Pharmacogenetic guided versus standard warfarin dosing for routine clinical care with its pharmacoeconomic impact: a randomized controlled clinical trial.

BACKGROUND: Empirical use of pharmacogenetic test(PGT) is advocated for many drugs, and resource-rich setting hospitals are using the same commonly. The clinical translation of pharmacogenetic tests in terms of cost and clinical utility is yet to be examined in hospitals of low middle income countries (LMICs). AIM: The present study assessed the clinical utility of PGT by comparing the pharmacogenetically(PGT) guided- versus standard of care(SOC)- warfarin therapy, including the health economics of the two warfarin therapies. METHODS: An open-label, randomized, controlled clinical trial recruited warfarin-receiving patients in pharmacogenetically(PGT) guided- versus standard of care(SOC)- study arms. Pharmacogenetic analysis of CYP2C9*2(rs1799853), CYP2C9*3(rs1057910) and VKORC1(rs9923231) was performed for patients recruited to the PGT-guided arm. PT(Prothrombin Time)-INR(international normalized ratio) testing and dose titrations were allowed as per routine clinical practice. The primary endpoint was the percent time spent in the therapeutic INR range(TTR) during the 90-day observation period. Secondary endpoints were time to reach therapeutic INR(TRT), the proportion of adverse events, and economic comparison between two modes of therapy in a Markov model built for the commonest warfarin indication- atrial fibrillation. RESULTS: The study enrolled 168 patients, 84 in each arm. Per-protocol analysis showed a significantly high median time spent in therapeutic INR in the genotype-guided arm(42.85%; CI 21.4-66.75) as compared to the SOC arm(8.8%; CI 0-27.2)(p < 0.00001). The TRT was less in the PG-guided warfarin dosing group than the standard-of-care dosing warfarin group (17.85 vs. 33.92 days) (p = 0.002). Bleeding and thromboembolic events were similar in the two study groups. Lifetime expenditure was ₹1,26,830 in the PGT arm compared to ₹1,17,907 in the SOC arm. The QALY gain did not differ in the two groups(3.9 vs. 3.65). Compared to SOC, the incremental cost-utility ratio was ₹35,962 per QALY gain with PGT test opting. In deterministic and probabilistic sensitivity analysis, the base case results were found to be insensitive to the variation in model parameters. In the cost-effectiveness-acceptability curve analysis, a 90% probability of cost-effectiveness was reached at a willingness-to-pay(WTP) of ₹ 71,630 well below one time GDP threshold of WTP used. CONCLUSION: Clinical efficacy and the cost-effectiveness of the warfarin pharmacogenetic test suggest its routine use as a point of care investigation for patient care in LMICs.

pH-Dependent Non-Covalent Release of Chemotherapy from Carriers.

Although Warburg discovered pH discrepancies between tumor and normal tissues nearly 100 years ago, developing therapies to take advantage of this concept was relatively slow for the first 70 years. During the last 30 years, there has been an exponential increase in the use of pH-dependent strategies for both low molecular weight drugs and nanoparticles. Two frequently discussed approaches are the chemotherapy's release from pH-sensitive covalent linkages of macromolecules or from pH-dependent disruption of charged polymeric nanoparticles. In contrast, pH-dependent non-covalent bonds between the chemotherapy agent and macromolecules have rarely been discussed, yet this underappreciated strategy has great potential. These non-covalent interactions are primarily ionic or hydrogen bonds with supporting roles from hydrophobic bonds. In addition to the facile coupling of the drug with the carrier, these non-covalent interactions may show marked pH dependence. Consistent with pH dependence, many of these drug-loaded carriers showed significant in vitro and, in some cases, striking in vivo activity. In this review, we will focus on pH-sensitive non-covalent bonds, highlighting the release of drugs from diverse carriers such as tetrahedron DNA structures, cyclodextrin, polymeric carriers, and carbon-based quantum particles.

Pharmacokinetic assessment of rifampicin and des-acetyl rifampicin in carbon tetrachloride induced liver injury model in Wistar rats.

