Loss of Appetite in Adult Patients: Effectiveness and Safety of an Appetite Stimulating Medication in an Open-Label, Investigator-Initiated Study in India

Loss of appetite (LOA) may have a negative impact on a patient’s well-being owing to loss of nutrition and associated conditions. The current study assessed the effects of an appetite-stimulating medication containing multivitamins, lysine, and zinc in Indian patients with a history of LOA. Using an investigator-initiated, single-center, open-label, single-arm design, we evaluated the effectiveness and safety of the appetite-stimulating medication (15 mL) in 50 male or female patients (18–55 years old) attending the outpatient department, with a confirmed diagnosis of LOA after two weeks of therapy and assessed the change in Council on Nutrition Appetite Questionnaire (CNAQ) score and safety of the medication after two weeks of treatment. CNAQ scores were presented as mean (standard deviation (SD)). The mean age of patients was 42.1 years, with the majority (66%) being males. At weeks 1 and 2, a statistically significant improvement was observed in the mean CNAQ scores of 25.48 (5.10) and 25.48 (4.29), respectively, vs. baseline (22.08 (2.76); P ≤ 0.0001 both). Majority of the patients had CNAQ appetite scores of 17–28 at baseline (94%), week 1 (66%), and week 2 (78%) of treatment. For patients with acute and chronic illness, a statistically significant improvement was observed in the mean CNAQ score at week 1 (26.75 (3.69), P = 0.0256; 25.24 (5.33), P = 0.0004) and at week 2 (26.63 (3.46), P = 0.0027; 25.26 (4.43), P ≤ 0.0001) from baseline (21.88 (3.31) and 22.12 (2.69), respectively). No serious adverse events were reported during the study. The study findings suggest that appetite-stimulating medication containing multivitamins, lysine, and zinc could be a suitable treatment option for the management of LOA with no significant safety concerns.

Efficacy and Safety of Subcutaneous Infusion of Non-formulated Furosemide in Patients with Worsening Heart Failure: a Real-World Study

We aimed to evaluate the efficacy (short-term changes in surrogates of decongestion) and safety following the ambulatory administration of subcutaneous furosemide (SCF) in patients with WHF. Fifty-five ambulatory patients were treated with SCF administered by an elastomeric pump for at least 72 h. Surrogates of congestion were assessed at baseline, 72 h, and 30 days. Spot urinary sodium (uNa+) was assessed at baseline, 24-48-72 h, and 30 days. The median (IQI) of NT-proBNP and uNa+ at baseline was 5218 pg/mL (2856-10878) and 68±3 mmol/L, respectively. Following administration of SCF (median dose of 100 mg/daily), we found a sustained increase in uNa+ during the first 72 h of treatment compared to baseline, paralleled with evidence of decongestion at 72 h, and 30 days. No significant safety concerns were observed. SCF was an effective and safe diuretic strategy for outpatient congestion management. Graphical abstract

