Mradul Kumar Daga

A randomized, double-blind, placebo-controlled, Phase 2b study to evaluate the safety and efficacy of recombinant human soluble thrombomodulin, ART-123, in patients with sepsis and suspected disseminated intravascular coagulation.

Objectives:To determine the safety and efficacy of recombinant thrombomodulin (ART-123) in patients with suspected sepsis-associated disseminated intravascular coagulation. Design:Phase 2b, international, multicenter, double-blind, randomized, placebo-controlled, parallel group, screening trial. Setting:Two hundred and thirty-three ICUs in 17 countries. Patients:All adult patients admitted with sepsis and suspected disseminated intravascular coagulation as assessed using a modified International Society on Thrombosis and Hemostasis score. Interventions:Patients were randomized to receive IV ART-123 (0.06 mg/kg/d) for 6 days or placebo, in addition to standard of care. The primary endpoint was reduction in mortality. Secondary endpoints included reversal of overt disseminated intravascular coagulation and reduction in disease severity. Measurements and Main Results:A total of 750 patients were randomized, nine of whom did not receive the allocated treatment so that 371 patients received ART-123 and 370 received placebo. There were no meaningful differences between the two groups in any of the baseline variables. Twenty-eight-day mortality was 17.8% in the ART-123 group and 21.6% in the placebo group (Cochran–Mantel–Haenszel two-sided p value of 0.273 in favor of ART-123, which met the predefined statistical test for evidence suggestive of efficacy). There were no statistically significant differences in event-free and alive days between the two groups. d-dimer, prothrombin fragment F1.2 and TATc concentrations were lower in the ART-123 group than in the placebo group. There were no differences between the two groups in organ function, inflammatory markers, bleeding or thrombotic events or in the development of new infections. In post hoc analyses, greatest benefit from ART-123 was seen in patients with at least one organ system dysfunction and an international normalized ratio greater than 1.4 at baseline. Conclusions:ART-123 is a safe intervention in critically ill patients with sepsis and suspected disseminated intravascular coagulation. The study provided evidence suggestive of efficacy supporting further development of this drug in sepsis-associated coagulopathy including disseminated intravascular coagulation. Future study should focus on using ART-123 in the subgroup of patients most likely to respond to this agent.

Effects of exogenous vitamin E supplementation on the levels of oxidants and antioxidants in chronic obstructive pulmonary disease

Oxidative stress has been recognized as a central feature of smoke induced chronic obstructive pulmonary disease (COPD). Imbalance between oxidant and antioxidant enzymes is also an established fact in these patients. But studies in regard to stable COPD patients and effect of vitamin E supplementation are lacking. Thirty patients with COPD were included in the study. Their baseline clinical examination, spirometry, plasma malondialdehyde (MDA), alpha-tocopherol and red blood cell superoxide dismutase (SOD) levels were measured. Twenty healthy non-smokers who were matched for age and sex served as controls. All the above parameters were repeated after 12 weeks of supplementation with 400IU of vitamin E daily. The mean malondialdehyde levels in the patients at baseline were higher than controls (5-91 ±1.23 nmol/ml vs 4.55 ± 1.51 nmol/ml,P = 0.001), so also was plasma alpha-tocopherol levels (P<0.00l), while SOD levels were lower in the patients compared to controls (1692 ± 259 units g/Hb vs 2451 ± 131 units g/Hb,P < 0001). Exogenous vitamin E (400 IU per day) supplementation did not bring about any significant change in plasma alpha-tocopherol and SOD levels. The Pearson’s co-efficient of correlation between the levels of MDA, vitamin E, SOD; and spirometric measurements were not significant either on day 1 or after 12 weeks of vitamin E supplementation. The present study shows that initially the plasma lipid peroxide (MDA) levels are high and antioxidants (alpha-tocopherol and SOD) are low in patients with COPD. Exogenous supplementation with vitamin E does not have any significant effect on the spirometric measurements though it brings down the levels of MDA showing attenuation of further damage. However, inclusion of larger number of patients and supplementation with vitamin E for longer periods may throw more light on free radical injury and protective effects of antioxidants.

