Intravenous Doxycycline, Azithromycin, or Both for Severe Scrub Typhus.

BACKGROUND: The appropriate antibiotic treatment for severe scrub typhus, a neglected but widespread reemerging zoonotic infection, is unclear. METHODS: In this multicenter, double-blind, randomized, controlled trial, we compared the efficacy of intravenous doxycycline, azithromycin, or a combination of both in treating severe scrub typhus. Patients who were 15 years of age or older with severe scrub typhus with at least one organ involvement were enrolled. The patients were assigned to receive a 7-day course of intravenous doxycycline, azithromycin, or both (combination therapy). The primary outcome was a composite of death from any cause at day 28, persistent complications at day 7, and persistent fever at day 5. RESULTS: Among 794 patients (median age, 48 years) who were included in the modified intention-to-treat analysis, complications included those that were respiratory (in 62%), hepatic (in 54%), cardiovascular (in 42%), renal (in 30%), and neurologic (in 20%). The use of combination therapy resulted in a lower incidence of the composite primary outcome than the use of doxycycline (33% and 47%, respectively), for a risk difference of -13.3 percentage points (95% confidence interval [CI], -21.6 to -5.1; P = 0.002). The incidence with combination therapy was also lower than that with azithromycin (48%), for a risk difference of -14.8 percentage points (95% CI, -23.1 to -6.5; P<0.001). No significant difference was seen between the azithromycin and doxycycline groups (risk difference, 1.5 percentage points; 95% CI, -7.0 to 10.0; P = 0.73). The results in the per-protocol analysis were similar to those in the primary analysis. Adverse events and 28-day mortality were similar in the three groups. CONCLUSIONS: Combination therapy with intravenous doxycycline and azithromycin was a better therapeutic option for the treatment of severe scrub typhus than monotherapy with either drug alone. (Funded by the India Alliance and Wellcome Trust; INTREST Clinical Trials Registry-India number, CTRI/2018/08/015159.).

Hypothalamic-Pituitary Adrenal Axis Status 3 Months After Recovery From COVID-19 Infection.

CONTEXT: Coronavirus disease 2019 (COVID-19) predominantly involves the lungs, albeit many other organ systems, including the hypothalamic-pituitary-adrenal (HPA) axis, can be affected due to the expression of the angiotensin-converting enzyme 2 (ACE2) binding receptor. Few studies have reported the involvement of adrenal gland and the HPA axis during the acute phase of COVID-19; however, the data on the long-term effect of COVID-19 on the HPA axis after acute infection is scarce. OBJECTIVE: To assess and compare the changes in HPA axis in mild, moderate and severe COVID-19 categories at ≥ 3 months after acute infection. METHODS: A prospective, observational study was conducted to assess the HPA axis status among COVID-19 subjects at least 3 months after recovery from acute infection. The study was conducted from June 2021 to May 2022. Subjects visited the hospital in the fasting state (8.00-9.00am), serum cortisol levels were measured at baseline, 30 and 60 minutes after a 1-µg short Synacthen test (SST). RESULTS: A total of 66 subjects ≥ 18 years of age were included in the study. The mean age (SD) was 49.13 ± 11.9 years, 45(68.18%) were male and 21 (31.81%) were female subjects. The mean BMI in the study was 25.91 ± 4.26 kg/m2. Seventeen (25.8%) subjects had mild, twelve (18.2%) had moderate and thirty-seven (56.1%) subjects had severe COVID-19 infection. Out of the sixty-six subjects with COVID-19, nine subjects (9/66, 13.63%) had peak serum cortisol < 496.62 nmol/L suggestive of adrenal insufficiency (AI). SST peak serum cortisol levels did not differ significantly across the disease severity [Mild, (628.50 ± 214.65 nmol/L) vs moderate, [603.39 ± 161.95 nmol/L) vs severe, (597.59 ± 163.05 nmol/L), P = 0.617]. Six subjects with AI came for follow-up at 12 months, and all had normal HPA axis. CONCLUSION: HPA axis is affected in 13.63% (9/66) of subjects at least 3 months after recovery from COVID-19 infection. AI in COVID-19 might be transient and would recover spontaneously. These findings have important implications for the clinical care and long-term follow-up of subjects after COVID-19 infection.

Predictors of adverse maternal outcome in jaundiced pregnant women identified as having pregnancy-specific liver disease (P-sLD).