73 Off-label use and safety of drug use in vascular anomalies

Primary Subject area Clinical Pharmacology and Toxicology Background Vascular anomalies (VA) represent a heterogeneous group of disorders associated with an abnormal development and proliferation of blood and/or lymphatic vessels displaying variable clinical presentations and severity. Infantile hemangiomas, venous, and lymphatic malformations, for example, are commonly encountered in children. Other, less frequent diagnostics include Klippel-Trenaunay syndrome and PIK-3CA-related overgrowth spectrum (PROS). Severe phenotypes can alter organ function and/or lead to pain and chronic functional impairment, and are associated with significant morbidity and mortality. Management includes surgical, interventional radiology, and pharmacologic modalities. Drugs are administered by systemic (e.g., oral, intravenous) or local (topical, intralesional) routes, or by sclerotherapy (endovascular or percutaneous venous, lymphatic, or arterial injection). Off-label drug use is common in pediatrics and in rare diseases, two characteristics applying to vascular anomalies (VA). Off-label use is associated with an increased risk of adverse drug reactions. Objectives To quantify off-label drug use in VA and assess its safety. Design/Methods A guidelines search was conducted to extract a list of drugs used in VA management. The labelling status and safety of each drug was assessed based on the product monograph, Micromedex, and the FDA data. A drug was considered to have significant safety concerns if a black box warning (the FDA’s most stringent warning dedicated to serious or life-threatening risks) or if a serious adverse drug reaction was reported in at least 1% of the patients (leading to hospitalization, congenital malformation, persistent or significant disability or incapacity, life-threatening condition, or death). Results Among 87 drugs, 13 were unlicensed and 73 off-label. Figure 1 describes the reason for considering the 73 drugs off-label. Among 74 licensed drugs, only the oral solution of propranolol hydrochloride (Hemangeol®) for the treatment of infantile hemangiomas (IH) is approved. 98.9% of the drugs are used off-label or unlicensed. Except infantile hemangioma, all other VA are exclusively treated with off-label drugs. Significant safety issues concerned 73% of the drugs and were more frequent among systemic than locally delivered drugs (Figure 2). Conclusion This first study determining the rate of off-label drug use in vascular anomalies shows that off-label drug use in VA is the rule and not the exception. Significant safety concerns are common. It is needed to carefully weigh risk and benefits for every patient when using systemic and local treatments carrying safety concerns. Patients and families should be openly informed and involved in the decision-making process.

Mortality rate during professionally guided scuba diving experiences for uncertified divers, 1992–2019

Introduction: The aim of this study was to re-examine the mortality rate among participants in the Professional Association of Diving Instructors’ (PADI)’s Discover Scuba Diving (DSD) programme. Methods: Fatalities reported to PADI as having occurred during DSD scuba dives were counted for each year between 1992 and 2019. DSD participant registrations were also counted for each year. The data were conveniently divided into two equal 14-year periods, 1992−2005 (‘early’) and 2006−2019 (‘late’). To smooth out the year-to-year variation in raw rates, Monte Carlo simulations were performed on the mean rate per 100,000 participants per year during each period. Results: There were a total of 7,118,731 DSD participant registrations and 79 fatalities during the study period. The estimated overall mean mortality rate in the early period was 2.55 per 100,000 DSD registrations whereas the estimated rate of 0.87 per 100,000 DSD registrations was significantly lower in the late period (P < 0.0001). Conclusions: PADI’s contemporary Discover Scuba Diving introductory scuba experiences, at 0.87 fatalities per 100,000 participants, have a calculated mortality rate that is less than half that calculated for 1992−2008. The late period’s rate improvement appears due either to significant under-registration in the early period, or to significant safety-performance improvement in the late period or, more likely, some combination of the two.

Optimal margins for early stage peripheral lung adenocarcinoma resection

Background A pathologically confirmed negative margin is required when performing sublobar resection in patients with early stage peripheral lung adenocarcinoma. However, the optimal margin distance to ensure complete tumor resection while preserving healthy lung tissue remains unknown. We aimed to establish a reliable distance range for negative margins. Methods A total of 52 intraoperative para-cancer tissue specimens from patients with peripheral lung adenocarcinoma with pathological tumors ≤2 cm in size were examined. Depending on the distance from the tumor edge (D), the para-cancer tissues were divided into the following five groups: D < 0.5 cm (group I); 0.5 cm ≤ D < 1.0 cm (group II); 1.0 cm ≤ D < 1.5 cm (group III); 1.5 cm ≤ D < 2.0 cm (group IV); and D ≥ 2.0 cm (group V). During pathological examination of the specimens under a microscope, the presence of atypical adenomatous hyperplasia or more severe lesions was considered unsafe, whereas the presence of normal lung tissue or benign hyperplasia was considered safe. Results Group V, in which the margin was the farthest from the tumor edge, was the safest. There were significant safety differences in between groups I and V (χ2 = 26.217, P < 0.001). Significant safety differences also existed between groups II and V (χ2 = 9.420, P < 0.005). There were no significant safety differences between group III or IV and group V (P = 0.207; P = 0.610). Conclusions We suggest that when performing sublobar resection in patients with early stage peripheral lung adenocarcinoma with pathological tumor sizes ≤2 cm, the resection margin distance should be ≥1 cm to ensure a negative margin.

