Analysis of COVID-19-related clinical trials registered in the Clinical Trial Registry of India in 2020: A descriptive study

Background: COVID-19 caused immense morbidity and mortality worldwide and was declared a pandemic on March 11, 2020, by the World Health Organization. Lack of effective treatments directed researchers to various interventional strategies, such as development of new drugs or vaccines, drug repurposing models, and AYUSH formulations, for prophylaxis and treatment of COVID-19. Aim and Objectives: The information obtained from registered COVID-19 trials for the year 2020, will help to identify the various aspects for therapeutics and types of study designs used for achieving different objectives, so as to guide researchers for similar future projects. Materials and Methods: A descriptive, observational study was conducted on COVID-19-related clinical trials registered in Clinical Trials Registry of India during calendar year 2020. The details were noted in a predesigned pro forma and evaluated. Results: Of the 946 registered trials, majority were single center (82.76%), interventional (50.7%), randomized (73.1%), open-labeled (61.9%), and prospective in nature (96%). Our study revealed that 40.16% trials used modern medicine while 26.53% used AYUSH formulations. The psychological impact of COVID-19 pandemic was studied in 121 trials, of which 118 trials showed negative impact on the mental well-being. Conclusion: Our study provides thorough insight about the on-going research in our country, especially about various drug repurposing strategies and government supported AYUSH interventions. This may act as a foundation for future investigators to identify any lacunae in the current studies, helping them to diversify their objectives accordingly, so as to encourage quality research in our country.

A study of chronopharmacological relevance of antihypertensive drugs prescription

Background: Chronopharmacology is the 搒cience dealing with the optimization of drug effects and minimization of adverse effects by timing the medications in relation to the biological rhythm.� In patients with hypertension, it is important to maintain a steady blood pressure throughout the day, which necessitates to have knowledge of chronopharmacology and drugs following it. Better understanding of the circadian rhythm and its application for drug administration serves productive utilization of drug. Aims and Objectives: This study aims to study the chronopharmacological relevance to the time of drug administration in general medicine inpatients at Gulbarga Institute of Medical Sciences, Kalaburagi. Materials and Methods: It is a prospective, non-interventional, observational study which was conducted on patients admitted in General Medicine wards at GIMS, Kalaburagi. A special pro forma was designed, and data were obtained from medical case records of patients suffering from various disorders admitted in the wards of general medicine. Demographic data, disease data, data pertaining to drug therapy, data pertaining to other comorbid illness, and adverse effects of drugs, if any, were collected. Descriptive statistics and other suitable statistical test were applied for analyzing the data. Results: A total of 110 patients who were on antihypertensive drugs and who meet the inclusion and exclusion criteria of the study were included in the study. The average age of both male and female was found to be between 45 and 68 years. Among 110 patients, 72 (65.45%) were male and 38 (34.54%) were female. In the current study, a total of 124 wide variety of antihypertensive drugs were recorded. The study of ideal time of administration of all antihypertensive drugs showed that, most of the prescription was according to chronopharmacological relevance. Conclusion: Updating the knowledge of chronopharmacology and its application in clinical practice will provide better health care. The current study highlights the importance of timing of administration of antihypertensive drugs in human health care.

Role of coping behavior and socio-demographic variables in alcohol relapse

Introduction: Although short term treatments for alcoholism is quite effective but one of the most distressing problems in alcoholism treatment is the relatively high rates of relapse to alcohol use following periods of abstinence. Preventing Relapse is a formidable challenge in the treatment of drug addiction. Several authors in western countries have described relapse as complex, dynamic and unpredictable phenomena. Therefore in this study we attempt to examine the role or association between different socio-demographic variables, coping strategies and relapse among alcoholic patients. Aim: To study role of coping behavior and socio-demographic variables in alcohol relapse. Materials and methods: It was an observational study. A total of 100 willing patients of alcohol dependence with relapse were enrolled for the study. For the purpose of study an episode of relapse was defined as per ICD-10, relapse in substance dependency is defined as re-emergence of substance dependence after at least 4 weeks of abstinent period. All participants fulfilling inclusion and exclusion criteria and given written informed consent were analyzed through a structured interview using CBI. Results: A significant association of many socio-demographic and psychosocial variables with relapse was found. Variables like male gender, nuclear family, early age of onset of drinking, positive family history, number of past relapses etc. were found significant in determining relapse. A strong association of seldom use of coping strategies in predicting relapse was found. The average mean score in CBI was found to be 1.04 with SD of 0.25. Conclusion: This study may conclude that there is significant association of demographic and psychosocial factors with relapse in alcohol dependence. There is significant role of coping behavior in determining or predicting relapse.

