A Comparative Study on Predictive Validity of Modified Shock Index, Shock Index, and Age Shock Index in Predicting the Need for Mechanical Ventilation among Sepsis Patients in a Tertiary Care Hospital.

Introduction: The shock index (SI), modified shock index (MSI), and age multiplied by SI (ASI) are used to assess the severity of shock. They are also used to predict the mortality of trauma patients, but their validity for sepsis patients is controversial. The aim of this study is to assess the predictive value of the SI, MSI, and ASI in predicting the need for mechanical ventilation after 24 h of admission among sepsis patients. Methods: A prospective observational study was conducted in a tertiary care teaching hospital. Patients with sepsis (235) diagnosed based on systemic inflammatory response syndrome criteria and quick sequential organ failure assessment were included in the study. The need for mechanical ventilation after 24 h is the outcome variables MSI, SI, and ASI were considered as predictor variables. The utility of MSI, SI, and ASI in predicting mechanical ventilation was assessed by receiver operative curve analysis. Data were analyzed using coGuide. Results: Among the study population, the mean age was 56.12 ± 17.28 years. MSI value at the time of disposition from the emergency room had good predictive validity in predicting mechanical ventilation after 24 h, as indicated by the area under the curve (AUC) of 0.81 (P < 0.001), SI and ASI had fair predictive validity for mechanical ventilation as indicated by AUC (0.78, P < 0.001) and (0.802, P < 0.001), respectively. Conclusion: SI had better sensitivity (78.57%) and specificity (77.07%) compared to ASI and MSI in predicting the need for mechanical ventilation after 24 h in sepsis patients admitted to intensive care units.

The impact of alcohol intoxication on early Glasgow Coma Scale-Pupil reactivity score in patients with traumatic brain injury: A prospective observational study.

Background: A simple arithmetic combination of the Glasgow Coma Scale (GCS) score and pupillary response, the GCS-Pupil (GCS-P), extends the information provided about the patient outcome to an extent comparable to that obtained using more complex methods. The objective of the study was to compare the changes in the GCS-P score of patients with traumatic brain injury (TBI) under alcohol intoxication and nontoxication over time. Methods: A prospective observational study was done in a hospital at the Level I trauma center. The patients admitted to the emergency department (ED) with TBI were the study participants. They were grouped into intoxicated and nonintoxicated based on blood alcohol concentration (BAC). BAC of 0.08% and above was considered intoxication. GCS-P score in the ED and the best day 1 GCS-P score were the outcome variables. For nonnormally distributed quantitative parameters, medians and interquartile range were compared between study groups using Mann-Whitney U-test. P <0.05 was considered statistically significant. Results: A total of 216 patients were included in the final analysis. There was no statistically significant difference between BAC in GCS-P score at different follow-up periods, GCS-P score (ED), and GCS-P score (best day 1). Conclusion: This prospective observational study showed a low GCS-P score for alcohol-intoxicated patients compared to nonintoxicated patients, which was not statistically significant. There was no significant difference in emergency GCS-P score and best day 1 score between alcohol-intoxicated and nonintoxicated patients.

Modified Shock Index as an Indicator for Prognosis Among Sepsis Patients With and Without Comorbidities Presenting to the Emergency Department.

OBJECTIVES: Modified shock index (MSI) is a simple bedside tool used in the emergency department. There are a few studies suggesting MSI as a good prognostic indicator than shock index in sepsis patients. However, there is not enough research emphasizing the role of MSI in patients with comorbidities. Hence, this study aims to assess the predictive validity of MSI in predicting the prognosis of sepsis patients with and without co-morbidities. METHODS: From January to December 2020, a prospective observational study was conducted in a tertiary care teaching hospital. Patients with sepsis diagnosed based on systemic inflammatory response syndrome criteria and quick sequential organ failure assessment (qSOFA) were included. The need for mechanical ventilation and step down from the intensive care unit were outcome variables, MSI was considered as a predictor variable, and co-morbidities as an explanatory variable. RESULTS: Among people with co-morbidities, the MSI value on arrival to the emergency department had fair predictive validity in predicting the need for mechanical ventilation after 24 hours, as indicated by the area under the curve of 0.749 (95% CI: 0.600-0.897; p-value = 0.002) and a sensitivity of 68.75% in predicting mechanical ventilation after 24 hours (MSI ≥ 1.59). Among people without co-morbidities, the MSI value on arrival to the emergency department had fair predictive validity in predicting the need for mechanical ventilation after 24 hours, as indicated by the area under the curve of 0.879 (95% CI: 0.770-0.988; p-value <0.001) and a sensitivity of 83.33% in predicting the need for mechanical ventilation after 24 hours (MSI ≥ 1.67). CONCLUSION: MSI can be used as an indicator in predicting the prognosis of sepsis patients in the emergency department. A simple bedside calculation of the MSI can indicate the need for mechanical ventilation and step down from the intensive care unit after 24 hours in patients with co-morbidities and without co-morbidities.

