8 major classes of biologic approaches that have been investigated in HL: monoclonal antibodies, immunotoxins, antibody-drug conjugates, radioimmunotherapy, adoptive immunotherapy, immunomodulators, chimeric antigen receptor T cells, and checkpoint inhibitors. An armamentarium of biologic therapies for HL that are well tolerated and potentially more effective is expected to be available in the near future. Copyright © 2015 by the National Comprehensive Cancer Network.

Clinical impact of concomitant immunomodulators on biologic therapy: Pharmacokinetics, immunogenicity, efficacy and safety.

PubMed

Xu, Zhenhua; Davis, Hugh M; Zhou, Honghui

2015-03-01

Immune-mediated inflammatory diseases encompass a variety of different clinical syndromes, manifesting as either common diseases such as rheumatoid arthritis (RA), inflammatory bowel disease (IBD) and psoriasis, or rare diseases such as cryopyrin-associated periodic syndromes. The therapy for these diseases often involves the use of a wide range of drugs including nonsteroidal anti-inflammatory drugs (NSAIDs), glucocorticoids, immunomodulators, and biologic therapies. Due to the abundance of relevant clinical data, this article provides a general overview on the clinical impact of the concomitant use of immunomodulators and biologic therapies, with a focus on anti-tumor necrosis factor-α agents (anti-TNFα), for the treatment of RA and Crohn's disease (CD). Compared to biologic monotherapy, concomitant use of immunomodulators (methotrexate, azathioprine, and 6-mercaptopurine) often increases the systemic exposure of the anti-TNFα agent and decreases the formation of antibodies to the anti-TNFα agent, consequently enhancing clinical efficacy. Nevertheless, long-term combination therapy with immunomodulators and anti-TNFα agents may be associated with increased risks of serious infections and malignancies. Therefore, the determination whether combination therapy is suitable for a patient should always be based on an individualized benefit-risk evaluation. More research should be undertaken to identify and validate prognostic markers for predicting patients who would benefit the most and those who are at greater risk from combination therapy with immunomodulators and anti-TNFα agents. © 2015, The American College of Clinical Pharmacology.

Update on the management of ulcerative colitis.

PubMed

Taba Taba Vakili, Sahar; Taher, Mohammad; Ebrahimi Daryani, Nasser

2012-01-01

The present treatment goals for inflammatory bowel diseases (IBD) especially ulcerative colitis (UC) include rapid induction of clinical remission, steroid-free maintenance of clinical remission, mucosal healing and improvement of quality of life in UC patients. Immunomodulators have been reserved for steroid- dependent or steroid- refractory UC patients. Among these agents, azathioprine/6-mercaptopurine should be used for maintenance of remission in quiescent UC. Calcineurin inhibitors can be prescribed as a short-term rescue therapy in steroid- refractory UC patients, but the long term efficacy of these agents remains unclear. According to retrospective studies, methotraxate is not recommended for inducing and maintaining remission in UC. Novel biological therapies targeting different specific immunological pathways continue to be developed and introduced for a variety of clinical scenarios in IBD. Infliximab is currently used for induction and maintenance therapy in patients who have moderately to severely active UC with an inadequate response to conventional agents such as aminosalicylates, corticosteroids, or immunomodulators. Other anti-TNF agents and biologic therapies are undergoing evaluation in clinical trials for their efficacy in IBD. Most patients who start biologics should continue treatment for the foreseeable future and potential consequences of discontinuation should be discussed with individual patients. Currently, data do not exist to administer biologics as first-line therapy in UC. Emerging data suggest that biologics may have the potential to prevent complications and limit disease progression. If such benefits are proven, biologics may be used in the future to modulate subclinical inflammation and to prevent the development of clinical disease.

The effectiveness of transcutaneous electrical neural stimulation therapy in patients with urinary incontinence resistant to initial medical treatment or biofeedback.

PubMed

Tugtepe, H; Thomas, D T; Ergun, R; Kalyoncu, A; Kaynak, A; Kastarli, C; Dagli, T E

2015-06-01

While there are many options for children with treatment refractory urinary incontinence, there is no single accepted method. This study's aim was to prospectively evaluate the effect of transcutaneous electrical nerve stimulation in children with urinary incontinence resistant to standard medical, urological therapy and/or biofeedback. This study was performed at a university hospital. For inclusion, patients >5 years of age first underwent evaluation with urinary ultrasonography, uroflow-electromyogram and voiding diaries. Treatment with biofeedback, alpha adrenergic blockers, anticholinergics and/or urotherapy was commenced according to uroflow-EMG and voiding diary findings. Patients with partial or no response to this standard therapy were then included in this study, performed between April 2012 and February 2014. Patients with anatomical or neurological causes for urinary incontinence were excluded. TENS was performed on S3 dermatome, every day for 3 months. Each session lasted 20 min with a frequency of 10 Hz and generated pulse of 350 μs. Intensity was determined by the child's sensitivity threshold. Medical treatment and urological therapy was continued during TENS. Uroflow parameters (voiding volume as percentage of expected bladder capacity, Qmax, Qave, flow and voiding time, postvoiding residual urine) and urinary system symptoms (presence of urinary tract infection, frequency, urge incontinence, fractionated voiding and constipation) were compared immediately before commencement and immediately after the completion of 3 months of TENS. Twenty-seven patients were included in this study (4 males, 23 females). Patients' average age was 7.2 years, 11 had overactive bladder and 16 had dysfunctional voiding. Comparison of urinary system symptoms and uroflow parameters before and after TENS are shown in Table. After 3 months of TENS; a statistically significant decrease was observed in the number of patients with frequency, urge incontinence, urinary tract infections and constipation. There was a decrease in the number of patients with fractionated voiding, although this change was not statistically significant. Similarly, for uroflow-EMG parameters; bladder capacity, Qmax, Qave and flow time increased while voiding time and PVR decreased. Changes seen in bladder capacity, Qmax and PVR were statically significant, while other changes were not. Patients' response rates after 3 months of TENS were; complete response in 70.4%, partial response in 22.2% and no response in 7.4%. This study has shown that transcutaneous electrical nerve stimulation is a promising treatment option for standard-treatment refractory children with urinary incontinence. Copyright © 2015 Journal of Pediatric Urology Company. Published by Elsevier Ltd. All rights reserved.

Impact of biologic agents with and without concomitant methotrexate and at reduced doses in older rheumatoid arthritis patients.

PubMed

Zhang, Jie; Xie, Fenglong; Delzell, Elizabeth; Yun, Huifeng; Lewis, James D; Haynes, Kevin; Chen, Lang; Beukelman, Timothy; Saag, Kenneth G; Curtis, Jeffrey R

2015-05-01

To examine whether concomitant methotrexate (MTX) use is associated with better biologic persistence and whether self-administered anti-tumor necrosis factor (anti-TNF) therapies are used at reduced doses in real-world clinical care settings, not just clinical trials. We conducted a retrospective cohort study among rheumatoid arthritis (RA) patients using Medicare claims data from 2006 to 2012. Subjects were new initiators of etanercept, infliximab, adalimumab, abatacept, and tocilizumab with at least 12 months of continuous medical and pharmacy coverage after treatment initiation. We examined the association between concomitant MTX use and persistence on biologic agents using Cox proportional hazards regression, adjusting for demographics and baseline comorbidities. We further identified a subgroup of patients who initiated and were adherent on etanercept or adalimumab for at least 12 months and examined the proportion of patients who subsequently used these therapies at reduced doses continuously for an additional 12, 18, and 24 months. Of 26,510 eligible RA patients, 10,511 initiated biologic monotherapy. Overall, patients who initiated biologic monotherapy were 1.4 (95% confidence interval [95% CI] 1.3-1.5) times more likely to discontinue at 1 year compared to those who initiated combination therapy, and 1.8 (95% CI 1.7-2.0) times more likely if starting infliximab monotherapy. Approximately 10-20% of patients who initiated and adhered to etanercept and adalimumab for ≥12 months subsequently received reduced-dose therapy for an 12 additional months and beyond. In real-world practice, concomitant MTX was associated with improved persistence on biologic therapy, especially for infliximab users; reduced-dose injectable anti-TNF therapy was used by a substantial proportion of RA patients. © 2015, American College of Rheumatology.

Depressive symptoms, depression, and the effect of biologic therapy among patients in Psoriasis Longitudinal Assessment and Registry (PSOLAR).

PubMed

Strober, Bruce; Gooderham, Melinda; de Jong, Elke M G J; Kimball, Alexa B; Langley, Richard G; Lakdawala, Nikita; Goyal, Kavitha; Lawson, Fabio; Langholff, Wayne; Hopkins, Lori; Fakharzadeh, Steve; Srivastava, Bhaskar; Menter, Alan

2018-01-01

Patients with psoriasis are at an increased risk for depression. However, the impact of treatment on this risk is unclear. Evaluate the incidence and impact of treatment on depression among patients with moderate-to-severe psoriasis. We defined a study population within the Psoriasis Longitudinal Assessment and Registry and measured the incidence of depressive symptoms (Hospital Anxiety and Depression Scale-Depression score ≥8) and adverse events (AEs) of depression within cohorts receiving biologics, conventional systemic therapies, or phototherapy. Patients were evaluated at approximately 6-month intervals. Multivariate modeling determined the impact of treatment on risk. The incidence rates of depressive symptoms were 3.01 per 100 patient-years (PYs) (95% confidence interval [CI], 2.73-3.32), 5.85 per 100 PYs (95% CI, 4.29-7.97), and 5.70 per 100 PYs (95% CI, 4.58-7.10) for biologics, phototherapy, and conventional therapy, respectively. Compared with conventional therapy, biologics reduced the risk for depressive symptoms (hazard ratio, 0.76; 95% CI, 0.59-0.98), whereas phototherapy did not (hazard ratio, 1.05; 95% CI, 0.71-1.54). The incidence rates for AEs of depression were 0.21 per 100 PYs (95% CI, 0.15-0.31) for biologics, 0.55 per 100 PYs (95% CI, 0.21-1.47) for phototherapy, and 0.14 per 100 PYs (95% CI, 0.03-0.55) for conventional therapy; the fact that there were too few events (37 AEs) precluded modeling. Incomplete capture of depression and confounders in the patients on registry. Compared with conventional therapy, biologics appear to be associated with a lower incidence of depressive symptoms among patients with psoriasis. Copyright © 2017 American Academy of Dermatology, Inc. Published by Elsevier Inc. All rights reserved.

Patients’ conceptions of their own influence on good treatment response to biological therapy in chronic inflammatory arthritis

PubMed Central

Larsson, Ingrid

2017-01-01

Background Biological therapies are common in the treatment of patients with chronic inflammatory arthritis (CIA). However, despite the fact that many patients respond well to their biological therapies, there are still a number of nonresponders. In order to design the best care for patients, it is important to understand how they conceive their own role in their treatment response. Objective To explore how patients with CIA conceive their own influence on a good treatment response to biological therapy. Methods This study had an exploratory and descriptive design with a phenomenographic approach. Interviews were conducted with 25 patients (11 women and 14 men) aged 17–79 years, with CIA who were undergoing biological therapy and who had low disease activity or were in remission. Results Patients with CIA undergoing biological therapy conceived their own influence on good treatment response in terms of adherence, physical activity, mental attitude, social support, and self-awareness. Adherence was described as the foundation for the patients’ own influence on good treatment response. Physical activity, mental attitude, and social support reflected three essential ways of understanding patients’ influence on good treatment response where the patients spoke about physical strength, mental strength, and social strength. Self-awareness reflected a comprehensive way of influencing good treatment response in which patients balanced their physical, mental, and social resources in partnership with health care professionals. Conclusion Patients conceived that they had a responsibility for adhering to the treatment as well as achieving balance in life in order to ensure good treatment response. Self-awareness was essential for maintaining a good treatment response, and this reflected the patients’ awareness of the complexity of living their lives with a chronic illness. PMID:28706444

Patients' conceptions of their own influence on good treatment response to biological therapy in chronic inflammatory arthritis.

PubMed

Larsson, Ingrid

2017-01-01

Biological therapies are common in the treatment of patients with chronic inflammatory arthritis (CIA). However, despite the fact that many patients respond well to their biological therapies, there are still a number of nonresponders. In order to design the best care for patients, it is important to understand how they conceive their own role in their treatment response. To explore how patients with CIA conceive their own influence on a good treatment response to biological therapy. This study had an exploratory and descriptive design with a phenomenographic approach. Interviews were conducted with 25 patients (11 women and 14 men) aged 17-79 years, with CIA who were undergoing biological therapy and who had low disease activity or were in remission. Patients with CIA undergoing biological therapy conceived their own influence on good treatment response in terms of adherence, physical activity, mental attitude, social support, and self-awareness. Adherence was described as the foundation for the patients' own influence on good treatment response. Physical activity, mental attitude, and social support reflected three essential ways of understanding patients' influence on good treatment response where the patients spoke about physical strength, mental strength, and social strength. Self-awareness reflected a comprehensive way of influencing good treatment response in which patients balanced their physical, mental, and social resources in partnership with health care professionals. Patients conceived that they had a responsibility for adhering to the treatment as well as achieving balance in life in order to ensure good treatment response. Self-awareness was essential for maintaining a good treatment response, and this reflected the patients' awareness of the complexity of living their lives with a chronic illness.

DRY CUPPING IN CHILDREN WITH FUNCTIONAL CONSTIPATION: A RANDOMIZED OPEN LABEL CLINICAL TRIAL.

PubMed

Shahamat, Mahmoud; Daneshfard, Babak; Najib, Khadijeh-Sadat; Dehghani, Seyed Mohsen; Tafazoli, Vahid; Kasalaei, Afshineh

2016-01-01

As a common disease in pediatrics, constipation poses a high burden to the community. In this study, we aimed to investigate the efficacy of dry cupping therapy (an Eastern traditional manipulative therapy) in children with functional constipation. One hundred and twenty children (4-18 years old) diagnosed as functional constipation according to ROME III criteria were assigned to receive a traditional dry cupping protocol on the abdominal wall for 8 minutes every other day or standard laxative therapy (Polyethylene glycol (PEG) 40% solution without electrolyte), 0.4 g/kg once daily) for 4 weeks, in an open label randomized controlled clinical trial using a parallel design with a 1:1 allocation ratio. Patients were evaluated prior to and following 2, 4, 8 and 12 weeks of the intervention commencement in terms of the ROME III criteria for functional constipation. There were no significant differences between the two arms regarding demographic and clinical basic characteristics. After two weeks of the intervention, there was a significant better result in most of the items of ROME III criteria of patients in PEG group. In contrast, after four weeks of the intervention, the result was significantly better in the cupping group. There was no significant difference in the number of patients with constipation after 4 and 8 weeks of the follow-up period. This study showed that dry cupping of the abdominal wall, as a traditional manipulative therapy, can be as effective as standard laxative therapy in children with functional constipation.

IL-27 as a novel therapy for inflammatory bowel disease: a critical review of the literature

PubMed Central

Andrews, Caroline; McLean, Mairi H; Durum, Scott K

2016-01-01

Inflammatory bowel disease (IBD) is an inflammatory disorder of the intestine that affects an estimated 329 per 100,000 people in the United States and is increasing in incidence within a number of cultures worldwide. Likely due to its incompletely understood pathophysiology and etiology, standard treatments for IBD are only efficacious in subsets of patients and often do not induce lasting remission. As a result, novel therapies are needed. The success of anti-tumor necrosis factor-α treatment in a subset of IBD patients demonstrated that therapy targeting a single cytokine could be efficacious in IBD, and clinical trials investigating the blockade of a variety of cytokines have commenced. IL-27 is a relatively recently discovered type I cytokine with established roles in infectious disease, autoimmunity, and cancer in a variety of organs. IL-27 was identified as a candidate gene for IBD, and a number of studies in mouse models of IBD have demonstrated that IL-27 therapy is protective. However, in contrast to these investigations, genetic deletion of the IL-27 receptor has been shown to be protective in some mouse models of IBD. The purpose of this review is to highlight recent literature investigating the role of IL-27 in IBD, and to discuss possible explanations for the sometimes conflicting results of these studies. Evidence supporting IL-27 therapy as a treatment for IBD will also be discussed. PMID:27243591

WE-FG-BRB-02: Spatial Mapping of the RBE of Scanned Particle Beams

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

Grosshans, D.

2016-06-15

The physical pattern of energy deposition and the enhanced relative biological effectiveness (RBE) of protons and carbon ions compared to photons offer unique and not fully understood or exploited opportunities to improve the efficacy of radiation therapy. Variations in RBE within a pristine or spread out Bragg peak and between particle types may be exploited to enhance cell killing in target regions without a corresponding increase in damage to normal tissue structures. In addition, the decreased sensitivity of hypoxic tumors to photon-based therapies may be partially overcome through the use of more densely ionizing radiations. These and other differences betweenmore » particle and photon beams may be used to generate biologically optimized treatments that reduce normal tissue complications. In this symposium, speakers will examine the impact of the RBE of charged particles on measurable biological endpoints, treatment plan optimization, and the prediction or retrospective assessment of treatment outcomes. In particular, an AAPM task group was formed to critically examine the evidence for a spatially-variant RBE in proton therapy. Current knowledge of proton RBE variation with respect to dose, biological endpoint, and physics parameters will be reviewed. Further, the clinical relevance of these variations will be discussed. Recent work focused on improving simulations of radiation physics and biological response in proton and carbon ion therapy will also be presented. Finally, relevant biology research and areas of research needs will be highlighted, including the dependence of RBE on genetic factors including status of DNA repair pathways, the sensitivity of cancer stem-like cells to charged particles, the role of charged particles in hypoxic tumors, and the importance of fractionation effects. In addition to the physical advantages of protons and more massive ions over photons, the future application of biologically optimized treatment plans and their potential to provide higher levels of local tumor control and improved normal tissue sparing will be discussed. Learning Objectives: To assess whether the current practice of a constant RBE of 1.1 should be revised or maintained in proton therapy and to evaluate the potential clinical consequences of delivering RBE-weighted dose distributions based on variable RBE To review current research on biological models used to predict the increased biological effectiveness of proton and carbon ions to help move towards a practical understanding and implementation of biological optimization in particle therapy To discuss potential differences in biological mechanisms between photons and charged particles (light and heavy ions) that could impact clinical cancer therapy H. Paganetti, NCI U19 CA21239D. Grosshans, Our research is supported by the NCIK. Held, Funding Support: National Cancer Institute of the National Institutes of Health, USA, under Award Number R21CA182259 and Federal Share of Program Income Earned by Massachusetts General Hospital on C06CA059267, Proton Therapy Research and Treatment Center.« less

Lassa fever presenting as acute abdomen: a case series.

PubMed

Dongo, Andrew E; Kesieme, Emeka B; Iyamu, Christopher E; Okokhere, Peter O; Akhuemokhan, Odigie C; Akpede, George O

2013-04-19

Lassa fever, an endemic zoonotic viral infection in West Africa, presents with varied symptoms including fever, vomiting, retrosternal pain, abdominal pain, sore-throat, mucosal bleeding, seizures and coma. When fever and abdominal pain are the main presenting symptoms, and a diagnosis of acute abdomen is entertained, Lassa fever is rarely considered in the differential diagnosis, even in endemic areas. Rather the diagnosis of Lassa fever is suspected only after surgical intervention. Therefore, such patients often undergo unnecessary surgery with resultant delay in the commencement of ribavirin therapy. This increases morbidity and mortality and the risk of nosocomial transmission to hospital staff. We report 7 patients aged between 17 months and 40 years who had operative intervention for suspected appendicitis, perforated typhoid ileitis, intussuception and ruptured ectopic pregnancy after routine investigations. All seven were post-operatively confirmed as Lassa fever cases. Four patients died postoperatively, most before commencement of ribavirin, while the other three patients eventually recovered with appropriate antibiotic treatment including intravenous ribavirin. Surgeons working in West Africa should include Lassa fever in the differential diagnosis of acute abdomen, especially appendicitis. The presence of high grade fever, proteinuria and thrombocytopenia in patients with acute abdomen should heighten the suspicion of Lassa fever. Prolonged intra-operative bleeding should not only raise suspicion of the disease but also serve to initiate precautions to prevent nosocomial transmission.

Lassa fever presenting as acute abdomen: a case series

PubMed Central

2013-01-01

Lassa fever, an endemic zoonotic viral infection in West Africa, presents with varied symptoms including fever, vomiting, retrosternal pain, abdominal pain, sore-throat, mucosal bleeding, seizures and coma. When fever and abdominal pain are the main presenting symptoms, and a diagnosis of acute abdomen is entertained, Lassa fever is rarely considered in the differential diagnosis, even in endemic areas. Rather the diagnosis of Lassa fever is suspected only after surgical intervention. Therefore, such patients often undergo unnecessary surgery with resultant delay in the commencement of ribavirin therapy. This increases morbidity and mortality and the risk of nosocomial transmission to hospital staff. We report 7 patients aged between 17 months and 40 years who had operative intervention for suspected appendicitis, perforated typhoid ileitis, intussuception and ruptured ectopic pregnancy after routine investigations. All seven were post-operatively confirmed as Lassa fever cases. Four patients died postoperatively, most before commencement of ribavirin, while the other three patients eventually recovered with appropriate antibiotic treatment including intravenous ribavirin. Surgeons working in West Africa should include Lassa fever in the differential diagnosis of acute abdomen, especially appendicitis. The presence of high grade fever, proteinuria and thrombocytopenia in patients with acute abdomen should heighten the suspicion of Lassa fever. Prolonged intra-operative bleeding should not only raise suspicion of the disease but also serve to initiate precautions to prevent nosocomial transmission. PMID:23597024

Female genital tract graft-versus-host disease: incidence, risk factors and recommendations for management.

PubMed

Zantomio, D; Grigg, A P; MacGregor, L; Panek-Hudson, Y; Szer, J; Ayton, R

2006-10-01

Female genital tract graft-versus-host disease (GVHD) is an under-recognized complication of allogeneic stem cell transplantation impacting on quality of life. We describe a prospective surveillance programme for female genital GVHD to better characterize incidence, risk factors and clinical features and the impact of a structured intervention policy. A retrospective audit was conducted on the medical records of all female transplant recipients surviving at least 6 months at a single centre over a 5-year period. Patients commenced topical vaginal oestrogen early post transplant with hormone replacement as appropriate for age, prior menopausal status and co-morbidities. A genital tract management programme included regular gynaecological review and self-maintenance of vaginal capacity by dilator or intercourse. The incidence of genital GVHD was 35% (95% confidence interval (CI) (25, 50%)) at 1 year and 49% (95% CI (36, 63%)) at 2 years. Topical therapy was effective in most cases; no patient required surgical intervention to divide vaginal adhesions. The main risk factor was stem cell source with peripheral blood progenitor cells posing a higher risk than marrow (hazard ratio=3.07 (1.22, 7.73), P=0.017). Extensive GVHD in other organs was a common association. We conclude that female genital GVHD is common, and early detection and commencement of topical immunosuppression with dilator use appears to be highly effective at preventing progression.

Mycophenolate mofetil is an effective and safe option for the management of systemic sclerosis-associated interstitial lung disease: results from the Australian Scleroderma Cohort Study.

PubMed

Owen, Claire; Ngian, Gene-Siew; Elford, Kathleen; Moore, Owen; Stevens, Wendy; Nikpour, Mandana; Rabusa, Candice; Proudman, Susanna; Roddy, Janet; Zochling, Jane; Hill, Catherine; Sturgess, Allan; Tymms, Kathleen; Youssef, Peter; Sahhar, Joanne

2016-01-01

To report the efficacy and tolerability of mycophenolate mofetil (MMF) and azathioprine (AZA) in the management of systemic sclerosis-associated interstitial lung disease (SSc-ILD). Patients in the Australian Scleroderma Cohort Study treated with at least 3 months of MMF or AZA for SSc-ILD confirmed on high resolution computed tomography (HRCT) chest were identified and their pulmonary function tests (PFTs) retrieved. Individuals with available results for T-1 (12 months prior to treatment commencement), T0 (date of treatment commencement) and at least one subsequent time point were included in the drug efficacy analysis. The Wilcoxon signed-rank test was used to compare absolute FVC at T1, T0, 12 months (T1), 24 months (T2) and 36 months (T3). Analysis of drug tolerability included all identified patients treated with MMF or AZA. 18/22 patients treated with MMF and 29/49 treated with AZA had adequate PFTs for inclusion in the drug efficacy analysis. Median absolute FVC at T1 for MMF treatment was 2.50L, declining to 2.12L at T0 (p=0.02). Following MMF therapy, FVC results were stable at T1 (2.13L, p=0.86), T2 (2.17L, p=0.65) and T3 (2.25L, p=0.78). In the AZA group, a statistically significant decline did not occur prior to treatment, however FVC results remained stable at T1, T2 and T3.Adverse events leading to early discontinuation (<12 months treatment) were less common in the MMF group (4/22 vs. 13/49). Gastrointestinal complications were the main cause of discontinuation in both groups. In patients with SSc-ILD with declining pulmonary function, MMF therapy was associated with stability for up to 36 months. Early adverse events leading to discontinuation occurred less frequently in patients treated with MMF than in AZA treated patients.

The impact of HIV-1 reverse transcriptase polymorphisms on responses to first-line nonnucleoside reverse transcriptase inhibitor-based therapy in HIV-1-infected adults.