Stability analysis and quantitative evaluation of metronidazole suspension.

Suspension is a heterogeneous mixture including solid particles that are satisfactorily bulky for sedimentation. Generally they must be larger than one micrometer. It is when particles are left floating around freely in a solvent. The inner phase (solid) is discrete all through the external phase (fluid) during mechanical stir, with utilizing of certain excipients or suspending agents. Metronidazole or 2-(2 methyl-5 nitro-1 H –imidazol-1 yl) ethanol belongs to the nitro imidazole group of antibiotics whose antimicrobial property through derive from the formation of toxic free radicals by intracellular reduction. The objective of present study was to prepare suspension of Metronidazole by using different suspending agents and stability testing was to provide evidence on how the quality of suspensions varies with the time under of influence of environmental factors such as temperature, light, oxygen, moisture, other ingredient or excipients in the dosage form, particle size of drug, microbial contamination etc. and to establish a recommended storage condition. The FTIR and DSC techniques are use for characterization of active ingredient MBZ. This suspension was evaluated for appearance, pH, sedimentation volume and dissolution study for in vitro drug release. Result of evaluation indicates 1% w/v xanthan gum give optimal characteristic suspension. Suspension containing 1% w/v was exposed for the stability studies as per ICH guidelines. The suspensions were evaluated for their physicochemical parameter, particle size, drug release, drug content and microbiological assessment. The suspension shows good stability at 25ºC ± 2 ºC /60%± 5% RH, 30 ºC ± 2 ºC /65%± 5% RH and good quantitative analysis result throughout the period of study. Suspension stored at 40 ºC ± 2 ºC /75%± 5% RH shows noncompliance with the analysis parameter after 4 week of storage. This indicate high temperature storage was shows degradation of the suspension which results in crystal growth in formulation and affect the physicochemical parameter as Appearance, pH, viscosity, specific gravity, drug dissolution profile and drug content.

Growth Kinetics of a Native Toxigenic Isolate of Bacillus Cereus under the Influence of Incubation Temperature, pH and Sodium Chloride in Broth System.

Aims: The growth behavior of vegetative cells and spores of a native toxigenic food isolate of Bacillus cereus CFR 1534 was studied under the influence of incubation temperature, pH and sodium chloride. Place and Duration of Study: The study was undertaken in the Department of Human Resource Development, CSIR-Central Food Technological Research Institute, Mysore 570020, India. The duration of study was during the period October 2009 to February 2010. Methodology: The experimental design was a central composite design (CCD) based on 3 factors and 5 levels. The factors for vegetative cells were incubation temperature (12- 48ºC), pH level (5.5-7.5) and sodium chloride (2-6%). With spores, the ranges of pH and NaCl levels were the same, while incubation temperature range was 22 to 42ºC. Results: Multiple regression analysis of experimental data relating to lag phase duration (LPD) and growth rate (GR) of B. cereus across the influencing factors in broth system revealed that LPD of vegetative cells and spores was primarily influenced by incubation temperature. In vegetative cells of B. cereus, the LPD was in the range of 3.1 to 31.5 h with the highest being observed at 48ºC and pH 6.5. The GR had the lowest of 0.2/h to highest of 2.2/h at 30ºC and pH 7.5. With spores, the lowest LPD of 5.8 h was at 42ºC and highest of 20.5 h at 22ºC and that of GR was in the range of 0.2/h at 22ºC to 0.7/h at 32ºC. Experimental tubes of vegetative cells with GR estimates of 1.3/h and above revealed positive reactions for toxigenic traits of haemolytic and lecithinase activities associated with B. cereus. Conclusion: In the case of vegetative cells, incubation temperature in the range of 12- 20ºC resulted in higher LPD, while in spores, higher LPD was observed with incubation temperatures of 22-26ºC. This could provide a basis to design protocols for a safe food in the food chain.

