Association of symptom characteristics and comorbid conditions with viral RNA positivity of Covid-19 patients in Kasaragod district in Kerala, India: A retrospective cohort study

BACKGROUND Symptoms of Covid-19 are known to be non-specific ranging from asymptomatic cases to severe illness affecting multiple organ systems. The duration of viral RNA positivity and transmission varies in individuals. We describe the association between symptom characteristics and comorbid conditions with viral RNA positivity of SARSCoV-2 affected individuals. METHODS We conducted a record-based retrospective cohort study of 179 patients found to be positive for Covid-19 in Kasaragod district in Kerala. We included details of all patients found positive during the initial phases of the pandemic and recorded details regarding symptoms, duration of viral RNA positivity and the occurrence of transmission. The data were analysed using SPSS. RESULTS Any symptom was present in 68%. Fever (43%) was the most common symptom while 50% had at least one respiratory symptom. Increased duration of viral RNA positivity was found to be associated with presence of comorbid conditions. The majority of individuals who transmitted disease (75%) had some symptom, predominantly a respiratory symptom. CONCLUSION Respiratory symptoms are seen in half of the patients and viral RNA positivity was for a longer duration in patients with comorbid conditions.

Genotype shift of dengue virus (DENV1) during the 2017 outbreak of dengue fever in Thiruvananthapuram, Kerala, India

An unprecedented outbreak of dengue occurred during 2017 in Kerala. Thiruvananthapuram was worst affected. We carried out a joint investigation with the Health department of the State, to understand the epidemiological and entomological factors involved in this outbreak, so as to develop strategies to contain it. Blood samples from suspected patients were collected from three worst affected areas and genomic analysis of the Dengue virus (DENV) was performed. Also, a cross sectional entomological survey was carried out in these areas. The data obtained was compared with the available secondary data of DENV in Kerala. The investigations revealed a genetic shift from the erstwhile predominant DENV2/DENV3 serotypes to the newly introduced DENV1 Asian genotype during the current outbreak. Breeding indices of Aedes aegypti, the predominant vector species was also found to be remarkably high. Asian genotype of DENV1 was detected in field collected Ae. aegypti also. The index cases of the Asian genotype of DENV1 in Kerala were detected from Erumeli village (gateway to the famous Sabarimala shrine) among two plantation workers migrated from the neighbouring Karnataka state, during 2013. This introduced virus strain attained an epidemic proportion in 2017 in Thiruvananthapuram, owing to immunologically naïve population and high receptivity.

A descriptive pilot study of mitochondrial mutations & clinical phenotype in fibromyalgia syndrome

Background & objectives: Fibromyalgia syndrome (FMS) is one of the most common chronic pain conditions of unknown aetiology. Mitochondrial dysfunction has been reported in FMS with some studies reporting the presence of mitochondrial mutation namely A3243G, which also causes mitochondrial encephalomyopathy, lactic acidosis and stroke-like episodes. This pilot study was conducted to assess this mutation and also detect large deletions in mitochondrial DNA (mtDNA) in patients with FMS. Methods: Thirty female patients with FMS participated and 30 matched controls were included. Genomic DNA was subjected to polymerase chain reaction (PCR) amplification using specific primers followed by restriction digestion with Apa I enzyme to detect the specific A3243G mtDNA mutation. Long-range PCR was done in two sets to detect the large deletions in the mtDNA. Biochemical parameters including thyroid-stimulating hormone and vitamin D levels were also looked at. Results: None of the patients were found to carry the common mutation or large deletions. Low vitamin D level was a common finding. Hypothyroidism was found in a few patients. Interpretation & conclusions: Although the common mutation or large mtDNA deletions were not detected in blood mtDNA in the FMS patients, mutations in the muscle and sequence variation in mtDNA remained a possibility. Future studies in both blood and muscle tissue including mtDNA sequencing are warranted in such patients to determine if a subset of FMS patients have mitochondrial myopathy.

Inhibition of cytochrome P450 3A enzyme by Millettia aboensis: its effect on the pharmacokinetic properties of efavirenz and nevirapine

ABSTRACT The chronic and comorbid nature of HIV infection necessitate the use of multiple drugs including herbs to relieve symptoms with a possible increase in herb–drug interaction cases. This study was designed to evaluate the effect of Millettia aboensis (Hook. f.) Baker, Fabaceae, on cytochrome P450 3A isoenzyme and the influence of this effect on the bioavailability of two antiretroviral agents. In vitro effect of ethanol extract of M. aboensis on intestinal and liver microsomes extracted from female rats was assessed using erythromycin-N-demethylation assay method while in vivo effects were determined by estimating simvastatin plasma concentrations in rats. The effect of the extract on pharmacokinetic parameters of orally administered efavirenz (25 mg/kg) and nevirapine (20 mg/kg) was determined in rats divided into groups (n = 5). Plasma drug concentrations were assayed using HPLC and pharmacokinetic parameters determined through a non-compartmental analysis as implemented in WinNonlin pharmacokinetic program. The extract inhibited both intestinal and liver microsomal cytochrome P450 3A isoenzyme activities in vitro and enhanced simvastatin absorption in vivo with possible inhibition of metabolizing enzymes as indicated by significant (p < 0.05) increase in maximal concentration, area under curve and mean resident time of the drug. However, further in vivo interaction studies in animal model did not produce significant (p > 0.05) changes in the pharmacokinetic parameters of efavirenz and nevirapine. HPLC fingerprinting indicated the presence of quercetin and kaempferol in the extract. These findings revealed M. aboensis as an inhibitor of cytochrome P450 3A enzyme but, with no significant effect on the bioavailability of orally administered nevirapine and efavirenz.

