Maximize Treatment Benefits Research Articles

D-Cycloserine augmentation of cognitive behavior therapy for pediatric OCD: Predictors and moderators of outcome

BackgroundOver half of children receiving cognitive behavioral therapy (CBT) for obsessive compulsive disorder (OCD) do not fully remit. To improve response rates and enhance extinction learning, d-cycloserine (DCS) has been examined as an augmenting agent of CBT. To direct children with OCD towards treatments with the highest likelihood of success, the current study evaluated the conditions under which DCS augmentation works best (i.e., moderators) and the baseline characteristics associated with outcome, irrespective of treatment type (i.e., predictors). MethodsData came from a two-site randomized controlled trial (N = 142) in which children received either DCS + CBT (n = 70) or placebo + CBT. ResultsNo baseline variables moderated the effects of DCS augmentation on CBT outcome. However, several predictor variables were associated with a decreased likelihood of achieving remission status, including higher family accommodation scores, higher impairment scores, higher depression scores, and higher externalizing scores. Furthermore, better insight at pre-treatment was associated with more improvement longitudinally on a clinician-rated summary measure of illness severity. LimitationsThe current study did not examine all variables that had previously been shown to moderate or predict treatment outcome (e.g., family history of OCD or cognitive profile). ConclusionsThe absence of significant moderators suggests that baseline factors cannot yet be used to determine who benefits most from DCS. To maximize treatment benefits for children presenting with identified predictors of worse treatment outcome, clinicians might need to adapt existing CBT protocols and administer additional interventions that address patients’ specific problem areas.

Treatment Thresholds and Targets in Hypertension: Different Readings of the Same Evidence?

See related article, pp e13–e115 The new 2017 High Blood Pressure Clinical Practice Guideline released by the American College of Cardiology (ACC) and the American Heart Association (AHA)1 presents several novel aspects with potential significant impact on hypertension management. Important news of the guideline is related to blood pressure (BP) measurement modalities, BP thresholds for the initiation of nonpharmacological as well as pharmacological treatment, BP targets to pursue to maximize treatment benefits from BP lowering and last but not least a novel definition of hypertension. Overall, this is an important document but its translation into clinical practice seems to pose a huge challenge for clinicians According to the novel definition of stage 1 hypertension starting at systolic or diastolic BP values of ≥130 mm Hg or ≥80 mm Hg almost 50% of adults in the US population (and in many other countries around the world) have hypertension, whereas the remaining 50% resides either in the elevated (ie, 120–129 mm Hg) or in the normal systolic BP range (ie, <120 mm Hg). Given that BP thresholds and targets are inevitably related to the hypertension definition, the new selected threshold (ie, 130/80 mm Hg) will introduce an epidemiological revolution that will not remain unquestioned in the United States and around the world. Beyond the immediate overnight striking increase (by 14%) of hypertension prevalence in the United States after the presentation of the new guideline, the incidence rate of hypertension is expected to decrease because of the increased disease duration, as the new diagnosis of hypertension is expected to be anticipated at a younger age. It is, however, questionable whether diagnosing hypertension in younger otherwise healthy subjects by tightening up the hypertension definition will indeed improve prevention strategies, for example, by lifestyle modifications, as intended by the authors of the guideline. In …

Barriers and Facilitators to Treatment Engagement Among Clients in Inpatient Substance Abuse Treatment.

There is a call for drawing on client voice to provide a rich, nuanced understanding of factors influencing substance treatment engagement as to maximizing treatment benefits. We interviewed 60 clients in a short-term inpatient substance treatment program and examined facilitators and barriers to treatment engagement. Thematic analysis yielded four themes, including perceived treatment needs, trust and counselor rapport, peer inspiration, and organizational factors. Perceived treatment needs serve as both a facilitator and a barrier wherein the acknowledgment of needs led to greater treatment engagement whereas a lack of perceived needs hindered treatment engagement. The establishment of trust and counselor rapport and peer inspiration facilitated treatment engagement. Clients rated several organizational factors including a lack of treatment provision, gender-responsive treatment and infrastructure, and ineffective communication with nonclinical staff as barriers to treatment engagement. Clinical implications include enhancing treatment motivation and counselor rapport, establishing gender-responsive treatment programs, and providing trainings for staff.