ICON 2013: Practical consensus recommendations for hormone receptor-positive Her2-negative advanced or metastatic breast cancer.

The management of hormone receptor‑positive Her2‑negative breast cancer patients with advanced or metastatic disease is a common problem in India and other countries in this region. This expert group used data from published literature, practical experience, and opinion of a large group of academic oncologists, to arrive at practical consensus recommendations for use by the community oncologists.

A clinicopathologic analysis of 88 lung resections of suspected metastatic carcinomas with proven primaries.

Background: The lung is the most common site for metastatic carcinomas. Very few studies have comprehensively analyzed all pulmonary resections for metastatic carcinomas. Aims and Objectives: To analyze all lung resections for suspected metastatic carcinomas accrued over 10 years to evaluate: The most frequent primary site, The interval between primary tumor diagnosis and lung metastases, and The proportion of inadvertently resected benign lesions, clinicoradiologically mistakenfor metastatic deposits. Materials and Methods: Between 2002 and 2011, 88 pulmonary metastasectomies were done for suspected metastatic carcinomas, which form the basis of this study. Results: In 81 of 88 cases (92%) the diagnosis of metastatic carcinoma was histologically confirmed, whereas 7 cases (8%) were non-neoplastic. The mean interval between primary tumor and metastases was 2.5 years. The primary sites were colorectum (30; 37%), kidney and breast (14; 17.3% each), cervix (9; 10%), salivary gland carcinoma (3), thyroid carcinoma (2), squamous carcinoma (2, one each of mandible and larynx), papillary urothelial carcinoma (2), hepatocellular carcinoma (1), endometrioid adenocarcinoma (1), carcinosarcoma of endometrium (1), adrenocortical carcinoma (1), and neuroendocrine carcinoma (1). The 7 non-neoplastic lesions (8%) histologically revealed tuberculosis (4), bronchopneumonia (2), and aspergillosis (1). Conclusions: Almost three fourths (71.6%) of the metastatic pulmonary resections comprised primaries from colorectum, breast and kidney. The interval between primary tumor and metastases ranged from zero months to 10 years (mean 2.5 years). Tuberculosis was the most common histologic diagnosis among the 8% of the non-neoplastic lesions, which were mistaken for metastatic carcinoma on clinical evaluation.

Can combination metronomic therapy overcome chemoresistance in cholangiocarcinoma: A literature review.

Cholangiocarcinoma (CCa) is relatively resistant to chemotherapy as well as radiation therapy, and complete resection is the main curative therapy for these patients. The prognosis for patients with unresectable intrahepatic CCa (iCCa) is extremely poor. A 55‑year‑old woman presented at our hospital with abdominal pain. After evaluation, she was diagnosed to have multifocal iCCa. She did not opt for standard chemotherapy and therefore received oral metronomic therapy with a combination of celecoxib, etoposide, and cyclophosphamide for a total of 30 months. Presently, she is 57 months post diagnosis and 27 months post cessation of all treatment and continues to be in complete radiological remission. In the present report, we review the literature and discuss whether metronomic scheduling of biologic agents and anticancer drugs will be able to overcome chemoresistance and improve the outcome in cholangiocarcinoma. References for the review were identified through searches of Pubmed for the last 10 years as well as searches of the files of the authors themselves. The final list was generated on the basis of originality and relevance to this review.

Epidermal growth factor receptor mutation subtypes and geographical distribution among Indian non-small cell lung cancer patients.

