2023 Update in ambulatory general internal medicine.

The practice of outpatient medicine is demanding, encompasses a wide scope of practice, and leaves little time for internists to stay up to date with the current literature. This article reviews 5 studies published in 2022 and 2023 that have the potential to change the practice of outpatient medicine. Topics covered include chronic kidney disease, secondary cardiovascular disease, kidney stones, obesity, and lipid management.

Qualitative Analysis of Single-Site Headache Surgery: Is It Different From Multiple-Site Surgery?

BACKGROUND: Migraine surgery has been shown to be efficacious, but nuanced effects of surgery on pain and individuals' lives remain incompletely understood. Surgery may be performed at a single or multiple "primary" sites. The aims of this study were to investigate patient perceptions following single-site surgery and compare themes in patients undergoing single-site surgery with those from a previously published conceptual framework generated with patients undergoing multisite surgery. METHODS: Patients who underwent single-site headache surgery participated in open-ended interviews at least 1 year after surgery. Participants (n = 14) had undergone either occipital, temporal, or nasoseptal site surgery. A multidisciplinary team analyzed transcripts. Recurring themes were identified and compared and contrasted to those observed in patients who underwent multiple-site surgery (n = 15) in a previous study (Plast Reconstr Surg 2019;144(4):956-964). RESULTS: Similar recurring themes emerged from the single-site cohort, and the conceptual framework was applicable to all participants. Two new themes emerged from the single-site analysis. First, 5 of 14 participants described being "migraine-free" postoperatively, a finding not observed in the multisite group. Second, several individuals described financial benefits after surgery, via decreased prescription medication requirements, raises at work, and improved productivity. CONCLUSIONS: Single-site headache surgery appears to positively impact patients' lives in ways that support and expand upon previously published outcomes. Patients undergoing surgery at a single site may be more likely to experience a "pain-free" state, which may relate to the underlying pathophysiology of chronic headache. The effect of surgery on finances appears to be an outcome of interest to patients, which should be explored further.

Phenolic benzotriazoles: a class comparison of toxicokinetics of ultraviolet-light absorbers in male rats.

Phenolic benzotriazoles are ultraviolet-light absorbers used in a variety of industrial and consumer applications. We investigated the toxicokinetic behaviour of 9 compounds, covering unsubstituted, monosubstituted, disubstituted, and trisubstituted compounds, following a single gavage (30 and 300 mg/kg) and intravenous (IV) (2.25 mg/kg) administration in male rats.Following IV administration, no distinct pattern in plasma elimination was observed for the compounds with half-lives ranging from 15.4-84.8 h. Systemic exposure parameters, maximum concentration (Cmax) and area under the concentration time curve (AUC), generally increased with the degree of substitution.Following gavage administration, Cmax and AUC of unsubstituted compound were lower compared to the substituted compounds. Cmax and AUC increased ≤7-fold with a 10-fold increase in the dose except for the AUC of the unsubstituted compound where the increase was 30-fold. Plasma elimination half-lives for the class ranged from 1.57 to 192 h with the exception of 30 mg/kg drometrizole.Oral bioavailability was low with ∼ 6% estimated for unsubstituted compound and 12.8-23% for others at 30 mg/kg dose. Bioavailability was lower following administration of the higher dose.Taken collectively, these data point to low oral absorption of phenolic benzotriazoles. The absorption decreased with increasing dose. Substituted compounds may be less metabolized compared to the unsubstituted.

Toxicokinetics of the plasticizer, N-butylbenzenesulfonamide, in plasma and brain following oral exposure in rodents: Route, species, and sex comparison.