Recent Developments in the Management of Insomnia in Later Life.

Insomnia impacts a significant proportion of older adults yet is not an inevitable consequence of aging and is amenable to intervention. The aim of this narrative review is to provide an overview of recent recommendations and empirical findings regarding the management of insomnia in older adults. The treatment of insomnia with cognitive behavioral therapy for insomnia (CBT-I) continues to be empirically supported and the recommended first-line intervention for adults. Accumulating evidence indicates that other non-pharmacological therapies for insomnia, such as mindfulness-based therapies, light therapy, and physical activity interventions, as well as treatment delivered by non-clinician "sleep coaches" also positively impact insomnia symptoms. Finally, recent systematic reviews offer guidelines and recommendations for pharmacological management of insomnia. CBT-I remains the recommended first-line treatment for insomnia across adult ages. There is a continued need to increase the availability and optimize the delivery of CBT-I and other therapies for older adults with insomnia to maximize treatment benefits. There is also evidence for some benefit of pharmacological agents to treat insomnia; however, these are not without risks, particularly in the geriatric population.

Stomatitis associated with mammalian target of rapamycin inhibition: A review of pathogenesis, prevention, treatment, and clinical implications for oral practice in metastatic breast cancer

BackgroundPatients with metastatic breast cancer may develop oral morbidities that result from therapeutic interventions. Mammalian target of rapamycin (mTOR) inhibitor–associated stomatitis (mIAS) is a common adverse event (AE), secondary to mTOR inhibitor therapy, that can have a negative impact on treatment adherence, quality of life, and health care costs. A multidisciplinary team approach is important to minimize mIAS and to maximize treatment benefits to patients with breast cancer. In this review, we discuss the pathophysiology, diagnosis, and natural history of mIAS. Current and new management strategies for the prevention and treatment of mIAS are described in the context of fostering a coordinated team care approach to optimizing patient care. Types of Studies ReviewedThe authors conducted a PubMed search from 2007 through 2017 using the terms “stomatitis,” “mIAS,” “everolimus,” “mTOR,” “metastatic breast cancer,” and “oral care.” They selected articles published in peer-reviewed journals that reported controlled trials and evidence-based guidelines. ResultsmIAS can be distinguished from mucositis caused by cytotoxic chemotherapy or radiotherapy on the basis of cause, clinical presentation, and treatment paradigms. Specific preventive and therapeutic management strategies can be implemented across the continuum of patient oral health care. Practical ImplicationsOral health care providers are on the frontline of oral health care for patients with metastatic breast cancer and are uniquely positioned to provide patient education, advocate accurate reporting of mIAS, and support early identification, monitoring, and prompt intervention to mitigate the severity and duration of this manageable, potentially dose-limiting AE.

Tolerability of Ustekinumab in Induction and Maintenance for the Treatment of Crohnʼs Disease

