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Objective Little attention has been given, so far, to the early colonial diet in New France from an isotopic perspective. Historical records that compare France to New France suggest a shift toward a more diverse diet, including a higher protein intake due to an improvement in living conditions in the New World, despite the retention of ancestral dietary habits. This hypothesis will be explored here. Materials and methods Stable carbon (organic and mineral) and nitrogen isotopes were measured on 43 individuals from Notre Dame cemetery (first Catholic parish church cemetery in Montreal, 1683-1803) as well as 13 French compatriots from La Rochelle, France (Protestant Hospital Cemetery, 1765-1792). Intragroup variation (age at death, sex, and/or burial location) was investigated and compared to compiled data from various northeastern North American sites ( N = 99). Results The Notre Dame sample means are as follows: −19.6‰ versus VPDB for δ13Ccollagen, −12.22‰ versus VPDB for δ13Ccarbonate, and 11.5‰ versus AIR for δ15N. They are significantly lower than both La Rochelle (−18.4‰, −11.67‰, and 12.7‰, respectively, p ≤ .005) and the northeastern North American groups used for this comparison ( p = .000). Discussion The isotopic values obtained from Notre Dame cemetery suggest that the diet was mainly based on C3 resources with limited C4 resources. Although different from all comparable contemporary sites, colonial Montreal's diet remains most similar to La Rochelle, France. This study agrees with historians who have suggested that French dietary traditions seem to have been retained among the early colonial inhabitants of Montreal. [ABSTRACT FROM AUTHOR]

Importance: Urinary tract infection (UTI) is the second most common infection leading to hospitalization and is often associated with gram-negative multidrug-resistant organisms (MDROs). Clinicians overuse extended-spectrum antibiotics although most patients are at low risk for MDRO infection. Safe strategies to limit overuse of empiric antibiotics are needed., Objective: To evaluate whether computerized provider order entry (CPOE) prompts providing patient- and pathogen-specific MDRO risk estimates could reduce use of empiric extended-spectrum antibiotics for treatment of UTI., Design, Setting, and Participants: Cluster-randomized trial in 59 US community hospitals comparing the effect of a CPOE stewardship bundle (education, feedback, and real-time and risk-based CPOE prompts; 29 hospitals) vs routine stewardship (n = 30 hospitals) on antibiotic selection during the first 3 hospital days (empiric period) in noncritically ill adults (≥18 years) hospitalized with UTI with an 18-month baseline (April 1, 2017-September 30, 2018) and 15-month intervention period (April 1, 2019-June 30, 2020)., Interventions: CPOE prompts recommending empiric standard-spectrum antibiotics in patients ordered to receive extended-spectrum antibiotics who have low estimated absolute risk (<10%) of MDRO UTI, coupled with feedback and education., Main Outcomes and Measures: The primary outcome was empiric (first 3 days of hospitalization) extended-spectrum antibiotic days of therapy. Secondary outcomes included empiric vancomycin and antipseudomonal days of therapy. Safety outcomes included days to intensive care unit (ICU) transfer and hospital length of stay. Outcomes were assessed using generalized linear mixed-effect models to assess differences between the baseline and intervention periods., Results: Among 127 403 adult patients (71 991 baseline and 55 412 intervention period) admitted with UTI in 59 hospitals, the mean (SD) age was 69.4 (17.9) years, 30.5% were male, and the median Elixhauser Comorbidity Index count was 4 (IQR, 2-5). Compared with routine stewardship, the group using CPOE prompts had a 17.4% (95% CI, 11.2%-23.2%) reduction in empiric extended-spectrum days of therapy (rate ratio, 0.83 [95% CI, 0.77-0.89]; P < .001). The safety outcomes of mean days to ICU transfer (6.6 vs 7.0 days) and hospital length of stay (6.3 vs 6.5 days) did not differ significantly between the routine and intervention groups, respectively., Conclusions and Relevance: Compared with routine stewardship, CPOE prompts providing real-time recommendations for standard-spectrum antibiotics for patients with low MDRO risk coupled with feedback and education significantly reduced empiric extended-spectrum antibiotic use among noncritically ill adults admitted with UTI without changing hospital length of stay or days to ICU transfers., Trial Registration: ClinicalTrials.gov Identifier: NCT03697096.