PubMed

Mackie, Nicola E; Dunn, David T; Dolling, David; Garvey, Lucy; Harrison, Linda; Fearnhill, Esther; Tilston, Peter; Sabin, Caroline; Geretti, Anna M

2013-09-10

HIV-1 genetic variability may influence antiretroviral therapy (ART) outcomes. The study aim was to determine the impact of polymorphisms in regions known to harbor major nonnucleoside reverse transcriptase inhibitor (NNRTI) resistance mutations (codons 90-108, 135-138, 179-190, 225-348) on virologic responses to first-line NNRTI-based ART. Reverse transcriptase sequences from ART-naive individuals who commenced efavirenz (EFV) or nevirapine (NVP) with at least two nucleos(t)ide reverse transcriptase inhibitors (NRTIs) without major drug resistance mutations were analyzed. The impact of polymorphisms on week 4 viral load decrease and time to virologic failure was measured over a median 97 weeks. Among 4528 patients, most were infected with HIV-1 subtype B (67%) and commenced EFV-based ART (84%). Overall, 2598 (57%) had at least one polymorphism, most frequently at codons 90, 98, 101, 103, 106, 135, 138, 179, and 238. Virologic failure rates were increased in patients with two (n = 597) or more than two (n = 72) polymorphisms [adjusted hazard ratio 1.43; 95% confidence interval (CI) 1.07-1.92; P = 0.016]. Polymorphisms associated with virologic failure occurred at codons 90 (mostly V90I), 98 (mostly A98S), and 103 (mostly K103R), with adjusted hazard ratios of 1.78 (1.15-2.73; P = 0.009), 1.55 (1.16-2.08; P = 0.003), and 1.75 (1.00-3.05: P = 0.049), respectively. Polymorphisms at codon 179, especially V179D/E/T, predicted reduced week 4 responses (P = 0.001) but not virologic failure. The occurrence of multiple polymorphisms, though uncommon, was associated with a small increase in the risk of NNRTI treatment failure; significant effects were seen with polymorphisms at codon 90, 98, and 103. The mechanisms underlying the slower suppression seen with V179D/E/T deserve further investigation.

Comparison of the efficacy of biologics versus conventional systemic therapies in the treatment of psoriasis at a comprehensive psoriasis care center.

PubMed

Au, Shiu-Chung; Madani, Abdulaziz; Alhaddad, Marwan; Alkofide, Maha; Gottlieb, Alice B

2013-08-01

The efficacy of biologic treatment for psoriasis has not been compared to that of conventional systemic therapies and phototherapy outside of clinical trial settings. Retrospective, cross-sectional. All patient visits with a code for psoriasis (ICD-9 696.1) in the clinical practice of two dermatologists with a high percentage (over 70% of chief complaints) of psoriasis patients from Jan 1, 2008 to Jan 4, 2012 inclusive were included in this retrospective data analysis. Patients were excluded if the baseline Physician's Global Assessment (PGA) at start of treatment was unknown, or less than 3 (moderate). The practice is a comprehensive psoriasis care center in the Northeastern United States serving a metropolitan population of over 4 million people. Patients were divided by treatment type (biologic, conventional systemic or both) and history of previous treatments. Patients were evaluated by Body Surface Area (BSA), PGA, Simple-Measure for Assessing Psoriasis Activity (S-MAPA, calculated by BSA multiplied by PGA). Patients were evaluated at baseline, 8, 12, 16, and 24 weeks after start of treatment. Patients must have completed at least 8 weeks on a single treatment in order to be included. 46 courses of biologics, 12 courses of conventional systemic therapies, and 18 courses of both together were identified with PGA 3 or greater at baseline. Baseline S-MAPA for biologics was 74, for non-biologic systemics was 62.25. At week 24, S-MAPA improved 70.2% over baseline in patients treated with biologics, patients treated with non-biologic systemics improved by only 40.4% (P<0.05). The average number of prior treatments for patients on biologics was 1.87 versus 1.25 for patients on conventional systemic therapies (P=0.169). Biologics show superior results to conventional systemic therapies (70% improvement versus 40% improvement) for the treatment of patients with moderate to severe psoriasis, as measured by decrease in S-MAPA (PGA multiplied by BSA) at week 24. These results were observed despite the fact that patients on biologics had a greater baseline severity and had a greater number of previous treatments.

Parenting from before conception.

PubMed

Lane, Michelle; Robker, Rebecca L; Robertson, Sarah A

2014-08-15

At fertilization, the gametes endow the embryo with a genomic blueprint, the integrity of which is affected by the age and environmental exposures of both parents. Recent studies reveal that parental history and experiences also exert effects through epigenomic information not contained in the DNA sequence, including variations in sperm and oocyte cytosine methylation and chromatin patterning, noncoding RNAs, and mitochondria. Transgenerational epigenetic effects interact with conditions at conception to program the developmental trajectory of the embryo and fetus, ultimately affecting the lifetime health of the child. These insights compel us to revise generally held notions to accommodate the prospect that biological parenting commences well before birth, even prior to conception. Copyright © 2014, American Association for the Advancement of Science.

Development and Translation of a Tissue-Engineered Disc in a Preclinical Rodent Model

DTIC Science & Technology

2012-10-29

PCL nanofiber AF and a hyaluronic acid hydrogel NP, and designed and commencement of construction of a multi-axis bioreactor that will be used to...of a PCL nanofiber AF and a hyaluronic acid hydrogel NP, and design and commencement of construction of a novel multi-axis bioreactor that will be... nanofiber AF and a hyaluronic acid hydrogel NP We have commenced fabrication and in vitro pre-culture of composite DAPS constructs. An AF region

Economical impact associated with a biological therapy prioritization protocol in patients with rheumatoid arthritis in the Hospital of Sagunto.

PubMed

Borrás-Blasco, Joaquín; Casterá, M Dolores-Elvira; Cortes, Xavier; Rosique-Robles, J Dolores; Abad, F Javier

2014-11-01

Until 2010 the cost of biological treatments in Rheumatoid Arthritis (RA) was increasing annually by 15% in our hospital. In 1st January 2011, a Hospital Commission of Biological Therapies involving rheumatology and pharmacy services was created to improve the management of biological drugs and a biological therapy prioritization protocol in RA patients was also established to improve the efficient usage of biological drugs in RA. To evaluate the economic impact associated with a biological therapy prioritization protocol for RA patients in the Hospital of Sagunto. Observational, ambispective study comparing the associated cost of RA patients treated with biological drugs in the pre-protocol (2009 - 2010) versus post-protocol periods (2011 - 2012). RA patients treated with Abatacept (ABA), Adalimumab (ADA), Etanercept (ETN) or Infliximab (IFX) for at least 6 months during the study period (2009 - 2012) were included. In 2012, Tocilizumab (TCZ) was also included in the prioritization protocol. Prioritization protocol was established based on both clinical and economical aspects and supervised case by case by our Commission. Cost savings and economic impact were calculated using Spanish official prices. In the pre-protocol period (2009 - 2010), total expenses were increasing by €110,000, up to €1,761,000 in 2010 (€11,362 pat/year). After protocol implementation, total expenses decreased by 53,676€ on the 2010 - 2011 period, and 149,200€ on the 2011 - 2012 period. On the 2010 - 2011 period the cost of biological therapy per patient-year decreased 355€ (11,007€ pat/year) and additional 653€ (up to 10,354€ pat/year) by 2012, with a cumulative effect of the protocol implementation of 1,008€ per patient-year. In the pre-protocol period (2009), the annual cost/patient was 10.812€ with ETN, 10.942€ with IFX, 12.961€ with ADA and 12.739€ with ABA. By 1st January 2013, the annual cost per patient was 9,469€ with ETN, 10,579€ with IFX, 11,117€ with ADA, 13,540€ with ABA and 14,932€ with TCZ. The creation of our Commission of Biological Therapies is key to rational management of RA patients and optimization of resources, allowing us to save 200,000€ after 2-year efficiency protocol implementation.

Patients' Concerns and Perceptions Regarding Biologic Therapies in Ankylosing Spondylitis: Insights from a Large-Scale Survey of Social Media Platforms.

PubMed

Dzubur, Eldin; Khalil, Carine; Almario, Christopher V; Noah, Benjamin; Minhas, Deeba; Ishimori, Mariko; Arnold, Corey; Park, Yujin; Kay, Jonathan; Weisman, Michael H; Spiegel, Brennan M R

2018-05-21

Few studies have examined ankylosing spondylitis (AS) patients' concerns and perceptions of biologic therapies outside of traditional surveys. In this study, we used social media data to examine AS patients' knowledge, attitudes, and beliefs regarding biologic therapies. We collected posts from 601 social media sites made between 1/1/06-4/26/17. Each post mentioned both an AS keyword and a biologic. To explore themes within the collection in an unsupervised manner, a latent Dirichlet allocation topic model was fit to the dataset. Each discovered topic was represented as a discrete distribution over the words in the collection, similar to a word cloud. The topics were manually reviewed to identify themes, which were confirmed with thematic data analysis. We examined 27,416 social media posts and found 112 themes. The majority of themes (60%, 67/112) focused on discussions surrounding AS treatment. Other themes including psychological impact of AS, reporting of medical literature, and AS disease consequences accounted for the remaining 40% (45/112). Within AS treatment discussions, most topics (54%) involved biologics, and most subthemes (78%) centered on side-effects (e.g., fatigue, allergic reactions), biologic attributes (e.g., dosing, frequency), and concerns with biologic use (e.g., increased cancer risk). Additional implicit patient needs (e.g., support) were identified using qualitative analyses. Social media reveals a dynamic range of themes governing AS patients' experience and choice with biologics. The complexity of selecting among biologics and navigating their risk-benefit profiles suggests merit in creating online tailored decision-tools to support patients' decision-making with AS biologic therapies. This article is protected by copyright. All rights reserved. This article is protected by copyright. All rights reserved.

Accomplishments in 2007 in the treatment of advanced colorectal cancer.

PubMed

Goldberg, Richard M; Carrato, Alfredo

2008-05-01

Overview of the Disease IncidencePrognosis Prognostic or Predictive FactorsCurrent General Therapy Standards and Regional Variations STANDARDS IN THE US AND EUROPE: Combination Therapy Plus a Biologic FOCUS and CAIRO 1: Serial Single Agents vs. Combination TherapyStop-and-Go StrategyLimited Availability of Biologics in Some RegionsAccomplishments During the Year TherapyWhat Needs To Be Done Controversies and Disagreements BOND-2 and PACCE: Chemotherapy + Bevacizumab + Cetuximab or PanitumumabSpecial Populations (Elderly and Poor Performance Status)Future Directions Comments on ResearchObstacles to Progress.

Accomplishments in 2007 in the Treatment of Advanced Colorectal Cancer

PubMed Central

Carrato, Alfredo

2008-01-01

Overview of the Disease IncidencePrognosis Prognostic or Predictive FactorsCurrent General Therapy Standards and Regional Variations Standards in the US and Europe: Combination Therapy Plus a Biologic FOCUS and CAIRO 1: Serial Single Agents vs. Combination TherapyStop-and-Go StrategyLimited Availability of Biologics in Some RegionsAccomplishments During the Year TherapyWhat Needs To Be Done Controversies and Disagreements BOND-2 and PACCE: Chemotherapy + Bevacizumab + Cetuximab or PanitumumabSpecial Populations (Elderly and Poor Performance Status)Future Directions Comments on ResearchObstacles to Progress PMID:19352463

Tuberculosis screening prior to anti-tumor necrosis factor therapy among patients with immune-mediated inflammatory diseases in Japan: a longitudinal study using a large-scale health insurance claims database.

PubMed

Tomio, Jun; Yamana, Hayato; Matsui, Hiroki; Yamashita, Hiroyuki; Yoshiyama, Takashi; Yasunaga, Hideo

2017-11-01

Tuberculosis screening is recommended for patients with immune-mediated inflammatory diseases (IMIDs) prior to anti-tumor necrosis factor (TNF) therapy. However, adherence to the recommended practice is unknown in the current clinical setting in Japan. We used a large-scale health insurance claims database in Japan to conduct a longitudinal observational study. Of more than two million beneficiaries in the database between 2013 and 2014, we enrolled those with IMIDs aged 15-69 years who had initiated anti-TNF therapy. We defined tuberculosis screening primarily as tuberculin skin test and/or interferon-gamma release assay (TST/IGRA) within 2 months before commencing anti-TNF therapy. We analyzed the proportions of the patients who had undergone tuberculosis screening and the associations with primary disease, type of anti-TNF agent, methotrexate prescription prior to anti-TNF therapy, and treatment for latent tuberculosis infection (LTBI). Of 385 patients presumed to have initiated anti-TNF therapy, 252 (66%) had undergone tuberculosis screening by TST/IGRA (22% TST, 56% IGRA, and 12% both TST and IGRA), and 231 (60%) had undergone TST/IGRA and radiography. Patients with psoriasis tended to be more likely to undergo tuberculosis screening than those with other diseases; however, this association was not statistically significant. Treatment for LTBI was provided to 43 (11%) patients; 123 (32%) received neither TST/IGRA nor LTBI treatment. Tuberculosis screening was often not performed prior to anti-TNF therapy despite the guidelines' recommendations; thus, patients could be put at unnecessary risk of reactivation of tuberculosis. © 2017 Asia Pacific League of Associations for Rheumatology and John Wiley & Sons Australia, Ltd.

Association between anti-TNF-α therapy and all-cause mortality.

PubMed

Herrinton, Lisa J; Liu, Liyan; Chen, Lang; Harrold, Leslie R; Raebel, Marsha A; Curtis, Jeffrey R; Griffin, Marie R; Solomon, Daniel H; Saag, Kenneth G; Lewis, James D

2012-12-01

To compare mortality among patients with selected autoimmune diseases treated with anti-tumor necrosis factor alpha (TNF-α) agents with similar patients treated with non-biologic therapies. Cohort study set within several large health care programs, 1998-2007. Autoimmune disease patients were identified using diagnoses from computerized healthcare data. Use of anti-TNF-α agents and comparison of non-biologic therapies were identified from pharmacy data, and mortality was identified from vital records and other sources. We compared new users of anti-TNF-α agents to new users of non-biologic therapies using propensity scores and Cox proportional hazards analysis to adjust for baseline differences. We also made head-to-head comparisons among anti-TNF-α agents. Among the 46 424 persons included in the analysis, 2924 (6.3%) had died by the end of follow-up, including 1754 (6.1%) of the 28 941 with a dispensing of anti-TNF-α agent and 1170 (6.7%) of the 17 483 who used non-biologic treatment alone. Compared to use of non-biologic therapies, use of anti-TNF-α therapy was not associated with an increased mortality in patients with rheumatoid arthritis (adjusted hazard ratio [aHR] 0.93 with 95% confidence intervals (CI) 0.85-1.03); psoriasis, psoriatic arthritis, or ankylosing spondylitis (combined aHR 0.81 with CI 0.61-1.06; or inflammatory bowel disease (aHR 1.12 with CI 0.85-1.46). Mortality rates did not differ to an important degree between patients treated with etanercept, adalimumab, or infliximab. Anti-TNF-α therapy was not associated with increased mortality among patients with autoimmune diseases. Copyright © 2012 John Wiley & Sons, Ltd.

Strengths weaknesses opportunities and threats of blended learning: students' perceptions.

PubMed

Hande, S

2014-05-01

Blended learning (BL) in a cell biology course of the premedical program at the Kasturba Medical College International Centre, Manipal, India, commenced in 2006. The program provides training in basic sciences to students, especially from the United States and Canada. The approach to the study was phenomenographic, with a qualitative study design using an open-ended questionnaire, focused interviews and empirical observations. The aim of this study was to identify the strengths, weaknesses, opportunities and threats (SWOT) of BL in a premedical class. It was a cross-sectional study. Ninety six students in a premedical cell biology class participated in the study. SWOT analysis of students' perceptions was conducted manually. Statistical analysis included content analysis of qualitative data to classify data and aligning them into the SWOT analysis matrix. The outcomes of the study revealed student perceptions in terms of SWOT of BL and the potential uses of this strategy. The study provides background for educators and curriculum experts to plan their modules while incorporating a BL approach.

Laser biostimulation of patients suffering from multiple sclerosis in respect to the biological influence of laser light

NASA Astrophysics Data System (ADS)

Peszynski-Drews, Cezary; Klimek, Andrzej; Sopinski, Marek; Obrzejta, Dominik

2003-10-01

The authors discuss the results, obtained so far during three years' clinical examination, of laser therapy in the treatment of patients suffering from multiple sclerosis. They regard both the results of former laboratory experiments and so far discovered mechanisms of biological influence of laser light as an objective explanation of high effectiveness of laser therapy in the csae of this so far incurable disease. They discuss wide range of biological mechanisms of laser therapy, examined so far on different levels (cell, tissue, organ), allowing the explanation of beneficial influence of laser light in pathogenetically different morbidities.

A prospective observational study of pigmented naevi changes in psoriasis patients on biologic therapy.

PubMed

Choi, Seohee Deanne; D'Souza, Mario I; Menzies, Scott W; Weninger, Wolfgang

2018-05-23

Patients on biologic therapy are thought to be at increased risk of developing non-melanoma skin cancers and melanomas. It is unknown whether biologic therapy alters the natural history of melanocytic naevi. Therefore, a prospective observational study was conducted to determine whether psoriasis patients on biologic therapy develop changes in naevi. Clinical and dermoscopic assessment of all melanocytic naevi was performed in 45 psoriasis patients on biologic therapy versus a control cohort of 43 subjects, using sequential digital dermoscopic imaging and total body photography. The mean follow-up period was 1.5 years. The study and control patients had comparable age, gender, previous and family history of non-melanoma skin cancers and melanomas, as well as previous sun exposure and total number of naevi. The number of naevi with major dermoscopic changes was 3% in the study and 1.9% in the control group, with an adjusted incidence rate ratio of 1.45 (95% confidence interval 0.90-2.33; P = 0.125). The rate of minor changes was 15.9% in the study group versus 19.4% in the control (adjusted incidence rate ratio 0.77, 95% confidence interval 0.57-1.08; P = 0.14). There were six new dysplastic naevi in 4/45 biologic patients and four in 4/43 controls; however, the difference was not significant (relative risk 0.96, 95% confidence interval -0.12 to 0.12; P = 0.95). There were no melanomas in either group. Over a mean follow-up period of 1.5 years there was no evidence of significantly different changes in naevi or development of new dysplastic naevi in psoriasis patients on biologic treatment compared to controls. © 2018 The Australasian College of Dermatologists.

47 CFR 73.318 - FM blanketing interference.

Code of Federal Regulations, 2010 CFR

2010-10-01

... begins with the commencement of program tests, or commencement of programming utilizing the new antenna... antenna systems, or the use of high gain antennas or antenna booster amplifiers. Mobile receivers and non...

[Smart therapeutics based on synthetic gene circuits].

PubMed

Peng, Shuguang; Xie, Zhen

2017-03-25

Synthetic biology has an important impact on biology research since its birth. Applying the thought and methods that reference from electrical engineering, synthetic biology uncovers many regulatory mechanisms of life systems, transforms and expands a series of biological components. Therefore, it brings a wide range of biomedical applications, including providing new ideas for disease diagnosis and treatment. This review describes the latest advances in the field of disease diagnosis and therapy based on mammalian cell or bacterial synthetic gene circuits, and provides new ideas for future smart therapy design.

Quantitative imaging as cancer biomarker

NASA Astrophysics Data System (ADS)

Mankoff, David A.

2015-03-01

The ability to assay tumor biologic features and the impact of drugs on tumor biology is fundamental to drug development. Advances in our ability to measure genomics, gene expression, protein expression, and cellular biology have led to a host of new targets for anticancer drug therapy. In translating new drugs into clinical trials and clinical practice, these same assays serve to identify patients most likely to benefit from specific anticancer treatments. As cancer therapy becomes more individualized and targeted, there is an increasing need to characterize tumors and identify therapeutic targets to select therapy most likely to be successful in treating the individual patient's cancer. Thus far assays to identify cancer therapeutic targets or anticancer drug pharmacodynamics have been based upon in vitro assay of tissue or blood samples. Advances in molecular imaging, particularly PET, have led to the ability to perform quantitative non-invasive molecular assays. Imaging has traditionally relied on structural and anatomic features to detect cancer and determine its extent. More recently, imaging has expanded to include the ability to image regional biochemistry and molecular biology, often termed molecular imaging. Molecular imaging can be considered an in vivo assay technique, capable of measuring regional tumor biology without perturbing it. This makes molecular imaging a unique tool for cancer drug development, complementary to traditional assay methods, and a potentially powerful method for guiding targeted therapy in clinical trials and clinical practice. The ability to quantify, in absolute measures, regional in vivo biologic parameters strongly supports the use of molecular imaging as a tool to guide therapy. This review summarizes current and future applications of quantitative molecular imaging as a biomarker for cancer therapy, including the use of imaging to (1) identify patients whose tumors express a specific therapeutic target; (2) determine whether the drug reaches the target; (3) identify an early response to treatment; and (4) predict the impact of therapy on long-term outcomes such as survival. The manuscript reviews basic concepts important in the application of molecular imaging to cancer drug therapy, in general, and will discuss specific examples of studies in humans, and highlight future directions, including ongoing multi-center clinical trials using molecular imaging as a cancer biomarker.

26 CFR 1.181-4 - Special rules.

Code of Federal Regulations, 2014 CFR

2014-04-01

... before computing gain or loss from the disposition. (2) Principal photography not commencing prior to the... for which principal photography does not commence prior to the date of expiration of section 181, the...

26 CFR 1.181-4 - Special rules.

Code of Federal Regulations, 2012 CFR

2012-04-01

... before computing gain or loss from the disposition. (2) Principal photography not commencing prior to the... for which principal photography does not commence prior to the date of expiration of section 181, the...

26 CFR 1.181-4 - Special rules.

Code of Federal Regulations, 2013 CFR

2013-04-01

... before computing gain or loss from the disposition. (2) Principal photography not commencing prior to the... for which principal photography does not commence prior to the date of expiration of section 181, the...

Perianal disease, small bowel disease, smoking, prior steroid or early azathioprine/biological therapy are predictors of disease behavior change in patients with Crohn's disease.

PubMed

Lakatos, Peter Laszlo; Czegledi, Zsofia; Szamosi, Tamas; Banai, Janos; David, Gyula; Zsigmond, Ferenc; Pandur, Tunde; Erdelyi, Zsuzsanna; Gemela, Orsolya; Papp, Janos; Lakatos, Laszlo

2009-07-28

To assess the combined effect of disease phenotype, smoking and medical therapy [steroid, azathioprine (AZA), AZA/biological therapy] on the probability of disease behavior change in a Caucasian cohort of patients with Crohn's disease (CD). Three hundred and forty well-characterized, unrelated, consecutive CD patients were analyzed (M/F: 155/185, duration: 9.4 +/- 7.5 years) with a complete clinical follow-up. Medical records including disease phenotype according to the Montreal classification, extraintestinal manifestations, use of medications and surgical events were analyzed retrospectively. Patients were interviewed on their smoking habits at the time of diagnosis and during the regular follow-up visits. A change in disease behavior was observed in 30.8% of patients with an initially non-stricturing, non-penetrating disease behavior after a mean disease duration of 9.0 +/- 7.2 years. In a logistic regression analysis corrected for disease duration, perianal disease, smoking, steroid use, early AZA or AZA/biological therapy use were independent predictors of disease behavior change. In a subsequent Kaplan-Meier survival analysis and a proportional Cox regression analysis, disease location (P = 0.001), presence of perianal disease (P < 0.001), prior steroid use (P = 0.006), early AZA (P = 0.005) or AZA/biological therapy (P = 0.002), or smoking (P = 0.032) were independent predictors of disease behavior change. Our data suggest that perianal disease, small bowel disease, smoking, prior steroid use, early AZA or AZA/biological therapy are all predictors of disease behavior change in CD patients.

The Andalusian Bipolar Family (ABiF) Study: Protocol and sample description.

PubMed

Guzman-Parra, Jose; Rivas, Fabio; Strohmaier, Jana; Forstner, Andreas; Streit, Fabian; Auburger, Georg; Propping, Peter; Orozco-Diaz, Guillermo; González, Maria José; Gil-Flores, Susana; Cabaleiro-Fabeiro, Francisco Javier; Del Río-Noriega, Francisco; Perez-Perez, Fermin; Haro-González, Jesus; de Diego-Otero, Yolanda; Romero-Sanchiz, Pablo; Moreno-Küstner, Berta; Cichon, Sven; Nöthen, Markus M; Rietschel, Marcella; Mayoral, Fermin

2017-06-12

Here, we present the first description of the Andalusian Bipolar Family (ABiF) Study. This longitudinal investigation of families from Andalusia, Spain commenced in 1997 with the aim of elucidating the molecular genetic causes of bipolar affective disorder. The cohort has since contributed to a number of key genetic findings, as reported in international journals. However, insight into the genetic underpinnings of the disorder in these families remains limited. In the initial 1997-2003 study phase, 100 multiplex bipolar disorder and other mood disorder families were recruited. The ongoing second phase of the project commenced in 2013, and involves follow-up of a subgroup of the originally recruited families. The aim of the follow-up investigation is to generate: i) longitudinal clinical data; ii) results from detailed neuropsychological assessments; and iii) a more extensive collection of biomaterials for future molecular biological studies. The ABiF Study will thus generate a valuable resource for future investigations into the aetiology of bipolar affective disorder; in particular the causes of high disease loading within multiply affected families. We discuss the value of this approach in terms of new technologies for the identification of high-penetrance genetic factors. These new technologies include exome and whole genome sequencing, and the use of induced pluripotent stem cells or model organisms to determine functional consequences. Copyright © 2017 SEP y SEPB. Publicado por Elsevier España, S.L.U. All rights reserved.

Malnutrition among vaccinated children aged 0-5 years in Batouri, Republic of Cameroon.

PubMed

Nagahori, Chikako; Kinjo, Yoshihide; Tchuani, Jean Paul; Yamauchi, Taro

2017-12-01

Malnutrition continues to contribute to a high infant mortality rate. This study aimed to determine the prevalence of malnutrition and its potential association with the time at which complementary feeding was introduced among children aged 0-5 years in Batouri, Republic of Cameroon. Mothers (n=212) were interviewed using a structured questionnaire. Child height or length, and weight measurements were determined and the appropriate Z -scores calculated. Multiple regression analysis was performed with the values of all nutritional status indicators as dependent variables and the time of commencing complementary feeding, and the child's age and sex, as independent variables. The prevalence of stunting (height/length for age<-2 standard deviation [SD]), underweight (weight for age<-2SD), and wasting (weight for height/length<-2SD) was 45.8%, 30.2%, and 11.3%, respectively. Even taking into consideration the biological variables, there was a significant association in the effects of time of starting complementary foods on the nutritional status indicators. Furthermore, adding socio-economic variables did not produce a rise in adjusted R 2 values for all age group models concerned. Approximately 30% of the children in the study region were underweight, and approximately half of the children exhibited stunting, indicating chronic malnutrition. Commencing complementary feeding at an appropriate time had a positive effect on nutritional status from approximately 2 years of age.