Synthesis and crystal structure of 1-hy-droxy-8-methyl-9H-carbazole-2-carbaldehyde.

Two crystallographically independent mol-ecules are present in the asymmetric unit of the title compound, C14H11NO2, with virtually identical geometries. The carbazole units are planar. The hy-droxy group at position 1, carbaldehyde group at position 2, and methyl group at position 8 (with the exception of two H atoms) are coplanar with the attached benzene rings. The dihedral angle between the two benzene rings is 2.20 (9)° in mol-ecule A and 2.01 (9)° in mol-ecule B. The pyrrole ring makes dihedral angles of 0.82 (10) and 1.40 (10)° [0.84 (10) and 1.18 (10)° in mol-ecule B] with the (-CH3)-substituted and (-OH and -CHO) substituted benzene rings, respectively. The mol-ecular structure is stabilized by the intra-molecular O-H⋯O hydrogen bonds, while the crystal structure features N-H⋯O and C-H⋯O hydrogen bonds. A range of π-π contacts further stabilizes the crystal structure.

Experience of Indian association of medical microbiology external quality assurance scheme centre, New Delhi: Challenges and quality assessment of clinical microbiology laboratories.

Introduction: EQAS program at New Delhi under IAMM was started in January 2014 across North and North east regions of India with 217 participants, which grew up to 540 by 2018. Materials and Methods: In 2014, 4 analytes per year were sent for 3 exercises, i.e. smear culture and serology. 2018 onwards PT analytes were increased from 4 to 12 and comparative performance of techniques analysed. Results: Out of the 22 smears sent for gram staining, ZN staining, Kinyoun staining and Albert staining, completely correct results ranged between 29.55% - 79.9%, 94.3% - 99.2%, 35.5% & 93.8%, respectively. Correct results for culture isolate identification & susceptibility testing and serology exercises varied between 70 & 92.4% and 73.1 & 98.59%, respectively. In the year 2018, 470 responses were received for bacterial culture identification & antibiotic susceptibility testing out of which manual and automated systems were used by 54% & 46% and 52.5% & 47.5% participants, respectively. Techniques used in BBV assays for HBsAg, HCV & HIV found all methods like ELISA, ELFA, CLIA and Card Test performing similarly. The major challenges in running the EQA program included requirement of large amount of specimens for PT item preparation, stability in hot and humid conditions and timely delivery of PT challenges in remote parts of the country. Conclusion: A large number of the participating laboratories (77%) had an overall score of >80% for all exercises, demonstrating acceptable baseline performance of EQAS registered laboratories. However, continued EQAS participation could further improve the quality of results.

Crystal structure of (E)-2-(furan-2-yl-methyl-idene)-2,3,4,9-tetra-hydro-1H-carbazol-1-one.

The title compound, C17H13NO2, crystallizes with two conformationally very similar independent mol-ecules (A and B) in the asymmetric unit. In the crystal, the individual mol-ecules are linked by pairs of N-H⋯O hydrogen bonds forming A-A and B-B inversion dimers, with R22(10) rings. They stack alternately up the a-axis direction and are linked by C-H⋯π inter-actions, forming sheets parallel to the ab plane.

Application of UV-Vis spectrophotometric process for the assessment of indoloacridines as free radical scavenger.

