Browsing by Author "Somayaji, Ranjani"
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- ItemOpen AccessAzithromycin and the microbiota of cystic fibrosis sputum(2021-03-30) Acosta, Nicole; Thornton, Christina S; Surette, Michael G; Somayaji, Ranjani; Rossi, Laura; Rabin, Harvey R; Parkins, Michael DAbstract Background Azithromycin is commonly prescribed drug for individuals with cystic fibrosis (CF), with demonstrated benefits in reducing lung function decline, exacerbation occurrence and improving nutrition. As azithromycin has antimicrobial activity against components of the uncultured microbiome and increasingly the CF microbiome is implicated in disease pathogenesis – we postulated azithromycin may act through its manipulation. Herein we sought to determine if the CF microbiome changed following azithromycin use and if clinical benefit observed during azithromycin use associated with baseline community structure. Results Drawing from a prospectively collected biobank we identified patients with sputum samples prior to, during and after initiating azithromycin and determined the composition of the CF microbial community by sequencing the V3-V4 region of the 16S rRNA gene. We categorized patients as responders if their rate of lung function decline improved after azithromycin initiation. Thirty-eight adults comprised our cohort, nine who had not utilized azithromycin in at least 3 years, and 29 who were completely naïve. We did not observe a major impact in the microbial community structure of CF sputum in the 2 years following azithromycin usage in either alpha or beta-diversity metrics. Seventeen patients (45%) were classified as Responders – demonstrating reduced lung function decline after azithromycin. Responders who were naïve to azithromycin had a modest clustering effect distinguishing them from those who were non-Responders, and had communities enriched with several organisms including Stenotrophomonas, but not Pseudomonas. Conclusions Azithromycin treatment did not associate with subsequent large changes in the CF microbiome structure. However, we found that baseline community structure associated with subsequent azithromycin response in CF adults.
- ItemOpen AccessCystic fibrosis physicians’ perspectives on the timing of referral for lung transplant evaluation: a survey of physicians in the United States(2017-01-19) Ramos, Kathleen J; Somayaji, Ranjani; Lease, Erika D; Goss, Christopher H; Aitken, Moira LAbstract Background Prior studies reveal that a significant proportion of patients with cystic fibrosis (CF) and advanced lung disease are not referred for lung transplant (LTx) evaluation. We sought to assess expert CF physician perspectives on the timing of LTx referral and investigate their LTx knowledge. Methods We developed an online anonymous survey that was distributed by the Cystic Fibrosis Foundation (CFF) to the medical directors of all CFF-accredited care centers in the United States in 2015. The survey addressed only adult patients (≥18 years old) and was sent to 119 adult CF physicians, 86 CFF-affiliated CF physicians (who see adults and children, but have smaller program sizes than adult or pediatric centers), and 127 pediatric CF physicians (who see some adults, but mostly children). The focus of the questions was on CFF-care center characteristics, physician experience and indications/contraindications to referral for LTx evaluation. Results There were 114/332 (34%) total responses to the survey. The response rates were: 57/119 (48%) adult physicians, 12/86 (14%) affiliate physicians and 43/127 (34%) pediatric physicians; 2 physicians did not include their CFF center type. Despite the poor ability of FEV1 < 30% to predict death within 2 years, 94% of responding CF physicians said they would refer an adult patient for LTx evaluation if the patient’s lung function fell to FEV1 < 30% predicted. Only 54% of respondents report that pulmonary hypertension would trigger referral. Pulmonary hypertension is an internationally recommended indication to list a patient for LTx (not just for referral for evaluation). Very few physicians (N = 17, 15%) employed components of the lung allocation score (LAS) to determine the timing of referral for LTx evaluation. Interestingly, patient preference not to undergo LTx was “often” or “always” the primary patient-related reason to defer referral for LTx evaluation for 41% (47/114) of respondents. Conclusions Some potential barriers to timely LTx referral for patients with CF include physician knowledge regarding non-lung function-based recommendations related to timing of referral and listing for LTx, and patient preference not to undergo LTx. Further exploration of physician-level and CF patient-level barriers to timely LTx referral is warranted.