Current advancement in radiation therapy for uterine cervical cancer.

PubMed

Nakano, Takashi; Ohno, Tatsuya; Ishikawa, Hitoshi; Suzuki, Yoshiyuki; Takahashi, Takeo

2010-01-01

Radiation therapy is one of the effective curative treatments for uterine cervical cancer. However poor clinical results for the advanced stages require further improvement of the treatment. Intensive studies on basic and clinical research have been made to improve local control, primarily important for long term survival in radiation therapy. Regarding current advancement in radiation therapy for uterine cervical cancer, the following three major subjects are pointed out; technological development to improve dose distribution by image guided radiation therapy technology, the concomitant anticancer chemotherapy with combination of radiation therapy, and radiation biological assessment of the radiation resistance of tumors. The biological factors overviewed in this article include hypoxia relating factors of HIF-1alpha, SOD, cell cycle parameters of pMI, proliferation factors of Ki67, EGFR, cerbB2, COX-2, cycle regulation proteins p53, p21, apoptosis regulation proteins Bcl2 and Bax and so on. Especially, the variety of these radiation biological factors is important for the selection of an effective treatment method for each patient to maximize the treatment benefit.

Breast Cancer Subtypes: Morphologic and Biologic Characterization

PubMed Central

2016-01-01

Advances in basic science, technology and translational research have created a revolution in breast cancer diagnosis and therapy. Researchers' discoveries of genes defining variability in response to therapy and heterogeneity in clinical presentations and tumor biology are the foundation of the path to personalized medicine. The success of personalized breast cancer care depends on access to pertinent clinical information and risk factors, optimal imaging findings, well-established morphologic features, and traditional and contemporary prognostic/predictive testing. The integration of these entities provides an opportunity to identify patients who can benefit from specific therapies, and demonstrates the link between breast cancer subtypes and their association with different tumor biology. It is critical to recognize specific types of breast cancer in individual patients and design optimal personalized therapy. This article will highlight the roles of morphologic features and established tumor biomarkers on patient outcome. PMID:26756229

25 CFR 226.19 - Use of surface of land.

Code of Federal Regulations, 2012 CFR

2012-04-01

... the surface owner commencement money in the amount of $25 per seismic shot hole and commencement money... operations and shall not exceed one and one-half acres in area unless authorized by the Superintendent...

25 CFR 226.19 - Use of surface of land.

Code of Federal Regulations, 2011 CFR

2011-04-01

... the surface owner commencement money in the amount of $25 per seismic shot hole and commencement money... operations and shall not exceed one and one-half acres in area unless authorized by the Superintendent...

25 CFR 226.19 - Use of surface of land.

Code of Federal Regulations, 2013 CFR

2013-04-01

... the surface owner commencement money in the amount of $25 per seismic shot hole and commencement money... operations and shall not exceed one and one-half acres in area unless authorized by the Superintendent...

25 CFR 226.19 - Use of surface of land.

Code of Federal Regulations, 2014 CFR

2014-04-01

... the surface owner commencement money in the amount of $25 per seismic shot hole and commencement money... operations and shall not exceed one and one-half acres in area unless authorized by the Superintendent...

25 CFR 226.19 - Use of surface of land.

Code of Federal Regulations, 2010 CFR

2010-04-01

... the surface owner commencement money in the amount of $25 per seismic shot hole and commencement money... operations and shall not exceed one and one-half acres in area unless authorized by the Superintendent...

Bone healing in 2016

PubMed Central

Buza, John A.; Einhorn, Thomas

2016-01-01

Summary Delayed fracture healing and nonunion occurs in up to 5–10% of all fractures, and can present a challenging clinical scenario for the treating physician. Methods for the enhancement of skeletal repair may benefit patients that are at risk of, or have experienced, delayed healing or nonunion. These methods can be categorized into either physical stimulation therapies or biological therapies. Physical stimulation therapies include electrical stimulation, low-intensity pulsed ultrasonography, or extracorporeal shock wave therapy. Biological therapies can be further classified into local or systemic therapy based on the method of delivery. Local methods include autologous bone marrow, autologous bone graft, fibroblast growth factor-2, platelet-rich plasma, platelet-derived growth factor, and bone morphogenetic proteins. Systemic therapies include parathyroid hormone and bisphosphonates. This article reviews the current applications and supporting evidence for the use of these therapies in the enhancement of fracture healing. PMID:27920804

What has happened in the last 50 years in immunology.

PubMed

Wong, Melanie

2015-02-01

Fifty years ago, in 1964, our understanding of the immune system was very rudimentary. Gell and Coombs had just described classes of hypersensitivity reactions, and Bruton had described and commenced immunoglobulin replacement in agammaglobulinaemia. The distinction between T and B cells was not identified and characterised until the 1960s and 1970s. This was followed by increasing recognition of T and B cell collaboration in immune responses and identification of significant immunodeficiencies. CD4 and CD8 T cells were only recognised in the 1970s and 1980s. We now know of five CD4 subsets; dysfunction of each is associated with different disorders. By 2014, advances in technology have enabled identification of the genetic basis of over 240 primary immunodeficiencies. Research into the gut microbiome and vitamin D holds promise for the understanding, treatment and prevention of autoimmune and allergic diseases. Immunoglobulin preparations for the treatment of antibody deficiencies improved with the development of preparations for intravenous then subcutaneous administration, giving patients choice and the ability for home-based treatment, especially if experiencing infusion associated adverse effects. Newborn screening for severe combined immunodeficiency is a reality. Improvements in haemopoietic stem cell transplantation and now gene therapy, albeit still only available in the research setting, are improving long-term survival in primary immunodeficiencies. Biologic therapeutic agents are improving the control of autoimmune disease but potentially leading to secondary immunodeficiency, increasing the risk of opportunistic infection and malignancy. It is an exciting time. © 2015 The Author. Journal of Paediatrics and Child Health © 2015 Paediatrics and Child Health Division (Royal Australasian College of Physicians).

Practical Radiobiology for Proton Therapy Planning

NASA Astrophysics Data System (ADS)

Jones, Bleddyn

2017-12-01

Practical Radiobiology for Proton Therapy Planning covers the principles, advantages and potential pitfalls that occur in proton therapy, especially its radiobiological modelling applications. This book is intended to educate, inform and to stimulate further research questions. Additionally, it will help proton therapy centres when designing new treatments or when unintended errors or delays occur. The clear descriptions of useful equations for high LET particle beam applications, worked examples of many important clinical situations, and discussion of how proton therapy may be optimized are all important features of the text. This important book blends the relevant physics, biology and medical aspects of this multidisciplinary subject. Part of Series in Physics and Engineering in Medicine and Biology.

Prevention and treatment of tuberculosis infection in candidates for biologic therapy: A multidisciplinary consensus statement adapted to the dermatology patient.

PubMed

Rodríguez-Jiménez, P; Mir-Viladrich, I; Chicharro, P; Solano-López, G; López-Longo, F J; Taxonera, C; Sánchez-Martínez, P; Martínez-Lacasa, X; García-Gasalla, M; Dorca, J; Arias-Guillén, M; García-García, J M; Dauden, E

2018-06-02

Patients with chronic inflammatory diseases being treated with immunosuppressive drugs, and with tumor necrosis factor inhibitors in particular, have an increased risk of infection by Mycobacterium tuberculosis. Screening for latent tuberculosis infection and preventive therapy to reduce the risk of progression to active tuberculosis are mandatory in this group of patients. This updated multidisciplinary consensus document presents the latest expert opinions on the treatment and prevention of tuberculosis in candidates for biologic therapy and establishes recommendations based on current knowledge relating to the use of biologic agents. Copyright © 2018 AEDV. Publicado por Elsevier España, S.L.U. All rights reserved.

COMMENCEMENT BAY AQUATIC ECOSYSTEM RESTORATION

EPA Science Inventory

Commencement Bay is a large Washington Superfund site with widespread sediment contamination. Under the ESA, all federal agencies are directed to utilize their authorities to support the conservation and recovery of endangered or threatened species. EPA uses a comprehensive an...

47 CFR 1.946 - Construction and coverage requirements.

Code of Federal Regulations, 2011 CFR

2011-10-01

... Wireless Radio Services, requirements for construction and commencement of service or commencement of... certain Wireless Radio Services, licensees must comply with geographic coverage requirements or... Section 1.946 Telecommunication FEDERAL COMMUNICATIONS COMMISSION GENERAL PRACTICE AND PROCEDURE Wireless...

47 CFR 1.946 - Construction and coverage requirements.

Code of Federal Regulations, 2010 CFR

2010-10-01

... Wireless Radio Services, requirements for construction and commencement of service or commencement of... certain Wireless Radio Services, licensees must comply with geographic coverage requirements or... Section 1.946 Telecommunication FEDERAL COMMUNICATIONS COMMISSION GENERAL PRACTICE AND PROCEDURE Wireless...

Geomagnetic sudden impulses and storm sudden commencements - A note on terminology

NASA Technical Reports Server (NTRS)

Joselyn, J. A.; Tsurutani, B. T.

1990-01-01

The definitions of and distinctions between storm sudden commencements (SSCs) and geomagnetic sudden impulses (SIs) are examined and present definitions of SIs and SSCs are modernized. Quantitative definitions of the two terms are recommended.

78 FR 79699 - Cellular, Tissue, and Gene Therapies Advisory Committee; Notice of Meeting

Federal Register 2010, 2011, 2012, 2013, 2014

2013-12-31

... Harvey, Food and Drug Administration, Center for Biologics Evaluation and Research, 1401 Rockville Pike... Biologics Evaluation and Research (CBER), FDA. On February 26, 2014, from 1 p.m. to approximately 5 p.m... and gene therapy products. CBER published guidance on this topic in July 2013 ( http://www.fda.gov...

Top-down approach to biological therapy of Crohn's disease.

PubMed

Hirschmann, Simon; Neurath, Markus F

2017-03-01

Crohn's disease (CD) is a chronic, immune-mediated condition with a potentially disabling and destructive course. Despite growing data on when to use a therapeutic 'top-down' strategy, clinical management of this complex disorder is still challenging. Currently, the discussion of 'top-down' strategy in CD mostly includes biological therapy alone or in combination. Areas covered: This article is based on a review of existing literature regarding the use of biological therapy in a 'top-down' approach for the treatment of Crohn's disease. The authors reviewed all the major databases including MEDLINE as well as DDW and ECCO abstracts, respectively. Expert opinion: A 'top-down' therapeutic approach in Crohn's disease is strongly supported by existing data in patients with several risk factors for a severe course of disease. Moreover, there is an increasing amount of published data recommending a more individualised therapeutic strategy to identify candidates for 'top-down' treatment, based on enhanced diagnostics using biomarkers. Emerging therapeutic approaches besides existing therapy concepts using biologicals may possibly redefine the 'top-down' therapeutic strategy for Crohn's disease in the future.

[Therapy for childhood uveitis: biologics: too often--too late?].

PubMed

Mackensen, F; Lutz, T

2011-03-01

Pediatric uveitis differs from uveitis seen in adulthood not only because of the uveitis presentation and severity of disease but also by a worse prognosis and age-specific problems that may occur under therapy. Biologics are selective acting proteins that are manufactured by biotechnology. The greatest amount of knowledge to date exists for the TNF alpha blocking agents. Experimental and clinical studies showed that TNF alpha plays a significant role in the process of intraocular inflammation, so it was a logical step to use TNF blocking agents in uveitis therapy. Randomized controlled studies are rare, but pooled data (as presented here) of case series published show good evidence for the efficacy especially of infliximab and adalimumab. It is to be hoped that blindness and severe sight disabilities can be further reduced by this treatment in the future. From pediatric rheumatology we have learned about even newer biologics. With this review we want to show the weaknesses and strengths of therapy with biologics and want to help in choosing this treatment at the indicated time point in the disease.

Detection of interferon-γ response to tuberculosis in blood collected at commencement of exsanguination at slaughter from cattle sensitized with Mycobacterium bovis.

PubMed

Okafor, Chika C; Grooms, Daniel L; Bolin, Steven R; Kaneene, John B

2012-06-01

To determine whether an interferon (IFN)-γ response sufficient to categorize cattle as positive for tuberculosis can be detected in blood collected at commencement of exsanguination at slaughter. 15 Holstein cows. 12 cows were experimentally sensitized by SC injection with inactivated Mycobacterium bovis in mineral oil, which induced an immune response that mimicked natural infection with M bovis. Three nonsensitized control cows were injected SC with mineral oil alone. By 5 weeks after injection, only the 12 sensitized cows had positive results for tuberculosis with whole blood IFN-γ assay. At that time, all 15 cows were sent to slaughter and samples of blood were collected from each cow immediately before stunning and at commencement of exsanguination (within 90 seconds after stunning). A whole blood IFN-γ assay was performed on the samples. Conditional probability and paired t tests were used to analyze changes in the categorical test interpretation and qualitative IFN-γ production, respectively. All 12 sensitized cows had positive results for tuberculosis in samples obtained immediately before stunning, and 9 retained positive results for samples obtained at commencement of exsanguination. There was a significant decrease in the mean background-corrected IFN-γ ELISA optical density values for samples obtained at commencement of exsanguination. IFN-γ response sufficient to classify cattle as positive for tuberculosis could be detected in blood collected at commencement of exsanguination. These findings support further development and use of the IFN-γ assay on blood samples collected at exsanguination as part of a bovine tuberculosis surveillance program.

A New Era for Cancer Target Therapies: Applying Systems Biology and Computer-Aided Drug Design to Cancer Therapies.

PubMed

Wong, Yung-Hao; Chiu, Chia-Chiun; Lin, Chih-Lung; Chen, Ting-Shou; Jheng, Bo-Ren; Lee, Yu-Ching; Chen, Jeremy; Chen, Bor-Sen

In recent years, many systems biology approaches have been used with various cancers. The materials described here can be used to build bases to discover novel cancer therapy targets in connection with computer-aided drug design (CADD). A deeper understanding of the mechanisms of cancer will provide more choices and correct strategies in the development of multiple target drug therapies, which is quite different from the traditional cancer single target therapy. Targeted therapy is one of the most powerful strategies against cancer and can also be applied to other diseases. Due to the large amount of progress in computer hardware and the theories of computational chemistry and physics, CADD has been the main strategy for developing novel drugs for cancer therapy. In contrast to traditional single target therapies, in this review we will emphasize the future direction of the field, i.e., multiple target therapies. Structure-based and ligand-based drug designs are the two main topics of CADD. The former needs both 3D protein structures and ligand structures, while the latter only needs ligand structures. Ordinarily it is estimated to take more than 14 years and 800 million dollars to develop a new drug. Many new CADD software programs and techniques have been developed in recent decades. We conclude with an example where we combined and applied systems biology and CADD to the core networks of four cancers and successfully developed a novel cocktail for drug therapy that treats multiple targets.

Changes in c-Kit expression levels during the course of radiation therapy for nasopharyngeal carcinoma.

PubMed

Jiang, Feng; Hu, Wei; Zhang, Bicheng; Xu, Jing; Shui, Yongjie; Zhou, Xiaofeng; Ren, Xiaoqiu; Chen, Xiaozhong; Shen, Li; Wei, Qichun

2016-10-01

In the era of intensity-modulated radiotherapy, distant metastasis is currently the main cause of treatment failure for nasopharyngeal carcinoma (NPC). Additional therapeutic strategies are required to control the metastasis and improve survival. One strategy is targeted therapy, for example against c-Kit. In the current study, the frequency of c-Kit expression was determined immunohistochemically in 106 NPC patients. c-Kit expression changes during the course of radiation therapy were detected in 41 cases via weekly biopsy. Twelve cases (11.3%) had c-Kit expression scores of 3 + and 16 (15.1%) had scores of 2 + . Thus, c-Kit overexpression (2 + or 3 + ) was observed in 28 (26.4%) patients. There were 35 (33.0%) and 43 (40.6%) patients with c-Kit expression scores of 1 + and 0, respectively. Furthermore, a trend of decreased c-Kit expression was observed after commencing radiotherapy according to the 41 NPC patients who were biopsied weekly. Therefore, c-Kit overexpression was identified to be common in NPC, and evaluating c-Kit as a therapeutic target for metastatic NPC via c-Kit overexpression subsequent to first line treatment may be of interest. To the best of our knowledge, the present study is the first to demonstrate a trend of decreased c-Kit expression during the course of radiotherapy.

Determinants of Oxygen Therapy in Childhood Pneumonia in a Resource-Constrained Region

PubMed Central

Kuti, Bankole Peter; Adegoke, Samuel Ademola; Ebruke, Benard E.; Howie, Stephen; Oyelami, Oyeku Akibu; Ota, Martin

2013-01-01

Childhood pneumonia is a leading cause of morbidity and mortality among underfives particularly in the resource-constraint part of the world. A high proportion of these deaths are due to lack of oxygen, thereby making oxygen administration a life-saving adjunctive when indicated. However, many primary health centres that manage most of the cases often lack the adequate manpower and facilities to decide which patient should be on oxygen therapy. Therefore, this study aimed to determine factors that predict hypoxaemia at presentation in children with severe pneumonia. Four hundred and twenty children aged from 2 to 59 months (40% infants) with severe pneumonia admitted to a health centre in rural Gambia were assessed at presentation. Eighty-one of them (19.30%) had hypoxaemia (oxygen saturation < 90%). Children aged 2–11 months, with grunting respiration, cyanosis, and head nodding, and those with cardiomegaly on chest radiograph were at higher risk of hypoxaemia (P < 0.05). Grunting respiration (OR = 5.210, 95% CI 2.287–7.482) and cyanosis (OR = 83.200, 95% CI 5.248–355.111) were independent predictors of hypoxaemia in childhood pneumonia. We conclude that children that grunt and are centrally cyanosed should be preferentially commenced on oxygen therapy even when there is no facility to confirm hypoxaemia. PMID:23819060

Clinical update on fluid therapy and nutritional support in acute pancreatitis.

PubMed

DiMagno, Matthew J

2015-01-01

The aim of this focused review is to provide a valuable and updated source of information for clinical practice on fluid therapy (FT) and nutritional support in acute pancreatitis (AP). The review encompasses important new clinical information that has become available for understanding and offering these specific treatments since the 2013 publication of two guidelines, both the joint International Association of Pancreatology and American Pancreatic Association and the American College of Gastroenterology. The 2015 Revised Japanese Guideline is discussed selectively. To this end, the review is divided into 7 sections, including timing and cause of mortality; severity classification systems; predicting severity; response to treatment; nutritional support; fluid therapy and steps for further research. In mild AP, begin oral feeding when nausea, vomiting and abdominal pain are improving. In (predicted) severe AP, feeding decisions should commence by 72 h, offering oral feeding if GI symptoms improve or enteral feeding if patients are symptomatic and/or intolerant to orals. All patients should be offered goal-directed FT during the first 6-12 h of presentation. Cautious FT is advised in those age >55 years or with preexisting organ failure or predictors of developing fluid sequestration. Copyright © 2015 IAP and EPC. Published by Elsevier India Pvt Ltd. All rights reserved.

Fetus dose estimation in thyroid cancer post-surgical radioiodine therapy.

PubMed

Mianji, Fereidoun A; Diba, Jila Karimi; Babakhani, Asad

2015-01-01

Unrecognised pregnancy during radioisotope therapy of thyroid cancer results in hardly definable embryo/fetus exposures, particularly when the thyroid gland is already removed. Sources of such difficulty include uncertainty in data like pregnancy commencing time, amount and distribution of metastasized thyroid cells in body, effect of the thyroidectomy on the fetus dose coefficient etc. Despite all these uncertainties, estimation of the order of the fetus dose in most cases is enough for medical and legal decision-making purposes. A model for adapting the dose coefficients recommended by the well-known methods to the problem of fetus dose assessment in athyrotic patients is proposed. The model defines a correction factor for the problem and ensures that the fetus dose in athyrotic pregnant patients is less than the normal patients. A case of pregnant patient undergone post-surgical therapy by I-131 is then studied for quantitative comparison of the methods. The results draw a range for the fetus dose in athyrotic patients using the derived factor. This reduces the concerns on under- or over-estimation of the embryo/fetus dose and is helpful for personal and/or legal decision-making on abortion. © The Author 2014. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

Changes in Water Mobility Measured by Diffusion MRI Predict Response of Metastatic Breast Cancer to Chemotherapy

PubMed Central

Theilmann, Rebecca J; Borders, Rebecca; Trouard, Theodore P; Xia, Guowei; Outwater, Eric; Ranger-Moore, James; Gillies, Robert J; Stopeck, Alison

2004-01-01

Abstract A goal of oncology is the individualization of patient care to optimize therapeutic responses and minimize toxicities. Achieving this will require noninvasive, quantifiable, and early markers of tumor response. Preclinical data from xenografted tumors using a variety of antitumor therapies have shown that magnetic resonance imaging (MRI)-measured mobility of tissue water (apparent diffusion coefficient of water, or ADCw) is a biomarker presaging cell death in the tumor. This communication tests the hypothesis that changes in water mobility will quantitatively presage tumor responses in patients with metastatic liver lesions from breast cancer. A total of 13 patients with metastatic breast cancer and 60measurable liver lesionsweremonitored by diffusion MRI after initiation of new courses of chemotherapy. MR images were obtained prior to, and at 4, 11, and 39 days following the initiation of therapy for determination of volumes and ADCw values. The data indicate that diffusion MRI can predict response by 4 or 11 days after commencement of therapy, depending on the analytic method. The highest concordance was observed in tumor lesions that were less than 8 cm3 in volume at presentation. These results suggest that diffusion MRI can be useful to predict the response of liver metastases to effective chemotherapy. PMID:15720810

30 CFR 285.637 - When may I commence commercial operations on my commercial lease?

Code of Federal Regulations, 2010 CFR

2010-07-01

... INTERIOR OFFSHORE RENEWABLE ENERGY ALTERNATE USES OF EXISTING FACILITIES ON THE OUTER CONTINENTAL SHELF... require a FERC license (i.e., wind), then you may commence commercial operations 30 days after the CVA or...

40 CFR 164.20 - Commencement of proceeding.

Code of Federal Regulations, 2011 CFR

2011-07-01

... Section 164.20 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED) PESTICIDE PROGRAMS..., ARISING FROM REFUSALS TO REGISTER, CANCELLATIONS OF REGISTRATIONS, CHANGES OF CLASSIFICATIONS, SUSPENSIONS... registration or to change the classification of a pesticide. A proceeding shall likewise be commenced whenever...

40 CFR 164.20 - Commencement of proceeding.

Code of Federal Regulations, 2010 CFR

2010-07-01

... Section 164.20 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED) PESTICIDE PROGRAMS..., ARISING FROM REFUSALS TO REGISTER, CANCELLATIONS OF REGISTRATIONS, CHANGES OF CLASSIFICATIONS, SUSPENSIONS... registration or to change the classification of a pesticide. A proceeding shall likewise be commenced whenever...

Vitamin D deficiency in patients with either rheumatic diseases or inflammatory bowel diseases on biologic therapy.

PubMed

Bruzzese, Vincenzo; Zullo, Angelo; Picchianti Diamanti, Andrea; Ridola, Lorenzo; Lorenzetti, Roberto; Marrese, Cinzia; Scolieri, Palma; De Francesco, Vincenzo; Hassan, Cesare; Migliore, Alberto; Laganà, Bruno

2016-09-01

Vitamin D deficiency has been reported in patients with chronic inflammatory conditions, such as rheumatic and inflammatory bowel diseases (IBD). We evaluated the role of biologic therapy on vitamin D, calcium and parathormone (PTH) levels. This cross-sectional study enrolled consecutive patients with either rheumatic diseases or IBD who underwent an ambulatory visit. Patients receiving vitamin D/calcium supplementation were excluded. Vitamin D deficiency or insufficiency was diagnosed when values were <20 ng/mL and 21-29 ng/ml, respectively. Patients were sub-grouped according to biologic therapy. A multivariate analysis was performed. Two-hundred patients, including 136 with a rheumatic disease (M/F 37/99; mean age 60.7 ± 12.9 years) and 64 with IBD (M/F 41/23; Mean age 49.6 ± 13.1 years) were enrolled. Vitamin D deficiency/insufficiency was detected in as many as 63.5 % patients, being 61.8 and 67.2 % in patients with either rheumatic diseases or IBD, respectively. The prevalence of vitamin D deficiency/insufficiency was higher in those receiving biologics than other therapies (78.3 vs 43.2 %; p < 0.0001), in either rheumatic diseases (78.7 vs 41 %; p < 0.0001) or IBD (75 vs 50 %; p = 0.03) group. At multivariate analysis, only biologic therapy was independently associated with vitamin D deficit (OR 4.61; p = 0.001). Patients with vitamin D deficiency/insufficiency had hypocalcemia more frequently than controls (22.8 vs 10.9 %; p = 0.03), while PTH values did not differ significantly. This study finds that the prevalence of vitamin D deficiency/insufficiency was very high in patients with either rheumatic diseases or IBD receiving a biologic therapy.

Does Variation in Either Age at Start of Therapy or Duration of Therapy Make Chemoprevention with Finasteride Cost-Effective?

PubMed Central

Stewart, Suzanne Biehn; Scales, Charles D.; Moul, Judd W.; Reed, Shelby D.

