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

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

Bio-evaluation of poly(lactic-co-glycolic) acid nanoparticles loaded with radiolabelled rifampicin.

AIMS: The poly(lactic-co-glycolic) acid (PLGA) nanoparticles of tubercular drugs have been demonstrated to have a sustained release profile over 7 days. There is no information on the location or mode of release of these nanoparticles in living systems. Therefore, we have planned the study to explore the pharmacokinetics and biodistribution of PLGA rifampicin nanoparticles in healthy human volunteers. We aim to study the distribution pattern of PLGA-loaded nano-formulation of radiolabelled rifampicin in humans. METHODS: Rifampicin was labelled with 99m Tc by indirect method and nanoparticles were prepared by a single emulsion evaporation method. To investigate the pharmacokinetics and biodistribution of nanoparticles, a single dose of 450 mg of rifampicin was administered orally to healthy human volunteers divided into two different groups. RESULTS: Following a single oral dosage of the rifampicin nanoformulation, the pharmacokinetic (PK) parameters were significantly different between the nanoparticle and conventional groups: area under the concentration-time curve (AUC = 113.8 vs. 58.6; P < .001), mean residence time (MRT = 16.2 vs. 5.8; P < .01) and elimination rate constant (Ke = 0.04 vs. 0.10; P < .05). Also, Single-photon emission computed tomography/computed tomography (SPECT/CT) images revealed biodistribution of nanoparticles in the distal portions of the intestine, which is consistent with our dosimetry analysis. CONCLUSIONS: Significant difference in PK parameters and biodistribution of nanoparticles in spleen and lymph nodes with maximum deposition were observed in the large intestine. The nanoparticle distribution pattern may be advantageous for the treatment of intestinal or lymph node tuberculosis (TB) and has the potential to result in a lower dose of rifampicin nanoformulation for the treatment of pulmonary TB.

A Low-Cost, 3D-Printed Biosensor for Rapid Detection of Escherichia coli.

Detection of bacterial pathogens is significant in the fields of food safety, medicine, and public health, just to name a few. If bacterial pathogens are not properly identified and treated promptly, they can lead to morbidity and mortality, also possibly contribute to antimicrobial resistance. Current bacterial detection methodologies rely solely on laboratory-based techniques, which are limited by long turnaround detection times, expensive costs, and risks of inadequate accuracy; also, the work requires trained specialists. Here, we describe a cost-effective and portable 3D-printed electrochemical biosensor that facilitates rapid detection of certain Escherichia coli (E. coli) strains (DH5α, BL21, TOP10, and JM109) within 15 min using 500 µL of sample, and costs only USD 2.50 per test. The sensor displayed an excellent limit of detection (LOD) of 53 cfu, limit of quantification (LOQ) of 270 cfu, and showed cross-reactivity with strains BL21 and JM109 due to shared epitopes. This advantageous diagnostic device is a strong candidate for frequent testing at point of care; it also has application in various fields and industries where pathogen detection is of interest.

The Genetics of Ethambutol-Induced Optic Neuropathy: A Narrative Review.

Tuberculosis (TB) is a global health problem with the major brunt of disease occurring in developing countries. The cornerstone of treatment of TB is anti-tubercular therapy (ATT), which includes rifampicin, isoniazid, pyrazinamide and ethambutol. Because of emerging drug resistance, treatment failures, defaulters and increasing incidence of disseminated and extrapulmonary TB, the guidelines have been modified in some countries. Ethambutol is prescribed for longer times (in some cases >8 months) and hence the incidence of ethambutol-induced optic neuropathy (EtON) is expected to rise. The fundamental question which needs explanation is why only a small subset of patients on ethambutol are prone to develop loss of vision. This review focuses on available genetic studies which provide evidence that mitochondria are the likely substrates involved in the final pathway of reactive oxidative damage of the papillo-macular bundle. Genetic analysis of mitochondrial mutations encoding genes involved in oxidative phosphorylation pathways may help in isolating the subset of patients who are genetically susceptible. If the groups having high risk of developing EtON are recognised then prolonged duration of ethambutol treatment can be avoided in these susceptible individuals. A better understanding of the pathophysiology will also pave the way for the development of management strategies in this condition.

A multicentre point prevalence survey (PPS) of antimicrobial use amongst admitted patients in tertiary care centres in India.

