Feasibility and impact of screening for venous thromboembolism in treatment?naive lung cancer patients–Results of a prospective cohort study

Background: Venous thromboembolism (VTE) in cancer remains underdiagnosed. This prospective study aimed to evaluate the feasibility of screening for VTE in lung cancer (LC) patients. We assess the incidence of VTE, its risk factors, and effects on overall survival (OS). Methods: Consecutive treatment?naive LC patients were screened for deep venous thrombosis (DVT) with compression ultrasonography and pulmonary thromboembolism (PTE) with computed tomography pulmonary angiography (CTPA) at diagnosis and after 3 months of treatment. The incidence rate of VTE (DVT and/or PTE) was calculated. Risk factors associated with VTE were assessed using logistic regression analysis. All participants were followed?up to 1 year after enrollment. OS was compared in LC subjects with and without VTE, using the Cox proportional hazard analysis. Results: Around 301 subjects with LC (stages IIIB?IV accounted for 83.1%) were enrolled, of which 16 had VTE (5.3%). The incidence rate of VTE was 90 per 1000 person?years (PY). PTE was asymptomatic in 27.3% of cases while all DVT episodes were symptomatic. The incidence rate of asymptomatic PTE identified during the screening was 17 per 1000 PY. The median duration from LC diagnosis to the VTE event was 96.5 days. Median OS was significantly less in VTE patients [161 versus 311 days; P = 0.007] and death was attributable to VTE in 50%. After adjusting for covariates, VTE (hazard ratio [HR] = 2.1), smoking (HR = 1.7), and Eastern cooperative oncology group performance status ?2 (HR = 1.6) were independently associated with poor OS in LC. Conclusions: VTE occurs in approximately 1 in 20 newly?diagnosed patients with LC and is associated with decreased OS. Screening for PTE may be considered even in resource?limited settings

Separation and pain perception of Elastomeric, Kesling and Kansal separators

Abstract Introduction: Various types of separators have been advocated, but the ideal separator should produce optimum separation with minimal pain and discomfort. Objective: The objective of this study was to evaluate and compare the amount of separation achieved by three different types of separators (Elastomeric, Kesling and Kansal), and to assess the associated pain and discomfort. Methods: A random single-blind split-mouth study was conducted on 108 patients seeking fixed orthodontic treatment, in which two different separators were used on each side in both the arches for a single patient. After five days, the amount of separation was measured with a feeler gauge. Visual Analogue Scale (VAS) scoring was performed by the patient on each day, to evaluate pain perception. Discomfort was evaluated by questionnaire filled by the patient at the time of separator removal. Results: The greatest amount of separation was seen with the elastomeric separators, while the smallest separation was seen with Kansal separators. VAS scoring showed maximum pain at day 1 with all the three separator types. Highest pain was perceived in the Elastomeric separators group, followed by Kesling and Kansal separators, respectively. Statistically significant difference was found in VAS score of Elastomeric separators, when compared to both Kesling and Kansal, on day 1 and 2 (p= 0.001). Analysis of the questionnaires revealed that a greater number of patients experienced discomfort with elastomeric separators placement (69.4%), which was statistically significant (p< 0.01) when compared to the other two types of separators. Answers to the other questions were comparable, except for the need for medications, which was reportedly highest with elastomeric separators. Conclusion: Kesling separators produce adequate separation with minimal discomfort and pain, compared to Elastomeric and Kansal separators.

