Challenges to decarbonizing medication prescribing and use practices: A call to action.

Climate change undeniably impacts the social and environmental determinants of one's health. The healthcare sector, encompassing medications and the pharmaceutical industry supply chain, accounts for a significant portion of global health care contributions to greenhouse gas (GHG) and waste production. Despite these realities, healthcare professionals - physicians, pharmacists, nurses, and others - may be unaware of GHG emissions and the long-term environmental effects of the medications they prescribe, dispense, and administer daily. In this commentary, we identify existing challenges and explore potential strategies to recognize and reduce the climate change impacts associated with medication use.

Evaluation of temperature excursions from USP <659> recommendations during mail transit.

BACKGROUND: Patients use mail delivery as a convenient alternative to acquiring medications in person. Federal laws require nonspecialty oral medications to be stored at controlled room temperature during distribution; however, no laws or regulations govern temperature requirements for medication transport among patients, which may expose medications to harmful temperature excursions. OBJECTIVE: The purpose of this study was to evaluate temperature excursions during mail transit based on the shipment method, carrier, and season. METHODS: This prospective study monitored temperature fluctuations during simulated mail transit between New Jersey, California, and Tennessee over winter (December 2019-February 2020) and summer (August-September 2020) time frames. Packages with data-logging thermometers were shipped to 3 U.S. destinations via 3 common mail carriers and 2 popular shipping methods. Three packages were mailed for each combination of season, carrier, and shipping method, representing 36 individual packages. The primary end point was percent of transit time out of range (OOR) based on the United States Pharmacopeia <659> recommended range, 68°F to 77°F. Additional end points include package transit durations and extreme temperatures. RESULTS: Evaluated packages spent an average of 68.3% of transit time OOR. In winter, 3-day and next business day packages spent similar time OOR (80.1% vs. 78%). In summer, 3-day packages spent more time OOR compared with next business day shipping (43.1% vs. 13.6%). Mean transit time was statistically significantly longer for 3-day packages (406.6 hours vs. 303.1 hours; P < 0.0001). Mean winter transit time was statistically significantly longer than summer (475.7 hours vs. 233.9 hours; P < 0.001) regardless of the shipping method. The minimum and maximum temperatures recorded were 5.1°F and 102.3°F, respectively. CONCLUSION: Package temperatures were outside of the recommended range for most of the transit time regardless of the shipping method, carrier, or season.

Comprehensive Assessment of Ankle Syndesmosis Injury Using 3D Isotropic Turbo Spin-Echo Sequences: Diagnostic Performance Compared With That of Conventional and Oblique 3-T MRI.

OBJECTIVE: The objective of this study is to evaluate the diagnostic performance of 3D sampling perfection with application-optimized contrasts using different flip angle evolution (SPACE) sequences in the evaluation of ankle syndesmosis injuries, compared with that of conventional orthogonal MRI and oblique proton density-weighted turbo spin-echo (TSE) sequences performed with 3-T MRI. MATERIALS AND METHODS: This retrospective study included 98 patients with suspected ankle syndesmosis injuries who underwent both MRI and surgery. Fifty patients (mean [± SD] age, 34.5 ± 15.3 years) had acute injuries, and 48 patients (mean age, 28.5 ± 9.6 years) had chronic injuries. For both groups, the diagnostic performance of each MRI sequence with regard to syndesmosis injuries was evaluated. Arthroscopy findings were used as a reference standard to confirm diagnosis. RESULTS: No statistically significant differences in the sensitivity, specificity, accuracy, and AUC values were noted between images of the syndesmosis obtained using proton density-weighted TSE sequences and images of the syndesmosis obtained using 3D SPACE sequences (p > 0.05). Interobserver agreement regarding the diagnosis of both acute and chronic syndesmosis injuries was almost perfect for proton density-weighted TSE images (κ > 0.80) and was substantial for 3D SPACE images (κ > 0.75). Both methods of obtaining images of the syndesmosis had a diagnostic performance superior to that of conventional orthogonal MRI. CONCLUSION: The performance of 3D SPACE sequences is comparable to that of 2D proton density-weighted MR images for the diagnosis of acute and chronic syndesmosis injuries.

Deltoid ligament in acute ankle injury: MR imaging analysis.

OBJECTIVE: To identify the pattern of deltoid ligament injury after acute ankle injury and the relationship between ankle fracture and deltoid ligament tear by magnetic resonance imaging (MRI). MATERIALS AND METHODS: Thirty-six patients (32 male, and 4 female; mean age, 29.8 years) with acute deltoid ligament injury who had undergone MRI participated in this study. The deltoid ligament was classified as having 3 superficial and 2 deep components. An image analysis included the integrity and tear site of the deltoid ligament, and other associated injuries. Association between ankle fracture and deltoid ligament tear was assessed using Fisher's exact test (P < 0.05). RESULTS: Of the 36 patients, 21 (58.3 %) had tears in the superficial and deep deltoid ligaments, 6 (16.7 %) in the superficial ligaments only, and 4 (11.1 %) in the deep ligaments only. The most common tear site of the three components of the superficial deltoid and deep anterior tibiotalar ligaments was their proximal attachments (94 % and 91.7 % respectively), and that of the deep posterior tibiotalar ligament (pTTL) was its distal attachment (82.6 %). The common associated injuries were ankle fracture (63.9 %), syndesmosis tear (55.6 %), and lateral collateral ligament complex tear (44.4 %). All the components of the deltoid ligament were frequently torn in patients with ankle fractures (tibionavicular ligament, P = 0.009). CONCLUSION: The observed injury pattern of the deltoid ligament was complex and frequently associated with concomitant ankle pathology. The most common tear site of the superficial deltoid ligament was the medial malleolar attachment, whereas that of the deep pTTL was near its medial talar insertion.