We aimed to study the factors including model for end stage liver disease (MELD) score in predicting mortality in women with pregnancy-specific liver diseases (P-sLD). A total of 154 women with clinical jaundice were studied of which 138 women were diagnosed with P-sLD. The most common P-sLD was HELLP syndrome (51.9%) followed by acute fatty liver of pregnancy (AFLP) (17.5%). The mean age was 26.3 ± 4.7 years and the mean gestational age was 35.1 ± 4.2 weeks. The maternal death rate was 26.8% and the most common cause was coagulopathy followed by sepsis. The mean MELD score among non survivors was 25.98 ± 8.17 compared to 17.29 ± 8.12 among survivors (p value .00). On univariate analysis, gestational age at admission, presence of hypertension, the platelet count, serum creatinine, INR and MELD score were found to significant. The AUC for INR (0.82) and MELD score (0.77) was better than platelet count (0.72) and serum creatinine (0.67). On multivariate analysis, only the INR and presence of AKI were found to be significantly associated with maternal mortality. The performance of INR was better than MELD score in predicting mortality in women with P-sLD. Additional factors like platelet count may be incorporated in to MELD score for the prediction of mortality in pregnant women.IMPACT STATEMENTWhat is already known on this subject? Pregnancy-specific liver disorders (P-sLD) have significant effect on maternal and foetal outcome, often considered as a spectrum of disease with significant overlap of clinical and laboratory parameters. MELD score is used reliably outside the pregnancy to predict mortality may not be good in pregnant women. There are only few studies that looked at the factors predictive of adverse maternal outcome.What do the results of this study add? Though we have demonstrated that MELD score was significantly high among non-survivors, serum bilirubin an important component of MELD score was not found to be significant. The other factors which were found to be significant on univariate analysis include gestational age at admission, hypertension and platelet count. However, international normalised ratio (INR) and acute kidney injury (AKI) were the factors independently associated with mortality.What are the implications for clinical practice and/or further research? The utility of MELD score in P-sLD should be studied prospectively in different populations. Moreover, the feasibility of developing a simple model which incorporates platelet count in addition to other components of MELD score should also be explored in future studies.

Presepsin vs Procalcitonin as Predictors of Sepsis Outcome.

BACKGROUND: Sepsis diagnosis and management is aided by the use of newer biomarkers like procalcitonin and presepsin. For prognostication, presepsin may be better than procalcitonin. METHODOLOGY: Ninety-two participants, suspected to be suffering from sepsis of varied etiologies were included in this study at the time of their presentation to the emergency health services. Presepsin and procalcitonin were estimated and the patient followed up till discharge or death. Receiver operating curve (ROC) curves, sensitivity, specificity, and positive and negative likelihood ratios were calculated. Association between these markers and mortality was estimated. RESULTS: Out of 92 participants enrolled on day 1, 73 survived till day 3. Patients who had thrombocytopenia, high neutrophil counts, and elevated levels of bilirubin, urea, presepsin, and procalcitonin were associated with poor outcomes. Presepsin and procalcitonin levels increased significantly from day 0 to day 3 in the nonsurvivor group as compared to the survivor group. On comparing the ROC curve of presepsin and procalcitonin, the area under the curve (AUC) of presepsin was more than procalcitonin, signifying that it was a better biomarker of mortality due to sepsis. At a cutoff value of 1.47 ng/dL, presepsin was a predictor of mortality in sepsis [odds ratio (OR) = 14]. It had similar sensitivity but better specificity than procalcitonin in predicting mortality.

Core Procedural Skills to be Taught for III-Year Undergraduate Medical Students: A Modified Delphi Study.

