HIV preexposure prophylaxis (PrEP) has been purposefully incorporated into our family medicine resident training within existing didactic lectures, readings, and routine office visit precepting. This ...mixed-methods evaluation assesses training strategies for PrEP use via survey and drug use evaluation (DUE).
We surveyed 80 current and former family medicine residents (2014-2018) about their exposure to training components, self-reported confidence and competency in PrEP use, and practice behaviors reflecting CDC guidelines for patient eligibility and testing. In addition, we conducted a DUE of patients receiving PrEP from 2012-2018 for adherence to CDC guidelines. We report results with descriptive statistics, with χ2 analysis for group comparisons.
Survey response rate was 56.3%. Among respondents, 46.7% have prescribed PrEP and 55.5% self-assessed as competent to prescribe PrEP, with the majority (84%) rating precepting as most effective for building competence. Those self-assessed as competent were more likely to endorse practice behaviors reflecting CDC guidelines for monitoring PrEP (P<.05). DUE identified 68 patients; 98.5% men who have sex with men. No women with recent sexually transmitted infections, nor persons who inject drugs (PWID) received PrEP. Initial testing completion ranged from 79.4% (HIV) to 54.4% (hepatitis B). Follow-up testing completion ranged from 41.5% (HIV) to 26.4% (syphilis).
Residents rated precepting as the most effective training. However, DUE demonstrated that PrEP underuse, as well as suboptimal testing, limited experiential training on CDC guidelines. Curricular updates should further emphasize appropriate patient selection for PrEP, including women, minorities, and PWID, as well as robust testing, to continue expanding PrEP access.
Celiac disease, an immune reaction to gluten causing nutrient malabsorption, and long-term glucocorticoid therapy adversely affect bone metabolism and increase fracture risk.
A patient with ...long-standing celiac disease on a strict gluten-free diet and long-term glucocorticoid therapy status post kidney transplant for Sjögren syndrome–induced interstitial nephritis presented for management of osteoporosis. Initial evaluation was notable for secondary hyperparathyroidism, which resolved after switching to a gluten-free calcium citrate supplement. Given normal serum total alkaline phosphatase (ALP) and parathyroid hormone (PTH), she began treatment of osteoporosis with abaloparatide. Two months later, she reported abrupt onset of diarrhea with significant weight loss. Biochemical investigation revealed a threefold increase in serum ALP level. As a precaution, abaloparatide was suspended, yet symptoms persisted with elevated ALP and PTH levels. Endoscopy revealed a celiac flare. The clinic-based pharmacist found that her pharmacy had inadvertently dispensed prednisone tablets containing wheat starch. A switch to a gluten-free formulation led to rapid resolution of the diarrhea with weight regain. Serum ALP and PTH levels normalized, and abaloparatide was resumed without biochemical abnormalities.
An unintended switch to a gluten-containing prednisone formulation resulted in uncontrolled celiac disease causing calcium malabsorption, secondary hyperparathyroidism, elevated ALP levels, and an interruption in osteoporosis therapy. Common supplements and drugs can be a hidden source of gluten. Collaboration with a clinic-based pharmacist enhances the detection and prevention of medication-induced adverse reactions.
This case highlights the importance of a careful review of gluten-containing medications and supplements in patients with celiac disease.
Abstract
Disclosure: J. Aurora: None. A. Saraswat: None.