A conventional approach has been used to synthesis Indole fused acridine, 4a-e. In this paper to achieve the target molecule, 4 the reaction was performed via two steps. In step 1, there was a reaction between Carbazolone, 1 and benzophenone, 2 to get dihydroindoloacridine, 3. In step 2, compound, 3 was treated with 5% Palladium/Carbon in the presence of diphenyl ether for 5h to give a dark brown product, 4. The column chromatography was used to purify final product, 4. All the synthesized compounds such as 3 and 4 were characterized by melting point, FTIR, (1)H NMR, and Mass spectra. Further to check the purity of the compounds it was subjected to CHN analyzer. The target molecules such as 3 and 4 were screened for antimicrobial studies against bacteria such as Bacillus subtilis (B. subtilis), Staphylococcus aureus (S. aureus), Klebsiella pneumonia (K. pneumonia), Salmonella typhi (S. typhi); and fungi like Aspergillus niger (A. niger), Aspergillus fumigatus (A. fumigatus). The obtained results clearly proves that the target molecules shown reasonable activity against K. pneumonia and A. niger. Further the compounds were screened for free radical scavenging activity using 2,2-diphenyl-1-picrylhydrazyl (DPPH). The free radical scavenging property was performed using UV-Visible spectroscopy. The results were compared with the standard BHT (Butylated Hydroxy Toluene). Compounds, 4a and 4e were shown higher percentage of inhibition when compare to the standard. The result confirms that further research on indoloacridine will leads effective drug to the market.

Benzoquinoline amines - Key intermediates for the synthesis of angular and linear dinaphthonaphthyridines.

A systematic study on the condensation reaction of 2,4-dichlorobenzo[h]quinoline and naphth-1-ylamine in the presence of CuI as catalyst to functionalised mono- and di-substituted (naphthalen-1-yl)benzo[h]quinoline amines was described. Subsequently these mono- and di-substituted amines on polyphosphoric acid catalysed cyclisation reaction with aromatic/heteroaromatic carboxylic acids led to the construction of angular and linear aromatic/heteroaromatic substituted dinaphthonaphthyridines in good yields.

Comparative evaluation of two rapid Salmonella-IgM tests and blood culture in the diagnosis of enteric fever.

PURPOSE: Enteric fever is a major public health problem in developing countries like India. An early and accurate diagnosis is necessary for a prompt and effective treatment. We have evaluated the diagnostic accuracy of two Rapid Salmonella-IgM tests (Typhidot-IgM and Enteroscreen-IgM) as compared to blood culture in rapid and early diagnosis of enteric fever. MATERIALS AND METHODS: A total of 2,699 patients' serum samples were tested by Rapid Salmonella-IgM tests and blood culture. Patients were divided into two groups. Test group - patients with enteric fever and blood culture positives for Salmonella Typhi; and three types of Controls, i.e. patients with non-enteric fever illnesses, normal healthy controls and patients positive for S. Paratyphi- A. In addition to this we have also evaluated the significance of positive Salmonella-IgM tests among blood culture-negative cases. RESULTS: The overall sensitivity, specificity, positive predictive value (PPV) and negative predictive value (NPV) of the Typhidot-IgM test and Enteroscreen-IgM test considering blood culture as gold standard were 97.29% and 88.13%, 97.40% and 87.83%, 98.18% and 92.03%, 96.15% and 82.27%, respectively. Typhidot-IgM test was found to be significantly more sensitive and specific as compared to Enteroscreen-IgM. Among blood culture-negative patients, Rapid Salmonella-IgM tests detected 72.25% additional cases of enteric fever. Although the Rapid Salmonella-IgM tests are meant to diagnose S. Typhi only, but these tests detect S. Paratyphi- A also. Thirty-eight patients who were blood culture-positive for S. Paratyphi- A were also positive by Rapid Salmonella-IgM tests. CONCLUSION: Rapid Salmonella-IgM tests offer an advantage of increased sensitivity, rapidity, early diagnosis and simplicity over blood culture.

In vivo anti-diabetic, antioxidant and molecular docking studies of 1, 2, 8-trihydroxy-6-methoxy xanthone and 1, 2-dihydroxy-6-methoxyxanthone-8-O-ß-D-xylopyranosyl isolated from Swertia corymbosa.

