Achievement of LDL-C <55 mg/dL among US adults: Findings from the cvMOBIUS2 registry.

BACKGROUND: Reflecting clinical trial data showing improved outcomes with lower LDL-C levels, guidelines across the globe are increasingly recommending a goal of LDL-C <55 mg/dL in persons with atherosclerotic cardiovascular disease (ASCVD). What proportion of patients with ASCVD are already meeting those goals in the US remains understudied. METHODS: Using electronic health record data from 8 large US health systems, we evaluated lipid-lowering therapy (LLT), LDL-C levels, and factors associated with an LDL-C <55 mg/dL in persons with ASCVD treated between 1/1/2021-12/31/2021. Multivariable modeling was used to evaluate factors associated with achievement of an LDL-C <55 mg/dL. RESULTS: Among 167,899 eligible patients, 22.6% (38,016) had an LDL-C <55 mg/dL. While 76.1% of individuals overall were on a statin, only 38.2% were on a high-intensity statin, 5.9% were on ezetimibe, and 1.7% were on a PCSK9i monoclonal antibody (mAb). Factors associated with lower likelihood of achieving an LDL-C <55 mg/dL included: younger age (odds ratio [OR] 0.91 per 10y), female sex (OR 0.69), Black race (OR 0.76), and noncoronary artery disease forms of ASCVD including peripheral artery disease (OR 0.72) and cerebrovascular disease (OR 0.85), while high-intensity statin use was associated with increased odds of LDL-C <55 mg/dL (OR 1.55). Combination therapy (statin+ezetimibe or statin+PCSK9i mAb) was rare (4.4% and 0.5%, respectively) and was associated with higher odds of an LDL-C <55 mg/dL (OR 1.39 and 3.13, respectively). CONCLUSION: Less than a quarter of US patients with ASCVD in community practice are already achieving an LDL-C <55 mg/dL. Marked increases in utilization of both high intensity statins and combination therapy with non-statin therapy will be needed to achieve LDL-C levels <55 mg/dL at the population level in secondary prevention.

Nonalcoholic Fatty Liver Disease and Cardiovascular Risk: A Scientific Statement From the American Heart Association.

Nonalcoholic fatty liver disease (NAFLD) is an increasingly common condition that is believed to affect >25% of adults worldwide. Unless specific testing is done to identify NAFLD, the condition is typically silent until advanced and potentially irreversible liver impairment occurs. For this reason, the majority of patients with NAFLD are unaware of having this serious condition. Hepatic complications from NAFLD include nonalcoholic steatohepatitis, hepatic cirrhosis, and hepatocellular carcinoma. In addition to these serious complications, NAFLD is a risk factor for atherosclerotic cardiovascular disease, which is the principal cause of death in patients with NAFLD. Accordingly, the purpose of this scientific statement is to review the underlying risk factors and pathophysiology of NAFLD, the associations with atherosclerotic cardiovascular disease, diagnostic and screening strategies, and potential interventions.

A four-year review of orthodontic cases appearing before the General Dental Council Professional Conduct Committee.

OBJECTIVES: To evaluate the characteristics of orthodontic cases at the General Dental Council's (GDC) Professional Conduct Committee (PCC). DESIGN: Review of data from the GDC website for orthodontically related hearings or those involving orthodontic treatment providers during 2015-2018. SETTING: Observational descriptive study. METHODS: Data were accessed from the GDC website by a single researcher to retrieve orthodontic cases. The press office of the GDC was contacted to ensure all data were captured. For each case that met the inclusion criteria, demographic details of the registrant, the charges proved/not proved and final outcome of the case were recorded. RESULTS: A total of 23 registrant cases involved orthodontics and this was 8% of the total number of PCC hearings during 2015-2018. Nine (39%) of the registrants had a Membership in Orthodontics qualification although only 7 (30%) were registered as orthodontists on the UK GDC Specialist List in Orthodontics. Charges related to clinical assessment, consent and record keeping were mostly proved for dentists (13/16 hearings for each) whereas a poor standard of treatment and not cooperating with the GDC were mostly proved for orthodontists (4/7 hearings for each). Overall, conditions were imposed in 10 (44%) cases, erasure in 7 (30%) cases, suspension in 5 (22%) cases and a reprimand in 1 (4%) case. CONCLUSION: The GDC continue to view misdemeanours seriously and it would be prudent for registrants to be familiar with the nature of these hearings to reduce the risk of finding themselves in such a predicament.

