Effectiveness and safety of 0.5% timolol solution in the treatment of pyogenic granuloma: A randomized, double-blind and placebo-controlled study

Introduction: Pyogenic granulomas are benign vascular lesions of the skin and mucosa which are often a source of concern because of their recurrent bleeding even with minimal trauma. Current treatment for pyogenic granuloma is ablative; no medical therapy is standardized to date. Timolol, due to its vasoconstrictive effect, vascular growth factor inhibition and apoptosis promotion properties, is a potential therapeutic option. Objectives: To assess the effectiveness and safety of topical timolol in the treatment of pyogenic granulomas. Methods: A two-centre, double-blind and placebo-controlled trial (Registration CTRI/2019/04/018581) was conducted. Patients of either sex were recruited with pyogenic granuloma lesions of less than eight weeks duration. Topical treatment with 0.5% timolol or matching glycerin placebo was continued for six weeks. Changes in color, size, bleeding tendency, physicians’ and patients’ global assessments and adverse events were assessed. Results: Forty subjects were randomized between the two groups which were comparable in age, sex, duration of illness and baseline lesion size.Significant improvement was noted with timolol, with color change from first follow-up onwards and lesion size reduction from second follow-up onward. Patients’ assessment of bleeding tendency also showed imrovement from the second visit onward. Between-group comparison showed significant difference with respect to percentage reduction in size (timolol 40.9%, placebo 3.4%; P = 0.002). Rescue treatment (electrosurgery) was required in five patients on placebo and in one in the timolol group (P = 0.182). Complete resolution occurred in 2 (10%) patients with timolol and in no patients on placebo (P = 0.231). Limitations: We observed effects of treatment for only six weeks. Conclusion: Topical timolol may be a treatment option for early pyogenic granulomas but complete resolution is unlikely in six weeks. Studies of longer duration are required to assess resolution and recurrence rates

Electrocardiographic Parameters in Indian Newborns

Objective: To generate data of electrocardiogram (ECG) parameters according to gestationalage in Indian newborns. Methods: An observational study was carried out over 7 months inneonatology unit of a tertiary care teaching hospital. Following auscultation, ECG parameterswere recorded simultaneously in 12 leads, on third day of life, in hemodynamically stableneonates. Data from 364 babies were analyzed, keeping at least 30 records for eachgestational age between 30 to 42 weeks. Results: There was no difference in mean heart raterecorded through auscultation and ECG traces. The mean (SD) values recorded were: Pwave duration 0.04 (0.01) s, P wave amplitude 1.3 (0.4) mm, T wave duration 0.07 (0.02) s, Twave amplitude 1.1 (0.6) mm, PR interval 0.09 (0.02) s, QRS duration 0.04 (0.01) s, QTinterval 0.26 (0.02) s, QTc 0.4 (0.03) s and QRS axis 127 (22) degree. Gestation age-wisepercentile charts of different ECG parameters were generated. Conclusion: Thesegestational age-wise percentile charts of different ECG parameters for Indian newborns canbe used as reference for neonatal ECG

Extended Sick Neonate Score (ESNS) for Clinical Assessment and Mortality Prediction in Sick Newborns referred to Tertiary Care

Objective:To evaluate utility of a new Extended Sick Neonate Score (ESNS). to predict ‘in-hospital mortality’ and compare with Score for Neonatal Acute Physiology – PerinatalExtension II (SNAPPE II) and Sick Neonate Score (SNS). Design:Prospective observationalstudy. Methods:All extramural sick newborns transported to the neonatology unit of a tertiarycare teaching hospitalover a period of one year.Correlation between ESNS, SNAPPE-II andSNS scoring, and sensitivity/specificity of each score to predict mortality were determined.Results:961 newborns were enrolled in the study. ESNS, SNAPPE II and SNS were stronglycorrelated, even when stratified by gestation. ESNS of ≤11 had the best sensitivity (85.9%)and specificity (89.8%). For preterms, ESNS ≤12 had the best sensitivity (92.3%) andspecificity (76.7%). Conclusion:ESNS can predict ‘in-hospital mortality’ outcome withsatisfactory sensitivity and specificity

Is elevated blood glucose a marker of occult tissue hypoperfusion in off-pump coronary artery bypass grafting?

