Comprehensive review of statin-intolerance and the practical application of Bempedoic Acid.

Statin-intolerance (SI) has prevalence between 8.0 % and 10 %, and muscular complaints are the most common reason for discontinuation. Bempedoic acid (BA), an ATP citrate lyase inhibitor, decreases hepatic generation of cholesterol, upregulates low-density lipoprotein (LDL) receptor expression in the liver, and eventually clears circulating LDL-cholesterol from the blood. Multiple randomized clinical trials studying BA demonstrate a reduction in LDL levels by 17-28 % in SI. The CLEAR OUTCOME trial established significant cardiovascular benefits with BA. A dose of 180 mg/day of BA showed promising results. BA alone or in combination with ezetimibe is US Food and Drug Administration-approved for use in adults with heterozygous familial hypercholesterolemia and/or established atherosclerotic cardiovascular disease. BA reduced HbA1c by 0.12 % (p < 0.0001) in patients with diabetes. Adverse events of BA include myalgia (4.7 %), anemia (3.4 %), and increased aminotransferases (0.3 %). BA can cause up to four times higher risk of gout in those with a previous gout diagnosis or high serum uric acid levels. Reports of increased blood urea nitrogen and serum creatinine were noted. Current evidence does not demonstrate a reduction in deaths from cardiovascular causes. More studies that include a diverse population and patients with both high and low LDL levels should be conducted. We recommend that providers consider BA as an adjunct to statin therapy in patients with a maximally tolerated dosage to specifically target LDL levels.

Pulsed laser source digital holography efficiency measurements.

In this paper, a 1064 nm pulsed laser source and a short-wave IR (SWIR) camera are used to measure the total system efficiency associated with a digital holography system in the off-axis image plane recording geometry. At a zero path-length difference between the signal and reference pulses, the measured total system efficiency (15.9%) is consistent with that previously obtained with a 532 nm continuous-wave laser source and a visible camera [Appl. Opt.58, G19 (2019)APOPAI0003-693510.1364/AO.58.000G19]. In addition, as a function of the temporal delay between the signal and reference pulses, the total system efficiency is accurately characterized by a component efficiency, which is formulated from the ambiguity function. Even with multimode behavior from the pulsed laser source and substantial dark current noise from the SWIR camera, the system performance is accurately characterized by the resulting ambiguity efficiency.

Improving self-efficacy in seizure first aid: Developing a seizure first aid certification program in the United States.

OBJECTIVES: Seizures and epilepsy are very common neurologic disorders, yet knowledge of how to help a person having a seizure is sorely lacking, increasing the potential for injury and early death for people with seizures. We developed a standardized seizure first aid (SFA) training certification for the general public and evaluated its impact on knowledge and self-efficacy about SFA and program satisfaction. METHODS: The Epilepsy Foundation's SFA certification was developed by a multidisciplinary group of experts, with extensive review, feasibility testing, and analysis of pilot tests from 10 sessions with 177 participants. Pre/post assessments were conducted immediately prior to and after participation in the 60-90-min program. Data from 94 people with complete pre/post assessments were used for analysis of demographics, program outcomes, and satisfaction. Descriptive statistics, paired sample T-tests, and Cronbach α coefficients were conducted. RESULTS: Participants were over age 18, primarily female, and white/Caucasian. Significant improvements were seen in both SFA knowledge and self-efficacy on pre/post assessments across all pilot sites. Fourteen of 23 scale items had significant pre/post improvements. Training satisfaction was rated high by almost all participants. CONCLUSIONS: The Epilepsy Foundation's Seizure First Aid certification focuses on ability to recognize seizure symptoms, respond with correct first aid steps, and know when emergency help is needed. Pilot assessments support increased knowledge and self-confidence, critical to promoting positive behavior change. This program offers an easy and scalable way for the general public to learn SFA and enhance seizure recognition and safety of people with seizures.

Developing epilepsy training capacity for primary care providers using the project ECHO telementoring model.

