Can the Emergency Medical Service (EMS) System Help in Improving the Healthcare Access - Evidence from Maharashtra EMS.

Background: For many people in the remote regions of India, medical help is inaccessible as 66% of rural Indians do not have access to critical medicine and 31% of the population travel more than 30 km seeking health care in rural India. Timely non-availability of doctors in healthcare facilities, especially in primary health centers (PHCs), leads to more dependency on the private healthcare practitioners for the out-patient department services. This needs immediate attention. Materials and Methods: The healthcare authority in Maharashtra has allowed doctors in 108 emergency ambulances to provide consulting services. The current study is based on the total consultations managed by the doctors on-board on the 108 ambulances in the state of Maharashtra in the years 2020, 2021, and 2022. The data are procured from the state-run Emergency Response Centre, and the analysis is done by using the basic statistical technique in MS Excel and SPSS16.0. Results: More than 9.35 lakh medical consultations were provided with an average 856 consultations per ambulance in the year 2022, showing a significant growth of 452% over the consultations in 2020. The base location of the 32% ambulance (298) in the PHCs has improved the round the clock accessibility in 16% of the total PHCs in the state of Maharashtra. Conclusion: The availability of the doctors in the state-run emergency ambulances for general healthcare services has improved the adherence of Indian Public Health Standards, and such practice must be examined for implementation in other states.

Prognostic potential of markers of bone turnover in delayed-healing tibial diaphyseal fractures.

INTRODUCTION: Clinical and radiographic examinations detect delayed or nonunion only after the event has occurred. Biochemical markers of bone turnover (BTMs) are promising laboratory tools that offer an early insight into the likelihood of delayed union. We hypothesized that BTMs display temporal variations following fractures and the behavior of BTMs differ between normal and delayed union of fractures. METHODS: This was a prospective study of patients with closed fracture of tibia treated with intramedullary, interlocking nailing. BTM assays (NTX, BSAP, P1NP and osteocalcin) and clinical and radiographic assessments were obtained preoperatively and postoperatively at 8,12, 24, 36 and 72 weeks. Temporal trend of elevation of serum levels of BTMs post-fracture was the primary assessment criterion and radiographic and clinical assessment of fracture union were the secondary assessment criteria. RESULTS: The average time for fracture union was 15.24 weeks (range 15-19 weeks). The values of both bone formation and resorption markers peaked at the eighth week following the fracture. Resorption markers returned to baseline by 36 weeks. Among the formation markers, BSAP levels showed the smallest increase and returned to baseline earlier (36 weeks) than P1NP and osteocalcin (72 weeks). P1NP showed the most dramatic change, increasing to 2.5 times the mean baseline level at 8 weeks in normal union of fractures. The levels of bone formation markers (BSAP, OC, PINP) were significantly lower in patients with delayed union. There was no significant difference in the levels of the resorption marker (NTX) between normal and delayed union patients. CONCLUSION: Serial monitoring of biochemical markers of bone turnover can be used as an adjunct to clinical and radiological observations to predict delayed union LEVEL OF EVIDENCE: Level 2 (prospective observational study).

Synthesis and Biological Evaluation of New Hydrazone Derivatives of Quinoline and Their Cu(II) and Zn(II) Complexes against Mycobacterium tuberculosis.

A new series of quinoline hydrazone derivatives and their metal complexes have been synthesized and their biological properties have been evaluated against Mycobacterium tuberculosis (H37 RV strain). Most of the newly synthesized compounds displayed 100% inhibitory activity at a concentration of 6.25-25 µg/mL, against Mycobacterium tuberculosis. Fluorescence properties of all the synthesized compounds have been studied.

Design, synthesis and pharmacological evaluation of novel polycyclic heteroarene ethers as PDE10A inhibitors: part II.

We report the design and synthesis of novel pyrrolo[3,2-b]quinoline containing heteroarene ethers as PDE10A inhibitors with good to excellent potency, selectivity and metabolic stability. Further optimization of this primary series resulted in the identification of 1-methyl-3-(4-{[3-(pyridine-4-yl)pyrazin-2-yl]oxy}phenyl)-1H-pyrrolo[3,2-b]pyridine 13a with good hPDE10A potency (IC50: 6.3 nM), excellent selectivity over other related PDEs and desirable physicochemical properties. The compound exhibited high peripheral and adequate brain levels upon oral dosing in rodents. The compound also showed excellent efficacy in multiple preclinical animal models related to psychiatric disorders, particularly schizophrenia.

Design, synthesis and pharmacological evaluation of novel polycyclic heteroarene ethers as PDE10A inhibitors: Part I.

We report analogue-based rational design and synthesis of two novel series of polycyclic heteroarenes, pyrrolo[3,2-b]quinolines and pyrido[2,3-b]indoles, tethered to a biaryl system by a methyl-, ethyl- or propyl ether as PDE10A inhibitors. A number of analogues were prepared with variable chain length and evaluated for their ability to block PDE10A enzyme using a radiometric assay. Detailed SAR analyses revealed that compounds with an ethyl ether linker are superior in potency compared to compounds with methyl or propyl ether linkers. These compounds, in general, showed poor metabolic stability in rat and human liver microsomes. The metabolic profile of one of the potent compounds was studied in detail to identify metabolic liabilities of these compounds. Structural modifications were carried out that resulted in improved metabolic stability without significant loss of potency.