Surge of Midazolam Use in the Midst of Lorazepam Shortage.

BACKGROUND: Lorazepam is a widely prescribed benzodiazepine that is used to manage anxiety, insomnia, and status epilepticus and is used for pre-anesthetic care as well as several off-label indications including aggression, alcohol withdrawal, panic disorder, chemotherapy-associated anticipatory nausea, and catatonia. Recent increases in demand, manufacturing changes, and quality control issues have resulted in a shortage of injectable and oral lorazepam, prompting clinicians to use alternatives. One such alternative is midazolam, a drug that has been used primarily in the intensive care unit and anesthesia settings. PROCEDURES: This article examines the significant pharmacologic differences between lorazepam and midazolam. In addition, this article provides dosage guidelines based on the current scientific knowledge and recommendations for conversion equivalencies. RESULTS: The clinical preference for lorazepam can be attributed to its simpler metabolism with no active metabolites, better suitability for patients with less severe hepatic and renal impairment, less risk of adverse reactions, fewer drug-drug interactions, and greater desirability for special populations. In periods of shortages, midazolam has been shown to be effective for a number of off-label uses. To manage conditions that have not been extensively studied, clinicians may opt to use conversion equivalencies, with the caveat that guidelines may vary greatly between institutions and online sources; therefore, it would be best to start low and titrate slowly. CONCLUSIONS: Our goal is to aid clinicians in safely and effectively prescribing midazolam during the shortage of injectable lorazepam so that patients are provided the same effects and benefits.

Association of Risk Factors and Comorbidities With Chronic Pain in the Elderly Population.

INTRODUCTION/OBJECTIVE: Chronic pain disorders affect about 20% of adults in the United States, and it disproportionately affects individuals living in the neighborhoods of extreme socioeconomic disadvantage. In many instances, chronic pain has been noted to arise from an aggregation of multiple risk factors and events. Therefore, it is of importance to recognize the modifiable risk factors. The aim of this study was to investigate the comorbid medical conditions and risk factors associated with chronic pain disorders in patients aged 65 years and older. METHODS: Our team retrospectively reviewed medical records of elderly patients (65 years and older) who were evaluated in our outpatient medicine office between July 1, 2020 and June 30, 2021 for acute problems, management of chronic medical problems, or well visits. We divided our patients into a group who suffered from chronic pain disorder, and another group who did not have chronic pain disorder. The association of variables were compared between those groups. RESULTS: Of the 2431 patients, 493 (20.3%) had a chronic pain disorder. A higher frequency of females in the group with chronic pain disorder was found compared to the group without a chronic pain disorder (60.6% vs 55.2%; P = .033). The mean ages between the two groups were similar in the group with a chronic pain disorder compared to the group without (76.35 ± 7.5 year vs 76.81 ± 7.59 year; P = .228). There were significant associations of certain comorbidities in the group with a chronic pain disorder compared to the group without a chronic pain disorder, such as depression (21.9% vs 15.2%; P < .001), anxiety (27.0% vs 17.1%; P < .001), chronic obstructive pulmonary disease (8.7% vs 6.1%; P = .036), obstructive sleep apnea (16.8% vs 11.6%; P = .002), gastroesophageal reflux disease (40.8% vs 29.0%; P < .001), osteoarthritis (49.3% vs 26.1%; P < .001), other rheumatologic diseases (24.9% vs 19.4%; P = .006), and peripheral neuropathy (14.4% vs 5.3%; P < .001). CONCLUSION: Female sex, depression, anxiety, chronic obstructive pulmonary disease, obstructive sleep apnea, gastroesophageal reflux disease, osteoarthritis, other rheumatologic diseases, and peripheral neuropathy were significantly associated with chronic pain disorder in elderly patients, while BMI was not associated with chronic pain disorder.

Self-Forming Norbornene-Tetrazine Hydrogels with Independently Tunable Properties.

