Netarsudil monotherapy as the initial treatment for open-angle glaucoma and ocular hypertension in Indian patients: A real-world evaluation of efficacy and safety

Purpose: Glaucoma is the second leading cause of blindness worldwide, affecting more than 64 million people aged 40–80. The best way to manage primary open?angle glaucoma (POAG) is by lowering the intraocular pressure (IOP). Netarsudil is a Rho kinase inhibitor, the only class of antiglaucoma medications that reorganizes the extracellular matrix to improve the aqueous outflow through the trabecular pathway. Methods: An open?label, real?world, multicentric, observation?based 3?month study was performed for assessing the safety and ocular hypotensive efficacy of netarsudil ophthalmic solution (0.02% w/v) in patients with elevated IOP. Patients were given netarsudil ophthalmic solution (0.02% w/v) as a first?line therapy. Diurnal IOP measurements, best?corrected visual acuity, and adverse event assessments were recorded at each of the five visits (Day?1: screening day and first dosing day; subsequent observations were taken at 2 weeks, 4 weeks, 6 weeks, and 3 months). Results: Four hundred and sixty?nine patients from 39 centers throughout India completed the study. The mean IOP at baseline of the affected eyes was 24.84 ± 6.39 mmHg (mean ± standard deviation). After the first dose, the IOP was measured after 2, 4, and 6 weeks, with the final measurement taken at 3 months. The percentage reduction in IOP in glaucoma patients after 3 months of once?daily netarsudil 0.02% w/v solution use was 33.34%. The adverse effects experienced by patients were not severe in the majority of cases. Some adverse effects observed were redness, irritation, itching, and others, but only a small number of patients experienced severe reactions, as reported in a decreasing order: redness > irritation > watering > itching > stinging > blurring. Conclusion: We found that netarsudil 0.02% w/v solution monotherapy when used as the first?line treatment in primary open?angle glaucoma and ocular hypertension was both safe and effective.

Kawasaki Disease: Highlighting Importance of Laboratory Criteria and Minor Atypical Features of This Enigmatic Entity- A Case Series

@#Introduction: Kawasaki disease (KD) is an acute febrile illness of unknown etiology that primarily affects children younger than 5 years of age. The diagnosis is predominantly clinical and at times difficult, due to the absence of any confirmatory and specific diagnostic test. Early diagnosis of this disease is of paramount importance due to long term cardiovascular complications related to coronary artery aneurysm. Literature search has revealed many atypical presentations of Kawasaki disease not fulfilling the clinical diagnostic criteria. The reason for this could be the diversity in clinical manifestations involving gastrointestinal, endocrinal, musculoskeletal and nervous system. Case Series: Here we describe three cases with non-classic presentation of Kawasaki disease. These three cases presented with persistent fever unresponsive to antibiotics. Two cases (case one and three) later developed perianal rash and peeling that helped in early diagnosis. In the remaining case (case two) sequential appearance of features helped in the establishment of diagnosis. It was interesting to note that all the three cases were having identical laboratory parameters, highlighting the importance of laboratory investigations in case of atypical presentation. Conclusion: This case series culminates the importance of keeping the possibility of atypical Kawasaki disease (KD) as one of the differentials in patients with prolonged fever not responding to antibiotics, in the absence of classical diagnostic criteria.

Comparative study of patient-based versus case-based teaching in prescription writing skills of second year MBBS students

Background: Prescription writing errors can lead to deficiencies in healthcare. Although prescription writing is a part of the medical students' curriculum with traditional methods, their prescribing skills are still poor due to inadequate training. To fulfil the need for new educational interventions this study aims to compare patient-based teaching with case-based teaching in improving prescription writing skills of second year MBBS students.Methods: This prospective comparative study was carried out after orientation of participants to prescription writing as per WHO prescribing guidelines (n=71). Group A (n=37) and group B (n=34) were given patient-based teaching and case-based teaching respectively of prescription writing for the same five common clinical conditions. The prescription writing skill was assessed by evaluating the prescriptions written by both the groups and scored by 19-point scoring system. Feedback from the group A students was also taken.Results: Statistical analysis of mean scores of group A (15.90) and group B (13.14) was done by Mann-Whitney U test (p<0.001). Comparison of both the groups for the individual parameters was done by Chi-square test which found significant difference in writing some important parameters like doctor’s registration no., contacts of prescriber, name of the medicine, strength of drug, dosage form, dosing instructions, total quantity of medicine and duration of medication etc. Group A students’ feedback brought out the fact that patient-based teaching is a good tool for teaching and learning.Conclusions: Patient-based teaching for prescription writing improves students’ prescription writing skills in an effective way in comparison with traditional case-based teaching.

