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This paper is an attempt to reveal the effectiveness of Critical Thinking (CT) strategies in teaching English literature in general and short stories in particular. Critiquing against the conventional teacher dominated practices in English Language Teaching (ELT) in Nepal, this also offers a set of critical thinking strategies in order to make it more participatory and effective. This heavily draws on my experience of exploiting those techniques while teaching short stories in EFL/ESL classroom in Nepal. Journal of NELTA, Vol. 17 No. 1-2, December 2012, Page 93-103 DOI: http://dx.doi.org/10.3126/nelta.v17i1-2.8101

This paper begins with a patient perspective from the first author. Faced with cascading health problems, this author describes her gradual embrace of alternative treatments. While these improved her health, they also set her apart and prompted antagonism from those in conventional medicine. She found she was not alone in benefiting from a more open view of healing, and not alone in being buffeted by the opposing medical views. Two invited commentaries from medical professionals follow, as well as the first author’s response.

This paper begins with a patient perspective from the first author. Faced with cascading health problems, this author describes her gradual embrace of alternative treatments. While these improved her health, they also set her apart and prompted antagonism from those in conventional medicine. She found she was not alone in benefiting from a more open view of healing, and not alone in being buffeted by the opposing medical views. Two invited commentaries from medical professionals follow, as well as the first author’s response.

The Philadelphia negative myeloproliferative neoplasms, including polycythemia vera, essential thrombocythemia, and myelofibrosis, are associated with substantial vascular and transformative complications. Standard therapy for high-risk disease, particularly in patients that have failed initial therapy, remains controversial. Non-pegylated interferon has previously been shown to be effective in controlling erythrocytosis, thrombocytosis and thrombotic complications, but was found to have poor tolerability and excessive adverse effects. Recently, pegylated interferon alpha-2a was introduced and found to be better tolerated and less toxic than standard interferon. In addition, in recent phase II trials, pegylated interferon alpha-2a therapy was found to induce both hematologic and molecular remissions. We retrospectively analyzed 118 myeloproliferative patients who underwent pegylated interferon alpha-2a treatment. Responses were evaluated by ELN, IWG-MET and EUMNET standardized criteria sets and adverse effects were analyzed.

We have previously reported the benefits of combination therapy with thalidomide and prednisone for the improvement of cytopenias and splenomegaly for patients with myelofibrosis (MF); both primary and those arising from an antecedent polycythemia vera (PV) and essential thrombocythemia (ET). We report here the overall efficacy of three different thalidomide-prednisone based regimens (alone or in combination with either oral cyclophosphamide for three months or continuous weekly etanercept) when assessed by the IWG-MRT response criteria which were developed after completion of these studies. Additionally we report on the durability of response and long-term follow-up. We observed an overall response rate of 28% by IWG-MRT criteria (mostly clinical improvement - 22% anemia, 8% splenomegaly) with a median duration of response of 8.5 months. Toxicities primarily consisted of neuropathy (Grade 3 or higher neuropathy in 6%) and cytopenias (Grade 3 or higher in 20%). After a median follow-up of three years, fourteen patients (28%) had expired from MF at the time of this analysis with median survival of 36 months.

