Lucknow, India

Predict Tooth Wear

Upfront Surgery Vs Induction Chemotherapy Followed By Surgery In Oral Cancers:

Cytomegalovirus Reactivation in ICU Patients Requiring Prolong Mechanical Ventilation

Cytomegalovirus (CMV) is a latent infection virus that is widespread in the population. CMV may reactivate under certain circumstances, and its hazardous nature has been proven, especially in immunosuppressed patients. However, several studies have found that CMV reactivation also exists in immunocompetent patients with a critical illness. Among those patients, the incidence of CMV reactivation, which is more than 30%, is associated with increased duration of hospital stay, and higher mortality. Traditionally, critically ill patients have been considered immunocompetent but the presence of sepsis and its immunomodulatory effects may lead to reactivation of dormant viral infections. Sepsis due to its immunomodulatory effects may lead to reactivation of CMV due to the release of pro-inflammatory cytokines such as TNF-alpha and IL-1beta which has the ability to activate several transcription factors contributing in the CMV reactivation. Clari et al showed that CMV infection in critically ill patients was consistently associated with undetectable IFN-γ T cell responses within the first 2 days of admission to the ICU, and that viral load was inversely related to IFN-γ T cell responses. Similar results were also found by Venet et al that septic patients display immune system paralysis, reduced Th1 cell function, increased IL-10 production (anti-inflammatory), global lymphopenia affecting natural killer cells (NK) quantitatively and qualitatively related to their interferon production. Studies have documented significantly higher organ failure rates and mortality in critically ill patients with CMV reactivation. Phillips Lachance et al performed a systematic review to investigate the association between CMV reactivation and clinical outcomes in immunocompetent critically ill patients. In this review, twenty-two studies were included. CMV reactivation was associated with increased ICU mortality, overall mortality, duration of mechanical ventilation, nosocomial infections, ICU length of stay. CMV reactivation has also been studied in specific critically ill cohorts, exhibiting there impact on mortality. David S Y Yong et al studied the effect of CMV reactivation on mortality in immunocompetent acute respiratory distress syndrome (ARDS) patients. Of 399 ARDS patients, 68 % were CMV seropositive and reactivation occurred in 27 % of them which was associated with overall increased ICU mortality. In another study among septic shock cohort (329 patients), herpesvirus reactivations were documented in 68% patients without prior immunodeficiency and concluded that reactivations could be independently associated with mortality. However, currently no study is currently available investigating the CMV reactivation and it's kinetics during critical illness in non-immunosuppressed patients requiring prolonged mechanical ventilation. In this planned observational study, the investigators aimed to find out the prevalence of CMV reactivation, viral load and it's association with the severity of illness in non-immunosuppressed ICU patients requiring prolong mechanical ventilation. All adult ICU patients requiring prolong mechanical ventilation will be considered for inclusion and will be screened for the presence of Anti CMV IgG antibodies in blood. If patient is IgG seropositive and meets inclusion/ exclusion criteria, then they will be included in study and will be followed up for CMV reactivation during their ICU stay (on weekly basis till maximum 28-days after the initiation of mechanical ventilation). In patients who had CMV reactivation, viral load kinetics will be further followed up on weekly basis for the next 3 weeks or ICU discharged (whichever comes first). Blood samples will be collected in all; while tracheal aspirate sample will be collected in whom who had an artificial airway.

A Research Study to See How Much CagriSema (1.0 mg Once Weekly) Lowers Blood Sugar and Body Weight Compared to Tirzepatide (5 mg Once Weekly) in People With Type 2 Diabetes Treated With Metformin, SGLT2 Inhibitor or Both

Study of Efficacy and Safety of Iptacopan in Patients With C3 Glomerulopathy.

