Developing Parametric and Nonparametric Models for Model-Informed Precision Dosing: A Quality Improvement Effort in Vancomycin for Patients With Obesity.

BACKGROUND: Both parametric and nonparametric methods have been proposed to support model-informed precision dosing (MIPD). However, which approach leads to better models remains uncertain. Using open-source software, these 2 statistical approaches for model development were compared using the pharmacokinetics of vancomycin in a challenging subpopulation of class 3 obesity. METHODS: Patients on vancomycin at the University of Vermont Medical Center from November 1, 2021, to February 14, 2023, were entered into the MIPD software. The inclusion criteria were body mass index (BMI) of at least 40 kg/m2 and 1 or more vancomycin levels. A parametric model was created using nlmixr2/NONMEM, and a nonparametric model was created using metrics. Then, a priori and a posteriori predictions were evaluated using the normalized root mean squared error (nRMSE) for precision and the mean percentage error (MPE) for bias. The parametric model was evaluated in a simulated MIPD context using an external validation dataset. RESULTS: In total, 83 patients were included in the model development, with a median age of 56.6 years (range: 24-89 years), and a median BMI of 46.3 kg/m2 (range: 40-70.3 kg/m2). Both parametric and nonparametric models were 2-compartmental, with creatinine clearance and fat-free mass as covariates to c clearance and volume parameters, respectively. The a priori MPE and nRMSE for the parametric versus nonparametric models were -6.3% versus 2.69% and 27.2% versus 30.7%, respectively. The a posteriori MPE and RMSE were 0.16% and 0.84%, and 13.8% and 13.1%. The parametric model matched or outperformed previously published models on an external validation dataset (n = 576 patients). CONCLUSIONS: Minimal differences were found in the model structure and predictive error between the parametric and nonparametric approaches for modeling vancomycin class 3 obesity. However, the parametric model outperformed several other models, suggesting that institution-specific models may improve pharmacokinetics management.

Association between maternal periodontal disease and adverse pregnancy outcomes: an analysis of claims data.

BACKGROUND: While a number of studies have explored the link between periodontal disease and adverse pregnancy outcomes, both epidemiological studies and intervention trials have reached contradictory results with relatively small sample sizes. Utilizing large-scale claims data, we aim to investigate the association between maternal periodontal disease and adverse pregnancy outcomes. OBJECTIVE: Utilizing large-scale claims data, we aim to investigate the association between maternal periodontal disease and adverse pregnancy outcomes. METHODS: Using de-identified claims data from a national commercial insurer in the USA, records of all observed pregnancies from 2015 to 2019 were included in this retrospective cohort study. Adverse pregnancy outcomes, including low birthweight (LBW) of the newborn, preterm birth (PTB) and spontaneous abortion, were primary outcomes. To evaluate the association between periodontal disease and pregnancy outcomes, logistic mixed-effect model was estimated with periodontal disease status, age, existing clinical conditions of mothers and geographic location as covariates. RESULTS: Out of 748 792 observed pregnancy records, 18.66% resulted in adverse pregnancy outcomes; 5.92% in LBW, 14.46% in PTB and 2.22 % in spontaneous abortion. Adjusting for individual-level risk factors, periodontal disease was significantly associated with maternal complications with odds ratios of 1.19 (95% CI:1.15, 1.24) for any adverse pregnancy outcomes, 1.10 (95% CI:1.03, 1.17) for LBW, 1.15 (95% CI:1.10, 1.19) for PTB and 1.34 (95% CI:1.23, 1.46) for spontaneous abortions. CONCLUSIONS: Maternal periodontal disease may be associated with an increased risk of maternal complications and neonatal morbidity. A timely diagnosis and treatment of periodontal disease during pregnancy should be encouraged by considering oral health as part of routine prenatal care.

Identification of Risk Factors for Initial Elevated Vancomyin Trough Concentrations.

Background: Recent literature suggests that elevated vancomycin trough concentrations (>20 µg/mL) may be associated with an increased risk of nephrotoxicity and lead to an increase in mortality and hospital length of stay. Objective: The purpose of this study was to identify variables that may be predictive of elevated initial vancomycin trough concentrations. Methods: Retrospective case-control study of all adult patients who had an initial vancomycin trough concentration measured between January 1, 2013, and December 31, 2014. Case patients had an initial trough concentration >20 µg/mL, while control patients had an initial trough concentration of ≤20 µg/mL. Patients were excluded from the study if they were in the intensive care unit, had unstable renal function, or if they had cystic fibrosis, solid organ transplant, or bone marrow transplant. Results: Of the 512 vancomycin trough concentrations reviewed, 54 patients met the case definition, while 140 patients were randomly selected as controls. In a multivariate model, baseline serum creatinine, body mass index, heart failure, and malignancy were all independently predictive of an initial vancomycin concentration >20 µg/mL. Conclusions: Reduced baseline renal function coupled with increasing body mass index is associated with an increased risk of an elevated initial vancomycin trough concentration. This risk is further enhanced by the presence of heart failure and/or malignancy. When these risk factors are present, it may be prudent to consider implementation of individualized dosing to achieve initial target concentrations.