Background: The Medical Oncology Department at Tata Memorial Hospital, the single largest tertiary cancer care center in Asia, receives in-house registered and referral patient samples from all parts of the country. Our recent studies establish 23% EGFR mutation frequency among Indian population. Here, we extend our study and report further analysis of distribution of different types of EGFR mutations in 1018 non small cell lung cancer patient, and its co-relation with clinical parameters and geographical variations across the country. Material and Methods: This study is a retrospective analysis on all the patients who were referred for EFGR testing as a routine service over a 1.5 year period. This was part of standard care. EGFR kinase domain mutations in exon 18-21 were probed by TaqMan probe-based assays in 1018 NSCLC patients. Results and Discussion: While EGFR exon 19 mutations, the most frequent EGFR mutation, were found be higher among non smokers females, we find surprisingly higher incidence of exon 21 mutations among EGFR mutation positive male smokers of Indian ethnicity. Furthermore, as Indian population is known to be composed of a gradient admixture of Ancestral North Indian (with genetic influence from Middle Easterners, Central Asians, and Europeans harboring variant EGFR mutation frequency) and Ancestral South Indians, as a paradox our study indicates comparable EGFR mutation frequency across different geographical locations within India Conclusion: Geographically there is uniform distribution in the EGFR mutation frequency within India. Further more, while exon 19 mutations are predominant among non smokers, higher incidence of exon 21 mutations exists among EGFR mutation positive male smokers of Indian ethnicity.

A year of anaplastic large cell kinase testing for lung carcinoma: Pathological and technical perspectives.

BACKGROUND: An in‑frame fusion protein between echinoderm microtubule‑associated protein‑like 4 (EML4) and anaplastic large cell kinase (ALK) genes is seen in some non‑small cell lung cancer (NSCLC). EML4‑ALK demonstrates constitutive kinase activity. These ALK‑positive lung carcinomas have been shown to respond to ALK kinase inhibitors. ALK gene rearrangement is commonly detected using fluorescent in situ hybridization (FISH). AIMS: To study the pathological features of ALK positive and negative NSCLC and evaluate the causes of uninterpretable FISH results. MATERIALS AND METHODS: This is a retrospective, observational study. The molecular pathology records of patients on whom test for ALK had been performed in a period of 1 year (February 2012 to February 2013) were accessioned. A total 224 cases were identified. Histological features were reviewed. The in situ hybridization was performed using Vysis ALK Dual Color Break Apart Rearrangement Probe (Abbott Molecular Inc.). Signal interpretation under the fluorescent microscope was performed in accordance with College of American Pathologists guidelines. RESULTS: Five patients showed ALK gene rearrangement, 182 were negative and 37 cases were uninterpretable. Five patients with ALK gene rearrangement had a mean age of 48 years and the male to female ratio was 2:3. In the ALK negative cases, the mean age was 54 years and male to female ratio was 3.2:1. Histologically, amongst the rearranged cases, three showed solid pattern, one showed acinar and one showed acinar with signet ring cells on histology. CONCLUSION: The percentage of ALK gene rearrangement was 2.7% (excluding the uninterpretable cases). These ALK positive patients were relatively younger than ALK negative patients. Solid pattern on histology was associated with ALK positivity. In a quarter of the uninterpretable results, the material submitted was fixed and processed outside.

Pathological complete response in locally advanced breast cancer: Determinants and predictive significance.

Background. Neoadjuvant chemotherapy is now the standard approach for most large breast cancers including locally advanced cancers of the breast. The majority of patients respond satisfactorily to chemotherapy with effective downsizing of tumours to consider breast conservation surgery. Pathological complete response (pathCR) is known to be a strong predictor of good outcome; however, many factors are known to influence the extent of response to chemotherapy. It has been observed that smaller the tumour, better is the response achieved in contrast to larger and locally advanced tumours where only one-third may respond well enough to merit breast conservation. Various other clinical, biological and molecular factors are also being evaluated as effective predictors of chemosensitivity. Most of these are either not easily available for all patients in developing countries or are overtly expensive and not applicable for all patients. Methods. We evaluated the clinical and pathological predictors of response to chemotherapy in 1402 women with locally advanced breast cancer. Results. There was a higher rate of pathCR in smaller tumours, younger women and ER-negative as well as triple negative tumours. The presence of ductal carcinoma in situ (DCIS) and lymphatic and vascular invasion (LVI) were associated with lower pathCR. Conclusion. In the absence of ready availability of expensive molecular and genomic assays, clinical parameters and standard histopathological variables can also be useful indicators of response to neoadjuvant chemotherapy. Additionally, they can help identify those who could be eventually conserved or have a better outcome.