In vitro and in vivo cytochrome P450 3A enzyme inhibition by Aframomum melegueta and Denniettia tripetala extracts

Objective To evaluate the in vitro and in vivo inhibitory effects of two commonly used herbs, Aframomum melegueta (A. melengueta) and Dennettia tripetala (D. tripetala) on CYP 3A enzymes. Methods In vitro inhibition of the enzymes were assessed with microsomes extracted from female albino rats using erythromycin-N-demethylation assay (EMND) method while their in vivo effects were measured by estimating simvastatin plasma concentrations in rats. Pharmacokinetic parameters were determined using non-compartmental analysis as implemented in WinNonlin pharmacokinetic program. Results EMND assay with intestinal microsomes indicated that aqueous extracts of D. tripetala and A. melengueta significantly (P < 0.05) inhibited intestinal CYP 3A activity at both 50 μg and 100 μg concentrations. Petroleum ether extract of D. tripetala and ethanol extracts of A. melengueta inhibited intestinal CYP3A activity at 100 μg but not at 50 μg concentrations. All the extracts showed an in vitro dose dependent CYP 3A inhibition with liver microsomes. In vivo analysis showed that pre-treatment with the extracts enhanced systemic absorption of simvastatin with reductions in metabolizing enzymes activity as indicated in significant increases in maximal concentration, area under curve, area under moment curve and mean resident time of simvastatin (P < 0.05). Conclusions Herbal preparations containing these plants' extracts should be used with caution especially in patients on CYP450 3A substrate medications.

In vitro and in vivo cytochrome P450 3A enzyme inhibition by Aframomum melegueta and Denniettia tripetala extracts

OBJECTIVE@#To evaluate the in vitro and in vivo inhibitory effects of two commonly used herbs, Aframomum melegueta (A. melengueta) and Dennettia tripetala (D. tripetala) on CYP 3A enzymes.@*METHODS@#In vitro inhibition of the enzymes were assessed with microsomes extracted from female albino rats using erythromycin-N-demethylation assay (EMND) method while their in vivo effects were measured by estimating simvastatin plasma concentrations in rats. Pharmacokinetic parameters were determined using non-compartmental analysis as implemented in WinNonlin pharmacokinetic program.@*RESULTS@#EMND assay with intestinal microsomes indicated that aqueous extracts of D. tripetala and A. melengueta significantly (P < 0.05) inhibited intestinal CYP 3A activity at both 50 μg and 100 μg concentrations. Petroleum ether extract of D. tripetala and ethanol extracts of A. melengueta inhibited intestinal CYP3A activity at 100 μg but not at 50 μg concentrations. All the extracts showed an in vitro dose dependent CYP 3A inhibition with liver microsomes. In vivo analysis showed that pre-treatment with the extracts enhanced systemic absorption of simvastatin with reductions in metabolizing enzymes activity as indicated in significant increases in maximal concentration, area under curve, area under moment curve and mean resident time of simvastatin (P < 0.05).@*CONCLUSIONS@#Herbal preparations containing these plants' extracts should be used with caution especially in patients on CYP450 3A substrate medications.

Transsphenoidal encephalocele presenting as complex partial seizure disorder

A 47-year-old man presented with history of recurrent complex partial seizures of 10 years duration with normal clinical findings. Imaging showed a suspected destructive mass lesion in the sphenoid sinus with widespread erosion of the surrounding bone including the temporal base. Transnasal endoscopic sphenoidotomy showed an encephalocele mass, a rare variant of basal encephalocele. Unusual presentation of an encephalocele as a seizure disorder is described

Screening for HIV infection by health professionals in India.

