bluuebunny/crossref_metadata_2025 huggingface dataset:
The Optimal Blend: The Approved Synopsis and the Final Protocol
Authors: Tansey Michael
Published: November 2020

The main objective is the rapid realization of a final protocol that accurately meets the development objectives, reflects the results of protocol feasibility, and can be implemented without unnecessary amendments. To recapitulate, the steps to an approved protocol are as follows: 1. The approved draft protocol synopsis. This is the penultimate version of the core of the final protocol and is used to assess protocol feasibility, as described in chapter 4. 2. The approved protocol synopsis. The synopsis has been amended as appropriate to ensure optimal feasibility without diminishing the validity of the study and has been approved. At this stage, the protocol is, in effect, locked and ready to be implemented. 3. The approved final protocol. This step involves incorporating the contents of the approved protocol synopsis into the template for the full version of the protocol and having it approved for completeness and consistency. Unfortunately, approval of each step is essential, with its implications of time-wasting micromanagement, formality, pedantry, and bureaucracy. How to minimize these aspects while ensuring that the essential value of the approval process is maintained is described later in this chapter. But first, we review the final steps to the definitive protocol. The only difference between this version of the synopsis and the draft synopsis is that all changes resulting from the feasibility process have been incorporated. The protocol is now complete from a purely operational perspective. That begs the question: “Why go through the process of approving this version and not just go on to the full, definitive protocol?” The reason is that it is much quicker and simpler, and less likely to lead to inconsistencies, to amend the draft synopsis and get on with all that can be done, without having to wait for the full protocol or having to plow through all the redundant (from an operational perspective) material it contains. The synopsis and the protocol have differing important functions, so that finalizing both as soon as possible is a priority.
What Is Known about the Cause
Authors: Ahlskog J. Eric
Published: November 2020

Most of the research into the cause of Lewy disorders has focused on Parkinson’s disease, since that is the best defined of these conditions and, therefore, the most straightforward to study. Dementia with Lewy bodies (DLB) is more difficult to diagnose with certainty, especially in the early years of the disease. What we collectively learn about Parkinson’s disease will likely be very relevant to our understanding of DLB. Multiple investigations have linked Parkinson’s disease to both environmental exposures and genetic factors. However, these associations have all been modest, and none of them accounts for more than a few percent of the contribution to the cause of sporadic Parkinson’s disease (i.e., the attributable risks are low). These investigations are ongoing and hopefully will soon provide a more complete understanding of the cause(s). Perhaps the most important clue to all Lewy conditions is located in the brain: the Lewy body itself. A recent sophisticated analysis of Lewy bodies revealed approximately 300 different component proteins. However, we already knew that Lewy bodies contain high concentrations of a normal protein called alpha synuclein. In fact, Lewy bodies are conventionally identified under the microscope with antibody stains that specifically bind to alpha synuclein. Could this be the crucial protein among the nearly 300? While the alpha synuclein story is focused on Parkinson’s disease, it may be just as relevant to DLB, as we shall see. The story starts with a large Italian-American family with Parkinson’s disease, studied by Dr. Lawrence Golbe and colleagues at the Robert Wood Johnson Medical Center in New Brunswick, New Jersey. In this rare family, many members of multiple generations had been affected by Parkinson’s disease (with Lewy bodies), consistent with a single gene passed on with dominant inheritance. It took a number of years to identify that abnormal gene, which ultimately was proven to be the gene coding for alpha synuclein. It was quickly discovered that this genetic error is not present in usual cases of Parkinson’s disease.
Which Drug for Parkinsonism? Walking, Stiffness, Tremor, and Slowness
Authors: Ahlskog J. Eric
Published: November 2020

