Faculty Bibliography

BACKGROUND:Heart failure accounts for more than one million US hospitalizations annually, with 30-day all-cause readmission approaching 25% and triggering CMS Hospital Readmissions Reduction Program penalties. The 2022 ACC/AHA/HFSA guideline and the 2023 ESC focused update elevated SGLT2 inhibitors to Class I therapy for heart failure with reduced ejection fraction (HFrEF) [1, 2]. The DAPA ACT HF-TIMI 68 prespecified meta-analysis demonstrated reductions in cardiovascular death or worsening heart failure (HR 0.71) and all-cause mortality (HR 0.57). Real-world prescribing patterns and 30-day readmission outcomes in the post-guideline US era are not well characterized. The relative contribution of clinical stability variables versus co-prescribed guideline-directed medical therapy (GDMT) to confounding has not been directly quantified in this setting. METHODS:We conducted a retrospective cohort study at four NYU Langone Health hospitals from January 2023 to January 2026. Adults with a primary heart failure discharge diagnosis were included. The prespecified primary analysis was in the HFrEF subgroup (LVEF ≤ 40%). The primary outcome was 30-day all-cause readmission. Stabilized inverse probability of treatment weighting (IPTW) was the primary adjustment, with overlap weighting (ATO) as sensitivity analysis. Hierarchical logistic regression decomposed the confounding contribution of clinical stability parameters relative to GDMT. The E-value assessed robustness to unmeasured confounding. RESULTS:Among 438 patients, 122 (27.9%) received in-hospital SGLT2 inhibitor initiation. The HFrEF rate was 41.6%, a sixfold increase from 6.6% reported in INSIGHT-HF (2020-2021). Patients with prior heart failure hospitalization received SGLT2 inhibitors at 11.4% versus 29.7% in those without (p < 0.001). In HFrEF (n = 221), 30-day readmission was 12.1% versus 31.8% (crude OR 0.29, 95% CI 0.14-0.61). The primary IPTW estimate was OR 0.34 (95% CI 0.13-0.91, p = 0.032). Sensitivity analyses were directionally consistent. Clinical stability parameters contributed only 9.3% confounding attenuation; GDMT was the dominant confounder. CONCLUSIONS:In a contemporary US post-guideline cohort, in-hospital SGLT2 inhibitor initiation reached 41.6% in HFrEF but remained low in patients with recent heart failure hospitalization. In-hospital SGLT2 inhibitor initiation was associated with lower 30-day all-cause readmission, though initiation was strongly bundled with discharge GDMT optimization and cannot be distinguished from a GDMT optimization effect with this study design. These findings should be considered hypothesis-generating. Because short-term safety events and post-discharge persistence were not systematically captured, these findings should not be interpreted as establishing the benefit-risk profile of inpatient SGLT2 inhibitor initiation. The prescribing gap in high-risk patients is an actionable quality-improvement target.

Orthostatic hypotension is defined as a decrease in systolic blood pressure of at least 20 mmHg or a decrease in diastolic blood pressure of at least 10 mmHg (or both), within three minutes of moving from a supine to an upright or standing position. Droxidopa is a synthetic amino acid analog that is directly metabolized to norepinephrine by dopa-decarboxylase, subsequently providing alpha and beta-agonist effects to increase blood pressure. It is indicated in the treatment of neurogenic orthostatic hypotension caused by primary autonomic failure that is associated with Parkinson disease, multi-system atrophy, pure autonomic failure, dopamine beta-hydroxylase deficiency, and/or non-diabetic autonomic neuropathy. In addition, it has been studied in other disease states, such as diabetic autonomic neuropathy-associated orthostatic hypotension and supine hypotension. We report on two cases of off-label droxidopa use. The first case was for diabetic autonomic neuropathy-associated orthostatic hypotension, and the second case was for hypotension due to autonomic dysfunction associated with rheumatoid arthritis. Although the outcomes differed in each case, this article contributes to the literature demonstrating that droxidopa may have varying effects in treating orthostatic hypotension of non-neurogenic etiology.

We present a case of a 36-year-old female who came into the emergency department with right-side abdominal pain. She went to the operating room for a diagnostic laparoscopy and appendectomy. She received intravenous (IV) acetaminophen every six hours both preoperatively and postoperatively for pain control. The patient's aspartate aminotransferase and alanine aminotransferase levels were elevated and peaked at 4,833 and 6,600 IU/L, respectively, from baselines of 14 and 15, respectively, while she was receiving 16 doses of IV acetaminophen. The patient was transferred to a regional liver transplant center for evaluation for a transplant. She was treated with IV N-acetylcysteine and discharged with a normal liver-function test without a transplant. This case report supports the possibility of hepatotoxicity associated with IV acetaminophen.