Importance: Pneumonia is the most common infection requiring hospitalization and is a major reason for overuse of extended-spectrum antibiotics. Despite low risk of multidrug-resistant organism (MDRO) infection, clinical uncertainty often drives initial antibiotic selection. Strategies to limit empiric antibiotic overuse for patients with pneumonia are needed., Objective: To evaluate whether computerized provider order entry (CPOE) prompts providing patient- and pathogen-specific MDRO infection risk estimates could reduce empiric extended-spectrum antibiotics for non-critically ill patients admitted with pneumonia., Design, Setting, and Participants: Cluster-randomized trial in 59 US community hospitals comparing the effect of a CPOE stewardship bundle (education, feedback, and real-time MDRO risk-based CPOE prompts; n = 29 hospitals) vs routine stewardship (n = 30 hospitals) on antibiotic selection during the first 3 hospital days (empiric period) in non-critically ill adults (≥18 years) hospitalized with pneumonia. There was an 18-month baseline period from April 1, 2017, to September 30, 2018, and a 15-month intervention period from April 1, 2019, to June 30, 2020., Intervention: CPOE prompts recommending standard-spectrum antibiotics in patients ordered to receive extended-spectrum antibiotics during the empiric period who have low estimated absolute risk (<10%) of MDRO pneumonia, coupled with feedback and education., Main Outcomes and Measures: The primary outcome was empiric (first 3 days of hospitalization) extended-spectrum antibiotic days of therapy. Secondary outcomes included empiric vancomycin and antipseudomonal days of therapy and safety outcomes included days to intensive care unit (ICU) transfer and hospital length of stay. Outcomes compared differences between baseline and intervention periods across strategies., Results: Among 59 hospitals with 96 451 (51 671 in the baseline period and 44 780 in the intervention period) adult patients admitted with pneumonia, the mean (SD) age of patients was 68.1 (17.0) years, 48.1% were men, and the median (IQR) Elixhauser comorbidity count was 4 (2-6). Compared with routine stewardship, the group using CPOE prompts had a 28.4% reduction in empiric extended-spectrum days of therapy (rate ratio, 0.72 [95% CI, 0.66-0.78]; P < .001). Safety outcomes of mean days to ICU transfer (6.5 vs 7.1 days) and hospital length of stay (6.8 vs 7.1 days) did not differ significantly between the routine and CPOE intervention groups., Conclusions and Relevance: Empiric extended-spectrum antibiotic use was significantly lower among adults admitted with pneumonia to non-ICU settings in hospitals using education, feedback, and CPOE prompts recommending standard-spectrum antibiotics for patients at low risk of MDRO infection, compared with routine stewardship practices. Hospital length of stay and days to ICU transfer were unchanged., Trial Registration: ClinicalTrials.gov Identifier: NCT03697070.

Objectives: This isotopic study explores the mobility patterns of a growing urban population from Notre Dame's Catholic cemetery (1691-1796), located in Montreal (Canada). The site offers a unique opportunity to investigate early colonial settlement in Nouvelle France through individual life patterns., Materials and Methods: Stable oxygen isotopic compositions (δ 18 O) were measured on the enamel of 32 individuals from the Notre Dame collection. Premolars and third molars were selected, as they reflected the δ 18 O of the drinking water during childhood (2.5-5.5 years) and pre-adulthood (9.5-15.5 years). Firstly, premolars from three children (4-8 years of age) allowed us to provide a mean δ 18 O for the water consumed locally (22.7 ±  1.0 ‰ vs. VSMOW). Then, our δ 18 O were compared with published data from various geographical regions in North America (Eastern Canada and the United States) and Europe (France and the British Isles) to highlight mobility patterns of each individual., Results: Forty-eight percent of our sample (14 out of 29 individuals) did not reflect any long-distance mobility, as all their δ 18 O reflected Montreal's variation during their lifetime. The remaining (15 out of 29 individuals) experienced mobility within (n = 8) and outside (n = 7) North America and at different phases of their life (five at pre-adulthood, six at adulthood and four during both phases). Their migration patterns were analyzed according to age, sex, diet and possible ancestry in order to propose some "biographies.", Discussion: This study highlights high population diversity in early colonial Montreal. Historians wrote that the city was growing, not only with the arrival of Europeans (e.g., young male workers, sailors), but also other groups (e.g., Indigenous people, slaves from North America). Additional analyses (e.g., ancient DNA) will be needed to explore further this phenomenon., (© 2021 Wiley Periodicals LLC.)