Introduction: While medical students are expected to learn procedural skills during their training, there is no consensus on their level of learning. Further, the most essential procedural skills across medical curricula which need to be taught during their III-year clinical posting are often not considered. The purpose of this study was to identify the core procedural skills needed to be taught during the III-year undergraduate medical students clinical posting. Methods: A three-round, online Modified Delphi method was used to identify consensus on selecting the most essential procedural skills prescribed in National Medical Commission (NMC) curriculum 2019. In Round 1, a list of 54 procedural skills from the National Medical Commission's (NMC) Graduate Medical Education Regulations (GMER) 2019 curriculum was distributed to 22 experts in pre-clinical medical education and multidisciplinary clinicians.They rated the skills in terms of importance. In Round 2, the skills that received consensus in Round 1 were presented, resulting in 13 skills for evaluation. Round 3 further narrowed down the skills to a final consensus of 6. An interclass correlation coefficient of 0.767 among experts indicates a substantial level of reliability. Results: Consensus was achieved for six procedural skills, each demonstrating over 80% agreement among the experts. These skills include basic life support, intravenous cannulation, urinary catheterization for both male and female patients, nasogastric tube insertion, oxygen administration, and basic suturing. Notably, all these skills received the highest level of agreement, surpassing 90% consensus. Conclusions: The results of the modified Delphi study offer crucial insights into the procedural skills that should be included in the curriculum for third-year undergraduate medical students during their clinical rotations in a tertiary care teaching hospital. Faculty members at these institutions differ in their opinions regarding the importance of teaching specific procedural skills, influenced by their teaching background and the student cohorts they instruct. From a comprehensive list, six skills have been pinpointed as the most vital through the modified Delphi technique. Moreover, the Delphi technique is acknowledged as a valuable method for achieving a consensus on prioritizing the training of certifiable skills.

Male Hypogonadism After Recovery from Acute COVID-19 Infection: A Prospective Observational Study.

BACKGROUND: The severe acute respiratory syndrome coronavirus 2 can affect the hypothalamic-pituitary-gonadal axis (HPG) due to the expression of the angiotensin-converting enzyme 2 receptor. OBJECTIVES: To assess the prevalence of hypogonadism and Sertoli cell dysfunction in coronavirus disease 2019 (COVID-19) male survivors. METHOD: Male subjects recovered from acute COVID-19 infection were prospectively observed. The primary outcomes included the proportion of hypogonadism, defined biochemically as serum testosterone<230 ng/dL or CFT of<6.4 ng/mL if the total testosterone is between 230-320 ng/m. Sertoli cell dysfunction was defined as inhibin-B level<54.5 pg/mL. Subjects with hypogonadism were followed up at 12 months to assess the recovery of the HPG axis. RESULTS: Eighty-three subjects aged≥18 years were evaluated at a median of 120 (±35) days post-recovery. Their mean age was 49.50±12.73 years, and the mean BMI was 26.84±5.62 kg/m2. Low testosterone was detected in 21 (24.71%) and low inhibin-B was detected in 14 (19.71%) out of 71 subjects at 3 months. Subjects with low testosterone were younger, with a mean age of 43.29±12.03 years (P-0.08) and higher BMI (P-0.012). The severity of COVID-19 infection, duration of hospitalization, and other factors were not significantly associated with low testosterone. At 12 months, 18 out of 21 subjects came for follow-up, of which 9 (50%) showed persistently low testosterone, suggestive of hypogonadism. CONCLUSION: Following COVID-19 infection, testosterone levels recovered over time; however, a significant proportion of subjects had low levels at 12-month follow-up. These findings have long-term implications for the management of COVID-19 subjects.

A protocol to evaluate the effectiveness of competency-based simulation training modules on the educational outcomes among MBBS students - A mixed method study.

BACKGROUND: The growing recognition of the importance of simulation-based training has been a present focus of medical education curriculum planners. This study aims to design, develop, implement, and evaluate the educational outcomes of training modules for a list of essential skills that MBBS students in a tertiary care teaching hospital in South India need to learn as part of their competency-based MBBS curriculum. MATERIALS AND METHODS: This sequential transformative mixed method study will be implemented in three phases: i) identification of essential skills for simulation-based training following the modified Delphi method, ii) development of skill training modules using ADDIE model of instructional design, implementation of the modules and collection of data on the educational outcomes and iii) a qualitative study involving in-depth interview and focus group discussion on understanding the potential for incorporating the modules into the present MBBS curriculum. Data on educational outcomes relevant to the study objectives will be collected using appropriate tools and analyzed using descriptive statistics and qualitative analytic methods. RESULTS: Phase one will tabulate the list of five essential skills and phase two educational outcomes will contain descriptive statistics on knowledge and skill acquisition, perception of simulation-based teaching and learning, and higher-order thinking skills. Phase three qualitative analysis will highlight the enabling and barrier aspects for incorporating this approach of simulation-based skill training within the current MBBS curriculum. CONCLUSIONS: The study outcomes will provide curriculum planners and educators insights into designing and implementing simulation-based skill training for undergraduate medical students. It will also help policymakers develop policies in medical education technologies to provide quality medical education and fulfill the objective of quality healthcare for all.