OBJECTIVES: Preclinical evidence is needed to assess drug-metabolite behaviour in compromised liver function for developing the best antitubercular treatment (ATT) re-introduction regimen in drug-induced liver injury (DILI). The pharmacokinetic behavior of rifampicin (RMP) and its active metabolite des-acetyl-rifampicin (DARP) in DILI's presence is unknown. To study the pharmacokinetic behavior of RMP and DARP in the presence of carbon tetrachloride (CCl4) plus ATT-DILI in rats. METHODS: Thirty rats used in the experiment were divided equally into six groups. We administered a single 0.5 mL/kg CCl4 intraperitoneal injection in all rats. Groups II, III, IV, and V were started on daily oral RMP alone, RMP plus isoniazid (INH), RMP plus pyrazinamide (PZA), and the three drugs INH, RMP, and PZA together, respectively, for 21-days subsequently. Pharmacokinetic (PK) sampling was performed at 0, 0.5, 1, 3, 6, 12, and 24 h post-dosing on day 20. We monitored LFT at baseline on days-1, 7, and 21 and sacrificed the rats on the last day of the experiment. RESULTS: ATT treatment sustained the CCl4-induced liver injury changes. A significant rise in mean total bilirubin levels was observed in groups administered rifampicin. The triple drug combination group demonstrated 1.43- and 1.84-times higher area-under-the-curve values of RMP (234.56±30.66 vs. 163.55±36.14 µg h/mL) and DARP (16.15±4.50 vs. 8.75±2.79 µg h/mL) compared to RMP alone group. Histological and oxidative stress changes supported underlying liver injury and PK alterations. CONCLUSIONS: RMP metabolism inhibition by PZA, more than isoniazid, was well preserved in the presence of underlying liver injury.

Scopoletin a potential phytochemical therapy for antitubercular treatment drug induced liver injury (ATT-DILI) model in Wistar rats.

OBJECTIVES: The hepatoprotective properties of scopoletin have been explored in carbon tetrachloride (CCl4) induced liver injury but not in drug-induced liver injury (DILI) scenarios. Only N-acetyl-cysteine (NAC) has proven efficacy in DILI treatment. Accordingly, we conducted a study to assess the hepatoprotective action of scopoletin in the anti-tubercular treatment (ATT)-DILI model in Wistar rats, if any. METHODS: A total of 36 rats were evaluated, with six in each group. A 36-day ATT at 100 mg/kg dose for isoniazid, 300 mg/kg for rifampicin and 700 mg/kg for pyrazinamide were fed to induce hepatotoxicity in rats. Group I and II-VI received normal saline and ATT, respectively. Oral scopoletin (1,5 and 10 mg/kg) and NAC 150 mg/kg were administered in groups III, IV, V and VI, respectively, once daily for the last 15 days of the experiment. LFT monitoring was performed at baseline, days 21, 28, and 36. Rats were sacrificed for the histopathology examination. RESULTS: Aspartate transaminase (AST), alanine transaminase (ALT), alkaline phosphatase (ALP) and bilirubin levels were significantly increased in group II (receiving ATT) compared to normal control on day 28 and day 36 (p<0.05). All three doses of scopoletin and NAC groups led to the resolution of AST, ALT, ALP, and bilirubin changes induced by ATT medications effect beginning by day 28 and persisting on day 36 (p<0.01). An insignificant effect was observed on albumin and total protein levels. The effect was confirmed with antioxidants and histopathology analysis. CONCLUSIONS: The study confirms the hepatoprotective efficacy of scopoletin in a more robust commonly encountered liver injury etiology.

Pharmacokinetic Assessment of Pyrazinamide and Pyrazinoic Acid in Carbon tetrachloride-induced Liver Injury Model in Wistar Rats.

Background: We investigated the pharmacokinetic behavior of pyrazinamide (PZA) and pyrazinoic acid (PA) in the presence of carbon-tetrachloride (CCl4) plus antitubercular treatment (ATT) drug-induced liver injury (DILI) in rats. Methods: Thirty rats utilized in the experiment were separated equally into five groups. Each rat was injected with 0.5 ml/kg CCl4 intra-peritoneal injection on day zero. Group, I rats did receive only CCl4 (single i.p. injection, 0.5 ml/Kg in olive oil in a 1:1 ratio). Groups II, III, IV, and V did receive daily oral PZA, PZA plus isoniazid (INH), rifampicin (RMP) plus pyrazinamide (PZA), and three drugs together, respectively, for 21-days. Pharmacokinetic sampling was performed at 0, 0.5,1,3,6,12 and 24 hours post-dosing on day-20. Liver function test (LFT) was assessed at days 0,1,7, and 21 days after CCl4 and ATT administration, and rats were sacrificed on the last experiment day. Results: ATT treatment maintained the liver function changes initiated by CCl4 administration. An evidential LFT rise was observed in groups administered with pyrazinamide. Co-administration of Isoniazid caused a 2.02 and 1.78 times increase in Area-under-the-curve (AUC) values of PZA and PA, respectively (p < 0.05). Histological and oxidative-stress changes supported the biochemical and pharmacokinetic observations. Conclusion: The enzyme inhibitory capacity of isoniazid is well-preservd in CCl4-induced liver injury.

