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The coronavirus disease 2019 (COVID-19) pandemic, which is caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has killed more than one million people as of October 1, 2020. Consequently, a search is on for a treatment that can bring the pandemic to an end. However, treatments (vaccine, antiviral, plasma) that are directed at specific viral proteins (RNA polymerase, spike proteins) may not work well against all strains of the virus. Therefore, it is hypothesized that a therapy based on multiple treatments is needed for COVID-19 patients and to bring the pandemic to an end. Here, it is proposed that a combination of cool air therapy (CAT) and purified air technology (PAT) in an oxygen species cool air respirator (OSCAR) could be used to reduce viral (SARS-CoV-2) load and severity of illness in COVID-19 patients through the individual dose-response relationship. In addition, the proposed therapy (CAT + PAT in OSCAR), which works by a more general physical and chemical mechanism, should work well with other treatments (vaccine, antiviral, plasma) that target specific viral proteins (RNA polymerase, spike proteins) to provide a safe and effective multiple therapy approach for ending the COVID-19 pandemic caused by SARS-CoV-2., (Published by Elsevier Ltd.)

Objective: Pilocytic astrocytoma (PCA) is a low-grade glioma that primarily presents in children, but can also present in adulthood. Ideal primary treatment for PCA is gross total resection. However, for patients who are only able to undergo subtotal resection, the optimal course of post-operative therapy remains unclear. We investigated the association of patient characteristics and radiation therapy (RT) with overall survival specifically for adult PCA patients who underwent subtotal tumor resection., Methods: Information on adult patients (age ≥18 years old) who underwent subtotal PCA resection between 2004 and 2016 was collected from the National Cancer Database (NCDB). A multivariate Cox proportional hazards model was utilized to determine factors associated with overall survival., Results: A total of 451 patients were identified. The mean age of our patient cohort was 36.8 years old, and the majority of patients (83.4%) did not receive RT following subtotal PCA resection. Overall median survival was >93.8 months. On multivariate analysis, patients who were older at diagnosis (hazard ratio [HR] = 1.04, 95% confidence interval [CI] = 1.02-1.06, p < 0.01), black (HR = 2.35, CI = 1.05-5.23, p = 0.037), had a Charlson/Deyo comorbidity score ≥ 1 (HR = 2.27, CI = 1.00-5.14, p = 0.049), or received RT during their initial treatment (HR = 3.77, CI = 1.77-8.03, p < 0.01) had a significantly higher risk of death following subtotal PCA resection., Conclusion: Post-operative RT was associated with a significantly higher risk of death among adults who underwent subtotal PCA resection. Our findings provide support for further inquiry into the efficacy of RT within this patient population., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2020 Elsevier Ltd. All rights reserved.)

Background: Cytoreductive Surgery (CRS) and Hyperthermic Intraperitoneal Chemotherapy (HIPEC) is reported to have a prolonged length of stay (LOS). We incorporated an enhanced recovery after surgery (ERAS) protocol to examine whether we could reduce our LOS., Methods: Patients were identified who underwent CRS/HIPEC from 2015 to 2018 before and after initiation of ERAS protocol. The protocol included pre-operative, peri-operative and post-operative interventions. Primary end point was LOS. Secondary endpoints were morbidity and mortality., Results: Forty patients were identified, thirty-one of which underwent CRS/HIPEC: 16 before and 15 after ERAS. The median LOS prior to ERAS was 11 days (5-20) and 7 days (5-27) after ERAS (P < 0.05). There was no significant difference in 30-day morbidity (Clavien-Dindo ≥3) or mortality between the groups., Conclusions: An ERAS protocol can safely be implemented in patients undergoing CRS/HIPEC with earlier return of bowel function and decrease in LOS without increasing morbidity or mortality., (Copyright © 2019 Elsevier Inc. All rights reserved.)