1, 2, 8-trihydroxy-6-methoxy xanthone (1) and 1, 2- dihydroxy-6-methoxyxanthone-8-O-ß-d-xylopyranosyl (2) are the main constituents of petroleum ether and ethyl acetate extracts from Swertia corymbosa (Gentinaceae), a medicinal plant used in Indian traditional system for the treatment of diabetes. The present study was designed to examine the antihypoglycemic, antihyperlipidemic and antioxidant effect of compounds 1 and 2 in streptozotocin (STZ) induced diabetic rats. Diabetes was induced in male Wistar rats by a single intraperitoneal injection of STZ (60 mg/kg b.w.). The isolated compounds 1 and 2 at a dose of 50 mg/kg b.w., produced the maximum fall of 83% in the blood glucose level in the diabetic rats after 3h of the treatment. The administration of 1 and 2 (50 mg/kgb.w.) daily for 28 days in STZ induced diabetic rats, resulted in a significant decrease in blood glucose, glycosylated hemoglobin, SGOT, SGPT, ALP serum urea and creatinine with significant rise in plasma insulin level. Test compounds 1 and 2 showed antihyperlipidemic activities as evidenced by significant decrease in serum TC, TG, LDL-C, VLDL-C levels coupled together with elevation of HDL-C level in diabetic treated rats when compared to diabetic untreated rats, indicate the protective role against liver and kidney damage. The results of histopathology also showed 1 and 2 protected tissues (pancreas, liver and kidney) against peroxidation damage and maintained tissue integrity. Further, the molecular interaction study of the ligands 1, 2 and glibenclamide with various diabetes mellitus related protein targets like glucokinase (PDB ID: 1V4S), fructose-1, 6-bisphosphatase 1 (PDB ID: 2JJK) 11-ß-hydroxysteroid dehydrogenase (PDB ID: 2BEL) and modeled protein sulfonylurea receptor 1 (SUR1) showed that ligand 1 and 2 possess binding affinity with all protein targets except for 2BEL target protein for which ligand 1 has no interaction. The ligand pose with 2BEL and SUR1 protein target of ligand 2 gave the best binding conformation. Hence 1 and 2 can be considered for developing into a potent antidiabetic drug.

Solvent-free synthesis of heteroannulated carbazoles: a novel class of anti-tumor agents.

A series of novel carbazole analogues that hold pyrido, isoxazolo, pyrimido and pyrazolo templates were designed and synthesised in good yield by grinding conditions. All the synthesised compounds were screened for their anti-tumor activity and displayed enviable selective growth inhibition on HeLa cell line compared to AGS cell line. Among these compounds, compound 2-(3',4'-diethoxy-benzylidene)-6-methyl-2,3,4,9-tetrahydro-carbazol-1-one,6-chloro-2-(3',4'-diethoxy-benzylidene)-2,3,4,9-tetrahydro-carbazol-1one, 2-(3',4'-diethoxy-benzylidene)-8-methyl-2,3,4,9-tetrahydro-carbazol-1-one, 3-(3',4'-diethoxyphenyl)-7-methyl-4,5-dihydro-10H-isoxazolo[3,4-a]carbazole, 7-chloro-3-(3',4'-diethoxyphenyl)-4,5-dihydro-10H-isoxazolo[3,4-a]carbazole, 4-(3',4'-diethoxyphenyl)-2-ethoxy-8-methyl-6,11-dihydro-5H-pyrido[2,3-a]carbazole-3-nitrile, 8-chloro-4-(3',4'-diethoxyphenyl)-2-ethoxy-6,11-dihydro-5H-pyrido[2,3-a]carbazole-3-nitrile, 4-(3',4'-diethoxyphenyl)-2-ethoxy-10-methyl-6,11-dihydro-5H-pyrido[2,3-a]carbazole-3-nitrile were found to have promising anti-tumor properities with reference to the standard ellipticine against the HeLa cancer cell line. All these intermediates showed IC50 outranged the standard ellipticine. The same compounds showed moderate activity against AGS cancer cell lines. The efforts were undertaken to optimize potency and selectivity of this class of compounds.