Hypersensitivity reaction with metformin: a case report

Metformin is a biguanide derivative widely used for treatment of diabetic patients. The most common toxic effects of metformin are gastrointestinal (anorexia, nausea, vomiting, abdominal discomfort and diarrhoea). As with other drugs, allergic reactions can occur with metformin also, but these are very rare. A case of hypersensitivity reaction with metformin was reported in adverse drug monitoring centre. A 59-year-old female, newly diagnosed case of diabetes mellitus II, started on metformin tablet 500 mg twice daily, developed purpuric skin lesions on her arms, legs and back few days after starting the drug. metformin was stopped and patient was put on glimepiride tablet. The lesions slowly started subsiding after stopping metformin.

A study to assess the magnitude of various minor physical anomalies in bipolar disorders and to compare them between bipolar disorder patients and their first degree relatives

Background: Bipolar disorder appears to be related to anatomic abnormalities in medial temporal lobe, in particular amygdale, prefrontal cortex and cerebellum. Two recent MRI findings have supported a neuro developmental etiology of bipolar disorders.Methods: It was a cross-sectional comparative hospital based study. The subjects were recruited for the study by the purposive sampling technique. The study was conducted at the Institute of Mental Health and Hospital Mathura Road Agra. The study sample consisted of 20 bipolar disorder patients diagnosed as per ICD-10 DCR (WHO, 1992) criteria, 20 first degree relatives, one for each patient. Total sample size is 40.Results: It was observed that in bipolar patients’ maximum anomalies were seen in Mouth (0.35±0.48) head (0.30±0.57) followed by anomalies of eyes (0.25±0.55) hand (0.20±0.41) and ear (0.05±0.22). It was observed that in Bipolar FDRs maximum anomalies were seen in mouth (0.20±0.04) ear (0.15±0.45) head (0.1±0.3) and then anomalies of eye and hand in equal propensity (0.05±0.22) and least anomalies in feet (0.00±0.00).Conclusions: The rate of MPAs in bipolar patients was more than their FDRs but not statically significant. Both sibling groups had fewer MPAs than the patients. When viewed within a vulnerability-stress model, the results are consistent with the theory that MPAs may reflect early, largely extra-genetic, stressful events.

Comparison of the Effect of Transpalatal Arch on Periodontal Stress and Displacement of Molars When Subjected to Orthodontic Forces. A Finite Element Analysis.

Introduction: The transpalatal arch has been used successfully for decades during routine orthodontic treatment for various purposes, including reinforcing anchorage. In the light of current scientific advancements with more precise knowledge of biology of tooth movement, it is prudent to study whether transpalatal arch is effective in preserving anchorage. Objectives: The aim of this finite element study was to evaluate and compare the effects of the transpalatal arch on periodontal stresses of molars and displacements when subjected to orthodontic forces. Methods: Stress patterns and displacements between models with and without a transpalatal arch were investigated by means of 3-dimensional finite element analysis. A finite element model of the maxillary first molars, periodontal ligament, alveolar bone, and transpalatal arch was created, that consisted of 1, 69,036 elements and 29,518 nodes. A simulated orthodontic retraction force of 2N was applied to the maxillary first molar in a mesial direction. Resultant von mises stresses were evaluated and compared in models with and without transpalatal arch, as well as displacement in models with and without transpalatal arch. Results: Results suggested that the presence of a transpalatal arch has no effect on molar tipping, decreases molar rotations, and reduces periodontal von mises stress magnitudes by less than 1%. Conclusions: The presence of the transpalatal arch induces only minor changes in the dental and periodontal stress distribution. Alternative methods can be used where absolute anchorage is required however transpalatal arch should not be considered an unnecessary tool in the treatment of orthodontic patients because of its various functions.

The effect of different grades polymer blends on release profiles of diclofenac sodium from hydrophilic matrices.