N-Butylbenzenesulfonamide (NBBS) is a widely used plasticizer and hence there is potential for human exposure via oral routes. This work investigates the toxicokinetic behavior of NBBS in rodents following a single gavage (20, 60, and 200 mg/kg body weight) or multi-day feed administration (500, 1000, and 2000 ppm). In male and female rats following gavage administration, maximum plasma NBBS concentration, Cmax, was reached at ≤0.539 h. Cmax increased proportionally to the dose. Area under the curve (AUC) increased more than proportionally to the dose and was 4- to 5-fold higher in females than in males. In mice, plasma Cmax was reached at ≤0.136 h and increased proportionally to the dose in female mice and more than proportionally to the dose in males. AUC increased more than proportionally to the dose with no apparent sex difference. Elimination of NBBS in plasma was faster in mice (half-life (h); mice ≤0.432, rat ≤3.55). Oral bioavailability was higher in female rats (≥60%) than males (23-52%) with apparent saturation of clearance at ∼200 mg/kg body weight in females. In mice, bioavailability (5-14%) was lower with no apparent sex difference. NBBS was detected in brains of rats and mice but with low brain:plasma ratios (rats, ≤5; mice, ≤1) suggesting low potential to cross the blood brain barrier. Systemic exposure in male rats and mice following a single gavage administration was ≥48-fold higher than multi-day feed exposure. These data demonstrate potential species, sex, dose- and route-related difference in toxicokinetics of NBBS in rodents.

Linking internal dosimetries of the propyl metabolic series in rats and humans using physiologically based pharmacokinetic (PBPK) modeling.

The metabolic series approach has successfully linked internal dosimetries of metabolically related compounds reducing cost and time for chemical risk assessments. Here, we developed a physiologically based pharmacokinetic (PBPK) model in rats and humans for the propyl metabolic series including propyl acetate, 1-propanol, propionaldehyde, and propionic acid. Manufacturers use these compounds as organic solvents and intermediates during chemical synthesis. Public exposures can occur through using consumer products containing propyl compounds like cosmetics, aerosol sprays, or foods, and occupational exposures can occur at manufacturing facilities. To develop the PBPK model, we measured in vitro metabolism of propyl acetate in blood and liver S9 fractions. We measured concentrations of propyl compounds in blood following intravenous (iv) infusion of 13C-propanol or 13C-propionic acid and closed chamber inhalation exposures to propyl acetate or propanol in rats. Using these studies and other published data, we modified an existing PBPK model for the butyl metabolic series to simulate time course concentrations of propyl compounds in rats and humans. Consistent with measured in vitro and in vivo data, the optimized propyl series model predicts rapid clearance of propyl acetate, higher concentrations of propanol in blood from propyl acetate inhalation compared to propanol inhalation in rats but not in humans, and low concentrations of propionic acid in blood from exposures to propyl acetate or propanol. Regulators can use this model as a tool for propyl compound risk assessment by linking internal dosimetries under various exposure scenarios.

"Like a Normal Person Again": A Qualitative Analysis of the Impact of Headache Surgery.

BACKGROUND: Outcomes after migraine surgery have been previously assessed using quantitative measurements, including the migraine headache index. Qualitative methodologies offer the ability to analyze patients' perceptions and pain experience, and may point to changes in domains not captured by quantitative instruments. The purpose of this study was to characterize individual patients' experiences with migraines and to analyze how patients' experience of headaches changes in relation to surgery. METHODS: Patients who previously underwent migraine surgery performed by a single surgeon participated in semistructured interviews at least 1 year after surgery. Purposive sampling was used to recruit patients [n = 15 (73 percent female)]. Interviews were transcribed verbatim. A multidisciplinary team with backgrounds in surgery, pain management, medicine, and health services research coded and analyzed transcripts. RESULTS: Participants reported improvements in one or more domains of pain following surgery, and changes in medication use and effectiveness. Even in individuals with persistent pain postoperatively, surgery appeared to facilitate an improvement in headache self-efficacy, including an ability to participate in daily activities. Migraineurs frequently described a new degree of control over at least one aspect of their pain. CONCLUSIONS: Migraine surgery appears to positively impact patients' lives in ways that support and expand on previously published outcomes. Patients report benefiting from surgery in ways that are not currently captured in commonly used metrics. This study's findings support the need for more specific patient-reported outcome measures to help clinicians and patients understand the impact of surgery and which outcomes matter most to patients.