Context: Hyperglycemia has been found to occur during myocardial infarction and cardiac surgery even in nondiabetic patients. These being essentially stressful processes associated with hypoperfusion, we decided to find a possible relationship between the occurrence of global tissue hypoperfusion (GTH) and elevated blood glucose level in adult nondiabetic patients undergoing elective off-pump coronary artery bypass grafting (CABG). Aims: This study aims to observe for the occurrence of global tissue hypoperfusion and its effect on blood glucose level and whether raised blood glucose level can be used as a marker for GTH. Design: Prospective, observational study. Settings: Cardiothoracic operation theater and intensive care unit of a tertiary care teaching hospital. Materials and Methods: The occurrence of global tissue hypoperfusion were detected with the help of combined markers of mixed venous oxygen saturation and arterial lactate level at various perioperative study points together with arterial blood glucose level. Blood glucose level compared between the patients with and without GTH. Statistical Analysis Used: Numerical variables were compared between groups by Student's t-test and categorical variables by Fisher's exact test. Two-tailed P ≤ 0.05 was considered for statistically significant. Results: The incidence of GTH was 67%. Blood glucose level was raised in patients with GTH at some study time points but with poor sensitivity and specificity values. Conclusions: Global tissue hypoperfusion is a common occurrence in even nondiabetic patients undergoing elective off-pump CABG. A relationship exists between rise in blood glucose level and global tissue hypoperfusion in such patients, although it cannot be viewed as marker of the same.

Efficacy and safety of a centrally acting analgesic flupirtine in primary knee osteoarthritis in comparison to tramadol: a randomized controlled trial

Background: Osteoarthritis (OA) is a chronic, degenerative joint disorder responsible for considerable morbidity, particularly in old age. Flupirtine, a new centrally acting analgesic, is devoid of the adverse effects of NSAIDs and opioid analgesics. In this study author compared the effectiveness and safety of flupirtine with tramadol in knee OA.Methods: An open label, randomized, controlled trial was done with patients of primary knee OA of both sexes, age >50 years. Patients were recruited from Rheumatology OPD of SSKM Hospital. A minimum WOMAC score of 35 was essential for recruitment. Patients with serious comorbidities were excluded. They were treated orally with either flupirtine (100mg thrice daily) or tramadol (50mg thrice daily) for 12 weeks.Results: Ninety patients were recruited and data of 42 on flupirtine and 41 on tramadol were analysed. There was significant improvement in pain, stiffness and physical function compared to baseline in both the groups. However, there was no significant difference between groups at 4, 8 and 12 weeks. Responder rate (50% reduction in pain score from baseline) was 66.67% with flupirtine and 48.78% with tramadol (p = 0.122). Flupirtine caused 4 adverse events compared to 16 with tramadol. However, both the drugs were well-tolerated.Conclusions: The effectiveness of flupirtine in knee OA is comparable to tramadol, while causing minimal adverse effects. Long-term benefits need to be explored.

Clinicopathological characteristics of patients of certain molecular subtypes and elevated postoperative cancer antigen 15.3 levels and its correlation with menopausal status.

Context: It is well established that breast cancer subtypes differ in their outcome and treatment response. Aim: To observe tumor characteristics of different molecular subgroup and patients with postoperative (PO) raised cancer antigen 15.3 (CA 15.3) group and variation of tumor nature between pre‑ and post‑menopausal breast cancer patients. Materials and Methods: Blood samples and tumor blocks were collected from 95 nonmetastatic female breast cancer patients. Immunohistochemical stains for estrogen receptors (ER), progesterone receptor (PR), and HER2/Neu were used to classify molecular subtypes. CA 15.3 level was detected by ELISA. Significance levels were ascertained by Pearson Chi‑square test. Results: Prevalence of luminal A tumor with grade 3 was high. Triple negative and ER positive (ER+) types showed tumors with high grade and high lymph node (LN) metastasis. More nodal involvement was noticed in patients with PO raised CA 15.3. In addition, premenopausal patients with triple‑negative and ER+ subtypes exhibited more aggressive tumors which were characterized by high grade and large numbers of LN metastasis. Conclusion: Clinicopathological characteristics of certain molecular subtypes and influence of menopausal status on it can predict disease recurrence or overall survival of breast cancer patients.