Although photopolymerization reactions are commonly used to form hydrogels, these strategies rely on light and may not be suitable for delivering therapeutics in a minimally invasive manner. Here, hyaluronic acid (HA) macromers are modified with norbornene (Nor) or tetrazine (Tet) and upon mixing click into covalently crosslinked Nor-Tet hydrogels via a Diels-Alder reaction. By incorporating a high degree of Nor and Tet substitution, Nor-Tet hydrogels with a broad range in elastic moduli (5 to 30 kPa) and fast gelation times (1 to 5 min) are achieved. By pre-coupling methacrylated HANor macromers with thiolated peptides via a Michael addition reaction, Nor-Tet hydrogels are peptide-functionalized without affecting their physical properties. Mesenchymal stem cells (MSCs) on RGD-functionalized Nor-Tet hydrogels adhere and exhibit stiffness-dependent differences in matrix mechanosensing. Fluid properties of Nor-Tet hydrogel solutions allow for injections through narrow syringe needles and can locally deliver viable cells and peptides. Substituting HA with enzymatically degradable gelatin also results in cell-responsive Nor-Tet hydrogels, and MSCs encapsulated in Nor-Tet hydrogels preferentially differentiate into adipocytes or osteoblasts, based on 3D cellular spreading regulated by stable (HA) and degradable (gelatin) macromers.

Risk Factors Associated With Atrial Fibrillation in Elderly Patients.

Background: Atrial fibrillation (AF) is the most common arrhythmia with a growing prevalence worldwide, especially in the elderly population. Patients with AF are at higher risk of serious life-threatening events and complications that may lead to long-term sequelae and reduce quality of life. The aim of our study was to examine the association of additional risk factors and comorbid medical conditions with AF in patients 65 years, or older. Methods: We performed a retrospective electronic medical record review of patients aged 65 years and older, who visited our internal medicine office between July 1, 2020 and June 30, 2021. Results: Among 2,433 patients, 418 patients (17.2%) had AF. Our analysis showed that for each unit increased in age, there was a 4.5% increase in the odds of AF (95% confidence interval (CI) 2.2-6.9%; P < 0.001). Compared to patients of Caucasian descent, African-American patients had significantly decreased odds of AF (odds ratio (OR) 0.274, 95% CI 0.141 - 0.531; P < 0.001). Patients with hypertension had 2.241 greater odds of AF (95% CI 1.421 - 3.534; P = 0.001). Additional comorbidities with significantly greater odds of AF included other cardiac arrhythmias (OR 2.523, 95% CI 1.720 - 3.720; P < 0.001), congestive heart failure (OR 3.111, 95% CI 1.674 - 5.784; P < 0.001), osteoarthritis (OR 3.014, 95% CI 2.138 - 4.247; P < 0.001), liver disease (OR 2.129, 95% CI 1.164 - 3.893; P = 0.014), and colorectal disease (OR 1.500 95% CI 1.003 - 2.243; P = 0.048). Comorbidities with significantly decreased odds of AF included other rheumatological disorder (OR 0.144, 95% CI 0.086 - 0.243; P < 0.001), non-steroidal anti-inflammatory drugs (NSAIDs) use (OR 0.206, 95% CI 0.125 - 0.338; P < 0.001), and corticosteroid use (OR 0.553, 95% CI 0.374 - 0.819; P = 0.003). Conclusions: Increasing age, hypertension, presence of other cardiac arrhythmias, congestive heart failure, osteoarthritis, liver disease, and colorectal disease are associated with increased odds of having AF.

Comorbidities and Risk Factors Associated With Insomnia in the Elderly Population.

