Choice Of Initial Therapy Research Articles

Sequential Treatment With Targeted and Immune Checkpoint Therapy in Patients With BRAF Positive Metastatic Melanoma: The Importance of Timing?

Background: Immune checkpoint- and targeted therapy have dramatically improved the therapeutic landscape in the management of BRAF mutation positive metastatic melanoma. However, pending the results of clinical trials, not only is it currently unclear whether immune checkpoint- or targeted therapy should be commenced up front, but the optimal time for changing treatment, specifically to prevent resistance whilst maintaining disease control, is unknown.Methods: We retrospectively identified eleven patients with BRAF V600 mutated metastatic melanoma who commenced targeted therapy between 11/2012 and 12/2017 in our center. In 5 cases the decision was made to “electively” switch to immune checkpoint therapy (elective group) following the development of a complete or partial response. In the remaining 6 cases the initial “reactive” switch was necessitated by disease progression or the development of intolerable side-effects (reactive group).Results: Overall, the elective cohort had a more favorable course in terms of overall survival (1,003 vs. 827 days), and 80% of the patients remain alive, in contrast to 17 % of the patients in the reactive group. However, it should be borne in mind that multiple switches due to disease progression were undertaken and this undoubtedly also impacted upon overall survival.Conclusion: Elective switching from targeted to immune checkpoint therapy was associated with a better outcome in terms of survival, at least in everyday clinical practice. It remains unclear whether the choice of initial therapy confers long–term survival and disease-control advantages and this should be addressed in prospective studies.

Long-term outcomes in Chinese patients with chronic hepatitis B receiving nucleoside/nucleotide analogue therapy in real-world clinical practice: 5-year results from the EVOLVE study.

In China, the optimal management of individuals living with chronic HBV infection (CHB) remains an unmet need. The EVOLVE Study was a 5-year prospective, longitudinal, observational study that compared the clinical outcomes in treatment-naive CHB patients receiving entecavir (ETV) or lamivudine (LAM)-based therapies. Males or females aged ≥18 years, diagnosed with CHB regardless of cirrhosis or hepatitis B e antigen (HBeAg) status were enrolled from tier 2 city hospitals (between 2012-2014). The choice of initial therapy and subsequent treatment modifications was at the discretion of treating physicians. Key outcomes included treatment modifications, virological response (HBV DNA <300 copies/ml) and HBV disease progression. Of the 3,408 patients enrolled, 1,807 and 628 received ETV and LAM-based therapy, respectively. The mean age was 39.5 years, 74% were male and 22.9% had cirrhosis. The rate of treatment modification was higher in the LAM-based versus ETV group (25.9% versus 13.7%); viral breakthrough was the most common reason in the LAM-based group versus financial reasons in the ETV group. At week 240, the virological response rate was 73% in both treatment groups. Compared with LAM-based therapy, ETV was associated with a significantly lower incidence of viral breakthrough (12.6% versus 2.1%) and genotypic resistance (10.1% versus 1.2%; P<0.0001 for both); significantly lower risk of HBV disease progression (14.0% versus 10.7%; P=0.0113); and lower rates of progression to decompensated cirrhosis (9.6% versus 6.4%) and hepatocellular carcinoma (1.9% versus 0.8%). This real-world, longitudinal study demonstrated a significantly lower risk of HBV-related disease progression, viral breakthrough and resistance with ETV versus LAM-based therapy. ClinicalTrials.gov NCT01726439.

Pathological Findings and Magnetic Resonance Imaging Concordance at Salvage Radical Prostatectomy for Local Recurrence following Partial Ablation Using High Intensity Focused Ultrasound.

We describe the pathological characteristics of recurrence following high intensity focused ultrasound partial ablation in men treated with salvage robot-assisted radical prostatectomy. We assessed the sensitivity of magnetic resonance imaging before salvage robot-assisted radical prostatectomy in these men. A total of 35 men underwent salvage robot-assisted radical prostatectomy after high intensity focused ultrasound partial ablation from 2012 to 2018. We compared clinicopathological characteristics before ultrasound and before salvage prostatectomy after ultrasound to histopathology on salvage prostatectomy. We assessed infield recurrence, out of field disease, positive surgical margins and magnetic resonance imaging sensitivity before salvage robot-assisted radical prostatectomy. Before high intensity focused ultrasound 55.9% of men had multifocal disease and 47.1% had Gleason 3 + 3 disease outside the treatment field. Median time to salvage prostatectomy was 16 months (IQR 11-26). Indications for salvage prostatectomy were infield recurrence in 55.8% of cases, out of field recurrence in 20.6%, and infield and out of field recurrence in 23.5%. On salvage prostatectomy histopathology revealed significant cancer, defined as ISUP (International Society of Urological Pathology) 2 or greater, infield in 97.1% of cases, out of field in 81.3%, and infield and out of field in 79.4%. Of the cases 82.4% were adversely reclassified at salvage prostatectomy compared to 67.6% before ultrasound. The positive surgical margin rate was 40.0%. Of the positive margins 84.6% were in the region of previous ultrasound despite wide excision, including pT2 in 28.6%, pT3 in 47.6% and size 3 mm or greater, pT3 or multifocal (ie significant) in 31.4%. After ultrasound the sensitivity of magnetic resonance imaging for infield and out of field recurrence was 81.8% and 60.7%, respectively. Salvage robot-assisted radical prostatectomy may confer a higher risk of positive surgical margins, upgrading and up-staging than primary robot-assisted radical prostatectomy. High intensity focused ultrasound carries a risk of recurrence inside and outside the ablation zone. This information may inform salvage surgical planning and patient counseling regarding the choice of initial therapy and salvage treatment after high intensity focused ultrasound.