Background: Concentrated regular U-500 (U-500R) insulin is commonly used in patients with T2DM who are highly insulin-resistant, requiring ...more than 200 units of insulin per day. Utilizing U-500R reduces the number of daily injections, decreases injection volume, and improves cost effectiveness. There have been clinical trials using U-500R for continuous subcutaneous insulin infusion (CSII), particularly in Omnipod which has been shown to improve glycemic control and patient satisfaction without an increase in hypoglycemia (1). In addition, U-500R administration via multiple daily injections (MDI) and an investigational U-500R CSII, have been compared and demonstrated improved glycemic control with both modalities, but an increase in nocturnal hypoglycemia with CSII (2). Automated insulin delivery (AID) systems, or hybrid closed loop systems, have not formally been studied in patients with T2DM using U-500R. We present a case of a patient with T2DM with high insulin resistance using U-500R with Omnipod 5 AID system. Clinical Case: A 54-year-old female with T2DM with high insulin resistance was initially on Omnipod Dash with U-100 insulin lispro with baseline A1c 12.1%. She was transitioned to Omnipod 5 in 2022, and over 4 months A1c improved to 8.8%, GMI 8.8%, TIR 38%, TAR 62%, TBR 0%, CV 35.9%, and automated mode 97%. However, her total daily dose was 134 units leading to pod changes every 1.5 days. She expressed interest in switching to U-500R to reduce pod changes while utilizing her current CSII technology. We switched to U-500R, continued automated mode, increased her 24-hour BG target from 120 mg/dL to 130 mg/dL to reduce hypoglycemia risk, and increased her active insulin time from 3 to 6 hours to reflect U-500R kinetics. After 4 weeks, her GMI improved to 8.0%, TIR 47%, TAR 52%, TBR 1%, CV 45.9%, and automated mode 94%. Although nocturnal BG readings were normal, ranging from 70-130 mg/dL, she was having nightly symptoms of relative hypoglycemia. We then adjusted her BG target overnight to 150 mg/dL, which kept BG between 80-130 mg/dL with resolution of her symptoms. Conclusion: U-500R proved to be safe and effective with Omnipod 5 AID. Despite setting a higher BG target, the algorithm continuously kept BG well below this, particularly overnight. However, the safety mechanisms incorporated with the CSII suspended insulin delivery for predicted hypoglycemia. Further research will be required to adapt the automated dosing algorithm to U-500R to reduce the risk of nocturnal hypoglycemia.
References: 1. Lane WS, et al. A prospective trial of U500 insulin delivered by Omnipod in patients with type 2 diabetes mellitus and severe insulin resistance. Endocr Pract. 2010;16(5):778-784.2.Grunberger G, et al. Human regular U-500 insulin via continuous subcutaneous insulin infusion versus multiple daily injections in adults with type 2 diabetes: The VIVID study. Diabetes Obes Metab. 2020;22(3):434-441.
Presentation: Friday, June 16, 2023
Abstract
Background
In primary aldosteronism (PA), aldosterone is inappropriately released into the systemic circulation and binds to the mineralocorticoid receptor (MR) in the distal tubule and ...collecting duct of the kidney. As a result, there is sodium reabsorption and potassium wasting leading to extracellular volume expansion, hypertension, hypokalemia, and, ultimately, suppressed renin. For medication management of aldosterone-producing adenomas with MR antagonists, spironolactone or eplerenone, are recommended. Finerenone is a novel, selective, non-steroidal MR antagonist approved July 2021 to reduce the risk of kidney and heart complications in patients with diabetic kidney disease. Interestingly, finerenone is at least as potent as spironolactone, and more selective for the MR (at least 500-fold) than eplerenone (1). We present a case using finerenone for the treatment of PA.
Clinical Case
OA 62-year-old male with CKD Stage G4/A3, T2DM, obesity, refractory hypertension and persistent hypokalemia underwent two radiofrequency ablations of a left adrenal nodule for the management of PA. Because of biochemical evidence for persistent hyperaldosteronism, pharmacologic therapy was initiated with eplerenone, which was chosen over spironolactone based on tolerability profile. Other antihypertensives included labetalol and nifedipine. Eplerenone was gradually titrated to 150 mg twice daily along with potassium replacement, but PRA remained below goal at 0.35 ng/mL/h with average BP 164/97 mmHg lying, 169/92 mmHg sitting, and 139/90 mmHg standing. Other pertinent labs included average SCr 4.62 mg/dL and eGFR 15 mL/min/1.73m2. A joint decision was made to replace eplerenone with finerenone 10 mg once daily. Two weeks after starting finerenone, PRA increased to 0.59 ng/mL/h, and SCr, eGFR, and potassium were 4.79 mg/dL, 14 mL/min/1.73m2, and 4.2 mEq/L, respectively. BP was 165/92 mmHg lying, 154/92 mmHg sitting, and 118/82 mmHg standing. Finerenone was increased to 20 mg once daily with close follow-up monitoring revealing an average PRA 0.42 ng/mL/h, SCr 4.28 mg/dL, eGFR 16 mL/min/1.73m2, potassium 3.5 mEq/L, and average BP 163/90 mmHg lying, 164/94 mmHg sitting, and 149/84 mmHg standing. Finerenone was well-tolerated and no changes were made to potassium replacement during this time.