BACKGROUND: Tolerance to therapy is critical for patients to receive the maximal treatment benefit. In Phase 3 clinical trials for ustekinumab (UST) for moderate to severe Crohn's disease (CD), UNITI-1 enrolled anti-TNF failures and UNITI-2 enrolled conventional therapy failures. In UNITI-1, 36.4% had previous intolerance (infusion-related reactions [IRR], delayed hypersensitivity reactions, or injection site reactions [ISR]) that led to discontinuation of the anti-TNF. UNITI-2 enrolled patients that were not intolerant to anti-TNFs, but some were intolerant to immunomodulators (39%) or corticosteroids (15%). Here we assess tolerability as measured by IRR, delayed hypersensitivity, or ISR to UST in the Phase 3 CD trials. METHODS: All enrolled patients in UNITI-1 and UNITI-2 were given an intravenous (IV) induction infusion of UST 130mg, UST ˜6 mg/kg, or placebo (PBO). The IM-UNITI maintenance study began 8 weeks after IV induction; UST IV responders were randomized to UST 90mg SC Q8W, UST 90mg SC Q12W, or PBO. Non-randomized patients, included non-responders to placebo who received 130mg IV UST, then continued to UST 90mg SC Q12W maintenance therapy; non-responders to IV UST who received UST 90 mg SC, then continued UST 90 mg SC Q8W in maintenance; and IV placebo responders who received placebo SC in maintenance. RESULTS: Overall, IRR were infrequent: 4.0% and 1.9% of all patients in UNITI 1 & 2, respectively, experienced infusion reactions to the single IV dose. There were no differences in IRR between PBO & UST, or between UST doses (UNITI 1 IRRs in 2.0%, PBO and 4.5% UST 130mg and 3.6%, UST ˜6 mg/kg; UNITI 2 IRRs in 2.9%, PBO and 2.4% UST 130mg and 1.4%, UST ˜6 mg/kg). During IM-UNITI, in non-randomized patients who were non-responders to placebo induction and received a 130mg IV injection, IRR to PBO and UST were similar and infrequent (2.5% and 1.8%, respectively). There were no anaphylactic or delayed hypersensitivity reactions to any IV dose. After SC administration, ISRs were infrequent and not different across groups. In the combined (randomized and non- randomized) population, ISRs were 1.7% with PBO, and 3.0% with UST. No serious ISRs were reported. The most common ISR was erythema, reported in 1.1% of PBO, and 1.7% of UST. There were no anaphylactic or delayed hypersensitivity reactions to any SC dose. Amongst randomized patients, ISRs were infrequent and consistent between groups. ISRs occurred in 3/418 (0.7%) of all UST 90mg Q12W injections and in 12/599 (2.0%) of all UST 90mg Q8W injections. One patient in the entire phase 3 program discontinued therapy due to ISR. CONCLUSION(S): In a broad population of patients with Crohn's disease, many of whom were intolerant to previous therapies, UST had a tolerable profile. Rates of IRR and ISR were minimal, and were not different between groups, nor populations.

Perspectives in Head and Neck Medical Oncology.

The modern treatment of locoregionally advanced disease often requires a multimodality combination approach. A number of chemotherapeutic agents can be combined with radiation, but the platinum agent cisplatin, a potent radiation sensitizer, is best studied in head and neck cancer. Newer agents such as cetuximab can be used in combination with radiation therapy for those patients who cannot tolerate cisplatin. For chemotherapy-naïve patients with metastatic head and neck cancer who demonstrate a good performance status, platinum doublet regimens are commonly used. Doublet regimens generally improve response rates compared to single-agent chemotherapies, although they have not demonstrated a survival benefit over single agents and they have added toxicity. Immunotherapies, alternative cytotoxic chemotherapies, and targeted therapies are second-line options for patients with disease that has progressed on platinum-based therapy. Immunotherapy, in particular, has gained focus by enhancing the ability of the immune system to recognize and destroy malignant cells. When multimodal approaches are used, as in combined chemotherapy and radiation therapy, toxicities are increased. It is imperative that patients are followed closely in order to maximize treatment benefit while minimizing complications.

Stratified approach for low back pain

A stratified approach for low back pain (LBP) involves targeted treatment for subgroups of patients classified according to their key characteristics such as prognostic psychological factors. This approach tailors therapeutic decisions in ways that maximize treatment benefit and reduce medical care costs. A stratified approach was known as the “Holy Grail” in back pain research over a decade ago.

Tolerability of Ustekinumab in Induction and Maintenance for the Treatment of Crohnʼs Disease