Resumo Introdução: diversos tipos de separadores de dentes já foram descritos e seu uso, justificado na literatura. Porém, o separador ideal deve produzir uma força adequada para realizar a separação com o mínimo de dor e desconforto. Objetivo: o objetivo do presente estudo foi avaliar e comparar a separação ortodôntica obtida por meio de três diferentes tipos de separadores (Elastômeros, Kesling e Kansal), bem como a dor e o desconforto a eles vinculados. Métodos: foi conduzido um estudo randomizado, cego e de boca dividida em 108 pacientes interessados em realizar tratamento ortodôntico, nos quais foram utilizados dois separadores diferentes, um em cada lado de ambas as arcadas de cada paciente. Cinco dias após a inserção dos dispositivos, a quantidade de separação foi mensurada com o auxílio de um medidor (calibrador de folga). Para avaliar a dor, os pacientes preencheram uma Escala Visual Analógica (EVA) a cada dia do estudo; e, para a avaliação do desconforto, preencheram um questionário no dia da remoção dos separadores. Resultados: os Elastômeros obtiveram a maior quantidade de separação, enquanto os separadores Kansal conseguiram a menor separação. A análise das EVAs apontou a maior intensidade de dor no primeiro dia, para os três tipos de separadores, sendo os maiores índices relatados no grupo de Elastômeros, seguido pelos grupos Kesling e Kansal, respectivamente. Diferenças estatisticamente significativas foram encontradas nas escalas EVA dos Elastômeros em comparação aos separadores Kesling e Kandal, nos dias 1 e 2 (p= 0,001). A análise dos questionários mostrou que um grande número de pacientes relatou desconforto após a inserção dos Elastômeros (69,4%), valor estatisticamente significativo em comparação aos outros dois tipos de separadores (p< 0,01). As respostas às outras questões foram semelhantes entre os grupos, com exceção da necessidade de uso de medicamentos, a qual foi maior no grupo dos Elastômeros. Conclusão: os separadores Kesling produziram uma separação adequada, com o mínimo de dor e desconforto, em comparação aos Elastômeros e separadores Kansal.

Does awareness of diagnosis influence health related quality of life in north Indian patients with lung cancer.

Background & objectives: Several patients with cancer in India are not aware of their diagnosis. We evaluated the impact of awareness of cancer diagnosis on health-related quality of life (HRQL) in newly diagnosed patients with lung cancer. Methods: A total of 391 treatment-naïve patients with lung cancer, seen at the Lung Cancer Clinic of a tertiary care hospital in north India, were categorized into those aware of their diagnosis (group A) and those not aware (group B). All patients answered Hindi versions of abbreviated World Health Organization Quality of Life questionnaire (WHOQOL-Bref) and European Organization for Research and Treatment of Cancer Quality of Life questionnaire (EORTC QLQ-C30), and its lung cancer module, EORTC QLQ-LC13. Various domain scores were computed and compared between the two groups. Analysis of covariance was used to determine significance of differences after adjustment for potential confounding factors. Results: Only 117 (29.9%) patients were aware of their diagnosis. Of all, 302 (77.2%) patients had non-small cell lung cancer, and 301 (77.0%) had advanced disease. All HRQL domain scores were similar between the two groups, except that group B patients had significantly poorer median (interquartile range) Physical [39.3 (28.6-50.0) vs 46.4 (28.6-57.1)] and Environment [46.9 (40.6-56.3) vs 53.1 (0.6-65.6)] domain scores of WHOQOL-Bref, and Physical function [60.0 (40.0-73.3) vs 66.7 (46.7-80.0)] and Fatigue [66.7 (55.6-77.8) vs 66.7 (44.4-66.7)] scores of QLQ-C30. After adjusting for gender, age, education, family income, and tumour extent, these differences were not significant. Interpretation & conclusions: Disclosure of cancer diagnosis, or lack of it, had no significant impact on HRQL in patients with lung cancer after adjustment of potential confounders.

Utility of adenosine deaminase (ADA), PCR & thoracoscopy in differentiating tuberculous & non-tuberculous pleural effusion complicating chronic kidney disease.

Background & objectives: Pleural effusion is a common occurrence in patients with late-stage chronic kidney disease (CKD). In developing countries, many effusions remain undiagnosed after pleural fluid analysis (PFA) and patients are empirically treated with antitubercular therapy. The aim of this study was to evaluate the role of adenosine deaminase (ADA), nucleic acid amplification tests (NAAT) and medical thoracoscopy in distinguishing tubercular and non-tubercular aetiologies in exudative pleural effusions complicating CKD. Methods: Consecutive stage 4 and 5 CKD patients with pleural effusions underwent PFA including ADA and PCR [65 kDa gene; multiplex (IS6110, protein antigen b, MPB64)]. Patients with exudative pleural effusion undiagnosed after PFA underwent medical thoracoscopy. Results: All 107 patients underwent thoracocentesis with 45 and 62 patients diagnosed as transudative and exudative pleural effusions, respectively. Twenty six of the 62 patients underwent medical thoracoscopy. Tuberculous pleurisy was diagnosed in six while uraemic pleuritis was diagnosed in 20 subjects. The sensitivity and specificity of pleural fluid ADA, 65 kDa gene PCR, and multiplex PCR were 66.7 and 90 per cent, 100 and 50 per cent, and 100 and 100 per cent, respectively. Thoracoscopy was associated with five complications in three patients. Interpretation & conclusions: Uraemia remains the most common cause of pleural effusion in CKD even in high TB prevalence country. Multiplex PCR and thoracoscopy are useful investigations in the diagnostic work-up of pleural effusions complicating CKD while the sensitivity and/or specificity of ADA and 65 kDa gene PCR is poor.

