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BACKGROUND Selinexor, a selective inhibitor of nuclear export compound that blocks exportin 1 (XPO1) and forces nuclear accumulation and activation of tumor suppressor proteins, inhibits nuclear factor κB, and reduces oncoprotein messenger RNA translation, is a potential novel treatment for myeloma that is refractory to current therapeutic options. METHODS We administered oral selinexor (80 mg) plus dexamethasone (20 mg) twice weekly to patients with myeloma who had previous exposure to bortezomib, carfilzomib, lenalidomide, pomalidomide, daratumumab, and an alkylating agent and had disease refractory to at least one proteasome inhibitor, one immunomodulatory agent, and daratumumab (triple-class refractory). The primary end point was overall response, defined as a partial response or better, with response assessed by an independent review committee. Clinical benefit, defined as a minimal response or better, was a secondary end point. RESULTS A total of 122 patients in the United States and Europe were included in the modified intention-to-treat population (primary analysis), and 123 were included in the safety population. The median age was 65 years, and the median number of previous regimens was 7; a total of 53% of the patients had high-risk cytogenetic abnormalities. A partial response or better was observed in 26% of patients (95% confidence interval, 19 to 35), including two stringent complete responses; 39% of patients had a minimal response or better. The median duration of response was 4.4 months, median progression-free survival was 3.7 months, and median overall survival was 8.6 months. Fatigue, nausea, and decreased appetite were common and were typically grade 1 or 2 (grade 3 events were noted in up to 25% of patients, and no grade 4 events were reported). Thrombocytopenia occurred in 73% of the patients (grade 3 in 25% and grade 4 in 33%). Thrombocytopenia led to bleeding events of grade 3 or higher in 6 patients. CONCLUSIONS Selinexor-dexamethasone resulted in objective treatment responses in patients with myeloma refractory to currently available therapies. (Funded by Karyopharm Therapeutics; STORM ClinicalTrials.gov number, NCT02336815. © 2019 Massachusetts Medical Society.

Background: Swine flu (H1N1) is very infectious respiratory disease occurring in different parts of world showing pandemicity from time to time. Thorough knowledge about its epidemiology and clinical symptoms, attitude towards disease and practices to prevent its occurrence and spread are essential in all age groups especially in school children. To assess the awareness, practices, their attitude and myths regarding swine flu among adolescent school going children in Kolhapur district Maharashtra.Methods: A pre-tested questionnaire was designed emphasized on the demographic profile, knowledge and misconceptions about cause, transmission, prevention and cure of swine flu (H1N1) and social responsibility of every student about spreading awareness. The questionnaires were distributed to school students of 9th& 10th standard only. Maximum 15 minutes were allotted to participants. A power point presentation regarding swine flu was delivered to participants and staff members.Results: Total 210 study participants were included. 80.47% students knew cause of swine flu is viral and 69.04% knew it spreads through airborne route. 73.33% students correctly knew about symptoms of swine flu. 71.90% mentioned all the correct preventive methods as wearing face mask of appropriate size, vaccination against swine flu and maintaining hand hygiene. In reality only 32.38% students exclusively practicing hand hygiene.Conclusions: Although the term was well known, better recognition of pandemic influenza cases is needed. Children were not aware about certain important treatment and prevention aspects of the disease.

Promising new drugs are being evaluated for treatment of multiple myeloma (MM), but their impact should be measured against the expected outcome in patients failing current therapies. However, the natural history of relapsed disease in the current era remains unclear. We studied 286 patients with relapsed MM, who were refractory to bortezomib and were relapsed following, refractory to or ineligible to receive, an IMiD (immunomodulatory drug), had measurable disease, and ECOG PS of 0, 1 or 2. The date patients satisfied the entry criteria was defined as time zero (T-0). The median age at diagnosis was 58 years, and time from diagnosis to T-0 was 3.3 years. Following T-0, 213 (74%) patients had a treatment recorded with one or more regimens (median = 1; range 0-8). The first regimen contained bortezomib in 55 (26%) patients and an IMiD in 70 (33%). A minor response or better was seen to at least one therapy after T0 in 94 patients (44%) including >= partial response in 69 (32%). The median overall survival and event-free survival from T-0 were 9 and 5 months, respectively. This study confirms the poor outcome, once patients become refractory to current treatments. The results provide context for interpreting ongoing trials of new drugs. Leukemia (2012) 26, 149-157; doi:10.1038/leu.2011.196; published online 29 July 2011

