RESUMO
BACKGROUND: Treatment options are limited for patients with recurrent or metastatic squamous cell carcinoma of the head and neck (HNSCC) following progression after first-line platinum-based therapy, particularly in Asian countries. PATIENTS AND METHODS: In this randomised, open-label, phase III trial, we enrolled Asian patients aged ≥18 years, with histologically or cytologically confirmed recurrent/metastatic HNSCC following first-line platinum-based therapy who were not amenable for salvage surgery or radiotherapy, and had an Eastern Cooperative Oncology Group (ECOG) performance status of 0/1. Patients were randomised (2 : 1) to receive oral afatinib (40 mg/day) or intravenous methotrexate (40 mg/m2/week), stratified by ECOG performance status and prior EGFR-targeted antibody therapy. The primary end point was progression-free survival (PFS) assessed by an independent central review committee blinded to treatment allocation. RESULTS: A total of 340 patients were randomised (228 afatinib; 112 methotrexate). After a median follow-up of 6.4 months, afatinib significantly decreased the risk of progression/death by 37% versus methotrexate (hazard ratio 0.63; 95% confidence interval 0.48-0.82; P = 0.0005; median 2.9 versus 2.6 months; landmark analysis at 12 and 24 weeks, 58% versus 41%, 21% versus 9%). Improved PFS was complemented by quality of life benefits. Objective response rate was 28% with afatinib and 13% with methotrexate. There was no significant difference in overall survival. The most common grade ≥3 drug-related adverse events were rash/acne (4% with afatinib versus 0% with methotrexate), diarrhoea (4% versus 0%), fatigue (1% versus 5%), anaemia (<1% versus 5%) and leukopenia (0% versus 5%). CONCLUSIONS: Consistent with the phase III LUX-Head & Neck 1 trial, afatinib significantly improved PFS versus methotrexate, with a manageable safety profile. These results demonstrate the efficacy and feasibility of afatinib as a second-line treatment option for certain patients with recurrent or metastatic HNSCC. CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov identifier: NCT01856478.
Assuntos
Afatinib/administração & dosagem , Antineoplásicos/administração & dosagem , Neoplasias de Cabeça e Pescoço/tratamento farmacológico , Metotrexato/administração & dosagem , Recidiva Local de Neoplasia/tratamento farmacológico , Carcinoma de Células Escamosas de Cabeça e Pescoço/tratamento farmacológico , Adulto , Afatinib/efeitos adversos , Idoso , Idoso de 80 Anos ou mais , Antineoplásicos/efeitos adversos , Povo Asiático , Carboplatina/uso terapêutico , Cisplatino/uso terapêutico , Progressão da Doença , Intervalo Livre de Doença , Estudos de Viabilidade , Feminino , Neoplasias de Cabeça e Pescoço/mortalidade , Neoplasias de Cabeça e Pescoço/patologia , Humanos , Masculino , Metotrexato/efeitos adversos , Pessoa de Meia-Idade , Recidiva Local de Neoplasia/mortalidade , Recidiva Local de Neoplasia/patologia , Intervalo Livre de Progressão , Carcinoma de Células Escamosas de Cabeça e Pescoço/mortalidade , Carcinoma de Células Escamosas de Cabeça e Pescoço/patologiaRESUMO
Lagophthalmos is one of the well-known complications of leprosy due to involvement of the facial nerve. In the present study an attempt has been made to elucidate the role of early intervention with steroids and adjunct physiotherapy in early reported lagophthalmos in patients affected with leprosy at a tertiary referral institute under the Disability Prevention and Medical rehabilitation (DPMR) programme. During April 2008 to March 2014, 62 patients affected with leprosy reported to Regional leprosy Training and Research Institute with lagophthalmos. Cases reporting within six months of difficulty in closure were categorized as early reporting group. These were either referred from a peripheral health centre (63%) or self-reported (37%). These patients were examined clinically and details were noted in a pretested Performa. The standard dosages of the steroids were given to patients as per NLEP guidelines. Lid gaps on direct gaze and with both gentle and forced closure were assessed using standard measuring technique by a physiotherapist. During the follow-up period the patients were imparted active and passive physiotherapy and any change in the lid gap was recorded. The data was analysed and appropriate test of significance was applied. Out of 62 lagophthalmos patients, 49(79.1%) were males and 13 (20.9%) were females. 56 (90.3%) cases were from MB category and 6 (9.7%) cases were from PB category. 53(85.4%) patients presented with unilateral eye involvement, while 9 (14.6%) had bilateral lagophthalmos. 53 (74.6%) of the eyes achieved complete lid closure, while the remaining 18 (25.4%) eyes had gap on gentle closure. During six month follow-up the amount of recession of lid gap among the early reported lagophthalmos was 4.15 mm with standard steroid regimen and physiotherapy. With the use of the steroid and regular physiotherapy lagophthalmos diagnosed and treated in initial stages shows significant improvement in the lid gap reduction.