Clitoral Length and Anogenital Ratio in Indian Newborn Girls.

Objective: To generate normative data on clitoris length, anogenital distance and anogenital ratio in Indian newborns. Design: Cross-sectional study. Setting: Neonatal unit of a tertiary care teaching hospital in Kolkata. Participants: 378 female neonates, who were hemo-dynamically stable without critical illness or chromosomal anomaly, and without any vulval hematoma or genital abnormalities. Interventions: Measurements were recorded using a digital vernier caliper between 24-72 hours. Infant was held in position by an assistant, while the investigator measured clitoral length by gently retracting the labia majora. Anogenital distance (centre of the anus to posterior convergence of the fourchette) and anogenital ratio (anogenital distance divided by the distance from centre of the anus to base of the clitoris) was also measured. Main outcome measures: Gestational age- and birthweight-wise normative values of clitoral length, anogenital distance and anogenital ratios. Results: Mean clitoral length was 3.1 (1.54) mm for the whole cohort while anogenital distance and anogenital ratio were 10.2 (2.78) mm and 0.34 (0.07) mm, respectively. The gestation age-wise percentile charts of clitoral length, anogenital distance and anogenital ratio have been generated. There was no correlation between clitoral length and gestational age, body length, head circumference and birth weight. Correlations were also weak for anogenital distance. Conclusions: The normative values generated can serve as reference standard in the assessment of clitoromegaly, ambiguous genitalia, virilizing effects and suspected in utero androgen exposure.

Normative Blood Pressure Data for Indian Neonates.

Objective: To establish the normative blood pressure (BP) values in healthy Indian neonates using oscillometric method, and to develop BP percentile charts. Design: Prospective observational study. Setting: Neonatal unit of a teaching hospital in Eastern India. Participants: 1617 hemodynamically stable inborn neonates without birth asphyxia, major congenital anomaly, maternal complications (e.g. preeclampsia, hypertension, diabetes) or critical neonatal illness. Procedure: Quite state measurements of systolic BP (SBP), diastolic BP (DBP) and mean arterial pressure (MAP) were recorded by oscillometric method on day 4, 7 and 14 of postnatal life. The averages of three readings at 2-minute intervals were used. Results: Percentile charts (providing 5th, 10th, 25th, 50th, 75th, 95th, and 99th percentile values) have been developed. SBP, DBP and MAP showed a steady rise from day 4 to day 14, and were comparable between males and females, but were significantly lower in preterms than in term neonates Conclusions: Normative neonatal BP data along with gestational age-wise percentile charts shall be of help for decision-making and planning for sick newborns.

Hepatoprotective and Antioxidant Activities of LST-02, A Proprietary Herbal Formulation.