Children with Heterozygous Familial Hypercholesterolemia in the United States: Data from the Cascade Screening for Awareness and Detection-FH Registry.

OBJECTIVE: To describe enrollment characteristics of youth in the Cascade Screening for Awareness and Detection of FH Registry. STUDY DESIGN: This is a cross-sectional analysis of 493 participants aged <18 years with heterozygous familial hypercholesterolemia recruited from US lipid clinics (n = 20) between April 1, 2014, and January 12, 2018. At enrollment, some were new patients and some were already in care. Clinical characteristics are described, including lipid levels and lipid-lowering treatments. RESULTS: Mean age at diagnosis was 9.4 (4.0) years; 47% female, 68% white and 12% Hispanic. Average (SD) highest Low-density lipoprotein cholesterol (LDL-C) was 238 (61) mg/dL before treatment. Lipid-lowering therapy was used by 64% of participants; 56% were treated with statin. LDL-C declined 84 mg/dL (33%) among those treated with lipid-lowering therapy; statins produced the greatest decline, 100 mg/dL (39% reduction). At enrollment, 39% had reached an LDL-C goal, either <130 mg/dL or ≥50% decrease from pre-treatment; 20% of those on lipid-lowering therapy reached both goals. CONCLUSIONS: Among youth enrolled in the Cascade Screening for Awareness and Detection of FH Registry, diagnosis occurred relatively late, only 77% of children eligible for lipid-lowering therapy were receiving treatment, and only 39% of those treated met their LDL-C goal. Opportunities exist for earlier diagnosis, broader use of lipid-lowering therapy, and greater reduction of LDL-C levels.

Evaluation of a Chair-Mounted Passive Trunk Orthosis: A Pilot Study on Able-Bodied Subjects.

Trunk stability is important for adequate arm function due to their kinematic linkage. People with Duchenne muscular dystrophy (DMD) can benefit from trunk-assistive devices for seated daily activities, but existing devices limit trunk movement to forward bending. We developed a new trunk orthosis that has spring and pulley design. This study evaluated orthosis performance with 40 able-bodied subjects under with and without orthosis condition in 20 seated tasks for trunk rotation, forward bending, and side bending movements. Subjects adopted static posture in specific trunk orientation while their muscle activity was recorded. They also rated the subjective scales of perceived exertion and usability. A percent change in muscle activity for each task, due to orthosis use, is reported. Significant muscle activity reductions up to 31% and 65% were observed in lumbar and thoracic erector spinae muscles, respectively. Using three-way ANOVA, we found these reductions to be specific to the task direction and the choice of upper limb that is used to perform the asymmetric tasks. A total of 70% participants reported acceptable usability and ~1-point increase in exertion was found for maximum voluntary reaching with the orthosis. The outcomes of this study are promising, though tested on able-bodied subjects. Hence, orthosis mounted on wheelchairs should be further evaluated on DMD patients.

Implications of Islamic Governance towards Psychosocial Work Stressors and Work Productivity.

This is a cross-sectional study, using multivariate regression analysis, to explore the relationship of Islamic governance on psychosocial work stressors and work productivity in healthcare settings. The results revealed that Islamic governing components that are culturally assimilating were significantly related to positive aspects of psychosocial work stressors and increased productivity. Organisational goals that are re-directed towards the Maqasid, i.e. higher order of objectives in Islam, had direct benefits in reducing work-family conflict, promoting general health, increasing job satisfaction and improving commitment to work. Benefits, challenges and recommendations for future studies to expand the field of Islamic governance in organisational and cross-disciplinary healthcare research were discussed.

Inhibition of Angiopoietin-Like Protein 3 With a Monoclonal Antibody Reduces Triglycerides in Hypertriglyceridemia.

