Final Efficacy and Safety Results of Pemetrexed Continuation Maintenance Therapy in the Elderly from the PARAMOUNT Phase III Study

Introduction:The PARAMOUNT Phase III trial showed that maintenance pemetrexed after pemetrexed plus cisplatin induction was well tolerated and effective for patients with advanced nonsquamous non–small-cell lung cancer. Approximately 17% of patients receiving maintenance therapy in this study were 70 years of age or older. Here we report efficacy and safety results from the PARAMOUNT study for elderly (≥70 years) and non-elderly (<70 years) patients.Methods:Final efficacy and safety data from the PARAMOUNT study were analyzed post hoc using subgroup analyses for elderly and non-elderly patients.Results:The median age was 73 years in the elderly subgroup (n = 92) and 60 years in the non-elderly subgroup (n = 447). Subgroups had similar baseline characteristics, except for a higher percentage of males and patients with a performance status of one in the elderly subgroup. For elderly patients, the median PFS was 6.4 months for pemetrexed and 3.0 months for placebo; the median OS was 13.7 months for pemetrexed and 12.1 months for placebo. For non-elderly patients, the median PFS was 4.0 months for pemetrexed and 2.8 months for placebo; the median OS was 13.9 months for pemetrexed and 10.8 months for placebo. Elderly patients experienced similar levels of low-grade toxicities, but had a higher percentage of grade 3/4 anemia and neutropenia than non-elderly patients, although importantly, this did not translate into increased febrile neutropenia.Conclusions:Continuation maintenance pemetrexed had comparable survival and toxicity profiles in the elderly and non-elderly subgroups. However, grade 3/4 anemia and neutropenia were numerically higher for elderly patients

Development of understanding in hydro-climate services in India to inform food and water security

This project aims to improve understanding of hydro-climate services in India in order to inform food and water security. It involves collaboration between UCL and the Centre for Ecology and Hydrology (CEH) in the UK and the National Institute of Hydrology (NIH), Roorkee and Indian Institute of Technology (IIT), Bombay in India. This report is structured around the three main themes of the project: catchment hydrological modelling, assessment of environmental flows under climate change, and a feasibility study to assess the potential of developing guidance for India similar to that of the Flood Estimation Handbook for the UK

Two successful pregnancies in a woman with chronic myeloid leukemia exposed to nilotinib during the first trimester of her second pregnancy: case study

The occurrence of chronic myeloid leukemia in pregnancy is rare and its management poses a clinical challenge for physicians treating these patients. We report a 30-year-old woman with chronic myeloid leukemia who became pregnant twice successfully. Philadelphia-positive CML in its chronic phase was diagnosed at 16 weeks of her first gestation. At that time, she received no treatment throughout her pregnancy. At 38 weeks of gestation, a normal infant was delivered by cesarean section. At six weeks postpartum, the patient underwent imatinib mesylate therapy but she could not tolerate the treatment. The treatment was then changed to nilotinib at 400 mg orally b.i.d. Two years later, she became pregnant again while she was on nilotinib 200 mg b.i.d. The unplanned pregnancy was identified during her 7.4 weeks of gestation. Because the patient elected to continue her pregnancy, nilotinib was stopped immediately, and no further treatment was given until delivery. Neither obstetrical complications nor structural malformations in neonates in both pregnancies were observed. Both babies' growth and development have been normal. Although this experience is limited to a single patient, the success of this patient demonstrates that the management of chronic myeloid leukemia in pregnant women may be individualized based on the relative risks and benefits of the patient and fetus

Standardisation of Various Processes in the Preparation of Kousheyashma Bhasma Accounting its Clinical Utility