Conclusion
Current MR antagonists, spironolactone and eplerenone, have concerns with tolerability due to minimal selectivity and efficacy, respectively. A new generation of MR antagonists, such as finerenone, with high potency and selectivity may lead to practice changes for management of PA. Based on our patient, finerenone increased PRA and similarly controlled BP compared to eplerenone. Further research will be required to evaluate finerenone for PA as a safe, effective, and convenient alternative MR antagonist, specifically with evaluation of dose-dependent effects beyond 20 mg daily as currently described in the literature.
Reference
1. Kolkhof P, Bärfacker L. 30 years of the mineralocorticoid receptor: mineralocorticoid receptor antagonists: 60 years of research and development. J Endocrinol. 2017;234(1): T125-T140.
Presentation: Sunday, June 12, 2022 12:30 p.m. - 2:30 p.m.
Abstract
Background: After surgical resection in adrenocortical carcinoma (ACC), mitotane is often used as adjuvant therapy. However, mitotane can cause adverse effects, such as inducing ...hypercholesterolemia by stimulating HMG-CoA reductase. In addition, mitotane is a strong CYP3A4 inducer which presents a challenge with statins, such as lovastatin, simvastatin, and atorvastatin. We present a case using a PCSK9 inhibitor in mitotane-induced hypercholesterolemia which was refractory to the maximum dose of rosuvastatin.
Clinical Case: A laparoscopic left adrenalectomy was performed on a 45-year old female with Stage 3 (T3, NX, M0) ACC (4.5 x 3.4 x 3.2 cm). Her ACC was determined to be high grade with a mitotic rate 20/50 HPF and Ki-67 of 18.7% with lymphovascular invasion and tumor invasion of periadrenal adipose tissue. Following surgical resection, she started adjuvant therapy mitotane and oral hydrocortisone replacement, as well as 6 weeks of radiation therapy. Prior to starting mitotane, her LDL-C was 133 mg/dL (normal range <130 mg/dL) and treated with simvastatin 40 mg daily. A drug interaction was identified between simvastatin and mitotane, with mitotane reducing effects of simvastatin via CYP3A4 induction, so rosuvastatin 10 mg daily was started instead. A trial of combination rosuvastatin and ezetimibe was used; however, patient discontinued ezetimibe due to reported side effects. As the dose of mitotane increased to achieve a blood concentration of 14–20 mcg/mL, LDL-C simultaneously increased along with a corresponding dose increase of rosuvastatin. While being on mitotane 2 g daily and rosuvastatin 40 mg daily, her lipids peaked with LDL-C 219 mg/dL. The decision was made to start evolocumab administered as 140 mg subcutaneously every 2 weeks in addition to rosuvastatin 40 mg daily. After 4 months of therapy with combination evolocumab and rosuvastatin, her LDL-C decreased to 111 mg/dL, a 49% reduction, while achieving a mitotane concentration of 13 mcg/mL using 4 g daily.
Conclusion: Utilizing a PCSK9 inhibitor, such as evolocumab, allows the dose of mitotane to be increased to achieve a therapeutic level while maintaining adequate control of cholesterol. With options for management of mitotane-induced hypercholesterolemia being limited, off-label use of a PCSK9 inhibitor can be justified clinically as moderate LDL-C reduction has also been shown in a prior published case report (1). Evolocumab is a well-tolerated subcutaneous injection, and should be considered for patients with resistant hypercholesterolemia while on mitotane.
References: (1) Tsakiridou ED, Liberopoulos E, Giotaki Z, et al. Proprotein convertase subtilisin-kexin type 9 (PCSK9) inhibitor use in the management of resistant hypercholesterolemia induced by mitotane treatment for adrenocortical cancer. J Clin Lipidol. 2018;12(3):826–829.