The purpose of this study is to evaluate the efficacy and safety of iptacopan compared to placebo and standard of care in patients with native C3G. CLNP023B12301 is a Phase 3 pivotal trial for registration of iptacopan in C3G. The study aims to determine the reduction in UPCR and improvement in eGFR in participants treated with iptacopan compared to placebo, as well as the proportion of participants who achieve a composite renal endpoint consisting of eGFR and UPCR elements. These effects of iptacopan in conjunction with increases in serum C3 levels will provide support for an iptacopan profile that includes stabilization of eGFR, clinically meaningful reductions in proteinuria and inhibition of the complement AP. Kidney biopsies will be performed in adult participants to evaluate histopathological improvements in immunofluorescence and light microscopy that support these functional benefits of iptacopan.

Comparative Diagnostic Yield of Endobronchial Cryo Biopsy Vs Forceps Biopsy in Patients with Suspected Sarcoidosis

The study will consist of consecutive patients undergoing routine EBUS-TBNA for suspected sarcoidosis AND subsequently confirmed on clinical, radiology and non-caseating granuloma on histopathology. . 150 patients will be randomized into either cryo-EBB or forceps biopsy from a computer-generated randomized table. 75 patients will be included in each arm. Determination of the sample size was based on the primary outcome of the proportion of diagnostic yield between two independent groups. Using the z test of proportion for two independent samples to detect a one-sided target difference between the groups of 15% with 85% power and a level of significance of 5%, each group required 69 participants. With an expected attrition rate of 8-10%, we capped the total number of participants in each arm of the study at 75. Subsequent to EBUS-TBNA, video bronchoscopy will be performed to obtain the endobronchial biopsy by using either forceps or cryo-proble. Three endobronchial biopsies from primary carina and both left and right secondary carina will be taken in each patients irrespective of the endobronchial abnormality. Additional biopsies will be taken from any endobronchial abnormality detected during the examination. The biopsy samples will be fixed in neutral 10% buffered formalin. In the pathology laboratory the sample will be embedded in paraffin followed by staining with hematoxylin and eosin or special stain according to the requirement to allow an exact classification. The samples will be analyzed and assessed by one pathologist according to common standards describing adequacy of the sample, crush artifacts, specific diagnosis. The pathologist will be blinded from the biopsy technique that has been used. Diagnostic yield will be defined by the ability to make an adequate diagnosis on histopathological examination of the sampled tissue. Diagnostic yield will be calculated for each biopsy technique as the number of diagnostic procedures divided by number of non-diagnostic procedures plus the number of diagnostic procedures.

Endothelin Receptor Antagonism with Ambrisentan to Treat Hepatorenal Syndrome

A Multicenter Observational Registry to Evaluate Safety and Performance of Vivo ISAR (SECURE Global Registry)

This study is a prospective, observational, multi-country, multi-Centre, single-arm registry designed to evaluate the clinical safety and performance of VIVO ISAR, Polymer Free Sirolimus Eluting Coronary Stent System. The study population is made up of subjects who have undergone PCI using VIVO ISAR and are receiving standard of care short DAPT treatment (≤ 3 months) . Subjects will be screened by site teams and offered the opportunity to participate in the registry after their procedure. Rationale for this study is to evaluate clinical outcomes and collect data of the Polymer Free Sirolimus Eluting Coronary Stent in real world CAD patients with follow-up at 1 month, 3 months and 12 months. All medications and procedures to be used/ performed in this registry are commonly used/performed for clinical indications as part of standard of care and have well-defined safety profiles. The study does not influence the choice of device utilized nor does it alter the routine standard of care. After a patient has been treated with the Vivo ISAR, informed consent will be requested and the eligible patient will be registered in the study. Baseline data will be completed using medical notes. All recruited subjects will then be followed as per routine practice together with telephonic follow-up at 30 days, 3 months and 12 months from the baseline PCI procedure date. The 30 day, 3 months and 12 month telephonic follow up will consist of a verbally report of the DAPT anticoagulation medications continued, about any lab assessments that might have happened, recording of any adverse events, and any interventional treatment that has occurred since previous contact.