BACKGROUND: Stigma and discrimination, particularly in access to healthcare, remains a major problem for people Infected with HIV in most parts of India. METHODS: We did a multicentre study (n = 10) with a cross-sectional survey design using a standardized, interviewer-administered questionnaire. RESULTS: A total of 2200 healthcare providers participated. The knowledge, attitude and practice (KAP) related to HIV service delivery were very poor with a mean overall KAP score of only 49.7% (CI: 49.1-50.3). Only 5%, 5% and 1% of the participants scored more than 75% separately for the dimensions of knowledge, attitude and practice, respectively. Only 24.4% and 36.7% of responders knew that HIV screening was not recommended prior to surgery and pre-employment check-up. Many doctors (19.4%) had refused treatment to people living with HIV/AIDS (PLHA) at least some of the time and nearly half (47.2%) identified and labelled them; 23.9% isolated them in separate care areas and 13.3% postponed or changed treatment based on the patient's HIV status. Screening for HIV prior to elective surgery was done by 67% of providers. While 64.7% of responders were aware of the existence of national guidelines on and recommendations for HIV testing, only 38.4% had read the policy document. CONCLUSION: There is a growing need to provide care, support and treatment to a large number of PLHA. The capacity of healthcare providers must be urgently built up so as to improve their knowledge of and attitude to HIV to enable them to deliver evidence-based and compassionate care to PLHA in various healthcare settings.

Sciatic nerve schwannoma

Isolated peripheral nerve schwannoma, which is not a part of neurofibromatosis Type-1 or unrelated to radiation is uncommon. They usually arise from a major nerve trunk and present commonly with progressive neurological deficits. Sciatic nerve schwannoma is one such uncommon occurrence that presented with a rather common neurological presentation, sciatica, which could be excised microscopically without any sequel

Postoperative nausea and vomiting in diagnostic gynaecological laparoscopic procedures: comparison of the efficacy of the combination of dexamethasone and metoclopramide with that of dexamethasone and ondansetron.

BACKGROUND AND OBJECTIVE: This study was conducted in a tertiary hospital with the aim of comparing the efficacy of a combination of dexamethasone and metoclopramide with dexamethasone and ondansetron for the prophylaxis of postoperative nausea and vomiting [PONV] after diagnostic gynaecological laparoscopic procedures. SUBJECTS AND METHODS: In this prospective, randomised, double-blind study, 120 women received either saline I.V. [Group I, n=40]; a combination of dexamethasone [8 mg] with metoclopramide [10 mg] [Group II, n=40]; or a combination of dexamethasone [8 mg] with ondansetron [4 mg] [Group III, n=40] prior to induction of general anaesthesia. PONV was evaluated at regular intervals. The results were analysed using one-way ANOVA, post-hoc, Chi-square, Kruskal-Wallace tests and Z test for proportions where appropriate through a SPSS V.9 package. RESULTS: The 3 groups were well matched for demographic characteristics. The incidence of nausea and emesis was significantly lower in Group III [[17.5%, P <0.02] and [10%, P <0.01] respectively]. Nausea scores were also lower in Group III [P <0.02]. Rescue anti-emetic requirements were higher in Group I [P <0.05] as compared to Groups II and III. CONCLUSIONS: A combination of dexamethasone and ondansetron was more efficacious as compared to that of metoclopramide and dexamethasone. The combination of metoclopramide and dexamethasone seems to offer no additional benefit as compared to saline placebo.

An indigenously developed method for sweat collection and estimation of chloride for diagnosis of cystic fibrosis.

An indigenously developed method for sweat collection and titration method for estimation of chloride was validated. The mean difference in estimated chloride value from the known strength of saline in 50 samples was -1.04 +/- 4.13 mEq/L (95% CI: -0.07 to 2.28). The mean difference in the estimated chloride values between two observers when the test was performed on known strengths of saline solution was -2.5 +/- 4.24 mEq/L (95% CI: -3.67 to 1.33). The inter observer variability between two observers when the test was performed on sweat samples obtained from 50 individuals was -1.12 +/- 4.34 mEq/L (95% CI: -2.23 to 0.8 ). Sweat weight of more than 100 mg could be collected in first attempt in 602 of 757 (80%) patient with an average sweat weight of 230 mg. This inexpensive method of sweat collection and chloride estimation has acceptable accuracy and repeatability and can be used in resource poor setting for making a diagnosis of cystic fibrosis.

Unexpected presentations--four cases of lead poisoning.

OBJECTIVE: To describe the clinical presentation and response to treatment of four patients who presented with abdominal pain and were diagnosed to have lead poisoning. METHODS: After ruling out the more obvious causes of abdominal pain by barium studies, gastrointestinal endoscopies, and biochemical studies, blood lead levels were estimated by atomic absorption spectrophotometry. The patients were treated with oral d-penicillamine. RESULTS: The four patients had blood lead levels from 79 microg/dL to 365 microg/dL. All four of them showed marked improvement in their clinical condition and lowering of blood lead levels on follow up. CONCLUSIONS: Clinicians need to develop a high index of suspicion of lead poisoning as a possible cause of unexplained abdominal pain or altered sensorium, especially against a background of environmental lead contamination in India.

Chorea due to nonketotic hyperglycemia.

A 62 year old diabetic and hypertensive male presented with sudden onset generalized chorea. Investigations revealed uncontrolled diabetes with absent ketones and normal serum osmolality. Achievement of euglycemia with insulin therapy abolished the involuntary movements completely within a day. The direct effect of hyperglycemia causing striatal neuronal dysfunction could be the pathogenesis of the chorea in our patient.