Background Morbidity and mortality in tumor lysis syndrome (TLS) remains high despite increasing efforts for prevention, early detection and treatment in recent years. The current risk stratification system and treatment guidelines are largely consensus based without strong evidence. There is paucity of data on the in-hospital mortality and predictors of poor clinical outcome in this population. Methods We used the 2009-2011 Nationwide Inpatient Sample database to identify hospitalizations in patients ≥18 years with a diagnosis of TLS (International Classification of Diseases, 9th Revision, Clinical Modification [ICD-9-CM] code 277.88). Nationwide Inpatient Sample is the largest all-payer publicly available inpatient care database in the US. It contains data from five to eight million hospital stays from about 1,000 hospitals across the country and approximates a 20% sample of all US hospitals. The interval 2009-2011 was selected as ICD-9-CM code 277.88 for TLS was only introduced from the year 2009 onwards. Univariate and multivariate logistic regression were used to determine the independent predictors of in-hospital mortality. Data analysis was done using STATA version 13.0 (College Station, TX). Results Among the 997 admissions (mean age ± SD 67.58±3.33, 62.6 % males, and 80.4 % white) with TLS, in-hospital mortality was 14.44 %. Based on the results of univariate analyses (table 1), we used obesity, coronary artery disease, cardiac dysrhythmias, acute kidney injury and sepsis in the final regression model. We found that cardiac dysrhythmias (OR 4.79; 95% CI, 1.67-13.77; p=0.004) and sepsis (OR 19.70; 95% CI, 5.33-72.78; p Conclusion In this study of large national database, patients with TLS had an in-hospital mortality of 14.44 %. Independent predictors of in-hospital mortality were cardiac dysrhythmias and sepsis. Our findings might help physicians to identify sub-group of patients with TLS that are at increased risk of in-hospital mortality. Table 1 Baseline characteristics of patients with tumor lysis syndrome according to in-hospital survival Characteristics Survivors (n=853) Non-survivors (n=144) p Age( in years) Mean 68.40±3.06 67.58±3.33 0.73 Male sex 62.1 65.8 0.69 Race 0.16 White 81.52 73.54 Black 14.98 22.8 Hispanic 2.27 0 Others/unknown 1.22 3.66 Insurance status 0.41 Medicare 65.55 48.15 Medicaid 5.56 13.34 Private insurance 24.89 32.58 Self-Pay 0.65 2.99 No charge 0.63 0 Other 2.72 2.93 Region 0.13 Northeast 27.59 37.74 Midwest 28.23 12.92 South 31.34 39.9 West 12.84 9.44 Location/teaching status 0.59 Rural 7.87 10.16 Urban nonteaching 26.01 33.52 Urban teaching 66.12 56.32 Bed-size 0.84 Small 11.11 8.91 Medium 21.04 24.55 Large 67.85 66.54 Malignancies ALL 1.19 6.79 0.25 AML 2.34 6.99 0.29 CLL 27.86 16.83 0.18 CML 1.85 3.19 0.68 NHL 36.33 22.37 0.1 HD 0.53 0 0.32 Multiple Myeloma 7.39 6.56 0.82 Other hematologic malignancies 38.67 25.99 0.16 Solid tumors 35.87 26.8 0.32 Co-morbidities Smoking 15.89 21.87 0.46 Obesity 5.16 0 0.005 Dyslipidemia 27.8 16.86 0.18 Hypertension 54.17 49.19 0.63 Diabetes mellitus 27.81 16.65 0.15 PVD 1.71 3.19 0.65 CAD 13.78 3.19 0.02 AKI 60.06 79.54 0.03 CKD 28.81 25.23 0.65 Stroke 0.63 0 0.32 Sepsis 3.58 31.81 0.003 Cardiac dysrhythmias 17.96 43.42 0.04 Acute CHF 11.44 7.08 0.43 AKI=Acute Kidney Injury; ALL=Acute Lymphoblastic Leukemia; AML=Acute Myelogenous Leukemia; CAD=Coronary Artery Disease; CHF=Congestive Heart Failure; CKD=Chronic Kidney Disease; CLL=Chronic Lymphocytic Leukemia; CML=Chronic Myelogenous Leukemia; HD=Hodgkin Disease; NHL=Non Hodgkin Lymphoma; PVD=Peripheral Vascular Disease Disclosures No relevant conflicts of interest to declare.

Abstract 2818 Background: Pegylated interferon alpha-2a (Peg INF2a) has been demonstrated to be active therapy for high-risk essential thrombocythemia (ET) and polycythemia vera (PV), as well as treatment for early myelofibrosis (MF). We retrospectively analyzed the outcomes of Peg INF2a therapy in MPN patients treated outside the constraints of a clinical trial in the USA and EU. Methods: Clinical records of MPN patients treated at the participating centers, receiving Peg INF2a outside of the context of a clinical trial, were analyzed for response (ET and PV by ELN criteria; MF by EUNMET and IWG-MRT criteria), toxicity, and duration of response. Results: Patients: 115 patients were identified (54 PV (47%), 44 ET (38%), 17 MF (15%)) with a median age at diagnosis (48) and gender distribution (59% females) typical for the disorders. The patients had been diagnosed with the MPN a median of 44 months (0.0–312 months) prior to initiation of the Peg IFN2a and 64% harbored the JAK2-V617F mutation. The majority of patients (81%) had received at least one prior cytoreductive therapy for their disease (73 hydroxyurea, 39 anagrelide, 37 aspirin, 21 prior interferon (non pegylated), 3 phlebotomy alone). Therapy: Median starting dose of Peg INF2a was 45 micrograms/week (range: 22.5–180) with peak starting doses ranging from 30 to 300 micrograms/week. A total of 84 patients (73%) remain on Peg IFN2a with median duration of treatment of 17 months (range: 1.0–92). Toxicity: Overall the Peg INF2a was well tolerated. Hematological toxicity was Gr 3 or lower. There were 6 cases with anemia (5%), 10 with thrombocytopenia (9%) and 8 had leukopenia (7%). Most common non-hematologic toxicities were Gr 1–3 fatigue in 27 (23%), Gr 1 LFT elevation in 6 (5%), Gr 2–3 skin/allergic reaction in 6 (5%), Gr 1–2 nausea in 5 (4%), and Gr 2 mood disorder in 5 (4%) patients. Twenty patients (17%) discontinued therapy secondary to toxicity. Response: ET-PV: By ELN criteria, 30 PV patients achieved CR (55%), 17 achieved PR (31%), 4 achieved NR (7%), and 3 patients (5%) were lost to follow up or were too early to evaluate for response. In ET, the responses were CR in 27 (61%), PR in 7 (16%), NR in 4 (9%), and 6 patients (14%) were lost to follow up or were too early to evaluate for response. MF: The responses by IWG criteria were 1 CR (6%), 2 PR (12%), 2 CI (12%) and 9 SD (53%). By EUNMET, there were 2 CR (12%), 4 major responses (24%), 4 moderate responses (24%), 1 minor response (6%), 2 no response (12%), and 3 patients (17%) were lost to follow up or were too early to evaluate for response. Conclusions: Peg INF2a used at doses consistent with published clinical trials is active and well-tolerated when administered in a clinical setting outside of the support of a clinical trial. Given the majority of patients had previously failed cytoreductive therapy these results substantiate prior reports of efficacy of Peg INF2a in MPNs. Upcoming randomized clinical trials through the Myeloproliferative Disorders Research Consortium will help further define the role of Peg INF2a as first line therapy in high-risk MPNs. Disclosures: Mesa: Incyte: Research Funding; Lilly: Research Funding; SBio: Research Funding; Astra Zeneca: Research Funding; NS Pharma: Research Funding; Celgene: Research Funding.

