Validation of EORTC quality-of-life questionnaire in Indian women with operable breast cancer

Background: The European Organization for Research and Treatment of Cancer (EORTC) module QLQ-C30 and the breast cancer-specific module BR-23 have been validated world-wide to assess the quality of life ( QOL) in women with breast cancer. No such study has been published on Indian women using EORTC questionnaires. Methods: QOL was assessed in relation to surgery, adjuvant chemotheraphy, radiation therapy and hormone therapy in 299 Indian women with operable breast cancer (OBC) at the Breast Unit of Tata Memorial Hospital( TMH), Mumbai, from October 1998 to September 2001. The QLQ-C30 module was used to assess physical health, emotional, cognitive and social functioning, and the BR-23 module to assess breast cancer treatment-related symptoms. Assessment was done at 3 visits: visit 1 ( after surgery); visit 2 ( during adjuvant therapy) and visit 3 ( on completion of adjuvant therapy). Results: Of the 299 women at first visit, 274 (91.6%) completed the visit 2 questionnaire and 239 ( 80%) completed the visit 3 questionnaire. Only those women who filled the questionnaires at all 3 visits were included as 'valid visits' for analysis ( 193 of 299; 64.5%). The reliability and validity of the English and translated versions of the questionnaires were tested by Cronbach alpha (0.61-0.96) and item-scale correlation (0.63-0.93). Women with breast conversion treatment had a superior body image as compared to those with mastectomy (p<0.01). Physical, emotional and cognitive functions were not related to the type of surgery. Global QOL, physical, sexual and role functioning were found to deteriorate with chemo-therapy ( p≤0.01). Radiotherapy had only local adverse wffects (p<0.001), while hormone theraphy had no adverse impact on QOL. Conclusion: QLQ-C30 and BR-23 questionnaires can be used reliably to assess QOL in Indian patients. The translated versions were found to be valid for further use in clinical trials on Indian women with breast cancer

Multicentricity of breast cancer: whole-organ analysis and clinical implications

We studied the spatial relationship within the breast between multicentric foci (MCF) and the primary tumour in 30 modified radical mastectomy specimens using Egan's correlated pathological-radiological method using 5 mm slices of the whole breast. The relative positions within the breast of the primary tumour and MCF were used to calculate the relative distribution of primary tumour and MCF in the four quadrants of the breast and the per cent breast volume that would be required to be excised to include all MCF. Nineteen (63%) breast harboured MCF. The relative distribution of primary tumour and MCF in the four breast quadrants was significantly different (P = 0.034). MCF were present beyond the index quadrant (25% of breast volume including the tumour) in as many as 79% (15/19) of breasts that harboured MCF; and in half the cases (15/30) when all breast were considered. This is in variance with the suggestion put forward previously that MCF are contained within the index quadrant in 90% of cases. Although the number of patients in the present series is small, the probability of our finding being due to play of chance is 1 in 1500. In a large series of breast conservation studies > 90% of early breast recurrences have been found to occur in the index quadrant. Our finding, that in half the patients (15/30) MCF are present in quadrants other than the index quadrant, suggests that MCF do not give rise to early breast recurrence

Prognosis of operable squamous cell carcinoma of the esophagus. Relationship with clinicopathologic features and DNA ploidy

Background: Reports on the influence of various prognostic factors in carcinoma of the esophagus are conflicting. The prognostic value of a set of clinicopathologic factors and DNA ploidy were examined in 74 patients with surgically resected squamous cell carcinoma of the lower and middle third of the esophagus. Methods: All patients had surgery performed in a single thoracic surgical unit at the Tata Memorial Hospital between January, 1984 and December, 1987. The clinicopathologic factors studied were (1) gross residual disease at operation; (2) morphology of the tumor; (3) depth of microscopic invasion; (4) lymph node involvement; (5) histologic grade; (6) vascular and lymphatic embolism; and (7) sex. DNA ploidy and S-phase fraction (SpF) were determined by flow cytometry on archival tissues extracted from paraffin blocks. Ploidy status could be determined successfully in all 74 tumors, whereas SpF could be assessed only in 25. Results: Of the various prognostic factors examined with the Cox stepwise regression model, residual disease (P = 0.000), depth of invasion (P = 0.047), and lymph node status (P = 0.077) were found to be correlated with overall survival. Conclusions: DNA ploidy was not related to prognosis. The overall survival of this group of patients at 36 months was 28%, and median survival was 18 months

Reflection of light from a disordered medium backed by a phase-conjugating mirror

This is a theoretical study of the interplay of optical phase-conjugation and multiple scattering. We calculate the intensity of light reflected by a phase-conjugating mirror when it is placed behind a disordered medium. We compare the results of a fully phase-coherent theory with those from the theory of radiative transfer. Both methods are equivalent if the dwell time \tau_{dwell} of a photon in the disordered medium is much larger than the inverse of the frequency shift 2\Delta\omega acquired at the phase-conjugating mirror. When \tau_{dwell} \Delta\omega < 1, in contrast, phase coherence drastically affects the reflected intensity. In particular, a minimum in the dependence of the reflectance on the disorder strength disappears when \Delta\omega is reduced below 1/\tau_{dwell}. The analogies and differences with Andreev reflection of electrons at the interface between a normal metal and a superconductor are discussed.Comment: 27 pages RevTeX with 11 figures included with psfi

