Anna Wentz

Summary: Background: There is growing interest in hydrogen sulfide small intestinal bacterial overgrowth (H ₂ S SIBO). However, basic questions including how clinicians are making the diagnosis, what symptoms are present, and what clinicians are using for treatment, remain unanswered. Aims: To address this, we created an online, survey-based, clinical registry of H ₂ S SIBO cases. Methods: Participants in this study were clinicians diagnosing and treating patients with H ₂ S SIBO and input data on patient presentation, diagnosis, treatment, and treatment response. We describe the population and summarize our results using descriptive statistics. We use Pearson’s chi-squared test and modified Poisson regression in exploratory analyses. Results: 131 total cases were submitted by 99 providers across a spectrum of health disciplines. The mean patient age was 45.6 (71.4% female). The most common symptoms were bloating (77.0%), constipation (50.8%) and abdominal pain (50.8%). Diagnosis was made based on flatline hydrogen in the 3rd hour of a lactulose breath test (42.5%), symptom presentation (empiric) (31.9%), or H ₂ S levels (25.7%). The most common treatments used were a low sulfur diet (46.6%), oregano (44.0%), and bismuth (39.7%). Fifty-eight percent of cases were responders. Of the most common interventions used, only a low sulfur diet (73% responder; p=0.01) and bismuth (76% responder; p=0.01) were significantly associated with treatment response. Interestingly, response rates differed based on how H ₂ S SIBO was diagnosed, with empiric underperforming flatline diagnoses (relative risk 0.60; p=0.04). Conclusions: This case registry represents the largest collection of H ₂ S SIBO cases to-date, providing important early descriptive information on this emerging diagnosis.

Introduction: Urolithiasis causes severe acute pain and is commonly treated with opioid analgesics in the emergency department (ED). We examined opioid analgesic use after episodes of acute pain. Methods: Using data from a longitudinal trial of ED patients with urolithiasis, we constructed multivariable models to estimate the adjusted probability of opioid analgesic use 3, 7, 30, and 90 days after ED discharge. We used multiple imputation to account for missing data and weighting to account for the propensity to be prescribed an opioid analgesic at ED discharge. We used weighted multivariable regression to compare longitudinal opioid analgesic use for those prescribed vs not prescribed an opioid analgesic at discharge, stratified by reported pain at ED discharge. Results: Among 892 adult ED patients with urolithiasis, 79% were prescribed an opioid analgesic at ED discharge. Regardless of reporting pain at ED discharge, those who were prescribed an opioid analgesic were significantly more likely to report using it one, three, and seven days after the visit in weighted multivariable analysis. Among those who were not prescribed an opioid analgesic, an estimated 21% (not reporting pain at ED discharge) and 30% (reporting pain at discharge) reported opioid analgesic use at day three. Among those prescribed an opioid analgesic, 49% (no pain at discharge) and 52% (with pain at discharge) reported using an opioid analgesic at day three. Conclusion: Urolithiasis patients who received an opioid analgesic at ED discharge were more likely to continue using an opioid analgesic than those who did not receive a prescription at the initial visit, despite the time-limited nature of urolithiasis.

Study Objective: Emergency department (ED)‐based naloxone distribution and peer‐based behavioral counseling have been shown to be feasible, but little is known about utilization maintenance over time and clinician, patient, and visit level factors influencing implementation.Methods: We conducted a retrospective cohort study of an ED overdose prevention program providing take‐home naloxone, behavioral counseling, and treatment linkage for patients treated for an opioid overdose at two Rhode Island EDs from 2017 to 2020: one tertiary referral center and a community hospital. Utilizing a Reach, Effectiveness, Adoption, Implementation, and Maintenance (RE‐AIM) framework, we evaluated program reach, adoption, implementation modifiers, and maintenance using logistic and Poisson regression.Results: Seven hundred forty two patients were discharged after an opioid overdose, comprising 966 visits (median: 32 visits per month; interquartile range: 29, 41). At least one intervention was provided at most (86%, 826/966) visits. Take‐home naloxone was provided at 69% of visits (637/919). Over half (51%, 495/966) received behavioral counseling and treatment referral (65%, 609/932). Almost all attending physicians provided take‐home naloxone (97%, 105/108), behavioral counseling (95%, 103/108), or treatment referral (95%, 103/108) at least once. Most residents and advanced practice practitioners (APPs) provided take home naloxone (78% residents; 72% APPs), behavioral counseling (76% residents; 67% APPs), and treatment referral (80% residents; 81% APPs) at least once. Most clinicians provided these services for over half of the opioid overdose patients they cared for. Patients were twice as likely to receive behavioral counseling when treated by an attending in combination with a resident and/or APP (adjusted odds ratio: 2.29; 95% confidence interval, 1.68, 3.12) compared to an attending alone. There was no depreciation in use over time.Conclusions: ED naloxone distribution, behavioral counseling, and referral to treatment can be successfully integrated into usual emergency care and maintained over time with high reach and adoption. Further work is needed to identify low‐cost implementation strategies to improve services use and dissemination across clinical settings.