LST-02 is a proprietary polyherbal formulation prepared by blending 50% standardized hydroethanolic extract of ten well-known herbs, namely Tinospora cordifolia, Phyllanthus amarus, Emblica officinalis, Terminalia chebula, Terminalia bellerica, Azadirachta indica, Adhatoda vasica, Picrorrhiza kurroa, Swertia chirata and Boerhaavia diffusa. The formulation was evaluated for hepatoprotective and antioxidant properties. The phenolic content and 2,2-diphenyl-1-picrylhydrazyl (DPPH) radical scavenging abilities were evaluated to ascertain antioxidant property. In vitro hepatoprotective action was examined in carbon tetrachloride (CCl4) challenged isolated rat hepatocytes. Finally, LST-02 pretreatment was examined in D-galactosamine (GalN) induced (200 mg/kg; intraperitoneal) hepatitis in male Wistar rats, with silymarin 25 mg/kg as positive control. In vitro studies confirmed that LST-02 is rich in phenolic compounds. It could inhibited DPPH free radicals and exerted significant (p<0.05) protective activity against CCl4 induced injury in rat hepatocytes. Short-term pre-treatment with LST-02 (100 mg/kg and 200 mg/kg; oral) exhibited dose dependent protection against GalN induced hepatitis in rats (p<0.05). It significantly reduced GalN induced elevation of liver enzymes in serum and resisted oxidative stress by modulating catalase and reduced glutathione in hepatic parenchyma (p<0.05). The combination of herbal ingredients in LST-02 exerts hepatoprotective activity and a possible mechanism of this action is its antioxidant property.

Post-treatment alterations of serum cancer antigen 125, cancer antigen 19.9 and carcinoembryonic antigen levels in patients with gynecological malignancies in a tertiary care hospital in eastern India.

Gynecological carcinomas form a significant proportion of all malignancies in women across the globe. These are associated with an increase in the serum concentrations of certain tumor markers such as cancer antigen (CA)125, CA19.9 and carcinoembryonic antigen (CEA) that correlate with the tumor burden. Methods: Pre- and post-treatment serum levels of CA125, CA19.9 and CEA were determined in 36 patients of ovarian carcinoma, 31 patients of cervical carcinoma and 20 patients of endometrial carcinoma using enzyme-linked immunosorbent assay. The pre- and the post-treatment levels of these markers have been compared and correlated. Results: With primary treatment, CA125 level was significantly reduced in ovarian, endometrial (ps < 0.001) and cervical (p = 0.001) carcinomas and that of CA19.9 was significantly decreased in cervical and endometrial carcinomas (ps < 0.001). Surprisingly, post-treatment CEA level was significantly increased in cervical carcinoma (p = 0.001) with significant increase after radiotherapy (p = 0.003), but not after surgery (p = 0.091). Treatment had no effects on CA19.9 level in ovarian carcinoma and on CEA levels in ovarian and endometrial carcinomas. Pre- and post-treatment levels of CA125, CA19.9 and CEA showed strong positive correlation in cervical carcinoma, while those of CA19.9 showed very strong positive correlation in endometrial carcinoma. Conclusions: Post-treatment serum CA125 level best reflects the treatment effect in all three types of gynecological carcinomas. CA19.9 is reliable to evaluate treatment effect in patients of cervical and endometrial carcinomas. Studies involving larger population size should be conducted to identify the changes in CEA while assessing treatment effect in cervical carcinoma patients.

Growth of Children with Juvenile Idiopathic Arthritis.

Objective: To evaluate the growth pattern in children with juvenile idiopathic arthritis and its subtypes in comparison with age, sex and temporally matched controls. Study design: Prospective study. Setting: Pediatric rheumatology clinic of a tertiary care hospital in Eastern part of India. Participants: Seventy-five children (2-12 years) diagnosed as juvenile idiopathic erthritis by International League of Associations for Rheumatology criteria and 75 age- and sex- matched controls. Intervention: Weight, height and body mass index were recorded at six monthly interval in both groups over a period of 3 years. Main outcome measures: weight, height and body mass index. Results: Subtype distribution of juvenile idiopathic arthritis was: oligoarthritis (49%, n=37), rheumatoid factor negative polyarthritis (27%, n=20), rheumatoid factor positive polyarthritis (8%, n=6), systemic onset (15%, n=11) and enthesitis related arthritis (1.3%, n=1). Anthropometric parameters in children with juvenile idiopathic arthritis were not significant different from controls. Comparison between the subtypes showed significant differences in height (P=0.011), weight (P=0.005), and growth velocity (P=0.005), but not in body mass index. Systemic onset disease led to significant restriction in height (P=0.018; 95% CI 2.13-33.77) and weight (P=0.008; 95% CI 1.47-14.43) compared to controls. Growth velocity was significantly affected in rheumatoid factor positive polyarthritis (P=0.003; 95% CIO. 46-3.14). Conclusions: Children with juvenile idiopathic arthritis do not have significantly lower values of anthropometric parameters compared to controls. Significant restriction in height and weight is seen in systemic onset disease, and growth velocity is significantly reduced in rheumatoid factor positive subjects.