Chronic Urticaria: An Overview of Treatment and Recent Patents.

Background: Up to 1% of the general population in the USA and Europe suffer from chronic urticaria (CU) at some point in their lifetime. CU has an adverse effect on the quality of life.Objective: This study aims to provide an update on the epidemiology, pathogenesis, clinical manifesta-tions, diagnosis, aggravating factors, complications, treatment and prognosis of CU.Methods: The search strategy included meta-analyses, randomized controlled trials, clinical trials, reviews and pertinent references. Patents were searched using the key term “chronic urticaria” at the following links: www.google.com/patents, www.uspto.gov, and www.freepatentsonline.com.Results: CU is a clinical diagnosis, based on the episodic appearance of characteristic urticarial lesions that wax and wane rapidly, with or without angioedema, on most days of the week, for a period of six weeks or longer. Triggers such as medications, physical stimuli, and stress can be identified in 10 to 20% of cases. C-reactive protein/erythrocyte sedimentation rate, and complete blood cell count with differential are the screening tests that may be used to rule out an underlying disorder. The mainstay of therapy is reassurance, patient education, avoidance of known triggers, and pharmacotherapy. Second-generation H1 antihistamines are the drugs of choice for initial therapy because of their safety and efficacy profile. If satisfactory improvement does not occur after 2 to 4 weeks or earlier if the symptoms are intolerable, the dose of second-generation H1 antihistamines can be increased up to fourfold the manufacturer’s recom-mended dose (all be it off license). If satisfactory improvement does not occur after 2 to 4 weeks or earlier if the symptoms are intolerable after the fourfold increase in the dosage of second-generation H1 antihis-tamines, omalizumab should be added. If satisfactory improvement does not occur after 6 months or earli-er if the symptoms are intolerable after omalizumab has been added, treatment with cyclosporine and sec-ond-generation H1 antihistamines is recommended. Short-term use of systemic corticosteroids may be considered for acute exacerbation of CU and in refractory cases. Recent patents for the management of chronic urticaria are also discussed. Complications of CU may include skin excoriations, adverse effect on quality of life, anxiety, depression, and considerable humanistic and economic impacts. On average, the duration of CU is around two to five years. Disease severity has an association with disease duration.Conclusion: CU is idiopathic in the majority of cases. On average, the duration of CU is around two to five years. Treatment is primarily symptomatic with second generation antihistamines being the first line. Omalizumab has been a remarkable advancement in the management of CU and improves the quality of life beyond symptom control.

Primary therapy of Graves' disease and cardiovascular morbidity and mortality: a linked-record cohort study

Graves' disease is routinely treated with antithyroid drugs, radioiodine, or surgery, but whether the choice of initial therapy influences long-term outcomes is uncertain. We evaluated cardiovascular morbidity and mortality according to the method and effectiveness of primary therapy in Graves' disease. In this retrospective cohort study, we identified patients with hyperthyroidism, diagnosed between Jan 1, 1998, and Dec 31, 2013, from a thyroid-stimulating hormone (TSH)-receptor antibody (TRAb) test register in south Wales, UK, and imported their clinical data into the All-Wales Secure Anonymised Information Linkage (SAIL) Databank (Swansea University, Swansea, UK). Patients with Graves' disease, defined by positive TRAb tests, were selected for the study, and their clinical data were linked with outcomes in SAIL. We had no exclusion criteria. Patients were matched by age and sex to a control population (1:4) in the SAIL database. Patients were grouped by treatment within 1 year of diagnosis into the antithyroid drug group, radioiodine with resolved hyperthyroidism group (radioiodine group A), or radioiodine with unresolved hyperthyroidism group (radioiodine group B). We used landmark Kaplan-Meier and Cox regression models to analyse the association of treatment with the primary outcome of all-cause mortality and the secondary outcome of major adverse cardiovascular events (myocardial infarction, heart failure, ischaemic stroke, or death) with the landmark set at 1 year after diagnosis. We analysed the association between outcomes and concentration of TSH using Cox regression and outcomes and free thyroxine (FT4) concentration using restricted cubic-spline regression models. We extracted patient-level data on 4189 patients (3414 [81·5%] females and 775 [18·5%] males) with Graves' disease and 16 756 controls (13 656 [81·5%] females and 3100 [18·5%] males). In landmark analyses, 3587 patients were in the antithyroid drug group, 250 were in radioiodine group A, 182 were in radioiodine group B. Patients had increased all-cause mortality compared with controls (hazard ratio [HR] 1·22, 95% CI 1·05-1·42). Compared with patients in the antithyroid drug group, mortality was lower among those in radioiodine group A (HR 0·50, 95% CI 0·29-0·85), but not for those in radioiodine group B (HR 1·51, 95% CI 0·96-2·37). Persistently low TSH concentrations at 1 year after diagnosis were associated with increased mortality independent of treatment method (HR 1·55, 95% CI 1·08-2·24). Spline regressions showed a positive non-linear relationship between FT4 concentrations at 1 year and all-cause mortality. Regardless of the method of treatment, early and effective control of hyperthyroidism among patients with Graves' disease is associated with improved survival compared with less effective control. Rapid and sustained control of hyperthyroidism should be prioritised in the management of Graves' disease and early definitive treatment with radioiodine should be offered to patients who are unlikely to achieve remission with antithyroid drugs alone. National Institute for Social Care and Health Research, Wales.