Curative cancer therapies are uncommon and nearly always involve multi-drug combinations developed by experimentation in humans; unfortunately, the mechanistic basis for the success of such combinations has rarely been investigated in detail, obscuring lessons learned. Here, we use isobologram analysis to score pharmacological interaction, and clone tracing and CRISPR screening to measure cross-resistance among the five drugs comprising R-CHOP, a combination therapy that frequently cures Diffuse Large B-Cell Lymphomas. We find that drugs in R-CHOP exhibit very low cross-resistance but not synergistic interaction: together they achieve a greater fractional kill according to the null hypothesis for both the Loewe dose-additivity model and the Bliss effect-independence model. These data provide direct evidence for the 50 year old hypothesis that a curative cancer therapy can be constructed on the basis of independently effective drugs having non-overlapping mechanisms of resistance, without synergistic interaction, which has immediate significance for the design of new drug combinations., Competing Interests: AP, CC No competing interests declared, PS is a member of the SAB or Board of Directors of Merrimack Pharmaceuticals, Glencoe Software, Applied Biomath and RareCyte Inc and has equity in these companies. In the last five years the Sorger lab has received research funding from Novartis and Merck. PKS declares that none of these relationships are directly or indirectly related to the content of this manuscript, (© 2019, Palmer et al.)

The success of combination antiretroviral therapy (cART) has transformed HIV infection into a chronic condition, resulting in an increase in the number of older, cART-treated adults living with HIV. This has increased the incidence of age-related, non-AIDS comorbidities in this population. One of the most common comorbidities is depression, which is also associated with cognitive impairment and a number of neuropathologies. In older people living with HIV, treating these overlapping disorders is complex, often creating pill burden or adverse drug-drug interactions that can exacerbate these neurologic disorders. Depression, NeuroHIV and many of the neuropsychiatric therapeutics used to treat them impact the dopaminergic system, suggesting that dopaminergic dysfunction may be a common factor in the development of these disorders. Further, changes in dopamine can influence the development of inflammation and the regulation of immune function, which are also implicated in the progression of NeuroHIV and depression. Little is known about the optimal clinical management of drug-drug interactions between cART drugs and antidepressants, particularly in regard to dopamine in older people living with HIV. This review will discuss those interactions, first examining the etiology of NeuroHIV and depression in older adults, then discussing the interrelated effects of dopamine and inflammation on these disorders, and finally reviewing the activity and interactions of cART drugs and antidepressants on each of these factors. Developing better strategies to manage these comorbidities is critical to the health of the aging, HIV-infected population, as the older population may be particularly vulnerable to drug-drug interactions affecting dopamine., (Copyright © 2019 Elsevier B.V. All rights reserved.)

Glioblastoma (GBM) is one of the most lethal cancers. Various prognostic factors impact the survival of GBM patients. To further understand this extremely poor prognosis disease, we evaluated the effect of the treatment facility volumes on overall survival (OS) over the years, especially after the approval of multimodality therapy using temozolomide (TMZ) in 2005. National Cancer Data Base (NCDB) was utilized to identify GBM cases from 2004 through 2013 using ICD-O-3 code 9440/3 to identify eligible patients. We focused on studying the association between treatment facility volume and OS after adjusting for the patient-, disease-, and facility-characteristics. A total of 60,672 eligible GBM patients with median age of 65 years, treated at 1166 facilities were included in this analysis. The median annual facility volume was 3 patients/year (range: 0.1-55.1) and median OS was 8.1 months. There was an improvement in OS across all facilities after 2005, when multimodality therapy with TMZ was approved. Treatment at quartile 4 centers (Q4; >7 patients/year) was independently associated with decreased all-cause mortality in a multivariate analysis (Q3 hazard ratio [HR]: 1.11, 95% CI 1.09, 1.13; Q2 HR: 1.15, 95% CI 1.12, 1.19; Q1 HR: 1.25, 95% CI 1.17, 1.33). Treatment facility volume independently affects OS among GBM patients. Factors that are variable in high- and low-volume centers should be addressed to mitigate outcome disparities., (Copyright © 2019 Elsevier Ltd. All rights reserved.)