In Chapters 1 and 4, we briefly summarized the symptoms of parkinsonism. Parkinsonism implies movement problems that are typical of Parkinson’s disease. They remain treatment issues during the lifetime of people with Parkinson’s disease, even if dementia develops. Similarly, parkinsonism also typically occurs in DLB, although to variable degrees. In these disorders parkinsonism primarily reflects low brain dopamine levels and improves with dopamine replacement therapy, often markedly. Parkinsonism occurs when a region of the brain called the basal ganglia ceases to work properly (see Figure 4.2 in Chapter 4). As discussed in Chapter 4, the substantia nigra is a crucial regulator of basal ganglia activity, which is mediated by dopamine release in the striatum. The substantia nigra degenerates in these Lewy disorders and, as a result, brain dopamine declines. With a decline in dopamine, movement slows. Bradykinesia is the medical term for such slowness. This manifests as not only slowed movement but also less movement and smaller than normal movements. Unconscious automatic movements, such as blinking or arm swing, diminish. A unique tremor of the hands (sometimes legs) often develops when these limbs are in a relaxed position (rest tremor). For unknown reasons, the brain is not affected symmetrically, hence, neither is the body. Typically, one side of the body is much more impaired than the other. The extent to which these symptoms develop differs from person to person and includes various combinations of the following components. The slowness may be apparent on one or both sides of the body. For example, one leg may lag behind when walking. The overall appearance is characterized by moving much slower than expected for one’s age. The person feels as if they are moving in molasses—everything slows down. Many of our daily activities involve repeated small movements, such as writing or brushing teeth. In the Lewy conditions of DLB and PDD, the size (amplitude) of repetitive movements diminishes, impairing the activity. This is exemplified by the small handwriting of someone with parkinsonism, termed micrographia. Clinicians assess repetitive motor function by asking the patient to repetitively tap the thumb and index finger.
Beginning Carbidopa/Levodopa Treatment: Background, Starting Dosages, and Side Effects
Authors: Ahlskog J. Eric
Published: November 2020

In the previous chapter the symptoms and signs of parkinsonism were described, along with the rationale for selecting carbidopa/levodopa as the primary drug for treating parkinsonism. In most cases of DLB or PDD, carbidopa/levodopa should be the only drug used for dopamine replenishment. This strategy results in the greatest likelihood of substantial benefits and least risk of side effects. If parkinsonism is minimal and causing no disability, carbidopa/levodopa does not need to be started. Certain non-motor parkinsonism symptoms in DLB and PDD may also respond to carbidopa/levodopa treatment, including anxiety, insomnia, and sometimes pain. Treatment of these non-motor symptoms will be discussed in Chapter 9. This chapter outlines levodopa treatment guidelines for people whose parkinsonism is troublesome and untreated. The guidelines presented here are also relevant to those taking only low doses of carbidopa/levodopa. If other drugs are being taken for parkinsonism it may be wise to begin tapering those off, one by one, before adding carbidopa/levodopa. This process is addressed in further detail in Chapter 7. Tapering off other drugs for parkinsonism should not be done without the clinician’s input. Drugs to consider for slow elimination include ropinirole (Requip), pramipexole (Mirapex), rotigotine (Neupro patch), selegiline (Eldepryl), rasagiline (Azilect), benztropine (Cogentin), and trihexyphenidyl (Artane). Amantadine may also fall into this category, although there are circumstances where it may be indicated (for hard-to-treat dyskinesias). Entacapone, taken as either Comtan or Stalevo, is also addressed in the next chapter. This chapter begins with a discussion of basic facts and principles relating to carbidopa/levodopa, before outlining specific treatment algorithms. The chapter ends with a discussion of possible side effects. Carbidopa/levodopa is usually well tolerated, as long as it is not combined with other parkinsonism drugs. The active ingredient in this formulation is levodopa. Everyone has levodopa in their bodies, and small amounts are present in the diet. This natural substance is the precursor to dopamine. An enzyme, dopa decarboxylase, is present in the brain and body that converts levodopa to dopamine.
Daytime Drowsiness
Authors: Ahlskog J. Eric
Published: November 2020