OBJECTIVES: Data from point prevalence surveys (PPSs) in India are scarce. Conducting PPSs is especially challenging in the absence of electronic medical records, a lack of dedicated resources and a high patient load in resource-poor settings. This multicentre survey was conducted to provide background data for planning and strengthening antimicrobial stewardship programmes across the country. METHODS: This inpatient PPS was conducted over 2 weeks in May 2019 simultaneously across five study centres in India. Data about patient characteristics, indications for antimicrobials use and details of each antimicrobial prescribed including supportive investigation reports were collected in predesigned forms. RESULTS: A total of 3473 admitted patients in wards and ICUs were covered across five study centres. Of these, 1747 (50.3%) patients were on antimicrobials, with 46.9% patients being on two or more antimicrobials. Out of the total antimicrobials prescribed, 40.2% of the antimicrobials were prescribed for community-acquired infection requiring hospitalization followed by surgical prophylaxis (32.6%). Third-generation cephalosporins and drugs from the 'Watch' category were prescribed most commonly. Only 22.8% of the antimicrobials were based on microbiology reports. CONCLUSIONS: The survey demonstrated a high use of antimicrobials in admitted patients with a considerable proportion of drugs from the 'Watch' category. The targets for interventions that emerged from the survey were: improving surgical prophylaxis, decreasing double anaerobic cover, initiating culture of sending cultures and de-escalation with targeted therapy.

Meta-analysis of cardiovascular superiority trials published in the New England Journal of Medicine to elucidate the concept of superiority margin.

OBJECTIVE: To show that overpowered trials claim statistical significance detouring clinical relevance and warrant the need of superiority margin to avoid such misinterpretation. DESIGN: Selective review of articles published in the New England Journal of Medicine between 1 January 2015 and 31 December 2018 and meta-analysis following Preferred Reporting Items for Systematic Reviews and Meta-Analyses checklist. ELIGIBILITY CRITERIA FOR SELECTING STUDIES AND METHODS: Published superiority trials evaluating cardiovascular diseases and diabetes mellitus with positive efficacy outcome were eligible. Fixed effects meta-analysis was performed using RevMan V.5.3 to calculate overall effect estimate, pooled HR and it was compared with mean clinically significant difference. RESULTS: Thirteen eligible trials with 164 721 participants provided the quantitative data for this review. Largely, the primary efficacy endpoint in these trials was the composite of cardiovascular death, non-fatal myocardial infarction, unstable angina requiring rehospitalisation, coronary revascularisation and fatal or non-fatal stroke. The pooled HR was 0.86 (95% CI 0.84 to 0.89, I2=45%) which was lower than the mean clinically significant difference of 0.196 (19.6%, range: 0.09375-0.35) of these studies. There was a wide 95% CI in these studies from 0.56 to 0.99. The upper margin of CI in most of the studies was close to the line of no difference. Absolute risk reduction was small (1.19% to 2.3%) translating to a high median number needed to treat of 63 (range: 43 to 84) over a follow-up duration of 2.95 years. CONCLUSIONS: The results of this meta-analysis indicate that overpowered trials give statistically significant results undermining clinical relevance. To avoid such misuse of current statistical tools, there is a need to derive superiority margin. We hope to generate debate on considering clinically significant difference, used to calculate sample size, as superiority margin.

Qualitative Analysis of the Most Cited Publications from Leading Indian Medical Institutions.

BACKGROUND AND OBJECTIVES: The most important responsibility of physicians is research - advancement of medical knowledge is the core on which the other responsibilities, patient care and research, are based. This study was planned to conduct a qualitative analysis of the major publications from the the country's leading medical institutions. METHODS: We used Scopus to generate a list of total number of publications from the topmost institutions, the number of citations, and citations per article. We calculated the h-index, g-index, i-10 index, and h5-index for these institutions. A more detailed analysis was carried out for the top 20 most cited papers in each of the institutions. Only descriptive statistics were used. RESULTS: Among the top 10 medical institutions included, AIIMS, Delhi and PGIMER, Chandigarh were the top institutes, accounting for more publications and citations than the next eight institutions combined. The other institutions also managed to publish a large number of highly-cited papers. AIIMS was the leading institution when other indices were calculated. Among the most-cited articles, >80% had first/corresponding authors from outside India. A large number papers remained uncited, even after many years of publication. INTERPRETATION AND CONCLUSIONS: Uncited papers could be a result research conducted with the purpose of getting the numbers needed for promotion (NNP). Importance of collaborative research was seen to be an important factor when citations are considered. Even with the huge resource deficit, our institutes managed to publish a decent number of highly cited articles, which can be boosted if funding situation is improved.