Pharmacokinetic Assessment of Isoniazid and Acetylisoniazid in Carbon Tetrachloride-Induced Liver Injury Model in Wistar Rats.

Background: N-acetyl transferase 2 (NAT2) polymorphism testing could not see the light of success as a biomarker tool in tuberculosis management. Additionally, the antitubercular treatment (ATT) drug's reintroduction regimen variations exist because of the scarcity of robust preclinical evidence on ATT drug metabolism. Objective: The experiment was planned to understand the pharmacokinetic (PK) behavior of isoniazid and acetylisoniazid (AcINH) in a Wistar rat model of acute liver injury induced by carbon tetrachloride (CCl4) and preclinical drug-induced liver injury (DILI) model induced with CCl4 + anti-Tuberculosis (TB) drugs together. Materials and Methods: Thirty rats were used for the experiment and were divided into five groups. All rats were administered a single 0.5 ml/kg CCl4 intraperitoneal injection on day 0 to induce an animal model of DILI. Group I rats received CCl4 alone. Groups II-V were started on additional gavage feedings of isoniazid (H) alone, H plus rifampicin (R), H plus pyrazinamide (Z), and H, R, and Z together, respectively, daily for 21 days subsequently. Isoniazid and AcINH PK assessment was accomplished on day 20 of continuous once-daily dosing. Liver function test (LFT) monitoring was done at baseline on days 1, 7, and 21. On the last day of experiments, all experimental rats were sacrificed. Results: Three-week ATT administration sustained the CCl4-induced LFT changes. Area under the curve (AUC) values for isoniazid and AcINH were found to be 2.24 and 1.69 times higher in the H + R group compared with the CCl4 + H group, respectively (P < 0.05). Isoniazid and AcINH maximum concentration (Cmax) reached the highest, while isoniazid clearance reached the lowest in the H + R group. AcINH AUC increased by double in the CCl4 + Isoniazid+Rifampicin+Pyrazinamide (HRZ) group compared with the CCl4 + H group (P < 0.05). Biochemical, histological, and antioxidant changes were consistent with the new liver injury model's development. Conclusion: Rifampicin almost doubles up the isoniazid and AcINH exposure, in presence if DILI.

Efficacy of Fiberoptic Laryngeal Surgery in Benign VocalCord Lesions in Comparision with Microlaryngeal Surgery.

The use of operating microscope and rigid telescope in laryngeal surgery represents one of the most exciting advances. Both systems provide good illumination, magnification and relative ease of operation. Microlaryngeal surgery (MLS) with suspension laryngoscope is currently considered the gold standard for surgical approach to the larynx for excision of benign lesions of vocal folds. The limitation of this technique is intubation, general anesthesia (GA) related and in difficult exposure of larynx. The development of ideal anesthetic system has not been successful in satisfying both the surgeon and the anesthesiologist. Fiberoptic Laryngeal Surgery (FLS) is convenient as it avoids GA, is an outpatient procedure with less morbidity and reduced costs. FLS is preferable for the patients who have medical contraindications for general GA. To compare the efficacy of MLS and FLS surgical procedures in terms of functional outcome. This is a comparative clinical study done on 42 patients who were diagnosed to have benign vocal fold pathology. Pre and post-operative speech evaluation was done for all the patients by the same examiner, which included GRABS scale, Maximum Phonation Time, voiced consonants, voiceless consonants, s/z ratio along with stroboscopy. In Group A, MLS was the treatment modality, done under GA, while in Group B, FLS was the treatment modality done under Local Anesthesia (LA). After one-month, post-operative evaluation of voice was done. When the Maximum Phonation Time, S/Z ratio and stroboscopic parameters (mucosal wave) were compared between the two study groups there appeared no statistically significant difference between the two groups. Our study shows that when benign vocal cord pathologies were treated by MLS or FLS the voice Quality improvement remains the same. FLS is the procedure of choice when MLS under general anesthesia is contraindicated.

An Innovative Single Staged Surgical Repair of Benign Tracheoesophageal Fistula - A Case Report.