Characterization of Post-COVID-19 Clinical Manifestations Among Patients Visiting a Post-COVID-19 Clinic in a Tertiary Care Center: A Descriptive Study.

Background On December 21, 2019, a pneumonia-like outbreak of an unknown cause or origin was found to be emerging in Wuhan, China. In India, the first case of COVID-19 was found in Kerala and then started to spread all over India. Most of the infected people have recovered from the disease, but some patients were found to have symptoms at post-discharge follow-up. Although there are many studies on COVID-19 symptoms and signs during hospital stays, there is a scarcity of information regarding post-COVID-19 manifestations. The purpose of this study is to analyze the clinical characteristics of post-COVID-19 symptoms in patients attending the post-COVID-19 clinics. Methods A descriptive study was started on August 2021 at a tertiary care hospital in Southern India after institutional research and ethics committee clearance. All patients attending the post-COVID clinic, who tested positive for COVID-19 (RT-PCR or rapid antigen test (RAT) diagnosed or radiographically diagnosed COVID-19 (COVID-19 Reporting and Data System [CO-RADS] 5) were recruited. The proportion of people developing post-COVID-19 manifestations and categorization of symptoms in post-COVID-19 and its relationship to the severity of COVID-19 infections and the differences in post-COVID symptoms between hospitalized and non-hospitalized patients were studied. Results We enrolled 227 post-COVID patients who presented to the post-COVID clinic. The median age (IQR) of the participant was 52 (38-59) years, and the male-to-female ratio was 126/101 (1.24). Among 227 patients, 164 (72%) patients had exertional dyspnea, 109 (48%) patients had cough with expectoration, 96 (42.2%) patients with fatigue, 28 (12.33%) patients had myalgia, 18 (7.92) patients had a fever, 12 (5.28%) patients had hair loss, and 30 (13%) had other issues (loss of smell, sleep disturbances, and headache). Among 227, 142 (62.5%) patients were admitted to the hospital for acute COVID-19, and 85 (37.4) patients were in home isolation, but no statistical significance was found between in symptoms. Conclusion From this descriptive study, a high prevalence of post-COVID symptoms was noted, such aslike post-SARS syndrome. Mostly, researchers and clinicians have focused on acute COVID-19, but long-term follow-up with multidisciplinary evaluation and treatment is needed in all patients who recovered from acute COVID-19.

Predictors of Mortality among Patients Hospitalized with COVID-19 during the First Wave in India: A Multisite Case-Control Study.

Severe acute respiratory syndrome coronavirus 2 disease (COVID-19) has caused more than 6 million deaths globally. Understanding predictors of mortality will help in prioritizing patient care and preventive approaches. This was a multicentric, unmatched, hospital-based case-control study conducted in nine teaching hospitals in India. Cases were microbiologically confirmed COVID-19 patients who died in the hospital during the period of study and controls were microbiologically confirmed COVID-19 patients who were discharged from the same hospital after recovery. Cases were recruited sequentially from March 2020 until December-March 2021. All information regarding cases and controls was extracted retrospectively from the medical records of patients by trained physicians. Univariable and multivariable logistic regression was done to assess the association between various predictor variables and deaths due to COVID-19. A total of 2,431 patients (1,137 cases and 1,294 controls) were included in the study. The mean age of patients was 52.8 years (SD: 16.5 years), and 32.1% were females. Breathlessness was the most common symptom at the time of admission (53.2%). Increasing age (adjusted odds ratio [aOR]: 46-59 years, 3.4 [95% CI: 1.5-7.7]; 60-74 years, 4.1 [95% CI: 1.7-9.5]; and ≥ 75 years, 11.0 [95% CI: 4.0-30.6]); preexisting diabetes mellitus (aOR: 1.9 [95% CI: 1.2-2.9]); malignancy (aOR: 3.1 [95% CI: 1.3-7.8]); pulmonary tuberculosis (aOR: 3.3 [95% CI: 1.2-8.8]); breathlessness at the time of admission (aOR: 2.2 [95% CI: 1.4-3.5]); high quick Sequential Organ Failure Assessment score at the time of admission (aOR: 5.6 [95% CI: 2.7-11.4]); and oxygen saturation < 94% at the time of admission (aOR: 2.5 [95% CI: 1.6-3.9]) were associated with mortality due to COVID-19. These results can be used to prioritize patients who are at increased risk of death and to rationalize therapy to reduce mortality due to COVID-19.