Evaluation of evidence for pharmacokinetics-pharmacodynamics-based dose optimization of antimicrobials for treating Gram-negative infections in neonates.

BACKGROUND & OBJECTIVES: Neonates present a special subgroup of population in whom optimization of antimicrobial dosing can be particularly challenging. Gram-negative infections are common in neonates, and inpatient treatment along with critical care is needed for the management of these infections. Dosing recommendations are often extrapolated from evidence generated in older patient populations. This systematic review was done to identify the knowledge gaps in the pharmacokinetics-pharmacodynamics (PK-PD)-based optimized dosing schedule for parenteral antimicrobials for Gram-negative neonatal infections. METHODS: Relevant research questions were identified. An extensive electronic and manual search methodology was used. Potentially eligible articles were screened for eligibility. The relevant data were extracted independently in a pre-specified data extraction form. Pooling of data was planned. RESULTS: Of the 340 records screened, 24 studies were included for data extraction and incorporation in the review [carbapenems - imipenem and meropenem (n=7); aminoglycosides - amikacin and gentamicin (n=9); piperacillin-tazobactam (n=2); quinolones (n=2); third- and fourth-generation cephalosporins (n=4) and colistin nil]. For each of the drug categories, the information for all the questions that the review sought to answer was incomplete. There was a wide variability in the covariates assessed, and pooling of results could not be undertaken. INTERPRETATION & CONCLUSIONS: There is a wide knowledge gap for determining the doses of antimicrobials used for Gram-negative infections in neonates. A different profile of newborns in the developing countries could affect the disposition of antimicrobials for Gram negative infections, necessitating the generation of PK-PD data of antimicrobials in neonates from developing countries. Further, guidelines for treatment of neonatal conditions may incorporate the evidence-based PK-PD-guided dosing regimens.

A meta-analysis to assess usefulness of procalcitonin-guided antibiotic usage for decision making.

BACKGROUND & OBJECTIVES: Development of antibacterial resistance and its association with antibiotic overuse makes it necessary to identify a specific and sensitive biomarker for the diagnosis of bacterial infection and guiding antibiotic therapy. Procalcitonin (PCT), as a sepsis biomarker, may play a role in guiding antibiotics treatment in hospital settings. The aim of the current meta-analysis was to analyze the utility of PCT on various outcomes of interest in inpatients. METHODS: Different databases were searched for randomized controlled trials comparing PCT-guided therapy with standard therapy in admitted patients with bacterial infections. Twenty six articles were found suitable for full text search and of these, 16 studies were considered finally for data extraction. RESULTS: There were no significant differences found in total mortality [pooled odds ratio (OR) 1.04, 95% confidence interval (CI) 0.89-1.22, P=0.63], 28-day mortality (pooled OR 0.97, 95% CI 0.80-1.19, P=0.79), need of Intensive Care Unit admission (OR=0.80, 95% CI 0.59-1.09, P=0.16) and duration of stay in hospital (pooled mean difference -0.01, 95% CI -0.50-0.49, P=0.98) between treatment and control groups. PCT-guided treatment significantly decreased the duration of antibiotic treatment (pooled mean difference -2.79, 95% CI -3.52--2.06, P<0.00001). INTERPRETATION & CONCLUSIONS: PCT-guided therapy significantly decreased antibiotics exposure and thus treatment cost. However, the hard endpoints did not demonstrate any significant benefits, possibly due to low power to detect differences and/or the presence of comorbidities.

Efficacy of tranexamic acid in haemoptysis: A randomized, controlled pilot study.