Metastatic melanoma therapies have proliferated over the last ten years. Prior to this, decades passed with only very few drugs available to offer our patients, and even then, those few drugs had minimal survival benefits. Many treatment options emerged over the last ten years with diverse mechanisms of action. Further, combination regimens have demonstrated superiority over monotherapy, especially for targeted agents. Each therapeutic combination possesses different advantages and side effect profiles. In this review, we outline the United States Food and Drug Administration-approved melanoma treatment agents and therapies currently in clinical development, focusing on combination approaches., (Copyright © 2018 Elsevier B.V. All rights reserved.)

Background: The chronic phase of Spinal Cord (SC) injury is characterized by the presence of a hostile microenvironment that causes low activity and a progressive decline in neurological function; this phase is non-compatible with regeneration. Several treatment strategies have been investigated in chronic SC injury with no satisfactory results. OBJECTIVE- In this proof-of-concept study, we designed a combination therapy (Comb Tx) consisting of surgical glial scar removal plus scar inhibition, accompanied with implantation of mesenchymal stem cells (MSC), and immunization with neural-derived peptides (INDP)., Methods: This study was divided into three subsets, all in which Sprague Dawley rats were subjected to a complete SC transection. Sixty days after injury, animals were randomly allocated into two groups for therapeutic intervention: control group and animals receiving the Comb-Tx. Sixty-three days after treatment we carried out experiments analyzing motor recovery, presence of somatosensory evoked potentials, neural regeneration-related genes, and histological evaluation of serotoninergic fibers., Results: Comb-Tx induced a significant locomotor and electrophysiological recovery. An increase in the expression of regeneration-associated genes and the percentage of 5-HT+ fibers was noted at the caudal stump of the SC of animals receiving the Comb-Tx. There was a significant correlation of locomotor recovery with positive electrophysiological activity, expression of GAP43, and percentage of 5-HT+ fibers., Conclusion: Comb-Tx promotes motor and electrophysiological recovery in the chronic phase of SC injury subsequent to a complete transection. Likewise, it is capable of inducing the permissive microenvironment to promote axonal regeneration., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

Immune checkpoint inhibitors (ICIs) have recently revolutionized cancer treatment, providing unprecedented clinical benefits. However, primary or acquired therapy resistance can affect up to two-thirds of patients receiving ICIs, underscoring the urgency to elucidate the mechanisms of treatment resistance and to design more effective therapeutic strategies. Conventional cancer treatments, including cytotoxic chemotherapy, radiation therapy, and targeted therapy, have immunomodulatory effects in addition to direct cancer cell-killing activities. Their clinical utilities in combination with ICIs have been explored, aiming to achieve synergetic effects with improved and durable clinical response. Here, we will review the immunomodulatory effects of chemotherapy, targeted therapy, and radiation therapy, in the setting of ICI, and their clinical implications in reshaping modern cancer immunotherapy.

Despite updated management of glioblastoma (GB), progression is virtually inevitable. Previous data suggest a survival benefit from resection at progression; however, relatively few studies have evaluated the role of surgery in the context of contemporary GB treatment and widespread use of bevacizumab and chemotherapy. As such, the purpose of this study is to evaluate outcomes following surgical resection in patients with progressive GB since 2008. The records of all patients who underwent biopsy or resection of GB between January 1, 2008, and December 31, 2015, were retrospectively reviewed to identify 368 patients with progressive GB. Median survival and 95% confidence intervals were generated with the Kaplan-Meier method. Multivariate analysis, which controlled for age, Karnofsky Performance Status (KPS), extent of resection, adjuvant chemotherapy and radiation, tumor location, and tumor multifocality, of post-progression survival was carried out using a Cox proportional hazards model. Of 368 patients with progressive disease, 77 (20.9%) underwent resection at first documented progression. The median post-progression survivals for patients who did and did not undergo resection at this time were 12.8 and 7.0 months, respectively. In multivariate analysis, KPS ≥ 70 at progression (HR 0.438), receipt of bevacizumab at first progression (HR 0.756), and receipt of chemotherapy at first progression (HR 0.644) were associated with increased post-progression survival. Thus, surgery for progressive GB may not improve post-progression survival in the context of contemporary maximal non-surgical therapy. Further investigation is necessary to elucidate what role, if any, bevacizumab has in prolonging post-progression survival in patients with progressive GB., (Copyright © 2018 Elsevier Ltd. All rights reserved.)