Dapagliflozin for heart failure: is it a class effect?

Dapagliflozin, an SGLT2 inhibitor used in the management of Type 2 diabetes mellitus, has been recently approved for the control of worsening cardiovascular events, including deaths and hospitalizations, in adults with heart failure with reduced ejection fraction. Previously, canagliflozin had a label change with regards to its additional usage in the reduction of risk of hospitalization for heart failure in patients with both Type 2 diabetes mellitus and diabetic nephropathy with albuminuria. On the other hand, the therapeutic application of empagliflozin and ertugliflozin in heart failure is yet to be delineated comprehensively. The beneficial effects of these SGLT2 inhibitors, dapagliflozin in particular, in heart failure are found to be independent of neither the glucose-lowering nor the SGLT2 inhibiting effects.

Clinical outcomes of suspected Catheter Related Blood Stream Infection at a tertiary care center in south India.

BACKGROUND: Catheter related blood stream infection (CRBSI) makes up a significant proportion of Hospital acquired infection and increases the morbidity and mortality of those affected. AIMS AND OBJECTIVES: Primary aim was to study the clinical outcomes of patients with suspected Catheter Related Blood Stream Infection (CRBSI). RESULTS: Of the 150 participants suspected of having CRBSI, 100(67%) had CRBSI, 26(16%) patients were colonizers and 24(17%) patients had BSI from another source. Gram negative microbes were predominant. Clinical outcomes were studied with respect to mortality, complications and length of hospital stay. CRBSI participants had a significantly prolonged hospital stay. However no specific factors related to the host or the pathogen influenced this outcome. CONCLUSION: CRBSI prolongs the hospital stay for patients who would have otherwise been discharged, hence increases the burden on hospital and human resources.

Utility of quick sepsis-related organ failure assessment (qSOFA) score to predict outcomes in out-of-ICU patients with suspected infections.

BACKGROUND: Referral of sepsis patients at the level of primary care is often delayed due to the lack of an assessment tool which effectively predicts sepsis. The quick Sepsis-related Organ Failure Assessment score (qSOFA) can be used in such scenarios to improve patient outcomes. AIM: To assess the prognostic accuracy of qSOFA score in predicting adverse outcomes in patients with suspected infections and to compare it with the SIRS (Systemic Inflammatory Response Syndrome) and the SOFA (Sequential Organ failure Assessment Score). METHODS: This study included 180 participants admitted in the emergency wards of the Department of Medicine, over a period of one year with suspected infection. The primary outcome was the combined outcome of mortality and/or ICU stay of more than three days. Secondary outcomes were the duration of ICU stay, duration of inotrope use, and duration of mechanical ventilation. STATISTICAL ANALYSIS: Descriptive statistics using SPSS version 19.0 was applied in the study. RESULTS: Of the 180 participants, 54 had a qSOFA score of 2 at admission, 52 participants had an SIRS score of 2. The qSOFA score had the highest AUC for both mortality and the combined outcome of mortality and prolonged ICU stay (0.740 and 0.835, respectively). For a combined outcome of mortality and ICU stay >3 days, the qSOFA score had a sensitivity of 75% and a specificity of 82%. The positive likelihood ratio was 4.17. CONCLUSION: In a primary care setting, the qSOFA score of more than 2 can be used reliably to refer patients for admission and intensive care as they are likely to need longer hospital stay and can have worse outcomes.

Microbiological profile of pathogens in spontaneous bacterial peritonitis secondary to liver cirrhosis: a retrospective study.

Spontaneous bacterial peritonitis (SBP) is an acute bacterial infection of ascitic fluid without an obvious source. The prevalence of SBP in patients with cirrhosis is in the range of 10%-30%. With increasing use of antibiotics, there is a gradual shift in the causative flora of SBP from Gram-negative bacteria to Gram-positive and, more importantly, to drug-resistant bacteria. The aim of this retrospective study on 721 cases was to identify the prevalence of various organisms causing SBP along with their drug sensitivity and resistance patterns. A prevalence of 38.2% culture positivity was observed in our South Indian population. Escherichia coli was the most common pathogen isolated. Third-generation cephalosporins showed high rates of resistance, but a susceptibility of 74.5% to amikacin was found. Nonetheless, 42% of culture-positive isolates exhibited multidrug resistance, the highest rates being seen with Enterococcus faecium (64.2%) and Acinetobacter baumannii (71.4%).