The argument for using imatinib in CML.

June 2018 was the 20th anniversary of the clinical use of the first tyrosine kinase inhibitor (TKI), imatinib, for chronic myeloid leukemia. Since then, the change in prognosis for patients with this disease is one of the major success stories of modern cancer medicine. The dilemmas that face physicians and patients are no longer only those concerned with delaying inevitable progression to the terminal blastic phase or selecting the individuals most likely to benefit from allogeneic stem-cell transplantation; rather, they are now focused also on the choice of TKI, the management of comorbidities and adverse effects, strategies to improve quality of life, and the appropriateness of a trial of therapy discontinuation. Interestingly, with 4 TKIs approved for frontline use, the choice of initial therapy continues to cause controversy, a situation made more complicated by the tantalizing prospect of treatment-free remission. In this manuscript, we will explore the factors influencing this decision and try to provide a pragmatic and clinically applicable solution.

Improvements in Imaging of Hodgkin Lymphoma: Positron Emission Tomography.

18-Fluoro-2-deoxy-D-glucose positron emission tomography/computed tomography (FDG PET/CT) is currently the criterion standard of lymphoma imaging and recommended through all stages of Hodgkin lymphoma management. Accurate staging is important for risk stratification and initial choice of therapy and also for the planning of postchemoradiotherapy. 18-Fluoro-2-deoxy-D-glucose PET/CT frequently leads to upstaging and potentially a more intensive treatment. Visual-only assessment of staging and interim scans is being accompanied by quantitative and semiquantitative methods to measure metabolic tumor volume, total lesion glycolysis, and so on. It is still unclear if these methods significantly improve the value of FDG PET/CT by visual assessment only. Because of the good prognostic value of FDG PET/CT, a large number of studies have used interim FDG PET to tailor treatment to the individual patients, according to their early metabolic response rather than according to their pretreatment prognostic features. 18-Fluoro-2-deoxy-D-glucose PET/CT is standard of care for posttreatment response assessment but has no place in routine follow-up of Hodgkin lymphoma patients in remission.

Multiple Myeloma: Front Line Therapy and Autologous Stem Cell Transplantation

Prognosis of multiple myeloma (MM) has improved during the past two decades. This has been attributed to the better understanding of the biology of disease leading to introduction of two new classes of molecules, namely immune-modulators (e.g. thalidomide, lenalidomide), and proteasome inhibitors (e.g. bortezomib), use of high dose chemotherapy and autologous stem cell transplantation (ASCT) and better supportive care. Current management of myeloma for young patients (≤65 years) includes initial induction therapy followed by consolidation with ASCT followed by maintenance therapy with low dose thalidomide or lenalidomide or bortezomib for 1-2 years. The choice of initial therapy for patients of MM is based upon their eligibility for ASCT which in turn is based on their age and major co-morbid conditions pertaining to cardiac and renal systems. Patients who are ≤65 years of age (or 65 to 70 years) with no major co-morbid conditions are considered potential candidates for ASCT. Four cycles of induction therapy are administered; a combination of 3 drugs (bortezomib, thalidomide, and dexamethasone (BTD) or bortezomib, lenalidomide, and dexamethasone (BLD) or bortezomib, cyclophosphamide and dexamethasone (BCD) is associated with higher complete response (CR) (approx. 30-40%) and very good partial response (VGPR) and better progression free survival (PFS). Further consolidation with ASCT results in CR rates of 50%–70%; patients who achieve CR, have improved event-free and overall survival. Our initial experience with 225 ASCT supports these observations. It is now possible to individualize therapy in a given patient. For example, for patients with renal failure (present in 20-30% of patients at diagnosis) —bortezomib, dexamethasone and/or doxorubicin combination could be an option; for patients with pre-existing peripheral neuropathy—lenalidomide and dexamethasone is preferred; for patients at high risk of venous thrombo-embolism bortezomib- based regimens can be used safely. Treatment with bortezomib or bortezomib + lenalidomide for patients with poor cytogenetics (chromosome deletion t(4;14), t(14;16), 17p–) appears to result in an outcome similar to that in patients without these abnormalities. In conclusion, from being incurable, myeloma is now a chronic illness. Along with earlier diagnosis, improved treatment and better management of complications have resulted in longer disease control and survival with a better quality of life. Novel agents have provided an opportunity to tailor therapy in an individual patient. Further research is needed to improve outcome for patients who fail to achieve complete response, those with ISS stage III, and extra-medullary disease. Availability of oral proteasome inhibitors and monoclonal antibodies (e.g. IL-6 receptor) are likely to expand choice of agents for maintenance therapy in future.

