Enhancing PET Degrading Enzymes: A Combinatory Approach.

Plastic waste has become a substantial environmental issue. A potential strategy to mitigate this problem is to use enzymatic hydrolysis of plastics to depolymerize post-consumer waste and allow it to be reused. Over the last few decades, the use of enzymatic PET-degrading enzymes has shown promise as a great solution for creating a circular plastic waste economy. PsPETase from Piscinibacter sakaiensis has been identified as an enzyme with tremendous potential for such applications. But to improve its efficiency, enzyme engineering has been applied aiming at enhancing its thermal stability, enzymatic activity, and ease of production. Here, we combine different strategies such as structure-based rational design, ancestral sequence reconstruction and machine learning to engineer a more highly active Combi-PETase variant with a melting temperature of 70 °C and optimal performance at 60 °C. Furthermore, this study demonstrates that these approaches, commonly used in other works of enzyme engineering, are most effective when utilized in combination, enabling the improvement of enzymes for industrial applications.

Biliary colic in the emergency department: A state-wide analysis of one-year costs and clinical outcomes.

Importance: Approximately 335,000 cases of biliary colic present to US emergency departments (EDs) annually, and most patients without complications are discharged from the ED. It is unknown what are the subsequent surgery rates, subsequent complications of biliary disease, ED revisits, repeat hospitalizations and cost; and, how does the ED disposition decision (admission versus discharge) affect long-term outcomes. Objective: To determine whether there is a difference in one-year surgery rates, complications of biliary disease, ED revisits, repeat hospitalizations, and cost in ED patients with uncomplicated biliary colic who are admitted to the hospital versus those that are discharged from the ED. Design setting and participants: A retrospective observational study was conducted using records collected from the Maryland Healthcare Cost and Utilization Project (HCUP) in the Ambulatory Surgery, the Inpatient, and the ED setting between 2016 and 2018. After applying inclusion criteria, 7036 ED patients with uncomplicated biliary colic were followed for one year after their index ED visit for repeat healthcare utilization across multiple settings. A multivariable logistic regression study was performed to asses for risk factors for surgery allocation and hospital admission. Medicare Relative Value Units (RVUs) and HCUP Cost-Charge Ratio files were used to estimate direct costs. Exposures: Episodes of biliary colic were ascertained using ICD-10 codes at the index ED visit. Main outcomes and measures: The primary outcome was the one-year surgery rate, defined as a cholecystectomy. Secondary outcomes included the rate of new acute cholecystitis or other related complications, ED revisits, hospital admission and costs. Associations with hospital admission and surgeries were measured using adjusted odds ratios (ORs) with 95 % CIs. Results: Of the 7036 patients analyzed, 793 (11.3 %) were admitted and 6243 (88.7 %) were discharged on their initial ED visit. When comparing the groups who were initially admitted versus discharged, we observed similar one-year cholecystectomy rates (42 % versus 43 %, mean difference 0.5 %, 95 % CI -3.1 %-4.2 %; P < 0.001), lower rates of new cholecystitis occurrences (18 % versus 41 %, mean difference 23 %, 95 % CI, 20 %-26 %; P < 0.001), lower rates of ED revisits (96 vs 198 per 1000 patients, mean difference 102, 95 % CI, 74-130; P < 0.001) and higher costs ($9880 versus $1832, mean difference 8048, 95 % CI, 7478-8618; P < 0.001). Initial ED hospital admission was associated with increased age (adjusted odds ratio [aOR], 1.44; 95 % CI, 1.35-1.53; P < 0.001), obesity (aOR, 1.38; 95 % CI, 1.32-1.44; P < 0.001), ischemic heart disease (aOR, 1.39; 95 % CI, 1.30-1.48; P < 0.001), mood disorders (aOR, 1.18; 95 % CI, 1.13-1.24; P < 0.001), alcohol-related disorders (aOR, 1.20; 95 % CI, 1.12-1.27; P < 0.001), hyperlipidemia (aOR, 1.16; 95 % CI, 1.09-1.23; P < 0.001), hypertension (aOR, 1.15; 95 % CI, 1.08-1.21; P < 0.001), and nicotine dependence (aOR, 1.09; 95 % CI, 1.03-1.15; P = 0.003) but not associated with race (P > 0.9), ethnicity (P > 0.9), or income-stratified zip code (aOR, 1.04; 95 % CI, 0.98-1.09; P = 0.17). Conclusions and relevance: In our analysis of ED patients with uncomplicated biliary colic from a single state, the majority of patients do not receive a cholecystectomy within one year and hospital admission at the initial visit was not associated with an overall change in rates of cholecystectomy but was associated with increased costs. These findings inform our understanding of the long-term outcomes and are important considerations when communicating care options with ED patients with biliary colic.