Utility of Urinary Neutrophil Gelatinase Associated Lipocalin (NGAL) in Decompensated Cirrhosis.

BACKGROUND AND AIMS: Renal failure occurring in the setting of cirrhosis increases mortality by more than threefold. Serum creatinine, the conventional marker for renal dysfunction has inherent limitations in identifying and categorizing renal dysfunction in patients with chronic liver disease (CLD). Neutrophil gelatinase associated lipocalin (NGAL) is a novel biomarker which gets upregulated as early as 2-6 hours following the insult to renal tubules. In this study, we aim to check the utility of uNGAL to identify the different phenotypes of renal dysfunction in patients with CLD. We also intend to assess the utility of NGAL to predict 90-day transplant-free survival in patients with CLD. METHODS: A total number of 120 adult patients, with cirrhosis of liver were recruited. Those with pre-existing renal parenchymal disease, receiving nephrotoxic medications, spontaneous bacterial peritonitis, septic shock, proteinuria, hematuria, urinary tract infection and anuria were excluded. Urine samples for NGAL was measured at admission and at 48 hours thereafter. Patients were followed up for 90 days post admission. RESULTS: Among the study population, 16 patients (13.3%) had normal kidney function, 43 (35.8%) had prerenal azotemia and 54 (45%) had Hepatorenal Syndrome (HRS - AKI) and 7 (5.8%) had acute tubular necrosis (ATN). Urinary NGAL (uNGAL) levels were considerably lower in patients with normal kidney function and prerenal azotemia. An uNGAL level of 124 ng/ml on admission could distinguish severe forms of renal injury, with a sensitivity of 86% and specificity of 84%. The non survivors had higher uNGAL levels at admission [209.6 ng/ml (118.7-376.8) vs. 123 (33.6-344.3); P = 0.013].The receiver operated curves for uNGAL and serum creatinine at admission did not show any significant difference for predicting 90 day mortality (AUC for uNGAL: 0.632 vs 0.580 for serum creatinine; difference in AUC 0.053, P value 0.17). CONCLUSION: uNGAL levels are elevated in patients with HRS-AKI and ATN. A higher uNGAL level at admission was suggestive of severe renal dysfunction. An elevated uNGAL on admission is associated with inferior survival. However, uNGAL is not superior to serum creatinine in predicting 90-day mortality.

Association of N- terminal Pro Brain Natriuretic Peptide with Echocardiographic Measures of Diastolic Dysfunction in Cirrhosis.

BACKGROUND: Liver cirrhosis is associated with cardiac dysfunction in 40%-60% of the patients. Serum NT-ProBNP is a potential additional marker of cirrhotic cardiomyopathy. MATERIALS AND METHODS: It was a cross-sectional analytical study done in a tertiary care center in South India on 100 patients of cirrhosis of liver. Diastolic function was assessed from mitral inflow parameters as well as tissue Doppler imaging of the left ventricle in 95 patients. Serum NT-ProBNP levels was measured once at the time of inclusion into the study. Cirrhotic cardiomyopathy was diagnosed in those with abnormal echocardiographic parameters and its association with NT-Pro BNP levels was analyzed. Data were analyzed using SPSS version 22. RESULTS: Diastolic dysfunction was found in 40 (42.1%) participants. Twenty-two (23.2%) had Grade I, 16 (16.8%) had Grade II, and 2 (2.1%) had Grade III diastolic dysfunction. The mean NT-Pro-BNP was elevated (107.38 [±66.76] ng/ml) in patients with diastolic dysfunction. NT-ProBNP was higher in Child-Pugh B and C disease when compared to milder disease. NT-ProBNP was not a good screening tool for cardiomyopathy in cirrhotic patients. Area under the curve was 0.517 with 95% confidence interval and the P = 0.77. However, positive correlation was present between the NT-ProBNP value and two echocardiographic parameters of diastolic dysfunction (E/A, E/E'). CONCLUSION: Increased serum NT-ProBNP levels in cirrhosis of liver have a positive correlation with echocardiographic measures of diastolic dysfunction of the heart but it is not a good tool for screening for cirrhotic cardiomyopathy.