Drowsiness is common in those with DLB and PDD, and can interfere with thinking and memory, as well as quality of life. There are a variety of potential reasons for this, many treatable. Getting a little sleepy during a boring task or napping after lunch on the weekend is not a sign of a medical problem. However, daytime drowsiness should draw attention in certain circumstances: 1. More than one nap most days, or near-daily naps that span 2 to 3 hours 2. Falling asleep during conversations or eating 3. Frequently falling asleep during reading, watching TV, doing computer work or other vigilant tasks 4. Returning to sleep after breakfast These are signs that could indicate that nighttime sleep was not adequate (nonrestorative) but could have other explanations. Daytime drowsiness has limited causes: 1. Insomnia at bedtime 2. Awakening during the night 3. Insufficient time spent in bed at night 4. Poor quality sleep at night (despite adequate time in bed) 5. Daytime medications inducing drowsiness 6. A primary sleep disorder directly causing drowsiness (which may be DLB or PDD related) We will explore each of these possible causes and how they might be diagnosed and treated. If a person with DLB or PDD is excessively drowsy, at least one of these could be the problem. Inability to get to sleep at bedtime can translate into sleepiness during the daytime. Many people with DLB or PDD who experience insomnia benefit from nighttime carbidopa/levodopa doses. The benefits of carbidopa/levodopa dosing at bedtime for Lewy-related insomnia were addressed in Chapter 9. Various other factors, however, may contribute to insomnia. Sometimes medications taken in the evening are alerting. Such drugs include duloxetine (Cymbalta) or venlafaxine (Effexor), used for depression and often dosed twice daily. Elimination of all but the morning dose may allow sleep in such cases. Other drugs for depression from the Prozac class (SSRIs; see the list in Chapter 18) may also cause insomnia if taken at bedtime. A simple strategy is to simply switch to morning dosing on a trial basis. The tricyclic antidepressants, such as nortriptyline, amitriptyline, or protriptyline, should not cause insomnia; they may induce sleep. Occasionally, sleepy people are prescribed stimulants with long-acting properties, such as extended-release methylphenidate (Concerta), modafinil (Provigil), or armodafinil (Nuvigil).
General Medical Issues
Authors: Ahlskog J. Eric
Published: November 2020

People with DLB and PDD tend to be middle-aged and older. In this age group, selected general health issues deserve discussion. Comprehensive medical care is beyond the scope of this book, but several general medical topics should be addressed here. People with Lewy disorders commonly experience walking difficulties. The risk of falling may surface early or later in the condition. Fracture risk is also a concern, and preemptive action is wise. Falls can be tolerated if bones are strong; witness athletes who fall on a football field. Over the course of a lifetime, bones tend to lose their strength and become more prone to fractures. When the loss of bone integrity is substantial we categorize this as osteoporosis. There are specific criteria that doctors use to define osteoporosis. While bone integrity is measured in several ways, the most common and accepted measurement is by imaging with a nuclear medicine technique. A quick scan after injection of a radioisotope that is taken up by bones generates a picture and numeric data; these can be compared to those of normal subjects. This analysis is termed a nuclear medicine bone density study and sometimes is called a DEXA scan. Using the numeric measures from a bone density scan, reductions of bone integrity fall into two classes. We have already mentioned that substantial loss of bone strength is termed osteoporosis. A less severe reduction of bone integrity has been defined and termed osteopenia. Restated, mild bone weakening is osteopenia, and marked loss of bone integrity is osteoporosis. Conventionally, osteoporosis is treated with prescription medications, whereas the lesser problem of osteopenia is not. However, if there is a substantial fall risk, some clinicians would advise treating osteopenia with a prescription drug (see below). Who is at risk for osteoporosis? In the general population, advancing age is the major risk factor. Women over age 60 and men over age 70 fall into these risk categories, as well as those with very sedentary lives. In the context of DLB or PDD, osteoporosis is especially important to consider.
Hospitalization and Nursing Facilities: Keeping Everyone on the Same Page
Authors: Ahlskog J. Eric
Published: November 2020