INTRODUCTION/OBJECTIVES: Sleep disorders affect around 50 to 70 million Americans, with chronic insomnia being the most common, especially in the elderly population. With an 11-fold increase in the US office visits due to insomnia, from 0.8 to 9.4 million, between 1993 and 2015, it is imperative to identify the modifiable risk factors. The aim of our study was to examine the association of risk factors and comorbid medical conditions with insomnia in patients 65 years, and older. METHODS: We performed a retrospective electronic medical record review of the patients aged 65 years and older, who visited our suburban internal medicine office between July 1, 2020 and June 30, 2021. Patients were divided into insomnia group, and the group without insomnia. The associated variables were compared. RESULTS: Among 2431 patients, 247 patients (10.2%) had insomnia. Mean ages of the patients in the insomnia group and the group without insomnia were comparable (77 ± 8.1 year vs 76 ± 7.5 year; P = .211). There was a significantly greater frequency of women in the insomnia group compared to the group without insomnia (63.2% vs 55.5%; P = .022). In the insomnia group, there were significantly higher frequencies of association of certain comorbidities compared to the group without insomnia, such as dementia (6.5% vs 3.4%; P = .015), depression (30.8% vs 14.9%; P < 0.001), anxiety disorder (34.4% vs 17.4%; P < .001), atrial fibrillation (19.4% vs 13.4%; P = .01), and chronic pain disorders (32.8% vs 18.9%; P < .001). Logistic regression analysis showed significantly greater odds of insomnia in patients who had depression (OR = 1.860, 95% CI 1.342-2.576; P < .001), anxiety (OR = 1.845, 95% CI 1.342-2.537; P < .001), and chronic pain disorders (OR = 1.901, 95% CI 1.417-2.549; P < .001). CONCLUSIONS: Female sex, dementia, depression, anxiety, chronic pain disorders, and atrial fibrillation are associated with insomnia in the elderly patients. Presence of depression, anxiety, and chronic pain disorders are associated with greater odds of having insomnia in the elderly patients.

Human induced mesenchymal stem cells display increased sensitivity to matrix stiffness.

The clinical translation of mesenchymal stem cells (MSCs) is limited by population heterogeneity and inconsistent responses to engineered signals. Specifically, the extent in which MSCs respond to mechanical cues varies significantly across MSC lines. Although induced pluripotent stem cells (iPSCs) have recently emerged as a novel cell source for creating highly homogeneous MSC (iMSC) lines, cellular mechanosensing of iMSCs on engineered materials with defined mechanics is not well understood. Here, we tested the mechanosensing properties of three human iMSC lines derived from iPSCs generated using a fully automated platform. Stiffness-driven changes in morphology were comparable between MSCs and iMSCs cultured atop hydrogels of different stiffness. However, contrary to tissue derived MSCs, no significant changes in iMSC morphology were observed between iMSC lines atop different stiffness hydrogels, demonstrating a consistent response to mechanical signals. Further, stiffness-driven changes in mechanosensitive biomarkers were more pronounced in iMSCs than MSCs, which shows that iMSCs are more adaptive and responsive to mechanical cues than MSCs. This study reports that iMSCs are a promising stem cell source for basic and applied research due to their homogeneity and high sensitivity to engineered mechanical signals.

Injectable hydrogel with immobilized BMP-2 mimetic peptide for local bone regeneration.

Osteoporosis is a disease characterized by a decrease in bone mineral density, thereby increasing the risk of sustaining a fragility fracture. Most medical therapies are systemic and do not restore bone in areas of need, leading to undesirable side effects. Injectable hydrogels can locally deliver therapeutics with spatial precision, and this study reports the development of an injectable hydrogel containing a peptide mimic of bone morphogenetic protein-2 (BMP-2). To create injectable hydrogels, hyaluronic acid was modified with norbornene (HANor) or tetrazine (HATet) which upon mixing click into covalently crosslinked Nor-Tet hydrogels. By modifying HANor macromers with methacrylates (Me), thiolated BMP-2 mimetic peptides were immobilized to HANor via a Michael addition reaction, and coupling was confirmed with 1H NMR spectroscopy. BMP-2 peptides presented in soluble and immobilized form increased alkaline phosphatase (ALP) expression in MSCs cultured on 2D and encapsulated in 3D Nor-Tet hydrogels. Injection of bioactive Nor-Tet hydrogels into hollow intramedullary canals of Lewis rat femurs showed a local increase in trabecular bone density as determined by micro-CT imaging. The presented work shows that injectable hydrogels with immobilized BMP-2 peptides are a promising biomaterial for the local regeneration of bone tissue and for the potential local treatment of osteoporosis.

Non-surgical management of spontaneous splenic rupture due to Babesia microti infection.

Babesiosis is an emerging tick-borne infection. We describe 2 hospitalized patients from the United States with spontaneous splenic rupture attributable to Babesia microti infection. The first patient was a 36-year-old previously healthy man with a low-grade splenic rupture not requiring surgical intervention. The second was a 70-year-old healthy man whose splenic rupture required proximal splenic artery embolization. Since the spleen is an important organ involved in controlling Babesia infection, management of splenic rupture in an infected patient using an organ preserving approach when appropriate may be preferred.