Purpose: Lymphoma is a health outcome of interest for drug safety studies. Studies using administrative claims data require the accurate identification of lymphoma cases. We developed and validated an International Classification of Diseases, Tenth Revision, Clinical Modification (ICD-10-CM)-based algorithm to identify lymphoma in healthcare claims data., Methods: We developed a three-component algorithm to identify patients aged ≥15 years who were newly diagnosed with Hodgkin (HL) or non-Hodgkin (NHL) lymphoma from January 2016 through July 2018 among members of four Data Partners within the FDA's Sentinel System. The algorithm identified potential cases as patients with ≥2 ICD-10-CM lymphoma diagnosis codes on different dates within 183 days; ≥1 procedure code for a diagnostic procedure (e.g., biopsy, flow cytometry) and ≥1 procedure code for a relevant imaging study within 90 days of the first lymphoma diagnosis code. Cases identified by the algorithm were adjudicated via chart review and a positive predictive value (PPV) was calculated., Results: We identified 8723 potential lymphoma cases via the algorithm and randomly sampled 213 for validation. We retrieved 138 charts (65%) and adjudicated 134 (63%). The overall PPV was 77% (95% confidence interval: 69%-84%). Most cases also had subtype information available, with 88% of cases identified as NHL and 11% as HL., Conclusions: Seventy-seven percent of lymphoma cases identified by an algorithm based on ICD-10-CM diagnosis and procedure codes and applied to claims data were true cases. This novel algorithm represents an efficient, cost-effective way to target an important health outcome of interest for large-scale drug safety and public health surveillance studies., (© 2021 John Wiley & Sons Ltd.)

The human renin infused rat model (HRIRM) was used as an in vivo small-animal model for evaluating the efficacy of a collection of inhibitors of human renin. The intravenous infusion of recombinant human renin (2.4 microg x kg(-1) x min(-1)) in the ganglion-blocked, nephrectomized rat produced a mean blood pressor response of 47+/-3 mm Hg (1 mm Hg = 133.3 Pa), which was reduced by captopril, enalkiren, and losartan in a dose-dependent manner following oral administration, with ED50 values of 0.3+/-0.1, 2.5+/-0.9, and 5.2+/-1.6 mg/kg, respectively. A series of peptidomimetic P2-P3 butanediamide renin inhibitors inhibited purified recombinant human renin in vitro in a concentration-dependent manner, with IC50 values ranging from 0.4 to 20 nM at pH 6.0, with a higher range of IC50 values (0.8-80 nM) observed at pH 7.4. Following i.v. administration of renin inhibitors, the pressor response to infused human renin in the HRIRM was inhibited in a dose-dependent manner, with ED50 values ranging from 4 to 600 microg/kg. The in vivo inhibition of human renin following i.v. administration in the rat correlated significantly better with the in vitro inhibition of human renin at pH 7.4 (r = 0.8) compared with pH 6.0 (r = 0.5). Oral administration of renin inhibitors also resulted in a dose-dependent inhibition of the pressor response to infused human renin, with ED50 values ranging from 0.4 to 6.0 mg/kg and the identification of six renin inhibitors with an oral potency of <1 mg/kg. The ED50 of renin inhibitors for inhibition of angiotensin I formation in vivo was highly correlated (r = 0.9) with the ED50 for inhibition of the pressor response. These results demonstrate the high potency, dose dependence, and availability following oral administration of the butanediamide series of renin inhibitors.