Correlation between serum isoniazid concentration and therapeutic response in patients of pulmonary tuberculosis in Central India: A prospective observational study.

BACKGROUND: Tuberculosis (TB), an infectious disease caused by Mycobacterium tuberculosis is one of the top ten causes of death worldwide. Isoniazid (INH) is an important component of anti-tuberculosis therapy (ATT). Low isoniazid levels can serve as a risk factor for the development of treatment failure, relapse of disease and acquired secondary resistance. Hence, serum level of isoniazid becomes a critical factor in determining the treatment outcome of patients on ATT. This study aimed to evaluate the correlation between serum isoniazid concentration and therapeutic response in patients of pulmonary tuberculosis in Central India. METHODS: This was a prospective single cohort observational study conducted at a tertiary care hospital. Therapeutic response in newly diagnosed patients of pulmonary TB was determined based the microbiological, clinical and radiological parameters. Serum INH levels were estimated based on a spectrophotometric method using nano-spectrophotometer. RESULTS: In this study, patients had a significant improvement in treatment outcome as evident by a significant decrease in the TB score I at end of IP (p = 0.001) and a significant decline in the Timika score at end of CP (p = 0.001). Although all patients converted to sputum negative at end of CP, 20% remained positive at end of IP. Lower INH levels were seen in 13.3% of the study population. Higher INH levels were observed in sputum converters, patients with low TB score I and low Timika score, although no statistically significant difference was noted (p > 0.05). CONCLUSION: In this study, we could not find any statistically significant association between serum INH levels and therapeutic outcome of the patients. Further studies on a larger population could provide better understanding about the prevalence of low serum isoniazid levels among the Indian population and establish its relationship with therapeutic outcome. Also, the usage of a comparatively less expensive spectrophotometric method of analysis makes this feasible in almost every district hospital without the need of high-performance liquid chromatography which is costlier and needs more expertise.

Evidences and therapeutic advantages of donanemab in the treatment of early Alzheimer's disease.

The humanised monoclonal antibody donanemab is being developed to treat early onset Alzheimer's disease (AD). This drug targets N-truncated pyroglutamate amyloid-peptide at position 3 (N3pG), a modified form of deposited amyloid-peptide. The symptoms of Alzheimer's disease include gradual memory loss and other cognitive impairments. This disease is characterized by amyloid plaques, which are formed as a result of an accumulation of amyloid-(A-ß) peptides. Despite granting donanemab breakthrough therapy designation in June 2021, the FDA rejected donanemab's accelerated approval application in January 2023, due to inadequate safety data. According to the baseline amyloid level, the time to achieve plaque clearance (amyloid plaque level <24.1 centiloids) varied. Patients with higher baseline levels were more likely to achieve amyloid clearance. The safety of the drug was demonstrated by amyloid-related imaging abnormalities (ARIA), which ranged from 26.1 to 30.5 % in the studies. Clinical trial results have shown that donanemab delays cognitive and functional deterioration in patients with mild to moderate AD. However, it is not yet known whether donenameb offers therapeutic benefits that can change and improve the clinical condition of AD patients. To achieve significant clinical benefits in AD patients with cognitive impairment, further studies may be needed to investigate the interaction between A-ß plaque reduction and toxic tau levels.

Teplizumab: type 1 diabetes mellitus preventable?

Type 1 diabetes mellitus (T1DM) is an autoimmune condition driven by T lymphocytes that specifically declines the function of beta cells of pancreas. Immunological treatments aim to stop this decline in ß-cell function thus preventing TIDM. Although TIDM occur at any age, it is one of the most common chronic disorders in children. T1DM accounts for 5 to 10% of all cases of diabetes amounting 21-42 million affected persons. Teplizumab is a novel drug recently approved by the US FDA for the treatment of T1DM. This drug reduces abnormal glucose tolerance who are at high risk for developing T1DM and have antibodies suggesting an immunological attack on their pancreas. A 14-day infusion of the drug prevents T cells' attack of the insulin-producing cells of the pancreas. Adverse events due to teplizumab reported so far mild and of limited duration. This review gives an overview of the preclinical and clinical research on teplizumab for their role in new-onset T1DM.