Disseminated Intravascular Coagulation (DIC) Score and Organ Dysfunction in Septic Shock Patients

Background and rationale for the study Septic shock patients and DIC commonly coexist and progression to overt DIC is serial process. Sepsis and septic shock condition is a prevalent condition as studied by Stephen et al especially in low medium income countries with incidence of 31.5 million per year. Divatia JV et al found incidence of severe sepsis and septic shock 28.3% in study covering different ICUs in India. Rhee C et al found incidence of severe sepsis and septic shock as high as 52.8%. Marx,G., et al observed incidence of septic shock in German ICUs to be 12.6 % whereas Mulatu HA et al found it to be 26.5% in African ICUs. Also, septic shock has very high mortality rates. In India, Divatia JV et al observed that mortality in septic shock patients was 53.4 % and Chatterjee et al observed it to be 62.8%. Mortality rate according to different geographical locations have variations but still consistently high: 22.8% mortality in Greece ICUs, 79% in Turkish ICUs observed by Baykara et al in Japan 27%, in Taiwan 43.8%, in China 51.9 %. Disseminated intravascular coagulation (DIC) is prevalent entity in sepsis/septic shock patients as observed in different studies: Ko BS et al observed prevalence to be 17.6%, Dhainut J.F et al found it to be 28.9%, Saito et al in Japan to be 29% and J Kienast et al in Germany observed it to be 40.7%. DIC itself has high mortality: 29.1%, 40.7%, 50% and as high as 56%. Mortality rates further increases when DIC co exists with severe sepsis as seen 67.6% by Ogura H et al, 44.6% vs. 55.3 % without and with DIC respectively seen by Hayakawa et al, 11.7% vs. 54.1% without and with DIC respectively seen by Solanki D et al . Septic shock patients are at high risk of develop multiple organ dysfunction (MODS). In fact, both DIC score and organ dysfunction were found increased in patients with septic shock as compared to patients without septic shock so the resultant higher mortality and MODS. Studies also found mortality risk further increases in septic shock patients with the presence of DIC. Methodology Study design: This prospective observational study will be conducted at the Department of Critical Care Medicine in collaboration with the Department of Haematology, SGPGIMS, Lucknow after the approval from the Institutional Ethics Committee (IEC) Study protocol: During the study period, all adult ICU participants with the diagnosis of septic shock will be considered, as per inclusion and exclusion criteria, DIC scores and SOFA scores will be calculated and followed-up for the 14 days. Definition and scores: Septic shock is defined as a subset of sepsis in which particularly profound circulatory, cellular, and metabolic abnormalities are associated with a greater risk of mortality than with sepsis alone. Participants with septic shock can be clinically identified by a vasopressor requirement to maintain a mean arterial pressure of 65 mmHg or greater and serum lactate level greater than 2mmol/L in the absence of hypovolemia (Sepsis -3 recommendations). DIC score for overt and non-overt DIC will be used as per International Society on Thrombosis and Haemostasis. (ISTH) Sample collection for DIC score calculation Blood samples will be collected as below Baseline sampling : At inclusion Second sampling : At 72 hours ±12 hours Third sampling : After 72 hours (±12 hours) of second sampling. Data collections: Demographic and relevant clinical characteristics of included participants will be collected on structured case report form. Sample size and statistical analysis: Based on the study conducted by the H Ogura et al. (2014), SOFA score was during the day 1 (10.7±3.8) to day 4 (8.9±5.0) [Change in score: Cohen d effect size =0.398). At minimum two-sided 95% confidence and 80% power of the study, minimum estimated sample size for the study is 52. Finally minimum 60 participants to be enrolled in the study. Sample size was estimated using software G*power version 3.1.9.7. Descriptive statistics of the continuous variables will be presented as mean ± SD / Median (IQR) whereas categorical variables in Frequency (%). To compare the observations between baseline to follow-up data (quantitative variable), with the outcomes, two-way repeated measures ANOVA will be used. One way Analysis of covariance to be used to compare the post observations into outcomes after the adjusting the baseline measurements. Change in the SOFA score with change in the DIC score to be compared using spearman rank correlation coefficient. Decision trees analysis including Classification and regression trees to be used to identify the factors and subgroups predicting the outcomes. General linear regression model to be used to identify the factors predicting the change in the SOFA score. A p value < 0.05 to be considered as statistically significant. Statistical analysis to be performed using software "Statistical package for social sciences version 23 (SPSS-23) and MedCalc.