Patients with complicated gallstone disease in the emergency department: clinical impact and cost-effectiveness of emergency department disposition decision.

Objective: The objective of this study was to assess the 1-year outcomes of emergency department (ED) patients with complicated gallstone disease, including surgery rates, initial admission rates, ED revisits, repeat hospitalizations, and cost. Methods: Using 3 linked statewide databases from the Maryland Healthcare Cost and Utilization Project, we identified patients with a primary diagnosis of complicated gallstone disease treated in an ED between 2016 and 2018. We measured the healthcare use and direct costs in the ambulatory surgery, inpatient, and ED settings for 1 year after the initial ED visit. Finally, we performed a multivariate logistic regression analysis comparing initially admitted versus discharged patients. Results: Of the 8751 patients analyzed, 86.8% were admitted to the hospital and 13.2% were discharged on their initial ED visit. Of the admitted patients, 78.7% received a cholecystectomy during the initial hospitalization plus 6.1% at a later date; of the discharged patients, 41.5% received a cholecystectomy. Admitted patients demonstrated lower recurrent gallbladder complications compared with those discharged (7.5% vs 44.5%), fewer ED revisits (4% vs 20.3%), and fewer repeat hospitalizations (4.5% vs 16.7%). Despite this, the 1-year cost in the admitted patients was higher ($9448 vs $2933). Obesity, age, and mood disorders but not race, ethnicity, or zip code were associated with admission at initial ED visit. Conclusions: In our single-state analysis of ED patients with complications of gallstone disease, most patients are admitted on the initial visit and receive a cholecystectomy during that hospitalization. The discharged group had higher rates of 1-year complications, ED revisits, and repeat hospitalizations but lower cost.

A randomized control trial of a multiplex gastrointestinal PCR panel versus usual testing to assess antibiotics use for patients with infectious diarrhea in the emergency department.

OBJECTIVE: This study analyzed physician treating behavior through the use of a multiplex gastrointestinal polymerase chain reaction (GI PCR) test compared with usual testing in emergency department (ED) patients with suspected acute infectious diarrhea to assess differences in antibiotic management. METHODS: A prospective, single-center, randomized control trial was designed to investigate antibiotic use in ED patients with moderate to severe suspected infectious diarrhea, comparing those who received GI PCR to those who received usual testing. ED patients with signs of dehydration, inflammation, or persistent symptoms were randomized to either the experimental arm (GI PCR) or the control arm (usual testing or no testing). RESULTS: A total of 74 patients met study criteria and were randomized to either the experimental GI PCR arm (n = 38) or to the control arm (n = 36). Participants in the GI PCR arm received antibiotics in 87% of bacterial or protozoal diarrheal infections (13/15) whereas those in the control arm received antibiotics in 46% of bacterial or protozoal infections (6/13) (P value 0.042) with 2-proportion difference 0.41 (95% confidence interval 0.07 and 0.68). CONCLUSIONS: ED use of multiplex GI PCR led to an increase in antibiotic use for bacterial and protozoal causes of infectious diarrhea compared to usual testing. This increase in antibiotics appears to be appropriate given patients' moderate to severe symptoms and a definitive identification of a likely bacterial or protozoal cause of symptoms. Results should be interpreted with caution because of the small sample size.

Factors associated with clinical severity in emergency department patients presenting with symptomatic SARS-CoV-2 infection.