Assuntos
Doenças Palpebrais/tratamento farmacológico , Hanseníase/complicações , Modalidades de Fisioterapia , Esteroides/uso terapêutico , Adolescente , Adulto , Doenças Palpebrais/epidemiologia , Doenças Palpebrais/terapia , Feminino , Humanos , Índia/epidemiologia , Hanseníase/epidemiologia , Masculino , Pessoa de Meia-Idade , Adulto JovemRESUMO
The infection caused by grain mold in rainy season grown sorghum deteriorates the physical and chemical quality of the grain, which causes a reduction in grain size, blackening, and making them unfit for human consumption. Therefore, the breeding for grain mold resistance has become a necessity. Pedigree breeding has been widely used across the globe to tackle the problem of grain mold. In the present study, a population breeding approach was employed to develop genotypes resistant to grain mold. The complex genotype × environment interactions (GEIs) make the task of identifying stable grain mold-resistant lines with good grain yield (GY) challenging. In this study, the performance of the 33 population breeding derivatives selected from the four-location evaluation of 150 genotypes in 2017 was in turn evaluated over four locations during the rainy season of 2018. The Genotype plus genotype-by-environment interaction (GGE) biplot analysis was used to analyze a significant GEI observed for GY, grain mold resistance, and all other associated traits. For GY, the location explained a higher proportion of variation (51.7%) while genotype (G) × location (L) contributed to 21.9% and the genotype contributed to 11.2% of the total variation. For grain mold resistance, G × L contributed to a higher proportion of variation (30.7%). A graphical biplot approach helped in identifying promising genotypes for GY and grain mold resistance. Among the test locations, Dharwad was an ideal location for both GY and grain mold resistance. The test locations were partitioned into three clusters for GY and two clusters for grain mold resistance through a "which-won-where" study. Best genotypes in each of these clusters were selected. The breeding for a specific cluster is suggested. Genotype-by-trait biplots indicated that GY is influenced by flowering time, 100-grain weight (HGW), and plant height (PH), whereas grain mold resistance is influenced by glume coverage and PH. Because GY and grain mold score were independent of each other, there is a scope to improve both yield and resistance together.
RESUMO
OBJECTIVE: To estimate the effectiveness of BCG vaccination in the prevention of leprosy. METHODS: study design: Population-based pair-matched case-control study. The study was carried out in the field operation area of Regional Leprosy Training and Research Centre, Raipur, Chattisgarh, India. It included 201 cases of leprosy (diagnosed by WHO criteria), born onwards 1964. Each case was pair-matched with one neighbourhood control for age and sex. BCG vaccination status was assessed by examination for the presence of BCG scar, immunization records if available and information from subjects/parents of children. Subjects uncertain about BCG vaccination were not included. RESULTS: A marginally non-significant protective association between BCG and leprosy was observed (OR = 0.65, 95% CI 0.40-1.04). The overall vaccine effectiveness (VE) was 35%. The BCG effectiveness was lower for pauci-bacillary leprosy as compared to multibacillary leprosy. The sub-group analysis revealed that the BCG effectiveness was statistically non-significant in less than or equal to 14 years of age and females category. The overall prevented fraction of leprosy was calculated to be 20% (95% CI--1.8-41.4). CONCLUSION: The current study identified a marginally beneficial role of BCG vaccination in the prevention of leprosy in study population.