A 2-year-old girl was found with an empty bottle of levothyroxine and blue coloring around her mouth. Forty tablets of 150-microg levothyroxine tablets were missing. Her 6-hour postingestion total thyroxine (T4) level was 68.1 microg/dL (normal range: 5-12 microg/dL), and her total triiodothyronine (T3) level was 472 ng/dL (normal range: 40-130 ng/dL). Serum levels of thyrotropin, T3, and T4 were then checked on days 3, 5, 7, and 10. On postingestion day 5, the child presented for follow-up with hyperthermia, vomiting, irritability, and increased lethargy. She was referred to the emergency department, where a heart rate of 220 beats per minute, a blood pressure of 130/80 mm Hg, and a temperature of 101 degrees F were recorded. She also had multiple episodes of diarrhea. The patient was treated with oral propranolol (0.8 mg/kg) every 6 hours, intravenous normal saline, and ibuprofen; all her vital signs improved. Serial T3, T4, and thyrotropin serum levels were measured. Her total T3 levels were >800, 798, 445, 446, and 98 ng/dL on days 3, 5, 6, 9, and 13, respectively. Total T4 measurement was repeated on day 13, and the concentration was found to be 11.9 microg/dL. Her thyrotropin levels remained undetectable throughout the course of treatment. The patient was discharged from the hospital after a 4-day PICU stay, in good condition, on oral propranolol 0.8 mg/kg every 8 hours. Propranolol administration was discontinued 8 days after initiation with no further tachycardia, hypertension, or hyperthermia. The child tolerated the recommended regimen.

CONTEXT/BACKGROUND:Although the circumstances are not well studied, grandparents' medications account for 10% to 20% of unintentional pediatric intoxications in the United States. OBJECTIVES/OBJECTIVE:To characterize circumstances leading to and outcomes from pediatric pharmaceutical exposures. To identify preventable risk factors associated with this pattern of injury, referred to as the "granny syndrome." DESIGN, SETTING, AND PARTICIPANTS/METHODS:Retrospective review of records of telephone calls made to a certified regional poison control center in the United States. Records were analyzed for all calls concerning children aged 6 years or younger who were exposed to grandparents' medication(s). For statistical analysis, regression and chi(2) analysis as well as Fisher exact tests were used. The sample size provided 80% power to detect a 10% difference at the 5% level of significance. Statistical significance was set at P< or =.05. MAIN OUTCOMES MEASURED/METHODS:Use of child-resistant containers (CRCs), the location of pharmaceuticals prior to pediatric ingestion, and drug classes involved (eg, analgesics, cardiovascular drugs). RESULTS:Of the 200 incidents analyzed, 90 (45%) cases involved CRCs, and 110 (55%) involved containers that were not child resistant. For these incidents, the average age of the child was 18.8 months; the grandparent was aged on average 58.7 years. Most medications had been placed on tables or countertops (91 [46%]), low shelves (57 [29%]), or in pocketbooks (34 [17%]). The type of container in which the pharmacologic agent was stored (CRC vs non-CRC) was not statistically significant (P>.1). Ease of access to medication, regardless of the type of container used, was the only statistically significant outcome (P<.001). In the present study, accidental pediatric exposures most frequently involved cardiovascular (90 [45%]), analgesic (84 [42%]), and psychotropic (32 [16%]) medications. CONCLUSION/CONCLUSIONS:Pediatric exposure to pharmaceutical agents is a preventable cause of injury. Physicians have an important opportunity to assist in preventing pediatric pharmaceutical exposures by instructing parents and grandparents on how to better limit children's access to medications as an essential component to enhance child safety.

Although acetaminophen (APAP)-associated liver injury is well recognized, there are few reports describing APAP nephrotoxicity, and most of them are single cases. It has also been suggested that N-acetylcysteine (NAC), used to treat the hepatotoxicity, may be harmful to the kidneys. To examine this contention and to determine whether renal involvement in APAP poisoning is at all common, we analyzed the incidence and outcome of acute renal dysfunction in patients hospitalized for APAP overdose reported to our regional poison center over a year. Eleven APAP-poisoned patients had elevated liver function tests; nine of them had azotemia. Those with higher AST levels tended to be younger and to have lower APAP levels on admission. Two patients with acute renal injury died after admission. The other seven patients with renal dysfunction recovered in 2 to 7 days. Six of these received NAC; their mean serum creatinine fell from 3.2 +/- 2.0 versus 1.7 +/- 0.9 mg/dL (p < 0.05). We conclude that acute renal failure is not uncommon in APAP poisoning and appears to be unrelated to the degree of liver injury. NAC therapy did not seem to worsen nephrotoxicity.