Design of experiment approach for formulating multi-unit colon-targeted drug delivery system: in vitro and in vivo studies.

OBJECTIVE: The objective of the present investigation was to develop systematically optimized multiunit formulation for colon targeted delivery of metronidazole (MTZ) by employing design of experiment (DoE) and evaluate it for in vitro as well as in vivo drug release study. METHODS: Core of mini-tablets of MTZ was prepared using drug along with suitable swelling agents to provide pH sensitive pulsatile drug delivery. Eudragit® S 100 (ES) and ethyl cellulose (EC) were used as coating polymers to prevent initial drug release in gastric region. The coating composition was systematically optimized using 3(2)-full factorial design and optimized formulation was evaluated in vitro and then in vivo, to confirm colon targeting ability of the developed system. Stability study of optimized formulation was performed for 6 months as per ICH guidelines. RESULTS: The optimized coating composition was selected from the results of design batches. The optimized formulation showed 6.99 ± 1.5% drug release up to 5 h and 100% drug release within 7.2 ± 0.2 h indicating pH sensitive pulsatile behavior of formulation. Similar drug release profile was observed while performing in vivo study in rabbits with a lag time of 4 h and Cmax of 190 ± 4.9 ng/ml being achieved after 7 h. Stability study indicated insignificant difference in properties of tablets and their drug release patterns. CONCLUSION: Optimization of coating composition (EC and ES) and thickness could offer pH sensitive pulsatile release of drugs at colon. Furthermore, in vivo results confirmed the successful development of colon targeted formulation of MTZ.

Post COVID sequelae among COVID-19 survivors: insights from the Indian National Clinical Registry for COVID-19.

INTRODUCTION: The effects of COVID-19 infection persist beyond the active phase. Comprehensive description and analysis of the post COVID sequelae in various population groups are critical to minimise the long-term morbidity and mortality associated with COVID-19. This analysis was conducted with an objective to estimate the frequency of post COVID sequelae and subsequently, design a framework for holistic management of post COVID morbidities. METHODS: Follow-up data collected as part of a registry-based observational study in 31 hospitals across India since September 2020-October 2022 were used for analysis. All consenting hospitalised patients with COVID-19 are telephonically followed up for up to 1 year post-discharge, using a prestructured form focused on symptom reporting. RESULTS: Dyspnoea, fatigue and mental health issues were reported among 18.6%, 10.5% and 9.3% of the 8042 participants at first follow-up of 30-60 days post-discharge, respectively, which reduced to 11.9%, 6.6% and 9%, respectively, at 1-year follow-up in 2192 participants. Patients who died within 90 days post-discharge were significantly older (adjusted OR (aOR): 1.02, 95% CI: 1.01, 1.03), with at least one comorbidity (aOR: 1.76, 95% CI: 1.31, 2.35), and a higher proportion had required intensive care unit admission during the initial hospitalisation due to COVID-19 (aOR: 1.49, 95% CI: 1.08, 2.06) and were discharged at WHO ordinal scale 6-7 (aOR: 49.13 95% CI: 25.43, 94.92). Anti-SARS-CoV-2 vaccination (at least one dose) was protective against such post-discharge mortality (aOR: 0.19, 95% CI: 0.01, 0.03). CONCLUSION: Hospitalised patients with COVID-19 experience a variety of long-term sequelae after discharge from hospitals which persists although in reduced proportions until 12 months post-discharge. Developing a holistic management framework with engagement of care outreach workers as well as teleconsultation is a way forward in effective management of post COVID morbidities as well as reducing mortality.

An epidemiological investigation of a cholera outbreak in peri-urban slum settlements of Gujarat, India.