Stress and its risk factors in medical students: An observational study from a medical college in India.

Objectives: Stress in medical students is well established. It may affect academic performance and lead to anxiety, depression, substance abuse, and burnouts. There is limited data on stress in Indian medical students. We conducted an analytical observational study to assess the magnitude of stress and identify possible "stressors" in medical students of a teaching hospital in Kolkata. Materials And Methods: This questionnaire-based study was conducted in the Institute of Post Graduate Medical Education and Research, Kolkata with consenting undergraduate students of 3 rd , 6 th , and 9 th (final) semesters, during lecture classes in individual semesters on a particular day. The students were not informed about the session beforehand and were assured of confidentiality. The first part of the questionnaire captured personal and interpersonal details which could be sources of stress. The rest comprised three rating scales - the 28-item General Health Questionnaire to identify the existence of stress, the Warwick-Edinburgh mental well-being scale to assess the mental well-being, and the revised version of the Lubben social network scale to assess the social networking. The responses and scores were compared between the three semesters as well as between various subgroups based on baseline characteristics. Results: Data from 215 respondents were analyzed - approximately 75% were male, 45% came from rural background, 25% from low-income families, and 60% from vernacular medium. Totally, 113 (52.56%; 95% confidence interval: 43.35-61.76%) students were found to be stressed, without significant difference in stress incidence between the semesters. About 60% of the female students were stressed in contrast to 50% of the males, but this observed difference was not statistically significant. The mental well-being and social networking of stressed respondents suffered in comparison to their non-stressed counterparts. Conclusions: The stress incidence in medical students in this institution in India is high and is negatively affecting their mental well-being. Further multicentric and longitudinal studies are needed to explore the incidence, causes, and consequences of stress in our setting.

Normative data of cervical length in singleton pregnancy in women attending a tertiary care hospital in eastern India.

Background & objectives The length of cervix predicts the risk of preterm delivery. The objective of this study was to assess cervical length in pregnancy by transvaginal ultrasonography for generating normative data for nulliparous women at no special risk of preterm labour. Methods An observational study was carried out in a tertiary care teaching hospital in eastern India in nulliparous women who delivered at term. A single sonologist assessed 224 women (once per subject) between 20 and 34 wk of gestation. Nulliparous women carrying a single foetus of confirmed gestational age were included; 216 subjects were finally considered for generation of normative data, excluding those delivering earlier than 37 or later than 42 wk. Other exclusion criteria were history of cerclage, any previous cervical surgery, smoking, or any medical disorder complicating pregnancy. Results Cervix length at each week of gestation gradually decreased over the study period. Length at 20 and 34 wk was 40.5 ± 1.14 mm (mean ± SD) and 34.8 ± 1.34 mm respectively. The overall shortening over this 14 wk period was 5.7 mm, with 0.58 mm per week median rate of shortening. Pearson's correlation coefficient was - 0.69 (95% CI - 0.75 to - 0.60; P< 0.001) for cervical length vis-à-vis gestational age. Interpretation & conclusions The serial normative data generated in our setting can be used to decide cut-off points for predicting risk of preterm labour in future studies. Validity of such prediction needs to be tested in larger cohorts of women assessed at specific gestational ages.

Childhood lupus: Experience from eastern India.