Structure and emissive properties of heterobimetallic Ln-Au coordination polymers: role of Tb and Eu in non-aurophilic [nBu4N]2[Ln(NO3)4Au(CN)2] versus aurophilic Ln[Au(CN)2]3·3H2O/3D2O chains.

This investigation is focused on comparing photophysical properties between two series of lanthanide-dicyanoaurate coordination polymers that contain and lack aurophilic interactions, respectively. Luminescence and crystallographic studies have been carried out on five different coordination polymer chain frameworks: the non-aurophilic [(n)Bu4N]2[LnxGd1-x(NO3)4Au(CN)2] (Ln = Eu, Tb; x = 0.01, 0.02, 0.04, 0.08) and[(n)Bu4N]2[EuxTb1-x(NO3)4Au(CN)2] (x = 0.25, 0.5, 0.75), as well as the analogous solid-solutions of aurophilic LnxGd1-x[Au(CN)2]3·3H2O and EuxTb1-x[Au(CN)2]3·3H2O. The single-crystal structures of M[Au(CN)2]3 ·3H2O (M = Eu, Gd) are also reported for comparison. In the aurophilic frameworks the close proximity of gold(I) centers on neighboring chains allows for Au-Au interactions to take place that facilitate energy transfer between lanthanides. Terbium- and europium-doped aurophilic frameworks show energy transfer between one of the lanthanide ions and dicyanoaurate centers as observed via luminescence measurements. In the non-aurophilic frameworks the [(n)Bu4N] cations separate the Au-Au chains, thereby preventing interaction between them, and preventing energy transfer. By preparing the aurophilic EuxTb1-x[Au(CN)2]3·3D2O frameworks, it was shown that the O-H vibrational energy in the hydrated (aurophilic) samples can partially quench the Ln signal.

Advancing Oral Health Equity through Medical-Dental Integration: Dental hygienists as catalysts for change in an evolving health care system.

This report explores the changing landscape of oral health care delivery in the United States, highlighting the evolving role of dental hygienists. The 2021 National Institutes of Health report "Oral Health in America: Advances and Challenges" has become a key milestone in addressing oral health inequities, acknowledging the important role that dental hygienists could play in expanding innovative care models, and promoting medical-dental integration (MDI). The Rainbow Model of Integrated Care offers a framework to examine facilitators of MDI care models, revealing supportive policies, interprofessional collaborative practice, incremental change, and local leadership as some of the crucial components needed for success. Dental hygienists emerge as catalysts for change, as such, the overarching aim of this report is to contribute to the broader conversation about optimizing oral health care accessibility through integrated care models led by dental hygienists.

Oral Health Screening by MassHealth Accountable Care Organizations: An opportunity for equity-focused interventions.

Establishing reliable access to dental services for publicly insured patients is an important part of achieving equitable oral health care. In 2023, an oral health screening requirement was added to the MassHealth Accountable Care Organization contract, which has the capacity to affect over 1.3 million members enrolled in MassHealth Accountable Care Organizations throughout the state. The goal of the oral health screening requirement is to identify MassHealth-insured patients who do not have reliable access to dental services and to provide them with resources to establish a dental home with a MassHealth-participating dentist. Primary care providers were surveyed, and results indicate a need for a care coordination mechanism to assist MassHealth-insured patients with establishing a dental home, in addition to an option to request telehealth-enabled and/or urgent dental appointments. This report describes the oral health screening program at one MassHealth Accountable Care Organization and presents some of the data collected during the first year of its implementation, in addition to discussing how this data is being used to guide equity-focused interventions with the potential for policy implications.

Critical shear stress of sunken, No. 6 heavy fuel oil in fresh water.

