The prevalence of low muscle mass associated with obesity in the USA.

BACKGROUND: Sarcopenia is defined as age-related low muscle mass and function, and can also describe the loss of muscle mass in certain medical conditions, such as sarcopenic obesity. Sarcopenic obesity describes loss of muscle and function in obese individuals; however, as sarcopenia is an age-related condition and obesity can occur in any age group, a more accurate term is obesity with low lean muscle mass (OLLMM). Given limited data on OLLMM (particularly in those aged < 65 years), the purpose of this study was to estimate the prevalence of OLLMM in adults aged ≥ 20 years in the USA. METHODS: Data from the National Health and Nutrition Examination Survey (NHANES) 2017-2018 and 1999-2006 were used. OLLMM was defined as an appendicular lean mass, adjusted for body mass index (BMI), cut-off point < 0.789 for males and < 0.512 for females, measured by dual-energy X-ray absorptiometry (DXA). DXA was only measured in individuals 20-59 years old in NHANES 2017-2018; we therefore utilized logistic regression models to predict OLLMM from NHANES 1999-2006 for those aged ≥ 60 years. The prevalence of OLLMM was estimated overall, and by sex, age, race/ethnicity, and clinical subgroup (high BMI, prediabetes, type 2 diabetes mellitus [T2DM], non-alcoholic fatty liver disease [NAFLD] with fibrosis, or post-bariatric surgery). Prevalence estimates were extrapolated to the USA population using NHANES sampling weights. RESULTS: We estimated that, during 2017-2018, 28.7 million or 15.9% of the USA population had OLLMM. The prevalence of OLLMM was greater in older individuals (8.1%, aged 20-59 years vs 28.3%, aged ≥ 60 years), highest (66.6%) in Mexican-American females aged ≥ 60 years, and lowest (2.6%) in non-Hispanic Black males aged 20-59 years. There was a higher prevalence of OLLMM in adults with prediabetes (19.7%), T2DM (34.5%), NAFLD with fibrosis (25.4%), or post-bariatric surgery (21.8%), compared with those without each condition. CONCLUSIONS: Overall, the burden of OLLMM in the USA is substantial, affecting almost 30 million adults. The prevalence of OLLMM increased with age, and among those with prediabetes, T2DM, NAFLD with fibrosis, or post-bariatric surgery. A unified definition of OLLMM will aid diagnosis and treatment strategies.

Efficacy and Safety of Alirocumab in Adults With Homozygous Familial Hypercholesterolemia: The ODYSSEY HoFH Trial.

BACKGROUND: Homozygous familial hypercholesterolemia (HoFH) is characterized by extremely elevated low-density lipoprotein-cholesterol (LDL-C) levels and early onset atherosclerotic cardiovascular disease despite treatment with conventional lipid-lowering treatment. OBJECTIVES: This study was designed to assess LDL-C reduction with the proprotein convertase subtilisin/kexin type 9 inhibitor alirocumab in adult patients with HoFH. METHODS: This randomized, double-blind, placebo-controlled, parallel-group, phase 3 study evaluated efficacy and safety of alirocumab 150 mg every 2 weeks. The primary endpoint was percent reduction from baseline in LDL-C versus placebo after 12 weeks of treatment. RESULTS: Patients (N = 69) were randomized 2:1 to alirocumab or placebo. At baseline, background lipid-lowering treatment included 67 patients receiving statin (59 patients on high-intensity statin); 50 patients on ezetimibe; 10 patients on lomitapide; and 10 patients undergoing apheresis. Mean baseline LDL-C was 259.6 mg/dl in the placebo group and 295.0 mg/dl in the alirocumab group. At week 12, the least squares mean difference in LDL-C percent change from baseline was -35.6% (alirocumab [-26.9%] vs. placebo [8.6%]; p < 0.0001). Reductions (least squares mean difference) in other atherogenic lipids at week 12 were: apolipoprotein B, -29.8%; non-high-density lipoprotein cholesterol, -32.9%; total cholesterol, -26.5%; and lipoprotein(a), -28.4% (all p < 0.0001). No serious adverse events, permanent treatment discontinuations, or deaths due to treatment-emergent adverse events were reported during the double-blind treatment period. CONCLUSIONS: In the largest randomized controlled interventional trial in HoFH patients to date, alirocumab resulted in significant and clinically meaningful reductions in LDL-C at week 12. Alirocumab was generally well tolerated, with a safety profile comparable to that of placebo. (Study in Participants With Homozygous Familial Hypercholesterolemia [HoFH] [ODYSSEY HoFH] NCT03156621.).