A population pharmacokinetic (PK) model and exposure–response (E-R) analysis was developed using data collected from 5 phase 1b/2 and 2 phase 3 studies in subjects with multiple myeloma. Subjects receiving intravenous infusion on 2 consecutive days each week for 3 weeks (days 1, 2, 8, 9, 15, and 16) in each cycle at doses ranging from 15 to 20/56 mg/m2 (20 mg/m2 in cycle 1 and, if tolerated, escalated to 56 mg/m2 on day 8 of cycle 1). The population PK analysis indicated that among all the covariates tested, the only statistically significant covariate was body surface area on carfilzomib clearance; however, this covariate was unlikely to be clinically significant. Despite inclusion of different populations (relapsed or relapsed/refractory), treatments (carfilzomib monotherapy or combination therapy), infusion lengths (2 to 10 minutes or 30 minutes), and different doses, the E-R analysis of efficacy showed that after adjusting for baseline characteristics, higher area under the concentration–time curve was associated with improved overall response rate (ORR), from 15 to 20/56 mg/m2. No positive relationships between maximum concentration and ORR were identified, indicating that ORR would not be expected to be impacted by infusion length. For safety end points, no statistically significant relationship between exposure and increasing risk of adverse events was identified. The results of an E-R analysis provided strong support for a carfilzomib dose at 20/56 mg/m2 as a 30-minute infusion for monotherapy and combination therapy. This article illustrates an example of application of E-R analysis to support labeling dose recommendation in the absence of extensive clinical data. © 2016, The American College of Clinical Pharmacology

Introduction of new myeloma therapies offers new options for patients refractory to immunomodulatory drugs (IMiDs) and proteasome inhibitors (PIs). In this multicenter study, patients with relapsed multiple myeloma, who have received at least three prior lines of therapy, are refractory to both an IMiD (lenalidomide or pomalidomide) and a PI (bortezomib or carfilzomib), and have been exposed to an alkylating agent were identified. The time patients met the above criteria was defined as time zero (T 0). Five hundred and forty-three patients diagnosed between 2006 and 2014 were enrolled in this study. Median age at T 0 was 62 years (range 31-87); 61% were males. The median duration between diagnosis and T 0 was 3.1 years. The median number of lines of therapy before T 0 was 4 (range 3-13). The median overall survival (OS) from T 0 for the entire cohort was 13 (95% confidence interval (CI) 11, 15) months. At least one regimen recorded after T 0 in 462 (85%) patients, with a median (95% CI) progression-free survival and OS from T 0 of 5 (4, 6), and 15.2 (13, 17) months, respectively. The study provides the expected outcome of relapsed multiple myeloma that is refractory to a PI and an IMiD, a benchmark for comparison of new therapies being evaluated. © 2017 Macmillan Publishers Limited, part of Springer Nature. All rights reserved.

In this work, we have selected three number of stepped type solar stills of the same overall dimensions 620 mm (W) × 808 mm (L) but with different absorber surface areas due to the variation in the shape of the basin surface. The other design parameters like depth of water, thickness of glass cover, insulation thickness, type of condensing cover, absorbing material provided over the basin, and angle of inclination of the still were kept constant to study the effect of shape of the absorber surface over the distillate yield obtained. The shape of the absorber surface provided in the basins of solar stills A, E and F was flat, convex and concave respectively. When the convex and concave type stepped solar stills are used, the average daily water production has been found to be 56.60% and 29.24% higher than that of flat type stepped solar still respectively. Also an economic analysis was made. The payback period of flat type, convex type and concave type stepped solar still is 823 days, 525 days and 637 days respectively. Thus, the convex type solar still gives the returns within the least possible time as compared to other two types of stepped solar stills. The laboratory tests were conducted to test the quality of water after distillation. The tests indicate that the quality of water in terms of pH, electrical conductivity, total hardness, TDS, Alkalinity, Nitrates etc. is well within the desirable limits as prescribed by WHO for Indian specific conditions.