Lack of effect of the SLC47A1 and SLC47A2 gene polymorphisms on the glycemic response to metformin in type 2 diabetes mellitus patients.

Background This work aimed to evaluate the influence of single nucleotide polymorphisms (SNPs) in the SLC47A1 (922-158G>A; rs2289669) and SLC47A2 (-130G>A; rs12943590) genes on the relative change in HbA1c in type 2 diabetes mellitus (T2DM) patients of South India who are taking metformin as monotherapy. It also aims to study the effects of these SNPs on the dose requirement of metformin for glycemic control and the adverse effects of metformin. Methods Diabetes patients on metformin monotherapy were recruited based on the eligibility criteria (n=105). DNA was extracted and genotyping was performed with a real-time PCR system using TaqMan® SNP genotyping assay method. The HbA1c levels were measured using Bio-Rad D-10™ Hemoglobin Analyzer. Results After adjusting for multiple comparisons (Bonferroni correction) the difference found in the glycemic response between the "GG" genotype and "AG/AA" genotype groups of the SLC47A2 gene was not significant (p=0.027; which was greater than the critical value of 0.025). Patients with "GG" genotype showed a 5.5% decrease in HbA1c from baseline compared to those with the "AG/AA" genotype (0.1% increase). The SNP in the SLC47A1 gene also did not influence the glycemic response to metformin (p=0.079). The median dose requirements based on the genotypes of the rs12943590 variant (p=0.357) or rs2289669 variant (p=0.580) were not significantly different. Similarly, there was no significant difference in the occurrence of adverse effects across the genotypes in both the SLC47A1 (p=0.615) and SLC47A2 (p=0.309) genes. Conclusions The clinical response to metformin was not associated with the SNPs in the SLC47A1 and SLC47A2 genes coding for the multidrug and toxin extrusion protein (MATE) transporters. Furthermore, the studied SNPs had no influence on the dose requirement or adverse effects of metformin.

Leptospirosis: a diagnostic conundrum.

Leptospirosis is a serious public health concern worldwide. It is highly endemic in the Andaman Islands and its prevalence is increasing in other Indian states. Clinical features are non-specific and diagnosis relies on laboratory confirmation. The gold standard is microscopic agglutination testing, but this is not widely available. Real-time polymerase chain reaction testing of LipL32 antigen provides the earliest detection of pathogenic Leptospira in the body. We found it to be 100% specific, but it should be used in the first 10 days of illness for reliable results.

Genetic polymorphisms of multidrug and toxin extrusion proteins (MATE1 and MATE2) in South Indian population.

Introduction: Drug transporters are key determinants of pharmacokinetic and pharmacodynamic profiles of certain drugs. SLC47A1 (MATE1) and SLC47A2 (MATE2) are major efflux transporters involved in the hepatic and renal excretion of many cationic drugs including metformin. Our study was proposed to determine the normative frequencies of the single nucleotide polymorphisms (SNPs) rs2289669 and rs12943590 in the SLC47A1 and SLC47A2 genes, respectively, in South Indian population and also to compare those with those of the HapMap populations. Methods: One hundred two unrelated healthy volunteers from South India were enrolled in the study. Genomic DNA was extracted by 'phenol-chloroform extraction method' from the peripheral blood leucocytes and genotyping was accomplished by real-time polymerase chain reaction using TaqMan SNP genotyping assay method. Results: In contrast to other populations, the minor allele in SLC47A1 gene was found to be "G" with a frequency of 46.6% in South Indian population. The populations of Hans Chinese in Beijing (HCB) [P = 0.017] and Japanese in Tokyo (JPT) [P < 0.001] had significantly different genotype and allele frequencies (SNP rs2289669) compared to those of South Indian population. Similarly, in the SNP rs12943590 of SLC47A2 gene, the genotype and allele frequencies of South Indian population differed significantly from those of Yoruba in Ibadan, Nigeria (YRI) [P < 0.001] and Utah residents with Northern and Western European ancestry (CEU) [P = 0.005] populations. Conclusion: Thus, the allele and genotype distributions of SLC47A1 and SLC47A2 gene polymorphisms were established in South Indian population and were found to be different from the frequencies of other ethnicities.

Association of Angiotensin-Converting Enzyme Gene Polymorphisms and Nephropathy in Diabetic Patients at a Tertiary Care Centre in South India.