BACKGROUND: Hypertriglyceridemia is associated with increased cardiovascular risk and may be caused by impaired lipoprotein clearance. Angiopoietin-like protein 3 (ANGPTL3) inhibits lipoprotein lipase activity, increasing triglycerides and other lipids. Evinacumab, an ANGPTL3 inhibitor, reduced triglycerides in healthy human volunteers and in homozygous familial hypercholesterolemic individuals. Results from 2 Phase 1 studies in hypertriglyceridemic subjects are reported here. METHODS: Subjects with triglycerides >150 but ≤450 mg/dL and low-density lipoprotein cholesterol ≥100 mg/dL (n=83 for single ascending dose study [SAD]; n=56 for multiple ascending dose study [MAD]) were randomized 3:1 to evinacumab:placebo. SAD subjects received evinacumab subcutaneously at 75/150/250 mg, or intravenously at 5/10/20 mg/kg, monitored up to day 126. MAD subjects received evinacumab subcutaneously at 150/300/450 mg once weekly, 300/450 mg every 2 weeks, or intravenously at 20 mg/kg once every 4 weeks up to day 56 with 6 months of follow-up. The primary outcomes were incidence and severity of treatment-emergent adverse events. Efficacy analyses included changes in triglycerides and other lipids over time. RESULTS: In the SAD, 32 (51.6%) versus 9 (42.9%) subjects on evinacumab versus placebo reported treatment-emergent adverse events. In the MAD, 21 (67.7%) versus 9 (75.0%) subjects on subcutaneously evinacumab versus placebo and 6 (85.7%) versus 1 (50.0%) on intravenously evinacumab versus placebo reported treatment-emergent adverse events. No serious treatment-emergent adverse events or events leading to death or treatment discontinuation were reported. Elevations in alanine aminotransferase (7 [11.3%] SAD), aspartate aminotransferase (4 [6.5%] SAD), and creatinine phosphokinase (2 [3.2%) SAD, 1 [14.3%] MAD) were observed with evinacumab (none in the placebo groups), which were single elevations and were not dose-related. Dose-dependent reductions in triglycerides were observed in both studies, with maximum reduction of 76.9% at day 3 with 10 mg/kg intravenously (P<0.0001) in the SAD and of 83.1% at day 2 with 20 mg/kg intravenously once every 4 weeks (P=0.0003) in the MAD. Significant reductions in other lipids were observed with most evinacumab doses versus placebo. CONCLUSION: Evinacumab was well-tolerated in 2 Phase 1 studies. Lipid changes in hypertriglyceridemic subjects were similar to those observed with ANGPTL3 loss-of-function mutations. Because the latter is associated with reduced cardiovascular risk, ANGPTL3 inhibition may improve clinical outcomes. CLINICAL TRIAL REGISTRATION: https://www.clinicaltrials.gov. Unique identifiers: NCT01749878 and NCT02107872.

Statin-associated muscle symptoms and SLCO1B1 rs4149056 genotype in patients with familial hypercholesterolemia.

UNLABELLED: Patients with familial hypercholesterolemia (FH) may be at increased risk for statin-associated muscle symptoms because they require long-term treatment with high-intensity statin therapy. We sought to determine (1) whether other predisposing factors, including the well-known genetic variant associated with statin-associated muscle symptoms-solute carrier organic anion transporter family, member 1B1 (SLCO1B1) rs4149056-also increase the risk of statin-associated muscle symptoms in FH patients, and (2) the natural history and management for FH patients with statin-associated muscle symptoms. METHODS: We queried electronic records (2004-2014) of 278 genetically screened FH patients (113 men, 165 women; mean [SD] pretreatment low-density lipoprotein cholesterol [LDL-C] 259 [72] mg/dL) recruited from lipid clinics in the Dallas, TX, area from 2004 to 2014. Statin-associated muscle symptoms were defined as muscle symptoms arising while taking a statin and interrupting therapy. RESULTS: The risk of muscle symptoms was associated with age (odds ratio 1.6 [95% CI 1.2-2.2]), body mass index in non-African Americans (0.90 [0.83-0.97]), and hypertension (0.4 [0.2-0.9]). Simvastatin was the most commonly used statin, and it was the statin most associated with muscle symptoms. Among FH patients with muscle symptoms, 41% (n = 40) reestablished statin therapy ("eventually tolerant") and 29% (n = 28) never reestablished statin therapy ("never tolerant"). Rosuvastatin (43%) and pravastatin (30%) were the most common eventually tolerated statins, and eventually tolerant patients achieved lower treated LDL-C levels (eventually tolerant 127 vs never tolerant 192 mg/dL, P < .001). Never tolerant patients also developed muscle symptoms on nonstatins (16% vs 50%, P = .003). SLCO1B1 rs4149056 genotyping revealed 224 wild-type patients (TT) and 49 heterozygotes (TC). SLCO1B1 genotype was not associated with the risk of statin-associated muscle symptoms (odds ratio 1.40 [95% CI 0.74-2.64]). CONCLUSION: Age, not SLCO1B1 rs4149056 genotype, was the strongest risk factor for statin-associated muscle symptoms in FH patients. After developing muscle symptoms, many patients reestablished statin therapy and achieved significant LDL-C reductions. Overall, 10% of all FH patients had statin-associated muscle symptoms and never reestablished statin therapy. Such patients developed muscle symptoms even on nonstatin lipid-lowering drugs and continued to have elevations in LDL-C. Further insight is needed into the relationship between FH and statin-associated muscle symptoms so all FH patients can be adequately treated.