Estrogen, progesterone and HER2 receptor expression in breast tumors of patients, and their usage of HER2-targeted therapy, in a tertiary care centre in India.

Background: This study was undertaken to document the pattern of expression of estrogen (ER), progesterone (PR) and human epidermal growth factor receptor-2 (HER2) and the usage of HER2-targeted therapy in a large tertiary care hospital in India in the year 2008. Materials and Methods: The histopathology reports of all breast cancer patients registered in the hospital in 2008 were extracted from the electronic medical record system. All the cases were immunohistochemically evaluated for estrogen and progesterone receptor status (ER and PR), and c-erbB-2 protein (HER2) expression using standard immunoperoxidase method. The use of HER2-targeted therapies was evaluated by extracting relevant information from the database of the hospital pharmacy and case charts of patients enrolled in ongoing approved trials. Results: A total of 2001 new patients of invasive breast cancers with available pathology reports were registered in the hospital in the year 2008. ER and/or PR expression was positive in tumors of 1025 (51.2%) patients. HER2 3+ expression by immunohistochemistry (IHC) was found in 335 (16.7%) and HER2 2+ in 163 (8.1%). The triple negative phenotype was found in 596 (29.8%) patients. An estimated 441 patients were eligible to receive HER2-targeted therapy based on their HER2 status. Of these 38 (8.6%) patients received some form of HER2-targeted therapy; 20 patients (4.5%) as part of ongoing clinical trials and 18 (4.1%) as part of routine care. Conclusions: The overwhelming majority of patients eligible for HER2-targeted therapy in our institution are unable to receive it because of financial constraints and limited access to health insurance. There is a higher fraction of patients with the triple negative phenotype compared to the Western population.

A clinico-morphological study of 95 cases of sarcomas with metastases to the lungs.

Background: Metastasis of soft tissue sarcoma most commonly occurs to the lungs. There are very few studies on histology of pulmonary metastatectomy and hardly any wherein the histology of the primary tumor has been compared with the metastasis. Aims and Objectives: To review histologically all metastatic sarcomas to lung and compare with the primary where available. Materials and Methods: Ninety-five patients with pulmonary metastases from sarcoma were analyzed histologically for type of sarcoma, chemotherapy-related changes, and changes in adjacent lung. Various clinical parameters like laterality, multiplicity, and interval between primary and metastasis were also studied. Results: Osteosarcoma constituted half of the metastatic sarcomas (48 cases, 50.5%) followed by synovial sarcoma (16 cases, 16.8%) and high grade spindle cell sarcoma-NOS (10 cases, 10.5%). The histology of primary and the metastases was similar in 60% of cases of osteosarcoma. Conclusions: Osteosarcoma is the commonest metastatic sarcoma to the lung. There is often a change to fibroblastic histology in patients of conventional osteosarcoma treated with chemotherapy.

Pure choriocarcinoma of ovary diagnosed by fine needle aspiration cytology.

Pure ovarian choriocarcinoma is extremely rare and can develop as a germ cell tumor or as a metastasis from uterine or tubal gestational choriocarcinoma or rarely from an ovarian pregnancy. The cytomorphologic findings have been reported previously in different sites. However, this is the first case of pure ovarian choriocarcinoma diagnosed on cytology to the best of our knowledge. The distinction between a gestational and nongestational choriocarcinoma is difficult. A 19-year-old female patient presented with an irregular per-vaginal bleeding and a mass in lower abdomen. Fine needle aspiration cytology smears of the mass were hypocellular and showed large, multinucleated giant cells and malignant mononucleated cells. Background was hemorrhagic. Serum β hCG level was 3,80,000 mIU/ml. A diagnosis of choriocarcinoma was offered which was later confirmed by histopathology. The diagnosis of choriocarcinoma on fine needle aspiration cytology is based on the presence of large, multinucleated giant cells and malignant mononucleated cells. A high index of suspicion should be maintained and estimation of serum β hCG plays a key role in supporting the diagnosis.