OBJECTIVE: To measure the association of race, ethnicity, comorbidities, and insurance status with need for hospitalization of symptomatic emergency department patients with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. METHODS: This study is a cohort study of symptomatic patients presenting to a single emergency department (ED) with laboratory-confirmed SARS-CoV-2 infection from March 7-August 9, 2020. We collected patient-level information regarding demographics, insurance status, comorbidities, level of care, and mortality using a structured chart review. We compared characteristics of patients categorized by (1) home discharge, (2) general hospital ward admission, and (3) intensive care unit (ICU) admission or death within 30 days of the index visit. Univariate and multivariable logistic regression analyses were performed to report odds ratios (OR) and 95% confidence intervals (95% CI) between hospital admission versus ED discharge home and between ICU care versus general hospital ward admission. RESULTS: In total, 994 patients who presented to the ED with symptoms were included in the analysis with 551 (55.4%) patients discharged home, 314 (31.6%) patients admitted to the general hospital ward, and 129 (13.0%) admitted to the ICU or dying. Patients requiring admission were more likely to be Black or to have public insurance (Medicaid and/or Medicare). Patients who were admitted to the ICU or dying were more likely aged ≥ 65 years or male. In multivariable logistic regression, old age, public insurance, diabetes, hypertension, obesity, heart failure, and hyperlipidemia were independent predictors of hospital admission. When comparing those who needed ICU care versus general hospital ward admission in univariate logistic regression, patients with Medicaid (OR 2.4, 95% CI 1.2-4.6), Medicare (OR 4.2, 95% CI 2.1-8.4), Medicaid and Medicare (OR 4.3, 95% CI 2.4-7.7), history of chronic obstructive pulmonary disease (OR 2.2, 95% CI 1.2-4.2), hypertension (OR 1.7, 95% CI 1.1-2.7), and heart failure (OR 2.6, 95% CI 1.4-4.7) were more likely to be admitted into the ICU or die; Black (OR 1.1, 95% CI 0.4-2.9) and Hispanic/Latino (OR 1.0, 95% CI 0.6-1.8) patients were less likely to be admitted into the ICU; however, the associations were not statistically significant. In multivariable logistic regression, old age, male sex, public insurance, and heart failure were independent predictors of ICU care/death. CONCLUSION: Comorbidities and public insurance are predictors of more severe illness for patients with SARS-CoV-2. This study suggests that the disparities in severity seen in COVID-19 among Black patients may be attributable, in part, to low socioeconomic status and chronic health conditions.

Factors associated with clinical severity in Emergency Department patients presenting with symptomatic SARS-CoV-2 infection.

OBJECTIVE: To measure the association of race, ethnicity, comorbidities, and insurance status with need for hospitalization of symptomatic Emergency Department (ED) patients with Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) infection. METHODS: This study is a retrospective case-series of symptomatic patients presenting to a single ED with laboratory-confirmed SARS-CoV-2 infection from March 12-August 9, 2020. We collected patient-level information regarding demographics, public insurance status (Medicare or Medicaid), comorbidities, level of care, and mortality using a structured chart review. We compared demographics and comorbidities of patients who were (1) able to convalesce at home, (2) required admission to general medical service, (3) required admission to intensive care unit (ICU), or (4) died within 30 days of the index visit. Multivariable logistic regression analyses were performed to report adjusted odds ratios (aOR) and the associated 95% confidence intervals (95% CI) with hospital admission versus ED discharge home. RESULTS: In total, 993 patients who presented to the ED with symptoms were included in the analysis with 370 (37.3%) patients requiring hospital admission and 70 (7.1%) patients requiring ICU care. Patients requiring admission were more likely to be Black or African American, to be Hispanic or Latino, or to have public insurance (either Medicaid or Medicare.) On multivariable logistic regression analysis comparing which patients required hospital admission, African-American race (aOR 1.4, 95% CI 0.7-2.8) and Hispanic ethnicity (aOR 1.1, 95% CI 0.5-2.0) were not associated with need for admission but, public insurance (Medicaid: aOR 3.4, 95% CI 2.2-5.4; Medicare: aOR 2.6, 95% CI 1.2-5.3; Medicaid and Medicare: aOR 3.6 95% CI 2.1-6.2) and the presence of hypertension (aOR 1.8, 95% CI 1.2-2.7), diabetes (aOR 1.6, 95% CI 1.1-2.5), obesity (aOR 1.7, 95% CI 1.1-2.5), heart failure (aOR 3.9, 95% CI 1.4-11.2), and hyperlipidemia (aOR 1.8, 95% CI 1.2-2.9) were identified as independent predictors of hospital admission. CONCLUSION: Comorbidities and public insurance are predictors of more severe illness for patients with SARS-CoV-2. This study suggests that the disparities in severity seen in COVID-19 among African Americans and Hispanics are likely to be closely related to low socioeconomic status and chronic health conditions and do not reflect an independent predisposition to disease severity.