Introduction: Tolerance to therapy is critical for patients to receive the maximal treatment benefit. In Phase 3 clinical trials for ustekinumab (UST) for moderate to severe Crohn's disease (CD), UNITI-1 enrolled anti-TNF failures and UNITI-2 enrolled conventional therapy failures. In UNITI-1, 36.4% had previous intolerance (infusion-related reactions [IRR], delayed hypersensitivity reactions, or injection site reactions [ISR]) that led to discontinuation of the anti-TNF. UNITI-2 enrolled patients that were not intolerant to anti-TNFs, but some were intolerant to immunomodulators (39%) or corticosteroids (15%). Here we assess tolerability as measured by IRR, delayed hypersensitivity, or ISR to UST in the Phase 3 CD trials. Methods: All enrolled patients in UNITI-1 and UNITI-2 were given an intravenous (IV) induction infusion of UST 130mg, UST ˜6 mg/kg, or placebo (PBO). The IM-UNITI maintenance study began 8 weeks after IV induction; UST IV responders were randomized to UST 90mg SQ Q8W, UST 90mg Q12W, or PBO. Non-randomized patients could receive 130mg IV UST, then continued to SC PBO, UST 90mg Q8W, UST 90mg Q12W maintenance therapy, or discontinued. Results: Overall, IRR were infrequent: 4.0 % and 1.9 % of all patients in UNITI 1 & 2, respectively, experienced infusion reactions to the single IV dose. There were no differences in IRR between PBO & UST, or between UST doses (Table 1). During IM-UNITI, IRR to PBO and UST 130mg were similar and infrequent (Table 1). There were no anaphylactic or delayed hypersensitivity reactions to any IV dose. ISRs were infrequent and not different across groups (Table 2). In the combined (randomized and non- randomized) population, ISRs were 1.7 % with PBO, and 3.0% with UST. No serious ISRs were reported. The most common ISR was erythema, reported in 1.1 % of PBO, and 1.7% of UST. There were no anaphylactic or delayed hypersensitivity reactions to any SC dose. Amongst randomized patients, ISRs were infrequent and consistent between groups. ISRs occurred in 3/418 (0.7 %) of all UST 90mg Q12W injections and in 12/599 (2.0 %) of all UST 90mg Q8W injections. One patient in the entire phase 3 program discontinued therapy due to ISR.Table: Table. Infusion-related reactions*Table: Table. Injection site reactionsConclusion: In a broad population of patients with Crohn's disease, many of whom were intolerant to previous therapies, UST had a tolerable profile. Rates of IRR and ISR were minimal, and were not obviously different between groups, nor populations.

Multiple Myeloma: State of the Art

The treatment of newly diagnosed myeloma is a moving target given the rapid and important advances in the understanding of disease biology as well as a wealth of new agents with which to treat the disease. As such, it is important at the time of initial presentation, to have a defined treatment plan that includes induction, consolidation and maintenance therapy in order to maximize duration of initial response. Along the same lines, in the relapsed disease setting, following defined treatment approaches allows one to maximize treatment benefit and prolong duration of subsequent remissions. In this session, we will cover how to optimally utilize available agents for different risk groups of patients to maximize outcomes and duration of benefit.

Predicting Adherence and Persistence with Oral Bisphosphonate Therapy in an Integrated Health Care Delivery System.