Tracheo-oesophageal fistula (TOF) is defined as a pathological connection between the trachea and the oesophagus, leading to a spillover of oral and gastric secretions into the respiratory tract causing aspiration. The cause of TOF may be congenital or acquired. In this case report, a 48 years old female with acquired TOF, has been reported. The patient was on ventilator support for COVID-associated pneumonia and its complication with endotracheal tube for 3 weeks and then tracheostomy was done. Post recovery after weaning from the ventilator, the patient was diagnosed with TOF by bronchoscopy and confirmed by CT and MRI. Surgical closure was performed: the oesophageal defect was sutured in 2 layers and Tracheal wall was isolated and a pedicled strap muscle flap sutured into the defect between the trachea and esophagus. The etiology of TOF may be due to traumatic intubation, cuff pressure, or inflammation. A better knowledge about the cause, site, and size of the TOF will help in prompt surgical procedure and recovery of the patient. This single staged surgical closure can be safely performed in the majority of patients with acquired TOF for optimal outcomes. Supplementary Information: The online version contains supplementary material available at 10.1007/s12070-022-03382-w.

Comparison of Short-Term Hearing Outcome in Stapedotomy Using either Vein or Fat (Adipose Tissue) as Sealing Material

Abstract Introduction Otosclerosis is a common cause of conductive hearing loss in the adult population that is caused by fixation of the stapes footplate. Cochlear otosclerosis may also present with sensorineural or mixed hearing loss. Surgery is the definitive treatment of choice and, during the procedure, sealing of the oval window with autologous tissue graft around the stapes prosthesis has been routinely done to improve hearing outcome and to mitigate postoperative complications. Objectives To evaluate the efficacy of two different types of autologous tissue (vein or fat) grafts as oval window sealing materials in stapedotomy in improving short-term hearing outcomes. Methods In our study, 70 patients with otosclerosis who underwent primary stapedotomy were included. They were divided into group 1 (vein graft) and group 2 (fat graft) based on the type of sealing material used. All patients were followed-up at the end of 3 months, undergoing an audiometric examination to assess the hearing outcome. Results A total of 80% (n = 28) of the patients in group1 had an air-bone gap (ABG) closure < 10dB, and, in group 2, 85.7% had an ABG closure < 10 dB; this difference was found to be statistically insignificant. A total of 42.9% (n = 15) of the patients in group 1 and of 31.4% (n = 11) in group 2 had a significant improvement in bone conduction, while 14.3% (n = 5) of the patients in group 1 and 17.1% (n = 6) in group 2 had worsening of average bone conduction postoperatively, which was found to be statistically insignificant. Conclusions Both vein and fat grafts had comparable effects on hearing outcomes when used as sealing materials in stapedotomy.

Comparison of Short-Term Hearing Outcome in Stapedotomy Using either Vein or Fat (Adipose Tissue) as Sealing Material.

Introduction Otosclerosis is a common cause of conductive hearing loss in the adult population that is caused by fixation of the stapes footplate. Cochlear otosclerosis may also present with sensorineural or mixed hearing loss. Surgery is the definitive treatment of choice and, during the procedure, sealing of the oval window with autologous tissue graft around the stapes prosthesis has been routinely done to improve hearing outcome and to mitigate postoperative complications. Objective To evaluate the efficacy of two different types of autologous tissue (vein or fat) grafts as oval window sealing materials in stapedotomy in improving short-term hearing outcomes. Methods In our study, 70 patients with otosclerosis who underwent primary stapedotomy were included. They were divided into group 1 (vein graft) and group 2 (fat graft) based on the type of sealing material used. All patients were followed-up at the end of 3 months, undergoing an audiometric examination to assess the hearing outcome. Results A total of 80% ( n = 28) of the patients in group1 had an air-bone gap (ABG) closure < 10dB, and, in group 2, 85.7% had an ABG closure < 10 dB; this difference was found to be statistically insignificant. A total of 42.9% ( n = 15) of the patients in group 1 and of 31.4% ( n = 11) in group 2 had a significant improvement in bone conduction, while 14.3% ( n = 5) of the patients in group 1 and 17.1% ( n = 6) in group 2 had worsening of average bone conduction postoperatively, which was found to be statistically insignificant. Conclusion Both vein and fat grafts had comparable effects on hearing outcomes when used as sealing materials in stapedotomy.

Development and validation wise assessment of genotype guided warfarin dosing algorithm in Indian population.