Choroidal neovascular membrane in paediatric patients: clinical characteristics and outcomes

PurposeTo analyse the clinical characteristics and treatment outcomes of choroidal neovascular membranes (CNVM) in paediatric subjects at three paediatric retina referral centres.MethodsMedical charts of patients aged 18 years or less...

Geographic Variation of Adjuvant Breast Cancer Therapy Initiation in the United States: Lessons From Medicare Part D.

Background: Drug utilization under Medicare Part D varies significantly by geographic region. This study examined the extent to which geographic variation in Part D plan characteristics contributes to the variation in choice of initial endocrine therapy agent among women with incident breast cancer. Methods: Two-stage multivariate regression analyses were applied to the 16,541 women identified from Medicare claims as having incident breast cancer in 2006-2007. The first stage determined the effect of state of residence on the probability of having an aromatase inhibitor (AI), as opposed to tamoxifen, as initial endocrine therapy. The second stage provided estimates of the impact of state-specific Part D plan characteristics on variation in choice of initial therapy. Results: There was substantial residual geographic variation in the likelihood of using an AI as initial endocrine therapy, despite controlling for socioeconomic status, breast cancer treatment, and other factors. Regression-adjusted probabilities of starting an AI ranged from 57.3% in Wyoming to 92.6% in the District of Columbia. Results from the second stage revealed that variation in characteristics of Part D plans across states explained approximately one-third (30%) of the state-level variability in endocrine therapy. A higher number of plans with cost-sharing above the mean, greater spread in deductibles, and a greater spread in monthly drug premiums were associated with lower adjusted state probabilities of initiating an AI. In contrast, a higher number of drug plans with monthly premiums above the state mean and higher mean cost-sharing (in dollars) were both positively associated with likelihood of starting on an AI. Conclusions: Study findings suggest that variation in benefit design of Part D plans accounts for an important share of the large and persisting variability in use of AIs-the preferred oral therapy for breast cancer.

Azacitidine in Lower-Risk Myelodysplastic Syndromes: A Meta-Analysis of Data from Prospective Studies.

After erythropoiesis-stimulating agent (ESA) failure, lenalidomide and hypomethylating agents are the only remaining treatment options for most patients with lower-risk myelodysplastic syndromes (LR-MDS). Optimal choice of these agents as front-line therapy in non-del(5q) LR-MDS is unclear. Because azacitidine clinical data mainly describe experience in higher-risk MDS, we performed a meta-analysis of patient-level data to evaluate azacitidine in patients with red blood cell (RBC) transfusion-dependent LR-MDS. We searched English-language articles for prospective phase II and III azacitidine clinical trials and patient registries published between 2000 and 2015, and Embase abstracts from 2015 conferences. Patient-level data from identified relevant studies were provided by investigators. Meta-analyses followed Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. Efficacy endpoints were RBC transfusion independence (TI) and Clinical Benefit (RBC-TI, erythroid response, and complete or partial remission, per International Working Group 2006 criteria for MDS). Data for 233 patients from 6 clinical studies and 1 registry study met criteria for inclusion in analyses. Overall, 90.3% of patients had non-del(5q) LR-MDS. Pooled estimates from random-effects models of RBC-TI and Clinical Benefit were 38.9% and 81.1%, respectively; for the ESA-refractory subgroup, they were 40.5% and 77.3%; and for patients with isolated anemia, they were 41.9% and 82.5%. In multivariate analyses, planned use of ≥6 azacitidine treatment cycles was significantly predictive of response. Azacitidine effects in these patients, most with non-del(5q) LR-MDS, were promising and generally similar to those reported for lenalidomide in similar patients. The choice of initial therapy is important because most patients eventually stop responding to front-line therapy and alternatives are limited. Lower-risk myelodysplastic syndromes (LR-MDS) are primarily characterized by anemia. After erythropoiesis-stimulating agent (ESA) failure, lenalidomide and hypomethylating agents are the only remaining treatment options for most patients. This meta-analysis of 233 azacitidine-treated red blood cell (RBC) transfusion-dependent patients with LR-MDS (92.3% non-del[5q]) from 7 studies showed 38.9% became RBC transfusion-independent. There is no clear guidance regarding the optimal choice of lenalidomide or hypomethylating agents for patients with non-del(5q) LR-MDS following ESA failure. Clinical presentation (e.g., number of cytopenias) and potential outcomes after hypomethylating agent failure are factors to consider when making initial treatment decisions for LR-MDS patients.

Long-acting beta2-agonists versus long-acting muscarinic antagonists in patients with stable COPD: A systematic review and meta-analysis of randomized controlled trials.