An attempt was made to design matrix tablet of diclofenac sodium by using various grades of hydroxypropyl methyl cellulose (HPMC E50, E15 and E300LV). The effect of hydrophilic polymers was studied on release characteristics of the diclofenac matrix tablet. Dicalcium phosphate and magnesium stearate were used as an excipients. Tablets were prepared by direct compression method. The in vitro dissolution test carried out for 12 hrs using USP dissolution apparatus II at 50 rpm in 900ml phosphate buffer pH 6.8. Statistically significant difference was found among the drug release profile from different matrices. The tablet evaluation parameters of hardness, friability, thickness, content uniformity were founded within the limit. At a fixed polymer level, drug release from the higher viscosity grades E50 was slower as compared to the lower viscosity grades (E300LV and E15). Tablet prepared with HPMC E50 is more release retardant. As the drug to polymer ratio increased drug release decreased. The dissolution study revealed that maximum retardation of the drug was obtained by highest viscosity grade HPMC at higher concentrations. The release of the model drug from these HPMC matrix tablets was prolonged.

Adverse drug reaction monitoring in psychiatric outpatient department of a Tertiary Care Hospital.

Background:Pharmacovigilance in psychiatry units can play vital role in detecting adverse drug reactions (ADRs) and alerting physician to such events, thereby protecting the user population from avoidable harm. Objective: To assess the suspected ADRs profile of psychotropic drugs in psychiatry OPD of a tertiary care hospital and its comparison with available literature data as well as to create awareness among the consultant psychiatrists to these ADRs profile. Materials and Methods: A prospective study was conducted in the psychiatry OPD. Thirty five consecutive patients per day were screened irrespective of their psychiatric diagnosis for suspected ADRs on 3 fixed days in a week from January 2011 to December 2011. CDSCO form was used to record the ADRs. Causality was assessed by WHO causality assessment scale while severity was assessed using Hartwig and Siegel scale. Results: Out of 4410 patients were screened, 383 patients were suspected of having at least one ADR. Thus, 8.68 % of our study population reported ADRs. Of 407 events recorded, 369(90.60%) were “probable” and rest “possible” according to WHO-UMC causality assessment scale. According to Hartwig and Siegel scale, 268 ADRs (65.85%) were “moderate” category. Twenty one different kinds of ADRs were noted. Conclusion: This study enables to obtain information on the incidence and frequency of ADRs in the local population that allows opportunity for education to the physicians to improve the patient’s quality of life.

Leaf and Seed extracts of Bixa orellana L. exert anti-microbial activity against bacterial pathogens.

Methanol extracts of the leaf & seed of Bixa orellana L. were studied for in vitro antimicrobial activity against MTCC strains of Staphylococcus aureus, Salmonella typhi, Klebsiella pneumoniae, Pseudomonas aeruginosa, Enterococcus fecalis, Vibrio cholera, Moraxella catarrhalis, Acinetobacter sp., Brucella sp. along with fungal pathogens Candida albicans, Aspergillus niger and the dermatophytes Trichophyton mentagrophytes & Trichophyton rubrum. Leaf extract of B. orellana at 1000 μg/ml concentration showed significant inhibition against all the tested bacteria and fungus, with highest inhibition zone (18±0.3 mm) against S. typhi, Acinetobacter sp., T. mentagrophytes and T. rubrum. Seed extract of B. orellana was comparitively less efficacious in most of the tested pathogens, except Brucella sp. which was appreciably inhibited (15±0.1 mm). Minimum Inhibitory Concentration (MIC) of leaf extract was determined as 15.62 μg/ml against S. aureus and 31.25 μg/ml for K. pneumoniae, P. aeruginosa, E. fecalis & S. typhi, on average. Among the dermatophytes, 78.2% inhibition was seen in T. mentagrophytes & T. rubrum. Scanning Electron Microscopic (SEM) studies of the treated P. aeruginosa cells revealed disintegration & aggregation of cells after treatment with the leaf extract. Phytochemical analysis of leaf & seed extracts suggested the presence of flavonoids, tannins, saponins, steroids. Alkaloids were detected only in the leaf & anthroquinones, in the seeds.

Erythrocyte indicators of oxidative changes in patients with graded traumatic head injury.