Adverse event (AE)-related costs represent an important component of economic models for cancer care. However, since previous studies mostly focused on specific AEs, treatments, or cancer types, limited information is currently available. Therefore, this study assessed the incremental healthcare costs associated with a large number of AEs among patients diagnosed with some of the most prevalent types of cancer. Data were obtained from a large US claims database. Adult patients were included if diagnosed with and treated for one of the following cancer types: breast, digestive organs and peritoneum, genitourinary organs (including bladder and ovary and other uterine adnexa), lung, lymphatic and hematopoietic tissue, and skin. Treatment episodes were defined as the period from initiation of the first antineoplastic pharmacologic therapy to discontinuation (i.e., gap of ≥ 45 days), or change in treatment regimen, or end of data availability. A total of 36 AEs were selected from the product inserts of 104 treatments recommended by practice guidelines. A retrospective matched cohort design was used, matching a treatment episode with a certain AE with a treatment episode without that AE. A total of 412,005 patients were selected, for a total of 794,243 treatment episodes, resulting in 1,617,368 matched treatment episodes across all 36 AEs. Incremental healthcare costs associated with AEs of any severity ranged from $546 for cough/upper respiratory infections to $24,633 for gastrointestinal perforation. The three most costly AEs when considering any severity were gastrointestinal perforation ($24,633), central nervous system hemorrhage ($24,322), and sepsis/septicemia ($23,510). Incremental healthcare costs associated with severe AEs ranged from $15,709 for dermatitis and rash to $48,538 for gastrointestinal fistula. The three most costly severe AEs were gastrointestinal fistula ($48,538), gastrointestinal perforation ($41,281), and central nervous system hemorrhage ($38,428). In conclusion, AEs during treatment episodes for cancer were frequent and associated with a substantial economic burden.

Background: Low-Field Magnetic Stimulation (LFMS) is a novel, non-invasive, sub-threshold neuromodulation technique, shown in preliminary studies to have immediate mood elevating effects in both unipolar and bipolar depressed patients., Objective: We aimed to assess the antidepressant augmentation effects at 48 h of LFMS administered on two consecutive days compared to sham treatment in treatment resistant depression (TRD) subjects, using the Sequential Parallel Comparison Design (SPCD)., Methods: Eighty-four eligible subjects with TRD were randomly assigned to double-blind treatment with LFMS 20 min/day for four days, sham treatment 20 min/day for four days, or sham treatment 20 min/day for 2 days followed by LFMS treatment 20 min/day for two days, using the pre-randomization version of the SPCD (randomization 1:1:1). The SPCD analyses used a repeated measures linear modeling approach with maximum likelihood estimation to use all available data, and using a 60-40 weighting of Stage 1 vs. 2 responses, with the primary outcome being measured after 2 and 4 days., Results: Both primary and secondary outcome measures consistently showed no differences between LFMS-treated patients and those treated with sham, with the exception of a slight, non-significantly greater improvement than sham in the visual analogue scale (VAS) sad mood on LFMS-treated patients. LFMS treatment was relatively well tolerated., Conclusions: We did not observe a significantly greater, rapid efficacy of LFMS compared to sham therapy. Future studies need to examine the possible therapeutic effects of more intensive forms of LFMS, as other forms of neurostimulation typically require longer duration of exposure., (Copyright © 2017 Elsevier Inc. All rights reserved.)