Impacts of mindfulness-based programs on blood pressure remain equivocal, possibly because the programs are not adapted to engage with determinants of hypertension, or due to floor effects. Primary objectives were to create a customized Mindfulness-Based Blood Pressure Reduction (MB-BP) program, and to evaluate acceptability, feasibility, and effects on hypothesized proximal self-regulation mechanisms. Secondary outcomes included modifiable determinants of blood pressure (BP), and clinic-assessed systolic blood pressure (SBP). This was a Stage 1 single-arm trial with one year follow-up. Focus groups and in-depth interviews were performed to evaluate acceptability and feasibility. Self-regulation outcomes, and determinants of BP, were assessed using validated questionnaires or objective assessments. The MB-BP curriculum was adapted from Mindfulness-Based Stress Reduction to direct participants’ mindfulness skills towards modifiable determinants of blood pressure. Acceptability and feasibility findings showed that of 53 eligible participants, 48 enrolled (91%). Of these, 43 (90%) attended at least 7 of the 10 MB-BP classes; 43 were followed to one year (90%). Focus groups (n = 19) and semi-structured interviews (n = 10) showed all participants viewed the delivery modality favorably, and identified logistic considerations concerning program access as barriers. A priori selected primary self-regulation outcomes showed improvements at one-year follow-up vs. baseline, including attention control (Sustained Attention to Response Task correct no-go score, p<0.001), emotion regulation (Difficulties in Emotion Regulation Score, p = 0.02), and self-awareness (Multidimensional Assessment of Interoceptive Awareness, p<0.001). Several determinants of hypertension were improved in participants not adhering to American Heart Association guidelines at baseline, including physical activity (p = 0.02), Dietary Approaches to Stop Hypertension-consistent diet (p<0.001), and alcohol consumption (p<0.001). Findings demonstrated mean 6.1 mmHg reduction in SBP (p = 0.008) at one year follow-up; effects were most pronounced in Stage 2 uncontrolled hypertensives (SBP≥140 mmHg), showing 15.1 mmHg reduction (p<0.001). MB-BP has good acceptability and feasibility, and may engage with self-regulation and behavioral determinants of hypertension.

During states of low carbohydrate intake, mammalian ketone body metabolism transfers energy substrates originally derived from fatty acyl chains within the liver to extrahepatic organs. We previously demonstrated that the mitochondrial enzyme coenzyme A (CoA) transferase [succinyl-CoA:3-oxoacid CoA transferase (SCOT), encoded by nuclear Oxct1] is required for oxidation of ketone bodies and that germline SCOT-knockout (KO) mice die within 48 h of birth because of hyperketonemic hypoglycemia. Here, we use novel transgenic and tissue-specific SCOT-KO mice to demonstrate that ketone bodies do not serve an obligate energetic role within highly ketolytic tissues during the ketogenic neonatal period or during starvation in the adult. Although transgene-mediated restoration of myocardial CoA transferase in germline SCOT-KO mice is insufficient to prevent lethal hyperketonemic hypoglycemia in the neonatal period, mice lacking CoA transferase selectively within neurons, cardiomyocytes, or skeletal myocytes are all viable as neonates. Like germline SCOT-KO neonatal mice, neonatal mice with neuronal CoA transferase deficiency exhibit increased cerebral glycolysis and glucose oxidation, and, while these neonatal mice exhibit modest hyperketonemia, they do not develop hypoglycemia. As adults, tissue-specific SCOT-KO mice tolerate starvation, exhibiting only modestly increased hyperketonemia. Finally, metabolic analysis of adult germline Oxct1^+/−mice demonstrates that global diminution of ketone body oxidation yields hyperketonemia, but hypoglycemia emerges only during a protracted state of low carbohydrate intake. Together, these data suggest that, at the tissue level, ketone bodies are not a required energy substrate in the newborn period or during starvation, but rather that integrated ketone body metabolism mediates adaptation to ketogenic nutrient states.

Low-carbohydrate diets are used to manage obesity, seizure disorders, and malignancies of the central nervous system. These diets create a distinctive, but incompletely defined, cellular, molecular, and integrated metabolic state. Here, we determine the systemic and hepatic effects of long-term administration of a very low-carbohydrate, low-protein, and high-fat ketogenic diet, serially comparing these effects to a high-simple-carbohydrate, high-fat Western diet and a low-fat, polysaccharide-rich control chow diet in C57BL/6J mice. Longitudinal measurement of body composition, serum metabolites, and intrahepatic fat content, using in vivo magnetic resonance spectroscopy, reveals that mice fed the ketogenic diet over 12 wk remain lean, euglycemic, and hypoinsulinemic but accumulate hepatic lipid in a temporal pattern very distinct from animals fed the Western diet. Ketogenic diet-fed mice ultimately develop systemic glucose intolerance, hepatic endoplasmic reticulum stress, steatosis, cellular injury, and macrophage accumulation, but surprisingly insulin-induced hepatic Akt phosphorylation and whole-body insulin responsiveness are not impaired. Moreover, whereas hepatic Pparg mRNA abundance is augmented by both high-fat diets, each diet confers splice variant specificity. The distinctive nutrient milieu created by long-term administration of this low-carbohydrate, low-protein ketogenic diet in mice evokes unique signatures of nonalcoholic fatty liver disease and whole-body glucose homeostasis.