Nearly all of us end up in the hospital for something sooner or later. The unique problems of Lewy disorders and medications can challenge hospital care teams. On a related note, some individuals with DLB or PDD may require care in a nursing facility. This may be transient, requiring rehabilitation and stabilization following a hospitalization; in other cases, it is indefinite because of the complex care necessary for DLB and PDD. In this chapter, the focus is on the care teams in these facilities. Although many staff in these settings are familiar with the medications and problems of DLB and PDD, this knowledge is not universal. Little published literature addresses the special needs of those with PDD or DLB admitted to the hospital or living in extended care facilities. It is hoped that this chapter can be an aid in caring for those with PDD or DLB. People with DLB or PDD are, by definition, cognitively impaired. Sometimes this is associated with hallucinations or delusions. Most individuals also have dopamine deficiency states with parkinsonism. Another common component is autonomic nervous system dysfunction. This dysautonomia may be associated with bladder and bowel disorders but, more importantly, with orthostatic hypotension (potential for fainting when ambulating). Some people with PDD or DLB are mildly impaired by these problems, and others are quite compromised. What follows is a summary of crucial knowledge for nursing and paramedical staffs. 1. As with any dementia, novel environments are disorienting. 2. Hallucinations are a frequent component of DLB and PDD. These may be exacerbated by psychoactive medications, including narcotics for pain. 3. Carbidopa/levodopa is the least likely among the potent drugs for parkinsonism to provoke hallucinations. Other Parkinson drugs should generally not be started. 4. People with DLB or PDD commonly experience dream enactment behavior (REM sleep behavior disorder); this should not be misinterpreted as nocturnal hallucinations. 5. Anticholinergic medications for urinary urgency may cross the blood–brain barrier and impair cognition (e.g., oxybutynin). The only drug from this class that cannot get into the brain is trospium (Sanctura).
Fluid Saturation Evaluation
Authors: Doveton John H.
Published: November 2020

In his treatise on electricity and magnetism, Maxwell (1873) published an equation that described the conductivity of an electrolyte that contained nonconducting spheres as: . . . Ψ = co/cw = 2Φ/(3-Φ) . . . where the “meaning” of Ψ (psi) has been most commonly interpreted as some expression of tortuosity, Co and Cw are the conductivity of the medium and the electrolyte, respectively, and Φ is the proportion of the medium that is occupied by the electrolyte. Since that time, considerable efforts have been devoted to elucidation of the electrical properties of porous materials, particularly with the advent of the first resistivity log in 1927, which founded an entire industry focused on estimating fluid saturations in hydrocarbon reservoirs from downhole measurements. To some degree, spirited discussions in the literature reflect two schools of thought, one that considers the role of the resistive framework from a primarily empirical point of view, and the other that models the conductive fluid phase in terms of electrical efficiency. Clearly, the two concepts are intertwined because resistivity is the reciprocal of conductivity and the pore network is the complement of the rock framework. If the solid part of the rock is nonconductive, then the ability of a rock to conduct electricity is controlled by the conductive phase in the pore space, which should make the case for equations to be formulated from classical physical theory. This approach is typically developed using electrical flow through capillary tubes as a starting point. Unfortunately, the topological transformation of a capillary tube model to a satisfactory representation of a real pore network is a formidable challenge, so that mathematical solutions may not be acceptable, even though they are grounded in basic physics. The most successful model along these lines has been proposed by Herrick and Kennedy (1994), who maintain that while the Archie equation is a useful parametric function, it has no physical basis. Some of their conclusions are reviewed at the end of this chapter.
What Is Narrative Psychiatry?
Authors: Hamkins SuEllen
Published: November 2020