Background The present global, open-label, single-arm, multicenter, phase IIb study was designed to determine the efficacy and tolerability of oral vorinostat combined with standard doses of bortezomib in patients with multiple myeloma considered refractory to novel myeloma agents. Patients and Methods Eligible patients were age ≥ 18 years, had received ≥ 2 previous regimens, had disease refractory to ≥ 1 previous bortezomib-containing regimen, and had received ≥ 1 dose of an immunomodulatory drug (thalidomide or lenalidomide)-based regimen. The patients received 21-day cycles of bortezomib (1.3 mg/m2 intravenously on days 1, 4, 8, and 11) plus oral vorinostat (400 mg/d on days 1-14). Oral dexamethasone, 20 mg, on the day of and the day after each dose of bortezomib could be added for patients with progressive disease after 2 cycles or no change after 4 cycles. The primary endpoint was the objective response rate. Results The objective response rate was 11.3% (95% confidence interval, 6.6%-17.7%), and the median duration of response was 211 days (range, 64-550 days). The median overall survival duration was 11.2 months (95% confidence interval, 8.5-14.4 months), with a 2-year survival rate of 32%. The frequently reported adverse events were thrombocytopenia (69.7%), nausea (57.0%), diarrhea (53.5%), anemia (52.1%), and fatigue (48.6%); the overall safety profile was consistent with that of bortezomib and vorinostat. Conclusion The combination of vorinostat and bortezomib is active in patients with multiple myeloma refractory to novel treatment modalities and offers a new therapeutic option for this difficult-to-treat patient population (ClinicalTrials.gov identifier, NCT00773838). © 2016 Elsevier Inc.

Treatment of multiple myeloma has substantially changed over the past decade with the introduction of several classes of new effective drugs that have greatly improved the rates and depth of response. Response criteria in multiple myeloma were developed to use serum and urine assessment of monoclonal proteins and bone marrow assessment (which is relatively insensitive). Given the high rates of complete response seen in patients with multiple myeloma with new treatment approaches, new response categories need to be defined that can identify responses that are deeper than those conventionally defined as complete response. Recent attempts have focused on the identification of residual tumour cells in the bone marrow using flow cytometry or gene sequencing. Furthermore, sensitive imaging techniques can be used to detect the presence of residual disease outside of the bone marrow. Combining these new methods, the International Myeloma Working Group has defined new response categories of minimal residual disease negativity, with or without imaging-based absence of extramedullary disease, to allow uniform reporting within and outside clinical trials. In this Review, we clarify several aspects of disease response assessment, along with endpoints for clinical trials, and highlight future directions for disease response assessments. © 2016 Elsevier Ltd

Renal impairment (RI) is a major comorbidity in patients with multiple myeloma (MM). Here we present the pooled safety and efficacy analysis of three clinical trials (MM-002, MM-003, and MM-010) of pomalidomide + low-dose dexamethasone (POM + LoDEX) in patients with moderate RI (creatinine clearance [CrCl] ≥ 30 to

Purpose: The aim of the International Myeloma Working Group was to develop practical recommendations for the diagnosis and management of multiple myeloma–related renal impairment (RI). Methods: Recommendations were based on published data through December 2015, and were developed using the system developed by the Grading of Recommendation, Assessment, Development, and Evaluation Working Group. Recommendations: All patients with myeloma at diagnosis and at disease assessment should have serum creatinine, estimated glomerular filtration rate, and electrolytes measurements as well as free light chain, if available, and urine electrophoresis of a sample from a 24-hour urine collection (grade A). The Chronic Kidney Disease Epidemiology Collaboration, preferably, or the Modification of Diet in Renal Disease formula should be used for the evaluation of estimated glomerular filtration rate in patients with stabilized serum creatinine (grade A). International Myeloma Working Group criteria for renal reversibility should be used (grade B). For the management of RI in patients with multiple myeloma, high fluid intake is indicated along with antimyeloma therapy (grade B). The use of high-cutoff hemodialysis membranes in combination with antimyeloma therapy can be considered (grade B). Bortezomib-based regimens remain the cornerstone of the management of myeloma-related RI (grade A). High-dose dexamethasone should be administered at least for the first month of therapy (grade B). Thalidomide is effective in patients with myeloma with RI, and no dose modifications are needed (grade B). Lenalidomide is effective and safe, mainly in patients with mild to moderate RI (grade B); for patients with severe RI or on dialysis, lena-lidomide should be given with close monitoring for hematologic toxicity (grade B) with dose reduction as needed. High-dose therapy with autologous stem cell transplantation (with melphalan 100 mg/m2 to 140 mg/m2) is feasible in patients with RI (grade C). Carfilzomib can be safely administered to patients with creatinine clearance > 15 mL/min, whereas ixazomib in combination with lenalidomide and dex-amethasone can be safely administered to patients with creatinine clearance > 30 mL/min (grade A). © 2016 by American Society of Clinical Oncology.