- ItemOpen AccessEarly management of sepsis in medical patients in rural Thailand: a single-center prospective observational study(2019-12-02) Rudd, Kristina E; Hantrakun, Viriya; Somayaji, Ranjani; Booraphun, Suchart; Boonsri, Chaiyaporn; Fitzpatrick, Annette L; Day, Nicholas P J; Teparrukkul, Prapit; Limmathurotsakul, Direk; West, T. EAbstract Background The burden of sepsis is highest in low- and middle-income countries, though the management of sepsis in these settings is poorly characterized. Therefore, the objective of this study was to assess the early management of sepsis in Thailand. Methods Pre-planned analysis of the Ubon-sepsis study, a single-center prospective cohort study of Thai adults admitted to the general medical wards and medical intensive care units (ICUs) of a regional referral hospital with community-acquired sepsis. Results Between March 2013 and January 2017, 3,716 patients with sepsis were enrolled. The median age was 59 years (IQR 44-72, range 18-101), 58% were male, and 88% were transferred from other hospitals. Eighty-six percent of patients (N = 3,206) were evaluated in the Emergency Department (ED), where median length of stay was less than 1 hour. Within the first day of admission, most patients (83%, N = 3,089) were admitted to the general medical wards, while 17% were admitted to the ICUs. Patients admitted to the ICUs had similar age, gender, and comorbidities, but had more organ dysfunction and were more likely to receive measured sepsis management interventions. Overall, 84% (N = 3,136) had blood cultures ordered and 89% (N = 3,308) received antibiotics within the first day of hospital admission. Among the 3,089 patients admitted to the general medical wards, 38% (N = 1,165) received an adrenergic agent, and 21% (N = 650) received invasive mechanical ventilation. Overall mortality at 28 days was 21% (765/3,716), and 28-day mortality in patients admitted to the ICUs was higher than that in patients admitted to the general medical wards within the first day (42% [263/627] vs. 16% [502/3,089], p < 0.001). Conclusions Sepsis in a regional referral hospital in rural Thailand, where some critical care resources are limited, is commonly managed on general medical wards despite high rates of respiratory failure and shock. Enhancing sepsis care in the ED and general wards, as well as improving access to ICUs, may be beneficial in reducing mortality. Trial registration The Ubon-sepsis study was registered on clinicaltrials.gov (NCT02217592).
- ItemOpen AccessEvaluating hemoptysis hospitalizations among patients with bronchiectasis in the United States: a population-based cohort study(2021-12-01) Lim, Rachel K.; Tremblay, Alain; Lu, Shengjie; Somayaji, RanjaniAbstract Background The burden of hospitalizations and mortality for hemoptysis due to bronchiectasis is not well characterized. The primary outcome of our study was to evaluate in-hospital mortality in patients admitted with hemoptysis and bronchiectasis, as well as the rates of bronchial artery embolization, length of stay, and hospitalization costs. Methods The authors queried the Nationwide Inpatient Sample (NIS) claims database for hospitalizations between 2016 and 2017 using the ICD-10-CM codes for hemoptysis and bronchiectasis in the United States. Multivariable regression was used to evaluate predictors of in-hospital mortality, embolization, length of stay, and hospital costs. Results There were 8240 hospitalizations (weighted) for hemoptysis in the United States from 2016 to 2017. The overall in-hospital mortality was 4.5%, but higher in males compared to females. Predictors of in-hospital mortality included undergoing three or more procedures, age, and congestive heart failure. Bronchial artery embolization (BAE) was utilized during 2.1% of hospitalizations and was more frequently used in those with nontuberculous mycobacteria and aspergillus infections, but not pseudomonal infections. The mean length of stay was 6 days and the median hospitalization cost per patient was USD $9,610. Having comorbidities and procedures was significantly associated with increased length of stay and costs. Conclusion Hemoptysis is a frequent indication for hospitalization among the bronchiectasis population. In-hospital death occurred in approximately 4.5% of hospitalizations. The effectiveness of BAE in treating and preventing recurrent hemoptysis from bronchiectasis needs to be explored.
- ItemOpen AccessPostoperative complications after gastrointestinal pediatric surgical procedures: outcomes and socio-demographic risk factors(2022-06-22) Brock, Robert; Chu, Angel; Lu, Shengjie; Brindle, Mary E.; Somayaji, RanjaniAbstract Background Several socio-demographic characteristics are associated with complications following certain pediatric surgical procedures. In this comprehensive study, we sought to determine socio-demographic risk factors and resource utilization of children with complications after common pediatric surgical procedures. Methods We performed a population-based cohort study utilizing the 2016 Healthcare Cost and Use Project Kids’ Inpatient Database (KID) to identify and characterize pediatric patients (age 0–21 years) in the United States with common inpatient pediatric gastrointestinal surgical procedures: appendectomy, cholecystectomy, colonic resection, pyloromyotomy and small bowel resection. Multivariable logistic regression modeling was used to identify socio-demographic predictors of postoperative complications. Length of stay and hospitalization costs for patients with and without postoperative complications were compared. Results A total of 66,157 pediatric surgical hospitalizations were identified. Of these patients, 2,009 had postoperative complications. Male sex, young age, African American and Native American race and treatment in a rural hospital were associated with significantly greater odds of postoperative complications. Mean length of stay was 4.58 days greater and mean total costs were $11,151 (US dollars) higher in the complication cohort compared with patients without complications. Conclusions Postoperative complications following inpatient pediatric gastrointestinal surgery were linked to elevated healthcare-related expenditure. The identified socio-demographic risk factors should be considered in the risk stratification before pediatric surgical procedures. Targeted interventions are required to reduce preventable complications and surgical disparities.
