Drug utilization study in patients affected with COVID-19 in a dedicated COVID hospital

Background: There exists a treatment dilemma regarding the optimal and effective use of therapeutic drugs (hydroxychloroquine/chloroquine/azithromycin) for COVID-19. Furthermore, with changing guidelines, the data on drug utilization patterns across India are limited. Hence, this study was conducted to assess the prescription pattern and drug utilization trends in COVID-19 patients with the aim to study the drug utilization pattern in patients affected with COVID-19 in a dedicated COVID-19 hospital. Aims and Objectives: The objectives of the study are as follows: (1) To study drug utilization patterns according to the severity of the disease. (2) To study the prevalence of adverse drug reactions (ADRs). Materials and Methods: Data were collected retrospectively from 100 medical records of patients ?18 years irrespective of sex admitted in the COVID ward and ICU of a dedicated COVID hospital from May to August 2020. Pregnant and lactating women were excluded from the study. ADRs reported were also analyzed. Results: About 71% were mild in this study, 18% were moderate, and 11% were severe COVID-19 patients. Overall, the most common drugs prescribed were multivitamins, followed by pantoprazole, paracetamol, and azithromycin. Hydroxychloroquine was prescribed in 22%, favipiravir in 7%, and remdesivir in 3% of cases. The majority of moderate COVID patients received injectables piperacillin-tazobactam, methylprednisolone, and enoxaparin. The mean number of medications, duration of admission, and number of days on oxygen were higher and significant in moderate compared to mild and severe COVID patients. Overall, ADRs were encountered in 9% of cases. Conclusion: The prescribed pattern of drugs was by the national standard guidelines. Multivitamins, followed by pantoprazole, paracetamol, and azithromycin dominated the prescription pattern. Polypharmacy was encountered, which needs to be addressed for the rational use of drugs.

An evaluation of mini-laparotomy cholecystectomy in the laparoscopic era: a rural experience

Background: Laparoscopic cholecystectomy (LC) is the gold standard for the management of symptomatic cholelithiasis and complications of gallstone disease. Mini laparotomy cholecystectomy (MOC) may be a more appropriate option in the resource constrained rural setting due to its widespread applicability and comparable outcome with LC. The study aimed toprovide an epidemiological analysis of gallstone disease in the rural population and to evaluate the outcome of MOC in a rural hospital.Methods: A retrospective chart analysis of 248 patients undergoing cholecystectomy in a rural regional referral hospital in KwaZulu-Natal from January 2009 to December 2013 was undertaken.Results: Of the 248 patients, the majority were females (n = 211, [85%]). The most frequent indications for cholecystectomy included: biliary colic (n = 115, [46.3%]); acute cholecystitis (n = 80, [32.3%]); gallstone pancreatitis (n = 27, [10.8%]). Forty cases (16.1%) were converted to open cholecystectomy (OC). The median operative time was 40 minutes (range18­57). Twenty-three morbidities (9.3%) occurred including: bile leaks (n = 6, [2.4%]); bleeding from drain site (n = 1, [0.4%]), incisional hernia (n = 8 [3.2%]) and wound sepsis (n = 8 [3.2%]). The median length of hospital stay in patients who underwent MOC was 48 hours (range: 24­72 hours) and the median time to return to work was 10 days (range: 4­14 days). There was one mortality in the entire cohort.Conclusion: MOC is a safe and feasible operation for symptomatic cholelithiasis when cholecystectomy is indicated. The low operative morbidity and mortality in the context of a high risk patient profile and complicated gallstone disease makes this procedure an alternative to LC where LC is inaccessible

Tooth in the nose.

The finding of intranasal ectopic or supernumerary tooth although have been reported in the past, is still considered a rare presentation. It may remain silent for a long period of time, before manifesting with nasal symptoms. We report the case of a 33-year-old lady with an ectopic premolar tooth in the floor of her right nostril, presenting with intermittent epistaxis and foulsmelling nasal discharge. She was referred for a rhinolith in her nose. The tooth was successfully extracted via intranasal endoscopic approach.

Diagnostic value of biochemical predictive index in ovarian malignancy.