BACK GROUND: Haemoptysis is a life threatening condition irrespective of aetiology. Tranexamic acid (TA), a potent anti-fibrinolytic agent, has been shown to control bleeding, decrease transfusion requirement in knee & hip arthroplasty, coronary artery bypass grafting and heavy menstrual bleeding. TA also has mortality benefit in bleeding from surgical and trauma patients. But the studies, regarding efficacy and safety of TA in controlling haemoptysis are conflicting. METHOD: In this single blinded, prospective study, total 66 patients with sub-massive haemoptysis were randomized into treatment (T) and placebo control (C) groups. Group-T received intravenous (IV) TA in a loading dose of 1 g, followed by 1 g TA over 8 h infusion and group-C received IV 0.9% normal saline. The severity of haemoptysis was assessed by quantity, frequency and visual analogue scale (VAS) score. RESULTS: On day 2, frequency, quantity and VAS score of haemoptysis were 2.23 ± 2.11/day, 34.19 ± 67.0 ml and 14.72 ± 15.7 respectively in Group-T and 2.29 ± 2.0/day, 90.4 ± 79.0 ml and 31.33 ± 22.12 respectively in group-C. In group-T 16.27% patients needed intervention as compared to 38.1% in group-C (p 0.053). The mean blood transfusion (1.58 ± 0.88 & 1.67 ± 0.669 units) and hospital stay (4.14 ± 3.18 & 5.48 ± 3.26 days) was also lower in group-T as compared to group-C. Group-T had better outcomes as compared to group-C, but statistically significant only for VAS score (p 0.001). During study no adverse event of the drug was noted. CONCLUSION: TA decreases severity of haemoptysis and can be used as a bridging therapy in acute haemoptysis before definitive intervention can be under taken.

Probiotic VSL#3 reduces liver disease severity and hospitalization in patients with cirrhosis: a randomized, controlled trial.

BACKGROUND & AIMS: Little is known about whether probiotics can affect outcomes of patients with cirrhosis and hepatic encephalopathy (HE). We assessed the efficacy of a probiotic preparation in preventing the recurrence of HE (primary outcome) and reducing the number of hospitalizations and severity of liver disease in patients with cirrhosis. METHODS: We performed a double-blind trial at a tertiary care hospital in India. Patients with cirrhosis who had recovered from an episode of HE during the previous month were assigned randomly (using computer-generated allocation) to groups given a probiotic preparation (VSL#3, 9 × 10(11) bacteria; CD Pharma India Private Limited, New Delhi, India) (n = 66) or placebo (n = 64) daily for 6 months. RESULTS: There was a trend toward a reduction in the development of breakthrough HE among patients receiving the probiotic (34.8% in the probiotic group vs 51.6% in the placebo group; hazard ratio [HR], 0.65; 95% confidence interval [CI], 0.38-1.11; P = .12). Fewer patients in the probiotic group were hospitalized for HE (19.7% vs 42.2%, respectively; HR, 0.45; 95% CI, 0.23-0.87; P = .02) or for complications of cirrhosis (24.2%) than in the placebo group (45.3%) (HR, 0.52; 95% CI, 0.28-0.95; P = .034). Child-Turcotte-Pugh and model for end-stage liver disease scores improved significantly from baseline to 6 months in the probiotic group, but not in the placebo group. There were no adverse events related to VSL#3. CONCLUSIONS: Over a 6-month period, daily intake of VSL#3 significantly reduced the risk of hospitalization for HE, as well as Child-Turcotte-Pugh and model for end-stage liver disease scores, in patients with cirrhosis. ClinicalTrials.gov number: NCT01110447.

Guidelines for Diagnosis and Management of Bronchial Asthma: Joint Recommendations of National College of Chest Physicians (India) and Indian Chest Society.

Bronchial asthma is an important public health problem in India with significant morbidity. Several international guidelines for diagnosis and management of asthma are available, however there is a need for country-specific guidelines due to vast differences in availability and affordability of health-care facilities across the globe. The Indian Chest Society (ICS) and the National College of Chest Physicians (NCCP) of India have collaborated to develop evidence-based guidelines with an aim to assist physicians at all levels of health-care in diagnosis and management of asthma in a scientific manner. Besides a systematic review of the literature, Indian studies were specifically analysed to arrive at simple and practical recommendations. The evidence is presented under these five headings: (1) definitions, epidemiology and impact, (2) diagnosis, (3) pharmacologic management of stable disease, (4) management of acute exacerbations, and (5) non-pharmacologic management and special situations. The modified grade system was used for classifying the quality of evidence as 1, 2, 3, or usual practice point (UPP). The strength of recommendation was graded as A or B depending upon the level of evidence.

Superiority trials: raising the bar of null hypothesis statistical testing.

We propose a 'superiority margin', akin to the noninferiority margin used in non-inferiority trials. This would overcome several drawbacks of null hypothesis statistical testing and can be applicable to other types of analyses as well.

Dietary interventions (plant sterols, stanols, omega-3 fatty acids, soy protein and dietary fibers) for familial hypercholesterolaemia.