Bispecific antibodies and its applications: a novel approach for targeting SARS-Cov-2.

The COVID-19 pandemic remains a severe global threat, with the world engulfed in the struggle against the disease's second or third waves, which are approaching frightening proportions in terms of cases and mortality in many nations. Despite the critical need for effective therapy, there is still uncertainty about the optimal practices for treating COVID-19 with various pharmaceutical approaches. This being third year, global immunity and eradication of SARS-CoV-2 is currently seems to be out of reach. Efforts to produce safe and effective vaccinations have shown promise, and progress is being made. Additional therapeutic modalities, as well as vaccine testing in children, are required for prophylaxis and treatment of high-risk individuals. As a result, neutralising antibodies and other comparable therapeutic options offer a lot of promise as immediate and direct antiviral medications. Bispecific antibodies offer a lot of potential in COVID-19 treatment because of their qualities including stability, small size and ease of manufacture. These can be used to control the virus's infection of the lungs because they are available in an inhalational form. To combat the COVID-19 pandemic, innovative approaches with effective nanobodies, high-expression yield and acceptable costs may be required.

An observational multi-centric COVID-19 sequelae study among health care workers.

Background: India has seen more than 43 million confirmed cases of COVID-19 as of April 2022, with a recovery rate of 98.8%, resulting in a large section of the population including the healthcare workers (HCWs), susceptible to develop post COVID sequelae. This study was carried out to assess the nature and prevalence of medical sequelae following COVID-19 infection, and risk factors, if any. Methods: This was an observational, multicenter cross-sectional study conducted at eight tertiary care centers. The consenting participants were HCWs between 12 and 52 weeks post discharge after COVID-19 infection. Data on demographics, medical history, clinical features of COVID-19 and various symptoms of COVID sequelae was collected through specific questionnaire. Finding: Mean age of the 679 eligible participants was 31.49 ± 9.54 years. The overall prevalence of COVID sequelae was 30.34%, with fatigue (11.5%) being the most common followed by insomnia (8.5%), difficulty in breathing during activity (6%) and pain in joints (5%). The odds of having any sequelae were significantly higher among participants who had moderate to severe COVID-19 (OR 6.51; 95% CI 3.46-12.23) and lower among males (OR 0.55; 95% CI 0.39-0.76). Besides these, other predictors for having sequelae were age (≥45 years), presence of any comorbidity (especially hypertension and asthma), category of HCW (non-doctors vs doctors) and hospitalisation due to COVID-19. Interpretation: Approximately one-third of the participants experienced COVID sequelae. Severity of COVID illness, female gender, advanced age, co-morbidity were significant risk factors for COVID sequelae. Funding: This work is a part of Indian Council for Medical Research (ICMR)- Rational Use of Medicines network. No additional financial support was received from ICMR to carry out the work, for study materials, medical writing, and APC.

Antimicrobials in COVID-19: strategies for treating a COVID-19 pandemic.

The COVID-19 pandemic continues to pose a serious global challenge, with the world engulfed in fighting second, third and fourth waves of the disease, which is reaching scary proportions in terms of cases and mortality in countries like India. Despite the urgent need of proven management protocols, there is still confusion about the best practices for treating COVID-19 with different pharmaceutical interventions. Antimicrobials are empirically used in COVID-19 patients. During the initial phase of this pandemic, hydroxychloroquine, ivermectin, azithromycin and doxycycline were widely suggested for possible prophylaxis or treatment for COVID-19 in outpatient as well as hospitalized settings. Various national and international guidelines recommended its use. However, cumulative evidence from subsequent clinical trials has revealed no significant clinical benefits in any setting, with the risk of adverse effects being high particularly in combination with azithromycin. Yet, there is continued use of antimicrobials particularly in outpatient settings which should be avoided because there is no justifiable rationale for doing so. Antimicrobial resistance (AMR) was one of the top problems for global public health before the coronavirus 2019 (COVID-19) pandemic began. AMR, which is already a difficult problem, must now be handled in the context of a changing healthcare sector.