Efficacy and Safety of Alirocumab in Patients With Autosomal Dominant Hypercholesterolemia Associated With Proprotein Convertase Subtilisin/Kexin Type 9 Gain-of-Function or Apolipoprotein B Loss-of-Function Mutations.

Autosomal dominant hypercholesterolemia results from mutations affecting the low-density lipoprotein receptor pathway, including proprotein convertase subtilisin/kexin type 9 (PCSK9) gain-of-function mutations (GoFm) and apolipoprotein B (APOB) loss-of-function mutations (LoFm). This study examined the long-term efficacy and safety of alirocumab in patients with PCSK9 GoFm and APOB LoFm who participated in the open-label extension to a Phase 2 double-blind study (NCT01604824). Of the 23 patients who completed the 14-week double-blind period and 8-week follow-up, 21 opted to continue in the open-label extension (PCSK9 GoFm, n = 15; APOB LoFm, n = 6). Patients received alirocumab 150 mg every 2 weeks from week 32 up to 3 years for PCSK9 GoFm and 2 years for APOB LoFm. Mean duration of alirocumab exposure was 129 weeks (median: 144 weeks). After initiation of alirocumab treatment, low-density lipoprotein cholesterol (LDL-C) decreased in both groups. At week 80, mean percent reduction in LDL-C from baseline was 58.0% and 47.1% for PCSK9 GoFm and APOB LoFm groups, respectively. Treatment-emergent adverse events were reported in 19 patients (90.5%); no patients discontinued treatment due to treatment-emergent adverse events. In patients with autosomal dominant hypercholesterolemia and elevated LDL-C levels despite receiving maximally tolerated lipid-lowering therapies, alirocumab 150 mg every 2 weeks resulted in clinically meaningful reductions in LDL-C, sustained through to 3 years and 2 years for patients with PCSK9 GoFm and APOB LoFm, respectively. Alirocumab was generally well tolerated with no unexpected safety concerns.

Pharmacokinetic and pharmacodynamic assessment of alirocumab in patients with familial hypercholesterolemia associated with proprotein convertase subtilisin/kexin type 9 gain-of-function or apolipoprotein B loss-of-function mutations.

BACKGROUND: Familial hypercholesterolemia is characterized by high levels of low-density lipoprotein cholesterol (LDL-C), and causes of familial hypercholesterolemia include apolipoprotein B (APOB) loss-of-function mutations (LOFm) and proprotein convertase subtilisin/kexin type 9 (PCSK9) gain-of-function mutations (GOFm). OBJECTIVE: The aim of this study was to compare the pharmacokinetics and pharmacodynamics of alirocumab between patients with APOB LOFm vs PCSK9 GOFm. METHODS: Patients (6 APOB LOFm and 17 PCSK9 GOFm carriers) with LDL-C ≥70 mg/dL on maximally tolerated lipid-lowering therapies received alirocumab 150 mg at Weeks 0, 2, 4, and 6, placebo at Week 8, alirocumab at Week 10, placebo at Weeks 12 and 14, then completed a follow-up period at Week 22. RESULTS: At Week 8, mean ± standard error (SE) alirocumab concentration was lower in APOB LOFm carriers compared with PCSK9 GOFm carriers (12.12 ± 1.81 vs 16.74 ± 2.53 mg/L). APOB LOFm carriers had higher mean ± SE total PCSK9 (6.56 ± 0.73 mg/L) and lower mean ± SE free PCSK9 (0.025 ± 0.016 mg/L) at Week 8 compared with PCSK9 GOFm carriers (4.21 ± 0.35 and 0.11 ± 0.035 mg/L for total and free PCSK9, respectively). Despite this observed greater PCSK9 suppression, mean ± SE percent LDL-C reduction was lower in APOB LOFm (55.3 ± 1.0%) compared with PCSK9 GOFm carriers (73.1 ± 0.9%). Treatment-emergent adverse events occurred in 16 patients (94.1%) in the PCSK9 GOFm group and 5 patients (83.3%) in the APOB LOFm group. CONCLUSIONS: Overall, PCSK9 inhibition with alirocumab results in clinically meaningful reductions in LDL-C in both APOB LOFm and PCSK9 GOFm carriers, although reductions were greater in the PCSK9 GOFm carriers. The results indicate a possible underlying contributor to hypercholesterolemia other than PCSK9 in patients with APOB LOFm. CLINICAL TRIAL REGISTRATION: NCT01604824; clinicaltrials.gov.