BACKGROUND: A cholesterol-lowering diet and several other dietary interventions have been suggested as a management approach either independently or as an adjuvant to drug therapy in children and adults with familial hypercholesterolaemia (FH). However, a consensus has yet to be reached on the most appropriate dietary treatment. Plant sterols are commonly used in FH although patients may know them by other names like phytosterols or stanols. OBJECTIVES: To examine whether a cholesterol-lowering diet is more effective in reducing ischaemic heart disease and lowering cholesterol than no dietary intervention in children and adults with familial hypercholesterolaemia. Further, to compare the efficacy of supplementing a cholesterol-lowering diet with either omega-3 fatty acids, soya proteins, plant sterols or plant stanols. SEARCH METHODS: We searched the Cochrane Cystic Fibrosis and Genetic Disorders Group Inborn Errors of Metabolism Trials Register, which is compiled from electronic searches of the Cochrane Central Register of Controlled Trials (CENTRAL) (updated with each new issue of The Cochrane Library), quarterly searches of MEDLINE and the prospective handsearching of one journal - Journal of Inherited Metabolic Disease. Most recent search of the Group's Inborn Errors of Metabolism Trials Register: 22 August 2013. We also searched PubMed to 05 February 2012. SELECTION CRITERIA: Randomised controlled trials, both published and unpublished, where a cholesterol-lowering diet in children and adults with familial hypercholesterolaemia has been compared to other forms of dietary treatment or to no dietary intervention were included. DATA COLLECTION AND ANALYSIS: Two authors independently assessed the trial eligibility and risk of bias and one extracted the data, with independent verification of data extraction by a colleague. MAIN RESULTS: In the 2014 update of the review, 15 trials have been included, with a total of 453 participants across seven comparison groups. The included trials had either a low or unclear risk of bias for most of the parameters used for risk assessment. Only short-term outcomes could be assessed due to the short duration of follow up in the included trials. None of the primary outcomes, (incidence of ischaemic heart disease, number of deaths and age at death) were evaluated in any of the included trials. No significant differences were noted for the majority of secondary outcomes for any of the planned comparisons. However, a significant difference was found for the following comparisons and outcomes: for the comparison between plant sterols and cholesterol-lowering diet (in favour of plant sterols), total cholesterol levels, mean difference 0.30 mmol/l (95% confidence interval 0.12 to 0.48); decreased serum LDL cholesterol, mean difference -0.60 mmol/l (95% CI -0.89 to -0.31). Fasting serum HDL cholesterol levels were elevated, mean difference -0.04 mmol/l (95% CI -0.11 to 0.03) and serum triglyceride concentration was reduced, mean difference -0.03 mmol/l (95% CI -0.15 to -0.09), although these changes were not statistically significant. Similarly, guar gum when given as an add on therapy to bezafibrate reduced total cholesterol and LDL levels as compared to bezafibrate alone. AUTHORS' CONCLUSIONS: No conclusions can be made about the effectiveness of a cholesterol-lowering diet, or any of the other dietary interventions suggested for familial hypercholesterolaemia, for the primary outcomes: evidence and incidence of ischaemic heart disease, number of deaths and age at death,due to the lack of data on these. Large, parallel, randomised controlled trials are needed to investigate the effectiveness of a cholesterol-lowering diet and the addition of omega-3 fatty acids, plant sterols or stanols, soya protein, dietary fibers to a cholesterol-lowering diet.

Comparaison of Efficacy and Safety of Fentanyl Transdermal Patch with Oral Ketorolac for Pain Management in Dry Socket: A Randomized Clinical Trial.

Objectives: The aim of this study was to compare the efficacy and safety of transdermal Fentanyl patch with oral Ketorolac for pain management in dry socket patients. Study design: Sixty patients who were diagnosed with dry socket (VAS > 40 mm) were recruited in this prospective randomized controlled trial. Patients were divided into two groups. Group1 (n = 30) Transdermal Fentanyl patch (25mcg/hr) was given and in Group 2 (n = 30) Ketorolac 10 mg Oral tablet was prescribed for pain management. The primary endpoint was the mean pain scores within 72 h evaluated by visual analog scale (VAS). Secondary measures included the safety and tolerability, amount of rescue medication (analgesic and antiemetic) and effectiveness of treatment interventions by Brief Pain Inventory Questionnaire (BPI). Results: The mean VAS pain scores were significantly less in group 1 (Fentanyl) as compared to group 2 (ketorolac) on all follow-up days. Significant difference was noted in the mean amount of rescue analgesic medication. It was 2.16 + 1.53 in group 1 and 8.50 + 3.98 in group 2. Side effects were seen in both the groups. Nausea (46%) and vomiting (43%) were reported in group 1 while headache (36.6%) and epigastric pain (53.3%) in group 2. Conclusions: Thus, transdermal Fentanyl was better in pain control than Ketorolac with less need for rescue analgesic medication in dry socket.