2013-01-01

Background Incremental cost-effectiveness ratios (ICER) of finasteride for prostate cancer prevention are consistent with estimates beyond $100,000 per quality-adjusted life-year (QALY). The majority of these analyses are based on chemoprevention starting in men aged 50–55yrs. We sought to evaluate the impact of varying both age at commencement of therapy and length of therapy on the cost-effectiveness of finasteride. Methods A probabilistic Markov model was designed to estimate lifetime prostate health related costs and quality-adjusted survival for men receiving or not receiving chemoprevention with finasteride. ICERs across scenarios varying age at start of therapy and duration of chemoprevention were compared. Results The ICER for men starting chemoprevention at age 50 and continuing to age 75 was $88,800 per QALY when assuming finasteride causes a constant risk reduction across all tumor grades (base case 1) and $142,300 per when assuming a differential treatment effect according to Gleason score (base case 2). When starting age is increased, the ICERs trend downward and nadir at 65 years to $64,700 per QALY (base case 1) and $118,600 per QALY (base case 2). Altering duration of therapy had minimal impact. Patient-level experiences with finasteride and BPH significantly influenced the cost-effectiveness of chemoprevention. Conclusion Initiating chemoprevention at ages when prostate cancer incidence is higher improves its cost-effectiveness profile. Only when assuming a constant risk reduction for all tumor grades, did finasteride fall below $100,000 per QALY, but this finding was not upheld when accounting for side effects associated with the drug. PMID:22777393

Treatment of hyperthyroidism with antithyroid drugs corrects mild neutropenia in Graves' disease.

PubMed

Aggarwal, N; Tee, S A; Saqib, W; Fretwell, T; Summerfield, G P; Razvi, S

2016-12-01

Neutropenia secondary to antithyroid drug (ATD) therapy in Graves' disease (GD) is well recognized. However, the effect of hyperthyroidism, prior to and after ATD therapy, on neutrophil counts in patients with GD is unclear. To study the prevalence of neutropenia in newly diagnosed untreated GD and the effect of ATD on the neutrophil count. Prospective study from August 2010 to December 2014. Endocrinology outpatient clinic in a single centre. Consecutive patients (n = 206) with newly diagnosed GD. ATD therapy. Prevalence and factors predicting neutropenia (<2 × 10 9 /l) and change in neutrophil counts following ATD. At diagnosis, 29 (14·1%) of GD individuals had neutropenia. Non-Caucasians [odds ratio (95% CI) of 4·06 (1·14-14·45), P = 0·03] and patients with higher serum thyroid hormone levels [OR 1·07 (1·02-1·13), P = 0·002 for serum FT3] were the only independent predictors of neutropenia. All patients with neutropenia had normalized blood neutrophil levels after achieving euthyroidism with ATD therapy. In patients in whom data were available posteuthyroidism (n = 149), change in neutrophil count after achieving euthyroidism was independently related to reduction in thyroid hormone levels (P < 0·01). GD is associated with neutropenia in one in seven patients at diagnosis, especially in non-Caucasians and those with higher serum thyroid hormone levels. Neutrophil counts increase with treatment with ATD and are related to reduction in thyroid hormone concentrations. It is therefore important to check neutrophil levels in newly diagnosed patients with GD prior to commencing ATD therapy as otherwise low levels may incorrectly be attributed to ATD therapy. © 2016 John Wiley & Sons Ltd.

Fluctuations in the emotional intelligence of therapy students during clinical placements: Implication for educators, supervisors, and students.

PubMed

Gribble, Nigel; Ladyshewsky, Richard K; Parsons, Richard

2017-01-01

This study investigated the changes in emotional intelligence (EI) of occupational therapy, physiotherapy, and speech pathology students (therapy students). Clinical placements have multiple benefits including the development of interprofessional skills, enhancing practice skills and interpersonal skills. Higher EI competencies have been shown to have a positive impact on patient outcomes, teamwork skills, dealing with stress, and patient satisfaction. Data for this study were collected at two time points: before third-year therapy students commenced extended clinical placements (T1 with 261 students) and approximately 7 months later after students had completed one or more clinical placements (T2 with 109 students). EI was measured using the Emotional Quotient Inventory 2.0 (EQ-i 2.0 ). Only one EI score, assertiveness, demonstrated a significant decline. No EI score showed a significant increase. A third or more of the students showed increases of five points or more in self-actualisation, emotional expression, independence, reality testing and optimism. However, of concern were the five EI scores where therapy students' EI scores decreased by more than five points: assertiveness (where 38% of students declined), problem solving (37%), impulse control (35%), self-actualisation (35%), and stress tolerance (33%). With EI scores declining for some students during clinical placements, there are implications for clinical supervisors and interprofessional facilitators as clinical performance may decline concurrently. There is a range of potential reasons that clinical placements could negatively influence the EI competencies of a therapy student, including poor clinical supervision, conflict between a student, and supervisor and failing a clinical placement. The research suggests that interprofessional facilitators and university educators might consider students undertaking EI tests before clinical placements.

Mirror therapy enhances motor performance in the paretic upper limb after stroke: a pilot randomized controlled trial.

PubMed

Samuelkamaleshkumar, Selvaraj; Reethajanetsureka, Stephen; Pauljebaraj, Paul; Benshamir, Bright; Padankatti, Sanjeev Manasseh; David, Judy Ann

2014-11-01

To investigate the effectiveness of mirror therapy (MT) combined with bilateral arm training and graded activities to improve motor performance in the paretic upper limb after stroke. Randomized, controlled, assessor-blinded study. Inpatient stroke rehabilitation center of a tertiary care teaching hospital. Patients with first-time ischemic or hemorrhagic stroke (N=20), confined to the territory of the middle cerebral artery, occurring <6 months before the commencement of the study. The MT and control group participants underwent a patient-specific multidisciplinary rehabilitation program including conventional occupational therapy, physical therapy, and speech therapy for 5 d/wk, 6 h/d, over 3 weeks. The participants in the MT group received 1 hour of MT in addition to the conventional stroke rehabilitation. The Upper Extremity Fugl-Meyer Assessment for motor recovery, Brunnstrom stages of motor recovery for the arm and hand, Box and Block Test for gross manual hand dexterity, and modified Ashworth scale to assess the spasticity. After 3 weeks of MT, mean change scores were significantly greater in the MT group than in the control group for the Fugl-Meyer Assessment (P=.008), Brunnstrom stages of motor recovery for the arm (P=.003) and hand (P=.003), and the Box and Block Test (P=.022). No significant difference was found between the groups for modified Ashworth scale (P=.647). MT when combined with bilateral arm training and graded activities was effective in improving motor performance of the paretic upper limb after stroke compared with conventional therapy without MT. Copyright © 2014 American Congress of Rehabilitation Medicine. Published by Elsevier Inc. All rights reserved.

Maintenance of remission with combination etanercept-DMARD therapy versus DMARDs alone in active rheumatoid arthritis: results of an international treat-to-target study conducted in regions with limited biologic access.

PubMed

Pavelka, Karel; Akkoç, Nurullah; Al-Maini, Mustafa; Zerbini, Cristiano A F; Karateev, Dmitry E; Nasonov, Evgeny L; Rahman, Mahboob U; Pedersen, Ronald; Dinh, Andrew; Shen, Qi; Vasilescu, Radu; Kotak, Sameer; Mahgoub, Ehab; Vlahos, Bonnie

2017-09-01

In this transglobal, randomized, double-blind, placebo-controlled, treat-to-target study, the maintenance of efficacy was compared between biologic-and biologic-free-disease-modifying antirheumatic drug (DMARD) combination regimens after low disease activity (LDA) was achieved with biologic DMARD induction therapy. Patients with moderate-to-severe rheumatoid arthritis despite methotrexate therapy received open-label etanercept 50 mg subcutaneously once weekly plus methotrexate with or without other conventional synthetic (cs) DMARDs for 24 weeks. Patients achieving LDA [disease activity score in 28 joints based on erythrocyte sedimentation rate (DAS28-ESR) <3.2] at week 24 were randomized to receive etanercept-methotrexate combination therapy or placebo-methotrexate combination therapy, with or without other csDMARDs, for 28 weeks. In the open-label period, 72% of patients achieved DAS28-ESR LDA at week 24. Patients enrolled in the double-blind period had long-standing rheumatoid arthritis and high disease activity at baseline (mean duration, 8.1 years; DAS28-ESR, 6.4). In the etanercept and placebo combination groups, 44% versus 17% achieved DAS28-ESR LDA and 34 versus 13% achieved DAS28-ESR remission at week 52 (p < 0.001). Adverse events were reported in 37 and 43%, serious adverse events in 0 and 4%, and serious infections in 0 and 2% in these groups, respectively, in the double-blind period. After induction of response with etanercept combination therapy following a treat-to-target approach in patients with long-standing rheumatoid arthritis and high disease activity at baseline, the etanercept combination regimen was significantly more effective in maintaining LDA and remission than a biologic-free regimen. ClinicalTrials.gov identifier. NCT01578850.

Cost-utility Analysis: Thiopurines Plus Endoscopy-guided Biological Step-up Therapy is the Optimal Management of Postoperative Crohn's Disease.

PubMed

Candia, Roberto; Naimark, David; Sander, Beate; Nguyen, Geoffrey C

2017-11-01

Postoperative recurrence of Crohn's disease is common. This study sought to assess whether the postoperative management should be based on biological therapy alone or combined with thiopurines and whether the therapy should be started immediately after surgery or guided by either endoscopic or clinical recurrence. A Markov model was developed to estimate expected health outcomes in quality-adjusted life years (QALYs) and costs in Canadian dollars (CAD$) accrued by hypothetical patients with high recurrence risk after ileocolic resection. Eight strategies of postoperative management were evaluated. A lifetime time horizon, an annual discount rate of 5%, a societal perspective, and a cost-effectiveness threshold of 50,000 CAD$/QALY were assumed. Deterministic and probabilistic sensitivity analyses were conducted. The model was validated against randomized trials and historical cohorts. Three strategies dominated the others: endoscopy-guided full step-up therapy (14.80 QALYs, CAD$ 462,180), thiopurines immediately post-surgery plus endoscopy-guided biological step-up therapy (14.89 QALYs, CAD$ 464,099) and combination therapy immediately post-surgery (14.94 QALYs, CAD$ 483,685). The second strategy was the most cost-effective, assuming a cost-effectiveness threshold of 50,000 CAD$/QALY. Probabilistic sensitivity analysis showed that the second strategy has the highest probability of being the optimal alternative in all comparisons at cost-effectiveness thresholds from 30,000 to 100,000 CAD$/QALY. The strategies guided only by clinical recurrence and those using biologics alone were dominated. According to this decision analysis, thiopurines immediately after surgery and addition of biologics guided by endoscopic recurrence is the optimal strategy of postoperative management in patients with Crohn's disease with high risk of recurrence (see Video Abstract, Supplemental Digital Content 1, http://links.lww.com/IBD/B654).

Perianal disease, small bowel disease, smoking, prior steroid or early azathioprine/biological therapy are predictors of disease behavior change in patients with Crohn’s disease

PubMed Central

Lakatos, Peter Laszlo; Czegledi, Zsofia; Szamosi, Tamas; Banai, Janos; David, Gyula; Zsigmond, Ferenc; Pandur, Tunde; Erdelyi, Zsuzsanna; Gemela, Orsolya; Papp, Janos; Lakatos, Laszlo

2009-01-01

AIM: To assess the combined effect of disease phenotype, smoking and medical therapy [steroid, azathioprine (AZA), AZA/biological therapy] on the probability of disease behavior change in a Caucasian cohort of patients with Crohn’s disease (CD). METHODS: Three hundred and forty well-characterized, unrelated, consecutive CD patients were analyzed (M/F: 155/185, duration: 9.4 ± 7.5 years) with a complete clinical follow-up. Medical records including disease phenotype according to the Montreal classification, extraintestinal manifestations, use of medications and surgical events were analyzed retrospectively. Patients were interviewed on their smoking habits at the time of diagnosis and during the regular follow-up visits. RESULTS: A change in disease behavior was observed in 30.8% of patients with an initially non-stricturing, non-penetrating disease behavior after a mean disease duration of 9.0 ± 7.2 years. In a logistic regression analysis corrected for disease duration, perianal disease, smoking, steroid use, early AZA or AZA/biological therapy use were independent predictors of disease behavior change. In a subsequent Kaplan-Meier survival analysis and a proportional Cox regression analysis, disease location (P = 0.001), presence of perianal disease (P < 0.001), prior steroid use (P = 0.006), early AZA (P = 0.005) or AZA/biological therapy (P = 0.002), or smoking (P = 0.032) were independent predictors of disease behavior change. CONCLUSION: Our data suggest that perianal disease, small bowel disease, smoking, prior steroid use, early AZA or AZA/biological therapy are all predictors of disease behavior change in CD patients. PMID:19630105

Clinical, Functional, and Biological Correlates of Cognitive Dimensions in Major Depressive Disorder – Rationale, Design, and Characteristics of the Cognitive Function and Mood Study (CoFaM-Study)

PubMed Central

Baune, Bernhard T.; Air, Tracy

2016-01-01

Cross-sectional and longitudinal studies exploring clinical, functional, and biological correlates of major depressive disorder are frequent. In this type of research, depression is most commonly defined as a categorical diagnosis based on studies using diagnostic instruments. Given the phenotypic and biological heterogeneity of depression, we chose to focus the phenotypic assessments on three cognitive dimensions of depression including (a) cognitive performance, (b) emotion processing, and (c) social cognitive functioning. Hence, the overall aim of the study is to investigate the long-term clinical course of these cognitive dimensions in depression and its functional (psychosocial) correlates. We also aim to identify biological “genomic” correlates of these three cognitive dimensions of depression. To address the above overall aim, we created the Cognition and Mood Study (CoFaMS) with the key objective to investigate the clinical, functional, and biological correlates of cognitive dimensions of depression by employing a prospective study design and including a healthy control group. The study commenced in April 2015, including patients with a primary diagnosis of a major depressive episode of major depressive disorder or bipolar disorder according to DSM-IV-TR criteria. The assessments cover the three cognitive dimensions of depression (cognitive performance, emotion processing, and social cognition), cognitive function screening instrument, plus functional scales to assess general, work place, and psychosocial function, depression symptom scales, and clinical course of illness. Blood is collected for comprehensive genomic discovery analyses of biological correlates of cognitive dimensions of depression. The CoFaM-Study represents an innovative approach focusing on cognitive dimensions of depression and its functional and biological “genomic” correlates. The CoFaMS team welcomes collaborations with both national and international researchers. PMID:27616997

Clinical, Functional, and Biological Correlates of Cognitive Dimensions in Major Depressive Disorder - Rationale, Design, and Characteristics of the Cognitive Function and Mood Study (CoFaM-Study).

PubMed

Baune, Bernhard T; Air, Tracy

2016-01-01

Cross-sectional and longitudinal studies exploring clinical, functional, and biological correlates of major depressive disorder are frequent. In this type of research, depression is most commonly defined as a categorical diagnosis based on studies using diagnostic instruments. Given the phenotypic and biological heterogeneity of depression, we chose to focus the phenotypic assessments on three cognitive dimensions of depression including (a) cognitive performance, (b) emotion processing, and (c) social cognitive functioning. Hence, the overall aim of the study is to investigate the long-term clinical course of these cognitive dimensions in depression and its functional (psychosocial) correlates. We also aim to identify biological "genomic" correlates of these three cognitive dimensions of depression. To address the above overall aim, we created the Cognition and Mood Study (CoFaMS) with the key objective to investigate the clinical, functional, and biological correlates of cognitive dimensions of depression by employing a prospective study design and including a healthy control group. The study commenced in April 2015, including patients with a primary diagnosis of a major depressive episode of major depressive disorder or bipolar disorder according to DSM-IV-TR criteria. The assessments cover the three cognitive dimensions of depression (cognitive performance, emotion processing, and social cognition), cognitive function screening instrument, plus functional scales to assess general, work place, and psychosocial function, depression symptom scales, and clinical course of illness. Blood is collected for comprehensive genomic discovery analyses of biological correlates of cognitive dimensions of depression. The CoFaM-Study represents an innovative approach focusing on cognitive dimensions of depression and its functional and biological "genomic" correlates. The CoFaMS team welcomes collaborations with both national and international researchers.

Optimizing biological therapy in Crohn's disease.

PubMed

Gecse, Krisztina Barbara; Végh, Zsuzsanna; Lakatos, Péter László

2016-01-01

Anti-TNF therapy has revolutionized the treatment of inflammatory bowel diseases, including both Crohn's disease and ulcerative colitis. However, a significant proportion of patients does not respond to anti-TNF agents or lose response over time. Recently, therapeutic drug monitoring has gained a major role in identifying the mechanism and management of loss of response. The aim of this review article is to summarize the predictors of efficacy and outcomes, the different mechanisms of anti-TNF/biological failure in Crohn's disease and identify strategies to optimize biological treatment.

Review of the treatment of psoriatic arthritis with biological agents: choice of drug for initial therapy and switch therapy for non-responders.

PubMed

D'Angelo, Salvatore; Tramontano, Giuseppina; Gilio, Michele; Leccese, Pietro; Olivieri, Ignazio

2017-01-01

Psoriatic arthritis (PsA) is a heterogeneous chronic inflammatory disease with a broad clinical spectrum and variable course. It can involve musculoskeletal structures as well as skin, nails, eyes, and gut. The management of PsA has changed tremendously in the last decade, thanks to an earlier diagnosis, an advancement in pharmacological therapies, and a wider application of a multidisciplinary approach. The commercialization of tumor necrosis factor inhibitors (adalimumab, certolizumab pegol, etanercept, golimumab, and infliximab) as well as interleukin (IL)-12/23 (ustekinumab) and IL-17 (secukinumab) inhibitors is representative of a revolution in the treatment of PsA. No evidence-based strategies are currently available for guiding the rheumatologist to prescribe biological drugs. Several international and national recommendation sets are currently available with the aim to help rheumatologists in everyday clinical practice management of PsA patients treated with biological therapy. Since no specific biological agent has been demonstrated to be more effective than others, the drug choice should be made according to the available safety data, the presence of extra-articular manifestations, the patient's preferences (e.g., administration route), and the drug price. However, future studies directly comparing different biological drugs and assessing the efficacy of treatment strategies specific for PsA are urgently needed.

A safety assessment of biological therapies targeting the IL-23/IL-17 axis in inflammatory bowel diseases.

PubMed

Verstockt, Bram; Deleenheer, Barbara; Van Assche, Gert; Vermeire, Séverine; Ferrante, Marc

2017-07-01

Many different compounds targeting the interleukin 23/17 axis have been developed and successfully studied in several autoimmune diseases, including inflammatory bowel diseases. Nevertheless, interfering with key immunological pathways raises potential safety concerns. This review focuses on the safety profile of these novel biological therapies. Areas covered: A literature search until March 2017 was performed to collect safety data on different compounds targeting this pathway, with emphasis on ustekinumab and secukinumab. Firstly, the authors discuss briefly how genetics can inform about potential safety issues. Secondly, they extensively describe safety issues (common adverse events, infections, malignancies…), immunogenicity, exposure to ustekinumab in specific populations and provide advice for vaccination. Finally, they address safety profiles of secukinumab and other biological targeting the IL-23/17 axis in IBD. Expert opinion: Current evidence suggests that ustekinumab therapy overweigh the potential drug-related risks. Additional safety data beyond randomized-controlled trials, derived from statistically powered, large prospective studies with long-term follow-up are urgently needed to assess the real-life ustekinumab-related risks and to establish the correct position of these novel class of biologicals in IBD treatment. Combining immunomodulators with ustekinumab seems to be safe, though prospective data specifically addressing this topic are currently missing. Similarly, the combination of different biological therapies still has to be studied.

Risk of Serious Infection in Juvenile Idiopathic Arthritis Patients Associated With Tumor Necrosis Factor Inhibitors and Disease Activity in the German Biologics in Pediatric Rheumatology Registry.

PubMed

Becker, Ingrid; Horneff, Gerd

2017-04-01

To examine the effects of tumor necrosis factor inhibitors on the risk for serious infections and other influencing factors in a registry. Patients exposed for the first time to etanercept, adalimumab, or methotrexate and serious infections were identified in the German Biologic Registry for Pediatric Rheumatology (BIKER) registry. Serious infection rates per 1,000 observation-years and relative risks were calculated. Cox regression identified risk factors and provided hazard ratios (HRs) for occurrence of infections. A total of 3,350 patients with 5,919 observation-years fulfilled the inclusion criteria for the study. The first biologic agents were etanercept (1,720 cases) and adalimumab (177 cases). A total of 1,453 patients were treated with methotrexate and no biologic agent. In total, 28 serious infections were reported in 26 patients (4.7 per 1,000 patient-years), 5 with methotrexate (1.6 per 1,000 patient-years), 21 with etanercept (8.1 per 1,000 patient-years), and 2 with adalimumab (9.7 per 1,000 patient-years). Significant univariate risk factors for infection were therapy with biologic agents, disease duration before therapy start, corticosteroid medication, nonbiologic premedications, higher clinical Juvenile Arthritis Disease Activity Score including maximal 10 joints (cJADAS10) at therapy start, and higher mean cJADAS10 during therapy. In multivariate Cox regression, only biologic therapy and cJADAS10 at therapy start remained significant. Risk for infection was increased by etanercept (univariate HR 6.0 [95% confidence interval (95% CI) 2.0-17.5]) or adalimumab (HR 7.3 [95% CI 1.3-40.0]) compared to methotrexate as well as by an elevated cJADAS10 at therapy start (HR 1.1 [95% CI 1.0-1.2] per unit increase). The total rate of serious infections reported in the BIKER registry seems low. Treatment with etanercept or adalimumab increases the risk for serious infection slightly, compared to methotrexate. Disease activity expressed by cJADAS10 appears to be an independent risk factor. © 2016, American College of Rheumatology.

Impact of Biologics With and Without Concomitant MTX and at Reduced Doses in Older Rheumatoid Arthritis Patients

PubMed Central

Zhang, Jie; Xie, Fenglong; Delzell, Elizabeth; Yun, Huifeng; Lewis, James D; Haynes, Kevin; Chen, Lang; Beukelman, Timothy; Saag, Kenneth G; Curtis, Jeffrey R

2014-01-01

Background This study examines whether concomitant methotrexate (MTX) use is associated with better biologic persistence and whether self-administered anti-TNF therapies are used at reduced doses in real-world clinical care settings, not just clinical trials. Methods We conducted a retrospective cohort study among RA patients using Medicare claims data from 2006 to 2012. Subjects were new initiators of etanercept, infliximab, adalimumab, abatacept and tocilizumab with at least 12 months of continuous medical and pharmacy coverage after treatment initiation. We examined the association between concomitant MTX use and persistence on biologics using Cox proportional hazard regression adjusting for demographics and baseline co-morbidities. We further identified a subgroup of patients who initiated and were adherent on etanercept or adalimumab for at least 12 months and examined the proportion of patients who subsequently used these therapies at reduced doses continuously for an additional 12, 18, and 24 months. Results Of 26,510 eligible RA patients, 10,511 initiated biologic monotherapy. Overall, patients initiated biologic monotherapy were 1.4 (95% CI, 1.3–1.5) times more likely to discontinue at 1-year and 1.8 (95% CI, 1.7–2.0) times more likely if starting infliximab monotherapy. Approximately 10–20% of patients who initiated and adhered to etanercept and adalimumab for ≥ 12 months subsequently used reduced-dose therapy for an 12 additional months and beyond. Conclusion In real-world practice, concomitant MTX was associated with improved persistence on biologic therapy, especially for infliximab users; reduced-dose injectable anti-TNF therapy was used by a substantial proportion of RA patients. PMID:25370912

Update on the use of systemic biologic agents in the treatment of noninfectious uveitis

PubMed Central

Pasadhika, Sirichai; Rosenbaum, James T

2014-01-01

Uveitis is one of the leading causes of blindness worldwide. Noninfectious uveitis may be associated with other systemic conditions, such as human leukocyte antigen B27-related spondyloarthropathies, inflammatory bowel disease, juvenile idiopathic arthritis, Behçet’s disease, and sarcoidosis. Conventional therapy with corticosteroids and immunosuppressive agents (such as methotrexate, azathioprine, mycophenolate mofetil, and cyclosporine) may not be sufficient to control ocular inflammation or prevent non-ophthalmic complications in refractory patients. Off-label use of biologic response modifiers has been studied as primary and secondary therapeutic agents. They are very useful when conventional immunosuppressive therapy has failed or has been poorly tolerated, or to treat concomitant ophthalmic and systemic inflammation that might benefit from these medications. Biologic therapy, primarily infliximab, and adalimumab, have been shown to be rapidly effective for the treatment of various subtypes of refractory uveitis and retinal vasculitis, especially Behçet’s disease-related eye conditions and the uveitis associated with juvenile idiopathic arthritis. Other agents such as golimumab, abatacept, canakinumab, gevokizumab, tocilizumab, and alemtuzumab may have great future promise for the treatment of uveitis. It has been shown that with proper monitoring, biologic therapy can significantly improve quality of life in patients with uveitis, particularly those with concurrent systemic symptoms. However, given high cost as well as the limited long-term safety data, we do not routinely recommend biologics as first-line therapy for noninfectious uveitis in most patients. These agents should be used with caution by experienced clinicians. The present work aims to provide a broad and updated review of the current and in-development systemic biologic agents for the treatment of noninfectious uveitis. PMID:24600203

Treatment of ankylosing spondylitis with biologics and targeted physical therapy: positive effect on chest pain, diminished chest mobility, and respiratory function.

PubMed

Gyurcsik, Z; Bodnár, N; Szekanecz, Z; Szántó, S

2013-12-01

Biologics are highly effective in ankylosing spondylitis (AS). In this self-controlled study, we assessed the additive value of complex physiotherapy in decreasing chest pain and tenderness and improving respiratory function in AS patients treated with tumor necrosis factor α (TNF-α) inhibitors. The trial consisted of 2 parts. In study I, clinical data of AS patients with (n=55) or without biological therapy (n=20) were retrospectively analyzed and compared. Anthropometrical data, duration since diagnosis and patient assessment of disease activity, pain intensity, tender points, sacroiliac joint involvement determined by X-ray, functional condition, and physical activity level were recorded. Subjective, functional, and physical tests were performed. In study II, 10 voluntary patients (6 men and 4 women, age 52.4 ± 13.6 years) with definite AS and receiving anti-TNF therapy were recruited. It was a prospective, non-randomized physiotherapeutic trial. BASFI (Bath Ankylosing Spondylitis Functional Index), BASDAI (Bath Ankylosing Spondylitis Disease Activity Index), modified Schober Index, occiput-to-wall distance, and fingertip-to-floor distance were evaluated. Forced vital capacity, forced 1-s expiratory volume, peak expiratory flow, and maximum voluntary ventilation were recorded. Furthermore, typical tender points were recorded. A targeted physiotherapy program was conducted twice a week for 12 weeks and all above parameters were recorded at baseline and after 12 weeks. Differences in patient assessment of disease activity (p=0.019) and pain intensity (p=0.017) were found in study I. Pain and tenderness of the thoracic spine were observed in both groups. Back pain without biologic therapy was slightly higher than other group. In study II, we found that patient assessment of disease activity and pain intensity significantly improved after the physical therapy program (p=0.002 and p<0.001). BASFI and BASDAI increased after treatment (p=0.004 and p<0.001). The finger-to-floor distance, chest expansion, and modified Schober index increased (p=0.008, p<0.001, and p=0.031, respectively). The respiratory functional parameters showed a tendency towards improvement. AS patients already receiving biological therapy may benefit from additional targeted physiotherapy. Physical therapy may be of important additive value in AS patients being treated with biological. The exercise program presented here showed an improvement in functional parameters as well as spine and chest mobility, thereby enhancing the favorable effects of biological therapy.