Low Birthweight and Preterm Infant Feeding Trial and Supportive Care Package: Implementation Research

AIM: To improve feeding and growth outcomes among low birthweight (LBW; <2.5kg) or preterm (<37 weeks gestational age) infants admitted to NICUs in India, Malawi, and Tanzania by (1) supporting the initiation, establishment, and maintenance of maternal lactation and prioritized provision of human milk, Kangaroo Mother Care (KMC) and appropriate water, sanitation and hygiene (WASH) practices; and (2) facilitating feeding counseling at home post-discharge from the facility. OBJECTIVES: To implement and evaluate a co-designed facility-based lactation support/management and feeding counseling + KMC + WASH package (FB-FSP+: Facility-Based Feeding Support Package Plus) for LBW or preterm infants admitted to the neonatal intensive care unit (NICU) and their families from birth to discharge. To implement and evaluate a co-designed, scalable transition-to-home lactation support/management and feeding counseling + KMC + WASH package (TTH-FSP+: Transition to Home Feeding Support Package Plus) for LBW or preterm infants discharged home from the NICU in India and their mothers/families. STUDY DESIGN: This multi-site, mixed-methods adaptive implementation science research study will collect quantitative and qualitative data to evaluate the training of providers, the impact of each intervention on key infant feeding, growth, and other health outcomes, the feasibility and acceptability of each intervention for mothers and providers, and the overall experience of mother-infant dyads. Investigators will apply the RE-AIM framework to unpack Reach, Effectiveness, Adoption, Implementation, and Maintenance. Findings will lead to recommendations for iteration and scale-up of the FB- and TTH-FSP+. Investigators will evaluate multiple primary and secondary quantitative outcomes to assess effectiveness. SAMPLE SIZE: Overall, investigators will enroll 695 participants, 50% in India, 50% in Malawi & Tanzania: up to 520 infants (463 mothers assuming 11% twin rate), 110 mothers (in-depth interviews), 30 healthcare providers, 15 study staff, and 20 community providers. Objective 1: A sample of 80 infants and their mothers is sufficient to detect the effect sizes for each of the primary and secondary outcomes with 80% power, 0.05 alpha. Smaller improvements in key outcomes for the pre/post analysis can be detected for the implementation study (n=80 baseline vs 240 implementation) compared to the pilot study (n=80 baseline vs 80 pilot). Objective 2: Investigators will conduct up to 40 in-depth interviews (IDIs) with providers and 20 with mothers. A sample of 60 infants and their mothers is sufficient to detect the effect sizes for each of the primary and secondary outcomes with 80% power, 0.05 alpha. ENROLLMENT: OBJECTIVE 1 (FB-FSP+) Mother-infant dyads (quantitative): All infants born in a study facility will receive immediate maternal and newborn care per World Health Organization recommendations, including breast milk feeding/expression support within 1 hour. Inborn LBW or preterm infants admitted to the NICU will be screened for eligibility and their mothers consented. Mothers (qualitative): Mothers will be recruited and consented before discharge from study facilities. Research Nurses (qualitative): Research nurses providing the intervention will be consented prior to IDIs. Healthcare providers (quantitative): Appropriate labor ward, NICU, and step-down ward providers will be identified by facility and NICU leadership/staff to implement the FB-FSP+ and consented. Healthcare providers (qualitative): NICU providers will be recruited and consented during study implementation. ENROLLMENT FOR OBJECTIVE 2 (TTH-FSP+, INDIA ONLY) Mothers (quantitative): Mothers exposed to Objective 1 will be recruited around the time of discharge and consented. Community providers (quantitative): Community providers within a given cadre(s) who provide care to LBW or preterm infants within the catchment area will be recruited and consented. Mothers (qualitative): Mothers receiving the TTH-FSP+ will be recruited and consented during study visits. Community providers (qualitative): Community providers will be recruited and consented after beginning implementation of the TTH-FSP+. STUDY INTERVENTION: The FB-FSP+ and the TTH-FSP+ will build on an existing Specialized Lactation Support and Newborn Nutrition for the Small and Sick Newborn Training curriculum to include support for KMC and WASH. The FSP+ will include a training guide, Standard Operating Procedures and job aids specific to each hospital's and