Narrative psychiatry brings the muscle and agility of narrative theory and the spirit of compassion and social justice to the practice of psychiatry. What makes narrative psychiatry different from psychiatry-as-usual? Rather than focusing only on finding the source of the problem, narrative psychiatry also focuses on finding sources of strength and meaning. The result is compassionate, powerful healing. Narrative psychiatry combines narrative and biological understandings of human suffering and well-being. It begins with compassionate connection with patients, understanding that we live our lives in relationships and connect with one another through the stories we tell. It relishes discovering untold but inspiring stories of a person’s resiliency and skill in resisting mental health challenges while dismantling narratives that fuel problems. It examines what the doctor’s kit of psychiatry has to offer in light of the values and preferences of the person seeking consultation, authorizing the patient as the arbiter of what is helpful and what is not. Psychiatry as a field is seeking a more positive and patient-centered approach, which narrative psychiatry exemplifies. In his address at the American Psychiatric Association’s annual meeting on May 6, 2012, President-Elect Dilip Jeste, M.D., said that “ ‘positive psychiatry’—a psychiatry that aims not just to reduce psychiatric symptoms but to help patients grow and flourish—is the future.” Likewise, in 2012 the U.S. Substance Abuse and Mental Health Services Administration called for a focus on “recovery” that includes collaborative and culturally sensitive care that seeks to honor the patient’s values, self-determination, and preferred relationships and to foster not just the absence of symptoms, but also well-being. Narrative approaches to psychiatry, psychotherapy, and medicine have been burgeoning in the last decade, inspired by the wave of narrative theory that has progressively suffused philosophy, anthropology, literature, and the arts over the last fifty years. Training programs and courses teaching narrative approaches to mental health treatment and to medicine are flourishing.
The Assignment of the Absolute Configuration by NMR using Chiral Derivatizing Agents
Authors: Seco Josi M. , Quiqoa Emilio , Riguera Ricardo
Published: November 2020

Nuclear magnetic resonance spectroscopy (NMR spectroscopy) is a research technique that uses the magnetic properties of atomic nuclei to determine physical and chemical properties of atoms or the molecules in which they are contained. Proton NMR (1H NMR) is a technique that applies NMR spectroscopy specifically to the hydrogen-1 nuclei within the molecules of a substance, in order to determine the structure of that substance's molecules. The use of 1H NMR for the assignment of absolute configuration of organic compounds is a well-established technique. Recent research describes the technique's application to mono-, bi- and trifunctional compounds. In addition, several new auxiliary reagents, mono- and biderivatization procedures, on-resin methodologies and more recently, the use of 13C NMR, have been introduced to the field. In The Assignment of the Absolute Configuration by NMR Using Chiral Derivatizing Agents: A Practical Guide, eminent Professor of Organic Chemistry Ricardo Riguera organizes this cutting-edge NMR research. Professor Riguera offers a short and usable guide that introduces the reader to the research with a plethora of details and examples. The book briefly explains the theoretical aspects necessary for understanding the methodology, dedicating most of its space to covering the practical aspects of the assignment, with examples and spectra taken from the authors' own experiments. Upper-level undergraduates, graduate students, and chemical researchers will find this guide useful for their studies and practice.
Assignment of the Absolute Configuration of Monofunctional Compounds by Single Derivatization
Authors: Seco Josi M. , Quiqoa Emilio , Riguera Ricardo
Published: November 2020