[A case of radiation pneumonitis with eosinophilia in bronchoalveolar lavage fluid].

PubMed

Kawai, Seiko; Baba, Kenji; Tanaka, Hiroyuki; Takahashi, Daisuke; Yagi, Takeo; Hattori, Tsutomu; Etsuro, Yamaguchi

2008-01-01

A 78-year-old man was admitted to our hospital for irradiation therapy of non-resectable primary lung squamous cell carcinoma of the right middle lobe (T3N2M0). The Linac irradiation through opposing 2 gates (2Gy per day and 60Gy in total) was performed to the affected area including the metastatic right hilar and mediastinal lymphadenopathy. One week after completing the irradiation therapy, fever developed with infiltrates in the area from the right middle lobe to the right lower lobe, which did not necessarily coincide with the irradiated area. Antibiotic therapies were not effective. Both the serum LDH level and eosinophil count in the peripheral blood increased. Bronchoalveolar lavage was performed at the right B8, and differential cell counts of the lavage fluid were: macrophages, 17%; lymphocytes, 60%; neutrophils, 5%; and eosinophils, 18%. No significant organisms were obtained by culture of the lavage fluid. The %VC and DLCO/VA became lower than before the irradiation therapy. Thus, the patient was given a diagnosis of radiation pneumonitis. Treatment with 40mg/day oral prednisolone was commenced with a stepwise dose-reduction (5mg every two weeks) until reaching the maintenance dose of 15mg/day. The serum LDH level and blood eosinophil count recovered promptly to the normal range. The pulmonary infiltrates and the lung functions substantially improved. There have been few reports of radiation pneumonitis in which eosinophil counts increased in peripheral blood and bronchoalveolar lavage fluid after irradiation therapy. In the present case report, the possible mechanisms for the irradiation-induced eosinophilia were also reviewed.

Sublingual versus subcutaneous immunotherapy: patient adherence at a large German allergy center

PubMed Central

Lemberg, Marie-Luise; Berk, Till; Shah-Hosseini, Kija; Kasche, Elena-Manja; Mösges, Ralph

2017-01-01

Background Many placebo-controlled studies have demonstrated that allergen immunotherapy (AIT) is an effective therapy for treating allergies. Both commonly used routes, subcutaneous (SCIT) and sublingual immunotherapy (SLIT), require high patient adherence to be successful. In the literature, numbers describing adherence vary widely; this investigation compares these two routes of therapy directly. Methods All data were retrieved from the patient data management system of a center for dermatology, specific allergology, and environmental medicine in Germany. All 330 patients (aged 13–89 years) included in this study had commenced AIT between 2003 and 2011, thus allowing a full 3-year AIT cycle to be considered for each investigated patient. Results In this specific center, SCIT was prescribed to 62.7% and SLIT to 37.3% of all included patients. The total dropout rate of the whole patient cohort was 34.8%. Overall, SLIT patients showed a higher dropout rate (39.0%) than did SCIT patients (32.4%); however, the difference between these groups was not significant. Also, no significant difference between the overall dropout rates for men and for women was observed. A Kaplan–Meier curve of the patient collective showed a remarkably high dropout rate for the first year of therapy. Conclusion The analysis presented in this single-center study shows that most patients who discontinue AIT do so during the first year of therapy. Patients seem likely to finish the 3-year therapy cycle if they manage to adhere to treatment throughout the first year. Strategies for preventing nonadherence in AIT, therefore, need to be developed and standardized in future investigations. PMID:28115832

DRY CUPPING IN CHILDREN WITH FUNCTIONAL CONSTIPATION: A RANDOMIZED OPEN LABEL CLINICAL TRIAL

PubMed Central

Shahamat, Mahmoud; Daneshfard, Babak; Najib, Khadijeh-Sadat; Dehghani, Seyed Mohsen; Tafazoli, Vahid; Kasalaei, Afshineh

2016-01-01

Background: As a common disease in pediatrics, constipation poses a high burden to the community. In this study, we aimed to investigate the efficacy of dry cupping therapy (an Eastern traditional manipulative therapy) in children with functional constipation. Materials and Methods: One hundred and twenty children (4-18 years old) diagnosed as functional constipation according to ROME III criteria were assigned to receive a traditional dry cupping protocol on the abdominal wall for 8 minutes every other day or standard laxative therapy (Polyethylene glycol (PEG) 40% solution without electrolyte), 0.4 g/kg once daily) for 4 weeks, in an open label randomized controlled clinical trial using a parallel design with a 1:1 allocation ratio. Patients were evaluated prior to and following 2, 4, 8 and 12 weeks of the intervention commencement in terms of the ROME III criteria for functional constipation. Results: There were no significant differences between the two arms regarding demographic and clinical basic characteristics. After two weeks of the intervention, there was a significant better result in most of the items of ROME III criteria of patients in PEG group. In contrast, after four weeks of the intervention, the result was significantly better in the cupping group. There was no significant difference in the number of patients with constipation after 4 and 8 weeks of the follow-up period. Conclusion: This study showed that dry cupping of the abdominal wall, as a traditional manipulative therapy, can be as effective as standard laxative therapy in children with functional constipation. PMID:28852716

Should over-treatment of axial spondyloarthritis with biologics remain a concern after the issue of the new ASAS criteria? Data from REGISPONSERBIO (Spanish Register of Biological Therapy in Spondyloarthritides).

PubMed

Moreno, Mireia; Gratacós, Jordi; Navarro-Compán, Victoria; de Miguel, Eugenio; Font, Pilar; Clavaguera, Teresa; Linares, Luis Francisco; Joven, Beatriz; Juanola, Xavier

2018-05-08

To study whether disease status at treatment initiation has changed after the issue of the ASAS classification criteria. REGISPONSERBIO registers patients with axial spondyloarthritis (axSpA) on biological treatment since 2013. It includes patients starting biological treatment (incident) or already on biological therapies (prevalent). Patients in both groups were compared in terms of: age at disease onset and at treatment start, disease duration, gender, HLA-B27, body mass index (BMI), BASDAI, BASFI, C-reactive protein, ESR, metrological data, ASQoL, WAPAI, extra-articular manifestations, comorbidities, radiological study, type of biological treatment and concomitant treatments. 256 patients were included, of whom 174 (65%) were already on biologic therapy. Compared to incident patients, prevalent patients started treatment with longer disease duration (15 vs. 8.6 years; p<0.001), a higher proportion of them were men (83% vs. 67%; p=0.01), a smaller proportion of them showed non-radiographic axial spondylarthritis (nr-axSpA)(17% vs. 32%; p<0.01), and a higher proportion had HLAB27 (85% vs. 73%; p=0.02). There were no statistically significant differences in terms of disease activity, degree of disability, quality of life, or prevalence of extra-articular manifestations. Data suggest that, after the issue of the new classification criteria for SpA, biological therapy is being administered earlier than previously in SpA patients and in a higher proportion of patients with nr-axSpA. However, this change in prescribing profile, apparently, has not caused an over-treatment, as patients do not seem to have a lower disease burden than prior to the issue of the criteria.

Induction of potent NK cell-dependent anti-myeloma cytotoxic T cells in response to combined mapatumumab and bortezomib.

PubMed

Neeson, Paul J; Hsu, Andy K; Chen, Yin R; Halse, Heloise M; Loh, Joanna; Cordy, Reece; Fielding, Kate; Davis, Joanne; Noske, Josh; Davenport, Alex J; Lindqvist-Gigg, Camilla A; Humphreys, Robin; Tai, Tsin; Prince, H Miles; Trapani, Joseph A; Smyth, Mark J; Ritchie, David S

2015-09-01

There is increasing evidence that some cancer therapies can promote tumor immunogenicity to boost the endogenous antitumor immune response. In this study, we used the novel combination of agonistic anti-TRAIL-R1 antibody (mapatumumab, Mapa) with low dose bortezomib (LDB) for this purpose. The combination induced profound myeloma cell apoptosis, greatly enhanced the uptake of myeloma cell apoptotic bodies by dendritic cell (DC) and induced anti-myeloma cytotoxicity by both CD8 + T cells and NK cells. Cytotoxic lymphocyte expansion was detected within 24 h of commencing therapy and was maximized when myeloma-pulsed DC were co-treated with low dose bortezomib and mapatumumab (LDB+Mapa) in the presence of NK cells. This study shows that Mapa has two distinct but connected modes of action against multiple myeloma (MM). First, when combined with LDB, Mapa produced powerful myeloma cell apoptosis; secondly, it promoted DC priming and an NK cell-mediated expansion of anti-myeloma cytotoxic lymphocyte (CTL). Overall, this study indicates that Mapa can be used to drive potent anti-MM immune responses.

Induction of potent NK cell-dependent anti-myeloma cytotoxic T cells in response to combined mapatumumab and bortezomib

PubMed Central

Neeson, Paul J; Hsu, Andy K; Chen, Yin R; Halse, Heloise M; Loh, Joanna; Cordy, Reece; Fielding, Kate; Davis, Joanne; Noske, Josh; Davenport, Alex J; Lindqvist-Gigg, Camilla A; Humphreys, Robin; Tai, Tsin; Prince, H Miles; Trapani, Joseph A; Smyth, Mark J; Ritchie, David S

2015-01-01

There is increasing evidence that some cancer therapies can promote tumor immunogenicity to boost the endogenous antitumor immune response. In this study, we used the novel combination of agonistic anti-TRAIL-R1 antibody (mapatumumab, Mapa) with low dose bortezomib (LDB) for this purpose. The combination induced profound myeloma cell apoptosis, greatly enhanced the uptake of myeloma cell apoptotic bodies by dendritic cell (DC) and induced anti-myeloma cytotoxicity by both CD8+ T cells and NK cells. Cytotoxic lymphocyte expansion was detected within 24 h of commencing therapy and was maximized when myeloma-pulsed DC were co-treated with low dose bortezomib and mapatumumab (LDB+Mapa) in the presence of NK cells. This study shows that Mapa has two distinct but connected modes of action against multiple myeloma (MM). First, when combined with LDB, Mapa produced powerful myeloma cell apoptosis; secondly, it promoted DC priming and an NK cell-mediated expansion of anti-myeloma cytotoxic lymphocyte (CTL). Overall, this study indicates that Mapa can be used to drive potent anti-MM immune responses. PMID:26405606

Hip and groin pain in a cyclist resolved after performing a pelvic floor fascial mobilization.

PubMed

Navot, Sivan; Kalichman, Leonid

2016-07-01

Pelvic floor muscle assessment in situations of hip/groin pain in both male and female patients can be a key element in treatment success. We present herein, a 32 year old male professional cyclist, exhibiting right hip and groin pain during cycling and prolonged sitting. The pain commenced after the patient suffered a right hip severe contusion in 2013 causing a tear in the tensor fascia lata and gluteus medius muscle. The patient did not complain of pelvic floor dysfunctions. After receiving several series of conventional physical therapy for the hip/groin pain, the patient experienced partial pain relief and slight improvement of hip range of motion. His pelvic floor muscles and fascial involvement were subsequently assessed. Two sessions of Pelvic Floor Fascial Mobilization (PFFM) were performed and the patient fully recovered. The authors suggest that PFFM, a novel fascial-oriented manual therapy of the pelvic floor approach, can be used for both hip/groin and pelvic floor pain or dysfunction. Copyright © 2016 Elsevier Ltd. All rights reserved.

Successful Use of Tocilizumab in a Patient with Coexisting Rheumatoid Arthritis and Ulcerative Colitis

PubMed Central

Yalçın, Metin Devrim; Khan, Abdul; Piotrowicz, Andrzej

2016-01-01

Tocilizumab is an interleukin-6 receptor inhibitor licensed for moderate to severe rheumatoid arthritis (RA). We report a case of Tocilizumab monotherapy for severe active RA in a patient with coexisting ulcerative colitis (UC). The patient was intolerant to multiple disease-modifying drugs, so Tocilizumab monotherapy was commenced. We found clinical improvement in both RA and UC. There was no major adverse event after 2 years. Manufacturer advised caution in using Tocilizumab in patient with gastrointestinal ulceration due to an increased risk of bowel perforation. However, alternative treatments such as glucocorticoid and nonsteroidal anti-inflammatory drugs may carry a higher bowel perforation risk. The presence of gastrointestinal ulceration therefore should not constitute an absolute contraindication for Tocilizumab therapy. Future studies of registry data will inform clinician of the Tocilizumab-related risk of gastrointestinal toxicity in “real-life” settings. Contrary to previous case report, we found Tocilizumab therapy to have a positive effect on UC. Laboratory studies supported a role for interleukin-6 in the pathophysiology of UC. Further clinical trial to evaluate the therapeutic role of Tocilizumab in UC would be warranted. PMID:27818807

Successful Use of Tocilizumab in a Patient with Coexisting Rheumatoid Arthritis and Ulcerative Colitis.

PubMed

Szeto, Matthew Chak Hin; Yalçın, Metin Devrim; Khan, Abdul; Piotrowicz, Andrzej

2016-01-01

Tocilizumab is an interleukin-6 receptor inhibitor licensed for moderate to severe rheumatoid arthritis (RA). We report a case of Tocilizumab monotherapy for severe active RA in a patient with coexisting ulcerative colitis (UC). The patient was intolerant to multiple disease-modifying drugs, so Tocilizumab monotherapy was commenced. We found clinical improvement in both RA and UC. There was no major adverse event after 2 years. Manufacturer advised caution in using Tocilizumab in patient with gastrointestinal ulceration due to an increased risk of bowel perforation. However, alternative treatments such as glucocorticoid and nonsteroidal anti-inflammatory drugs may carry a higher bowel perforation risk. The presence of gastrointestinal ulceration therefore should not constitute an absolute contraindication for Tocilizumab therapy. Future studies of registry data will inform clinician of the Tocilizumab-related risk of gastrointestinal toxicity in "real-life" settings. Contrary to previous case report, we found Tocilizumab therapy to have a positive effect on UC. Laboratory studies supported a role for interleukin-6 in the pathophysiology of UC. Further clinical trial to evaluate the therapeutic role of Tocilizumab in UC would be warranted.

Predictors of Clinical Progression in HIV-1-Infected Adults Initiating Combination Antiretroviral Therapy with Advanced Disease in the Asia-Pacific Region: Results from the TREAT Asia HIV Observational Database

PubMed Central

Byakwaga, H.; Petoumenos, K.; Ananworanich, J.; Zhang, F.; Boyd, M. A.; Sirisanthana, T.; Li, P. C. K.; Lee, C.; Mean, C. V.; Saphonn, V.; Omar, S. F. S.; Pujari, S.; Phanuphak, P.; Lim, P. L.; Kumarasamy, N.; Chen, Y. M. A.; Merati, T. P.; Sungkanuparph, S.; Ditangco, R.; Oka, S.; Tau, G.; Zhou, J.; Law, M. G.; Emery, S.

2013-01-01

The majority of HIV-infected patients in developing countries commences combination antiretroviral therapy (cART) with advanced disease. We examined predictors of disease progression in patients initiating cART with CD4 count ≤200 cells/mm3 in the TREAT Asia HIV Observational Database. The main outcome measure was progression to either an AIDS-defining illness or death occurring 6 months after initiation of cART. We used survival analysis methods. A total of 1255 patients contributed 2696 person years of follow-up; 73 were diagnosed with AIDS and 9 died. The rate of progression to the combined end point was 3.0 per 100 person years. The factors significantly associated with a higher risk of disease progression were Indian ethnicity, infection through intravenous drug use, lower CD4 count, and hemoglobin ≤130 g/dL at 6 months. In conclusion, measurements of CD4 count and hemoglobin at month 6 may be useful for early identification of disease progression in resource-limited settings. PMID:23422741

17 CFR 240.14e-8 - Prohibited conduct in connection with pre-commencement communications.

Code of Federal Regulations, 2010 CFR

2010-04-01

... offer that has not yet been commenced, if the person: (a) Is making the announcement of a potential...; (b) Intends, directly or indirectly, for the announcement to manipulate the market price of the stock...

40 CFR 63.11194 - What is the affected source of this subpart?

Code of Federal Regulations, 2011 CFR

2011-07-01

... commence construction. (d) A boiler is a new affected source if you commenced fuel switching from natural gas to solid fossil fuel, biomass, or liquid fuel after June 4, 2010. (e) If you are an owner or...

40 CFR 63.11194 - What is the affected source of this subpart?

Code of Federal Regulations, 2012 CFR

2012-07-01

... commence construction. (d) A boiler is a new affected source if you commenced fuel switching from natural gas to solid fossil fuel, biomass, or liquid fuel after June 4, 2010. (e) If you are an owner or...

Management of Rheumatoid Arthritis Patients with Interstitial Lung Disease: Safety of Biological Antirheumatic Drugs and Assessment of Pulmonary Fibrosis

PubMed Central

Mori, Shunsuke

2015-01-01

Interstitial lung disease (ILD) is one of the major causes of morbidity and mortality of patients with rheumatoid arthritis (RA). Accompanying the increased number of reports on the development or exacerbation of ILD in RA patients following therapy with biological disease-modifying antirheumatic drugs (DMARDs), RA-associated ILD (RA-ILD) has aroused renewed interest. Although such cases have been reported mainly in association with the use of tumor necrosis factor inhibitors, the use of other biological DMARDs has also become a matter of concern. Nevertheless, it is difficult to establish a causative relationship between the use of biological DMARDs and either the development or exacerbation of ILD. Such pulmonary complications may occur in the natural course of RA regardless of the use of biological DMARDs. Since rheumatologists currently aim to achieve remission in RA patients, the administration of biological DMARDs is increasing, even for those with RA-ILD. However, there are no reliable, evidence-based guidelines for deciding whether biological DMARDs can be safely introduced and continued in RA-ILD patients. A standardized staging system for pulmonary conditions of RA-ILD patients is needed when making therapeutic decisions at baseline and monitoring during biological DMARD therapy. Based on the available information regarding the safety of biological DMARDs and the predictive factors for a worse prognosis, this review discusses candidate parameters for risk evaluation of ILD in RA patients who are scheduled to receive biological antirheumatic therapy. PMID:26401101

A multicenter report of biologic agents for the treatment of secondary amyloidosis in Turkish rheumatoid arthritis and ankylosing spondylitis patients.

PubMed

Pamuk, Ömer Nuri; Kalyoncu, Umut; Aksu, Kenan; Omma, Ahmet; Pehlivan, Yavuz; Çağatay, Yonca; Küçükşahin, Orhan; Dönmez, Salim; Çetin, Gözde Yıldırım; Mercan, Rıdvan; Bayındır, Özün; Çefle, Ayşe; Yıldız, Fatih; Balkarlı, Ayşe; Kılıç, Levent; Çakır, Necati; Kısacık, Bünyamin; Öksüz, Mustafa Ferhat; Çobankara, Veli; Onat, Ahmet Mesut; Sayarlıoğlu, Mehmet; Öztürk, Mehmet Akif; Pamuk, Gülsüm Emel; Akkoç, Nurullah

2016-07-01

In this multicenter, retrospective study, we evaluated the efficacy and safety of biologic therapies, including anti-TNFs, in secondary (AA) amyloidosis patients with ankylosing spondylitis (AS) and rheumatoid arthritis (RA). In addition, the frequency of secondary amyloidosis in RA and AS patients in a single center was estimated. Fifty-one AS (39M, 12F, mean age: 46.7) and 30 RA patients (11M, 19F, mean age: 51.7) with AA amyloidosis from 16 different centers in Turkey were included. Clinical and demographical features of patients were obtained from medical charts. A composite response index (CRI) to biologic therapy-based on creatinine level, proteinuria and disease activity-was used to evaluate the efficacy of treatment. The mean annual incidence of AA amyloidosis in RA and AS patients was 0.23 and 0.42/1000 patients/year, respectively. The point prevalence in RA and AS groups was 4.59 and 7.58/1000, respectively. In RA group with AA amyloidosis, effective response was obtained in 52.2 % of patients according to CRI. RA patients with RF positivity and more initial disease activity tended to have higher response rates to therapy (p values, 0.069 and 0.056). After biologic therapy (median 17 months), two RA patients died and two developed tuberculosis. In AS group, 45.7 % of patients fulfilled the criteria of good response according to CRI. AS patients with higher CRP levels at the time of AA diagnosis and at the beginning of anti-TNF therapy had higher response rates (p values, 0.011 and 0.017). During follow-up after anti-TNF therapy (median 38 months), one patient died and tuberculosis developed in two patients. Biologic therapy seems to be effective in at least half of RA and AS patients with AA amyloidosis. Tuberculosis was the most important safety concern.

Clinical application of cell, gene and tissue therapies in Spain.

PubMed

Gálvez-Martín, P; Ruiz, A; Clares, B

2018-05-01

Scientific and technical advances in the areas of biomedicine and regenerative medicine have enabled the development of new treatments known as "advanced therapies", which encompass cell therapy, genetics and tissue engineering. The biologic products that can be manufactured from these elements are classified from the standpoint of the Spanish Agency of Medication and Health Products in advanced drug therapies, blood products and transplants. This review seeks to provide scientific and administrative information for clinicians on the use of these biologic resources. Copyright © 2017 Elsevier España, S.L.U. and Sociedad Española de Medicina Interna (SEMI). All rights reserved.

Future Directions in Medical Physics

NASA Astrophysics Data System (ADS)

Jeraj, Robert

Medical Physics is a highly interdisciplinary field at the intersection between physics and medicine and biology. Medical Physics is aiming at development of novel applications of physical processes and techniques in various areas of medicine and biology. Medical Physics had and continues to have profound impact by developing improved imaging and treatment technologies, and helping to advance our understanding of the complexity of the disease. The general trend in medicine towards personalized therapy, and emphasis on accelerated translational research is having a profound impact on medical physics as well. In the traditional stronghold for medical physicists - radiation therapy - the new reality is shaping in the form of biologically conformal and combination therapies, as well as advanced particle therapy approaches, such as proton and ion therapies. Rapid increase in faster and more informative multi-modality medical imaging is bringing a wealth of information that is being complemented with data obtained from genomic profiling and other biomarkers. Novel data analysis and data mining approaches are proving grounds for employment of various artificial intelligence methods that will help further improving clinical decision making for optimization of various therapies as well as better understanding of the disease properties and disease evolution, ultimately leading to improved clinical outcomes.

Current approaches to the treatment of metastatic brain tumours

PubMed Central

Owonikoko, Taofeek K.; Arbiser, Jack; Zelnak, Amelia; Shu, Hui-Kuo G.; Shim, Hyunsuk; Robin, Adam M.; Kalkanis, Steven N.; Whitsett, Timothy G.; Salhia, Bodour; Tran, Nhan L.; Ryken, Timothy; Moore, Michael K.; Egan, Kathleen M.; Olson, Jeffrey J.

2014-01-01

Metastatic tumours involving the brain overshadow primary brain neoplasms in frequency and are an important complication in the overall management of many cancers. Importantly, advances are being made in understanding the molecular biology underlying the initial development and eventual proliferation of brain metastases. Surgery and radiation remain the cornerstones of the therapy for symptomatic lesions; however, image-based guidance is improving surgical technique to maximize the preservation of normal tissue, while more sophisticated approaches to radiation therapy are being used to minimize the long-standing concerns over the toxicity of whole-brain radiation protocols used in the past. Furthermore, the burgeoning knowledge of tumour biology has facilitated the entry of systemically administered therapies into the clinic. Responses to these targeted interventions have ranged from substantial toxicity with no control of disease to periods of useful tumour control with no decrement in performance status of the treated individual. This experience enables recognition of the limits of targeted therapy, but has also informed methods to optimize this approach. This Review focuses on the clinically relevant molecular biology of brain metastases, and summarizes the current applications of these data to imaging, surgery, radiation therapy, cytotoxic chemotherapy and targeted therapy. PMID:24569448

Biological Therapies for Cancer

MedlinePlus

... Partners & Collaborators Spotlight on Scientists Research Areas Cancer Biology Research Cancer Genomics Research Research on Causes of ... Collaborators Spotlight on Scientists NCI Research Areas Cancer Biology Cancer Genomics Causes of Cancer Diagnosis Prevention Screening & ...

47 CFR 22.946 - Service commencement and construction systems.

Code of Federal Regulations, 2010 CFR

2010-10-01

.... 22.946 Section 22.946 Telecommunication FEDERAL COMMUNICATIONS COMMISSION (CONTINUED) COMMON CARRIER SERVICES PUBLIC MOBILE SERVICES Cellular Radiotelephone Service § 22.946 Service commencement and... telephone network (PSTN) and must be providing service to mobile stations operated by its subscribers and...

40 CFR 60.540 - Applicability and designation of affected facilities.

Code of Federal Regulations, 2010 CFR

2010-07-01

... Performance for the Rubber Tire Manufacturing Industry § 60.540 Applicability and designation of affected... each of the following affected facilities in rubber tire manufacturing plants that commence... cementing operation in rubber tire manufacturing plants that commenced construction, modification, or...