A series of flume- and laboratory-based experiments defined and quantified the thresholds of sunken oil transport using No.6 heavy fuel oil mixed with kaolinite clay. When the sunken oil became mobile, the current-induced bed shear stress exceeded a threshold value specific to the oil, known as critical shear stress (CSS). The oil's CSS was evaluated as a function of water velocity, water temperature, oil condition, and sediment size. Based on experimental results, the stages of oil transport were defined and empirical relationships using the oil's kinematic viscosity (vo) and sediment size were developed to predict oil CSS at each transport stage. For vo<2 × 104 cSt, multiple thresholds of movement were observed: (1) gravity dispersion, (2) rope formation, (3) ripple formation, and (4) break-apart/resuspension. When vo> 6 × 104 cSt, transport was more likely to occur as a single event with the oil remaining intact, saltating over the bed in the direction of flow.

A descriptive study of the "lift-assist" call.

INTRODUCTION: Responses for "lift assists" (LAs) are common in many emergency medical services (EMS) systems, and result when a person dials 9-1-1 because of an inability to get up, is subsequently determined to be uninjured, and is not transported for further medical attention. Although LAs often involve recurrent calls and are generally not reimbursable, little is known of their operational effects on EMS systems. We hypothesized that LAs present an opportunity for earlier treatment of subtle-onset medical conditions and injury prevention interventions in a population at high risk for falls. Objectives. To quantify LA calls in one community, describe EMS returns to the same address within 30 days following an index LA call, and characterize utilization of EMS by LA patients. METHODS: Data from the computer-aided dispatch (CAD) system of a suburban fire-based EMS system were retrospectively reviewed. All LAs from 2004 to 2009 were identified using "exit codes" transmitted by paramedics after each call. The number and nature of return visits to the same address within 30 days were examined. RESULTS: From 2004 through 2009, there were 1,087 LA responses (4.8% of EMS incidents) to 535 different addresses. Two-thirds of the LA calls (726; 66.8%) were to one-third of these addresses (174 addresses; 32.5%); 563 of the return calls to the same address occurred within 30 days after the index LA. For 214 of these return visits, it was possible to compare patient age and sex with those associated with the initial LA, revealing that 85% of return visits were likely for the same patients. Of these, 38.5% were for another LA/refusal of transport, 8.2% for falls and other injuries, and 47.3% for medical complaints. Hospital transport was required in 55.5% of these return visits. The EMS crews averaged 21.5 minutes out of service per LA call. CONCLUSION: Lift-assist calls are associated with substantial subsequent utilization of EMS, and should trigger fall prevention and other safety interventions. Based on our data, these calls may be early indicators of medical problems that require more aggressive evaluation.

An Evaluation of STFM's National Addiction Curriculum.

BACKGROUND AND OBJECTIVES: Family physicians are well positioned to treat patients with substance use disorders (SUDs), expand access to care, destigmatize addiction, and provide a biopsychosocial treatment approach. There is a great need to train residents and faculty to competency in SUD treatment. Through the Society of Teachers of Family Medicine (STFM) Addiction Collaborative, we created and evaluated the first national family medicine (FM) addiction curriculum using evidence-based content and teaching principles. METHODS: After launching the curriculum with 25 FM residency programs, we collected formative feedback through monthly faculty development sessions and summative feedback through 8 focus groups with 33 faculty members and 21 residents. We used qualitative thematic analysis to assess the value of the curriculum. RESULTS: The curriculum enriched resident and faculty knowledge across all SUD topics. It changed their attitudes in viewing addiction as a chronic disease within the scope of FM practice, increased confidence, and decreased stigma. It nurtured behavior change, enhancing communication and assessment skills and encouraging collaboration across disciplines. Participants valued the flipped-classroom approach, videos, cases, role plays, ready-made teacher's guides, and one-page summaries. Having protected time to complete the modules and temporally coupling the modules with the live, faculty-led sessions enhanced learning. CONCLUSION: The curriculum provides a comprehensive, ready-made, evidenced-based platform for training residents and faculty in SUDs. It can be implemented by faculty with all levels of prior expertise, cotaught by physicians and behavioral health providers, tailored to each program's didactic schedule, and modified based on the local culture and resource availability.

The integration of oral health-related best practice recommendations in the management of patients with diabetes: a cross-sectional survey of primary care physicians.

OBJECTIVE: To determine whether best practice recommendations are being followed by primary care physicians (PCPs) by examining the integration of oral health-related practices in their management of patients with diabetes. METHODS: A cross-sectional study design was used to examine PCPs' knowledge of the bidirectional link between diabetes and periodontal disease (PD), their adherence to international best practice recommendations, and their experience of interprofessional collaboration with dentists via an online survey. RESULTS: In total, 79 of 173 PCPs completed the online survey. Almost 90 percent of PCPs neither inform patients with diabetes about the link with PD nor advise dental care. Approximately, one-third of PCPs (32 percent) felt confident facilitating access to dentists. However, 93 percent of PCPs do not refer patients with diabetes to dentists as part of diabetes management. CONCLUSION: PCPs tend not to inform their patients with diabetes of the bidirectional link with PD, or provide advice or referral to attend dental care as part of diabetes management.