OBJECTIVES: A study was conducted to develop and validate the warfarin pharmacogenetic dose optimization algorithm considering the clinical pharmacogenetic implementation consortium (CPIC) recommendations for the Asian ethnicity population. METHODS: The present prospective observational study recruited warfarin-receiving patients. We collected a three ml blood sample for VKORC1, CYP2C9*2, CYP2C9*3, and CYP4F2 polymorphism assessment during the follow-up visits. Clinical history, sociodemographic and warfarin dose details were noted. RESULTS: The study recruited 300 patients (250 in derivation and 50 in validation timed cohort) receiving warfarin therapy. The baseline characteristics were similar in both cohorts. BMI, presence of comorbidity, VKORC1, CYP2C9*2, and CYP2C9*3 were identified as covariates significantly affecting the warfarin weekly maintenance dose (p<0.001 for all) and the same were included in warfarin pharmacogenetic dose optimization algorithm building. The algorithm built-in the present study showed a good correlation with Gage (r=0.57, p<0.0001), and IWPC (r=0.51, p<0.0001) algorithms, widely accepted in western side of the globe. The receiver operating characteristic curve analysis showed a sensitivity of 73 %, a positive predictive value of 96 %, and a specificity of 89 %. The algorithm correctly identified the validation cohort's warfarin-sensitive, intermediate reacting, and resistant patient populations. CONCLUSIONS: Validation and comparisons of the warfarin pharmacogenetic dose optimization algorithm have made it ready for the clinical trial assessment.

Dose-Response Evaluation of Scopoletin, a Phytochemical, in a High-Fructose High-Fat Diet-Induced Dyslipidemia Model in Wistar Rats.

The putative hypolipidemic properties of scopoletin have not been fully confirmed due to a lack of validation in an irreversible chronic hyperlipidemia animal model. The druggability also needs to be studied in terms of bioavailability in the vascular compartment. Accordingly, we conducted a study to assess the hypolipidemic and pharmacokinetic behavior of scopoletin in the high-fructose high-fat diet (HFHFD)-induced dyslipidemia model in Wistar rats. A total of 42 rats were studied, with 6 in each of the 7 groups. A 60-day HFHFD opted for induction of dyslipidemia. Group I and groups II-VII received normal rat chow diet and HFHFD, respectively. Oral scopoletin (1, 5, 10 mg/kg) and atorvastatin 5 mg/kg were administered in groups III-VI, respectively, once daily for the next 15 days. A separate group, group VII, was used for the pharmacokinetic assessment comparing the scopoletin 10 mg/kg intraperitoneally (IP) in group VII versus the oral (group V). Pharmacokinetic blood sampling was performed on the 10th day of continuous once-daily therapy. Rats were sacrificed for the histological examination. All three scopoletin dosages significantly decreased the total cholesterol, low-density lipoproteins, and triglycerides (P < .05 for all), but not in a dose-dependent manner. Atherogenic Index of plasma, Castelli's risk indices, and histopathological findings confirmed the protective effect of scopoletin. The IP administration showed a 23.18% higher exposure than the oral route (P < .001 for area under the curve and P < .05 for concentration-maximum). This study confirms the hypolipidemic efficacy of scopoletin in a more robust irreversible model of dyslipidemia. Scopoletin's gut absorption in the disease state may also boost the initial phase exploratory clinical trial.

Scopoletin Improves Glucose Homeostasis in the High-Fructose High-Fat Diet-Induced Diabetes Model in Wistar Rats.