Clinical experience on use of oral EGFR-TKIs as first-line treatment of advanced NSCLC from a tertiary care centre in North India and implications of skin rash.

Background. Limited data are available from India on treatment outcomes with oral epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs) in newly diagnosed non-small cell lung cancer (NSCLC). We studied the demographic profile and treatment outcomes of patients with NSCLC, receiving first-line treatment with oral EGFR-TKIs. Methods. Retrospective study of newly diagnosed NSCLC patients treated with oral EGFR-TKIs over a 4-year period at a tertiary care institute in North India. Results. Of 76 patients studied, females and non-smokers constituted 32.9% and 48.7%, respectively. Majority of patients had adenocarcinoma (59.2%), stage IV (64.5%) disease and Karnofsky performance status <70 (74.5%). Gefitinib was the most frequently used EGFR-TKI (92.1%). Most common indication for the use of EGFR-TKIs was poor performance status (65.8%). Among assessable patients, disease control and progressive disease were evident in 66% and 34%, respectively. Most common side effects were skin rash (17%) and diarrhoea (10.6%). Patients with and without skin rash differed significantly in relation to objective response to treatment (100% versus 23.1%) and overall survival (median not reached versus 178 days). On multivariate logistic regression analysis, malignant pleural effusion was associated with occurrence of rash (odds ratio=0.19; 95% confidence interval = 0.04-0.95; p=0.04). Conclusions. Oral EGFR-TKIs appear to be useful for the treatment of clinically selected patients with advanced NSCLC. Occurrence of skin rash was independently associated with treatment response and better survival in the current study.

UPLC method development and validation for cefditoren pivoxil in active pharmaceutical ingredient.

The objective of the study was to develop UPLC method for the determination of purity of Cefditoren Pivoxil in API and its validation. UPLC is a better technique than HPLC in terms of performance and speed, so it was selected. The method was developed using Acetonitrile and Ammonium Acetate buffer (pH 6.7) and Kromacil column C18 (50×2.1mm, 3.5μ) as a stationary phase at a flow rate of 0.25ml/min. Validation was done by linearity, precision, and robustness studies. The precision was found to be within the limits. The linearity studies indicated the drug obeys Beer’s law and revealed the specified range of linearity for drug was between 80μg/ml and 120μg/ml. The robustness was observed from the insignificant variation in the analysis by changes in flow rate, mobile phase ratio, wavelength, column oven temperature and pH. Forced Degradation study revealed the drug degraded initially by the influence of acid, alkali, and peroxide. Solution stability study showed the drug was not stable for more than 2 h at 25˚C but stable at 5˚C. It can be concluded that the proposed method was simple, precise, and robust and can be useful for determination of purity of Cefditoren Pivoxil in API by using UPLC.

Blind transbronchial needle aspiration without an on-site cytopathologist: Experience of 473 procedures.