Establishing Antibiotic Stewardship Programs in Rural Hospitals to Decrease Fluoroquinolone Prescribing: The Vermont Experience.

Critical access and rural community hospitals struggle to develop effective antimicrobial stewardship programs (ASPs). We assisted six Vermont hospitals in developing their antimicrobial stewardship programs to meet the Centers for Disease Control and Prevention's core elements of antibiotic stewardship. We show that rural hospitals in Vermont can (1) extract antimicrobial use data from their electronic medical record; (2) develop interventions to decrease high use antimicrobial agents, such as fluoroquinolones; and (3) successfully develop sustained ASPs meeting the CDC core elements in less than 2 years.

An AUC Target Simulation for Vancomycin in Patients With Class III Obesity.

OBJECTIVE: The objective of this simulation is to compare 24-hour vancomycin (Vanc24) dosage requirements between a target area under the curve (AUC) versus a target trough approach in patients with class III obesity. METHODS: Adult patients were included if they received vancomycin in accordance with the University of Vermont Medical Center's class III obesity dosage protocol from June 2016 through December 2018. Patient-specific pharmacokinetic parameters were calculated for each patient using the Sawchuck-Zaske method. For this simulation, Vanc24 dosages were calculated to achieve an AUC of 400 mg/L h and a trough concentration of 15 mg/L. RESULTS: Sixty-three patients had Vanc24 dosage requirements calculated. The median age was 59 years (interquartile range [IQR]: 51.5-68), body mass index (BMI): 45.7 kg/m2 (IQR: 42.4-51.5), and 50.7% were male. The mean Vanc24 dosage requirements were 3995 mg (standard deviation [SD] ±1673) in the target trough approach versus 2783 mg (SD ±1149) in the target AUC approach (P < .0001). CONCLUSION: A target AUC approach required less vancomycin over a 24-hour time period relative to a target trough approach. Vancomycin therapeutic drug monitoring that explicitly targets AUC may reduce vancomycin exposure and potentially decrease the risk of nephrotoxicity in patients with class III obesity.

Variation in dental services by rurality among privately insured adults in the United States.

OBJECTIVES: Rurality is associated with reduced dental access and worse oral health outcomes. It is unknown whether there is variation in dental services received by rural adults who visit a dentist. METHODS: This was a retrospective analysis of claims data from a large private insurer. All individuals who had at least one dental visit in 2018 were included. Patient demographics, whether or not a patient's ZIP code was rural as defined by the Federal Office of Rural Health Policy, as well as ZIP code demographics were collected. Differences in the frequency of dental services received were evaluated using χ2 tests. Multilevel logistic regressions were used to evaluate the individual and ZIP code-level correlates of receiving a preventive dental procedure, a tooth extraction, or a denture-related dental procedure. RESULTS: Rates of preventive, oral and maxillofacial surgery, and denture-related procedures were higher among rural adults. Accounting for individual age and gender, and ZIP code average income and dentist density, rural dwellers were more likely to receive a preventive procedure [odds ratio (OR) 1.15, P < 0.0001] or tooth extraction (OR 1.08, P < 0.0001), and less likely to have a denture-related procedure (OR 0.94, P = 0.015) compared to nonrural dwellers. Female gender was the strongest predictor of receiving a preventive procedure (OR 1.30, P < 0.0001). CONCLUSIONS: Even among privately insured individuals with known access to dental care, rurality was associated with significant differences in the frequency of various dental procedures. Rural dental patients may have higher needs for oral surgical procedures, even when they have access to preventive care.

Utility of ampicillin-sulbactam for empiric treatment of ventilator-associated pneumonia in a trauma population.