Antihyperglycemic action of scopoletin needs to be validated before considering it for clinical trials. The present study explored antihyperglycemic action of scopoletin in high-fructose high-fat diet (HFHFD)-induced diabetes in rats. The animal study was performed using 48 rats, 6 in each group. HFHFD was administered for model induction for 74 days. Rats in Group I (normal control [NC]) and group II (experimental control [EC]) received normal saline and HFHFD, respectively, throughout the study. Groups III, IV, V, and VI received oral scopoletin (1 mg/kg [low dose, LD], 5 mg/kg [medium dose, MD], 10 mg/kg [high dose, HD]), and metformin (250 mg/kg; positive control [PC] for efficacy), respectively, once daily from day 60 to 74, in addition to HFHFD. Group VII (10 mg/kg oral scopoletin safety group) and VIII (0.1 mg/kg oral warfarin; PC for safety) were separately used for bleeding time-clotting time (BTCT) assessment on days 60, 68, and 74. Groups I, VII, and VIII rats were studied for safety assessment. Later, animals were sacrificed for histological examination. Scopoletin-treated groups showed a significant decline in glucose levels, especially in the MD (5.18 ± 0.12) and HD group (5.271 ± 0.11) in comparison to the EC (6.37 ± 0.05) on day 74 (P < .05). Two weeks after scopoletin treatment, ß-cell function significantly improved (53.073 ± 4.67) in the MD group versus 29.323 ± 8.505 in the NC group (P < .05). A statistically significant difference was observed when the MD group (53.07 ± 4.67) was compared to the metformin-treated group (24.80 ± 3.24; P < .05). The safety assessment in the form of BTCT findings did not observe a difference among groups I, VII, and VIII (P > .05). The study showed that scopoletin dose-independently reversed insulin resistance. Consequently, scopoletin can be a potential candidate for antidiabetic drug development.

Orbital spindle cell hemangioma with acute presentation.

ABSTRACT: We report an unusual presentation of an orbital spindle cell hemangioma in a 40-year-old male, who noted sudden redness and swelling of the left eye on waking up. On examination, the patient was found to have edema of upper eyelid edema, periorbital ecchymosis, and subconjunctival hemorrhage in the left eye at presentation. On treatment with topical medications, patient had transient symptomatic relief; however, he later developed blurring of vision. When seen 10 days later, the patient's left eye showed axial proptosis. Radiological investigations revealed an intraconal soft tissue mass in the left medial rectus. Emergency orbital decompression with mass excision was done; histopathological examination of the excised mass revealed spindle cell hemangioma. Postsurgery patient had complete restoration of vision. To our knowledge, an acute presentation of an orbital hemangioma with subconjunctival hemorrhage and periorbital ecchymosis, visual loss doesn't occur commonly; hence, such presentations have to be reviewed with care.

Navigation Assisted Frontal Sinus Osteoplastic Flap Surgeries - A Case Series.

Osteoplastic flap surgery of the frontal sinus is still a relevant surgical technique for frontal sinus pathologies despite advancements in endoscopic techniques due to the complex anatomy of frontal sinus and limitations of endoscopic techniques for certain pathologies. The most crucial step in this surgery is accurate delineation of the frontal sinus pneumatisation which guides the osteotomies and this is conventionally done with radiographs which is not without errors. Here we present three cases where we have utilized image guidance technology for osteoplastic flap surgery of the frontal sinus with superior results.

CT Cisternogram Findings in Idiopathic Cerebrospinal Fluid Leaks with Emphasis on Long Term Management.

To study the various computed tomography (CT) cisternogram findings in idiopathic cerebrospinal fluid (CSF) leaks and the long term treatment modalities after surgical repair of idiopathic CSF leaks. This was a descriptive study conducted among 25 patients in MCV memorial ENT trust hospital, Pollachi between May 2014 and May 2020 amongst patients who underwent CT cisternogram for unilateral or bilateral spontaneous rhinorrhea with or without associated headache, visual disturbances and papilloedema diagnosed to be idiopathic CSF leak by investigations. These patients then underwent CSF leak repair and postoperatively were managed with weight reduction, low salt diet and diuretic therapy. Post surgery these patients were followed up for a period of 12 months and were evaluated on the basis of presence or absence of headache, rhinorrhea and papilloedema at the end of 1st month, 3rd month, 6th month and 1 year and data was collected. CT cisternogram findings were evaluated by proportion method and evaluation of long term management was done using proportion and repeated measures ANOVA for all patients. Evidence of the presence of previously mentioned CT cisternogram or contrast MRI findings at the end of 1 year of post-surgical treatment was recorded where patients were willing for the same. CT Cisternography was done for all patients and 72% patients had empty sella appearance while 28% had partially empty sella. Other findings included perioptic filling, optic blunting and arachnoid pits which were found in 11(44%), 8(32%) and 12(48%) of patients respectively. Only 3(12%) out of 25 patients had an encephalocoele. The commonest site of leak in CT cisternography was the cribriform plate (52%) followed by lateral recess of sphenoid (48%). None of the patients had multiple sites of leak in CT cisternography. On follow up post surgery maximum resolution of symptoms was found at the end of 12 months where 23 out of 25 patients improved. In our study, out of 25 only 5 patients agreed to undergo post diuretic therapy MRI scan out of which 2 patients had partially empty sella and 3 had normal sella indicating resolution of BIH. CT cisternography is an important investigation which aids in the diagnosis of CSF rhinorrhea due to idiopathic intracranial hypertension (IIH). The medical management of IIH post surgery such as weight reduction, salt restriction and diuretic therapy is also crucial to prevent recurrence of symptoms.

