Evaluation of a successful intervention for sustainability and effects in post research phase.

INTRODUCTION: Promoting appropriate use of drugs is an essential element in achieving quality of health and medical cares for patients and the community, and also to minimize financial burden. OBJECTIVE: The objective of this paper is to assess the successful intervention for sustainability and effects in post research phase. To address these problems, a variety of educational, managerial and regulatory strategies to improve prescribing have been tried in Nepal. When training is combined with a managerial intervention i.e. peer-group discussion, it results into improved changes in prescribing practices of paramedics in several practices. METHODOLOGY: A prospective, three-way design study consisting of small group training, small group training followed by peer-group discussion and control was conducted in three regions of Nepal including one hill and two terai (plains) districts from each region. The study included all health post from the sampled districts, making 80 health posts the study population. RESULTS: The study revealed the effectiveness of the peer-group discussion approach in improving the prescribing practices. An assessment to identify the sustainability of the strategy and its effect within the district healthcare system after the completion of the research phase was undertaken. The study found that peer-group discussion was discontinued in all targeted districts and the improved practices were not sustained after the completion of the research. Various reasons have been found for not continuing the effective intervention.     

Population pharmacokinetic modeling for enterohepatic recirculation in Rhesus monkey.

Enterohepatic recirculation (EHR) occurs via biliary excretion and intestinal reabsorption of a drug. Drug recycling through EHR can lead to a change in pharmacokinetic (PK) properties, such as reduced clearance (CL), extended half-life (T(1/2)) and increased plasma exposure (AUC). As a result, EHR may prolong the pharmacological effect of drugs. In the present study, the compound (Cpd A) was found to exhibit EHR in Rhesus monkeys associated with a reduction in CL (from 3.8 to 0.33 Lh(-1), IV; from 2.3 to 0.4 Lh(-1), PO), and an increase in T(1/2) (from 0.9 to 18 h, IV) and in AUC (from 1.5 to 17.4 microg h/mL, IV; from 2.8 to 16.3 microg h/mL, PO), by comparing the PK in the monkeys via the interruption of EHR (bile-duct cannulation) with that in the intact monkeys. A population four-compartment model was constructed based on recirculation loops incorporating all possible inputs (bile secretion, a lag-time model for gall bladder emptying, routes and amounts of a single dose administration) to fully evaluate the EHR of Cpd A. The plasma concentrations versus time profiles predicted from the model had a good fit to the values observed in the subjects and were further simulated with 90% confidence interval to demonstrate its utility. Thus, the model could be applied as a useful tool to evaluate the drugs or compounds that undergo EHR in different species.     

Assessment of oral bioavailability and preclinical pharmacokinetics of DRF-6196, a novel oxazolidinone analogue, in comparison to linezolid.

The aim of this study was to determine the bioavailability of a novel oxazolidinone, DRF-6196, in mice and rats following intravenous (i.v) and oral dosing and to compare the pharmacokinetics with those obtained following linezolid dosing. Blood samples were drawn at predetermined intervals up to 24 h post-dose after either DRF-6196 or linezolid administration. The concentrations of DRF-6196 and linezolid in various plasma samples were determined by a HPLC method. Following oral administration maximum concentrations of DRF-6196 were achieved within 0.5 h irrespective of the species. While the doses increased in the ratio of 1 : 3 : 10, mean Cmax and AUC(0-infinity) values in mice for DRF-6196 increased in the ratio of 1 : 3.87 : 8.53 and 1 : 2.51 : 9.24, respectively. Both the Cmax and AUC(0-infinity) values increased almost proportional to the dose administered in mice. Following i.v administration, the concentration of DRF-6196 declined in a bi-exponential fashion with terminal elimination half-life of 1.5 h irrespective of the species. The systemic clearance and volume of distribution of DRF-6196 in mice were 1.14 L/h/kg and 0.66 L/kg, respectively after i.v administration, while the respective values in rats were 0.61 L/h/kg and 0.41L/kg, respectively. Elimination half-life ranged between 0.8-1.5 h. Absolute oral bioavailability of DRF-6196 was found to be 80-96% across the test dose range. Although plasma levels of DRF-6196 were lesser compared to linezolid in the initial hours, it may not have any consequences on the clinical effectiveness of the molecule.     

Targets and management of hypertension in heart failure: focusing on the stages of heart failure

Hypertension is highly prevalent worldwide and is the major risk factor for heart failure (HF). More than half of the patients with HF in Asia suffer from hypertension. According to the 2022 American Heart Association/American College of Cardiology/Heart Failure Society of America HF guideline, there are four stages of HF, including at risk for HF (stage A), pre‐HF (stage B), symptomatic HF (stage C), and advanced HF (stage D). Given the high prevalence of hypertension as well as HF and the stronger association between hypertension and cardiovascular diseases in Asians compared to the west, measures to prevent and alleviate the progression to clinical HF, especially controlling the blood pressure (BP), are of priority for Asian populations. After reviewing evidence‐based studies, we propose a BP target of less than 130/80 mmHg for patients at stages A, B, and C. However, relatively higher BP may represent an opportunity to maximize guideline‐directed medical therapy (GDMT), which could potentially result in a better prognosis for patients at stage D. Traditional antihypertensive drugs are the cornerstones for the management of hypertension at stages A and B. Notably, calcium channel blockers (CCBs) are inferior to other drug classes for the preventing of HF, whereas diuretics are superior to others. For patients at stage C, GDMT is essential which also helps the control of BP. In particular, sodium‐glucose cotransporter‐2 (SGLT2) inhibitors are newer therapies recommended for the treatment of HF and presumably even in hypertension to prevent HF. Regarding patients at stage D, GDMT is also recommended if tolerable and measures should be taken to improve hemodynamics.     

Seroprevalence to common infectious abortifacient and infertility causing agents in the dairy herds of India

Background:Information on the prevalence of infectious agents in dairy farms forms the basis for formulating a suitable control strategy; especially in endemic situations. Aims:A cross-sectional study was undertaken to determine the prevalence of six economically important bovine diseases, causing reproductive disorders including bovine abortion in organized dairy herds in India. Methods:A total of 1,075 animals (cattle and buffaloes) from 09 dairy farms were screened by ELISA tests. Results:Bovine viral diarrhoea (BVD) was the most prevalent (56.5%) disease followed by infectious bovine rhinotracheitis (IBR) (45.4%). Prevalence of Q-fever (5.4%) and neosporosis (6.1%) were less on the farms. Although 16.3% of the samples turned positive for brucellosis, the contribution of calf-hood vaccination (B. abortus S19 vaccine) to the prevalence of antibodies cannot be ruled out. The overall prevalence of bovine anaplasmosis, known to cause sporadic abortions in dairy herds, was 34.1% in the 9 farms with a prevalence of less than 20% in 5 farms. Infection of multiple abortifacient (seroprevalence to more than two pathogens) was recorded in 56.8% of animals. A very strong association was observed between BVD and brucellosis (Odds ratio 14.2; P<0.001). Further, a positive association was also seen between seroprevalence of IBR and anaplasmosis, and neosporosis and Q fever (P<0.05). Conclusion:Viral diseases were found to be more common in the dairy herds than bacterial and protozoan diseases. Increased susceptibility of IBR seropositive cows to other bacterial and viral infections was observed.Key Words: Abortion, Bovine viral diarrhoea, Brucellosis, Infectious bovine rhinotracheitis, Neosporosis