Background: Cholera is an acute diarrhoeal disease caused by consuming contaminated food and water. The burden may remain underreported due to several issues like the low capacity of epidemiological surveillance systems, laboratory testing facilities, and socioeconomic disparities in urban slums. The disease has very short incubation period resulted in quick clustering of cases. Aim: A thorough outbreak investigation was carried out with the objective of strengthening the surveillance activity, finding out the sources of infection, and recommending necessary actions to control the outbreak immediately. Methods: An unusual increase in cases of diarrhoea was reported in slum area of Kalol town during the first week of July 2021. The stool samples were taken and investigated for confirmation and declaration of the outbreak by the Rapid Response Team. Time, place, and person distribution were carried out to generate a hypothesis and provide an immediate public health response to contain the outbreak. This study was conducted during the emergency public health response, no ethical approval was sought before the survey. Results: The cholera outbreak was confirmed when three out of five stool samples were positive for the bacterium V. cholerae O1 biotype El Tor serotype Ogawa. The overall attack rate and case fatality rate were 3.6% and 1.1%, respectively. The leakages caused the mixing of drainage water with the drinking water supply, which could be the possible cause of outbreak. Conclusion: The early identification and management of the cases, source reduction, health education on water chlorination, and hand hygiene were initiated based on our recommendations, which controlled the present outbreak.

An epidemiological investigation of a multisource outbreak of Crimean-Congo hemorrhagic fever in Gujarat.

It all started with the report from Shalby Hospital, Ahmedabad of two deaths with unusual presentation on Jan 18, 2011. Immediately investigations were carried out; to identify the etiological agent, source of outbreak, and mode of transmission, as well as, to propose a control measure based on the findings of the investigation. Extensive literature search, discussion with various scientific institutions, scientists and laboratory diagnosis suggested it to be case of Crimean-Congo Hemorrhagic Fever (CCHF). Accordingly a Case definition was worked out to further investigate the episode/outbreak. Door-to-door survey was carried out and hospital records were scrutinized. Collected data was analyzed in terms of time, place, and person. Laboratory investigation reports of case patients were also collated. We conducted environment investigation to find out the source of Infection. A total 13 case patients of CCHF were identified out of which 9 are positive for CCHF virus, 2 were negative for CCHF virus and in 2 instances, samples could not be taken because of early deaths of the cases. Among these 13 cases, 30.76% mortality rate was noted. Cases were reported in middle age group only. Environmental investigation also confirmed the presence of CCHF virus in Ticks. The outbreak was due to CCHF virus. State wide sero surveillance in animals is needed to identify prevalence of disease in Gujarat.

Comparison of motor vehicle-involved e-scooter and bicycle crashes using standardized crash typology.

INTRODUCTION: The market share of e-scooters in the United States has proliferated in cities: 86 million trips were made on shared e-scooters in 2019, a more than 100% increase compared to 2018. However, the interaction of e-scooters with other road users and infrastructure remains uncertain. METHOD: This study scrutinized 52 e-scooter and 79 bicycle police-reported crashes in Nashville, Tennessee, from April 2018 to April 2020 from the Tennessee Integrated Traffic Analysis Network (TITAN) database. We used descriptive analysis and a recent prototype version of the Pedestrian and Bicycle Crash Analysis Tool (PBCAT) to classify crashes based on the locations of the crashes relative to roadway segments or intersections, as well as the maneuver of the motor vehicle and e-scooter/bicycle relative to the motor vehicle. RESULTS: Two crash typologies can explain the majority of e-scooter crashes, while bicycle crashes are distributed over several crash typologies. Additionally, 1 in 10 e-scooter- and bicycle-motor vehicle crashes leads to the injury or fatality of the e-scooter rider or bicyclist. Furthermore, we noted statistically significant differences in spatial and temporal distribution, demographics, lighting conditions, and crash distance from home for e-scooter and bicycle crashes. CONCLUSIONS: The police crash report provides a comprehensive picture of e-scooter safety complementing existing literature. We found that e-scooter crash characteristics do not fully overlap with features of bicycle crashes. PRACTICAL IMPLICATIONS: A generalized engineering, education, and enforcement treatment to reduce and prevent e-scooter and bicycle crashes, injuries, and fatalities might not result in equal outcomes for each mode. More rigorous enforcement could be implemented to deter e-scooters riders under the age of 18 years and e-scooter safety campaigns could target female riders.

Design, development and optimization of a novel time and pH-dependent colon targeted drug delivery system.

