Pfizer (India)

We present a calibrated model to scale-up a roller compaction process using minimal experimental data at small scales. The compression properties of three API-laden blends are evaluated for various drug loadings using a laboratory-scale roller compaction simulator (Int J Pharm 269:403-15, 2004). Using the generated blend compression properties, a calibrated model combining the Reynolds roller compaction model (Comput Chem Eng 34:1049-57 2010) and ribbon solid fraction measurements is developed to predict the ribbon solid fraction as a function of the roller compaction conditions (roll force and roll gap). The predictions of this model are compared with measurements from ribbons generated on the Gerteis minipactor at various scales using appropriate methods. The predicted solid fractions achieve good agreement with measured solid fractions for the three drug products. Further, the calibrated model is extended by developing a parametrized regression model where several API properties, formulation properties, and ribbon solid fraction predictions from the Reynolds model are taken as features to generate ribbon solid fractions for partially characterized active blends. The predictions of the hybrid model agree reasonably with measurements on ribbons produced on a Gerteis 3-W-Polygran. This hybrid model can then be deployed to run digital Design of Experiments (DOEs), which is then used to define operating ranges for the roller compaction of two drug products. This method enables the application of digital tools to aid the scale-up of fast-moving drug product processes using minimal experimental data.

Pneumococcal diseases caused by Streptococcus pneumoniae are vaccine-preventable diseases (VPDs); these are among the major causes of death worldwide. However, there is very little awareness of adult pneumococcal vaccination in India. In this cross-sectional, descriptive, questionnaire-based survey, we assessed the knowledge, attitude, and practice (KAP) of healthcare professionals (HCPs) to understand the barriers to pneumococcal vaccination in adults in India. Of the total 1,500 HCPs participating in the survey, most reported the prevalence of pneumococcal infections observed in routine practice to be 0-20%, commonly affecting patients aged >65 years. Factors such as awareness of disease burden, vaccine availability, and cost play an important role in HCPs' decision to advise the vaccination. Per HCPs, patient-level obstacles to vaccinations are limited information and understanding of vaccine safety and effectiveness, lack of affordability, and nonincentivized or nonmandatory vaccination, leading to a very low rate of pneumococcal vaccination in adults in India.

Pneumococcal disease (PD) remains a significant public health concern, particularly in adults aged >50 years and individuals with comorbidities. India bears approximately 23% of the global burden of community-acquired pneumonia (CAP). The highest rates of morbidity and mortality are linked to Streptococcus pneumoniae-related invasive pneumococcal disease (IPD) in adults aged >50 years. Despite the availability of effective vaccines, including the 13-valent pneumococcal conjugate vaccine (PCV13) and the 23-valent pneumococcal polysaccharide vaccine (PPSV23), adult vaccination coverage in India remains suboptimal. A key barrier to adult vaccination is the lack of awareness, with over 80% of adults being unaware of the vaccines available for them. Many people still believe that vaccines are only for children, highlighting the need for better awareness among patients and healthcare providers. Additionally, the absence of dedicated adult vaccination centres limits access, making it crucial to establish such centres and involve trained personnel such as doctors, nurses, and pharmacists in raising awareness. Often, healthcare professionals (HCPs) do not consider underlying comorbidities as risk factors for the development of pneumococcal disease. Additionally, the evidence on vaccine efficacy is scattered. Given these challenges, there is a critical need for a comprehensive review synthesizing the available evidence on pneumococcal vaccination in high-risk and at-risk populations. This review aims to consolidate the most recent findings on the effectiveness of pneumococcal vaccination practices, highlighting the importance of adhering to vaccination guidelines to reduce the public health burden of PD.

ABSTRACT Background: Linear Discriminant Analysis (LDA) is a powerful and widely used technique for classification with correlated variables. Principal Components (PCs) group these variables into linear combinations and produce independent variables. The LDA on these PC’s may provide better classification accuracy in clinical diagnostics than on usual measurements. Methodology: Two datasets were utilized for demonstration: one from a Sudden Sensorineural Hearing Loss (SSNHL) case-control study and the other from a Gall Bladder (GB) case-control study. Linear Discriminant Analysis (LDA) was conducted on the actual correlated measured variables for group classification, as well as on the derived principal component variables, to compare their classification accuracies. Performance metrics including Sensitivity, Specificity, Positive Predictive Value (PPV), Negative Predictive Value (NPV), Classification Accuracy, and F1 Score were assessed. For validation, a third simulated dataset was employed. Additionally, LDA was performed on each dataset using eigenvectors of the control group applied to the cases and vice versa, revealing a strong agreement in classification as measured by the kappa statistic. Results: When LDA was applied to the actual lipid measurements in the SSNHL dataset, the classification accuracy was 57.2%, and the F1 score was 39.7%. However, when LDA was performed using principal components (PCs), the classification accuracy markedly improved to 99.2%, with an F1 score of 98.5%. Similarly, for the GB cancer dataset, the classification accuracy and F1 score were initially 77.2% and 77.3%, respectively. Upon applying LDA with the PCs, these metrics were significantly enhanced to 98.4% and 98.3%, respectively. For the simulated dataset, both the classification accuracy and F1 score were 99.1%. The study also demonstrated that the classification accuracy and F1 score remained consistent regardless of whether the eigenvectors from the cases or controls were used to classify new subjects (Kappa Statistic = 0.962, P < 0.001). Conclusion: In group separation, utilizing principal components significantly improves classification accuracy and overall performance metrics, outperforming the use of the original correlated predictors.