Simulation training for surgical residents in pediatric trauma scenarios.

INTRODUCTION: Pediatric trauma requires several medical professionals working together as a highly functioning team. Since critical pediatric medical events are rare, routine practice can be one method of ensuring that all members communicate and provide quality care. The goal of this study was to evaluate whether high-fidelity simulation training improved surgery residents' knowledge and self-efficacy in relation to pediatric trauma scenarios. METHODS: Participants attended training that included initial assessments of knowledge and self-efficacy, lecture, and practice with three trauma scenarios. After the training, residents completed pretest measures again. RESULTS: Findings indicated that resident knowledge and self-efficacy significantly increased afterthe simulation training. CONCLUSION: The current study suggests that for the adequate care of pediatric patients during trauma/emergency situations, high-fidelity simulation training may be beneficial. This may be particularly true for emergencies that are less frequent and not well practiced by clinicians and students.

Comparison of use of the the Airtraq with direct laryngoscopy by paramedics in the simulated airway.

INTRODUCTION: Paramedics often encounter patients with difficult airways requiring emergent airway management. OBJECTIVE: The purpose of this study was to compare intubation utilizing the Airtraq with direct laryngoscopy (DL) in the manikin model. We evaluated the number of attempts, the time to successful intubation, and the Airtraq's learning curve. METHODS: This was a randomized, crossover study involving paramedics. Each participant was given a standardized lecture and a demonstration of the Airtraq device. After a 5-minute practice session on a Laerdal Airway Management Trainer with the Airtraq and DL, participants managed the following four scenarios on a Laerdal SimMan manikin: 1) normal airway; 2) tongue edema; 3) cervical spine immobilization; and 4) repeated normal airway. Results were analyzed using the Wilcoxon signed rank test. RESULTS: Thirty paramedics participated in this study. For scenario 1, there were no significant differences in either the number of attempts or the time to ventilation between the devices. For scenario 2, the mean time to ventilation was significantly faster, and fewer intubation attempts were observed with the Airtraq when compared with DL. For scenario 3, there were no significant differences in number of attempts and time to ventilation. Scenario 4 demonstrated significantly less time to ventilation and fewer intubation attempts with the Airtraq. A significant decrease in time to ventilation was observed with the Airtraq when comparing scenarios 1 and 4. CONCLUSIONS: The Airtraq was shown to be equal to or faster than DL. The Airtraq has a rapid learning curve demonstrated by a significantly decreased time to ventilation between scenarios 1 and 4.

The fifth vital sign--what does it mean?

Acute pain is reported as a presenting symptom in over 80% of physician visits. Chronic pain affects an estimated 76.2 million Americans--more than diabetes, heart disease, and cancer combined. It has been estimated to be undertreated in up to 80% of patients in some settings. Pain costs the American public more than $100 billion each year in health care, compensation, and litigation. That's why pain was officially declared "The Fifth Vital Sign." Henceforth the evaluation of pain became a requirement of proper patient care as important and basic as the assessment and management of temperature, blood pressure, respiratory rate, and heart rate. The numeric pain scale certainly has a place in care and in pain management; however, it is important to assess the patient's communication and self-management style and to recognize that patients, like pain, are on a continuum with varied styles of communication and adaptation. It is easy to get lost in the process, even when the process is initiated with the best of intentions. In the quest for individualized medicine, it might be best to keep pain assessment in the individualization arena.