Asbestos, one among the inosilicate group of minerals is listed under the Sikatha varga (Silicate compounds) in the Rasasastra treatises, in the name, Kousheyashma. Though the asbestos is vastly used for commercial purposes, it is not found to be used in clinical practices owing to its toxicity. But in Ayurveda, Acharyas have opined that by the judicious usage, even the poison can be bestowed medicinal value. And hence, after undergoing appropriate pharmaceutical processes as mentioned in the treatises, Kousheyashma can be effectively administered in Bhasma (after incineration) form in the treatment of various ailments like leucorrhoea, painful micturition, inflammation of urinary tract, menorrhagia. In this work, an attempt is made to expose the hidden medicinal values of asbestos by converting it into Bhasma form. Kousheyashma is a very cost effective and potent medicine which could be effectively used by Ayurvedic practitioners. In the present work, conversion of raw Kousheyashma into medicinal Bhasma form is discussed elaborately. The processes involved includes Sodhana and Marana of Kousheyashma. The liquid media used for the purpose of Sodhana was Gomutra and for Marana purpose, Harithamanjari swarasa was used. Three Putas were required to obtain Kousheyashma bhasma which satisfied the Bhasma pareekshas

Composite correction of a unilateral cleft lip nose deformity and alveolar bone grafting

Background: Managing the cleft lip nasal deformity has always been a challenge. Even now, there is no single established universally accepted method of correction. The open alveolar gap and the ipsilateral hypoplastic maxilla are two major problems in achieving consistently good results in a cleft lip nasal deformity. In our study, after first assuring the orthodontic realignment of maxillary arches, we combined bone grafting in the alveolar gap and along the pyriform margin, with a formal open rhinoplasty approach. Methods: All the patients underwent orthodontic treatment for preparation of the alveolar bone grafting. During the process of alveolar bone graft, a strip of septal cartilage graft was harvested from the lower border of the septum which also helps to correct the septal deviation. The cancellous bone graft harvested from the iliac crest was used to fill the alveolar gap and placed along the pyriform margin to gain symmetry. Through open rhinoplasty along the alar rim and additionally using Potter′s incision extending to the lateral vestibule, the lateral crura of the alar cartilage on the cleft side was released from its lateral attachment and advanced medially as a chondromucosal flap in a V-Y fashion, in order to bring the cleft-side alar cartilage into a normal symmetric position. The harvested septal cartilage graft was used as a columellar strut. The cleft nostril sill was narrowed by a Y-V advancement at the alar base and any overhanging alar rim skin was carefully excised to achieve symmetry. Results: The results of this composite approach were encouraging in our series of 15 patients with no additional morbidity and a better symmetry of the nose and airway especially in the adolescent age group. Conclusion: This concept of simultaneous approach when appropriate for nasal correction at the time of alveolar bone grafting showed an encouraging aesthetic and functional outcome

CRE: a cost effective and rapid approach for PCR-mediated concatenation of KRAS and EGFR exons [version 2; referees: 2 approved]

Molecular diagnostics has changed the way lung cancer patients are treated worldwide. Of several different testing methods available, PCR followed by directed sequencing and amplification refractory mutation system (ARMS) are the two most commonly used diagnostic methods worldwide to detect mutations at KRAS exon 2 and EGFR kinase domain exons 18-21 in lung cancer. Compared to ARMS, the PCR followed by directed sequencing approach is relatively inexpensive but more cumbersome to perform. Moreover, with a limiting amount of genomic DNA from clinical formalin-fixed, paraffin-embedded (FFPE) specimens or fine biopsies of lung tumors, multiple rounds of PCR and sequencing reactions often get challenging. Here, we report a cost-effective single multiplex-PCR based method, CRE (for Co-amplification of five KRAS and EGFR exons), followed by concatenation of the PCR product as a single linear fragment for direct sequencing. CRE is a robust protocol that can be adapted for routine use in clinical diagnostics with reduced variability, cost and turnaround time requiring a minimal amount of template DNA extracted from FFPE or fresh frozen tumor samples. As a proof of principle, CRE is able to detect the activating EGFR L858R and T790M EGFR mutations in lung cancer cell line and primary tumors