The role of microsomal triglyceride transfer protein inhibitors in the treatment of patients with familial hypercholesterolemia: risks, benefits, and management.

Statins fail to adequately reduce low-density lipoprotein-cholesterol (LDL-C) in patients with homozygous familial hypercholesterolemia, requiring these patients to undergo weekly or bi-weekly sessions of LDL apheresis. Although efficacious, LDL apheresis is an invasive procedure with high cost and low availability, and additional options, such as inhibitors of microsomal transfer protein (MTP), may have benefit. Inhibition of MTP reduces levels of circulating cholesterol and triglycerides by preventing the formation of very-low-density lipoprotein and chylomicrons. LDL-C levels decrease by as much as 50%. Unfortunately, adverse effects-the most common of which are gastrointestinal-related and hepatic lipid accumulation-limit broader use of the drug. Furthermore, the cardiovascular benefit of MTP inhibition remains unclear. However, MTP inhibition offers a viable additional lipid-lowering option for patients with homozygous familial hypercholesterolemia.

SURVIVAL ANALYSIS OF DIALYSIS PATIENTS IN SELECTED HOSPITALS OF LAHORE CITY.

BACKGROUND: There are several reasons which are directly or indirectly relate to affect the survival time of End Stage Renal Disease (ESRD) patients. This study was done to analyse the survival rate of ESRD patients in Lahore city, and to evaluate the influence of various risk factors and prognostic factors on survival of these patients. METHODS: A sample of 40 patients was taken from the Jinnah Hospital Lahore and Lahore General Hospital by using the convenience sampling technique. The Log Rank Test was used to determine the significant difference between the categories of qualitative variables of ESRD patients. Multivariate Cox Regression Analysis was used to analyse the effect of different clinical and socio-economic variables on the survival time of these patients. RESULTS: Different qualitative variables like: age, marital status, BMI, comorbid factors, diabetes type, gender, income level, place, risk factor like diabetes, ischemic heart disease, hypertension and Hepatitis status were analysed on the basis of Log Rank Test. While age and comorbid factors were found to be statistically significant which showed that the distribution of age and comorbid factors were different. By using the Cox Regression analysis the coefficient of Mass, serum albumin and family history of diabetes were found to be significant. CONCLUSIONS: There were some of the factors which had been taken for the analysis came out less or more significant in patients of ESRD. So it was concluded that mostly clinical factors which were Mass of the Patient, Serum Albumin and Family History of Diabetes made significant contribution towards the survival status of patients.

Social and Metabolic Characteristics Associated With Multiple DKA Admissions at a Large County Hospital.

Context: Diabetic ketoacidosis (DKA) is a preventable, deadly, and costly complication of type 1 diabetes mellitus (T1DM). Some individuals with T1DM have recurrent DKA admissions. Objective: We sought to characterize social factors that differ between patients with single vs multiple DKA admissions at an urban, safety-net hospital. Methods: We queried the electronic health records for T1DM patients admitted for DKA from 2019 to 2021. Admission laboratory values, demographic information, and detailed social histories were collected and analyzed statistically, including logistical regression. Results: A total of 243 patients were admitted for DKA, 64 of whom had multiple DKA admissions. There was no significant difference between the groups in their admission laboratory values, hospital length of stay, health-care payer status, history of homelessness, current employment, living alone, independence of activities of daily living, and barriers to discharge. T1DM patients with multiple DKA admissions had greater rates of substance use disorder (33.0% vs 60.9%; P < .001), especially with cannabis (6.7% vs 25.0%; P < .001), tobacco (26.3% vs 46.3%; P = .002), and psychoactive substance use (1.1% vs 6.3%; P = .043). Regression models of substance use showed increased risk with any substance use (odds ratio [CI] 3.17 [1.78-5.73]; P < .001) and cannabis (3.70 [1.55-8.83]; P = .003). Conclusion: We identified substance use as a possible predictor of T1DM patients at risk for multiple DKA admissions. Our findings identify a group of T1DM patients for whom interventions may help to decrease recurrence of DKA episodes within similar community hospital populations.