Background/ObjectiveCeliac disease, an immune reaction to gluten causing nutrient malabsorption, and long-term glucocorticoid therapy adversely affect bone metabolism and increase fracture risk.Case ...ReportA patient with long-standing celiac disease on a strict gluten-free diet and long-term glucocorticoid therapy status post kidney transplant for Sjögren syndrome-induced interstitial nephritis presented for management of osteoporosis. Initial evaluation was notable for secondary hyperparathyroidism, which resolved after switching to a gluten-free calcium citrate supplement. Given normal serum total alkaline phosphatase (ALP) and parathyroid hormone (PTH), she began treatment of osteoporosis with abaloparatide. Two months later, she reported abrupt onset of diarrhea with significant weight loss. Biochemical investigation revealed a threefold increase in serum ALP level. As a precaution, abaloparatide was suspended, yet symptoms persisted with elevated ALP and PTH levels. Endoscopy revealed a celiac flare. The clinic-based pharmacist found that her pharmacy had inadvertently dispensed prednisone tablets containing wheat starch. A switch to a gluten-free formulation led to rapid resolution of the diarrhea with weight regain. Serum ALP and PTH levels normalized, and abaloparatide was resumed without biochemical abnormalities.DiscussionAn unintended switch to a gluten-containing prednisone formulation resulted in uncontrolled celiac disease causing calcium malabsorption, secondary hyperparathyroidism, elevated ALP levels, and an interruption in osteoporosis therapy. Common supplements and drugs can be a hidden source of gluten. Collaboration with a clinic-based pharmacist enhances the detection and prevention of medication-induced adverse reactions.ConclusionThis case highlights the importance of a careful review of gluten-containing medications and supplements in patients with celiac disease.
In this book a group of outstanding researchers working on different areas of microalgae biotechnology offer a global vision of the genetic manipulation of microalgae and their applications.
IMPORTANCE: A substantial proportion of the 40 million people in the US who present to emergency departments (EDs) each year after traumatic events develop posttraumatic stress disorder (PTSD) or ...major depressive episode (MDE). Accurately identifying patients at high risk in the ED would facilitate the targeting of preventive interventions. OBJECTIVES: To develop and validate a prediction tool based on ED reports after a motor vehicle collision to predict PTSD or MDE 3 months later. DESIGN, SETTING, AND PARTICIPANTS: The Advancing Understanding of Recovery After Trauma (AURORA) study is a longitudinal study that examined adverse posttraumatic neuropsychiatric sequalae among patients who presented to 28 US urban EDs in the immediate aftermath of a traumatic experience. Enrollment began on September 25, 2017. The 1003 patients considered in this diagnostic/prognostic report completed 3-month assessments by January 31, 2020. Each patient received a baseline ED assessment along with follow-up self-report surveys 2 weeks, 8 weeks, and 3 months later. An ensemble machine learning method was used to predict 3-month PTSD or MDE from baseline information. Data analysis was performed from November 1, 2020, to May 31, 2021. MAIN OUTCOMES AND MEASURES: The PTSD Checklist for DSM-5 was used to assess PTSD and the Patient Reported Outcomes Measurement Information System Depression Short-Form 8b to assess MDE. RESULTS: A total of 1003 patients (median interquartile range age, 34.5 24-43 years; 715 weighted 67.9% female; 100 weighted 10.7% Hispanic, 537 weighted 52.7% non-Hispanic Black, 324 weighted 32.2% non-Hispanic White, and 42 weighted 4.4% of non-Hispanic other race or ethnicity were included in this study. A total of 274 patients (weighted 26.6%) met criteria for 3-month PTSD or MDE. An ensemble machine learning model restricted to 30 predictors estimated in a training sample (patients from the Northeast or Midwest) had good prediction accuracy (mean SE area under the curve AUC, 0.815 0.031) and calibration (mean SE integrated calibration index, 0.040 0.002; mean SE expected calibration error, 0.039 0.002) in an independent test sample (patients from the South). Patients in the top 30% of predicted risk accounted for 65% of all 3-month PTSD or MDE, with a mean (SE) positive predictive value of 58.2% (6.4%) among these patients at high risk. The model had good consistency across regions of the country in terms of both AUC (mean SE, 0.789 0.025 using the Northeast as the test sample and 0.809 0.023 using the Midwest as the test sample) and calibration (mean SE integrated calibration index, 0.048 0.003 using the Northeast as the test sample and 0.024 0.001 using the Midwest as the test sample; mean SE expected calibration error, 0.034 0.003 using the Northeast as the test sample and 0.025 0.001 using the Midwest as the test sample). The most important predictors in terms of Shapley Additive Explanations values were symptoms of anxiety sensitivity and depressive disposition, psychological distress in the 30 days before motor vehicle collision, and peritraumatic psychosomatic symptoms. CONCLUSIONS AND RELEVANCE: The results of this study suggest that a short set of questions feasible to administer in an ED can predict 3-month PTSD or MDE with good AUC, calibration, and geographic consistency. Patients at high risk can be identified in the ED for targeting if cost-effective preventive interventions are developed.