The aim of present study was to develop a time- and pH-dependent system for delivering mesalamine to the colon. The system consists of the core tablet of mesalamine which is compression coated with hydroxypropyl methylcellulose (HPMC K4M) (time-dependent factor). This is then coated with pH-dependent polymer Eudragit L100. The simplex lattice design was adopted to optimize the independent variables i.e. amount of HPMC (X1), dextrose (X2) and polyvinyl pyrollidone (PVP) (X3) and to study their effect on the dependent variables i.e. lag time and time for 50% drug dissolution (t50). The results of the linear interactive model and graphical representation revealed that as the amount of HPMC increases, the lag time and t50 value also increases and as the amount of dextrose and PVP were increased the lag time and t50 value decreases.

Polysaccharides: a targeting strategy for colonic drug delivery.

INTRODUCTION: Colon targeting has gained increasing importance for the topical treatment of diseases of the colon, such as Crohn's disease, ulcerative colitis, colorectal cancer and amebiasis. Various strategies used for targeting drugs to the colon include formation of a prodrug, coating with time or pH-dependent polymers, use of colon-specific biodegradable polymers, osmotic systems and pressure-controlled drug delivery systems. Among the different approaches used, polysaccharides that are precisely activated by the physiological conditions of the colon hold great promise, as they provide improved site specificity and meet the desired therapeutic needs. AREAS COVERED: This review aims to summarize the natural and modified properties of polysaccharides that are responsible for their colon targeting abilities. Emphasis is placed on describing formulation approaches that use polysaccharides as a strategy for targeting drugs to the colon. EXPERT OPINION: Polysaccharide-based colon-targeted drug delivery systems are effective when they are precisely activated by the physiological conditions of the colon. Absence of enzymes during colonic disorders might hinder the activation of the delivery system. To guarantee delivery of the drug to the colon, it is preferable to combine polysaccharides with enteric or cellulose polymers.

Safety and antiretroviral effectiveness of concomitant use of rifampicin and efavirenz for antiretroviral-naive patients in India who are coinfected with tuberculosis and HIV-1.

OBJECTIVE: To study the safety and antiretroviral effectiveness of concomitant use of rifampicin and efavirenz for antiretroviral-naïve patients in India who are coinfected with tuberculosis (TB) and HIV-1. DESIGN AND METHODS: The study was an observational longitudinal cohort investigation. HIV-1-infected patients with CD4 cell counts of < or = 200/microL who attended the Infectious Disease Clinic of Sterling Hospital (Ahmedabad, India) from June 2001 to December 2002 were recruited for the study. Patients were divided in 2 groups: group A, patients with active TB (n = 126); and group B, patients without TB (n = 129). Group A patients were given efavirenz with 2 nucleoside reverse transcriptase inhibitors along with rifampicin-containing anti-TB treatment. Group B patients were treated for presenting opportunistic infections and started therapy with efavirenz plus 2 nucleoside reverse transcriptase inhibitors. The nucleoside reverse transcriptase inhibitors were either zidovudine and lamivudine (n = 30) or stavudine and lamivudine (n = 225). Patients self-funded their investigations and medications (antiretroviral, anti-TB, and other opportunistic infection-related agents). Indian generic medications were used. RESULTS: Efavirenz-based highly active antiretroviral therapy with rifampicin for HIV/TB-coinfected patients resulted in an immunologic response that was comparable with that of the group not receiving rifampicin. Median CD4 cell counts at baseline, 3 months, 6 months, and 9 months in group A were 84/microL (range, 5-200/microL), 225/microL (range, 26-528/microL), 251/microL (range, 65-775/microL), and 275/microL (range, 61-611/microL), respectively, and in group B, these values were 118/microL (range, 2-200/microL), 244/microL (range, 38-881/microL), 294/microL (range, 23-1322/microL), and 295/microL (range, 26-991/microL), respectively. The overall increase in CD4 cell count was greater in group A than in group B at 9 months (190 vs. 176/microL, respectively). Patients in both groups tolerated the therapy well; the adverse effects profile was comparable except that group A patients had a higher incidence of hepatitis than group B patients (13.49% vs. 0, respectively; P < 0.0001). CONCLUSION: Clinical and immunologic benefits are comparable for patients receiving efavirenz-based antiretroviral therapy with or without rifampicin.