Context: Acute oxidative stress following a traumatic head injury (HI) has been implicated in inducing severe secondary brain damage and influencing the clinical outcome of HI patients. Aims: This study was performed to evaluate and compare the oxidative changes in patients with varying severity of HI in the early posttraumatic period using erythrocyte indicators. Settings and Design: Head injury patients were divided into two groups based on their Glasgow Coma Scale (GCS) scores recorded at admission to the hospital on the day of trauma itself. Accordingly, the study included 30 severe HI (SHI, GCS scores 8 or less) and 25 Mild HI (MHI, GCS scores more than 8) patients. Thirty age and sex-matched healthy individuals were included in this comparative study as controls. Materials and Methods: Blood samples were obtained from controls and HI patients (within 24 h of trauma onset). Erythrocyte oxidative changes were studied by estimating thiobarbituric acid reactive substances (TBARS), glutathione (GSH), superoxide dismutase (SOD) and glutathione reductase (GR). Results: Erythrocyte TBARS levels were significantly higher and GSH levels were significantly lower in SHI and MHI patients as compared to controls. The SOD activity was significantly increased only in SHI patients and remained unchanged in MHI patients as compared to controls. As compared to MHI patients, erythrocyte TBARS levels were significantly higher, GSH levels were significantly lower and SOD activity was markedly elevated in SHI patients. Erythrocyte GR activity did not show significant changes in both groups of patients as compared to controls. Conclusion: Oxidative stress is evident in both SHI and MHI patients in the early posttraumatic period as reflected by their erythrocyte indicators, but the severity of oxidative stress has varied relatively with the severity of head injury. The present findings provide indications that early oxidative changes could influence the neurological recovery of HI patients.

Time-relative changes in the erythrocyte antioxidant enzyme activities and their relationship with Glasgow Coma Scale scores in severe head injury patients in the 21-day posttraumatic study period.

BACKGROUND: Reactive oxygen species are indicated to play a prime role in the pathophysiology of brain damage following a severe head injury (SHI). AIM: The current study was designed to understand the time-relative changes and relationship between erythrocyte antioxidant enzyme activities and Glasgow Coma Scale (GCS) scores of SHI patients in the 21-day posttraumatic study period. SETTINGS AND DESIGN: The study included 24 SHI patients and 25 age- and sex-matched normal controls (NC). Activities of superoxide dismutase (SOD), glutathione reductase (GR) and glutathione peroxidase (GSH-Px) were assayed in these patients and controls. The GCS scores of these patients were also recorded for the comparative study. Materials and Methods: Venous blood samples were collected on day 7 (D7) and D21 from SHI patients and NC for the assay of SOD, GR and GSH-Px activities. These changes were correlated with age and changes in GCS scores of patients. STATISTICAL ANALYSIS: A one-way analysis of variance (ANOVA) was used to compare mean values of each parameter between group 1 (NC), group 2 (D7 changes in SHI patients) and group 3 (D21 changes in SHI patients). ANOVA was followed by Bonferroni post hoc tests. The Pearson correlation was applied to correlate between the antioxidant parameters and age and GCS scores of these patients. RESULTS: A significant increase in erythrocyte SOD and GSH-Px activities was observed in group 3 as compared to groups 1 and 2. The increase in GSH-Px activity was significant in group 2 as compared to group 1. Although not significant, there was an increase in mean GR activity in groups 2 and 3 as compared to group 1. CONCLUSION: These findings indicate that SHI patients have shown significantly enhanced erythrocyte SOD and GSH-Px activities during the 21-day posttraumatic study period.

Safety and radiosensitizing efficacy of sanazole (AK 2123) in oropharyngeal cancers: randomized controlled double blind clinical trial.