Clinical implications of anti-idiotype antibodies in COVID-19.

Idiotype-based therapeutics have failed to deliver their promise, necessitating rethinking of the concept and its potential to develop a viable immunotherapy method. The idiotype based hypothesis is discussed in this paper in order to produce effective anti-idiotype vaccinations. Polyclonal anti-idiotype reagents have been shown to be more successful in animal models, and a better understanding of the immune response in humans supports the idea that polyclonal anti-idiotype vaccines will be more effective than monoclonal-based anti-idiotype vaccines. This innovative approach can be used to produce therapeutic antibodies in a Biotech-standard manner. The idiotype network has been tweaked in the lab to provide protection against a variety of microbiological diseases. Antibodies to image-idiotype antigens, both internal and non-internal, can elicit unique immune responses to antigens. The current outbreak of severe acute respiratory syndrome 2 (SARS-2) has presented a fantastic chance to use idiotype/anti-idiotype antibodies as a protective regimen, which might be used to treat COVID-19 patients. The development of various effective vaccinations has been crucial in the pandemic's management, but their effectiveness has been limited. In certain healthy people, the development of viral variations and vaccinations can be linked to rare off-target or hazardous effects, such as allergic responses, myocarditis and immune-mediated thrombosis and thrombocytopenia. Many of these occurrences are most likely immune-mediated. The current analysis reveals successful idiotype/anti-idiotype antibody uses in a variety of viral illnesses, emphazising their importance in the COVID-19 pandemic.

An overview of post COVID sequelae.

After healing from COVID-19, patients often experience a slew of symptoms known as post COVID-19 sequelae. Despite the fact that the SARS-CoV-2 pandemic is still ongoing, post-Covid-19 syndrome is already a difficult problem to address: long-term multiorgan sequelae, while frequently described, have yet to be systematized. As a result, post-Covid-19 syndrome can have a major influence on surviving patients' working capacity as well as their personal lives. The clinical spectrum and long-term course of this clinical entity must be better understood. Post-Covid syndrome affects a wide spectrum of individuals (16-87%), with pneumological and cognitive symptoms being the most common. Pulmonary fibrosis was the most common organic consequence seen in post-Covid patients. In conclusion, post-Covid-19 syndrome can have a major impact on the health of survivors. Working-age patients should seek rehabilitation and follow-up in interdisciplinary rehabilitation programmes. Given the pandemic's global extent, it's obvious that COVID-19-related healthcare demands will continue to climb for the foreseeable future. For COVID-19 survivors' long-term mental and physical health, present outpatient infrastructure will be utilised, scalable healthcare models will be built, and cross-disciplinary collaboration will be required.

Antibody-dependent enhancement of virus infection and disease: implications in COVID-19.

Antibody-dependent enhancement (ADE) can be seen in a variety of viruses. It has a deleterious impact on antibody treatment of viral infection. This effect was first discovered in the dengue virus, and it has since been discovered in the coronavirus. Over 213 million people have been affected by the rapid spread of the newly emerging coronavirus, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), which causes coronavirus disease 2019 (COVID-19). The new coronavirus offers a significant threat and has sparked widespread concern. ADE in dengue virus and other viruses are discussed with possible effect on COVID-19 treatment and vaccine development will need to consider this phenomenon to ensure it is mitigated and avoided altogether. In these case scenarios, the role of ADE and its clinical consequences remains to be explored for this newly detected virus.

Development and optimization of drug-loaded nanoemulsion system by phase inversion temperature (PIT) method using Box-Behnken design.