Synthetic biology in mammalian cells: Next generation research tools and therapeutics

PubMed Central

Lienert, Florian; Lohmueller, Jason J; Garg, Abhishek; Silver, Pamela A

2014-01-01

Recent progress in DNA manipulation and gene circuit engineering has greatly improved our ability to programme and probe mammalian cell behaviour. These advances have led to a new generation of synthetic biology research tools and potential therapeutic applications. Programmable DNA-binding domains and RNA regulators are leading to unprecedented control of gene expression and elucidation of gene function. Rebuilding complex biological circuits such as T cell receptor signalling in isolation from their natural context has deepened our understanding of network motifs and signalling pathways. Synthetic biology is also leading to innovative therapeutic interventions based on cell-based therapies, protein drugs, vaccines and gene therapies. PMID:24434884

SU-F-T-193: Evaluation of a GPU-Based Fast Monte Carlo Code for Proton Therapy Biological Optimization

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

Taleei, R; Qin, N; Jiang, S

2016-06-15

Purpose: Biological treatment plan optimization is of great interest for proton therapy. It requires extensive Monte Carlo (MC) simulations to compute physical dose and biological quantities. Recently, a gPMC package was developed for rapid MC dose calculations on a GPU platform. This work investigated its suitability for proton therapy biological optimization in terms of accuracy and efficiency. Methods: We performed simulations of a proton pencil beam with energies of 75, 150 and 225 MeV in a homogeneous water phantom using gPMC and FLUKA. Physical dose and energy spectra for each ion type on the central beam axis were scored. Relativemore » Biological Effectiveness (RBE) was calculated using repair-misrepair-fixation model. Microdosimetry calculations were performed using Monte Carlo Damage Simulation (MCDS). Results: Ranges computed by the two codes agreed within 1 mm. Physical dose difference was less than 2.5 % at the Bragg peak. RBE-weighted dose agreed within 5 % at the Bragg peak. Differences in microdosimetric quantities such as dose average lineal energy transfer and specific energy were < 10%. The simulation time per source particle with FLUKA was 0.0018 sec, while gPMC was ∼ 600 times faster. Conclusion: Physical dose computed by FLUKA and gPMC were in a good agreement. The RBE differences along the central axis were small, and RBE-weighted dose difference was found to be acceptable. The combined accuracy and efficiency makes gPMC suitable for proton therapy biological optimization.« less

Immunogenicity of biologic therapies: causes and consequences.

PubMed

Boehncke, Wolf-Henning; Brembilla, Nicolo Costantino

2018-04-25

Antibodies or fusion proteins termed biologics allow the targeted therapy of diseases. Many of these agents have proven superior efficacy and safety to conventional therapies, and subsequently revolutionized the management of numerous chronic diseases. Repetitive administration of these protein-based therapeutics to immunocompetent patients elicit immune responses in the form of Anti Drug Antibodies (ADAs), which in turn impact their pharmacological properties and may trigger adverse events. Areas covered: Structural characteristics determining the immunogenicity of biologics are reviewed along with strategies to minimize it. Next, the different types of treatment-emerging ADAs, their potential clinical implications, and assays to detect them are addressed. Emphasis is put on the review of data on the immunogenicity of different types of biologics across numerous indications. Finally, practical considerations are discussed on how to manage patients with issues around the immunogenicity of their biologic treatment. Expert commentary: Immunogenicity is a clinically relevant criterion when selecting a biologic. Besides intrinsic properties of the agent (namely its structure), its respective mode of action, dosing regimen, comedication, and the indication treated must be considered. ADA detection assays need to be standardized to improve comparability of available data and to allow clinical decision-making.

Treatment of very early rheumatoid arthritis with symptomatic therapy, disease-modifying antirheumatic drugs, or biologic agents: a cost-effectiveness analysis.

PubMed

Finckh, Axel; Bansback, Nick; Marra, Carlo A; Anis, Aslam H; Michaud, Kaleb; Lubin, Stanley; White, Marc; Sizto, Sonia; Liang, Matthew H

2009-11-03

Long-term control or remission of rheumatoid arthritis (RA) may be possible with very early treatment. However, no optimal first therapeutic strategy has been determined. To assess the potential cost-effectiveness of major therapeutic strategies for very early RA. Decision analytic model with probabilistic sensitivity analyses. Published data, the National Data Bank for Rheumatic Diseases, and actual 2007 hospital costs. U.S. adults with very early RA (symptom duration

Changes in Psychological Parameters in Patients with Tension-type Headache Following Massage Therapy: A Pilot Study

PubMed Central

Moraska, Albert; Chandler, Clint

2009-01-01

Investigations into complementary and alternative medicine (CAM) approaches to address stress, depression, and anxiety of those experiencing chronic pain are rare. The objective of this pilot study was to assess the value of a structured massage therapy program, with a focus on myofascial trigger points, on psychological measures associated with tension-type headache. Participants were enrolled in an open-label trial using a baseline control with four 3-week phases: baseline, massage (two 3-week periods) and a follow-up phase. Eighteen subjects with episodic or chronic tension-type headache were enrolled and evaluated at 3-week intervals using the State-Trait Anxiety Inventory, Beck Depression Inventory, and the Perceived Stress Scale. The Daily Stress Inventory was administered over 7-day periods during baseline and the final week of massage. Twice weekly, 45-minute massage therapy sessions commenced following the baseline phase and continued for 6 weeks. A significant improvement in all psychological measures was detected over the timeframe of the study. Post hoc evaluation indicated improvement over baseline for depression and trait anxiety following 6 weeks of massage, but not 3 weeks. A reduction in the number of events deemed stressful as well as their respective impact was detected. This pilot study provides evidence for reduction of affective distress in a chronic pain population, suggesting the need for more rigorously controlled studies using massage therapy to address psychological measures associated with TTH. PMID:20046550

Evidence-based Peer Review for Radiation Therapy - Updated Review of the Literature with a Focus on Tumour Subsite and Treatment Modality.

PubMed

Huo, M; Gorayski, P; Poulsen, M; Thompson, K; Pinkham, M B

2017-10-01

Technological advances in radiation therapy permit steep dose gradients from the target to spare normal tissue, but increase the risk of geographic miss. Suboptimal target delineation adversely affects clinical outcomes. Prospective peer review is a method for quality assurance of oncologists' radiotherapy plans. Published surveys suggest it is widely implemented. However, it may not be feasible to review every case before commencement of radiation therapy in all departments. The rate of plan changes following peer review of cases without a specific subsite or modality is typically around 10%. Stereotactic body radiation therapy, head and neck, gynaecological, gastrointestinal, haematological and lung cases are associated with higher rates of change of around 25%. These cases could thus be prioritised for peer review. Other factors may limit peer review efficacy including organisational culture, time constraints and the physical environment in which sessions are held. Recommendations for peer review endorsed by the American Society for Radiation Oncology were made available in 2013, but a number of relevant studies have been published since. Here we review and update the literature, and provide an updated suggestion for the implementation of peer review to serve as an adjunct to published guidelines. This may help practitioners evaluate their current processes and maximise the utility and effectiveness of peer review sessions. Copyright © 2017 The Royal College of Radiologists. Published by Elsevier Ltd. All rights reserved.

Startup of the Kling Center for Proton Therapy

NASA Astrophysics Data System (ADS)

Bloch, C.; Hill, P. M.; Chen, K. L.; Saito, A.; Klein, E. E.

2013-04-01

In November of 2011 Mevion Medical Systems (formerly Still River Systems) delivered the Mevion S250 proton therapy system accelerator to the Kling Center for Proton Therapy at the Siteman Cancer Center in Saint Louis. The Mevion system is unique, with an in-room gantry-mounted superconducting synchrocyclotron. This is the first true single-room proton therapy system and it has a greatly reduced size as well as cost. A month after its arrival, the installation was complete and the superconducting magnet was ramped up to full current (˜2000 amperes). In March of 2012, full energy beam (250 MeV) was extracted and radiation surveys were performed to verify the shielding. Once that was shown to be sufficient, Mevion began fine-tuning the system to provide a highly isocentric beam from the 50 ton system. In June of 2012 the field-shaping system (energy degraders, contoured scatterers and range modulators) were installed and measurements of the clinical beam properties commenced. Monte Carlo simulations (MCNPX) have been performed for the system and validated with beam measurements done at the factory. These simulations have been used for a preliminary commissioning of our treatment planning system. Additionally, predictions of the neutron background have been made and validated with factory measurements. Final commissioning of the treatment planning system and verification of the neutron background will be accomplished with measurements made later in 2012. Based on current progress, patient treatments are scheduled to begin in late 2012. Beam and radiation background data will be presented.

Clinical translation and regulatory aspects of CAR/TCR-based adoptive cell therapies-the German Cancer Consortium approach.

PubMed

Krackhardt, Angela M; Anliker, Brigitte; Hildebrandt, Martin; Bachmann, Michael; Eichmüller, Stefan B; Nettelbeck, Dirk M; Renner, Matthias; Uharek, Lutz; Willimsky, Gerald; Schmitt, Michael; Wels, Winfried S; Schüssler-Lenz, Martina

2018-04-01

Adoptive transfer of T cells genetically modified by TCRs or CARs represents a highly attractive novel therapeutic strategy to treat malignant diseases. Various approaches for the development of such gene therapy medicinal products (GTMPs) have been initiated by scientists in recent years. To date, however, the number of clinical trials commenced in Germany and Europe is still low. Several hurdles may contribute to the delay in clinical translation of these therapeutic innovations including the significant complexity of manufacture and non-clinical testing of these novel medicinal products, the limited knowledge about the intricate regulatory requirements of the academic developers as well as limitations of funds for clinical testing. A suitable good manufacturing practice (GMP) environment is a key prerequisite and platform for the development, validation, and manufacture of such cell-based therapies, but may also represent a bottleneck for clinical translation. The German Cancer Consortium (DKTK) and the Paul-Ehrlich-Institut (PEI) have initiated joint efforts of researchers and regulators to facilitate and advance early phase, academia-driven clinical trials. Starting with a workshop held in 2016, stakeholders from academia and regulatory authorities in Germany have entered into continuing discussions on a diversity of scientific, manufacturing, and regulatory aspects, as well as the benefits and risks of clinical application of CAR/TCR-based cell therapies. This review summarizes the current state of discussions of this cooperative approach providing a basis for further policy-making and suitable modification of processes.

Sanfilippo syndrome: causes, consequences, and treatments

PubMed Central

Fedele, Anthony O

2015-01-01

Sanfilippo syndrome, or mucopolysaccharidosis (MPS) type III, refers to one of five autosomal recessive, neurodegenerative lysosomal storage disorders (MPS IIIA to MPS IIIE) whose symptoms are caused by the deficiency of enzymes involved exclusively in heparan sulfate degradation. The primary characteristic of MPS III is the degeneration of the central nervous system, resulting in mental retardation and hyperactivity, typically commencing during childhood. The significance of the order of events leading from heparan sulfate accumulation through to downstream changes in the levels of biomolecules within the cell and ultimately the (predominantly neuropathological) clinical symptoms is not well understood. The genes whose deficiencies cause the MPS III subtypes have been identified, and their gene products, as well as a selection of disease-causing mutations, have been characterized to varying degrees with respect to both frequency and direct biochemical consequences. A number of genetic and biochemical diagnostic methods have been developed and adopted by diagnostic laboratories. However, there is no effective therapy available for any form of MPS III, with treatment currently limited to clinical management of neurological symptoms. The availability of animal models for all forms of MPS III, whether spontaneous or generated via gene targeting, has contributed to improved understanding of the MPS III subtypes, and has provided and will deliver invaluable tools to appraise emerging therapies. Indeed, clinical trials to evaluate intrathecally-delivered enzyme replacement therapy in MPS IIIA patients, and gene therapy for MPS IIIA and MPS IIIB patients are planned or underway. PMID:26648750

Navigating the evolving paradigms in the diagnosis and treatment of myeloproliferative disorders.

PubMed

Mesa, Ruben A

2007-01-01

The diagnosis and management of the BCR-ABL-negative myeloproliferative disorders (MPDs) of polycythemia vera (PV), essential thrombocythemia (ET), and primary myelofibrosis (PMF) are at an explosive crossroads of scientific investigation and evolving paradigms since the discovery of the tyrosine kinase-activating JAK2V617F mutation in 2005. Additional discovery of relevant molecular lesions (JAK2 exon 12 mutations and c-MplW515L/K) have only further enriched our understanding of MPD pathogenesis. The improved diagnostic certainty these molecular markers provide have resulted in the modification, and simplification, of the World Health Organization (WHO) diagnostic algorithms for MPDs. Despite these scientific advances, however, the initial management of MPDs continues to rely upon a risk-based strategy to minimize the risk of vascular events with control of erythrocytosis, targeted antiplatelet therapy, and risk-based myelosuppressive therapy. No current medical therapy has altered the natural trend of the MPDs to lead to overt severe myelofibrosis or acute leukemia. Investigations into targeted therapies for MPDs are proceeding at a brisk pace with agents aimed at immunomodulation, decreasing marrow stromal reaction to the aberrant clone, DNA hypomethylation, or the inhibition of tyrosine kinases. Specific inhibition of JAK2 itself appears promising by in vitro investigations, and clinical trials with multiple agents are planned to commence enrollment in 2007. The potential impact of JAK2 inhibitors on the manifestations of the MPDs is unclear, but is awaited with great interest.

Endocrine Society of Australia position statement on male hypogonadism (part 2): treatment and therapeutic considerations.

PubMed

Yeap, Bu B; Grossmann, Mathis; McLachlan, Robert I; Handelsman, David J; Wittert, Gary A; Conway, Ann J; Stuckey, Bronwyn Ga; Lording, Douglas W; Allan, Carolyn A; Zajac, Jeffrey D; Burger, Henry G

2016-09-05

Part 1 of this position statement dealt with the assessment of male hypogonadism, including the indications for testosterone therapy. This article, Part 2, focuses on treatment and therapeutic considerations for male hypogonadism and identifies key questions for future research. Key points and recommendations are:Excess cardiovascular events have been reported in some but not all studies of older men without pathological hypogonadism who were given testosterone treatment. Additional studies are needed to clarify whether testosterone therapy influences cardiovascular risk.Testosterone is the native hormone that should be replaced in men being treated for pathological hypogonadism. Convenient and cost-effective treatment modalities include depot intramuscular injection and transdermal administration (gel, cream or liquid formulations).Monitoring of testosterone therapy is recommended for efficacy and safety, focusing on ameliorating symptoms, restoring virilisation, avoiding polycythaemia and maintaining or improving bone mineral density.Treatment aims to relieve an individual's symptoms and signs of androgen deficiency by administering standard doses and maintaining circulating testosterone levels within the reference interval for eugonadal men.Evaluation for cardiovascular disease and prostate cancer risks should be undertaken as appropriate for eugonadal men of similar age. Nevertheless, when there is a reasonable possibility of substantive pre-existing prostate disease, digital rectal examination and prostate-specific antigen testing should be performed before commencing testosterone treatment.Changes in management as result of the position statement: Treatment aims to relieve symptoms and signs of androgen deficiency, using convenient and effective formulations of testosterone. Therapy should be monitored for efficacy and safety.

Treatment of juvenile idiopathic arthritis-associated uveitis: challenges and update.

PubMed

Rabinovich, C Egla

2011-09-01

To update the current understanding of the risk factors for poor outcomes in juvenile idiopathic arthritis-related uveitis. In addition, current therapies, both traditional and biological, are reviewed. Male sex, independent of age or antinuclear antibody status, is associated with increased ocular morbidity. Having anterior chamber inflammation on first exam increases the risk of developing vision-threatening eye complications. Presence of one complication increases the risk of developing another. Risk of cataract development associated with topical glucocorticoid use is better defined. Longer duration of remission on therapy has been found to decrease the risk of disease flare after discontinuation of methotrexate. Recent studies of both nonbiological and biological therapies for arthritis-related uveitis are discussed. With a better understanding of risk factors associated with the ocular morbidity of uveitis associated with juvenile idiopathic arthritis, aggressive therapies can be targeted for improved visual outcomes. Alternative treatments to avoid long-term corticosteroid use include the use of antimetabolites and biological therapies. More prospective comparator studies and/or use of multicenter databases are needed to better understand best treatments.

Emerging evidence for CHFR as a cancer biomarker: from tumor biology to precision medicine.

PubMed

Derks, Sarah; Cleven, Arjen H G; Melotte, Veerle; Smits, Kim M; Brandes, Johann C; Azad, Nilofer; van Criekinge, Wim; de Bruïne, Adriaan P; Herman, James G; van Engeland, Manon

2014-03-01

Novel insights in the biology of cancer have switched the paradigm of a "one-size-fits-all" cancer treatment to an individualized biology-driven treatment approach. In recent years, a diversity of biomarkers and targeted therapies has been discovered. Although these examples accentuate the promise of personalized cancer treatment, for most cancers and cancer subgroups no biomarkers and effective targeted therapy are available. The great majority of patients still receive unselected standard therapies with no use of their individual molecular characteristics. Better knowledge about the underlying tumor biology will lead the way toward personalized cancer treatment. In this review, we summarize the evidence for a promising cancer biomarker: checkpoint with forkhead and ring finger domains (CHFR). CHFR is a mitotic checkpoint and tumor suppressor gene, which is inactivated in a diverse group of solid malignancies, mostly by promoter CpG island methylation. CHFR inactivation has shown to be an indicator of poor prognosis and sensitivity to taxane-based chemotherapy. Here we summarize the current knowledge of altered CHFR expression in cancer, the impact on tumor biology and implications for personalized cancer treatment.

38 CFR 21.7131 - Commencing dates.

Code of Federal Regulations, 2012 CFR

2012-07-01

...) VOCATIONAL REHABILITATION AND EDUCATION All Volunteer Force Educational Assistance Program (Montgomery GI... standard college degree. (1) When the student enrolls in a course offered by independent study, the commencing date of the award or increased award of educational assistance will be the date the student began...

38 CFR 21.7131 - Commencing dates.

Code of Federal Regulations, 2013 CFR

2013-07-01

...) VOCATIONAL REHABILITATION AND EDUCATION All Volunteer Force Educational Assistance Program (Montgomery GI... standard college degree. (1) When the student enrolls in a course offered by independent study, the commencing date of the award or increased award of educational assistance will be the date the student began...

38 CFR 21.7131 - Commencing dates.

Code of Federal Regulations, 2011 CFR

2011-07-01

...) VOCATIONAL REHABILITATION AND EDUCATION All Volunteer Force Educational Assistance Program (Montgomery GI... standard college degree. (1) When the student enrolls in a course offered by independent study, the commencing date of the award or increased award of educational assistance will be the date the student began...

38 CFR 21.7131 - Commencing dates.

Code of Federal Regulations, 2014 CFR

2014-07-01

...) VOCATIONAL REHABILITATION AND EDUCATION All Volunteer Force Educational Assistance Program (Montgomery GI... standard college degree. (1) When the student enrolls in a course offered by independent study, the commencing date of the award or increased award of educational assistance will be the date the student began...

12 CFR 252.133 - Applicability.

Code of Federal Regulations, 2014 CFR

2014-01-01

... (CONTINUED) ENHANCED PRUDENTIAL STANDARDS (REGULATION YY) Supervisory Stress Test Requirements for Covered... requirements of this subpart beginning with the stress test cycle that commences on October 1, 2013, unless... stress test cycle that commences on November 15, 2012, unless that time is extended by the Board in...

12 CFR 252.143 - Applicability.

Code of Federal Regulations, 2014 CFR

2014-01-01

... (CONTINUED) ENHANCED PRUDENTIAL STANDARDS (REGULATION YY) Company-Run Stress Test Requirements for Covered... requirements of this subpart beginning with the stress test cycle commencing on October 1, 2013, unless that... stress test cycle commencing on November 15, 2012, unless that time is extended by the Board in writing...

12 CFR 252.133 - Applicability.

Code of Federal Regulations, 2013 CFR

2013-01-01

... (CONTINUED) ENHANCED PRUDENTIAL STANDARDS (REGULATION YY) Supervisory Stress Test Requirements for Covered... requirements of this subpart beginning with the stress test cycle that commences on October 1, 2013, unless... stress test cycle that commences on November 15, 2012, unless that time is extended by the Board in...

12 CFR 252.143 - Applicability.

Code of Federal Regulations, 2013 CFR

2013-01-01

... (CONTINUED) ENHANCED PRUDENTIAL STANDARDS (REGULATION YY) Company-Run Stress Test Requirements for Covered... requirements of this subpart beginning with the stress test cycle commencing on October 1, 2013, unless that... stress test cycle commencing on November 15, 2012, unless that time is extended by the Board in writing...

15 CFR 705.3 - Commencing an investigation.

Code of Federal Regulations, 2010 CFR

2010-01-01

...) BUREAU OF INDUSTRY AND SECURITY, DEPARTMENT OF COMMERCE NATIONAL SECURITY INDUSTRIAL BASE REGULATIONS EFFECT OF IMPORTED ARTICLES ON THE NATIONAL SECURITY § 705.3 Commencing an investigation. (a) Upon... the effect on the national security of the imports of any article. (b) The Secretary shall immediately...

Commencement Bay Study. Volume IV. Invertebrates.

DTIC Science & Technology

1981-12-31

and anemones were abundant. Several species of starfish were observed here. The intertidal area at Transect 5, on Ruston Way at Commencement Park...of these forms (sea stars, anemones , gastropods) was observed in nearshore habitats at Nisqually Delta (Wissemann et al. 1977, Houghton and Kyte 1978

31 CFR 800.505 - Commencement of investigation.

Code of Federal Regulations, 2010 CFR

2010-07-01

... 31 Money and Finance: Treasury 3 2010-07-01 2010-07-01 false Commencement of investigation. 800.505 Section 800.505 Money and Finance: Treasury Regulations Relating to Money and Finance (Continued) OFFICE OF INVESTMENT SECURITY, DEPARTMENT OF THE TREASURY REGULATIONS PERTAINING TO MERGERS, ACQUISITIONS...

Role of sudden commencements in triggering magnetospheric substorms. M.S. Thesis; [based on ATS 1 data

NASA Technical Reports Server (NTRS)

Newell, R. E.

1974-01-01

Sudden commencement events are examined in terms of available auroral-zone and low-latitude magnetic field, data, interplanetary plasma and magnetic field data, and magnetospheric electron flux and magnetic field data from the geostationary satellite ATS 1.

5. 1859 sketch of the hospital, before construction commenced in ...

Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

5. 1859 sketch of the hospital, before construction commenced in 1860. Photocopied from Report of the Board of Managers of the Hospital of the Protestant Episcopal Church, 1859. - Hospital of Protestant Episcopal Church in Philadelphia, Front Street & Lehigh Avenue, Philadelphia, Philadelphia County, PA

Finding a Life Worth Living: Meaning in Life and Graduation from College.

PubMed

Wilt, Joshua; Bleidorn, Wiebke; Revelle, William

2016-01-01

Graduation from college is an important milestone for young adults, marked by mixed emotions and poignancy, and therefore is an especially salient context for studying meaning in life. The present research used experience-sampling methodology to examine the antecedents and consequences of students' experience of meaning in life over the course of graduation. Participants were 74 graduating students who provided a total of 538 reports over the span of three days, including commencement day. Increased levels of state meaning in life during the days around commencement were linked to spending time with people in general and with family in particular, as well as thinking about one's years in college. Thinking about one's years in college mediated the effects of present company on state meaning in life. Graduates who experienced higher levels of state meaning in life during the days around their commencement ceremony had higher trait levels of meaning in life one week following commencement. We discuss how making meaning of a poignant experience has implications for healthy psychological development.

2012 Brazilian Society of Rheumatology Consensus for the treatment of rheumatoid arthritis.

PubMed

da Mota, Licia Maria Henrique; Cruz, Boris Afonso; Brenol, Claiton Viegas; Pereira, Ivanio Alves; Rezende-Fronza, Lucila Stange; Bertolo, Manoel Barros; de Freitas, Max Victor Carioca; da Silva, Nilzio Antonio; Louzada-Júnior, Paulo; Giorgi, Rina Dalva Neubarth; Lima, Rodrigo Aires Corrêa; da Rocha Castelar Pinheiro, Geraldo

2012-01-01

To elaborate recommendations for the treatment of rheumatoid arthritis in Brazil. Literature review with articles' selection based on evidence and the expert opinion of the Rheumatoid Arthritis Committee of the Brazilian Society of Rheumatology. 1) The therapeutic decision should be shared with the patient; 2) immediately after the diagnosis, a disease-modifying antirheumatic drug (DMARD) should be prescribed, and the treatment adjusted to achieve remission; 3) treatment should be conducted by a rheumatologist; 4) the initial treatment includes synthetic DMARDs; 5) methotrexate is the drug of choice; 6) patients who fail to respond after two schedules of synthetic DMARDs should be assessed for the use of biologic DMARDs; 7) exceptionally, biologic DMARDs can be considered earlier; 8) anti-TNF agents are preferentially recommended as the initial biologic therapy; 9) after therapeutic failure of a first biologic DMARD, other biologics can be used; 10) cyclophosphamide and azathioprine can be used in severe extra-articular manifestations; 11) oral corticoid is recommended at low doses and for short periods of time; 12) non-steroidal anti-inflammatory drugs should always be prescribed in association with a DMARD; 13) clinical assessments should be performed on a monthly basis at the beginning of treatment; 14) physical therapy, rehabilitation, and occupational therapy are indicated; 15) surgical treatment is recommended to correct sequelae; 16) alternative therapy does not replace traditional therapy; 17) family planning is recommended; 18) the active search and management of comorbidities are recommended; 19) the patient's vaccination status should be recorded and updated; 20) endemic-epidemic transmissible diseases should be investigated and treated.