Examining drug exposure is essential to pharmacovigilance, especially for bisphosphonate (BP) therapy. To examine differences in 4 measures of oral BP exposure: treatment discontinuation, adherence, persistence, and nonpersistence. Among women aged ≥ 50 years who initiated oral BP therapy during 2002-2007 with at least 3 years of health plan membership follow-up, discontinuation was defined by evidence of no further treatment during the study observation period. Among those with at least 2 filled BP prescriptions during the study period, adherence was calculated for each year of follow-up using the (modified) proportion of days covered (mPDC) metric that allows for stockpiling of prescription/refills overlap ≤ 30 days supply. Persistence was quantified by treatment duration, allowing a gap of up to 60 days between prescription/refill days covered. Nonpersistence was quantified by the periods without drugs outside this allowable gap. Multivariable logistic regression was used to compare age and race groups and the relationships of early adherence (adherence during the first year) with subsequent adherence. Among 48,390 women initiating oral BP therapy and followed for 3 years, 26.7% discontinued in year 1, and 14.7% of the remaining 35,456 women discontinued in year 2. Discontinuation rates were slightly higher (29.4%, P < 0.001) for women aged ≥ 75 years and somewhat lower (21.1%, P < 0.001) for Asian women. During the first year, 60.4% of the women achieved an mPDC of ≥ 75%, with demographic differences in adherence similar to that seen for treatment discontinuation. Over the 3 years, the median mPDC levels for BP therapy were 86%, 84%, and 85% in years 1, 2, and 3, respectively, for those receiving treatment. Cumulative persistence was 2.3 years (median, IQR = 1.0-3.0) overall and slightly greater for Asian versus white women and lower for older women. There were 18,174 (42.9%) women with at least 1 period of nonpersistence during 3 years follow-up in excess of the 60-day allowable gap between prescription/refills (median cumulative nonpersistence = 0.65, IQR = 0.30-1.25 years). Women with mPDC ≥ 75% during the first year had a 12-fold and 6-fold increased odds of mPDC ≥ 75% during year 2 and year 3, respectively. BP discontinuation rates are highest for women during the first year. Among those continuing treatment in subsequent years, adherence rates were relatively stable. Persistence and adherence varied slightly by age and was somewhat higher in Asians, contributing to differences in cumulative BP exposure. We also found evidence that optimal adherence in the first year was highly predictive of optimal adherence in the subsequent 1-2 years. Hence, subgroups of patients receiving oral BP drugs may require different levels of support and monitoring to maximize treatment benefit, especially based on early patterns of use. This study was supported by grants from the Kaiser Permanente Northern California Community Benefit Program and the National Institutes of Health, 1R01AG047230-01A1. The opinions expressed in this publication are solely the responsibility of the authors and do not represent the official views of Kaiser Permanente or the National Institutes of Health. Hui, Yi, and Chandra have received past research funding from Amgen not related to the current study. Adams has received research funding from Amgen, Merck, and Otsuka not related to the current study. Niu has received research funding from Bristol-Myers Squibb not related to the current study. Ettinger has received past legal fees in litigation involving Fosamax. Lo has received past research funding from Amgen and current research funding from Sanofi not related to the current study. The data from this study were presented at the Academy of Managed Care Pharmacy Annual Meeting; April 19-22, 2016; San Francisco, California. Study concept and design were contributed primarily by Hui and Lo, along with Adams, Niu, Yi, and Ettinger. Hui took the lead in data collection, along with Chandra, and data interpretation was performed by Niu, Yi, and Lo, along with the other authors. The manuscript was written by Hui, Adams, and Lo, along with Niu, Yi, and Ettinger, and revised by Ettinger, Hui, Lo, and Niu, along with the other authors.

A Sound Therapy-Based Intervention to Expand the Auditory Dynamic Range for Loudness among Persons with Sensorineural Hearing Losses: Case Evidence Showcasing Treatment Efficacy.

Case evidence is presented that highlights the clinical relevance and significance of a novel sound therapy-based treatment. This intervention has been shown to be efficacious in a randomized controlled trial for promoting expansion of the dynamic range for loudness and increased sound tolerance among persons with sensorineural hearing losses. Prior to treatment, these individuals were unable to use aided sound effectively because of their limited dynamic ranges. These promising treatment effects are shown in this article to be functionally significant, giving rise to improved speech understanding and enhanced hearing aid benefit and satisfaction, and, in turn, to enhanced quality of life posttreatment. These posttreatment sound therapy effects also are shown to be sustained, in whole or part, with aided environmental sound and to be dependent on specialized counseling to maximize treatment benefit. Importantly, the treatment appears to be efficacious for hearing-impaired persons with primary hyperacusis (i.e., abnormally reduced loudness discomfort levels [LDLs]) and for persons with loudness recruitment (i.e., LDLs within the typical range), which suggests the intervention should generalize across most individuals with reduced dynamic ranges owing to sensorineural hearing loss. An exception presented in this article is for a person describing the perceptual experience of pronounced loudness adaptation, which apparently rendered the sound therapy inaudible and ineffectual for this individual. Ultimately, these case examples showcase the enormous potential of a surprisingly simple sound therapy intervention, which has utility for virtually all audiologists to master and empower the adaptive plasticity of the auditory system to achieve remarkable treatment benefits for large numbers of individuals with sensorineural hearing losses.