IMPORTANCE: Adverse posttraumatic neuropsychiatric sequelae after traumatic stress exposure are common and have higher incidence among socioeconomically disadvantaged populations. Pain, depression, ...avoidance of trauma reminders, reexperiencing trauma, anxiety, hyperarousal, sleep disruption, and nightmares have been reported. Wrist-wearable devices with accelerometers capable of assessing 24-hour rest-activity characteristics are prevalent and may have utility in measuring these outcomes. OBJECTIVE: To evaluate whether wrist-wearable devices can provide useful biomarkers for recovery after traumatic stress exposure. DESIGN, SETTING, AND PARTICIPANTS: Data were analyzed from a diverse cohort of individuals seen in the emergency department after experiencing a traumatic stress exposure, as part of the Advancing Understanding of Recovery After Trauma (AURORA) study. Participants recruited from 27 emergency departments wore wrist-wearable devices for 8 weeks, beginning in the emergency department, and completed serial assessments of neuropsychiatric symptoms. A total of 19 019 patients were screened. Of these, 3040 patients met study criteria, provided informed consent, and completed baseline assessments. A total of 2021 provided data from wrist-wearable devices, completed the 8-week assessment, and were included in this analysis. The data were randomly divided into 2 equal parts (n = 1010) for biomarker identification and validation. Data were collected from September 2017 to January 2020, and data were analyzed from May 2020 to November 2022. EXPOSURES: Participants were recruited for the study after experiencing a traumatic stress exposure (most commonly motor vehicle collision). MAIN OUTCOMES AND MEASURES: Rest-activity characteristics were derived and validated from wrist-wearable devices associated with specific self-reported symptom domains at a point in time and changes in symptom severity over time. RESULTS: Of 2021 included patients, 1257 (62.2%) were female, and the mean (SD) age was 35.8 (13.0) years. Eight wrist-wearable device biomarkers for symptoms of adverse posttraumatic neuropsychiatric sequelae exceeded significance thresholds in the derivation cohort. One of these, reduced 24-hour activity variance, was associated with greater pain severity (r = −0.14; 95% CI, −0.20 to −0.07). Changes in 6 rest-activity measures were associated with changes in pain over time, and changes in the number of transitions between sleep and wake over time were associated with changes in pain, sleep, and anxiety. Simple cutoffs for these biomarkers identified individuals with good recovery for pain (positive predictive value PPV, 0.85; 95% CI, 0.82-0.88), sleep (PPV, 0.63; 95% CI, 0.59-0.67, and anxiety (PPV, 0.76; 95% CI, 0.72-0.80) with high predictive value. CONCLUSIONS AND RELEVANCE: These findings suggest that wrist-wearable device biomarkers may have utility as screening tools for pain, sleep, and anxiety symptom outcomes after trauma exposure in high-risk populations.
We present a library of empirical stellar spectra created using spectra from the Sloan Digital Sky Survey's Baryon Oscillation Spectroscopic Survey. The templates cover spectral types O5 through L3, ...are binned by metallicity from −2.0 dex through +1.0 dex, and are separated into main-sequence (dwarf) stars and giant stars. With recently developed M dwarf metallicity indicators, we are able to extend the metallicity bins down through the spectral subtype M8, making this the first empirical library with this degree of temperature and metallicity coverage. The wavelength coverage for the templates is from 3650 to 10200 at a resolution of better than R ∼ 2000. Using the templates, we identify trends in color space with metallicity and surface gravity, which will be useful for analyzing large data sets from upcoming missions like the Large Synoptic Survey Telescope. Along with the templates, we are releasing a code for automatically (and/or visually) identifying the spectral type and metallicity of a star.
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