ABSTRACTBackgroundEtrasimod is an oral, once‐daily (q.d.), selective sphingosine 1‐phosphate (S1P)1,4,5 receptor modulator for the treatment of moderately to severely active ulcerative colitis (UC). Unlike the S1P receptor modulator ozanimod, etrasimod does not have a molecular structure to inhibit monoamine oxidase (MAO). Coadministration of drugs that inhibit MAO with opioids and antidepressants may increase the risk of adverse events (AEs).AimsThis post hoc analysis evaluated the incidence of AEs potentially related to serotonin syndrome in patients taking etrasimod and concomitant opioids or antidepressants in the Phase 3 ELEVATE UC 52 and ELEVATE UC 12 trials.MethodsSafety data pooled from both trials were analysed in subgroups of patients receiving etrasimod 2 mg q.d. (up to 52 weeks of exposure) with/without concomitant opioids or antidepressants. We report the proportions of patients who had ≥ 1 concurrent AE potentially associated with serotonin syndrome, including hypertension‐related events.ResultsAmong 527 patients receiving etrasimod, 77 (14.6%) and 35 (6.6%) were taking concomitant opioids or antidepressants, respectively. The incidence of AEs potentially related to serotonin syndrome, including hypertension‐related AEs, was low (≤ 8.6%) and generally comparable in all subgroups. No reported AEs were serious or led to treatment discontinuation among patients taking these concomitant medications.ConclusionsThe incidence of AEs was low and comparable in patients receiving etrasimod with or without concomitant opioids or antidepressants. This analysis further supports the low likelihood of clinically relevant drug–drug interactions between etrasimod and medications commonly prescribed to patients with UC, such as opioids or antidepressants.(ClinicalTrials.gov: NCT03945188; NCT03996369).

Abstract Objectives Infections remain a leading cause of mortality in patients with sickle cell disease (SCD) due to increased exposure to pathogens, malnutrition, and lower vaccination rates. This survey assessed infection risk awareness and identified knowledge gaps and barriers to vaccination among Indian patients with SCD. Methods A cross-sectional survey was conducted (between November 2023 and April 2024) in patients (aged 3-65 years) using a 6-domain questionnaire: (1) patient demographic and clinical characteristics; (2) level of awareness about infections; (3) surgical splenectomy; (4) awareness of vaccines; (5) awareness of the importance of vaccination, nutrition, hygiene, and the use of antibiotics; and (6) vaccines recommended by doctors. Participants were recruited through convenience sampling, with the inclusion criteria requiring a willingness to participate, a confirmed SCD diagnosis, and the ability to sign the electronic informed consent. The ethics committee approved the study. Results Out of 500 participants, 201 respondents participated in the study. The majority (85.1%) of participants were aware of the increased risk of severe infections with SCD, but only 22.4% knew about pneumococcal infections and associated complications. Approximately 45.8% of the respondents had been hospitalized due to pneumonia or other respiratory tract infections, emphasizing the seriousness of these complications. A significant portion of the respondents were unfamiliar with vaccines for meningococcal disease (82.6%), hepatitis B (67.2%), pneumococcal disease (73.1%), and influenza (72.1%). Conclusion The survey identified significant knowledge gaps in understanding the risk of infection and the role of vaccination among patients with SCD in India, contributing to vaccine hesitancy.

BackgroundEtrasimod is an oral, once-daily (QD), selective sphingosine 1-phosphate1,4,5 receptor modulator for the treatment of moderately to severely active ulcerative colitis (UC). Here, we evaluate the impact of etrasimod 2 mg QD on health-related quality of life (HRQoL) in patients with UC.MethodsThis post hoc analysis used data from the Phase 3 randomized controlled trials, ELEVATE UC 52 and ELEVATE UC 12. HRQoL measures included: Inflammatory Bowel Disease Questionnaire (IBDQ), 36-Item Short Form Survey (SF-36), and Work Productivity and Activity Impairment Questionnaire: Ulcerative Colitis (WPAI:UC) completed at baseline, Week 12 (both trials), and Week 52 (ELEVATE UC 52 only). For IBDQ analyses, patients were stratified by prior exposure to biologics/Janus kinase inhibitors (JAKi) and baseline modified Mayo score (MMS; 4-6 or 7-9).ResultsGenerally, significantly greater proportions of patients receiving etrasimod (N = 527) vs placebo (N = 260) achieved IBDQ remission (IBDQ total score ≥170) and IBDQ response (IBDQ total score increase from baseline ≥16), with significant improvement in all IBDQ domain scores at Week 12 and maintained through Week 52. Significant differences in IBDQ remission and IBDQ response rates between etrasimod and placebo were more consistent among biologic/JAKi-naive patients vs those who were biologic/JAKi-experienced and in those with baseline MMS 7-9 vs 4-6. Significant improvements were observed in several SF-36 domain and summary scores and WPAI:UC domain scores at Week 12 and Week 52.ConclusionsEtrasimod 2 mg QD demonstrated significant and clinically meaningful improvements across multiple HRQoL measures, including WPAI, vs placebo.Clinical Trial RegistrationClinicalTrials.gov: NCT03945188; NCT03996369