Urinary catheterization in medical wards

Aims: The study aims to determine the: 1. frequency of inappropriate catheterization in medical wards and the reasons for doing it. 2. various risk factors associated with inappropriate catheterization, catheter associated urinary tract infections (CAUTI) and bacterial colonization on Foleys catheters (BCFC). Settings and Design: Hospital-based prospective study. Materials and Methods: One hundred and twenty five patients admitted consecutively in the medical wards of a tertiary care hospital, who underwent catheterization with a Foleys catheter, at admission, have been included in the study. Patient profiles were evaluated using the following parameters: age, sex, diagnosis, functional status, mental status, indication, duration and place of catheterization, development of BCFC and CAUTI. Statistical tests used: Chi-square test. Results: Thirty-six out of 125 (28.8%) patients included were inappropriately catheterized. BCFC developed in 52.8% and 22.4% were diagnosed with a CAUTI. The most frequent indication for inappropriate catheterization was urinary incontinence without significant skin breakdown (27.8%). The risk factors for inappropriate catheterization were female sex (RR=1.29, 95% CI=0.99, 1.69, P<0.05) and catheterization in the emergency (RR=0.74, 95% CI=0.61, 0.90, P<0.05). The risk factors for developing a BCFC were age>60 years (RR=0.65, 95% CI=0.48, 0.89, P<0.05), non-ambulatory functional status (RR=0.57, 95% CI=0.39, 0.84, P<0.01), catheterization in the emergency (RR=2.01, 95% CI=1.17, 3.46, P<0.01) and duration of catheterization>3 days (RR=0.62, 95% CI=0.43, 0.89, P<0.01). The risk factors for acquiring a CAUTI were age>60 years (RR=0.47, 95% CI=0.25, 0.90, P<0.05), impaired mental status (RR=0.37, 95% CI=0.18, 0.77, P<0.01) and duration of catheterization>3 days (RR=0.24, 95% CI=0.10, 0.58, P<0.01). Conclusions: Inappropriate catheterization is highly prevalent in medical wards, especially in patients with urinary incontinence. The patients catheterized in the medical emergency and female patients in particular are at high risk. Careful attention to these factors can reduce the frequency of inappropriate catheterization and unnecessary morbidity.

Metastatic malignant melanoma in bone marrow with occult primary site – a case report with review of literature

BackgroundMetastases of malignant melanoma to the bone marrow are very rare. A few case reports are published in the literature with a known primary site.Case presentationHerein we present a case of metastatic malignant melanoma in bone marrow with occult primary site in a 22- year-old-male. Diagnosis was confirmed by morphology and immunohistochemistry. A pertinent review of literature is also presented by using relevant articles indexed in PubMed (National Library of Medicine) database. The search was based on the following terms: metastasis or metastases, malignant melanoma and bone marrow.ConclusionIn this report we discuss a rare case of metastatic malignant melanoma to the bone marrow with an unknown primary. Clinicians must be aware of the varied clinical manifestations of disseminated malignant melanoma even if the primary site is not evident.

Study of gastro-oesophageal reflux disease in patients with mild-to-moderate chronic obstructive pulmonary disease in India

Background and objective:  To study the incidence and pattern of gastro‐oesophageal reflux disease (GORD) in patients with mild‐to‐moderate chronic obstructive pulmonary disease (COPD) using dual‐probe 24‐h oesophageal pH recording.

Sequence-Specific Cleavage of BM2 Gene Transcript of Influenza B Virus by 10-23 Catalytic Motif Containing DNA Enzymes Significantly Inhibits Viral RNA Translation and Replication

One of the hallmarks of progression of influenza virus replication is the step involving the virus uncoating that occurs in the host cytoplasm. The BM2 ion channel protein of influenza B virus is highly conserved and is essentially required during the uncoating processes of virus, thus an attractive target for designing antiviral drugs. We screened several DNA enzymes (Dzs) containing the 10-23 catalytic motif against the influenza B virus BM2 RNA. Dzs directed against the predicted single-stranded bulge regions showed sequence-specific cleavage activities. The Dz209 not only showed significant intracellular reduction of BM2 gene expression in transient-expression system but also provided considerable protection against influenza B virus challenge in MDCK cells. Our findings suggest that the Dz molecule can be used as selective and effective inhibitor of viral RNA replication, and can be explored further for development of a potent therapeutic agent against influenza B virus infection.