Objective: Multisystemic therapy (MST) is perhaps the best validated treatment for youth who engage in serious and chronic antisocial behavior (Henggeler, Schoenwald, Borduin, Rowland, & Cunningham, 2009). Despite evidence suggesting that high treatment adherence is needed to achieve optimal MST outcomes, this research is limited because past studies have relied on adherence reports derived solely from treatment participants (i.e., caregivers, youth, and therapists). To address this gap in the literature, the present study assessed the reliability and predictive validity of an observational protocol for rating adherence to MST., Method: The sample was drawn from a randomized clinical trial of juvenile drug offenders (77.5% male, 65% African American) referred to one of four treatment conditions (Henggeler et al., 2006). Audiotaped sessions of youth and their families were selected from the first month of MST and trained undergraduate students independently rated therapist adherence to the nine MST treatment principles. We assessed the validity of MST adherence in predicting outcomes at post-recruitment and 12-month follow-up., Results: Good interrater reliability (ICC=0.642) was found across all raters for our composite index of adherence. High adherence to MST during the first month of therapy predicted decreases in externalizing behavior at post-recruitment and decreases in youth alcohol consumption at 12-month follow-up., Conclusions: These results provide independent support for the link between treatment fidelity and behavioral outcomes in the context of MST. Further, this study demonstrates the feasibility of using novice, undergraduate judges to reliably code therapist adherence., (Copyright © 2017 Elsevier Inc. All rights reserved.)

Combination therapies targeting multiple recovery mechanisms have the potential for additive or synergistic effects, but experimental design and analyses of multimodal therapeutic trials are challenging. To address this problem, we developed a data-driven approach to integrate and analyze raw source data from separate pre-clinical studies and evaluated interactions between four treatments following traumatic brain injury. Histologic and behavioral outcomes were measured in 202 rats treated with combinations of an anti-inflammatory agent (minocycline), a neurotrophic agent (LM11A-31), and physical therapy consisting of assisted exercise with or without botulinum toxin-induced limb constraint. Data was curated and analyzed in a linked workflow involving non-linear principal component analysis followed by hypothesis testing with a linear mixed model. Results revealed significant benefits of the neurotrophic agent LM11A-31 on learning and memory outcomes after traumatic brain injury. In addition, modulations of LM11A-31 effects by co-administration of minocycline and by the type of physical therapy applied reached statistical significance. These results suggest a combinatorial effect of drug and physical therapy interventions that was not evident by univariate analysis. The study designs and analytic techniques applied here form a structured, unbiased, internally validated workflow that may be applied to other combinatorial studies, both in animals and humans.

Background: Chemo-radiotherapy is standard of care in the treatment of unresectable stage III NSCLC. We aimed at assessing whether the addition of concurrent taxane-chemotherapy to thoracic irradiation following chemotherapy was able to improve treatment outcome., Material and Methods: In PITCAP trial, patients with unresectable stage III NSCLC were randomized to receive 2 cycles of platinum-paclitaxel followed by 60-61.2Gy thoracic irradiation (control arm) or by same radiotherapy with concomitant weekly paclitaxel (experimental arm). A literature-based meta-analysis including all studies with same design was also performed., Results: At the time of the second interim analysis, when 151 patients were randomized, accrual was terminated. With a median follow-up of 6.1 years, median survival was 13.2 vs 15.1 months, with a 3-year survival rate of 19.5 vs 21.2% in the control and experimental arm, respectively (HR: 0.97; 95% CI 0.69-1.36; p=0.845). Treatment toxicity was manageable in both arms. The meta-analysis of 5 trials (n=866) confirmed the lack of a meaningful effect on 1-year overall survival of a taxane added concurrently to radiotherapy., Conclusions: These results do not support a meaningful survival benefit with the addition of single agent taxane given concurrently to radiotherapy after platinum-based induction in locally advanced NSCLC., (Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.)

Purpose: To update the outcomes of an institutional clinical management approach using ipsilateral neck radiotherapy in the treatment of node-positive squamous cell carcinoma of the tonsil with a well-lateralized primary lesion., Methods and Materials: Between August 2003 and April 2014, 61 consecutive patients with ipsilateral node-positive squamous cell carcinoma of the tonsil without involvement of the base of the tongue or midline soft palate were treated at a community hospital-based cancer center with radiotherapy to the primary site and ipsilateral neck. Overall survival, disease-free survival and freedom from contralateral failure were calculated., Results: Median follow up was 37.2months (range 4-121months). Freedom from contralateral nodal failure at 5years was 98% with one contralateral nodal failure noted. The patient underwent a salvage neck dissection and was treated with post-operative radiotherapy with no evidence of disease to date. 5-year overall survival (OS) was 92.4% and 5year disease-free survival (DFS) was 86.7%., Conclusions: This represents the single largest series reported from a community hospital-based cancer center in which lateralized tonsil cancers with N+ disease were treated with ipsilateral neck radiotherapy. In this carefully selected cohort of patients with well-lateralized tonsil cancers, the risk of contralateral nodal failure appears to be <5%, suggesting that prophylactic radiation of the contralateral neck may not be necessary. Future planned studies will focus on prospectively selecting subgroups of patients eligible for treatment de-intensification as survivorship issues in excellent prognosis HPV positive patients are increasingly becoming relevant., (Copyright © 2015 Elsevier Ltd. All rights reserved.)