"Cell blocking" the parasitic imposter: In a rare case of isolated pulmonary cysticercosis.

Isolated pulmonary cysticercosis is a rare manifestation of human cysticercosis which mainly affects central nervous system, skeletal muscles, eyes and subcutaneous tissues. Pulmonary involvement is usually a part of disseminated disease and mainly presents as bilateral pulmonary nodules. We report a rare case of isolated pulmonary cysticercosis presenting as lung cyst with pleural effusion. The diagnosis was made on pleural fluid cytology and cell block preparation. Herein we wish to recapitulate the importance of cell block as a diagnostic aid for parasitic infections, where morphological features and architectural patterns are as clearly discernable as in histopathology.

Effect of a deacyl gymnemic acid on glucose homeostasis & metabolic parameters in a rat model of metabolic syndrome.

BACKGROUND & OBJECTIVES: Metabolic syndrome (MS) comprises several cardio-metabolic risk factors, which include obesity, hypertension, hyperglycaemia, hypertriglyceridaemia and decreased HDL cholesterol. Leaf extract of Gymnema sylvestre has been shown to possess glucose lowering activity in animal models. This study was carried out to evaluate the efficacy of deacyl gymnemic acid (DAGA), active constituent of G. sylvestre, in a rat model of MS. METHODS: Six groups consisting of six wistar rats in each, were studied. Group I received the normal diet, while the remaining five groups received high fructose diet (HFD ) for 20 days to induce MS. HFD was continued in these five groups for the next 20 days along with group II received vehicle solution, group III received pioglitazone and groups IV- VI received DAGA in variable doses. Systolic blood pressure (SBP) was measured using tail-cuff method. Oral glucose tolerance test (OGTT) was done at baseline and at days 20 and 40. Blood samples were collected for glucose, insulin and lipid profile. RESULTS: Administration of HFD for 20 days resulted in weight gain (>10%), increase in SBP, fasting plasma glucose (FPG) and triglycerides fulfilling the criteria for MS. Administration of DAGA (200 mg/kg) reduced SBP and significantly improved the FPG and HOMA-IR (homeostatis model assessment-insulin resistance) with modest improvement in lipid profile without decrease in body weight similar to pioglitazone. INTERPRETATION & CONCLUSIONS: Our findings show that DAGA decreases SBP and improves parameters of glucose-insulin homeostasis in a rat model of MS induced by HFD. Further studies are required to elucidate the mechanism of action.

Antibiotic Prophylaxis for Orthopaedic Implant Removal: What Does the Evidence Say?

Orthopaedic implant removal is considered a sterile procedure, but the current literature suggests it is associated with around a 20% Surgical Site Infection (SSI) rate. The use of antibiotic prophylaxis is still ambiguous and contentious. Taking into consideration this issue we conducted a meta-analysis for the use of antibiotic prophylaxis in orthopaedic implant removal surgery. OBJECTIVES: To determine whether or not antibiotic prophylaxis benefits orthopaedic implant removal surgeries. METHODS: Electronic and printed sources were searched up to February 2021 for randomised controlled trials (RCTs) using antibiotic prophylaxis and a control group. Data from eligible studies were pooled for the following outcomes: overall, superficial, and deep surgical site infection (SSI). Pooled odds ratios with a 95% confidence interval (CI) were calculated using Mantel Haenszel fixed-effect model preferentially. RESULTS: Two studies, including 766 patients were included in this meta-analysis. Heterogeneity was not statistically significant between the studies. There was no significant difference in the incidence of overall SSI in cefazolin and normal saline (NS) groups (Pooled OR 0.79; 95% CI 0.53- 1.17). In subgroup analysis, antibiotic prophylaxis showed statistically significant improvement for deep SSI (Pooled OR 0.20; 95% CI 0.06-0.70). CONCLUSION: Overall incidence of SSI is not reduced after the administration of antibiotic prophylaxis one hour before removal of orthopaedic implants.