Objective. To delineate the clinical behavior of SLE in children from Eastern India and to the differences in disease pattern. Methods. In the present study, all 44 patients of pediatric SLE who were diagnosed over a period of 5 years in our pediatric rheumatology clinic were followed prospectively. The resultant database was analyzed using standard statistical methods. Results. About 3.9% of all rheumatology cases dealt with in the clinic in the last five yrs (n=1063) were SLE. The number of children in 5-8 yrs and 8-12 yrs age groups were 13 and 27, respectively. The overall female (n=35) to male (n=9) ratio in this study was 3.8:1. Renal, hematological and Neuropsychiatric features were most common major organ manifestations(54%,54% and 25% respectively). Joints and skin were the most common minor organs involved. Two case were ANA negative SLE. Among the typical features of ANA negative disease, only nephritis was found in these patients. Anti dsDNA was positive in 50 % cases (n=21). C3 levels were studied in all cases with nephritis (n=22) and 68 % (n=15) had hypocomplementemia. Anti Ro and anti La antibodies were positive in two cases of neonatal lupus. APLA, Anti Sm antibody and anti U1RNP were negative in the cases where testing was done. Conclusions. This study has tried to delineate the disease trends of childhood lupus from Eastern India. Certain important trends have emerged which are different from other contemporary Indian and International observations.

Neurological disorders in children and adolescents.

OBJECTIVE: To ascertain the prevalence of active epilepsy, febrile seizures (FS), cerebral palsy (CP) and tic disorders (TD) in aged 19 years or less. METHODS: This was a cross-sectional observational study conducted as a two-stage door-to-door survey of a stratified randomly selected population in 2003-04. Trained field workers screened the population followed by case examination by the field neurologist. RESULTS: A total of 16979 (male 8898, female 8081) subjects aged <or= 19 years were surveyed. The prevalence rates per 100,000 population of active epilepsy, FS, CP and TD with 95% confidence intervals are 700.87 (580.60-838.68), 1113.14 (960.07-1283.59), 282.70 (CI 208.43-374.82) and 35.34 (12.96-76.92) respectively. Active epilepsy prevalence shows a rising trend and that of other disorders a declining trend with age. Of the epileptics who had brain CT scans, 23.4% showed single or multiple lesions suggestive of neurocysticercosis. Regarding treatment, 23.5% of the epileptics never received any antiepileptic drugs. Among those with history of FS, 9.5% developed epilepsy later on. The prevalence of FS among slum dwellers is lower than in the non-slum population. Among CP cases, 39.6% gave history of birth anoxia, 16.7% kernicterus and 31.3% epilepsy. Prevalence of CP is significantly associated with lower education status. CONCLUSION: The prevalence of CP and TD is lower than reported from western countries. CP prevalence is also comparatively lower than in many community studies from India. Compared to western nations, higher proportion of FS cases develops epilepsy. A third of the CP cases have seizures which is higher than in many Indian studies. Birth anoxia is a common cause of CP and educational underachievement is frequent.

New drugs in India over the past 15 years: analysis of trends.

BACKGROUND: New drugs are appearing in the Indian pharmaceutical market every day. To study the trends we analysed the pattern of new drug approvals and introductions in India over the past 15 years (1988-2002). METHODS: Lists of new drugs approved by the Drugs Controller General of India, released half-yearly, were obtained and entered into a computer database. Additional information, such as anatomical therapeutic chemical coding, availability status till 31 December 2002 and source were added to this database before analysing overall time trends and the situation in individual therapeutic categories. RESULTS: Excluding unrecognized and compound formulations and 28 veterinary products, 396 drugs were approved for clinical use during this period. Of these, 315 have also been launched in the market and 5 were subsequently withdrawn. Nervous system-related drugs accounted for the largest number of approvals (82), followed by antimicrobials (73) and cardiovascular drugs (57). Five new antimalarials have emerged but other tropical diseases have been mostly ignored. Eleven vaccines have been added. CONCLUSION: There has been a sharp spurt in the annual number of approvals and introductions. The proliferation of brands and fixed-dose combinations has kept pace with the introduction of new molecules. Unfortunately, most new drugs are not major therapeutic advances. In the context of this rapid proliferation, meeting the information needs of prescribers, establishing an effective nationwide pharmacovigilance system and reorienting the focus of pharmacology education--from information provision to development of self-learning and critical judgement skills-are some issues for concern.