The aim of the study was to determine if diagnostic performance of CA-125 in ovarian malignancy can be improved by considering age of the patient. The study was a retrospective analysis of the medical records of 306 patients who underwent a CA-125 measurement in our Institute. Of the 306 patients, 31% had malignant ovarian diseases, 45% had benign ovarian diseases, 6% had non-ovarian gynaecological diseases and 18% had non-gynaecological diseases. A positive association was found between age and CA-125 levels in patients with ovarian diseases. Patients were divided into three age groups of 18–37 yrs, 38–56 yrs and 57–74 yrs and were given age scores as 1, 2 and 3 respectively. Biochemical predictive index (BPI) was calculated by multiplying age score and CA-125 value. Among the age groups ranging 38–56 yrs and 57–74 yrs, the CA-125 and BPI values were significantly higher in malignant ovarian diseases compared to benign ovarian diseases. ROC curve analysis revealed a cut-off of 86 for the BPI with the sensitivity, specificity, positive predictive value and negative predictive value as 58%, 78%, 56% and 80% respectively. BPI had better specificity and negative predictive value compared to CA-125, can be used in the screening of ovarian pathology.

Serum butyrylcholinesterase of non-human primate shows amine sensitive aryl acyl amidase and metallopeptidase activities and characteristics similar to those of the human serum enzyme.

Butyrylcholinesterase (BChE) was purified from monkey serum and the catalytic activities were examined. The enzyme has a molecular mass of approximately equal to 74 kDa as seen by SDS-gel electrophoresis. Monkey serum BChE also exhibits an amine sensitive aryl acylamidase (AAA) and a metallocarboxypeptidase activity. The tyramine activation of the aryl acylamidase activity and the metal chelator inhibition of the peptidase activity were characteristics similar to those of the human enzyme. Studies on 65Zn2+ binding and zinc chelate Sepharose chromatography showed that monkey serum BChE and human serum BChE have similar characteristics. Limited alpha chymotrypsin digestion of monkey serum BChE followed by Sephadex gel chromatography cleaved the enzyme into a 36 kDa fragment exhibiting peptidase activity. However the 20 kDa fragment corresponding to cholinesterase and aryl acylamidase activity was not detectable possibly due to the unstable nature of the fragment. Immunological studies showed that a polyclonal antibody against human serum BChE cross reacted with monkey serum BChE. The identical nature of the catalytic activities of human serum BChE and monkey serum BChE supports the postulate that all three catalytic activities co-exist in the same enzyme. This is the first time that purification and characterisation of the monkey serum BChE which has the highest sequence identity and immunological identity with that of human serum BChE, is being reported.

Virus isolation from wild-caught mosquitoes during a Japanese encephalitis outbreak in Kerala in 1996.

Out of 5357 wild-caught mosquitoes in 163 pools tested for virus using antigen capture ELISA and an insect-bioassay (inoculation into Toxorhynchites splendens larvae and identification by IFA using JE virus-specific monoclonal antibody), 16 flavivirus isolations were made of which 12 (75%) were identified as JE virus. Of the 12 JE virus isolations, 7 were from Culex tritaeniorhynchus, 3 from Mansonia uniformis and 1 each from Ma. indiana and Anopheles subpictus. Four isolations from Mansonia species for the first time reported here are noteworthy.

Phosphorylation of casein, fibrinogen and calmodulin by a glycoprotein protein kinase from monkey cerebellum: a casein kinase II-like enzyme.

A glycoprotein protein kinase was isolated from monkey cerebellum by polylysine-Sepharose chromatography and affinity chromatography on Sepharose 4B coupled to the lectin, Concanavalin A. The protein kinase phosphorylated casein on serine and threonine residues and was stimulated by polylysine, polyarginine, spermine, histone, protamine and sphingosine, but was inhibited by heparin, poly (Glu, Ala, Tyr) and poly (Glu, Tyr). These characteristics were typical of casein kinase II. The protein kinase also phosphorylated fibrinogen and calmodulin and exhibited similar characteristics of stimulation by polylysine or polyarginine. The phosphorylation of fibrinogen (a glycoprotein), but not casein or calmodulin (non-glycoproteins), was significantly inhibited by Concanavalin A. Unlike casein kinase II, the enzyme did not undergo autophosphorylation. The collective results suggested that the enzyme from monkey cerebellum was a casein kinase II-like protein kinase and that phosphorylation of a glycoprotein substrate (fibrinogen) by the kinase could be influenced by a carbohydrate binding lectin.