Acute Pancreatitis Complicating Acute Hepatitis E Virus Infection: A Case Report and Review

Acute pancreatitis complicating fulminant viral hepatitis has been well recognized; however, acute pancreatitis occurring in nonfulminant hepatitis is very rare. The case presented describes moderate pancreatitis in a young male, manifesting during the course of nonfulminant acute hepatitis E infection. The diagnosis of acute viral hepatitis E was confirmed by serology and reverse transcriptase polymerase chain reaction (RT-PCR) to demonstrate Hepatitis E virus (HEV) RNA in both stool and serum. Patients with acute viral hepatitis presenting with severe abdominal pain should have a diagnosis of acute pancreatitis suspected and appropriate investigations including serum amylase, lipase, biliary ultrasonography and/or contrast-enhanced computed tomography of the abdomen should be undertaken. The identification of this unusual complication of Hepatitis E is important; however, the prognosis for patients with Acute Pancreatitis Complicating Acute Hepatitis E Virus Infection is good, and uncomplicated recovery with conservative treatment is expected.

Rare association of Visceral leishmaniasis with Hodgkin's disease: A case report

We present here a case of young male with complaints of fever and swelling in the neck for eight months. History of progressive weakness associated with weight loss was present. Physical examination revealed pallor, multiple enlarged cervical lymph nodes and hepatosplenomegaly. Investigations showed pancytopenia, hyperglobinemia and Leishman-Donovan bodies on bone marrow aspiration. Serological test confirmed diagnosis of visceral leishmaniasis. However, cervical lymph node aspiration and biopsy were suggestive of Mixed cellularity Hodgkins disease. This made it a very rare case of Leishmaniasis as an opportunistic infection in a patient of pre-chemotherapy Hodgkins disease. There was marked improvement in haematological profile and regression of hepatosplenomegaly with Amphotericin B treatment followed by favourable response to chemotherapy. The case emphasizes the suspicion for leishmaniasis as a masquerader and as an opportunistic infection in haematological malignancies.

Study of body composition, lung function, and quality of life following use of anabolic steroids in patients with chronic obstructive pulmonary disease.

BACKGROUND Chronic obstructive pulmonary disease (COPD) is characterized by irreversible airflow limitation and is associated with weight loss and decreased muscle strength and exercise capacity. METHODS A double-blinded randomized controlled trial of 32 male COPD patients (age, 54.94 ± 11.27 years) was carried out to assess effects of anabolic steroid in terms of a daily high-protein, high-calorie diet alone or one combined with anabolic steroids on body composition, lung function, and health-related quality of life (HRQL). Outcomes were assessed by anthropometric and spirometric measurements, peak expiratory flow rate, partial pressure of oxygen in arterial blood, 6-minute walk test (6MWT), hand grip test, and HRQL index scores. Measurements were made at baseline and end of treatment (6 weeks). RESULTS All patients showed significant difference (P < .001) in pulmonary function parameters and anthropometric measurements after 6 weeks of intervention (within-group changes); however, no significant improvement occurred in the pulmonary function parameters between the groups. The difference in exercise capacity (6MWT) and HRQL scores in the treatment group were statistically significant (P < .001) compared with control group after 6 weeks of intervention. In the treatment group, the average 6MWT distance increased from 213.5 m to 268.5 m at 6-week follow-up, and HRQL scores increased from 101.25 to 118.45. Also, HRQL and 6MWT parameters were positively correlated in response to steroid supplementation at the end of the study. CONCLUSION Weekly administration of anabolic steroids during 6 weeks increased exercise capacity and quality of life in patients with COPD.

Prevalence and correlates of tobacco smoking, awareness of hazards, and quitting behavior among persons aged 30 years or above in a resettlement colony of Delhi, India.

Aim: To assess the prevalence and correlates of current smoking, awareness of hazards, and quitting behavior among smokers 30 years and above. Materials and Methods: Study design: Cross-sectional; Setting: Gokulpuri, a resettlement colony in East Delhi, India; Sample size: 911, persons aged 30 years and above using systematic random sampling; Study tools: Semi-structured questionnaire. Results: Prevalence of current smoking was found to be 24.6% (95% CI 21.90 - 27.49). Majority 198 (88.4%) of current smokers smoked bidi exclusively, and on an average 13.5 bidi/cigarette were smoked per day. Multivariate analysis showed the factors associated with current smoking as male sex, advancing age, illiteracy, skilled occupation, low socio-economic status, and low BMI (P < 0.001). 64.2% were aware of the hazards of smoking. 63 (21.9%) had quit smoking in the past, majority due to the health problems. Low educational status was associated with poor hazard awareness and quitting behavior. Conclusion: Smoking is a significant problem among poor and illiterate males, shows an increasing trend with an advancing age and is directly associated with skilled occupation and low BMI. There are significant gaps in knowledge regarding hazards of smoking.