BACKGROUND: Ampicillin-sulbactam is guideline-recommended treatment for early-onset ventilator-associated pneumonia (VAP). However, intensive care unit clinicians are encountering increasing resistance to ampicillin-sulbactam. We sought to analyze the time period for early-onset VAP in our trauma population by using daily evaluation of resistance to ampicillin-sulbactam. METHODS: A retrospective cohort study was completed on all mechanically ventilated trauma patients admitted to a rural level-1 trauma center from January 2003 to December 2008 who were diagnosed with VAP. Daily bacterial resistance to ampicillin-sulbactam > 15% was defined as the threshold for early empiric antibiotic failure for the first episode of VAP. A univariate analysis of risk factors for multi-drug resistant pathogens (MDRPs) and comorbidities was completed to assess for predisposing factors for ampicillin-sulbactam resistance. RESULTS: One hundred sixty-three pathogens were identified in 121 trauma patients diagnosed with VAP. Of these isolates, 71% were gram-negative, 28% were gram-positive, and 1% was fungal. Methicillin-susceptible Staphylococcus aureus (23.9%), H aemophilus influenzae (20.9%), and Pseudomonas aeruginosa (11.7%) were the most common infecting organisms. Daily ampicillin-sulbactam resistance was 40%, 26%, 32%, 43%, 50%, and 60% on days 3 to 7 and ≥ 8 days, respectively. Only the presence of MDRP risk factors (89% vs. 65%, p < 0.01) and hospital LOS (36.8 [22.8-49.0] vs. 25.7 days [19.0-32.5], p < 0.01) was different between ampicillin- sulbactam resistant and ampicillin-sulbactam susceptible VAP groups. On univariate analysis, hospital length of stay >4 days and antibiotic use within 90 days were associated with ampicillin-sulbactam resistant VAP (p < 0.01). CONCLUSIONS: Ampicillin-sulbactam is not an effective empiric therapy for early-onset VAP in our rural trauma population. The utility of ampicillin-sulbactam should be reviewed at other institutions to assess for appropriate empiricism.

The detection of oral cancer and potentially malignant disorders in Ireland: An observational study of 100 cases.

OBJECTIVE: To describe the diagnostic details of a sample of histologically diagnosed malignant and potentially malignant oral lesions from Ireland; to examine how these lesions were first detected, and by whom; and to determine whether factors influenced how these lesions were detected, who detected them, and the type of lesion diagnosed. METHODS: A retrospective review was carried out of the clinical notes relating to oral lesions histologically diagnosed as squamous cell carcinoma (SCC), carcinoma in-situ, or epithelial dysplasia from biopsies performed in hospital-based specialist units and submitted to a diagnostic pathology service based in Dublin, Ireland, between June and December 2015. In addition to sex, age, and smoking status, details were collected relating to the diagnosis, how the lesion was detected, and by whom. RESULTS: There were 100 cases reviewed: SCC (29), carcinoma in-situ (5), and epithelial dysplasia (66). There were 49 opportunistic findings: dentists detected 47 (94 percent), and 51 presenting complaints: primary care physicians (PCPs) detected 30 (60 percent). There was a lower likelihood of opportunistic findings among males (odds ratio 0.41; 95 percent CI 0.18, 0.91). CONCLUSIONS: Dentists in Ireland detected significant proportions of malignant and potentially malignant oral lesions as opportunistic findings, although opportunistic findings were less likely to occur among male patients.

Potential influence of antisecretory therapy on the development of Candida-associated intraabdominal infection.

BACKGROUND: Concerns surrounding the potential extra gut complication of gastric acid suppression are becoming increasingly realized. OBJECTIVE: To determine whether chronic antisecretory treatment with a proton pump inhibitor (PPI) or histamine(2)-receptor antagonist (H(2)RA) is associated with the presence of Candida spp. in cases of complicated intraabdominal infection. METHODS: We conducted a case-controlled study of adult surgical intensive care unit patients with complicated intraabdominal infection during a 5-year period. Exclusion criteria consisted of primary peritonitis, diagnosis of intraabdominal infection more than 72 hours before hospital admission, or a stay in the intensive care unit of less than 72 hours. Patients were categorized into either the antisecretory group (H(2)RA or PPI therapy prior to admission) or control group (no prior antisecretory therapy). RESULTS: One hundred eighteen patients met inclusion criteria. Chronic antisecretory (n = 41) and control (n = 77) patients were similar except in median age (69.0 vs 59.0 y; p = 0.026) and preadmission antibiotic use (36.6% vs 15.6%; p = 0.010). The 2 groups had a similar proportion of patients with Candida (30.3% vs 32.1%; p = 0.857); the cultures included C. albicans, C. glabrata, and C. parapsilosis. Yeast was recovered more often in patients diagnosed with community-acquired intraabdominal infection and in patients who had used PPIs before hospital admission (p = 0.066). Additionally, Candida was cultured more often in antisecretory patients with a history of prior abdominal surgery than in control patients (91.7% vs 62.5%; p = 0.066). CONCLUSIONS: No significant difference was found in the number of patients in the antisecretory and control groups from whom peritoneal Candida was recovered. However, patients with prior abdominal surgery and those in the community with chronic PPI use may be predisposed to Candida-associated intraabdominal infections.