7-Methyl-1-phenyl-1,10-di-hydro-pyrazolo-[3,4-a]carbazole.

In the title mol-ecule, C20H15N3, the atoms in the carbazole unit deviate from planarity [maximum deviation from mean plane = 0.1082 (15) Å]. The pyrrole ring makes dihedral angles of 3.17 (8)/4.10 (9), 7.20 (9) and 44.62 (9)° with the fused benzene, pyrazole and phenyl rings, respectively. In the crystal, mol-ecules are linked via N-H⋯N hydrogen bonds, forming an infinite chain along [010]. Mol-ecules are further linked by nine π-π [centroid-centroid distances vary from 3.6864 (11) to 3.9802 (11) Å] and one C-H⋯π inter-action, forming a three-dimensional network.

10-Methyl-2-oxo-4-phenyl-2,11-di-hydro-pyrano[2,3-a]carbazole-3-carbo-nitrile.

In the title mol-ecule, C23H14N2O2, the atoms in the carbazole unit deviate from planarity [maximum deviation from mean plane = 0.1018 (8) Å]. The pyrrole ring makes dihedral angles of 4.44 (5), 3.84 (5), 2.18 (5) and 56.44 (5)° with the pyran, fused benzene rings and phenyl ring, respectively. In the crystal, pairs of N-H⋯O hydrogen bonds generate R 2 (2)(14) loops and a C-H⋯N inter-action is also found. Mol-ecules are further linked by a number of π-π interactions [centroid-centroid distances vary from 3.5702 (5) to 3.7068 (6) Å], forming a three-dimensional network.

(E)-2-[(Furan-2-yl)methyl-idene]-7-methyl-2,3,4,9-tetra-hydro-1H-carbazol-1-one.

In the title mol-ecule, C(18)H(15)NO(2), the atoms in the carbazole unit deviate from planarity [maximum deviation from mean plane = 0.1317 (12) Å]. The pyrrole ring makes dihedral angles of 1.01 (8) and 18.56 (10)° with the benzene and furan rings, respectively. The cyclo-hexene ring adopts a half-chair conformation. In the crystal, pairs of N-H⋯O hydrogen bonds form an R(2) (2)(10) ring. Mol-ecules are further linked by C-H⋯O and C-H⋯π inter-actions, forming a three-dimensional network.

A ten year analysis of multi-drug resistant blood stream infections caused by Escherichia coli & Klebsiella pneumoniae in a tertiary care hospital.

BACKGROUND & OBJECTIVES: Extensive use of antibiotics has added to the escalation of antibiotic resistance. This study was undertaken to evaluate the association, if any between antibiotic use and resistance in a hospital setting, and also detect the predominant mechanism of antibiotic resistance in Escherichia coli and Klebsiella pneumoniae over a period of 10 years. METHODS: In a retrospective study of 10 years, a total of 77,618 blood culture samples from 2000 to 2009 from indoor patients were screened and those yielding E. coli and K. pneumoniae were included in the study. Antibiotic susceptibility records as well as the percentage of ESBL producers were noted. A total of 423 isolates of 2009 were also screened for AmpC and carbapenemase production. Antibiotic consumption data of 10 years were analysed. RESULTS: ESBL producing E. coli increased from 40 per cent in 2002 to 61 per cent in 2009, similarly there was a significant (P<0.05) rise in resistance to cefotaxime (75 to 97%), piperacillin-tazobactum (55- 84%) and carbapenem (2.4-52%) in K. pneumoniae. A significant (P<0.05) association was observed between resistance and consumption of carbapenem and piperacillin and tazobactum consumption in K. pneumonia. INTERPRETATION & CONCLUSIONS: Our study demonstrated a rise in consumption and resistance to broad spectrum antimicrobial agents and also established an association between consumption and resistance to these antibiotics. Over a period of 10 years, the emergence of pan-resistance in K. pneumoniae could be due to the production of carbapenemases whereas ESBL production was the common mechanism of resistance in E. coli. This study warrants a directed effort towards continued surveillance and antibiotic stewardship to minimize selection pressure and spread.