BACKGROUND: Genetic polymorphisms of the angiotensin-renin pathway have been thought to influence the development of diabetic nephropathy. However, there are conflicting results regarding this association in previous studies on populations with varying ethnicity. AIMS: Primary aim was to compare the frequency of distribution of angiotensin-converting enzyme (ACE) gene (insertion/deletion [I/D]) polymorphism in Tamilian Indian type 2 diabetic individuals with and without microalbuminuria. Secondary objective was to compare the frequency of distribution of the 3 genotypes in diabetic patients with urinary albumin/creatinine ratio (ACR) < 30 mg/dL, urinary ACR = 30 to 300 mg/dL, and urinary ACR > 300 mg/dL. METHODS: A total of 179 consecutive diabetic individuals between 40 and 70 years, from Puducherry and Tamilnadu of Dravidian descent participated in the study conducted from 2012 to 2014. Inclusion criteria were as follows: age ≥ 40 years and duration of type 2 diabetes mellitus for ≥5 years. Patients were divided into 2 groups based on ACR values. Group 1 consisted of 50 individuals with urinary ACR < 30 mg/g of creatinine, and group 2 consisted of 129 individuals with urinary ACR > 30 mg/g. Angiotensin I-converting enzyme (ACE) gene polymorphism was determined by allele-specific polymerase chain reaction method using a primer pair flanking the polymorphic region of its intron 16. Furthermore, group 2 patients were subdivided into those with urinary ACR = 30 to 300 mg/g of creatinine and those with urinary ACR > 300 mg/g of creatinine, and distribution of ACE gene polymorphism was compared in the three groups. STATISTICS: Statistical analysis was done using SPSS version 17.0. Independent Student t test was used to compare mean values between the 2 groups. Odds ratio was calculated for testing association between ACE gene (I/D) polymorphism and presence of microalbuminuria. P < .05 was considered significant. Comparison of ACE genotypes among 3 groups of patients (ACR < 30 mg/g, ACR = 30-300 mg/g, and ACR > 300 mg/g) was done using 1-way analysis of variance with Bonferroni multiple comparison test as post hoc analysis. CONCLUSIONS: Heterozygous I/D genotype was more frequent in the study population (45.8%) than the other genotypes. There was no difference in the genotype distribution in patients with varying levels of albuminuria.

Assessment of Serum VASPIN Levels among Type 2 Diabetes Mellitus Patients with or without Acute Coronary Syndrome.

INTRODUCTION: Type 2 Diabetes Mellitus (DM) is on the verge of becoming a pandemic in India. Type 2 DM patient have two to four times increased risk of carotid artery disease. Adipokines have been regarded recently as direct link between diabetes and atherosclerosis. Visceral Adipose Tissue Derived Serine Protease Inhibitor (VASPIN); one of the most recently discovered adipokine, inhibits the proteases responsible for insulin resistance, carotid plaque development and rupture. In literature, few studies have addressed the role of VASPIN in pathogenesis of Acute Coronary Syndrome (ACS) in patients with type 2 DM. AIM: To find association between serum VASPIN with lipid profile, creatine kinase-total, creatine kinase-MB, troponin-I, age, height, weight, blood pressure, smoking, family history of ACS and to prove the hypothesis of low serum VASPIN level as predictor of ACS in patients with type 2 DM. MATERIALS AND METHODS: Forty-one type 2 DM patients (controls) and 41 type 2 DM patients with ACS (cases) were enrolled in the study. Anthropometric measurements were performed and fasting serum biochemical parameters and VASPIN were measured. The results of cases and controls were compared by student t-test or Mann-Whitney test. All the parameters were correlated with serum VASPIN by Pearson's or Spearman's correlation. RESULTS: Fasting serum VASPIN concentration was significantly (p< 0.0001) lower in the cases (0.43±0.22 pg/ml) than in the controls (0.83±0.29 pg/ml). Correlation analysis undertaken on all type 2 DM showed that serum VASPIN concentration was negatively correlated with age, waist circumference, hip circumference, systolic and diastolic blood pressure, duration of diabetes, serum Creative Kinase-Total, CK-MB and urea (p< 0.05). Utilizing Receiver Operating Characteristic (ROC) curve, the serum VASPIN level of less than 0.594pg/ml showed greatest risk of ACS among type 2 DM patients (p< 0.0001). CONCLUSION: Type 2 DM patients with low serum vaspin concentration were at risk of ACS independent of other cardiovascular risk factors.