User Perspectives and Psychophysiological Manifestations of Fatigue with Trunk Orthosis for Dystrophinopathy Patients.

The chair-mounted passive trunk orthosis (CMPTO) is designed to enhance wheelchair safety for individuals with dystrophinopathy during their daily activities. Given the disease's progressive nature, it is crucial to ensure that assistive devices are carefully evaluated to prevent overexertion. This study aims to assess the CMPTO's user experience and its impact on fatigue-related psychophysiological measurements. We conducted electromyography (EMG) evaluations of four trunk muscles and assessed perceived exertion using the Borg CR-10 scale in 40 healthy subjects while they performed seated maximal reaching tasks with the CMPTO. Additionally, fifteen dystrophinopathy patients evaluated the CMPTO for usability with the System Usability Scale. Paired t-tests were employed to compare the median frequency (MDF) of EMG signals, the Wilcoxon signed-rank test for evaluating exertion, and the Mann-Whitney U test to compare the usability reported by patients to those of healthy subjects. The 4-way ANOVA revealed that MDF patterns were significantly influenced by task orientation for each muscle. The CMPTO did not cause a significant reduction in the MDF. Tasks requiring greater trunk rotation were perceived as more exhaustive. Patients reported acceptable usability with the CMPTO, with scores higher than those of healthy subjects. The CMPTO's usability was comprehensively evaluated in both healthy subjects and patients with dystrophinopathy. Our findings indicate that the CMPTO can be safely used by individuals with dystrophinopathy as an assistive device to improve seated comfort and functional abilities.

Efficacy of audiovisual neurofeedback training for attention enhancement: a multimodal approach.

Attention is a cognitive process that involves focusing mental resources on specific stimuli and plays a fundamental role in perception, learning, memory, and decision-making. Neurofeedback (NF) is a useful technique for improving attention, providing real-time feedback on brain activity in the form of visual or auditory cues, and allowing users to learn to self-regulate their cognitive processes. This study compares the effectiveness of different cues in NF training for attention enhancement through a multimodal approach. We conducted neurological (Quantitative Electroencephalography), neuropsychological (Mindfulness Attention Awareness Scale-15), and behavioral (Stroop test) assessments before and after NF training on 36 healthy participants, divided into audiovisual (G1) and visual (G2) groups. Twelve NF training sessions were conducted on alternate days, each consisting of five subsessions, with pre- and post-NF baseline electroencephalographic evaluations using power spectral density. The pre-NF baseline was used for thresholding the NF session using the beta frequency band power. Two-way analysis of variance revealed a significant long-term effect of group (G1/G2) and state (before/after NF) on the behavioral and neuropsychological assessments, with G1 showing significantly higher Mindfulness Attention Awareness Scale-15 scores, higher Stroop scores, and lower Stroop reaction times for interaction effects. Moreover, unpaired t -tests to compare voxel-wise standardized low-resolution brain electromagnetic tomography images revealed higher activity of G1 in Brodmann area 40 due to NF training. Neurological assessments show that G1 had better improvement in immediate, short-, and long-term attention. The findings of this study offer a guide for the development of NF training protocols aimed at enhancing attention effectively.

Predicting the effectiveness of binaural beats on working memory.

Working memory is vital for short-term information processing. Binaural beats can enhance working memory by improving attention and memory consolidation through neural synchronization. However, individual differences in cognitive and neuronal functioning affect effectiveness of binaural beats, necessitating personalized approaches. This study aimed to develop a machine learning model to predict binaural beats's effectiveness on working memory using electroencephalography. Sixty healthy participants underwent a 5-min electroencephalography recording, an initial working memory evaluation, 15 min of binaural beats stimulation, and a subsequent working memory evaluation using digit span tests of increasing difficulty. Recall accuracy and response times were measured. Differential scores from pre-evaluation and post-evaluation labeled participants as active or inactive to binaural beats stimulation. electroencephalography data, recorded using 14 electrodes, provided brain activity estimates across theta, alpha, beta, and gamma frequency bands, resulting in 56 features (14 channels × 4 bands) for the machine learning model. Several classifiers were tested to identify the most effective model. The weighted K-nearest neighbors model achieved the highest accuracy (90.0%) and area under the receiver operating characteristic curve (92.24%). Frontal and parietal electroencephalography channels in theta and alpha bands were crucial for classification. This study's findings offer significant clinical insights, enabling informed interventions and preventing resource inefficiency.