Several long-acting bronchodilators have been developed and are widely used as first-line treatment in patients with stable chronic obstructive pulmonary disease (COPD). However, the initial choice of therapy is still uncertain. The aim of this study was to examine the clinical efficacy and safety of long-acting muscarinic antagonist (LAMA) and long-acting beta2-agonist (LABA) in patients with stable COPD. We searched several databases and manufacturers' websites to identify relevant randomized clinical trials for meta-analysis. Outcomes of interest were trough forced expiratory volume in 1 s (FEV1 ), acute exacerbations, transitional dyspnoea index (TDI) score, St George's Respiratory Questionnaire (SGRQ) score and adverse events. Sixteen trials with a total of 22 872 patients were included in this study. Compared with LABA, LAMA were associated with a greater reduction in acute exacerbations (OR: 0.84, 95% CI: 0.74-0.94, P = 0.003) and fewer adverse events (OR: 0.92, 95% CI: 0.86-0.97, P = 0.005). There were no significant differences in trough FEV1 , TDI and SGRQ scores. In patients with stable COPD, LAMA were associated with a greater reduction in acute exacerbations and fewer adverse effects compared with LABA.

Ten-year survival after randomized comparison of imatinib (IM) 400 mg vs. IM 800 mg vs. IM + IFN vs. IM + Ara C vs. IM after IFN in chronic myeloid leukemia (CML).

7049 Background: It is unclear whether IM 400 mg is the optimum choice for the successful treatment of CML. Treatment optimization was therefore attempted. Methods: From July 2002 to March 2012, 1551 newly diagnosed patients in chronic phase (CP) were randomized into a 5-arm study to analyze 2 IM doses and 3 combinations. 1536 patients were evaluable, 400 for IM 400 mg, 420 for IM 800 mg, 430 for IM + Interferon (IFN), 158 for IM + Ara C and 128 for IM after IFN. Recruitment to the latter two arms was stopped after a pilot phase. Results: 10-year overall survival (OS) of all patients was 82%, 10-year progression free survival (PFS) 80%. 10-year OS was 80% with IM 400 mg, 79% with IM 800 mg, 84% with IM + IFN, 84% with IM + Ara C and 79% with IM after IFN. The differences were not significant. 10-year PFS was 80% with IM 400mg, 77% with IM 800mg, 83% with IM + IFN, 82% with IM + Ara C and 75% with IM after IFN. The differences were not significant either. Survival with any treatment was not significantly different from IM 400mg at any risk level by any risk score (Euro Sokal, EUTOS, ELTS). 87 patients progressed to blast crisis (BC). The 10-year cumulative incidence of BC was 5.8% (95% CI: 4.7%; 7.1%) equally distributed across treatment arms. Most BC occurred in the first 2 years. Median survival after BC was 7.9 months across treatment arms. 275 patients have died, 23 after stem cell transplantation in first CP. Two thirds of deaths were unrelated to CML. Incidence of death due to CML by competing risk analysis with death unrelated to CML as competing risk was not different between the 5-treatment arms. 10-year relative survival probability was 92% when compared to matched general population data. Patients reaching the cytogenetic or molecular response landmarks according to European LeukemiaNet criteria ( &lt; 10% BCR-ABL IS at 3 months, &lt; 1% BCR-ABL IS or complete cytogenetic remission at 6 months, &lt; 0.1% BCR-ABL IS (MMR) at 12 months) had a significantly better survival than those not reaching the landmarks regardless of therapy. Conclusions: In conclusion, outcome of CML is currently more determined by prognostic markers than by choice of therapy. IM400 mg remains an excellent choice for initial therapy of CP-CML. Clinical trial information: NCT00055874.

Use of complementary and alternative medicines in Indian elderly patients

Background: Use of complementary and alternative medicine (CAM) is more common in elderly patients due to the prevalence of various age-related chronic medical conditions. The pharmacokinetics and pharmacodynamics change with age and are different in the elderly as compared to a young adult. Non-disclosure of CAM usage voluntarily by the patients, along with the practice of poly-pharmacy for various comorbidities and concurrent use of modern medicine with CAM, makes this age group particularly prone to adverse effects of drugs and the drug–drug interactions. Use of CAM assumes further importance in the context of Indian elderly, due to the widespread belief in traditional medicines and easy over-the-counter availability of many prescription drugs in India. Aims and Objective: The study was conducted to understand and analyze the knowledge, attitude, and perception of CAM usage specifically in elderly Indian patients, which to the best of our knowledge has yet not been assessed previously. Materials and Methods: It was a descriptive cross-sectional study assessing a representative sample of 325 elderly patients over the age of 60 years. Data collection was done after face-to-face interview-based survey administered on a semi-structured questionnaire. Results: The number of CAM users (65.5%) was significantly more than the non-users (P ≤ 0.05). In the age group between 60 and 69 years, 59% had used CAM, as compared to a significantly more number of 76% patients (P ≤ 0.05), in the age group above 70 years. The CAM practice in the elderly was not influenced significantly by gender, education, rural or urban background, and distance from the health-care facility of modern medicine system. CAM was the initial choice of therapy for 65.7% of the users. Ayurveda was the most popular practice (64.8%), followed by homeopathy (62.4%) with many patients using both the practices together. Use of CAM practices concomitantly with modern medicine was not considered unsafe by 56.8% of patients. The physicians of modern medicine did not ask 91.5% of elderly patients about CAM usage and 85.5% of patients did not volunteer any information on CAM usage unless asked for. Conclusions: The study suggests the need to acknowledge and explore the high prevalence of CAM usage with increasing age in the Indian elderly, both to identify the irrational usage of CAM alone or in combination with the modern medicine system and to facilitate the integration of rational CAM practices in the mainstream medicine.