HslVU ATP-dependent protease utilizes maximally six among twelve threonine active sites during proteolysis.

HslVU is a bacterial ATP-dependent protease distantly related to eukaryotic proteasomes consisting of hexameric HslU ATPase and dodecameric HslV protease. As a homolog of the 20 S proteasome beta-subunits, HslV also uses the N-terminal threonine as the active site residue. However, unlike the proteasome that has only 6 active sites among the 14 beta-subunits, HslV has 12 active sites that could potentially contribute to proteolytic activity. Here, by using a series of HslV dodecamers containing different numbers of active sites, we demonstrate that like the proteasome, HslV with only approximately 6 active sites is sufficient to support full catalytic activity. However, a further reduction of the number of active sites leads to a proportional decrease in activity. Using proteasome inhibitors, we also demonstrate that substrate-mediated stabilization of the HslV-HslU interaction remains unchanged until the number of the active sites is decreased to approximately 6 but is gradually compromised upon further reduction. These results with a mathematical model suggest HslVU utilizes no more than 6 active sites at any given time, presumably because of the action of HslU. These results also suggest that each ATP-bound HslU subunit activates one HslV subunit and that substrate bound to the HslV active site stimulates the HslU ATPase activity by stabilizing the HslV-HslU interaction. We propose this mechanism plays an important role in supporting complete degradation of substrates while preventing wasteful ATP hydrolysis in the resting state by controlling the interaction between HslV and HslU through the catalytic engagement of the proteolytic active sites.

Changes of the growth plate in children: 3-dimensional magnetic resonance imaging analysis.

PURPOSE: This pilot study assessed changes in the growth plate and growth rates in children during a 6-month period. METHODS: The study included 31 healthy children (17 boys, 14 girls) under evaluation for growth retardation. Height, weight, bone age, insulin like growth factor-1 (IGF-1), and insulin like growth factor binding protein 3 (IGF-BP3) were measured at baseline and after 6 months. In addition, the diameter, thickness, and volume of the femoral and tibial growth plates were measured using magnetic resonance imaging. RESULTS: The mean bone age in boys and girls was 11.7 and 10.7 years, respectively. In boys, height (z score) (-0.2 vs. 0.0), weight (z score) (0.8 vs. 1.1), body mass index (BMI) (z score) (1.27 vs. 1.5), IGF-1 (ng/mL) (343.6 vs. 501.8), and IGF-BP3 (ng/mL) (5,088.5 vs. 5,620.0) were significantly higher after 6 months. In girls, height (z score) (-1.0 vs. -0.7), weight (z score) (-0.5 vs. 0.1), BMI (z score) (-0.02 vs. 0.3), IGF-1 (ng/mL) (329.3 vs. 524.6), and IGF-BP3 (ng/mL) (4,644.4 vs. 5,593.6) were also significantly higher after 6 months. In both sexes, the mean diameter and volume of the femoral and tibial growth plates were significantly increased 6 months later. CONCLUSION: No significant correlation was found between changes in the growth plate and clinical parameters in children with growth retardation in this study, other than correlations of change in femoral diameter with weight and BMI. A larger, long-term study is needed to precisely evaluate the correlation between change in the growth plate and growth.

Deltoid Ligament and Tibiofibular Syndesmosis Injury in Chronic Lateral Ankle Instability: Magnetic Resonance Imaging Evaluation at 3T and Comparison with Arthroscopy.

OBJECTIVE: To evaluate the prevalence of deltoid ligament and distal tibiofibular syndesmosis injury on 3T magnetic resonance imaging (MRI) in patients with chronic lateral ankle instability (CLAI). MATERIALS AND METHODS: Fifty patients (mean age, 35 years) who had undergone preoperative 3T MRI and surgical treatment for CLAI were enrolled. The prevalence of deltoid ligament and syndesmosis injury were assessed. The complexity of lateral collateral ligament complex (LCLC) injury was correlated with prevalence of deltoid or syndesmosis injuries. The diagnostic accuracy of ankle ligament imaging at 3T MRI was analyzed using arthroscopy as a reference standard. RESULTS: On MRI, deltoid ligament injury was identified in 18 (36%) patients as follows: superficial ligament alone, 9 (50%); deep ligament alone 2 (11%); and both ligaments 7 (39%). Syndesmosis abnormality was found in 21 (42%) patients as follows: anterior inferior tibiofibular ligament (AITFL) alone, 19 (90%); and AITFL and interosseous ligament, 2 (10%). There was no correlation between LCLC injury complexity and the prevalence of an accompanying deltoid or syndesmosis injury on both MRI and arthroscopic findings. MRI sensitivity and specificity for detection of deltoid ligament injury were 84% and 93.5%, and those for detection of syndesmosis injury were 91% and 100%, respectively. CONCLUSION: Deltoid ligament or syndesmosis injuries were common in patients undergoing surgery for CLAI, regardless of the LCLC injury complexity. 3T MRI is helpful for the detection of all types of ankle ligament injury. Therefore, careful interpretation of pre-operative MRI is essential.