BACKGROUND: Primary care providers (PCPs) provide a large proportion of care for people with epilepsy (PWE) and need regular training for updates. However, PCPs treat patients in so many therapeutic areas that epilepsy often becomes a less important concern. We used an established telementoring program, Project ECHO (Extension for Community Healthcare Outcomes), and combined epilepsy education with general neurology topics to generate more interest among PCPs. METHODS: We offered 20 one-hour webinar sessions over a two-year period, each consisting of a panel of neurology experts, with a combination of case presentations, a 20-minute didactic presentation, and live, interactive question and answer. Attendees logged in from their own computers or phones, and all presentations were archived online for future viewing. Interviews with PCPs indicated a combination of epilepsy and general neurology topics would be better received, so epilepsy topics alternated monthly with general neurology topics (e.g., headache, stroke, and dementia). Session evaluation included participants' comfort in treating patients with neurological disorders and confidence in knowledge of the topic area. RESULTS: After the second session, mean attendance was 27.5 participants (range 15-38), with a total of 164 unique individual participants. Attendees were a mix of mostly regional, some out of state, and a few international learners, including practicing PCPs, trainees, and nurse practitioners. Archived presentations on our website were viewed 212 times; seizure topics were the most viewed. Mean evaluation scores for relevance, value, and increased knowledge were all in the "agree to strongly agree" range. Over 97% of respondents reported greater interest in improving care of patients with epilepsy or neurological disorders, and over 98% reported greater comfort and self-efficacy when treating patients with these conditions. Only eight cases were submitted for review prior to the sessions. CONCLUSIONS: We successfully piloted a telementoring program using Project ECHO methodology, which was effective in educating PCPs about epilepsy treatment. Combining epilepsy and other neurology topics was an effective strategy in garnering interest among PCPs, but additional methods are needed to encourage participants to present their own cases.

Bridging the divide between epilepsy and mental health to drive solutions.

Since its establishment in 2000, Epilepsy & Behavior has published more than 1000 papers on mental health issues among people with epilepsy, including about 200 reviews. These studies on prevalence, treatment, and guidance for future research are important contributions to the field, and they offer great promise. Yet these papers and the multitude published in other journals over the years have failed to result in systematic, scaled changes in how the epilepsy field in the United States addresses mental health issues. The mental health assessment and management gap is especially notable given decades-old, as well as more recent, recommendations from national initiatives on epilepsy, consensus statements, and other expert appeals to reduce psychiatric burden. Selected or comprehensive elements of emerging models and latest approaches from behavioral health (e.g., peer support) and public health (e.g., community-clinical linkages) highlight current opportunities to engage multiple community partners and sectors to bridge the epilepsy and behavioral health fields to implement solutions for improved mental healthcare for people with epilepsy. In honor of the 20th anniversary of Epilepsy & Behavior and its contribution to the literature and the field, we seek to build public health roadmaps to bridge the epilepsy and behavioral health divide-with new epilepsy partners who can expand community-based partnerships that may help facilitate systematic changes to close mental health treatment gaps. Special Issue: Epilepsy & Behavior's 20th Anniversary.

Innovative approaches reaching underserved and rural communities to improve epilepsy care: A review of the methodology of the Connectors Project.

OBJECTIVE: The Connectors Project, a collaboration between the Epilepsy Foundation and UCB Pharma, was a multiyear project designed to improve epilepsy care in underserved communities. A core objective of the Connectors Project was to pilot new and innovative approaches to epilepsy awareness and education in rural and underserved areas, including standardized curricula for healthcare providers and patients. METHODS: A series of consensus conferences explored opportunities and barriers to epilepsy care throughout the United States including access to local Epilepsy Foundations, neurologists, and epilepsy centers. Data from QuintilesIMS™ were examined for access to newer antiepileptic drugs (AEDs)-a proxy for quality of epilepsy care-in different regions. State factors (e.g., local epilepsy foundation office, access to newer vs. older AEDs, and geographic density and diversity) were used in selecting four states as examples of rural and underserved areas to pilot the awareness and educational programs. For each state, a work team assessed challenges and opportunities, tailored educational curricula, and developed strategies for effective delivery of the educational programs. Interventions were held between June 2016 and June 2017. Interventions consisted of outreach and awareness programs, in-person health education to healthcare providers and patients/families, and digital health education. RESULTS: Michigan, Nevada, Oklahoma, and West Virginia were identified as pilot states representing geographically diverse areas, ranging from a state with a large high-density population center with several epilepsy centers and a local Epilepsy Foundation office (Michigan) to a state with predominately rural areas and a few small urban cores, two epilepsy centers, and no in-state Epilepsy Foundation office (West Virginia). State work teams tailored interventions and examined options for type, intent, ease of use, and impact. All states implemented outreach and awareness initiatives and in-person health education for patients and healthcare providers; use of digital health education was variable. Measurement of the interventions was agreed to be performed by the use of patient and physician surveys and reevaluation of data from QuintilesIMS for access to newer AEDs. CONCLUSION: Local Epilepsy Foundation offices successfully connected healthcare providers in rural and underserved areas to epilepsy education designed to enhance quality care in epilepsy. Educational opportunities for people with epilepsy and their families addressed critical gaps in accessing quality epilepsy care and self-management. Tailored and innovative educational approaches can be used to increase awareness levels and to overcome geographic challenges in reaching underserved populations. Relationship building and repeated, consistent engagement with healthcare providers and patients can assist in improving communication and self-management skills among patients with epilepsy.