Pilot Initiative of Fitness Testing for Treatment Selection in Elderly Acute Myelogenous Leukemia (AML)

Introduction: The optimal treatment of older patients with Acute Myeloid Leukemia (AML) is unclear. Traditional induction chemotherapy is less effective in older patients and often more toxic. Clinical trials for elderly AML patients feature inclusion/exclusion criteria based on "fitness" for chemotherapy that often include subjective assessments and variable enrollment criteria. Determining "fitness" remains controversial, and there are few validated objective markers to assist in determining whether a patient is "fit" or "unfit" for intensive induction chemotherapy. Previously published work identified a Short Physical Performance Battery (SPPB) score < 9 and a Modified Mini-Mental Status (3MS) score <77 as independent predictors of worse survival in patients treated with intensive therapy in AML (Klepin et al Blood 2013). Other data suggests using objective measures that include SPPB and 3MS scores to categorize risk in elderly AML patients as "fit", vulnerable or frail (Klepin et al Hematology 2014). Use of the geriatric assessment and quality of life measurements has been suggested to be incorporated in the initial evaluation of AML patients in order to help predict which patients will have poor outcomes with intensive therapy (Deschler et al Haematologica 2013). Based on these publications, a pilot initiative was begun to establish the feasibility of incorporating the SPPB and 3MS tests into practice as objective measures to assist in determination of "fitness" for intensive chemotherapy.Methods: Beginning December 2015, patients age ≥ 60 who presented with new or relapsed AML were evaluated using the 3MS and SPPB tests. To increase objectivity, the 3MS and SPPB tests were performed by a non-treating provider when possible. Patients who were determined to be a fall risk by history had their SPPB test performed by a specially trained physical therapist. Scores were made immediately available to the treating physician and were used as a guide to determine if the patient was "fit" for intensive therapy or "unfit". If "unfit" the patient was evaluated for a clinical trial for "unfit" patients, hypomethylating agents or best supportive care (BSC). Scores were taken into context with age and comorbidities for treatment decisions.Results: Testing was feasible using the SPPB and 3MS and easy to implement, with testing taking approximately 15 minutes. A total of 21 new or relapsed AML patients have been evaluated. The median age was 72, ranging from age 60-83. There were10 male and 11 female patients. Three patients had relapsed disease. Fifteen patients had evaluable data >60 days. Seven were determined "fit" for intensive chemotherapy. Median SPPB and 3MS scores were 9 and 95, respectively. Six achieved remission following intensive induction therapy. One patient underwent allogeneic stem cell transplant and remains in remission. Three relapses occurred at days 44, 50 and 54 from initial induction therapy. Two deaths occurred from relapsed disease at days 148 and 175 from initial induction and one death from infection at day 54 during consolidation therapy.Eight patients were determined to be "unfit" for intensive chemotherapy. Median SPPB and 3MS scores were 5 and 93, respectively. Two patients received BSC based on clinical judgement and died at days 32 and 50 from initial diagnosis. Both were the only patients of 21 evaluated to have a 3MS score < 77. Four patients were eligible for clinical trials at our institution. Two deaths occurred 95 and 52 days from initiation of clinical trial, and 2 remain on trial at 61 and 65 days from initial therapy with one in complete remission. Two patients were given decitabine. One died at 34 days from initial therapy due to infectious complications and the other remains on treatment.Conclusion: Performance of the SPPB and 3MS tests on patients age ≥ 60 is feasible and should be considered at diagnosis for elderly AML patients. Our group found that the use of objective measures was most helpful in identifying the two patients who had impaired cognition at baseline with 3MS scores < 77. The use of a second provider as an examiner allowed for thoughtful discussion regarding choice of initial therapy. Based on this pilot, further investigation and validation of SPPB and 3MS testing for "fitness" prior to determining choice of therapy in patients with new or relapsed AML age ≥ 60 should be pursued. DisclosuresNo relevant conflicts of interest to declare.

Extended Non-Vitamin K Antagonist Oral Anticoagulation Therapy for Prevention of Recurrent Venous Thromboembolism. a Review of Phase III and Phase IV Studies