Objectives: To determine and compare costs of a nurse-administered behavioral intervention for pregnant substance users that integrated motivational enhancement therapy with cognitive behavioral therapy (MET-CBT) to brief advice (BA) administered by an obstetrical provider. Both interventions were provided concurrent with prenatal care., Methods: We conducted a micro-costing study that prospectively collected detailed resource utilization and unit cost data for each of the two intervention arms (MET-CBT and BA) within the context of a randomized controlled trial. A three-step approach for identifying, measuring and valuing resource utilization was used. All cost estimates were inflation adjusted to 2011 U.S. dollars., Results: A total of 82 participants received the MET-CBT intervention and 86 participants received BA. From the societal perspective, the total cost (including participants' time cost) of the MET-CBT intervention was $120,483 or $1,469 per participant. In contrast, the total cost of the BA intervention was $27,199 or $316 per participant. Personnel costs (nurse therapists and obstetric providers) for delivering the intervention sessions and supervising the program composed the largest share of the MET-CBT intervention costs. Program set up costs, especially intervention material design and training costs, also contributed substantially to the overall cost., Conclusions: Implementation of an MET-CBT program to promote drug abstinence in pregnant women is associated with modest costs. Future cost effectiveness and cost benefit analyses integrating costs with outcomes and benefits data will enable a more comprehensive understanding of the intervention in improving the care of substance abusing pregnant women.

The effects of the antidepressant venlafaxine (VEN-225 mg daily) and transdiagnostic cognitive behavioral treatment (CBT) alone and in combination on alcohol intake in subjects with co-morbid alcohol use disorders (AUDs) and anxiety disorders were compared. Drinking outcomes and anxiety were assessed for 81 subjects treated for 11 weeks with one of 4 conditions: 1) VEN-CBT, 2) VEN-Progressive Muscle Relaxation therapy (PMR), 3) Placebo (PLC)-CBT and 4) a comparison group of PLC-PMR. For subjects who reported taking at least one dose of study medication, the Time×Group interaction was significant for percent days of heavy drinking and drinks consumed per day. For the measure of percent days heavy drinking, the paired comparison of PLC-CBT versus PLC-PMR group indicated that the PLC-CBT group had greater drinking reductions, whereas other groups were not superior to the comparison group. In Week 11, the proportion of subjects in the PLC-CBT group that had a 50% reduction from baseline in percent days heavy drinking was significantly greater than those in the comparison group. Of the 3 "active treatment" groups only the PLC-CBT group had significantly decreased heavy drinking when contrasted to the comparison group. This finding suggests that the transdiagnostic CBT approach of Barlow and colleagues may have value in the management of heavy drinking in individuals with co-morbid alcoholism and anxiety., (Copyright © 2013 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Sorafenib (SOR) is the only systemic agent known to improve survival for hepatocellular carcinoma (HCC). However, SOR prolongs survival by less than 3 months and does not alter symptomatic progression. To improve outcomes, several phase I-II trials are currently examining SOR with radiation (RT) for HCC utilizing heterogeneous concurrent and sequential treatment regimens. Our study provides preclinical data characterizing the effects of concurrent versus sequential RT-SOR on HCC cells both in vitro and in vivo. Concurrent and sequential RT-SOR regimens were tested for efficacy among 4 HCC cell lines in vitro by assessment of clonogenic survival, apoptosis, cell cycle distribution, and γ-H2AX foci formation. Results were confirmed in vivo by evaluating tumor growth delay and performing immunofluorescence staining in a hind-flank xenograft model. In vitro, concurrent RT-SOR produced radioprotection in 3 of 4 cell lines, whereas sequential RT-SOR produced decreased colony formation among all 4. Sequential RT-SOR increased apoptosis compared to RT alone, while concurrent RT-SOR did not. Sorafenib induced reassortment into less radiosensitive phases of the cell cycle through G1-S delay and cell cycle slowing. More double-strand breaks (DSBs) persisted 24 h post-irradiation for RT alone versus concurrent RT-SOR. In vivo, sequential RT-SOR produced the greatest tumor growth delay, while concurrent RT-SOR was similar to RT alone. More persistent DSBs were observed in xenografts treated with sequential RT-SOR or RT alone versus concurrent RT-SOR. Sequential RT-SOR additionally produced a greater reduction in xenograft tumor vascularity and mitotic index than either concurrent RT-SOR or RT alone. In conclusion, sequential RT-SOR demonstrates greater efficacy against HCC than concurrent RT-SOR both in vitro and in vivo. These results may have implications for clinical decision-making and prospective trial design.