A systematic review of intervention studies to prevent hospitalizations of community-dwelling older adults with dementia.

OBJECTIVES: To conduct a systematic literature review to determine if there were any intervention strategies that had any measurable effect on acute-care hospitalizations among community-dwelling adults with dementia. DESIGN: Studies were identified by a professional research librarian and content experts. SETTING: Community dwelling. PARTICIPANTS: Participants were diagnosed with dementia, severity ranging from mild to severe, and were recruited from health care and community agencies. MEASUREMENTS: A study met the inclusion criteria if it: (a) was published in English; (b) included a control or comparison group; (c) published outcome data from the intervention under study; (d) reported hospitalization as one of the outcomes; (e) included community-dwelling older adults; and (f) enrolled participants with dementia. Ten studies met all inclusion criteria. RESULTS: Of the 10 studies included, most assessed health services use (ie, hospitalizations) as a secondary outcome. Participants were recruited from a range of health care and community agencies, and most were diagnosed with dementia with severity ratings ranging from mild to severe. Most intervention strategies consisted of face-to-face assessments of the persons living with dementia, their caregivers, and the development and implementation of a care plan. A significant reduction in hospital admissions was not found in any of the included studies, although 1 study did observe a reduction in hospital days. CONCLUSIONS: The majority of studies included hospitalizations as a secondary outcome. Only 1 intervention was found to have an effect on hospitalizations. Future work would benefit from strategies specifically designed to reduce and prevent acute hospitalizations in persons with dementia.

Efficient Computational Screening of Organic Polymer Photovoltaics.

There has been increasing interest in rational, computationally driven design methods for materials, including organic photovoltaics (OPVs). Our approach focuses on a screening "pipeline", using a genetic algorithm for first stage screening and multiple filtering stages for further refinement. An important step forward is to expand our diversity of candidate compounds, including both synthetic and property-based measures of diversity. For example, top monomer pairs from our screening are all donor-donor (D-D) combinations, in contrast with the typical donor-acceptor (D-A) motif used in organic photovoltaics. We also find a strong "sequence effect", in which the average HOMO-LUMO gap of tetramers changes by ∼0.2 eV as a function of monomer sequence (e.g., ABBA versus BAAB); this has rarely been explored in conjugated polymers. Beyond such optoelectronic optimization, we discuss other properties needed for high-efficiency organic solar cells, and applications of screening methods to other areas, including non-fullerene n-type materials, tandem cells, and improving charge and exciton transport.

Miscibility of choline-substituted polyphosphazenes with PLGA and osteoblast activity on resulting blends.

The preparation of phosphazene tissue engineering scaffolds with bioactive side groups has been accomplished using the biological buffer, choline chloride. Mixed-substituent phosphazene cyclic trimers (as model systems) and polymers with choline chloride and glycine ethyl ester, alanine ethyl ester, valine ethyl ester, or phenylalanine ethyl ester were synthesized. Two different synthetic protocols were examined. A sodium hydride mediated route resulted in polyphosphazenes with a low choline content, while a cesium carbonate mediated process produced polyphosphazenes with higher choline content. The phosphazene structures and physical properties were studied using multinuclear NMR, differential scanning calorimetry (DSC), and gel permeation chromatography (GPC) techniques. The resultant polymers were then blended with PLGA (50:50) or PLGA (85:15) and characterized by DSC analysis and scanning electron microscopy (SEM). Polymer products obtained via the sodium hydride route produced miscible blends with both ratios of PLGA, while the cesium carbonate route yielded products with reduced blend miscibility. Heterophase hydrolysis experiments in aqueous media revealed that the polymer blends hydrolyzed to near-neutral pH media (∼5.8 to 6.8). The effect of different molecular structures on cellular adhesion showed osteoblast proliferation with an elevated osteoblast phenotype expression compared to PLGA over a 21-day culture period.