Comparative Neurological and Behavioral Assessment of Central and Peripheral Stimulation Technologies for Induced Pain and Cognitive Tasks.

Pain is a multifaceted, multisystem disorder that adversely affects neuro-psychological processes. This study compares the effectiveness of central stimulation (transcranial direct current stimulation-tDCS over F3/F4) and peripheral stimulation (transcutaneous electrical nerve stimulation-TENS over the median nerve) in pain inhibition during a cognitive task in healthy volunteers and to observe potential neuro-cognitive improvements. Eighty healthy participants underwent a comprehensive experimental protocol, including cognitive assessments, the Cold Pressor Test (CPT) for pain induction, and tDCS/TENS administration. EEG recordings were conducted pre- and post-intervention across all conditions. The protocol for this study was categorized into four groups: G1 (control), G2 (TENS), G3 (anodal-tDCS), and G4 (cathodal-tDCS). Paired t-tests (p < 0.05) were conducted to compare Pre-Stage, Post-Stage, and neuromodulation conditions, with t-values providing insights into effect magnitudes. The result showed a reduction in pain intensity with TENS (p = 0.002, t-value = -5.34) and cathodal-tDCS (p = 0.023, t-value = -5.08) and increased pain tolerance with TENS (p = 0.009, t-value = 4.98) and cathodal-tDCS (p = 0.001, t-value = 5.78). Anodal-tDCS (p = 0.041, t-value = 4.86) improved cognitive performance. The EEG analysis revealed distinct neural oscillatory patterns across the groups. Specifically, G2 and G4 showed delta-power reductions, while G3 observed an increase. Moreover, G2 exhibited increased theta-power in the occipital region during CPT and Post-Stages. In the alpha-band, G2, G3, and G4 had reductions Post-Stage, while G1 and G3 increased. Additionally, beta-power increased in the frontal region for G2 and G3, contrasting with a reduction in G4. Furthermore, gamma-power globally increased during CPT1, with G1, G2, and G3 showing reductions Post-Stage, while G4 displayed a global decrease. The findings confirm the efficacy of TENS and tDCS as possible non-drug therapeutic alternatives for cognition with alleviation from pain.

Sex-related differences in premature cardiovascular disease in familial hypercholesterolemia.

BACKGROUND: Familial hypercholesterolemia (FH) is associated with an increased prevalence of premature atherosclerotic cardiovascular disease (ASCVD), however, little is known about sex-specific differences in premature ASCVD and its risk factors. OBJECTIVE: The present study seeks to assess the burden and risk factors for premature ASCVD among men and women with FH. METHODS: In this study we retrospectively examined sex-specific differences in ASCVD prevalence, risk factor burdens, and lipid treatment outcomes in 782 individuals with clinically or genetically confirmed FH treated in 5 U.S. lipid and genetics clinics. A generalized linear model using Binomial distribution with random study site effect and sex-stratified analysis was used to determine the strongest predictors of premature ASCVD, and lipid treatment outcomes. Covariates included age, sex, diabetes mellitus (DM), hypertension, and current smoking. RESULTS: Among the cohort, 98/280 men (35%) and 89/502 women (18%) had premature ASCVD (defined as <55 years in men and <65 years in women). Women with premature ASCVD had higher mean treated total cholesterol (216 vs. 179 mg/dl, p=<0.001) and LDL-C (135 vs. 109 mg/dl, p= 0.005). CONCLUSION: These data confirm that high percentages of women and men with FH develop premature ASCVD, and suggest that FH may narrow the observed sex difference in premature ASCVD onset. These data support more aggressive prevention and treatment strategies in FH, including in women, to reduce non-lipid risk factors and residual hypercholesterolemia.

Contemporary Homozygous Familial Hypercholesterolemia in the United States: Insights From the CASCADE FH Registry.