Use of Anti-Thymocyte Globulin for Induction Therapy in Cardiac Transplantation: A Review

The most common causes of death after heart transplantation (HTx) include acute rejection and multi-organ failure in the early period and malignancy and cardiac allograft vasculopathy (CAV) in the late period. Polyclonal antibody preparations such as rabbit anti-thymocyte globulin (ATG) may reduce early acute rejection and the later occurrence of CAV after HTx. ATG therapy depletes T cells, modulates adhesion and cell-signaling molecules, interferes with dendritic cell function, and induces B-cell apoptosis and regulatory and natural killer T-cell expansion. Evidence from animal studies and from retrospective clinical studies in humans indicates that ATG can be used to delay calcineurin inhibitor (CNI) exposure after HTx, thus benefiting renal function, and to reduce the incidence of CAV and ischemia-reperfusion injury in the transplanted heart. ATG may reduce de novo antibody production after HTx. ATG does not appear to increase cytomegalovirus infection rates with longer prophylaxis (6–12 months). In addition, ATG may reduce the risk of lymphoproliferative disease and does not appear to confer an additive effect on acquiring lymphoma after HTx. Randomized, controlled trials may provide stronger evidence of ATG association with patient survival, graft rejection, renal protection through delayed CNI initiation, as well as other benefits. It can also help establish optimal dosing and patient criteria to maximize treatment benefits.

Treatment Adherence Intervention Studies in Dermatology and Guidance on How to Support Adherence

Adequate adherence to prescribed treatment regimens can help to break the cycle of treatment failure, disease progression and subsequent treatment escalation. Unfortunately, adherence in the treatment of skin disorders such as acne, atopic dermatitis/eczema and psoriasis is often inadequate. A review of the literature identified a number of studies that tested an intervention to improve adherence in dermatology, including the following: electronic messages and/or reminders; more frequent or 'extra' clinic visits; audio-visual and internet-based interventions; and patient support programmes and/or self-management, educational training programmes. While there is no one solution or action for improving adherence, some interventions were more successful than others. We provide practical guidance on how to support adherence based on aspects of the successful interventions identified and on our collective opinion and clinical practice experience. Holding patients accountable, providing a caring and supportive environment, raising awareness of poor adherence and helping patients build a solid medication-taking habit can help to improve adherence so that patients can experience maximal treatment benefits and desired clinical outcomes.

Pittsburgh response to endovascular therapy score as a pre-treatment prognostic tool: External validation in Trevo2.

Background Optimal patient selection is needed to maximize the therapeutic benefit of endovascular therapy for large vessel occlusion stroke. Aims To validate the Pittsburgh response to endovascular therapy (PRE) score in a randomized controlled trial (Trevo2) comparing stent retriever (Trevo) to the Merci device. Methods Trevo2 participants with internal carotid, M1 and M2 middle cerebral artery occlusions with prospectively collected baseline stroke severity (NIHSS), degree of hypodensity (CT ASPECTS), and three-month modified Rankin Scale (mRS) were included. Multivariable regression was used to confirm association between PRE score variables (age, NIHSS, and ASPECTS), medical comorbidities, randomization arm, and reperfusion status (mTICI2B/3) with good outcome (three-month modified Rankin Scale 0-2). Predictive power (area under the receiver operating characteristic curve) for good outcome of pre-treatment prognostic scores (PRE, THRIVE, HIAT2) was compared. Rates of good outcome were compared between successfully reperfused (mTICI2B/3) and non-reperfused (mTICI0-2A) patients across previously identified PRE score risk groups. Results Age, NIHSS, ASPECTS, reperfusion status, and randomization arm were independent predictors of good outcome. PRE score had moderate predictive power (AUC = 0.75) for good outcome and was comparable to other pre-treatment scores. Reperfusion resulted in maximal treatment benefit in patients with PRE score 0-24 (60% vs. 12.5%, p = 0.002) but not in those with PRE ≥50 (11.8% vs. 0.0%, p = 0.49). Conclusion The PRE score is a validated predictor of functional outcome and a tool for patient selection for endovascular therapy in anterior large vessel occlusion stroke. Our finding of limited benefit of reperfusion in patients with PRE score ≥50 needs to be prospectively validated.