A novel strategy to discover and use climate-adapted germplasm

Between 2012 and 2015, 150 researchers, research managers, gene bank managers, extension agents, university professors and staff of non-government organizations from Bhutan, Burkina Faso, Costa Rica, Côte d’Ivoire, Guatemala, Nepal, Rwanda, Uganda, Zambia and Zimbabwe acquired new knowledge and skills about the use of climate and crop modelling tools and data sources including the climate analogue tool introduced through the CGIAR research programme on Climate Change, Agriculture and Food Security (CCAFS). Applying these tools and data to their national context, they assessed the changing needs for national and foreign-sourced plant genetic resources for food and agriculture in the context of climate change adaptation. Research teams are now designing strategies to deploy germplasm that is better adapted to future climate changes and that could contribute to increased food security. They are integrating these strategies into organizational agenda’s that will be implemented with own resources

Therapeutic efficacy of artemether-lumefantrine in uncomplicated falciparum malaria in India

<p>Abstract</p> <p>Background</p> <p>Artemisinin-based combination therapy (ACT) is the treatment of choice for uncomplicated falciparum malaria. Artemether-lumefantrine (AL), a fixed dose co-formulation, has recently been approved for marketing in India, although it is not included in the National Drug Policy for treatment of malaria. Efficacy of short course regimen (4 × 4 tablets of 20 mg artemether plus 120 mg lumefantrine over 48 h) was demonstrated in India in the year 2000. However, low cure rates in Thailand and better plasma lumefantrine concentration profile with a six-dose regimen over three days, led to the recommendation of higher dose globally. This is the first report on the therapeutic efficacy of the six-dose regimen of AL in Indian uncomplicated falciparum malaria patients. The data generated will help in keeping the alternative ACT ready for use in the National Programme as and when required.</p> <p>Methods</p> <p>One hundred and twenty four subjects between two and fifty-five years of age living in two highly endemic areas of the country (Assam and Orissa) were enrolled for single arm, open label prospective study. The standard six-dose regimen of AL was administered over three days and was followed-up with clinical and parasitological evaluations over 28 days. Molecular markers <it>msp</it>-<it>1 </it>and <it>msp</it>-2 were used to differentiate the recrudescence and reinfection among the study subjects. In addition, polymorphism in <it>pfmdr</it>1 was also carried out in the samples obtained from patients before and after the treatment.</p> <p>Results</p> <p>The PCR corrected cure rates were high at both the sites viz. 100% (n = 53) in Assam and 98.6% (n = 71) in Orissa. The only treatment failure case on D7 was a malnourished child. The drug was well tolerated with no adverse events. Patients had pre-treatment carriage of wild type codons at positions 86 (41.7%, n = 91) and 184 (91.3%, n = 91) of <it>pfmdr1 </it>gene.</p> <p>Conclusion</p> <p>AL is safe and effective drug for the treatment of acute uncomplicated falciparum malaria in India. The polymorphism in <it>pfmdr</it>1 gene is not co-related with clinical outcome. However, treatment failure can also occur due to incomplete absorption of the drug as is suspected in one case of failure at D7 in the study. AL can be a viable alternative of artesunate plus sulphadoxine/pyrimethamine (AS + SP), however, the drug should be used rationally and efficacy needs to be monitored periodically.</p

Rethinking the patient: using Burden of Treatment Theory to understand the changing dynamics of illness

&lt;b&gt;Background&lt;/b&gt; In this article we outline Burden of Treatment Theory, a new model of the relationship between sick people, their social networks, and healthcare services. Health services face the challenge of growing populations with long-term and life-limiting conditions, they have responded to this by delegating to sick people and their networks routine work aimed at managing symptoms, and at retarding - and sometimes preventing - disease progression. This is the new proactive work of patient-hood for which patients are increasingly accountable: founded on ideas about self-care, self-empowerment, and self-actualization, and on new technologies and treatment modalities which can be shifted from the clinic into the community. These place new demands on sick people, which they may experience as burdens of treatment.&lt;p&gt;&lt;/p&gt; &lt;b&gt;Discussion&lt;/b&gt; As the burdens accumulate some patients are overwhelmed, and the consequences are likely to be poor healthcare outcomes for individual patients, increasing strain on caregivers, and rising demand and costs of healthcare services. In the face of these challenges we need to better understand the resources that patients draw upon as they respond to the demands of both burdens of illness and burdens of treatment, and the ways that resources interact with healthcare utilization.&lt;p&gt;&lt;/p&gt; &lt;b&gt;Summary&lt;/b&gt; Burden of Treatment Theory is oriented to understanding how capacity for action interacts with the work that stems from healthcare. Burden of Treatment Theory is a structural model that focuses on the work that patients and their networks do. It thus helps us understand variations in healthcare utilization and adherence in different healthcare settings and clinical contexts