▪Duration of anticoagulation can be categorised into initial treatment, lasting 3, 6 or 12 months, and long-term treatment beyond 12 months. There is a strong rationale for anticoagulation treatment beyond the acute phase in many patients with venous thromboembolism (VTE), being the risk of recurrent VTE after stopping anticoagulation high, particularly for unprovoked deep vein thrombosis (DVT). Several non-vitamin K antagonist oral anticoagulants (NOACs) have been approved in the acute setting; accumulating evidence suggests continuing treatment with these agents beyond 12 months offers additional benefits to patients with VTE.Apixaban, dabigatran and rivaroxaban have been studied in this setting in a series of phase III extension studies (AMPLIFY-EXT, RE-MEDY and RE-SONATE, and EINSTEIN EXT, respectively).AMPLIFY-EXT evaluated patients who had completed 6-12 months of anticoagulation treatment with apixaban. Patients received either a further 12 months of apixaban at a dose of 2.5 mg or 5 mg twice daily, or placebo. Recurrent VTE or mortality from any cause were 3.8%, 4.2% and 11.6%, respectively (relative risk [95% confidence interval (CI)] vs placebo: 0.33 [0.22-0.48] and 0.66 [0.25-0.53], respectively); for major bleeding, rates were 0.2%, 0.1% and 0.5%, respectively (relative risk [95% CI] vs placebo: 0.49 [0.09-2.64] and 0.25 [0.03-2.24], respectively).In RE-MEDY, patients received either dabigatran (150 mg twice daily) or warfarin for 6-36 months after at least 3 months of prior anticoagulation treatment. Recurrent or fatal VTE occurred in 1.8% of patients treated with dabigatran versus 1.3% of warfarin-treated patients (P=0.01 for non-inferiority); major bleeding rates were lower with dabigatran (0.9% vs 1.8%) but this difference was not statistically significant.In the RE-SONATE study, dabigatran (150 mg twice daily) or placebo was administered for up to 12 months. Recurrent or fatal VTE was significantly lower with dabigatran (0.4% vs 5.6%; P<0.001). Rates of major bleeding were low in both groups (0.3% with dabigatran; no major bleeding episodes occurred in the placebo group); however, for the composite of major or non-major clinically relevant bleeding, the rate was significantly greater with dabigatran (5.3% vs 1.8%; P=0.001).In EINSTEIN EXT, patients who had completed 6-12 months of rivaroxaban or VKA anticoagulation treatment were randomised to receive either rivaroxaban or placebo for 6 or 12 months. Extended rivaroxaban treatment was associated with a significantly lower rate of recurrent VTE (1.3% vs 7.1%, respectively; P<0.001), and there was a moderate, non-significant, increase in the rate of major bleeding complications (0.7% of patients in the rivaroxaban group vs none in the placebo group; P=0.11).The phase III extension studies demonstrate the benefits of extended NOAC use versus treatment cessation, with reduced recurrence rates versus placebo, although associated with a potential moderate increase in bleeding risk; in addition, based on outcomes in patients given placebo, it is clear that not prescribing anticoagulation treatment is not a viable approach.VTE is associated with substantial costs, and recurrent episodes increase costs further. The costs are attributable to hospitalisation, treatment facility and staff and outpatient management. The lack of routine coagulation monitoring needed with use of NOACs may simplify patient management, thereby further reducing the burden on healthcare providers and patients.US and European guidelines advise long-term therapy in certain instances. They support NOAC use where they have been selected as the initial therapy choice and therapy needs to be extended beyond 3 months.In addition to clinical trials of extended anticoagulation, assessment of this therapy in routine clinical practice is essential, in order to confirm whether the results of clinical trials apply to a broad range of patients beyond the highly controlled setting of a clinical study. Phase IV data are now emerging (Dresden Noacs Registry, Xalia Study, Einstein Choice Study, Start Register) and are supportive of the findings from phase III studies. Future studies involving all NOACs will be valuable in determining the safety and effectiveness of long-term NOAC use in a wider patient population. DisclosuresPiovella:GlaxoSmithKline: Speakers Bureau; Portola: Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; PFIZER/BMS: Speakers Bureau; Bayer: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau.

A Cost-Effectiveness Analysis of Treatment Options for Adult Eosinophilic Esophagitis Utilizing a Markov Model: 2016 ACG Presidential Poster Award

Introduction: Eosinophilic Esophagitis (EoE) has become increasingly prevalent over the past two decades. The 2013 American College of Gastroenterology EoE guidelines recommend dietary changes (six-food elimination diet [6-FED]), or topical steroids with either swallowed fluticasone (FLT) or viscous budesonide (BDN), as first line therapy. These treatment options vary significantly in their costs and effectiveness, so in an increasingly cost conscious healthcare system, we sought to evaluate the costeff ectiveness of these options. Methods: We developed a decision analytic Markov Model to compare the cost-effectiveness of 3 initial therapy options for a 30-year old man with a new diagnosis of EoE: 1-FLT, 2-BDN and 3-6-FED. Main health states included active disease (both initially and after failing therapy), histologic remission, stricture (either primarily or after initial remission) or death. If patients failed one therapy, they could progress to a second-line (6-FED if steroid first or BDN if 6-FED first) and then a third-line option (elemental diet). The 6-FED strategy required 6 endoscopies as part of treatment evaluation. We utilized a payer perspective, 3 months cycles and a 5-year time horizon. Transition probabilities, costs, and quality adjusted life years [QALY] data were taken from the published literature and available public data sources. Outcome measures were reported in incremental cost-effectiveness ratios (ICERs; 2015 US dollars per QALY). We set the willingness to pay (WTP) threshold at $100,000/QALY. Results: In the base case, 6-FED was the preferred treatment option (most effective and least costly) (Table 1). In 1-way sensitivity analysis (SA), the BDN strategy became the most cost effective when the cost of an endoscopy (EGD) increased to greater than $2417 (Figure 1) or when the probability of remission for those on the 6-FED was less than 0.678 (Figure 2).Figure 1Figure 2Table 1: Cost-Effectiveness Results Comparing Six-Food Elimination Diet to Fluticasone and Budesonide for Patients with New Diagnosis of Eosinophilic EsophagitisConclusion: Our results showed that the 6-FED was the most cost-effective strategy. Sensitivity analysis revealed that altering the cost of an EGD and the probability of remission for 6-FED had the greatest impact on choice of initial strategy. Current data suggests that adult who eliminate only wheat and dairy, frequently resolve symptoms, thus requiring fewer than six EGDs, and further demonstrating that 6-FED is the most effective strategy. These findings when taken together with the likelihood that a patient will comply with a 6-FED, can help guide initial choice of therapy.