Abstract 1647: Radiation response genome-wide analysis using paired pre and post-radiation FFPE human breast tumor samples

Abstract Background: Breast cancer is the most common female malignancy in the US, and radiotherapy is a routine part of multi-disciplinary breast cancer care. Radiation treatment (RT) tailored to target radiation response pathways could maximize treatment benefit in radiation resistant tumors, while minimizing unnecessary toxicity and cost in more radiation responsive breast tumor subtypes. Here we report on genome-wide analysis, gene expression profiles and biological pathways associated with RT response in breast cancer patients. Methods: Between 2010-2013, a total of 32 breast cancer patients were enrolled at Duke University Medical Center on an IRB approved Phase I clinical trial testing preoperative radiotherapy. Paired pre and post-RT FFPE biopsy samples were available for N = 26. Genome wide-analysis was performed using two distinct techniques: i) Microarray analysis using the Affymetrix GeneChip ® Human Transcriptome Array 2.0 (HTA 2.0); ii) RNA-Seq using TruSeq ®RNA Access Library kit (Illumina). All libraries were sequenced on the Illumina HiSeq 2000 generating 50 bp single reads at a sequencing depth of 40 million reads. The RNA-Seq data was processed using the TrimGalore toolkit. For the paired pre and post-RT differential gene expression analysis we used the linear model. Genes that had an FDR ≤ 5% in the RNA-Seq experiment were compared with all microarray probesets that had an FDR ≤ 5%. If at least one probeset that belonged to a gene in the RNA-Seq list was significant and showed the same direction of change between pre and post-RT samples, they were identified as consistent. Gene Set Enrichment Analysis (GSEA) and Database for Annotation, Visualization and Integrated Discovery (DAVID) were used to identify significant pathways and gene ontologies that were differentially regulated between the conditions. Results: 2648 genes showed the same significant results in response to RT in microarray and RNA-Seq including: i) a total of 1401 genes that had significantly higher expression levels, and ii) a total of 1247 genes that had significantly lower expression levels following RT. Principal Components Analysis (PCA) demonstrated distinct separation of pre and post-RT gene expression signatures. Differentially expressed genes were involved in major biological pathways such as cell cycle checkpoint, DNA replication and DNA repair pathways. A subset of these genes also demonstrated differential expression in radiation responsive vs. non-responsive breast cancer cell lines. Conclusion: New laboratory techniques have become available which provide the opportunity to use FFPE samples for microarray and RNA-seq analysis. Using these new techniques and our rare pre and post-RT FFPE breast tumor samples, we have been able to demonstrate distinct differences in gene expression profiles and modulation of biological pathways in response to RT in human breast tumors. Citation Format: Sharareh Siamakpour-Reihani, Wei Chen, David Corcoran, Chen-Ting Lee, Ying Zhou, Mark W. Dewhirst, Jen-Tsan A. Chi, Janet K. Horton. Radiation response genome-wide analysis using paired pre and post-radiation FFPE human breast tumor samples. [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr 1647.

The value of ECG parameters as markers of treatment response in Fabry cardiomyopathy

ObjectiveBest treatment outcomes in Fabry disease (FD) associated cardiomyopathy can be obtained when treatment is started as early as possible. The rationale of this study was to assess the role...

Long-Term Treatment Strategies for Pediatric Bipolar Disorder

Bipolar disorder is a serious psychiatric disorder that frequently begins in childhood and lasts a lifetime. In the last 10–15 years, many advances have been made in the short-term treatment of bipolar disorder in children and adolescents, especially mixed and manic episodes. Less is known about long-term treatment and treatment of depressive episodes. This paper reviews recent literature on long-term treatment strategies for pediatric bipolar disorder. Pharmacologically, several second generation antipsychotics and mood stabilizers were recently studied in long-term treatment trials. These agents showed comparable effectiveness in reducing manic symptoms. Most benefits were attained early in treatment. The majority of patients did not complete the studies. The agents varied in their side effect profiles. Based on these findings, we recommend (1) maximizing treatment benefits during acute phase, (2) choosing a pharmacological agent on the basis of side effect profile, and (3) using the lowest effective dose to minimize side effect burden. Despite the benefits of medications, a majority of patients will not adhere to permanent medication regimen. Thus, psychosocial treatments can theoretically fill the gap and complement pharmacological treatments. No definitive psychosocial treatment for pediatric bipolar disorder has been developed. However, psychosocial treatments can facilitate medication adherence and early symptom recognition through psychoeducation. Dialectical Behavioral Therapy can assist with emotional regulation and reduce suicidality, and cognitive behavioral therapy can improve adherence and satisfaction with treatment.