Resistance of presynaptic CaV2.2 channels to voltage-dependent inactivation: dynamic palmitoylation and voltage sensitivity.

Presynaptic CaV2.2 (N type) calcium channels gate the influx of calcium ions to trigger transmitter release. We have previously demonstrated at the chick ciliary ganglion presynaptic calyx terminal that the bulk of these channels are highly resistant to voltage dependent inactivation [E.F. Stanley, G. Goping, Characterization of a calcium current in a vertebrate cholinergic presynaptic nerve terminal, J. Neurosci. 11 (1991) 985-993; E.F. Stanley, Syntaxin I modulation of presynaptic calcium channel inactivation revealed by botulinum toxin C1, Eur. J. Neurosci. 17 (2003) 1303-1305; E.F. Stanley, R.R. Mirotznik, Cleavage of syntaxin prevents G-protein regulation of presynaptic calcium channels, Nature (Lond.) 385 (1997) 340-343]. Recent studies have suggested that CaV2.2 can be rendered inactivation resistant when expressed with the palmitoylated beta2A subunit and that this effect can be eliminated by tunicamycin, a general inhibitor of dynamic palmitoylation [J.H. Hurley, A.L. Cahill, K.P. Currie, A.P. Fox, The role of dynamic palmitoylation in Ca(2+) channel inactivation, Proc. Natl. Acad. Sci. U.S.A. 97 (2000) 9293-9298]. We find that while tunicamycin treatment had no effect on CaV2.2 current in the inactivation-sensitive isolated chick dorsal root ganglion (DRG) neuron, it caused a 10mV hyperpolarized shift in the profile of the inactivation-resistant presynaptic CaV2.2 population. This shift occurred without any effect on the voltage sensitivity of the inactivation process, as measured by a Boltzmann slope factor. Our findings suggest that dynamic palmitoylation contributes to the hyperpolarized steady inactivation profile of presynaptic CaV2.2. However, some other factor must also contribute since its inhibition does is not restore the inactivation profile to that of channels in the cell soma.

Case study II: application of the divalent cation bridging theory to improve biofloc properties and industrial activated sludge system performance-using alternatives to sodium-based chemicals.

The objective of this study was to investigate the application of the divalent cation bridging theory (DCBT) as a tool in the chemical selection process at an activated sludge plant to improve settling, dewatering, and effluent quality. According to the DCBT, to achieve improvements, the goal of chemical selection should be to reduce the ratio of monovalent-to-divalent (M/D) cations. A study was conducted to determine the effect of using magnesium hydroxide [Mg(OH)2] as an alternative to sodium hydroxide (NaOH) at a full-scale industrial wastewater treatment plant. Floc properties and treatment plant performance were measured for approximately one year during two periods of NaOH addition and Mg(OH)2 addition. A cost analysis of plant operation during NaOH and Mg(OH)2 use was also performed. During NaOH addition, the M/D ratio was 48, while, during Mg(OH)2 addition, this ratio was reduced to an average of approximately 0.1. During the Mg(OH)2 addition period, the sludge volume index, effluent total suspended solids, and effluent chemical oxygen demand were reduced by approximately 63, 31, and 50%, respectively, compared to the NaOH addition period. The alum and polymer dose used for clarification was reduced by approximately 50 and 60%, respectively, during Mg(OH)2 addition. The dewatering properties of the activated sludge improved dewatering as measured by decreased capillary suction time and specific resistance to filtration (SRF), along with an increase in cake solids from the SRF test. This corresponded to a reduction in the volume of solids thickened by centrifuges at the treatment plant, which reduced the disposal costs of solids. Considering the costs for chemicals and solids disposal, the annual cost of using Mg(OH)2 was approximately 30,000 dollars to 115,000 dollars less than using NaOH, depending on the pricing of NaOH. The results of this study confirm that the DCBT is a useful tool for assessing chemical-addition strategies and their potential effect on activated sludge performance.