2-Chloro-7,8,9,10-tetra-hydro-cyclo-hepta-[b]indol-6(5H)-one.

In the title mol-ecule, C(13)H(12)ClNO, the dihedral angle between the benzene and pyrrole rings is 1.38 (9)°. The cyclo-heptene ring adopts a distorted twist chair and sofa conformation. Inter-molecular N-H⋯O hydrogen bonds form an R(2) (2)(10) loop in the crystal packing. Further, weak C-H⋯O and C-H⋯π (involving the benzene ring) inter-actions are found in the crystal structure.

Utility of GenoType MTBDRplus assay in rapid diagnosis of multidrug resistant tuberculosis at a tertiary care centre in India.

PURPOSE: Molecular methods which allow rapid detection of tuberculosis as well as drug resistance directly from clinical samples have become the most popular diagnostic methodology with the emergence of multidrug resistant tuberculosis. The aim of the present study was to evaluate the performance of a line probe assay, GenoType MTBDRplus for the rapid detection of Mycobacterium tuberculosis and mutations causing rifampicin and INH resistance directly in smear positive pulmonary specimens and also in M. tuberculosis isolates grown from various clinical specimens. MATERIALS AND METHODS: The MTBDRplus assay was done directly on 37 smear positive pulmonary specimens and also on 69 M. tuberculosis isolates obtained by rapid automated culture using Bact/Alert 3D. The results were compared with phenotypic drug susceptibility testing (1% proportion method) using Bact/Alert 3D. RESULTS: The sensitivity and specificity for detection of resistance to rifampicin was 100% and 97.3%, and to INH was 91.9% and 98.4%, respectively, in comparison with the phenotypic drug susceptibility testing. CONCLUSION: MTBDRplus assay had good sensitivity and specificity with turn around time of less than 48 hours. It may be a useful tool for rapid detection of multidrug resistant tuberculosis at a tertiary care centre.

L-Proline anchored multicomponent synthesis of novel pyrido[2,3-a]carbazoles; investigation of in vitro antimicrobial, antioxidant, cytotoxicity and structure activity relationship studies.

The newly synthesized pyrido[2,3-a]carbazoles were prepared in good yields by multicomponent reactions under L-proline as promoter and structurally characterized. Few compounds showed significant activity toward both gram-positive, gram-negative bacterial strains. All compounds exerted negative efficacy for antifungal activity except compounds 5f and 7f which showed moderate activity. All compounds showed weak to moderate capacity for scavenging DPPH. The cytotoxicity was evaluated by Sulforhodamine B assay against A-549, B16F10, HCT-15, SKMel2 and SKOV3 cell lines and compared with standard drug cisplatin. Compound 5f outperformed cisplatin against A-549, HCT-15, SKMel2 and B16F10 cell lines. Compound 5e outranged cisplatin against A-549, HCT-15, and SKMel2 cell lines. 5b outperformed cisplatin specifically against B16F10. The preliminary structure activity relationships were carried out.

6-Methyl-2,3,4,9-tetra-hydro-1H-carbazole-1-thione.

In the title mol-ecule, C(13)H(13)NS, the dihedral angle between the benzene ring and the fused pyrrole ring is 0.71 (8)° and the cyclo-hexene ring is in an envelope form. The (CH(2))(3) atoms of the cyclo-hexene ring are disordered over two positions; the site-occupancy factor for the major component refined to 0.862 (4). In the crystal, inter-molecular N-H⋯S hydrogen bonds lead to the formation of centrosymmetric aggregates via an R(2) (2)(10) ring.

9-Ethyl-N-(3-nitro-benzyl-idene)-9H-carbazol-3-amine.

The title compound, C(21)H(17)N(3)O(2), crystallizes with two mol-ecules in the asymmetric unit. The carbazole groups show relatively small deviations from planarity [maximum displacements from the mean carbazole plane are 0.077 (7) and 0.101 (7) Å]. The dihedral angles between the 3-nitro-benzyl-idene-amine and carbazole groups are 37.9 (1) and 37.0 (1)° in the two mol-ecules.