Prospective Study of Patient-Reported Symptom Burden in Patients With Non–Small-Cell Lung Cancer Undergoing Proton or Photon Chemoradiation Therapy

ContextIntensity-modulated radiation therapy (IMRT), three-dimensional conformal radiation therapy (3DCRT), and proton-beam therapy (PBT) are chemoradiotherapy modalities for treating locally advanced non–small-cell lung cancer. Although therapy is carefully planned to maximize treatment benefit while minimizing risk for adverse side effects, most patients develop radiation-induced symptom burden. ObjectivesTo demonstrate the MD Anderson Symptom Inventory's ability to detect fine differences in symptom development among these modalities. MethodsThis was a longitudinal observational study. Patients with unresectable primary or recurrent non–small-cell lung cancer (n = 82) underwent 3DCRT, IMRT, or PBT. Patients rated MD Anderson Symptom Inventory symptoms weekly for up to 12 weeks. We used mixed-effect modeling to estimate development of symptoms and functional interference. ResultsThe PBT group received a significantly higher radiation target dose than did the IMRT and 3DCRT groups (P < 0.001). Fatigue was the most severe symptom over time for all groups. Controlling for patient and clinical factors (age, sex, race, cancer stage, performance status, body mass index, previous cancer therapy, total radiation dose), we found that pain, as a major esophagitis-related symptom, increased more during therapy (P = 0.019) and decreased more after (P = 0.013) therapy in the 3DCRT and IMRT groups than in the PBT group. Compared with the PBT group, the 3DCRT and IMRT groups reported greater decrease in systemic symptoms (fatigue, drowsiness, lack of appetite, disturbed sleep) after therapy (P = 0.016). ConclusionPatients receiving PBT reported significantly less severe symptoms than did patients receiving IMRT or 3DCRT. These results should be confirmed in a randomized study with comparable tumor burden among therapies.

Present, Emerging and Possible Future Biomarkers in Castration Resistant Prostate Cancer (CRPC).

Recently, an increasing number of systemic therapies with life extending capacity have become available in metastatic castration resistant prostate cancer (mCRPC) i.e. Abiraterone acetate, Enzalutamide, Sipuleucel-T, Docetaxel, Cabazitaxel and Radium-223. More compounds are currently being evaluated in promising pivotal trials (e.g. Tasquinimod, ARN-509, ODM-201, and more). Limitations of the currently available biomarkers make treatment decisions challenging. Considering the ever increasing complexity of treatment algorithms in mCRPC the current demand of research is to find and characterize biomarkers with prognostic, predictive and surrogate quality, allowing for information on clinically meaningful outcomes and on which therapy to offer patients in different and complex scenarios. A comprehensive English-language literature review was performed through PubMed to identify articles and abstract presentations of the major conferences on cancer during December 2014. In this review we address established biomarkers like prostate specific antigen, lactate dehydrogenase and alkaline phosphatase. Emerging biomarkers like circulating tumor cells, androgen receptor splice variants, cancer stem cells and imaging biomarkers have also been reviewed and placed in the context of prognostic, predictive and surrogate implications in the current field of CRPC. We elaborate on the requirements of good biomarkers and discuss possible future developments of biomarkers in CRPC. Advances in knowledge of biomarkers in CRPC and thus biomarker driven therapy monitoring and up-front therapy decisions may help in the future to tailor treatment algorithms, give information on which therapy to offer and when to continue a given therapy in equivocal scenarios. This could maximize treatment benefit and minimize toxicity.