Background. Transbronchial needle aspiration (TBNA) is an established procedure for sampling the mediastinal lymph nodes. Data reported from India are limited on this routine procedure. We describe our experience of the efficacy, diagnostic accuracy and safety of TBNA. Method. We retrospectively reviewed all TBNAs done at our centre between 2006 and 2009. Under local anaesthesia, accessible lymph node stations were sampled thrice without fluoroscopy and without an on-site cytopathologist. Data are presented in a descriptive manner. Results. A total of 4513 diagnostic bronchoscopies were done, of which 473 (10.5%) underwent TBNA. There were 297 men (63%) and 176 women (37%) with a mean (SD) age of 46.2 (13.98) years. The most common clinical diagnoses were sarcoidosis (50.5%), lung cancer (26.8%), tuberculosis (8.7%) and others (14%). The overall efficacy of TBNA in sampling a mediastinal/hilar lymph node was 72%. The accuracy of TBNA in achieving a pathological diagnosis was 40.4%, whereas the diagnostic yield of a successful procedure was 56.8% (lymph nodes were successfully sampled in 193 of 340 procedures). The most common diagnoses on cytology were sarcoidosis and lung cancer. In patients with a clinical diagnosis of lung cancer, the diagnostic accuracy of TBNA was 46.5% (59 of 127), whereas in patients with sarcoidosis it was 38.1% (91 of 239). TBNA provided an additional diagnostic yield in 5.6% (12 of 215) of patients with sarcoidosis who also underwent transbronchial lung biopsy. There were no periprocedural complications. Conclusion. Blind TBNA is a safe and effective procedure that can be routinely done in the bronchoscopy suite.

Pleural effusions associated with pulmonary thromboembolism: A systematic review.

Objective. To perform a review of the incidence, pathogenesis, clinical presentation, diagnosis and management of pleural effusions associated with pulmonary embolism (PE). Methods. A search of the MEDLINE and EmBase databases from 1975 to 2007 was performed. A manual search was also performed of the references of each article. Results. Pleural effusions occur in 19% to 61% of patients with PE. The incidence is higher if computed tomography (CT) of the chest is used for detection of pleural effusion (28.1% with chest radiograph and 43.3% with CT chest). The pleural fluid is almost always an exudate. Although usually unilateral, the pleural effusion can also be bilateral. The effusions are maximal by the third day, be larger in size, may develop loculations and can be associated with high leukocyte counts. The presence of pulmonary infarction may not be associated with large effusions. Conclusions. Pleural effusions are a common occurrence in patients with PE. The possibility of PE should be entertained in any patient with undiagnosed exudative pleural effusion. The results of this review further suggest that many traditional concepts with PE, viz, unilateral small effusions, absence of loculations and transudative nature of the pleural fluid need reappraisal.

Pulmonary hypertension as a presenting manifestation of allergic bronchopulmonary aspergillosis.

The case of a 46-year-old lady who presented with respiratory failure and pulmonary hypertension in the absence of clinical signs of asthma or bronchiectasis, and in whom a diagnosis of allergic bronchopulmonary aspergilloma [ABPA] was made subsequently on the basis of radiological and laboratory investigations is reported. Symptomatic and objective improvement was seen with corticosteroid therapy. To the best of the authors' knowledge, such an occurrence has not been reported previously. This case highlights the importance of keeping a high index of suspicion while investigating a patient with pulmonary hypertension in whom the aetiology is not apparent on initial evaluation. Identification of the disease, in its early-stage, can prevent progression to bronchiectasis and fibrotic lung disease, and thus, patients can be saved from the morbidity related to end-stage disease.

Manifestations of pulmonary tuberculosis in the elderly: a prospective observational study from north India.

BACKGROUND: There is scarcity of published literature on manifestations of pulmonary tuberculosis (PTB) among elderly patients in India. The aim of the present study was to compare the clinical, radiological and laboratory manifestations of PTB among young and elderly patients. METHODS: This prospective study involved 100 human immunodeficiency virus (HIV) negative patients with PTB. The demographic, clinical, radiological and laboratory manifestations were compared between young (n=50; under 60 years of age) and elderly (n=50; aged 60 years and above) with PTB. RESULTS: Elderly patients, in comparison to younger patients, tended to be heavier smokers and had more co-morbidities (40% vs 8%; p < 0.05). They presented more frequently with constitutional symptoms (except fever) and less frequently with respiratory symptoms. The mean duration of symptoms and rate of sputum smear-positivity for acid-fast bacilli was similar in both groups. Both the groups were similar with respect to physical examination and chest radiograph findings. Median values of erythrocyte sedimentation rate and total leukocyte count were significantly higher and lower respectively in the elderly patients. CONCLUSIONS: The presentation of PTB in elderly patients differs from that of younger patients by the predominance of constitutional rather than respiratory symptoms. A high index of suspicion is required to make a timely diagnosis of tuberculosis in the elderly.