The procedures shown in Chapter 3 allow the determination of the absolute configuration of several classes of compounds (Chapter 1, Figure 1.18), but they require the preparation of two derivatives and the comparison of their NMR spectra. Alternative methods have been developed for secondary alcohols and α-chiral primary amines. These are particularly suited for those cases where the amount of the available sample is low, and they require the preparation of only a single derivative [41–43, 55–56, 165]. There are three different approaches to using only a single derivatization to perform the assignment of those substrates [13, 165]. The first two are based on a controlled conformational change that is produced either by modification of the probe temperature [41, 165] or by selective complexation [42, 55, 56, 165]. The third one is based on the differences observed between the chemical shifts of the free alcohol and those of the 9-AMA ester derivative [43, 165]. In general, these single-derivatization procedures are limited to 1H NMR. Because the shift differences observed in 13C NMR are quite small, they produce insignificant Δδ values, and therefore the signs are not sufficiently accurate to produce a safe assignment [72]. Explanations and examples of applications are presented in the remainder of this chapter. For the assignment of secondary alcohols, a simple approach based on the use of a single MPA ester has proven to work very well [41, 165]. It is based on the controlled shift of the conformational equilibrium between the two main conformers (sp/ap) that were described in Chapter 1 for the MPA esters of secondary alcohols [36, 37]. Thus, for the assignment, it is only necessary to prepare either the (R)- or the (S)-MPA ester and then to compare the chemical shifts of L1/L2 in the spectra taken at room temperature and at a lower temperature [41]. Figure 4.2 presents a summary of the procedure and the graphical model expressing the ΔδT1T2 correlation between the sign and the stereochemistry for the assignment of secondary alcohols derivatized as (R)- or as (S)-MPA esters.
Predictors of hypertension detection in English general practices: a cross sectional study
Authors: Levene Louis S , Coles Briana D , Gillies Clare L , Shabnam Sharmin , Zaccardi Francesco , Khunti Kamlesh
Published: November 2020

Background

Worldwide, high systolic blood pressure is the leading risk factor for deaths and disability-adjusted life-years but has been historically under-detected. This study aimed to quantify differences between estimated and practice-detected prevalences of hypertension across English general practices, and to determine how variations in detected prevalence could be explained by population-level and service-level factors.

Methods

Descriptive statistics, pair wise correlations between the independent variables and a multivariable regression analysis were undertaken. In the regression model, the outcome was detected hypertension prevalence, adjusted for estimated prevalence, person-related and disease-related determinants of illness and characteristics of general practices.

Results

Detected prevalence was substantially lower than estimated prevalence (mean difference 16.23%; standard deviation 2.88%). Higher detected prevalence was associated with increased deprivation, increased non-white ethnicity and urban location. Lower detected prevalence was associated with larger list sizes, more general practitioners and being located in the South outside London. The final multivariable model’s adjusted R2 value was 0.75.

Conclusions

Substantial under-detection of hypertension is widespread across England. Independent of estimated prevalence, factors associated with greater morbidity and population density predicted higher detected prevalence. Identifying patients with undetected hypertension and coordinating care for these patients will require further resources and logistical support in community settings.
Selective Disclosure as a Self-Protective Process: Navigating Friendships as Asian and Latino Undocumented Young Adults
Authors: Cho Esther Yoona
Published: November 2020

Drawing on in-depth interviews with sixty-three undocumented, 1.5-generation Korean-origin and Mexican-origin young adults in the United States, I bring attention to the deep-seated effects of immigration status that extend into the most intimate aspects of undocumented immigrants’ lives. Findings show that the stigma of being undocumented leads undocumented young adults to be selective about whom they befriend and to whom they decide to disclose their status, feeling safer with those of shared immigrant descent. Furthermore, ethnoracial background shapes pathways of selective disclosure. Korean undocumented young adults in the study were more likely to be prompted to disclose their status to justify another personal circumstance, whereas Mexican respondents primarily sought empathy and community in times of distress. Moreover, Korean respondents more often created a distinction between individuals with whom they discussed the intimate details of their legal situation and those they deemed close but from whom they hid their status. This work demonstrates the ways in which undocumented immigrants engage in selective status disclosure as one of myriad strategies to mitigate the harmful affective and material effects of undocumented immigration status. By using a comparative qualitative approach, this study points to the nuanced and very personal ways in which ethnoracial background shapes everyday experiences of illegality.
Cytotoxicity and Genotoxicity of E-Cigarette Generated Aerosols Containing Diverse Flavoring Products and Nicotine in Oral Epithelial Cell Lines
Authors: Tellez Carmen S , Juri Daniel E , Phillips Loryn M , Do Kieu , Yingling Christin M , Thomas Cindy L , Dye Wendy W , Wu Guodong , Kishida Shosei , Kiyono Tohru , Belinsky Steven A
Published: November 2020