Background Homozygous familial hypercholesterolemia (HoFH) is a rare, treatment-resistant disorder characterized by early-onset atherosclerotic and aortic valvular cardiovascular disease if left untreated. Contemporary information on HoFH in the United States is lacking, and the extent of underdiagnosis and undertreatment is uncertain. Methods and Results Data were analyzed from 67 children and adults with clinically diagnosed HoFH from the CASCADE (Cascade Screening for Awareness and Detection) FH Registry. Genetic diagnosis was confirmed in 43 patients. We used the clinical characteristics of genetically confirmed patients with HoFH to query the Family Heart Database, a US anonymized payer health database, to estimate the number of patients with similar lipid profiles in a "real-world" setting. Untreated low-density lipoprotein cholesterol levels were lower in adults than children (533 versus 776 mg/dL; P=0.001). At enrollment, atherosclerotic cardiovascular disease and supravalvular and aortic valve stenosis were present in 78.4% and 43.8% and 25.5% and 18.8% of adults and children, respectively. At most recent follow-up, despite multiple lipid-lowering treatment, low-density lipoprotein cholesterol goals were achieved in only a minority of adults and children. Query of the Family Heart Database identified 277 individuals with profiles similar to patients with genetically confirmed HoFH. Advanced lipid-lowering treatments were prescribed for 18%; 40% were on no lipid-lowering treatment; atherosclerotic cardiovascular disease was reported in 20%; familial hypercholesterolemia diagnosis was uncommon. Conclusions Only patients with the most severe HoFH phenotypes are diagnosed early. HoFH remains challenging to treat. Results from the Family Heart Database indicate HoFH is systemically underdiagnosed and undertreated. Earlier screening, aggressive lipid-lowering treatments, and guideline implementation are required to reduce disease burden in HoFH.

In vitro fertilization and hypertriglyceridemic pancreatitis: Case report.

Few cases of hypertriglyceridemic pancreatitis have been reported in women during a vitro fertilization treatment (IVF) cycle. Here, we describe a 41-year-old woman with primary infertility and a history of acute pancreatitis (of unknown etiology) who was started on high dose ethinyl estradiol to prepare for transfer of cryopreserved embryos. She subsequently presented with nausea, vomiting, and abdominal pain to an emergency room and was found to have hypertriglyceridemic pancreatitis. Her hospitalization involved a prolonged intensive care unit stay in which she underwent three sessions of plasmapheresis. Eventually, with discontinuation of ethinyl estrogen, aggressive intravenous fluid hydration, plasmapheresis, a low-fat diet, and gemfibrozil, she had resolution of severe hypertriglyceridemia and all symptoms related to acute pancreatitis. Our case highlights the possibility that ethinyl estradiol, a commonly used form of estrogen for endometrial preparation during IVF cycles, may cause severe hypertriglyceridemia and acute pancreatitis in certain predisposed individuals. Only seven cases of hypertriglyceridemic pancreatitis during in vitro fertilization have been previously reported, and only one of these prior cases experienced pancreatitis during transfer of cryopreserved embryos like our patient. Our case, along with the few prior reported cases, demonstrate hypertriglyceridemic pancreatitis can occur during IVF. Further work is needed to understand the effects of exogenous estrogen on lipids for women undergoing IVF.

Revival of sun-and-beach tourism through the lens of regulatory and risk dimensions of environmental sustainability.

Environmental sustainability is essential in tourism literature, and sun-and-beach tourism (SBT) is one of the most popular subsections of the tourism field. The appropriate policies and strategies during the COVID-19 pandemic to revive SBT growth through the lens of the regulatory dimension (RED) and risk dimension (RID) of environmental sustainability are gaining timely ground to conduct this research. The current study examined the nexus between SBT, RED, and RID utilizing three novel indexes (i.e., weighted sun-and-beach tourism index, weighted regulatory dimension index, and weighted risk dimension index) by employing the principal component analysis within the framework of six stages of empirical estimation strategy. These three novel indexes combine the most commonly used SBT, RED, and RID indicators. This research tested the CSD and homogeneous, then employed the second generation CIPS-CADF panel unit root test, used an AMG estimator, and employed the panel Toda-Yamamoto (PTY) causality test. The findings revealed that the RED positively influences SBT while the RID mitigates SBT. Results also indicate bidirectional causality between SBT, RID, and RED. In other words, changes in RID and RED have predictive power for the SBT, which further highlights the role of SBT on the RID and RED. Therefore, concerned authorities can focus on environmental sustainability design initiatives and appropriate policy/strategy implications to boost SBT.