Lysosomal enzyme binding receptor protein from monkey brain and its phosphorylation.

The lysosomal enzyme binding receptor protein isolated from monkey brain by phosphomannan-Sepharose affinity chromatography was phosphorylated by [gamma-32P] ATP by protein kinases tightly associated with the receptor protein. A greater than 200 kDa protein was phosphorylated on both serine and tyrosine residues and a approximately 45 kDa protein was phosphorylated on only serine residues as evidenced by SDS-gel electrophoresis, autoradiography and phosphoamino acid analysis [(Panneerselvam, Ramamoorthy & Balasubramanian (1987) Biochem Biophys Res Commun, 147, 927-935)]. 125I-labelled lysosomal enzymes could be cross-linked to the receptor protein in the presence of disuccinimidyl suberate. Phosphorylation of the receptor on both serine and tyrosine residues was inhibited by quercetin, polylysine and polymyxin B. Catalytic subunit of cyclic AMP-dependent protein kinase preferentially phosphorylated the approximately 45 kDa protein. In the presence of Triton X-100, phosphorylation of a few additional protein bands on non-tyrosine residues was observed. There was a marked reduction in the efficiency of binding lysosomal enzymes by the phosphorylated receptor protein in comparison to the unphosphorylated receptor protein.

Isolation of a tripeptide showing weak acetylthiocholine hydrolysing activity from a soluble form of monkey basal ganglia acetylcholinesterase by limited trypsin digestion.

Acetylcholinesterase was purified from the soluble supernatant of monkey (Macaca radiata) brain basal ganglia by a three-step affinity purification procedure. The purified enzyme showed two major protein bands corresponding to molecular weights of approximately 65 kDa and approximately 58 kDa which could be labelled by [3H]diisopropylfluorophosphate. When the purified enzyme was subjected to limited trypsin digestion followed by gel filtration on Sephadex G-75 or Sephadex G-25 column, a peptide fragment of molecular weight approximately 300 Da having a weak acetylthiocholine hydrolysing activity was isolated. The amino acid sequence analysis of this peptide showed a sequence of Gly-Pro-Ser. When the [3H]DFP labelled enzyme was subjected to limited trypsin digestion and Sephadex G-75 column chromatography, a labelled peptide corresponding to approximately 430 Da was isolated. The kinetics, inhibition characteristics and binding characteristics to lectins of this peptide were compared with the parent enzyme. A synthetic peptide of sequence Gly-Pro-Ser was also found to exhibit acetylthiocholine hydrolysing activity. The kinetics and inhibition characteristics of the synthetic peptide were similar to those of the peptide derived from the purified acetylcholinesterase, except that the synthetic peptide was more specific towards acetylthiocholine than butyrylthiocholine. The specific activity (units/mg) of the synthetic peptide was about 123700 times less than that of the purified AChE.

Mammalian sulfoconjugate metabolism.

Sulfoconjugates occur ubiquitously as sulfopolysaccharides, sulfolipids and sulfoproteins. A variety of sulfotransferases catalyze the sulfation process with 3'- phosphoadenosine 5'-phosphosulfate as the sulfate donor. Sulfatases that catalyze the desulfation of different sulfoconjugates are known to be deficient in a number of genetic storage disorders.

The binding requirements of monkey brain lysosomal enzymes tο their immobilised receptor protein.

The lysosomal enzyme binding protein (receptor protein) isolated from monkey brain was immobilised on Sepharose 4B and used to study the binding of brain lysosomal enzymes. The immobilised protein could bind ß-D-glucosaminidase, α-D-mannosidase, α-Lfucosidase and ß-D-glucuronidase. The bound enzymes could be eluted either at an acid pH of 4·5 or by mannose 6-phosphate but not by a number of other sugars tested. Binding could be abolished by prior treatment of the lysosomal enzymes with sodium periodate. Alkaline phosphatase treatment of the enzymes did not prevent the binding of the lysosomal enzymes to the column but decreased their affinity, as seen by a shift in their elution profile, when a gradient elution with mannose 6-phosphate was employed. These results suggested that an 'uncovered' phosphate on the carbohydrate moiety of the enzymes was not essential for binding but can enhance the binding affinity.