Electronic cigarettes are the most commonly used nicotine containing product among teenagers. The oral epithelium is the first site of exposure and our recent work revealed considerable diversity among e-liquids for composition and level of chemical constituents that impact nicotine deposition in a human oral-trachea cast and affect the formation of reactive carbonyls. Here, we evaluate the dose response for cytotoxicity and genotoxicity of e-cigarette-generated aerosols from 10 diverse flavored e-liquid products with and without nicotine compared with unflavored in 3 immortalized oral epithelial cell lines. Three e-liquids, Blue Pucker, Love Potion, and Jamestown caused ≥20% cell toxicity assessed by the neutral red uptake assay. Nine products induced significant levels of oxidative stress up to 2.4-fold quantified by the ROS-Glo assay in at least 1 cell line, with dose response seen for Love Potion with and without nicotine across all cell lines. Lipid peroxidation detected by the thiobarbituric acid reactive substances assay was less common among products; however, dose response increases up to 12-fold were seen for individual cell lines. Micronuclei formation indicative of genotoxicity was increased up to 5-fold for some products. Blue Pucker was the most genotoxic e-liquid, inducing micronuclei across all cell lines irrespective of nicotine status. A potency score derived from all assays identified Blue Pucker and Love Potion as the most hazardous e-liquids. These in vitro acute exposure studies provide new insight about the potential for some flavored vaping products to induce significant levels of oxidative stress and genotoxicity.
Correlation of Hounsfield Unit Measurements on Computed Tomography of the Shoulder With Dual-Energy X-ray Absorptiometry Scans and Fracture Risk Assessment Tool Scores: A Potential for Opportunistic Screening
Authors: Earp Brandon E. , Kallini Jennifer R. , Collins Jamie E. , Benavent Kyra A. , Tintle Scott M. , Rozental Tamara D.
Published: November 2020

Background:

The diagnosis of bone mineral density (BMD) abnormalities involves dual-energy x-ray absorptiometry (DXA), but few patients complete this after a fragility fracture. The assessment of BMD using Hounsfield unit (HU) measurements from computed tomography (CT) scans has been correlated with DXA results in previous studies. We aimed to evaluate the correlation between shoulder CT HU and DXA scores.

Methods:

Billing databases of 3 academic institutions were queried for patients who underwent both DXA and CT scan of the upper extremity within 1 year of each other. DXA T-scores for spine, hip, and femoral neck were recorded. BMD status was defined based on composite T-scores, using the lowest T-score in the spine, hip, or proximal femur. CT scans were measured for HU over 4 slices, recorded to create a bone column, then averaged. The patients' risks of major osteoporosis-related fracture and hip fracture were calculated using the Fracture Risk Assessment Tool.

Results:

In total, 300 patients were included. A positive correlation was found between composite T-scores and HU for glenoid and proximal humerus (0.36; 0.17). The proximal humerus HU was significantly associated with the BMD T-score for the hip (P = 0.01); the glenoid HU was significantly associated with BMD T-scores for the hip, spine, and femoral neck (P = 0.002; P = 0.001; P = 0.002). A 10-year risk of hip fracture >3% was associated with lower proximal humerus HU.

Conclusions:

Our study is the first to discover significant correlations between HU at the glenoid and proximal humerus and risk factors as established by the Fracture Risk Assessment Tool scoring system.