Antipsychotic pharmacotherapy is the standard of care for the treatment of schizophrenia. Although pharmacotherapy effectively improves some symptoms, others can remain. Pharmacotherapy alone also tends to produce only limited improvement in social functioning and quality of life. Supportive psychosocial therapies have been used as adjuncts to pharmacotherapy to help alleviate residual symptoms and to improve social functioning and quality of life. Additionally, therapies with psychoeducational components can focus on improving medication adherence and reducing relapse and rehospitalization. This review describes the major psychosocial therapeutic strategies that have been used effectively in patients with schizophrenia (cognitive-behavioral therapy, family intervention, social skills, and cognitive remediation), with emphasis on their utility in improving medication adherence. Therapies that integrate various psychosocial therapeutic approaches are also discussed. It is concluded that psychosocial therapy is an effective adjunct to pharmacotherapy for schizophrenia. However, these therapies vary significantly in the functional domains that they address. It is therefore important to identify the form of psychosocial intervention most likely to benefit the individual patient, and to recognize that the effectiveness of any psychosocial intervention could be influenced by such factors as the presence and severity of psychotic or affective symptoms or cognitive impairment.

Background: The combination of prophylactic pancreatic stent placement (PSP) - a temporary plastic stent placed in the pancreatic duct - and rectal non-steroidal anti-inflammatory drugs (NSAIDs) is recommended for preventing post-endoscopic retrograde cholangiopancreatography (ERCP) pancreatitis (PEP) in high-risk cases. Preliminary data, however, suggest that PSP may be unnecessary if rectal NSAIDs are administered. Given the costs and potential risks of PSP, we aim to determine whether rectal indomethacin obviates the need for pancreatic stent placement in patients undergoing high-risk ERCP.Methods/design: The SVI (Stent vs. Indomethacin) trial is a comparative effectiveness, multicenter, randomized, double-blind, non-inferiority study of rectal indomethacin alone versus the combination of rectal indomethacin and PSP for preventing PEP in high-risk cases. One thousand four hundred and thirty subjects undergoing high-risk ERCP, in whom PSP is planned solely for PEP prevention, will be randomized to indomethacin alone or combination therapy. Those who are aware of study group assignment, including the endoscopist, will not be involved in the post-procedure care of the patient for at least 48 hours. Subjects will be assessed for PEP and its severity by a panel of independent and blinded adjudicators. Indomethacin alone will be declared non-inferior to combination therapy if the two-sided 95 % upper confidence bound of the treatment difference is less than 5 % between the two groups. Biological specimens will be obtained from trial participants and centrally banked.Discussion: The SVI trial is designed to determine whether PSP remains necessary in the era of NSAIDs pharmacoprevention. The associated bio-repository will establish the groundwork for important scientific breakthrough.Trial Registration: NCT02476279, registered June 2015. [ABSTRACT FROM AUTHOR]