community's needs identified through co-design workshops with key stakeholders that utilize human-centered design methods. DATA COLLECTION FOR OBJECTIVE 1 (FB-FSP+) Data will be collected in 3 phases. Baseline data collection will occur over 6 weeks among eligible mother-infant dyads prior to introducing the intervention. Baseline will be the comparison group for the implementation research study and the pilot study. A 6-week pilot study conducted by research staff in each country will assess the acceptability, feasibility, and impact of the ideal delivery of the FB-FSP+. A quick final iteration of the FSP+ will occur before implementing in phase 3. The FB-FSP+ will be implemented for 1 year using an adaptive models-based approach. Three consecutive models will be implemented for 4 months each. Investigators will collect panel data at 1.5, 5.5, and 10.5 months after the start of implementation for 1.5 months to assess effectiveness and inform model adaptations. Different mother-infant dyads will be surveyed at each time point to assess differences in the impact of implementation over time. Prior to start, healthcare providers will be selected and trained to implement the FSP+ as part of their regular workload. They will complete a knowledge, attitudes, and practices (KAP) survey on lactation support/management, feeding, KMC, and WASH (1) prior to training, (2) immediately post-training, and (3) 6 months post-training. Data collection with mother-infant dyads will take 1-2 hours at one time point between NICU admission and day of discharge during panel data collection. Mothers will be asked about their demographics, pregnancy history, health, and their infants' health. Study staff will take the mother's weight and height, the infants' weight, length, head circumference and mid-upper arm circumference (MUAC), and data from mothers' and infants' charts. A subset of 60 mothers exposed to the FB-FSP+ will be interviewed by study staff, 30 of whom whose babies received care in the NICU within 1.5 months of implementation and another 30 whose babies received care within 5.5 months. Interviews will explore mothers' experiences and perceptions of the acceptability and feasibility of the FB-FSP+. A subset of 15-30 healthcare providers across all sites will be interviewed per time point at 1.5 months and 5.5 months after implementing the FB-FSP+. Investigators aim to interview the same providers at both times to understand how implementation has affected their practices, skills and workload over time. Interviews will explore acceptability and feasibility of the FB-FSP+ and barriers and facilitators to its implementation. DATA COLLECTION FOR OBJECTIVE 2 (TTH-FSP+, INDIA ONLY) Baseline data collection will occur before implementing the TTH-FSP+ among mothers exposed to the FB-FSP+ and discharged home. Data collection points will be on the day of discharge and at 2 and 6 weeks post-discharge. The TTH-FSP+ will be implemented for 6 months, using an adaptive models-based approach. Three models will be consecutively implemented for 3 months each. Quantitative and qualitative analysis will begin after 2 months to inform model adaptations. Data collection points will be on the day of discharge and at 2 and 6 weeks post-discharge. Community providers will be trained to deliver the TTH-FSP+ for dyads residing in a defined catchment area once they are discharged home. Community providers will complete a KAP survey on feeding counseling, KMC, and WASH at three timepoints: (1) just prior to training, (2) immediately post-training, and (3) 6 months post-training. Data collection will begin on the day of discharge prior to leaving the facility, and mothers will respond to questions about their demographics, pregnancy history, health, and their infants' health. During 2 home visits, mothers will respond to questions on breastfeeding self-efficacy and health, as well as their infants' health and feeding practices. Mothers' weight and height will be measured at one study visit. The infants' weight, length, head circumference and MUAC will be measured at each study visit. Interviews with mothers will be done at 6 weeks post-discharge during implementation of Model 1 & 2 and will explore their experiences with the TTH-FSP+ and their perspectives on its acceptability and feasibility . Interviews with community providers will be conducted once during implementation of each Model 1 & 2. Investigators aim to interview the same providers at both time points. Interviews will explore community providers' experiences delivering the TTH-FSP+ and their perspectives on its acceptability and feasibility.