Essential oil nebulization in mild COVID-19(EONCO): Early phase exploratory clinical trial.

Background: Medications studied for therapeutic benefits in coronavirus disease 2019 (COVID-19) have produced inconclusive efficacy results except for steroids. Objective: A prospective randomized open-label, parallel-arm Phase I/II clinical trial was planned to compare essential oil (EO) blend versus placebo nebulization in mild COVID-19. Methods: A Phase I safety evaluation was carried out in a single ascending and multiple ascending dose study designs. We assessed Phase II therapeutic efficacy on COVID-19 and general respiratory symptoms on days 0, 3, 5, 7, 10, and 14 on the predesigned case record form. Viremia was evaluated on day 0, day 5, and day 10. Results: Dose-limiting toxicities were not reached with the doses, frequencies, and duration studied, thus confirming the formulation's preliminary safety. General respiratory symptoms (p < 0.001), anosmia (p < 0.05), and dysgeusia (p < 0.001) benefited significantly with the use of EO blend nebulization compared to placebo. Symptomatic COVID-19 participants with mild disease did not show treatment benefits in terms of symptomatic relief (p = 1.0) and viremia clearance (p = 0.74) compared to the placebo. EO blend was found to be associated with the reduced evolution of symptoms in previously asymptomatic reverse transcription polymerase chain reaction (RT-PCR)-positive study participants (p = 0.034). Conclusion: EO nebulization appears to be a safer add-on symptomatic relief approach for mild COVID-19. However, the direct antiviral action of the EO blend needs to be assessed with different concentrations of combinations of individual phytochemicals in the EO blend.

Development of an interview-based warfarin nomogram predicting the time spent in the therapeutic INR range: A cost-effective, and non-invasive strategy building from a cross sectional study in a low resource setting.

A cross-sectional study was conducted to predict time in therapeutic range (TTR) using clinical history, examination, and socioeconomic data. Study included warfarin-receiving patients from outpatient-clinic. In 203 patients studied, mean warfarin start-dose was 2.55 mg/day and maintenance-dose/week was 30.79 mg. Body mass index (BMI) (p = 0.03), warfarin maintenance dose/day (p = 0.02), and comorbidity presence (p = 0.04) were significantly associated with TTR. Occupation (p = 0.53), income (p = 0.83), education (p = 0.55), and socioeconomic score (p = 0.73) showed non-significant association with TTR. A TTR predicting nomogram was built from clinical history and examination findings.

A Case of Deep Neck Abscess with Viral Pneumonia in the Covid Era.

The coronavirus disease 2019 (COVID-19) pandemic has generated many challenges for physicians, including multiple post-covid long-term effects that are still being studied. We report a case of patient who developed a retropharyngeal abscess with a concomitant viral pneumonia resembling Covid and its management.

Novel Method of Cartilage Harvest in Otology with Micro Dermatome: A Descriptive Study.

Cartilage is used in middle ear surgery for reconstruction of tympanic membrane, ossicular chain, posterior canal wall and lateral attic wall. When used in tympanic membrane reconstruction, thickness of the cartilage is thought to interfere with the sound conduction. In our otology practice for tympanic membrane reconstruction, we prefer the sliced cartilage graft to achieve acoustic benefit. We have used a microdermatome for precise reduction of the thickness of the cartilage. This also allows us to select exact thickness of cartilage slice and also permits slicing from donor site directly. To describe the use of novel method of cartilage slicing using a micro dermatome and to report our preliminary experience. This is a descriptive study, with a total number of 350 cartilage grafts used in tympanoplasty and mastoidectomies have been prepared with micro dermatome from 2019 to 2021. Our study reports the technique of slicing the Conchal cartilage and how its uniform measurement can be obtained. Our modified technique using the micro dermatome is easy to master, provides precise cartilage thickness as per needs within a short span of time. Harvesting from the donor site is as per the graft requirement and rest of the cartilage is left in place for the future revision surgery if needed. The cartilage obtained were structurally integral without any undue breakage and functionally stable. The thickness of the cartilages obtained makes it pliable for easy handling and placement in ear surgeries.