Background: Obstructive lung diseases as asthma and Chronic Obstructive Pulmonary Disease (COPD) have considerable morbidity and mortality globally. Chronic obstructive pulmonary disease (COPD) remains a major public health problem. It is projected to rank fifth in 2020 in burden of disease worldwide, according to the WHO study. Aim and objectives was to evaluate clinical profiles of obstructive lung diseases patients attending tertiary care hospital.Methods: The data was collected from 112 obstructive lung diseases patients presenting to OPD of pulmonary medicine department from January 2009 to August 2010. Research tool comprised of questions about demographic characteristics, past or presenting symptoms, general and systemic examinations. For statistical analysis MS Excel and SPSS 16 were used.Results: Overall 72 (64.28%) were smokers. 63 (56.25%) were suffering from COPD and 49 (43.75%) were asthmatic. Breathlessness was found as most common symptom in 53 (84.12%) COPD and in 45 (91.83%) asthma patients. Among COPD patients, 26 (41.26%) were of moderate obstruction whereas in asthma patients, 17 (34.69%) were of moderate obstruction and 16 (32.65%) were of severe obstruction as per Pulmonary Function Tests (PFT).Conclusions: Males were most commonly affected in obstructive lung diseases. COPD was common after 35 years of age where as asthma occurs mostly before 35 years of age. Smoking was most common etiological factor. Breathlessness was the most common presenting symptom. Family history of asthma was most common risk factor for asthma patients. Most of the patients with both COPD as well as asthma had moderate type of obstructions.

Background: There is an increase in prevalence of childhood obesity and its chronic health effects especially in developing countries like India in last 2-3 decades. This study is small effort to know prevalence and risk factors causing obesity. Aim of the study was to estimate prevalence of obesity and its risk factors in school students of age group 11 to 16 years.Methods: About 207 adolescent school children from selected school were enrolled in the study. Research tool comprised of questions about demographic characteristics, daily physical activity, frequency of having junk food intake etc. Height and weight were measured on calibrated scales. For statistical analysis MS Excel and SPSS 16 were used.Results: Among participants 58.9% were boys. 66.7% students were in the 13 to 14 years of age group. As per body mass index, 46.9% children were underweight and 8.7% were obese. 77.3% participants were eating junk food more than once in a week.Conclusions: Health education on dietary habits and physical activity is needed for adolescent children to prevent development of obesity and complications related to it.