Oropharynx is an important site of cancer in India. Global comparison indicates higher incidences in India. Radiotherapy remains an important treatment modality. Efforts to improve loco-regional treatment and prolong survival are areas of focus. Radiosensitizers in hypoxic tumors have shown promise. AIM: To study the safety and radiosensitizing efficacy of sanazole in oropharyngeal squamous cell carcinoma (stage T2-4, N0-3, M0) as phase-II double blind controlled trial in patients treated with conventional radiotherapy. SETTINGS AND DESIGN: Single institutional, randomized, double-blind, placebo-controlled trial. MATERIALS AND METHODS: Group 1 (control; n = 23) received normal saline infusion, group 2 (test; n = 23) received sanazole biweekly 1.25 g intravenous infusion 15 minutes before radiotherapy. Surrogate end points of efficacy were tumor and nodal size; safety parameters were mucositis, salivary and skin reactions, dysphagia, vomiting, dysgeusia and neurological deficit. Investigators blinded to the trial evaluated patients, weekly during treatment for six weeks and thereafter monthly for three months. STATISTICAL METHODS: Non-parametric, Friedman's, Chi square, Mann-Whitney U tests. RESULTS: In the test, 15 (65%) patients had complete response, five (22%) partial/no response, two (9%) died, one (4%) lost to follow up. In the control, five (22%) patients had complete response, 16 (70%) partial/no response, one (4%) died, one (4%) lost to follow up. Short-term loco-regional response was better in the test (DF = 3, 95% Confidence Interval 0.418, 0.452, P = 0.0048). In the test group significant vomiting and one case of grade 3 neurological deficit was observed. CONCLUSION: The study validates the usefulness of sanazole for initial loco-regional control in oropharyngeal cancers.

T-cell rich B-cell lymphoma--a case report.

T-Cell-Rich B-Cell lymphoma (TCRBCL) is a recently described variant of diffuse large B-cell lymphoma characterized by a predominance of reactive T-cells and a minority of neoplastic large cells which may resemble the Reed-Sternberg cell or its variants. TCRBCL is a notorious mimicker of both lymphocyte predominance Hodgkin's disease (LPHD) and peripheral T-cell lymphoma (PTCL). Immunohistochemistry is mandatory for a definitive diagnosis. We report a case of TCRBCL which was mistaken for HD both on fine needle aspiration cytology and histopathology due to the presence of RS like cells. Immunohistochemistry resolved the diagnostic dilemma.

Cutaneous manifestations of non-Hodgkin's lymphoma.

Thirty-two confirmed cases of non -Hodgkin's lymphoma (NHL) were examined for cutaneous manifestations for a period of 2 years from November 1998 in KMC Hospital Attavar, Mangalore. Cutaneous manifestations in the study group were compared to a control group of 32 patients. Specific infiltrates were present in all (5/5) CTCL patients and one out of twenty-seven patients with low grade NHL. Morphologically they presented as papules, plaques, nodules and erythroderma. Infective conditions seen in the study group were superficial fungal (7/32) and viral infections (2/ 32). Non-infective conditions were acquired ichthyosis (10/32), generalised pruritus (5/32), insect bite reaction (1/32) and drug eruption (1/32). When compared to control patients only acquired ichthyosis and generalised pruritus were found to be statistically significant. The study group also showed changes due to chemotherapy like diffuse alopecia (24/29), bluish pigmentation of proximal part of nail (4/29), localised pigmentation of palms and soles (1 /29), diffuse pigmentation at injection site (1 /29), pigmentation at scar site (1 /29) and stomatitis (4/29).

Occurrence and severity of alopecia in patients on combination chemotherapy.

The aim of the study was to evaluate the occurrence and severity of alopecia resulting from combination chemotherapy on cancer patients. The study was conducted during the period 1994-1996 on 58 confirmed cases of malignancies attending the Kasturba Medical College Hospital, Mangalore, South India. The treatment regimens followed were standard protocols recommended for those malignancies and which are widely adopted. Specific drug combinations, their dosage and routes and schedules of administration were studied. The influence of 20 different treatment regimens, most of them in combination chemotherapy, were studied. The patients studied were not receiving any other medication which could have caused alopecia as observed in the present study. The pathophysiology of the hair, as influenced by the treatment regimens, were studied by examination of samples of the affected hairs under a Leica compound microscope. Alopecia was the most dominant side effect influencing 35 of the 58 patients undergoing the treatment (60%). The severity of alopecia was assessed by grouping them in four distinct grades. Specific drugs and their combinations causing varying degrees of severity were identified. The initiation of hair loss in different treatment regimens were analysed. It is seen that alopecia is an early manifestation of cutaneous side effects of cancer chemotherapy. In a majority of patients, the manifestation initiated after the first or the second cycle of administration of the rapeutic regimen, indicating a time interval of 1 to 8 weeks after the start of chemotherapy. Single agent drugs, when used alone or in combination with immunomodulator drugs seem to cause much less side effects, including alopecia, when compared to multiple drug regimens. Microscopic examination of the affected hair showed trichorrhexis, fragmentation, decrease in diameter and depigmentation of the hair shaft.