Systematic review: treatment pattern and clinical effectiveness and safety of pharmaceutical therapies for Crohn’s disease in Europe

PubMed Central

Lelli, Filippo; Nuhoho, Solomon; Lee, Xin Ying; Xu, Weiwei

2016-01-01

Background Although many clinical trials have been conducted in treatments of Crohn’s disease (CD), whether the trial results were representative of daily practice needs to be supported by studies conducted in real-world settings. Aim This study aims to identify how CD is treated and what are the clinical effectiveness and safety of the pharmaceutical therapies of CD in real-world settings. Methods A systematic literature review was conducted based on Medline®, Embase®, and Cochrane. All publications were assessed for title/abstract and full-text according to a predefined study protocol. Data were extracted and reported. Results A total of 1,998 publications were identified. Fifty studies including six publications reporting treatment pattern and 44 studies reporting clinical effectiveness and safety of pharmaceutical therapies in CD management in Europe were included. 5-Aminosalicylic acid and corticosteroids were reported to be used among 14%–74% of CD patients. Immunomodulators were used by 14%–25% and 29%–31% of CD patients as an initial and follow-up treatment, respectively. Biological therapies were used by 25%–33% of CD patients. A trend toward an increasing use of immunomodulators and biological therapies in Europe has been reported in recent years. Approximately 50% of patients achieved remission on immunomodulator or biologic treatment, although a relapse rate of up to 23% has been reported. Conclusion There is a trend of treatment shift to immunomodulators and biologics in CD management. Clinical effectiveness of immunomodulators and biologics has been demonstrated, though with a lack of sustainability of the effectiveness. PMID:27785086

Systematic review: treatment pattern and clinical effectiveness and safety of pharmaceutical therapies for Crohn's disease in Europe.

PubMed

Lelli, Filippo; Nuhoho, Solomon; Lee, Xin Ying; Xu, Weiwei

2016-01-01

Although many clinical trials have been conducted in treatments of Crohn's disease (CD), whether the trial results were representative of daily practice needs to be supported by studies conducted in real-world settings. This study aims to identify how CD is treated and what are the clinical effectiveness and safety of the pharmaceutical therapies of CD in real-world settings. A systematic literature review was conducted based on Medline ® , Embase ® , and Cochrane. All publications were assessed for title/abstract and full-text according to a predefined study protocol. Data were extracted and reported. A total of 1,998 publications were identified. Fifty studies including six publications reporting treatment pattern and 44 studies reporting clinical effectiveness and safety of pharmaceutical therapies in CD management in Europe were included. 5-Aminosalicylic acid and corticosteroids were reported to be used among 14%-74% of CD patients. Immunomodulators were used by 14%-25% and 29%-31% of CD patients as an initial and follow-up treatment, respectively. Biological therapies were used by 25%-33% of CD patients. A trend toward an increasing use of immunomodulators and biological therapies in Europe has been reported in recent years. Approximately 50% of patients achieved remission on immunomodulator or biologic treatment, although a relapse rate of up to 23% has been reported. There is a trend of treatment shift to immunomodulators and biologics in CD management. Clinical effectiveness of immunomodulators and biologics has been demonstrated, though with a lack of sustainability of the effectiveness.

Reuma.pt - the rheumatic diseases portuguese register.

PubMed

Canhão, H; Faustino, A; Martins, F; Fonseca, J E

2011-01-01

Since June 2008, Portuguese rheumatologists have been collecting on a routine basis, data into the nationwide Reuma.pt, the Rheumatic Diseases Portuguese Register from the Portuguese Society of Rheumatology (SPR), which includes rheumatic patients (rheumatoid arthritis - RA, ankylosing spondylitis - AS, psoriatic arthritis - PsA and juvenile idiopathic arthritis - JIA) receiving biological therapies or patients receiving synthetic disease modifying anti-rheumatic drugs (DMARDs). The aim of this publication is to describe the structure of Reuma.pt and the population registered since June 2008. Demographic and anthropometric data, life style habits, work status, co-morbidities, disease activity and functional assessment scores, previous and current therapies, adverse events codified by the Medical Dictionary for Regulatory Activities (MedDRA), reasons for discontinuation and laboratory measurements are registered at each visit. The platform is based on a structured electronic medical record linked to a SQL Server database. All Rheumatology Departments assigned to the Portuguese National Health Service (n=21), 2 Military Hospitals (Lisboa and Porto), 1 public-private Institution and 6 private centers adhered to the Register. Until now, 18 centers have entered data into Reuma.pt. By January 2011, 3438 patients and 16130 visits had been registered. 2162 (63%) were RA patients, 700 of them treated with biological agents and 1462 with synthetic DMARDs. From the 515 (15%) AS patients, 297 were medicated with biological and 218 with non-biological therapies. 293 (8%) were PsA patients, 151 treated with biological drugs and 142 with other treatment strategies. 368 (11%) had the diagnosis of JIA, 68 were under biological treatment and 300 were managed with other treatment options. The register also includes 100 (3%) patients with other rheumatic diseases, submitted to treatments that required hospital day care infusions including 18 exposed to biological therapies. Registers are crucial to ensure correct clinical use, adequate assessment of post-marketing biological therapies' efficacy and safety, thus contributing for a better cost-benefit ratio. Reuma.pt, is a powerful and accurate tool to answer to these unmet needs. It presents a national coverage of the rheumatology centers and constitutes an invaluable resource for scientific research and to improve rheumatic patients care.

Immunopathogenesis of inflammatory bowel disease and mechanisms of biological therapies.

PubMed

Ahluwalia, Bani; Moraes, Luiza; Magnusson, Maria K; Öhman, Lena

2018-04-01

Inflammatory bowel disease (IBD) is a chronic inflammatory disorder of the gastrointestinal tract with a multifactorial pathophysiology. Full comprehension of IBD pathology is still out of reach and, therefore, treatment is far from ideal. Nevertheless, components involved in IBD pathogenesis including environmental, genetic, microbial, and immunological factors are continuously being investigated and the improved knowledge contributes to the development of new therapies. In this article we review the aspects of the immunopathogenesis of IBD, with focus on mucosal immunity, and discuss mechanisms of action for current and emerging biological therapies.

Postextraction Alveolar Ridge Preservation: Biological Basis and Treatments

PubMed Central

Pagni, Giorgio; Pellegrini, Gaia; Giannobile, William V.; Rasperini, Giulio

2012-01-01

Following tooth extraction, the alveolar ridge undergoes an inevitable remodeling process that influences implant therapy of the edentulous area. Socket grafting is a commonly adopted therapy for the preservation of alveolar bone structures in combination or not with immediate implant placement although the biological bases lying behind this treatment modality are not fully understood and often misinterpreted. This review is intended to clarify the literature support to socket grafting in order to provide practitioners with valid tools to make a conscious decision of when and why to recommend this therapy. PMID:22737169

Patient Satisfaction with Treatments for Moderate-to-Severe Plaque Psoriasis in Clinical Practice

PubMed Central

Takeshita, J.; Krueger, G.G.; Robertson, A.D.; Troxel, A.B.; Shin, D.B.; Van Voorhees, A.S.; Gelfand, J.M.

2014-01-01

Background Treatment satisfaction among moderate-to-severe psoriasis patients has not been studied and compared across treatments using a validated instrument. Objectives To assess patient-reported satisfaction with systemic and phototherapy treatments for moderate-to-severe psoriasis in clinical practice and to correlate satisfaction with disease severity and quality of life measures. Methods Cross-sectional study of 1182 patients with moderate-to-severe psoriasis in the Dermatology Clinical Effectiveness Research Network in the United States. Patients receiving either topical therapies only; monotherapy with oral systemic therapies, biologics, or narrowband ultraviolet B phototherapy; or combination therapy with biologics and methotrexate completed the Treatment Satisfaction Questionnaire for Medication version II. Results Median unadjusted Overall Satisfaction scores were highest for patients receiving biologic monotherapies, biologic-methotrexate combinations, or phototherapy (83.3); scores were lowest for those receiving topical therapies only or acitretin (66.7). In fully adjusted models, compared to patients receiving methotrexate monotherapy, those receiving adalimumab, etanercept, ustekinumab, phototherapy, or adalimumab with methotrexate had significantly higher median Overall Satisfaction scores by 7.2 to 8.3 points, while those receiving topical therapies only had significantly lower Overall Satisfaction by 8.9 points. Adjusted Convenience scores were the lowest for patients receiving topical therapies only or infliximab. Modest but significant correlations were found between Overall Satisfaction and Psoriasis Area and Severity Index (ρ = −0.36, p < 0.001) and Dermatology Life Quality Index (−0.47, p < 0.001). Conclusions Discernable differences were found in treatment satisfaction among therapies, particularly regarding treatment effectiveness and convenience. Further application of treatment satisfaction measures may inform treatment decisions and guideline development. PMID:24266717

The phylotypic stage as a boundary of modular memory: non mechanistic perspective.

PubMed

Svorcová, Jana

2012-05-01

The concept of the phylotypic stage has been strongly integrated into developmental biology, thanks mostly to drawings presented by Haeckel (Anthropogenie oder Entwicklungsgeschichte des Menschen, 1874). They are printed in every textbook as proof of the existence of the phylotypic stage and the fact of its conservation, albeit many times criticized as misleading and simplifying (Richardson in Develop Biol 172:412-421, 1995, Richardson et al. in Anat Embryo 196:91-106, 1997; Bininda-Emons et al. in Proc R Soc Lond 270:341-346, 2003). Although generally accepted by modern biology, doubt still exists concerning the very existence or the usefulness of the concept. What kind of evolutionary and developmental horizons does it open indeed? This article begins with the history of the concept, discusses its validity and draws this into connotation with the idea of a memory activated throughout the development. Barbieri (The organic codes. An introduction to semantic biology, 2003) considers the phylotypic stage to be a crucial boundary when the genetic program ceases to suffice for further development of the embryo, and supracellular memory of the body plan is activated. This moment clearly coincides with the commencing of the modular development of the embryo. In this article the nature of such putative memory will be discussed.

29 CFR 502.35 - Commencement of proceeding.

Code of Federal Regulations, 2010 CFR

2010-07-01

... 29 Labor 3 2010-07-01 2010-07-01 false Commencement of proceeding. 502.35 Section 502.35 Labor Regulations Relating to Labor (Continued) WAGE AND HOUR DIVISION, DEPARTMENT OF LABOR REGULATIONS ENFORCEMENT OF CONTRACTUAL OBLIGATIONS FOR TEMPORARY ALIEN AGRICULTURAL WORKERS ADMITTED UNDER SECTION 218 OF THE...

29 CFR 501.35 - Commencement of proceeding.

Code of Federal Regulations, 2010 CFR

2010-07-01

... 29 Labor 3 2010-07-01 2010-07-01 false Commencement of proceeding. 501.35 Section 501.35 Labor Regulations Relating to Labor (Continued) WAGE AND HOUR DIVISION, DEPARTMENT OF LABOR REGULATIONS ENFORCEMENT OF CONTRACTUAL OBLIGATIONS FOR TEMPORARY ALIEN AGRICULTURAL WORKERS ADMITTED UNDER SECTION 218 OF THE...

27 CFR 40.512 - Change in ownership or control.

Code of Federal Regulations, 2010 CFR

2010-04-01

... continuing operation, such fiduciary shall, before commencing operations, make application for a permit in... inventory in accordance with § 40.523. However, where a fiduciary intends only to liquidate the business... date of the transfer. The proposed successor shall, before commencing operations, qualify as a...

28 CFR 2.10 - Date service of sentence commences.

Code of Federal Regulations, 2011 CFR

2011-07-01

... 28 Judicial Administration 1 2011-07-01 2011-07-01 false Date service of sentence commences. 2.10 Section 2.10 Judicial Administration DEPARTMENT OF JUSTICE PAROLE, RELEASE, SUPERVISION AND RECOMMITMENT OF PRISONERS, YOUTH OFFENDERS, AND JUVENILE DELINQUENTS United States Code Prisoners and Parolees § 2...

8 CFR 1003.14 - Jurisdiction and commencement of proceedings.

Code of Federal Regulations, 2010 CFR

2010-01-01

... proceedings. 1003.14 Section 1003.14 Aliens and Nationality EXECUTIVE OFFICE FOR IMMIGRATION REVIEW, DEPARTMENT OF JUSTICE GENERAL PROVISIONS EXECUTIVE OFFICE FOR IMMIGRATION REVIEW Immigration Court-Rules of... before an Immigration Judge commence, when a charging document is filed with the Immigration Court by the...

Infective spondylitis in Southern Chinese: a descriptive and comparative study of ninety-one cases.

PubMed

Yee, Dennis K H; Samartzis, Dino; Wong, Yat-Wa; Luk, Keith D K; Cheung, Kenneth M C

2010-03-15

A retrospective review of infective spondylitis patients assessed at a major, tertiary referral centre in Hong Kong. To assess the prevalence, risk factors, clinical features, and prognostic outcomes associated with tuberculous spondylitis to that of pyogenic spondylitis in Southern Chinese treated at a single institution. Previous studies in Asia suggest that tuberculous spondylitis is the predominant infection unless proven otherwise. Current clinical experiences suggest otherwise; however, the current trend and clinical profile of infective spondylitis among Southern Chinese remains speculative with no published studies examining their prevalence. A retrospective review was performed of all infective spondylitis cases presenting from January 2004 to July 2008 to a tertiary referral center. Cases were included on the basis of clinical and microbiological criteria. Radiographic imaging was used for further confirmation. Ninety-one patients were identified. Overall, tuberculous spondylitis and pyogenic spondylitis entailed 22 (24.2%) and 69 (75.8%) cases, respectively. Staphylococcus aureus was the most commonly isolated infective agent associated with pyogenic spondylitis. Individuals with pyogenic spondylitis were significantly much older than those with tuberculous spondylitis (P = 0.001). Intravenous drug addiction was the most commonly noted risk factor followed by diabetes, and found to be more prevalent in pyogenic spondylitis cases. At initial presentation, white cell count and c-reactive protein levels were higher in pyogenic spondylitis cases compared with tuberculous spondylitis (P < 0.05). The occurrence of tuberculous spondylitis cases was predominant in the thoracic region (40.9%) (P < 0.05). Surgical intervention was performed in 54.5% of tuberculous spondylitis and in 24.6% of the pyogenic spondylitis cases (P = 0.009). In Southern Chinese, compared to previous reports over the past 3 decades, a changing prevalence of decreasing tuberculous spondylitis was observed. Pyogenic spondylitis was found to be more common among patients hospitalized for infective spondylitis. This has important implications on the method of diagnosis and the need for establishing microbiological diagnosis before commencing treatment. "Best guess" therapy should not be targeted at tuberculous spondylitis only. There are clear distinctions in the biologic and clinical profiles between tuberculous and pyogenic spondylitis that would help to direct therapy.

Emerging therapies in systemic lupus erythematous: from clinical trial to the real life.

PubMed

Zhang, Huza; Chambers, William; Sciascia, Savino; Cuadrado, Maria J

2016-01-01

Systemic lupus erythematous (SLE) is a chronic autoimmune disease characterised by multisystem involvement and a relapsing remitting course. SLE is a highly heterogeneous condition, with wide variations in both the presentation and severity of disease and the biological markers identified. The use of biologics in SLE has lagged behind that of other rheumatological conditions such as rheumatoid arthritis, in part due to the diverse clinical manifestations of SLE, making it difficult to design appropriate trials for novel treatments. As such, broad immunosuppressive treatment regimens are still widely used in SLE. Nevertheless, in recent years, elucidation of some aspects of SLE pathogenesis have allowed the development of therapies targeted at molecular mediators of SLE. This review provides an update of biological available therapies and those currently under development.

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

Neuroanatomy: Cajal and after Cajal.

PubMed

Jones, Edward G

2007-10-01

This essay commences with a consideration of the relative contributions of Cajal and Golgi to the study of the anatomy of the nervous system. It demonstrates the extent to which Cajal depended upon Golgi's work and how his modifications of the Golgi technique permitted a remarkable series of investigations in which the foundations of the neuron doctrine were laid and in which the intrinsic connectivity of virtually every part of the central nervous system was charted. Cajal's readiness to seize on and develop new techniques was one of the many keys to his success. After him, neuroanatomical studies tended to be focused more on long tract connectivity, using techniques such as those of Nissl and Marchi that had been in place before Cajal commenced his studies. Development of degeneration-based techniques of tracing connections in the late 1950s spearheaded a revolution in neuroanatomy while introduction of mixed aldehyde fixation made possible similarly intensive studies of the fine structure of the nervous system. At this time, the Golgi technique experienced a brief resurgence as neuroanatomists made efforts to bridge the gap between light and electron microscopy. Later developments in techniques for tracing connections included anterograde tracing by autoradiography and retrograde tracing by horseradish peroxidase. These were soon superseded by tracing techniques of increasing sensitivity and specificity that rely upon the cellular and molecular biology of neurons. Although neuroanatomy in its traditional form is perhaps no longer fashionable as a discipline, the techniques of neuroanatomy remain preeminent in many, perhaps all areas of neuroscience.

Genetic modification of hematopoietic stem cells: recent advances in the gene therapy of inherited diseases.

PubMed

Bueren, Juan A; Guenechea, Guillermo; Casado, José A; Lamana, María Luisa; Segovia, José C

2003-01-01

Hematopoietic stem cells constitute a rare population of precursor cells with remarkable properties for being used as targets in gene therapy protocols. The last years have been particularly productive both in the fields of gene therapy and stem cell biology. Results from ongoing clinical trials have shown the first unquestionable clinical benefits of immunodeficient patients transplanted with genetically modified autologous stem cells. On the other hand, severe side effects in a few patients treated with gene therapy have also been reported, indicating the usefulness of further improving the vectors currently used in gene therapy clinical trials. In the field of stem cell biology, evidence showing the plastic potential of adult hematopoietic stem cells and data indicating the multipotency of adult mesenchymal precursor cells have been presented. Also, the generation of embryonic stem cells by means of nuclear transfer techniques has appeared as a new methodology with direct implications in gene therapy.

Strengths Weaknesses Opportunities and Threats of Blended Learning: Students’ Perceptions

PubMed Central

Hande, S

2014-01-01

Background: Blended learning (BL) in a cell biology course of the premedical program at the Kasturba Medical College International Centre, Manipal, India, commenced in 2006. The program provides training in basic sciences to students, especially from the United States and Canada. The approach to the study was phenomenographic, with a qualitative study design using an open-ended questionnaire, focused interviews and empirical observations. Aim: The aim of this study was to identify the strengths, weaknesses, opportunities and threats (SWOT) of BL in a premedical class. Subjects and Methods: It was a cross-sectional study. Ninety six students in a premedical cell biology class participated in the study. SWOT analysis of students’ perceptions was conducted manually. Statistical analysis included content analysis of qualitative data to classify data and aligning them into the SWOT analysis matrix. Results: The outcomes of the study revealed student perceptions in terms of SWOT of BL and the potential uses of this strategy. Conclusions: The study provides background for educators and curriculum experts to plan their modules while incorporating a BL approach. PMID:24971204

Radiosensitivity of cancer-initiating cells and normal stem cells (or what the Heisenberg uncertainly principle has to do with biology).

PubMed

Woodward, Wendy Ann; Bristow, Robert Glen

2009-04-01

Mounting evidence suggests that parallels between normal stem cell biology and cancer biology may provide new targets for cancer therapy. Prospective identification and isolation of cancer-initiating cells from solid tumors has promoted the descriptive and functional identification of these cells allowing for characterization of their response to contemporary cancer therapies, including chemotherapy and radiation. In clinical radiation therapy, the failure to clinically eradicate all tumor cells (eg, a lack of response, partial response, or nonpermanent complete response by imaging) is considered a treatment failure. As such, biologists have explored the characteristics of the small population of clonogenic cancer cells that can survive and are capable of repopulating the tumor after subcurative therapy. Herein, we discuss the convergence of these clonogenic studies with contemporary radiosensitivity studies that use cell surface markers to identify cancer-initiating cells. Implications for and uncertainties regarding incorporation of these concepts into the practice of modern radiation oncology are discussed.

Cancer metabolism: strategic diversion from targeting cancer drivers to targeting cancer suppliers.

PubMed

Kim, Soo-Youl

2015-03-01

Drug development groups are close to discovering another pot of gold-a therapeutic target-similar to the success of imatinib (Gleevec) in the field of cancer biology. Modern molecular biology has improved cancer therapy through the identification of more pharmaceutically viable targets, and yet major problems and risks associated with late-phase cancer therapy remain. Presently, a growing number of reports have initiated a discussion about the benefits of metabolic regulation in cancers. The Warburg effect, a great discovery approximately 70 years ago, addresses the "universality" of cancer characteristics. For instance, most cancer cells prefer aerobic glycolysis instead of mitochondrial respiration. Recently, cancer metabolism has been explained not only by metabolites but also through modern molecular and chemical biological techniques. Scientists are seeking context-dependent universality among cancer types according to metabolic and enzymatic pathway signatures. This review presents current cancer metabolism studies and discusses future directions in cancer therapy targeting bio-energetics, bio-anabolism, and autophagy, emphasizing the important contribution of cancer metabolism in cancer therapy.

75 FR 65640 - Cellular, Tissue and Gene Therapies Advisory Committee; Notice of Meeting

Federal Register 2010, 2011, 2012, 2013, 2014

2010-10-26

...] Cellular, Tissue and Gene Therapies Advisory Committee; Notice of Meeting AGENCY: Food and Drug... closed to the public. Name of Committee: Cellular, Tissue and Gene Therapies Advisory Committee. General... Branch, Office of Cellular, Tissue and Gene Therapies, Center for Biologics Evaluation and Research, FDA...

Particle Disease: A Current Review of the Biological Mechanisms in Periprosthetic Osteolysis After Hip Arthroplasty

PubMed Central

Sukur, Erhan; Akman, Yunus Emre; Ozturkmen, Yusuf; Kucukdurmaz, Fatih

2016-01-01

Background: Inflammatory responses to wear debris cause osteolysis that leads to aseptic prosthesis loosening and hip arthroplasty failure. Although osteolysis is usually associated with aseptic loosening, it is rarely seen around stable implants. Aseptic implant loosening is a simple radiologic phenomenon, but a complex immunological process. Particulate debris produced by implants most commonly causes osteolysis, and this is called particle-associated periprosthetic osteolysis (PPO). Objective: The objective of this review is to outline the features of particle-associated periprosthetic osteolysis to allow the physician to recognise this condition and commence early treatment, thereby optimizing patient outcome. Methods: A thorough literature search was performed using available databases, including Pubmed, to cover important research published covering particle-associated PPO. Results: Although osteolysis causes bone resorption, clinical, animal, and in vitro studies of particle bioreactivity suggest that particle-associated PPO represents the culmination of several biological reactions of many cell types, rather than being caused solely by the osteoclasts. The biological activity is highly dependent on the characteristics and quantity of the wear particles. Conclusion: Despite advances in total hip arthroplasty (THA), particle-associated PPO and aseptic loosening continue to be major factors that affect prosthetic joint longevity. Biomarkers could be exploited as easy and objective diagnostic and prognostic targets that would enable testing for osteolysis after THA. Further research is needed to identify new biomarkers in PPO. A comprehensive understanding of the underlying biological mechanisms is crucial for developing new therapeutic interventions to reverse or suppress biological responses to wear particles. PMID:27499822

Impact of Out-of-Pocket Costs on Prescription Fills Among New Initiators of Biologic Therapies for Rheumatoid Arthritis.

PubMed

Hopson, Sari; Saverno, Kim; Liu, Larry Z; AL-Sabbagh, Ahmad; Orazem, John; Costantino, Mary E; Pasquale, Margaret K

2016-02-01

Biologic disease-modifying antirheumatic drug (DMARD) therapies are a mainstay of treatment for rheumatoid arthritis (RA), yet high member out-of-pocket (OOP) costs for such therapies may limit patient access to these therapies. To understand whether there is a relationship between OOP costs and the initial fill and subsequent refills of biologic DMARD treatments for RA members. Members of a national Medicare Advantage and Prescription Drug (MAPD) plan with an adjudicated (paid or reversed) claim for a biologic DMARD indicated for RA were identified from July 1, 2007, to December 31, 2012, and followed retrospectively. The first adjudicated claim date was the index date. Members were required to have 180 days of continuous enrollment pre- and post-index and ≥ 1 diagnosis for RA (ICD-9-CM: 714.0 or 714.2) during pre-index or ≤ 30 days post-index. Low-income subsidy and Medicaid-Medicare dual-eligible patients were excluded. The analysis used multivariate regression models to examine associations between initial prescription (Rx) abandonment rates and OOP costs and factors influencing the refill of a biologic DMARD therapy based on pharmacy claims. The final sample size included 864 MAPD members with an adjudicated claim for a biologic DMARD. The majority were female (77.4%) and mean age was 63.5 years (SD = 10.9). Most (78%) had conventional nonbiologic DMARD utilization during pre-index. The overall initial abandonment rate was 18.2% for biologic DMARDs, ranging from 1.3% for the lowest OOP cost group ($0-$250) to 32.7% for the highest OOP cost group (> $550; P < 0.0001 for Cochran-Armitage trend test). ORs for abandonment rose from 18.4 to 32.7 to 41.2 for OOP costs of $250.01-$400.00, $400.01-$550.00, and > $550.00 respectively, relative to OOP costs of ≤ $250.00 (all P < 0.0001). Meeting the catastrophic coverage limit and utilization of a specialty pharmacy for the index claim were both associated with a decreased likelihood of abandoning therapy (OR = 0.29 and OR = 0.14, respectively; both P < 0.05). Among the subset of 533 members with a paid claim, 82.4% had at least 1 refill post-index. The negative association between OOP cost and likelihood of refilling an Rx was highly significant (P < 0.0001). This study suggests that the higher the member OOP cost, the less likely an MAPD member is to initiate or refill a biologic DMARD therapy for RA. Further research is needed to understand reasons for initial Rx abandonment and lack of refills, including benefit design and adverse events.

75 FR 62889 - Sunshine Act Meetings

Federal Register 2010, 2011, 2012, 2013, 2014

2010-10-13

... LEGAL SERVICES CORPORATION Sunshine Act Meetings Date and Time: The Legal Services Corporation... 2 p.m., Eastern Time. On Tuesday, October 19, the first meeting will commence at 8 a.m., Eastern Time. On each of these two days, each meeting other than the first meeting of the day will commence...

32 CFR 516.16 - Individual and supervisory procedures upon commencement of legal proceedings.

Code of Federal Regulations, 2010 CFR

2010-07-01

... 32 National Defense 3 2010-07-01 2010-07-01 true Individual and supervisory procedures upon commencement of legal proceedings. 516.16 Section 516.16 National Defense Department of Defense (Continued) DEPARTMENT OF THE ARMY AID OF CIVIL AUTHORITIES AND PUBLIC RELATIONS LITIGATION Reporting Legal Proceedings...