In contrast to the upfront setting in which the role of high-dose therapy with autologous hematopoietic cell transplantation (HCT) as consolidation of a first remission in patients with multiple myeloma (MM) is well established, the role of high-dose therapy with autologous or allogeneic HCT has not been extensively studied in MM patients relapsing after primary therapy. The International Myeloma Working Group together with the Blood and Marrow Transplant Clinical Trials Network, the American Society of Blood and Marrow Transplantation, and the European Society of Blood and Marrow Transplantation convened a meeting of MM experts to: (1) summarize current knowledge regarding the role of autologous or allogeneic HCT in MM patients progressing after primary therapy, (2) propose guidelines for the use of salvage HCT in MM, (3) identify knowledge gaps, (4) propose a research agenda, and (5) develop a collaborative initiative to move the research agenda forward. After reviewing the available data, the expert committee came to the following consensus statement for salvage autologous HCT: (1) In transplantation-eligible patients relapsing after primary therapy that did NOT include an autologous HCT, high-dose therapy with HCT as part of salvage therapy should be considered standard; (2) High-dose therapy and autologous HCT should be considered appropriate therapy for any patients relapsing after primary therapy that includes an autologous HCT with initial remission duration of more than 18 months; (3) High-dose therapy and autologous HCT can be used as a bridging strategy to allogeneic HCT; (4) The role of postsalvage HCT maintenance needs to be explored in the context of well-designed prospective trials that should include new agents, such as monoclonal antibodies, immune-modulating agents, and oral proteasome inhibitors; (5) Autologous HCT consolidation should be explored as a strategy to develop novel conditioning regimens or post-HCT strategies in patients with short (less than 18 months remissions) after primary therapy; and (6) Prospective randomized trials need to be performed to define the role of salvage autologous HCT in patients with MM relapsing after primary therapy comparing it to "best non-HCT" therapy. The expert committee also underscored the importance of collecting enough hematopoietic stem cells to perform 2 transplantations early in the course of the disease. Regarding allogeneic HCT, the expert committee agreed on the following consensus statements: (1) Allogeneic HCT should be considered appropriate therapy for any eligible patient with early relapse (less than 24 months) after primary therapy that included an autologous HCT and/or high-risk features (ie, cytogenetics, extramedullary disease, plasma cell leukemia, or high lactate dehydrogenase); (2) Allogeneic HCT should be performed in the context of a clinical trial if possible; (3) The role of postallogeneic HCT maintenance therapy needs to be explored in the context of well-designed prospective trials; and (4) Prospective randomized trials need to be performed to define the role salvage allogeneic HCT in patients with MM relapsing after primary therapy. © 2015 American Society for Blood and Marrow Transplantation.

Background: Menstrual disorders affect half of all female adolescents and represent leading cause of periodic college absenteeism but awareness regarding health seeking behaviour is less. Objective was to study association between common menstrual disorders and college absenteeism in first and second year medical students in Mumbai . Methods: 150 female students from first and second year MBBS were included in the study. Research tool comprised of questions about demographic characteristics, age at menarche, menstrual cycle pattern, complaints and its impact on daily activities including college absenteeism. Behaviour towards health and knowledge about menstrual cycle was observed. Percentage and chi square values were calculated using SPSS 16. The study was conducted in period between August to October 2012. Results: 150 first and second year female medical students participated in the study. Their mean age was 19.5 yrs. Mean age of menarche was 13-14 years in 78%. Menstrual cycle was regular in 72.6%. Menstrual flow was average in 73.3% of respondents and 88% reported duration as 3-5 days. 92% respondents had painful menses especially reporting moderate pain in 78% while in 70% of those pain resolved on its own. 67.4% reported mother as source of menstrual cycle information. Although menstrual disorder was cause of college absenteeism of 1-2 days in 44% students, 88% students didn’t seek medical advice for menstrual disorders . Conclusions: Improving health seeking behaviour towards common menstrual problems can reduce college absenteeism.

This International Myeloma Working Group consensus updates the disease definition of multiple myeloma to include validated biomarkers in addition to existing requirements of attributable CRAB features (hypercalcaemia, renal failure, anaemia, and bone lesions). These changes are based on the identification of biomarkers associated with near inevitable development of CRAB features in patients who would otherwise be regarded as having smouldering multiple myeloma. A delay in application of the label of multiple myeloma and postponement of therapy could be detrimental to these patients. In addition to this change, we clarify and update the underlying laboratory and radiographic variables that fulfil the criteria for the presence of myeloma-defining CRAB features, and the histological and monoclonal protein requirements for the disease diagnosis. Finally, we provide specific metrics that new biomarkers should meet for inclusion in the disease definition. The International Myeloma Working Group recommends the implementation of these criteria in routine practice and in future clinical trials, and recommends that future studies analyse any differences in outcome that might occur as a result of the new disease definition. © 2014 Elsevier Ltd.

The role of vertebral augmentation in multiple myeloma: International Myeloma Working Group Consensus Statement