OBJECTIVE: The objective of the present investigation was to develop a stable and optimized drug-loaded nanoemulsion system using the phase inversion temperature (PIT) method. SIGNIFICANCE: The PIT method has been widely used for the development of food-grade nanoemulsion systems. For the first time, a simple and cost-effective, PIT method was used for the development of a stable drug-loaded nanoemulsion system. METHODS: Box-Behnken experimental design was used for the development of an optimized drug-loaded nanoemulsion system by the PIT method. The independent variables were optimized for responses by using the desirability function. The hydrophobic drug, benidipine was used as a modal drug. Optimized oil phase (blend of long-chain triglycerides oil, medium-chain triglycerides oil and essential oil) was used for the development of oil in water (O/W) nanoemulsion system. RESULTS: Optimum nanoemulsion formulation was stable, transparent and contained 50% of oil to surfactant percentage with a droplet size of 96.57 ± 1.61 nm. The optimum formulation also showed higher in-vitro drug diffusion from dialysis membrane as compared to the marketed formulation. Nanoemulsion droplets were observed as spherical in the transmission electron microscopy (TEM) images. Box-Behnken statistical analysis revealed that all the independent variables had a significant impact on characteristics of nanoemulsion and the predicated value of independent variables was found to be valid. CONCLUSION: It was concluded that the PIT method produces a stable and efficient drug-loaded nanoemulsion system. Further, the optimized oil phase can be used as an alternative to costly, commercial medium-chain triglycerides (MCT) oils, for the development of a stable nanoemulsion system.

Techniques for Formulation of Nanoemulsion Drug Delivery System: A Review.

Nanoemulsion drug delivery systems are advanced modes for delivering and improving the bioavailability of hydrophobic drugs and the drug which have high first pass metabolism. The nanoemulsion can be prepared by both high energy and low energy methods. High energy method includes high-pressure homogenization, microfluidization, and ultrasonication whereas low energy methods include the phase inversion emulsification method and the self-nanoemulsification method. Low energy methods should be preferred over high energy methods as these methods require less energy, so are more efficient and do not require any sophisticated instruments. However high energy methods are more favorable for food grade emulsion as they require lower quantities of surfactant than low energy methods. Techniques for formulation of nanoemulsion drug delivery system are overlapping in nature, especially in the case of low energy methods. In this review, we have classified different methods for formulation of nanoemulsion systems based on energy requirements, nature of phase inversion, and self-emulsification.

Dohra- a mixture of potent carcinogens.

BACKGROUND & OBJECTIVES: Dohra is a areca nut preparation used with or without tobacco in a few of the areas of Uttar Pradesh (UP), India. There is evidence that it causes potentially malignant disorders and oral cancer. This study was undertaken to provide information on dohra by searching through literature and also through a survey in three areas of Uttar Pradesh (UP), India. METHODS: The information on dohra was collected through literature search, study tour to different areas of UP, where group discussions with dohra vendors and with community members of different age group were done to obtain information. RESULTS: Dohra was prepared by the users for their personal use or prepared by small-scale industry for sale. It was available mostly in betel shops or any other store/kiosks and was also available in special dohra shops. Dohra was available in both dry and wet form. Its common constituents were areca nut, catechu (Acacia catechu), edible lime, peppermint (Mentha piperita), cardamom (Elettaria cardamomum) and some flavoring agents. Dohra was consumed as such or with tobacco. INTERPRETATION & CONCLUSIONS: Different varieties of Dohra were available such as sukha dohra, sukha mulethi dohra and geela dohra. Different processing methods for producing dohra existed. As dohra increases the risk of cancer, it needs to be banned or it should be sold in packets with the details of its constituents and also statutory warning about its adverse health effects.

Acrophialophora fusispora: an emerging agent of human mycoses. A report of 3 new clinical cases.

Acrophialophora fusispora is a soil-borne fungus, which is emerging as a human pathogen. Only four cases of human infection had been described previously. We describe three more cases, two from Europe and one from India. Since this fungus has been misidentified in several other cases, it is probably more frequent than first thought.