Phase 3 Trial of 177Lu-Dotatate for Midgut Neuroendocrine Tumors

Background Patients with advanced midgut neuroendocrine tumors who have had disease progression during first-line somatostatin analogue therapy have limited therapeutic options. This randomized, controlled trial evaluated the efficacy and safety of lutetium-177 (177Lu)-Dotatate in patients with advanced, progressive, somatostatin-receptor-positive midgut neuroendocrine tumors. Methods We randomly assigned 229 patients who had well-differentiated, metastatic midgut neuroendocrine tumors to receive either 177Lu-Dotatate (116 patients) at a dose of 7.4 GBq every 8 weeks (four intravenous infusions, plus best supportive care including octreotide long-acting repeatable [LAR] administered intramuscularly at a dose of 30 mg) (177Lu-Dotatate group) or octreotide LAR alone (113 patients) administered intramuscularly at a dose of 60 mg every 4 weeks (control group). The primary end point was progression-free survival. Secondary end points included the objective response rate, overall survival, safety, and the side-effect profile. The final analysis of overall survival will be conducted in the future as specified in the protocol; a prespecified interim analysis of overall survival was conducted and is reported here. Results At the data-cutoff date for the primary analysis, the estimated rate of progression-free survival at month 20 was 65.2% (95% confidence interval [CI], 50.0 to 76.8) in the 177Lu-Dotatate group and 10.8% (95% CI, 3.5 to 23.0) in the control group. The response rate was 18% in the 177Lu-Dotatate group versus 3% in the control group (P<0.001). In the planned interim analysis of overall survival, 14 deaths occurred in the 177Lu-Dotatate group and 26 in the control group (P=0.004). Grade 3 or 4 neutropenia, thrombocytopenia, and lymphopenia occurred in 1%, 2%, and 9%, respectively, of patients in the 177Lu-Dotatate group as compared with no patients in the control group, with no evidence of renal toxic effects during the observed time frame. Conclusions Treatment with 177Lu-Dotatate resulted in markedly longer progression-free survival and a significantly higher response rate than high-dose octreotide LAR among patients with advanced midgut neuroendocrine tumors. Preliminary evidence of an overall survival benefit was seen in an interim analysis; confirmation will be required in the planned final analysis. Clinically significant myelosuppression occurred in less than 10% of patients in the 177Lu-Dotatate group. (Funded by Advanced Accelerator Applications; NETTER-1 ClinicalTrials.gov number, NCT01578239 ; EudraCT number 2011-005049-11

Energy dependence of multiplicity in proton-nucleus collisions and models of multiparticle production

This is a continuation of our earlier investigation (Gurtuet al 1974Phys. Lett. 50 B 391) on multiparticle production in proton-nucleus collisions based on an exposure of emulsion stack to 200 GeV/c beam at the NAL. It is found that the ratio Rem = &lt;ns&gt;/&lt;nch&gt;, where &lt;nch&gt; is the charged particle multiplicity in pp-collisions, increases slowly from about 1 at 10 GeV/c to 1.6 at 68 GeV/c and attains a constant value of 1.71 &#177; 0.04 in the region 200 to 8000 GeV/c. Furthermore, Rem = 1·71 implies an effective A-dependence of RA =A 0.18,i.e., a very weak dependence. Predictions of R em on various models are discussed and compared with the emulsion data. Data seem to favour models of hadron-nucleon collisions in which production of particles takes place through adouble step mechanism,e.g., diffractive excitation, hydrodynamical and energy flux cascade as opposed to models which envisage instantaneous production

Screen-detected vs clinical breast cancer: the advantage in the relative risk of lymph node metastases decreases with increasing tumour size

Screen-detected (SD) breast cancers are smaller and biologically more indolent than clinically presenting cancers. An often debated question is: if left undiagnosed during their preclinical phase, would they become more aggressive or would they only increase in size? This study considered a registry-based series (1988–1999) of 3329 unifocal, pT1a-pT3 breast cancer cases aged 50–70 years, of which 994 were SD cases and 2335 clinical cases. The rationale was that (1) the average risk of lymph node involvement (N+) is lower for SD cases, (2) nodal status is the product of biological aggressiveness and chronological age of the disease, (3) for any breast cancer, tumour size is an indicator of chronological age, and (4) for SD cases, tumour size is specifically an indicator of the duration of the preclinical phase, that is, an inverse indicator of lead time. The hypothesis was that the relative protection of SD cases from the risk of N+ and, thus, their relative biological indolence decrease with increasing tumour size. The odds ratio (OR) estimate of the risk of N+ was obtained from a multiple logistic regression model that included terms for detection modality, tumour size category, patient age, histological type, and number of lymph nodes recovered. A term for the detection modality-by-tumour size category interaction was entered, and the OR for the main effect of detection by screening vs clinical diagnosis was calculated. This increased linearly from 0.05 (95% confidence interval: 0.01–0.39) in the 2–7 mm size category to 0.95 (0.64–1.40) in the 18–22 mm category. This trend is compatible with the view that biological aggressiveness of breast cancer increases during the preclinical phase