Assuntos
Vacina BCG , Hanseníase/prevenção & controle , Adolescente , Adulto , Fatores Etários , Estudos de Casos e Controles , Criança , Feminino , Humanos , Índia/epidemiologia , Masculino , Fatores SexuaisRESUMO
OBJECTIVE: To study clinical-epidemiological aspects of children affected with leprosy in a high-endemicity area. METHODS: Hospital-based study (April 2010 to March 2015) of newly diagnosed children (=18 years) with leprosy, from a leprosy research institute in Chhattisgarh, India. RESULTS: 551 new childhood cases were diagnosed constituting 16% of the total newly leprosy cases examined; 221 (40.1%) were multibacillary cases with 11.2% smear positivity. 243 (44.1%) had known contact history of leprosy, 17.6% of children developed Lepra reaction, and 17.4% had visible deformity. 68% of subjects completed treatment within the prescribed time. CONCLUSION: Transmission of leprosy is still continuing in the area, and high disability and deformity rates are seen in children.
Assuntos
Doenças Endêmicas/estatística & dados numéricos , Hanseníase/epidemiologia , Adolescente , Criança , Pré-Escolar , Feminino , Seguimentos , Humanos , Índia/epidemiologia , MasculinoRESUMO
OBJECTIVE: To assess the prevalence and type of fluorosis among children from randomly selected villages of Chhattisgarh, and its relationship with fluoride levels in drinking water. METHODS: A community based door-to-door survey was conducted in the sampled villages of seven districts of Chhattisgarh state during the year 2013-14. The field case definitions were used for labelling types of fluorosis. The fluoride concentration in drinking water was estimated by ion selective electrode method. RESULTS: The prevalence of fluorosis ranged between 12 to 44% in children of surveyed districts. The fluoride levels in drinking water of selected villages were in the range of 0.1-9.0 ppm. CONCLUSION: Dental and skeletal fluorosis is endemic among children in the surveyed districts of Chhattisgarh State, and is related to drinking water with fluoride content of =1.5 ppm.
Assuntos
Fluorose Dentária/epidemiologia , Adolescente , Criança , Pré-Escolar , Estudos Transversais , Água Potável/efeitos adversos , Água Potável/química , Feminino , Fluoretos/efeitos adversos , Humanos , Índia/epidemiologia , Lactente , Recém-Nascido , Cifose , Masculino , Prevalência , Fatores Socioeconômicos , Inquéritos e QuestionáriosRESUMO
This study aims in linking the biophysical and socioeconomic data base layers with the technical coefficients or simulation models for agri-production estimates and land use planning under normal and extreme climatic events, and exploring the resource and inputs management options in village Shikohpur, Gurgaon district located in the northwest part of India. The socioeconomic profile of Shikohpur is highly skewed with mostly small and marginal farmers. Though the areas under wheat in Shikohpur are increasing, the productivity is declining or remaining stagnant over the years. Most of the area during kharif season (June-September) remains fallow. Pearl millet based cropping systems (pearl millet-mustard and pearl millet-wheat) are predominant. Soils are mostly loamy sand to sandy loam with average of 70-80% sand content. Organic C content in soil is less than 0.3%, due to high prevailing temperature with little rainfall and also intensive agriculture followed in this region. Though the annual average seasonal rainfall in Gurgaon did not have much variation over the years, occurrence of extreme climate events has increased in the last two decades. The crop intensity is low and the water table is declining. Water and nitrogen production functions were developed for the important crops of the region, for their subsequent use in scheduling of the inputs. InfoCrop, WTGROWS and technical coefficients were used for crop planning and resource management under climate change and its variability, extreme events, limited resource availability and crop intensification. These will help in disseminating necessary agro-advisories to the farmers so that they will be able to manipulate the inputs and agronomic management practices for sustained agricultural production under normal as well as extreme climatic conditions.
Assuntos
Agricultura , Água , Agricultura/economia , Clima , Simulação por Computador , Produtos Agrícolas , Fertilizantes , Humanos , Índia , Modelos Biológicos , Fatores Socioeconômicos , Fatores de Tempo , Tempo (Meteorologia)RESUMO
Forty elderly patients aged 50-94 years old with unstable intertrochanteric fractures were treated by external fixation at The Central Institute of Orthopaedics, Safdarjang Hospital, New Delhi, India from June 1993 to January 1995. Fracture union was achieved by an average time of 14 weeks in all the patients. Postoperative varus was increased in nine and deep pin-track infection was found in three cases. External fixation minimizes surgical damage and blood loss, and has an added advantage of early mobilization. This technique is simple, safe and economical. It is effective wherever early elective surgery is not possible due to limited resources. It is the method of choice for high-risk geriatric patients.