40 CFR 265.254 - Design and operating requirements.

Code of Federal Regulations, 2010 CFR

2010-07-01

... DISPOSAL FACILITIES Waste Piles § 265.254 Design and operating requirements. The owner or operator of each new waste pile on which construction commences after January 29, 1992, each lateral expansion of a waste pile unit on which construction commences after July 29, 1992, and each such replacement of an...

28 CFR 811.5 - Commencement of the obligation to register.

Code of Federal Regulations, 2010 CFR

2010-07-01

... 28 Judicial Administration 2 2010-07-01 2010-07-01 false Commencement of the obligation to register. 811.5 Section 811.5 Judicial Administration COURT SERVICES AND OFFENDER SUPERVISION AGENCY FOR... guilty by reason of insanity of a registration offense or is determined to be a sexual psychopath...

28 CFR 811.5 - Commencement of the obligation to register.

Code of Federal Regulations, 2012 CFR

2012-07-01

... 28 Judicial Administration 2 2012-07-01 2012-07-01 false Commencement of the obligation to register. 811.5 Section 811.5 Judicial Administration COURT SERVICES AND OFFENDER SUPERVISION AGENCY FOR... guilty by reason of insanity of a registration offense or is determined to be a sexual psychopath...

28 CFR 811.5 - Commencement of the obligation to register.

Code of Federal Regulations, 2011 CFR

2011-07-01

... 28 Judicial Administration 2 2011-07-01 2011-07-01 false Commencement of the obligation to register. 811.5 Section 811.5 Judicial Administration COURT SERVICES AND OFFENDER SUPERVISION AGENCY FOR... guilty by reason of insanity of a registration offense or is determined to be a sexual psychopath...

27 CFR 25.276 - Operations and records.

Code of Federal Regulations, 2010 CFR

2010-04-01

..., DEPARTMENT OF THE TREASURY LIQUORS BEER Pilot Brewing Plants § 25.276 Operations and records. (a) Commencement of operations. A person may commence operation of a pilot brewing plant upon receipt of the approved application and bond. (b) Reports. The operator of a pilot brewing plant is not required to file...

27 CFR 25.276 - Operations and records.

Code of Federal Regulations, 2011 CFR

2011-04-01

..., DEPARTMENT OF THE TREASURY LIQUORS BEER Pilot Brewing Plants § 25.276 Operations and records. (a) Commencement of operations. A person may commence operation of a pilot brewing plant upon receipt of the approved application and bond. (b) Reports. The operator of a pilot brewing plant is not required to file...

18 CFR 4.38 - Consultation requirements.

Code of Federal Regulations, 2010 CFR

2010-04-01

... 18 Conservation of Power and Water Resources 1 2010-04-01 2010-04-01 false Consultation... original license commences first stage pre-filing consultation on or after July 23, 2005 it shall file a... potential applicant for an original license that commences pre-filing consultation on or after July 23, 2005...

18 CFR 4.38 - Consultation requirements.

Code of Federal Regulations, 2011 CFR

2011-04-01

... 18 Conservation of Power and Water Resources 1 2011-04-01 2011-04-01 false Consultation... original license commences first stage pre-filing consultation on or after July 23, 2005 it shall file a... potential applicant for an original license that commences pre-filing consultation on or after July 23, 2005...

18 CFR 4.38 - Consultation requirements.

Code of Federal Regulations, 2013 CFR

2013-04-01

... 18 Conservation of Power and Water Resources 1 2013-04-01 2013-04-01 false Consultation... original license commences first stage pre-filing consultation on or after July 23, 2005 it shall file a... potential applicant for an original license that commences pre-filing consultation on or after July 23, 2005...

18 CFR 4.38 - Consultation requirements.

Code of Federal Regulations, 2014 CFR

2014-04-01

... 18 Conservation of Power and Water Resources 1 2014-04-01 2014-04-01 false Consultation... original license commences first stage pre-filing consultation on or after July 23, 2005 it shall file a... potential applicant for an original license that commences pre-filing consultation on or after July 23, 2005...

18 CFR 4.38 - Consultation requirements.

Code of Federal Regulations, 2012 CFR

2012-04-01

... 18 Conservation of Power and Water Resources 1 2012-04-01 2012-04-01 false Consultation... original license commences first stage pre-filing consultation on or after July 23, 2005 it shall file a... potential applicant for an original license that commences pre-filing consultation on or after July 23, 2005...

Using Arduino to Teach Programming to First-Year Computer Science Students

ERIC Educational Resources Information Center

Tan, Wee Lum; Venema, Sven; Gonzalez, Ruben

2017-01-01

Transitioning to university is recognised as a challenging endeavour for commencing students. For commencing Computer Science students specifically, evidence suggests a link between poor performance in introductory technical courses, such as programming, and high attrition rates. Building resilience in students, particularly at the start of their…

12 CFR 1253.7 - Failure to comply.

Code of Federal Regulations, 2010 CFR

2010-01-01

... cease offering a new product or engaging in a new activity immediately upon discovering or receiving notice from the Director that the Enterprise has— (1) Offered a new product or commenced a new activity without submitting a Notice; (2) Offered a new product or commenced a new activity after submitting a...

5 CFR 843.304 - Commencing and terminating dates of survivor annuities.

Code of Federal Regulations, 2013 CFR

2013-01-01

... (CONTINUED) CIVIL SERVICE REGULATIONS (CONTINUED) FEDERAL EMPLOYEES RETIREMENT SYSTEM-DEATH BENEFITS AND... annuities. (a) A current or former spouse annuity under this subpart commences on the day after the death of... 55 or dies. (c) A current spouse annuity under this subpart terminated for reasons other than death...

5 CFR 843.304 - Commencing and terminating dates of survivor annuities.

Code of Federal Regulations, 2011 CFR

2011-01-01

... (CONTINUED) CIVIL SERVICE REGULATIONS (CONTINUED) FEDERAL EMPLOYEES RETIREMENT SYSTEM-DEATH BENEFITS AND... annuities. (a) A current or former spouse annuity under this subpart commences on the day after the death of... 55 or dies. (c) A current spouse annuity under this subpart terminated for reasons other than death...

5 CFR 843.304 - Commencing and terminating dates of survivor annuities.

Code of Federal Regulations, 2014 CFR

2014-01-01

... (CONTINUED) CIVIL SERVICE REGULATIONS (CONTINUED) FEDERAL EMPLOYEES RETIREMENT SYSTEM-DEATH BENEFITS AND... annuities. (a) A current or former spouse annuity under this subpart commences on the day after the death of... 55 or dies. (c) A current spouse annuity under this subpart terminated for reasons other than death...

5 CFR 843.304 - Commencing and terminating dates of survivor annuities.

Code of Federal Regulations, 2012 CFR

2012-01-01

... (CONTINUED) CIVIL SERVICE REGULATIONS (CONTINUED) FEDERAL EMPLOYEES RETIREMENT SYSTEM-DEATH BENEFITS AND... annuities. (a) A current or former spouse annuity under this subpart commences on the day after the death of... 55 or dies. (c) A current spouse annuity under this subpart terminated for reasons other than death...

5 CFR 843.304 - Commencing and terminating dates of survivor annuities.

Code of Federal Regulations, 2010 CFR

2010-01-01

... (CONTINUED) CIVIL SERVICE REGULATIONS (CONTINUED) FEDERAL EMPLOYEES RETIREMENT SYSTEM-DEATH BENEFITS AND... annuities. (a) A current or former spouse annuity under this subpart commences on the day after the death of... 55 or dies. (c) A current spouse annuity under this subpart terminated for reasons other than death...

38 CFR 21.7551 - Extended period of eligibility.

Code of Federal Regulations, 2013 CFR

2013-07-01

... 38 Pensions, Bonuses, and Veterans' Relief 2 2013-07-01 2013-07-01 false Extended period of... Reserve Eligibility § 21.7551 Extended period of eligibility. (a) Period of eligibility may be extended...-689)(Nov. 18, 1988) (b) Commencing date. The reservist shall elect the commencing date of an extended...

38 CFR 21.7551 - Extended period of eligibility.

Code of Federal Regulations, 2012 CFR

2012-07-01

... 38 Pensions, Bonuses, and Veterans' Relief 2 2012-07-01 2012-07-01 false Extended period of... Reserve Eligibility § 21.7551 Extended period of eligibility. (a) Period of eligibility may be extended...-689)(Nov. 18, 1988) (b) Commencing date. The reservist shall elect the commencing date of an extended...

38 CFR 21.7551 - Extended period of eligibility.

Code of Federal Regulations, 2011 CFR

2011-07-01

... 38 Pensions, Bonuses, and Veterans' Relief 2 2011-07-01 2011-07-01 false Extended period of... Reserve Eligibility § 21.7551 Extended period of eligibility. (a) Period of eligibility may be extended...-689)(Nov. 18, 1988) (b) Commencing date. The reservist shall elect the commencing date of an extended...

38 CFR 21.7551 - Extended period of eligibility.

Code of Federal Regulations, 2014 CFR

2014-07-01

... 38 Pensions, Bonuses, and Veterans' Relief 2 2014-07-01 2014-07-01 false Extended period of... Reserve Eligibility § 21.7551 Extended period of eligibility. (a) Period of eligibility may be extended...-689)(Nov. 18, 1988) (b) Commencing date. The reservist shall elect the commencing date of an extended...

38 CFR 21.7551 - Extended period of eligibility.

Code of Federal Regulations, 2010 CFR

2010-07-01

... 38 Pensions, Bonuses, and Veterans' Relief 2 2010-07-01 2010-07-01 false Extended period of... Reserve Eligibility § 21.7551 Extended period of eligibility. (a) Period of eligibility may be extended...-689)(Nov. 18, 1988) (b) Commencing date. The reservist shall elect the commencing date of an extended...

13 CFR 134.202 - Commencement of cases.

Code of Federal Regulations, 2010 CFR

2010-01-01

... proceedings, see § 124.305 of this chapter; (5) For SBA Employee Disputes, see Standard Operating Procedure 37... 13 Business Credit and Assistance 1 2010-01-01 2010-01-01 false Commencement of cases. 134.202 Section 134.202 Business Credit and Assistance SMALL BUSINESS ADMINISTRATION RULES OF PROCEDURE GOVERNING...

32 CFR 516.16 - Individual and supervisory procedures upon commencement of legal proceedings.

Code of Federal Regulations, 2011 CFR

2011-07-01

... 32 National Defense 3 2011-07-01 2009-07-01 true Individual and supervisory procedures upon commencement of legal proceedings. 516.16 Section 516.16 National Defense Department of Defense (Continued) DEPARTMENT OF THE ARMY AID OF CIVIL AUTHORITIES AND PUBLIC RELATIONS LITIGATION Reporting Legal Proceedings...

41 CFR 60-30.23 - Summary judgment.

Code of Federal Regulations, 2011 CFR

2011-07-01

... time after the expiration of 20 days from the commencement of the action, or after service of a motion... after commencement of the action, move with or without supporting affidavits for summary judgment in its... part may support or oppose motions for summary judgment made by the Government or respondent, in...

41 CFR 60-30.23 - Summary judgment.

Code of Federal Regulations, 2010 CFR

2010-07-01

... time after the expiration of 20 days from the commencement of the action, or after service of a motion... after commencement of the action, move with or without supporting affidavits for summary judgment in its... part may support or oppose motions for summary judgment made by the Government or respondent, in...

40 CFR 60.4200 - Am I subject to this subpart?

Code of Federal Regulations, 2012 CFR

2012-07-01

... stationary compression ignition (CI) internal combustion engines (ICE) and other persons as specified in... commences is the date the engine is ordered by the owner or operator. (1) Manufacturers of stationary CI ICE... model year, for fire pump engines. (2) Owners and operators of stationary CI ICE that commence...

40 CFR 60.4200 - Am I subject to this subpart?

Code of Federal Regulations, 2014 CFR

2014-07-01

... stationary compression ignition (CI) internal combustion engines (ICE) and other persons as specified in... commences is the date the engine is ordered by the owner or operator. (1) Manufacturers of stationary CI ICE... model year, for fire pump engines. (2) Owners and operators of stationary CI ICE that commence...

40 CFR 60.4200 - Am I subject to this subpart?

Code of Federal Regulations, 2013 CFR

2013-07-01

... stationary compression ignition (CI) internal combustion engines (ICE) and other persons as specified in... commences is the date the engine is ordered by the owner or operator. (1) Manufacturers of stationary CI ICE... model year, for fire pump engines. (2) Owners and operators of stationary CI ICE that commence...

40 CFR 63.1351 - Compliance dates.

Code of Federal Regulations, 2011 CFR

2011-07-01

... that commenced construction before or on March 24, 1998, or (2) June 14, 1999 or startup for sources..., or (2) Startup for sources that commenced construction after December 20, 2006. (c) The compliance... September 9, 2013. (d) The compliance date for new sources is November 9, 2010 or startup, whichever is...

40 CFR 63.1351 - Compliance dates.

Code of Federal Regulations, 2012 CFR

2012-07-01

... that commenced construction before or on March 24, 1998, or (2) June 14, 1999 or startup for sources..., or (2) Startup for sources that commenced construction after December 20, 2006. (c) The compliance... September 9, 2013. (d) The compliance date for new sources is November 9, 2010 or startup, whichever is...

40 CFR 63.1351 - Compliance dates.

Code of Federal Regulations, 2013 CFR

2013-07-01

... or startup for sources that commenced construction after March 24, 1998. (b) The compliance date for... before or on December 20, 2006, or (2) Startup for sources that commenced construction after December 20... compliance date for new sources is February 12, 2013, or startup, whichever is later. (e) The compliance date...

40 CFR 63.1351 - Compliance dates.

Code of Federal Regulations, 2014 CFR

2014-07-01

... or startup for sources that commenced construction after March 24, 1998. (b) The compliance date for... before or on December 20, 2006, or (2) Startup for sources that commenced construction after December 20... compliance date for new sources is February 12, 2013, or startup, whichever is later. (e) The compliance date...

47 CFR 22.946 - Service commencement and construction systems.

Code of Federal Regulations, 2011 CFR

2011-10-01

... telephone network (PSTN) and must be providing service to mobile stations operated by its subscribers and roamers. A cellular system is considered to be providing service only if mobile stations can originate... 47 Telecommunication 2 2011-10-01 2011-10-01 false Service commencement and construction systems...

47 CFR 25.133 - Period of construction; certification of commencement of operation.

Code of Federal Regulations, 2010 CFR

2010-10-01

...) COMMON CARRIER SERVICES SATELLITE COMMUNICATIONS Applications and Licenses Earth Stations § 25.133 Period of construction; certification of commencement of operation. (a)(1) Each license for an earth station governed by this part, except for mobile satellite earth station terminals (METs), shall specify as a...

47 CFR 25.133 - Period of construction; certification of commencement of operation.

Code of Federal Regulations, 2014 CFR

2014-10-01

...) COMMON CARRIER SERVICES SATELLITE COMMUNICATIONS Applications and Licenses Earth Stations § 25.133 Period of construction; certification of commencement of operation. (a)(1) Each initial license for an earth... the earth station must be completed and the station must be brought into operation within 12 months...

43 CFR 4.351 - Commencement of the determination process.

Code of Federal Regulations, 2013 CFR

2013-10-01

... 43 Public Lands: Interior 1 2013-10-01 2013-10-01 false Commencement of the determination process. 4.351 Section 4.351 Public Lands: Interior Office of the Secretary of the Interior DEPARTMENT HEARINGS AND APPEALS PROCEDURES Rules Applicable in Indian Affairs Hearings and Appeals White Earth...

43 CFR 4.351 - Commencement of the determination process.

Code of Federal Regulations, 2012 CFR

2012-10-01

... 43 Public Lands: Interior 1 2012-10-01 2011-10-01 true Commencement of the determination process. 4.351 Section 4.351 Public Lands: Interior Office of the Secretary of the Interior DEPARTMENT HEARINGS AND APPEALS PROCEDURES Rules Applicable in Indian Affairs Hearings and Appeals White Earth...

47 CFR 25.133 - Period of construction; certification of commencement of operation.

Code of Federal Regulations, 2013 CFR

2013-10-01

...) COMMON CARRIER SERVICES SATELLITE COMMUNICATIONS Applications and Licenses Earth Stations § 25.133 Period of construction; certification of commencement of operation. (a)(1) Each license for an earth station governed by this part, except for mobile earth stations, shall specify as a condition therein the period in...

47 CFR 25.133 - Period of construction; certification of commencement of operation.

Code of Federal Regulations, 2012 CFR

2012-10-01

...) COMMON CARRIER SERVICES SATELLITE COMMUNICATIONS Applications and Licenses Earth Stations § 25.133 Period of construction; certification of commencement of operation. (a)(1) Each license for an earth station governed by this part, except for mobile satellite earth station terminals (METs), shall specify as a...

47 CFR 25.133 - Period of construction; certification of commencement of operation.

Code of Federal Regulations, 2011 CFR

2011-10-01

...) COMMON CARRIER SERVICES SATELLITE COMMUNICATIONS Applications and Licenses Earth Stations § 25.133 Period of construction; certification of commencement of operation. (a)(1) Each license for an earth station governed by this part, except for mobile satellite earth station terminals (METs), shall specify as a...

43 CFR 4.351 - Commencement of the determination process.

Code of Federal Regulations, 2010 CFR

2010-10-01

... 43 Public Lands: Interior 1 2010-10-01 2010-10-01 false Commencement of the determination process. 4.351 Section 4.351 Public Lands: Interior Office of the Secretary of the Interior DEPARTMENT HEARINGS AND APPEALS PROCEDURES Rules Applicable in Indian Affairs Hearings and Appeals White Earth...

43 CFR 4.351 - Commencement of the determination process.

Code of Federal Regulations, 2011 CFR

2011-10-01

... 43 Public Lands: Interior 1 2011-10-01 2011-10-01 false Commencement of the determination process. 4.351 Section 4.351 Public Lands: Interior Office of the Secretary of the Interior DEPARTMENT HEARINGS AND APPEALS PROCEDURES Rules Applicable in Indian Affairs Hearings and Appeals White Earth...

43 CFR 4.351 - Commencement of the determination process.

Code of Federal Regulations, 2014 CFR

2014-10-01

... 43 Public Lands: Interior 1 2014-10-01 2014-10-01 false Commencement of the determination process. 4.351 Section 4.351 Public Lands: Interior Office of the Secretary of the Interior DEPARTMENT HEARINGS AND APPEALS PROCEDURES Rules Applicable in Indian Affairs Hearings and Appeals White Earth...

Valuing Orientation Efficacy: Rethinking Undergraduate Business Student's First Impressions

ERIC Educational Resources Information Center

McPhail, Ruth; French, Ben; Wilson, Keithia

2015-01-01

Purpose: The purpose of this study was to improve the orientation experience of commencing first-year undergraduate business students to better prepare them for the reality of their academic studies through the development and implementation of a Commencing Student-Needs-Centred Orientation Framework. Design/methodology/approach: The methodology…

32 CFR 516.16 - Individual and supervisory procedures upon commencement of legal proceedings.

Code of Federal Regulations, 2013 CFR

2013-07-01

... litigation. (b) Supervisory procedures. When supervisors learn that legal proceedings in which the United... 32 National Defense 3 2013-07-01 2013-07-01 false Individual and supervisory procedures upon... to HQDA § 516.16 Individual and supervisory procedures upon commencement of legal proceedings. (a...

32 CFR 516.16 - Individual and supervisory procedures upon commencement of legal proceedings.

Code of Federal Regulations, 2012 CFR

2012-07-01

... litigation. (b) Supervisory procedures. When supervisors learn that legal proceedings in which the United... 32 National Defense 3 2012-07-01 2009-07-01 true Individual and supervisory procedures upon... to HQDA § 516.16 Individual and supervisory procedures upon commencement of legal proceedings. (a...

32 CFR 516.16 - Individual and supervisory procedures upon commencement of legal proceedings.

Code of Federal Regulations, 2014 CFR

2014-07-01

... litigation. (b) Supervisory procedures. When supervisors learn that legal proceedings in which the United... 32 National Defense 3 2014-07-01 2014-07-01 false Individual and supervisory procedures upon... to HQDA § 516.16 Individual and supervisory procedures upon commencement of legal proceedings. (a...

78 FR 78360 - Notice of Meeting

Federal Register 2010, 2011, 2012, 2013, 2014

2013-12-26

... (R18)''. Each SEP meeting will commence in open session before closing to the public for the duration... expertise. Each SEP meeting will commence in open session before closing to the public for the duration of..., the disclosure of which would constitute a clearly unwarranted invasion of personal privacy. Dated...

5 CFR 9001.104 - Prohibited financial interests.

Code of Federal Regulations, 2012 CFR

2012-01-01

... directly or indirectly own or control: (1) A security for which a waiver has been granted pursuant to... to the effective date of this part or the commencement of employment with FHFA or without specific... this part, commencement of employment with FHFA, or acquisition of such interest. Such financial...

5 CFR 9001.104 - Prohibited financial interests.

Code of Federal Regulations, 2013 CFR

2013-01-01

... directly or indirectly own or control: (1) A security for which a waiver has been granted pursuant to... to the effective date of this part or the commencement of employment with FHFA or without specific... this part, commencement of employment with FHFA, or acquisition of such interest. Such financial...

5 CFR 9001.104 - Prohibited financial interests.

Code of Federal Regulations, 2014 CFR

2014-01-01

... directly or indirectly own or control: (1) A security for which a waiver has been granted pursuant to... to the effective date of this part or the commencement of employment with FHFA or without specific... this part, commencement of employment with FHFA, or acquisition of such interest. Such financial...

40 CFR 60.1110 - Who must submit a siting analysis?

Code of Federal Regulations, 2012 CFR

2012-07-01

... Waste Combustion Units for Which Construction is Commenced After August 30, 1999 or for Which... construction of a small municipal waste combustion unit after December 6, 2000. (b) If you commence construction on your municipal waste combustion unit after August 30, 1999, but before December 6, 2000, you...

40 CFR 60.1005 - When does this subpart become effective?

Code of Federal Regulations, 2014 CFR

2014-07-01

... Municipal Waste Combustion Units for Which Construction is Commenced After August 30, 1999 or for Which... to municipal waste combustion unit planning and must be completed before construction is commenced on the municipal waste combustion unit. In particular, the preconstruction requirements in §§ 60.1050...

40 CFR 60.1005 - When does this subpart become effective?

Code of Federal Regulations, 2010 CFR

2010-07-01

... Municipal Waste Combustion Units for Which Construction is Commenced After August 30, 1999 or for Which... to municipal waste combustion unit planning and must be completed before construction is commenced on the municipal waste combustion unit. In particular, the preconstruction requirements in §§ 60.1050...

40 CFR 60.1005 - When does this subpart become effective?

Code of Federal Regulations, 2012 CFR

2012-07-01

... Municipal Waste Combustion Units for Which Construction is Commenced After August 30, 1999 or for Which... to municipal waste combustion unit planning and must be completed before construction is commenced on the municipal waste combustion unit. In particular, the preconstruction requirements in §§ 60.1050...

Emerging biological therapies for the treatment of myelodysplastic syndromes.

PubMed

Zeidan, Amer M; Stahl, Maximilian; Komrokji, Rami

2016-09-01

No drug has resulted in a survival advantage in patients with lower-risk myelodysplastic syndromes (MDS). While hypomethylating agents (HMA) have revolutionized treatment options for patients with higher-risk MDS, the prognosis remains dismal after HMA treatment failure. Novel effective therapies are urgently needed especially after HMA failure. This review covers the current approach to disease prognostication and risk-adaptive therapy, as well as novel therapeutic approaches. We discuss the recent advancements in the understanding of MDS disease biology as a basis of targeted drug development. Several classes of novel agents are reviewed including drugs targeting dysregulated epigenetic control mechanisms, signaling pathways, abnormal splicing, as well as agents that target the immune system and the MDS bone marrow niche. Significant advancements in the understanding of the underlying biology of MDS are only starting to be translated into novel treatment options for MDS. Epigenetic therapy has shown significant clinical activity with HMA but the results of clinical trials combining HMAs with histone deacetylase inhibitors (HDACi) have been disappointing to date. Similarly, targeting several aberrant pathways in MDS has not resulted in significant improvements in therapy. Future therapies will focus both on synergic combination of existing drugs as well as novel agents targeting dysregulated immune responses and abnormal RNA splicing in MDS.

Immunogenicity of biologics in inflammatory bowel disease

PubMed Central

Vermeire, Séverine; Gils, Ann; Accossato, Paola; Lula, Sadiq; Marren, Amy

2018-01-01

Crohn’s disease and ulcerative colitis are chronic inflammatory disorders of the gastrointestinal tract. Treatment options include biologic therapies; however, a proportion of patients lose response to biologics, partly due to the formation of anti-drug antibodies (ADAbs). Concomitant immunosuppressive agents reduce the development of ADAbs. This review article aims to assess the immunogenicity of biologic therapies and their clinical implications. A comprehensive literature search was conducted for articles published January 2009 to August 2015 reporting immunogenicity to adalimumab (ADM), certolizumab pegol (CZP), golimumab, infliximab (IFX), ustekinumab, and vedolizumab in inflammatory bowel disease (IBD). Eligible articles were reviewed and quality assessed by independent reviewers. Overall, 122 publications reporting 114 studies were assessed. ADAbs were reported for all agents, but the percentage of patients developing ADAbs was extremely variable, with the highest (65.3%) being for IFX administration to patients with IBD. ADAb presence was frequently associated with a reduction in primary efficacy and a loss of response, and, for IFX, an increase in adverse events (AEs). Lower serum levels of ADM, CZP and IFX were seen in ADAbs-positive rather than ADAbs-negative patients; pharmacokinetic data were unavailable for other therapies. Little information was available regarding the timing of ADAb development; studies reported their detection from as early as 10–14 days up to months after treatment initiation. Biologic therapies carry an intrinsic risk of immunogenicity, although reported rates of ADAbs vary considerably. The clinical implications of immunogenicity are a concern for effective treatment; further research, particularly into the more recently approved biologics, is required. PMID:29383030