Abstract 4094 Background: Our group has previously reported the benefits of thalidomide-prednisone based regimens for improvement of anemia, thrombocytopenia, and splenomegaly for patients with MF; both primary myelofibrosis (PMF), and arising from essential thrombocythemia and polycythemia (Post ET/PV MF). We sought to evaluate the overall efficacy of these commonly used regimens by evaluating long-term outcomes and applying the IWG-MRT response criteria (Tefferi et. al. Blood 2006) which arose after completion of these trials. Methods: We retrospectively analyzed the long-term outcomes, and assessed the initial therapeutic responses using IWG-MRT criteria from three parallel completed trials of MF using a thalidomide (THAL-50 mg/day) and prednisone (3 month taper beginning at 40mg, stopped at 3 months) backbone. The trials had identical eligibility criteria including adequate organ function and need for MF therapy (defined as symptomatic: anemia and/or splenomegaly). The trials were 1) THAL-PRED alone, THAL only after 3 months 2) THAL-PRED-etanercept (ETAN - TNF- alpha inhibitor at 25 micrograms subcutaneously twice a week), THAL and ETAN only after 3 months and 3) THAL-PRED – oral cyclophosphamide (CTX 25mg daily orally), THAL alone after 3 months. Results: Patients: A total of 50 pts were enrolled in these 3 trials (Males n=36, 72%) with median age of 68.5 years (Range 43–85), with 79% having PMF. Patients had advanced disease in general with 88% having intermediate 2 or high risk MF by IWG criteria (Cervantes et. al. Blood 2009), 62% patients with red cell transfusion dependence and 50% with an abnormal karyotype. Therapy initial results: 80 % of patients reached the three month juncture on the trials, with 40% reaching 6 months. Initial toxicity was myelosuppression with 3 cases of grade 3 anemia, 3 cases of grade 3 neutropenia and 4 cases of grade 3 thrombocytopenia. There were no grade 4 or higher hematological toxicities noted. Initial neuropathy was uncommon and seen in only 4% of patients. No complete responses were observed and only 1 patient had partial response (by IWG-MRT criteria). 14 patients (28% overall) met the new IWG-MRT criteria for clinical improvement; 11 for anemia (22%), 2 for thrombocytopenia (4%) and 3 for splenomegaly (6%). Responses occurred relatively quickly at an overall median of 8 weeks (range 4–12) after enrollment. Long Term Outcomes: After a median follow-up of 36 months across this cohort we observed an overall median duration of response of 8.5 months (range 3–42). Responses to THAL based regimens can lead to periods of prolonged stabilization after cessation of therapy. We observed an overall median time to institution of next therapy of 3 months (range 1–50). At the time of this analysis 14 patients (28%) have expired of their MF and median survival across the entire cohort was 36 months (3-106). Comparison of Regimens: Comparison of these three independent trials (Table 1) suggests greater toxicity and inferior response rate, duration of response, and time to next therapy with the cyclophosphamide containing regimen. Conclusion: THAL-PRED based regimens are active in a subset of MF patients for therapy primarily of anemia, and for some patients a response of good duration (even after cessation of therapy) may be obtained. IWG-MRT response assessment demonstrates utilizing additional agents to a THAL-PRED regimen do not appear to augment (and may detract from responses). Newer agents such as pomalidomide may have similar to greater efficacy without neuropathy and less myelosuppression. Disclosures: Off Label Use: There is no FDA approved agent in Myelofibrosis. All the drugs discussed; Thalidomide, Prednisone, Etanarcept and Cyclophosphamide are off-label. Mesa:SBio: Research Funding; Novartis: Research Funding; Celgene: Research Funding; Incyte: Research Funding; Roche: Research Funding; eisai: Research Funding; telik: Research Funding.