Off-Label Use and Safety of Drug Use in Vascular Anomalies

<b><i>Background:</i></b> Off-label drug use is associated with an increased risk of adverse drug reactions. It is common in pediatrics and in rare diseases, which are two characteristics applying to vascular anomalies (VA). <b><i>Objectives:</i></b> The aim of this work was to quantify off-label drug use in VA and assess its safety. <b><i>Methods:</i></b> A review was conducted to extract a list of drugs used in VA management. A drug was considered to have significant safety concerns if a black box warning was present or if a serious adverse drug reaction (SADR) was reported in at least 1% of the patients (SADR is defined as a noxious and unintended response to a drug that occurs at any dose and results in hospitalization, prolongation of existing hospitalization, congenital malformation, persistent or significant disability or incapacity, life-threatening condition, or death). The labelling status and safety of each drug was assessed based on the product monograph, Micromedex, and the FDA data. <b><i>Results:</i></b> We found that 98.9% of the inventoried drugs were used off-label or unlicensed for VA management. Only the oral solution of propranolol hydrochloride (Hemangeol®) for the treatment of infantile hemangiomas is approved. Significant safety issues concerned 73% of the drugs and were more frequent among systemic than locally delivered drugs. <b><i>Conclusions:</i></b> Off-label drug use in VA is the rule and not the exception. Significant safety concerns are common. It is necessary to carefully weigh risk and benefits for every patient when using systemic and local treatments carrying safety concerns. Patients should be openly informed and involved in the decision-making process.

Water-Based Safety Issues and Communication Opportunities

Safe and satisfactory recreation experiences are embedded in the mission of multiple land use management agencies that support 5.2 million recreation-related jobs in the United States. However, visitors are often unaware of potential risks and safety hazards associated with recreation and subsequently unprepared. With the advent of online information, opportunities exist to target communications and key messages. This research observed water-based visitors against recommended safety behaviors as well as online messaging related to safety among public, private and non-profit organizations in the recreation area. Results indicate significant safety issues and multiple opportunities to use and enhance online communications to increase safe recreation behaviors.

Harnessing Pivotal Advances for Production and Structural Derivation of the Promising Molecule Ursolic Acid

Ursolic acid (UA) is a ursane-type pentacyclic triterpenoid compound, naturally produced in plants via specialized metabolism and exhibits vast range of remarkable physiological activities and pharmacological manifestations. Owing to significant safety and efficacy in different medical conditions, UA may serve as a backbone to produce its derivatives with novel therapeutic functions. This review systematically provides an overview of the pharmacological activities, acquisition methods and structural modification methods of UA. In addition, we focused on the synthetic modifications of UA to yield its valuable derivatives with enhanced therapeutic potential. Furthermore, harnessing the essential advances for green synthesis of UA and its derivatives by advent of metabolic engineering and synthetic biology are highlighted. In combination with the advantages of UA biosynthesis and transformation strategy, large-scale production and applications of UA is a promising platform for further exploration.

Driving in the Dust: Challenges and Lessons Learned from Field Testing in Degraded Visual Environments

Degraded visual environments (DVEs) pose significant safety and efficiency problems in military ground vehicle operations. As part of a larger research program, two field tests were conducted to evaluate driving aids while indirect driving in DVEs. The current paper presents the results of one of these field tests, and focuses on the challenges and lessons learned in designing a challenging test course and producing consistent dust clouds for assessing Soldier driving performance and workload in degraded visual environments.