A Cross-Sectional study of Drug Prescription Pattern in Urticaria patients attending Dermatology &amp; Venereology Department in a Rural Tertiary Care Teaching Hospital

Background: Urticaria is a very common skin condition characterized by recurrent, pruritic (itchy), pink-to-red edematous (swollen) lesions that often have pale centers (wheals). Histamine is the main mediator of urticaria and H1 antihistamines represent the initial and mainstay treatment of urticaria. The newer second generation H1 antihistamines are preferred over the older first generation H1 antihistamines as the initial choice of therapy due to its less sedating and less cholinergic side effects. Although numerous treatments are available for urticaria, there is little information about the prescription pattern for the treatment of urticaria. Hence this study was conducted. Methods: This was a cross-sectional study conducted on 100 newly diagnosed and untreated patients of urticaria who attended Dermatology and Venereology outpatient department of a rural tertiary care teaching hospital. The prescriptions were collected for the duration of 18 months and details of prescription (particulars of the patient, diagnosis, name of the drugs, dose, route of administration, total duration etc.) were collected in case record forms. Results: Majority of the patients (34) belonged to the age group of 21-35years. The mean age of the patients was 34.35±15.26 years. Most of the patients were treated with oral antihistamines. Among oral antihistamines, most of the patients received 2nd generation antihistamines either as monotherapy or in combination with 1st generation antihistamines and H2 blockers. Among 2nd generation antihistamines, fexofenadine was prescribed highest either as monotherapy or in combination with levocetirizine and cetirizine. Patients with more severe form of disease were treated with combination of oral and parenteral therapy. Further long term study is required for proper assessment of prescription pattern in urticaria patients. Conclusion: Most of the patients with urticaria can be effectively treated with Oral antihistaminic medication, and additional parenteral therapy may be required only for severe cases of acute on chronic urticaria. Keywords: Urticaria, Oral medication, Parenteral therapy, Antihistamines

Evidence-based medical oncology and interventional radiology paradigms for liver-dominant colorectal cancer metastases.

Colorectal cancer metastasizes predictably, with liver predominance in most cases. Because liver involvement has been shown to be a major determinant of survival in this population, liver-directed therapies are increasingly considered even in cases where there is (limited) extrahepatic disease. Unfortunately, these patients carry a known risk of recurrence in the liver regardless of initial therapy choice. Therefore, there is a demand for minimally invasive, non-surgical, personalized cancer treatments to preserve quality of life in the induction, consolidation, and maintenance phases of cancer therapy. This report aims to review evidence-based conceptual, pharmacological, and technological paradigm shifts in parenteral and percutaneous treatment strategies as well as forthcoming evidence regarding next-generation systemic, locoregional, and local treatment approaches for this patient population.

Epidemiology and risk factors for nosocomial Non-Candida albicans candidemia in adult patients at a tertiary care hospital in North China.

Nosocomial candidemia extends the length of hospital stay, increases the costs of medical care, and is associated with a high mortality rate. Epidemiological data that assist in the choice of initial therapy may help to improve the prognosis. The present study was undertaken to investigate the epidemiology of nosocomial candidemia and identify risk factors for nosocomial candidemia caused by C. albicans and non-albicans Candida species (NAC). A retrospective chart review was undertaken to analyze cases of nosocomial candidemia treated at the Beijing Friendship Hospital between January 2008 and December 2012. All cases of candidemia were identified using the previously published criteria. Among 106 patients analyzed, 53.8% had nosocomial candidemia caused by NAC. Candida albicans was the most common causative agent, accounting for 46.2% of all cases, followed by C. glabrata (25.5%), C. tropicalis (15.1%), C. parapsilosis (10.4%) and C. Krusei (0.9%). Comparison of nosocomial C. albicans and NAC candidemia by multivariate logistic regression showed that factors independently associated with nosocomial NAC candidemia included exposure to azole agents (odds ratio [OR]: 3.359; 95% confidence interval [CI]: 1.136-10.154; P = .031) and artificial surgical implants (OR: 37.519; 95% CI: 2.5-562.998; P = .009). A significant risk factor for nosocomial C. albicans candidemia was cancer surgery (OR: 0.075; 95% CI: 0.013-0.437; P = .004). Clinical and epidemiological differences in the risk factors between nosocomial candidemia caused by C. albicans and NAC should be considered when selecting an initial antifungal regimen for the treatment of adult patients. This should be undertaken before the availability of species identification and/or antifungal susceptibility results.