- ItemOpen AccessThe Cardiovascular Implications of Gender-Affirming Estrogen Therapy Use in Transgender Women(2024-04-24) Rytz, Chantal Louise; Ahmed, Sofia Bano; Saad, Nathalie; Dumanski, Sandra Marie; Ronksely, Paul Everett; Raj, Satish R.; Somayaji, RanjaniCardiovascular disease is a leading cause of death globally, with transgender and gender diverse (TGD) individuals, and particularly transgender women (sex assigned male at birth who identify as women) facing significant rates of cardiovascular-related morbidity and mortality. While uncertainties exist regarding the potential contribution of gender-affirming estrogen therapy in the increased cardiovascular risk noted in this population, there remains a critical evidence gap in understanding how factors such as serum estradiol levels, sex assigned at birth, and gender identity impact cardiovascular risk. Therefore it was the objective of this thesis to determine the cardiovascular implications of gender-affirming hormone therapy in transgender women, which was explored from various angles through conducting three independent studies. Our first study provides an understanding of the association between serum estradiol and cardiovascular-related mortality, adverse cardiovascular events and cardiovascular related risk factors using a systematic review and meta-analysis approach. We determined that the rate of serum estradiol change across the use of gender-affirming estrogen therapy may influence cardiovascular risk factors, which may have implications for clinical cardiovascular outcomes. Using a cross-sectional approach, our second study evaluated the impact of gender identity and sex assigned at birth on measures of vascular hemodynamics and arterial stiffness in transgender women as compared to cisgender women and men. Our findings underscore the importance of considering gender identity in addition sex assigned at birth when evaluating measures of cardiovascular health and risk. Our final study addressed the major methodological limitation with retrospective studies within the TGD population by generating and validating numerous case-definitions to identify both transgender women and men in routinely-collected healthcare data in Alberta, Canada. By linking numerous administrative data sources and testing against a reference standard of self-identified gender identity, a combination of using sex assigned in provincial registry and exogenous hormone dispensations or TGD-related billing codes were the most sensitive at identifying TGD individuals, and were employed to approximate both prevalence and incidence per 100,000 person-years, providing a first-ever assessment of the TGD population within Alberta. Despite recent advances and calls for the incorporation of both sex and gender into health research and clinical care, gaps in the understanding of cardiovascular health in transgender women remain. Our findings highlight numerous factors that may be implicated in cardiovascular health and risk in the transgender women population. This thesis may inform areas for further interventions aimed at improving cardiovascular health, mitigating cardiovascular disease risk, and exploring clinical cardiovascular outcomes in transgender women.
- ItemOpen AccessThe effects of inhaled aztreonam on the cystic fibrosis lung microbiome(2017-05-05) Heirali, Alya A; Workentine, Matthew L; Acosta, Nicole; Poonja, Ali; Storey, Douglas G; Somayaji, Ranjani; Rabin, Harvey R; Whelan, Fiona J; Surette, Michael G; Parkins, Michael DAbstract Background Aztreonam lysine for inhalation (AZLI) is an inhaled antibiotic used to treat chronic Pseudomonas aeruginosa infection in CF. AZLI improves lung function and quality of life, and reduces exacerbations-improvements attributed to its antipseudomonal activity. Given the extremely high aztreonam concentrations achieved in the lower airways by nebulization, we speculate this may extend its spectrum of activity to other organisms. As such, we sought to determine if AZLI affects the CF lung microbiome and whether community constituents can be used to predict treatment responsiveness. Methods Patients were included if they had chronic P. aeruginosa infection and repeated sputum samples collected before and after AZLI. Sputum DNA was extracted, and the V3-hypervariable region of the 16S ribosomal RNA (rRNA) gene amplified and sequenced. Results Twenty-four patients naïve to AZLI contributed 162 samples. The cohort had a median age of 37.1 years, and a median FEV1 of 44% predicted. Fourteen patients were a priori defined as responders for achieving ≥3% FEV1 improvement following initiation. No significant changes in alpha diversity were noted following AZLI. Furthermore, beta diversity demonstrated clustering with respect to patients, but had no association with AZLI use. However, we did observe a decline in the relative abundance of several individual operational taxonomic units (OTUs) following AZLI initiation suggesting that specific sub-populations of organisms may be impacted. Patients with higher abundance of Staphylococcus and anaerobic organisms including Prevotella and Fusobacterium were less likely to respond to therapy. Conclusions Results from our study suggest potential alternate/additional mechanisms by which AZLI functions. Moreover, our study suggests that the CF microbiota may be used as a biomarker to predict patient responsiveness to therapy suggesting the microbiome may be harnessed for the personalization of therapies.