Extra genital heterologous malignant mixed mullerian tumor of primary peritoneal origin.

The case of an extragenital heterologous malignant mixed müllerian tumor (MMMT) of primary peritoneal origin occurring in a 76-year-old female is presented. A large tumor was seen between the uterus and rectosigmoid occupying the entire pelvis. The uterus, fallopian tubes and ovaries were uninvolved. The tumor was composed of carcinomatous areas showing endometrioid and serous papillary differentiation and sarcomatous areas showing cartilaginous differentiation. The extragenital primary MMMTs of the female peritoneum are thought to originate from the secondary müllerian system. This case is presented for its rarity. To the best our knowledge, this is the first case of extragenital MMMT of primary peritoneal origin in Indian literature.

Diagnosis of metastatic carcinoid in mesenteric lymph node by fine needle aspiration cytology.

Although carcinoid tumor is a relatively common neoplasm in surgical pathology, fine needle aspiration cytology (FNAC) as a method of primary diagnosis has only been reported a few times. We report the case of a 55-year-old male patient who presented with colicky pain in the abdomen and a vague mass in the right lumbar region. Ultrasonographic study showed an enlarged mesenteric lymph node. Ultrasonography-guided FNAC revealed cellular smears with neuroendocrine cellular arrangement and morphology. The cytomorphologic characteristics of carcinoid tumors are distinctive enough for diagnosis. A diagnosis of metastatic carcinoid was given. 5-hydroxyindolacetic acid in 24-hour urine turned out to be high. Histopathology and immunohistochemistry studies also confirmed the diagnosis. Thus, FNAC can be a useful and safe tool in the diagnosis of carcinoid tumors.

A t(X; 18) SYT-SSX2 positive synovial sarcoma in the pelvis of a young adult male: A rare case report with review of literature.

Synovial sarcoma is uncommonly documented in the pelvis. Rarely, such cases have dealt with molecular analysis. A 19-year-old boy presented with pain and swelling in his left lower limb of two months duration. He developed acute urinary retention four days prior to his hospital admission, wherein radiological examination unraveled a large soft tissue mass, displacing his pelvic muscles, along with a lytic lesion involving his right pubic bone. Biopsy showed a cellular spindle cell sarcoma, exhibiting hemangiopericytoma-like vascular pattern with focal necrosis. Immunohistochemistry (IHC) showed positivity for vimentin, BCL-2, calponin and MIC 2. Cytokeratin (CK) and epithelial membrane antigen (EMA) were negative. MIB 1 count was 70% (high). P53 was positive. Diagnosis of a poorly differentiated synovial sarcoma was offered and confirmed with a positive t(X; 18) SYT-SSX2 translocation. This case highlights the value of molecular analysis in diagnosis of a synovial sarcoma at rare sites, especially when IHC results are equivocal and the biopsy material is limited.

Cytomegalovirus oesophagitis in a patient with Non-Hodgkin's lymphoma.

Cytomegalovirus (CMV) infection is frequent in immunocompromised patients, especially in AIDS, organ transplantation and rarely in Hodgkin's disease and Non-Hodgkin's lymphoma (NHL). We present a case of NHL with CMV oesophagitis, which has rarely been documented in literature. Apart from fungal and herpes simplex infections, as the common differential diagnosis for oesophagitis in patients of lymphoma, CMV should be considered an important etiologic agent. Early diagnosis and prompt treatment of CMV oesophagitis with gancyclovir can avert significant morbidity and avoid unacceptable treatment delays.

Congenital amegakaryocytic thrombocytopenia (CAMT): a case report with review of literature.

Congenital amegakaryocytic thrombocytopenia (CAMT) is an uncommon cause of thrombocytopenia in children. Mutations in the thrombopoietin (Tpo) receptor gene C-mpl were found to be the likely cause of thrombocytopenia and complete marrow failure. Two types are identified: CAMT with or without congenital anomalies. We report a case of the latter type for its extreme rarity.