Analytical Considerations When Developing an LC-MS/MS Method for More than 30 Analytes.

BACKGROUND: While validation of analytical (LC-MS/MS) methods has been documented in any number of articles and reference texts, the optimal design and subsequent validation of a method for over 30 analytes presents special challenges. Conventional approaches to calibration curves, controls, and run time are not tenable in such methods. This report details the practical aspects of designing and implementing such a method in accordance with College of American Pathologists validation criteria. METHODS: Conventional criteria were followed in the design and validation of a method for 34 analytes and 15 internal standards by LC-MS/MS. These criteria are laid out in a standard operating procedure, which is followed without exception and is consistent with College of American Pathologists criteria. RESULTS: The method presented herein provides quality results and accurate medication monitoring. The method was optimized to negate interferences (both from within the method and from potential concomitant compounds), increase throughput, and provide reproducible quality quantification over relevant analyte concentrations ranges. CONCLUSIONS: The method was designed primarily with quality and accurate medication monitoring in mind. The method achieves these goals by use of novel approaches to calibration curves and controls that both improve performance and minimize risk (financial and operational). As automation and LC-MS/MS equipment continue to improve, it is expected that more methods like this one will be developed.

Dropping out of medical school in the UK: explaining the changes over ten years.

CONTEXT: In the context of changing admissions criteria and an expanding medical school intake in the UK, we analysed the determinants of the medical school dropout probability. OBJECTIVES: We aimed to analyse the determinants of the probability that a student will drop out of medical school during Year 1 and to compare the results of this analysis over time. METHODS: We carried out logistic regression analysis for the 6 intake cohorts of 1990-92 and 1998-2000. RESULTS: Between 1990-92 and 1998-2000, there were substantial increases in both the size of the entry cohort and the proportion of students dropping out of medical school. A logit model for the 1990-92 and 1998-2000 cohorts reveals that the probability of dropping out depended on both the medical school attended and the personal characteristics of the student, including academic preparedness. Almost none of the increase in the dropout rate between the 2 cohort groups can be explained by changes in observable characteristics of the students over this period. Instead, most of the increase in the dropout rate is associated with changes at the level of the institution and in unobserved student characteristics. CONCLUSIONS: University effects, rather than changes in observed student characteristics, explain most of the increased dropout rate over the time period considered. Candidate explanations behind these effects include: less effective admissions policies; changing curricula; greater costs of attending medical school, and a growing mismatch between student and school characteristics. Testing between these competing hypotheses is left for future work.

The impact of evidence on physicians' inpatient treatment decisions.

OBJECTIVE: Previous studies have shown that most medical inpatients receive treatment supported by strong evidence (evidence-based treatment), but they have not assessed whether and how physicians actually use evidence when making their treatment decisions. We investigated whether physicians would change inpatient treatment if presented with the results of a literature search. DESIGN: Before-after study. SETTING: Large public teaching hospital. PARTICIPANTS: Random sample of 146 inpatients cared for by 33 internal medicine attending physicians. INTERVENTIONS: After physicians committed to a specific diagnosis and treatment plan, investigators performed standardized literature searches and provided the search results to the attending physicians. MEASUREMENTS AND MAIN RESULTS: The primary study outcome was the number of patients whose attending physicians would change treatment due to the literature searches. These changes were evaluated by blinded peer review. A secondary outcome was the proportion of patients who received evidence-based treatment before and after the literature searches. Attending physicians changed treatment for 23 (18%) of 130 eligible patients (95% confidence interval, 12% to 24%) as a result of the literature searches. Overall, 86% of patients (112 of 130) received evidence-based treatments before the searches and 87% (113 of 130) after the searches. Changes were not related to whether patients were receiving evidence-based treatment before the search (P =.6). Panels of peer reviewers judged the quality of patient care as improved or maintained for 18 (78%) of the 23 patients with treatment changes. CONCLUSIONS: Searching the literature could improve the treatment of many medical inpatients, including those already receiving evidence-based treatment.