Level of Evidence:

Diagnostic Level III. See Instructions for Authors for a complete description of levels of evidence.
Sustained Improvement in Tracheal Intubation Safety Across a 15-Center Quality-Improvement Collaborative: An Interventional Study From the National Emergency Airway Registry for Children Investigators*
Authors: Nishisaki Akira , Lee Anthony , Li Simon , Sanders Ronald C. , Brown Calvin A. , Rehder Kyle J. , Napolitano Natalie , Montgomery Vicki L. , Adu-Darko Michelle , Bysani G. Kris , Harwayne-Gidansky Ilana , Howell Joy D. , Nett Sholeen , Orioles Alberto , Pinto Matthew , Shenoi Asha , Tellez David , Kelly Serena P. , Register Melinda , Tarquinio Keiko , Simon Dennis , Krawiec Conrad , Shults Justine , Nadkarni Vinay
Published: November 2020

Objectives:

To evaluate the effect of a tracheal intubation safety bundle on adverse tracheal intubation-associated events across 15 PICUs.

Design:

Multicenter time-series study.

Setting:

PICUs in the United States.

Patients:

All patients received tracheal intubations in ICUs.

Interventions:

We implemented a tracheal intubation safety bundle as a quality-improvement intervention that includes: 1) quarterly site benchmark performance report and 2) airway safety checklists (preprocedure risk factor, approach, and role planning, preprocedure bedside “time-out,” and immediate postprocedure debriefing). We define each quality-improvement phase as baseline (–24 to –12 mo before checklist implementation), benchmark performance reporting only (–12 to 0 mo before checklist implementation), implementation (checklist implementation start to time achieving > 80% bundle adherence), early bundle adherence (0–12 mo), and sustained (late) bundle adherence (12–24 mo). Bundle adherence was defined a priori as greater than 80% of checklist use for tracheal intubations for 3 consecutive months.

Measurements and Main Results:

The primary outcome was the adverse tracheal intubation-associated event, and secondary outcomes included severe tracheal intubation-associated events, multiple tracheal intubation attempts, and hypoxemia less than 80%.

From January 2013 to December 2015, out of 19 participating PICUs, 15 ICUs (79%) achieved bundle adherence. Among the 15 ICUs, the adverse tracheal intubation-associated event rates were baseline phase: 217/1,241 (17.5%), benchmark reporting only phase: 257/1,750 (14.7%), early 0–12 month complete bundle compliance phase: 247/1,591 (15.5%), and late 12–24 month complete bundle compliance phase: 137/1,002 (13.7%). After adjusting for patient characteristics and clustering by site, the adverse tracheal intubation-associated event rate significantly decreased compared with baseline: benchmark: odds ratio, 0.83 (0.72–0.97; p = 0.016); early bundle: odds ratio, 0.80 (0.63–1.02; p = 0.074); and late bundle odds ratio, 0.63 (0.47–0.83; p = 0.001).

Conclusions:

Effective implementation of a quality-improvement bundle was associated with a decrease in the adverse tracheal intubation-associated event that was sustained for 24 months.
Complementary Therapies Used by Indonesians With Myocardial Infarction
Authors: Muflihah Ulfatul , Chinnawong Tippamas , Kritpracha Charuwan
Published: November 2020

This descriptive, cross-sectional study was conducted to identify types, frequency, methods, duration, and purpose of complementary therapies used by Indonesians with myocardial infarction. The majority of the respondents used biologically based therapies, with the most common subtype being herbs. The purpose of using biologically based therapies was for health promotion.
Suppressive effects of an apoptotic mimicry prepared from jumbo-flying squid-skin phospholipids on the osteoclastogenesis in receptor activator of nuclear factor kappa B ligand/macrophage colony-stimulating factor-induced RAW 264.7 cells
Authors: Kao Yi-Feng , Tu Ming-Chieh , Chai Huey-Jine , Lin Yi-Ling , Chen Yi-Chen
Published: November 2020

Background:

Liposomes containing docosahexaenoic acid (DHA) and phosphatidylserine were claimed to inhibit osteoclast formation and bone resorption in the inflammatory status. Herein, we proposed that an apoptotic mimicry (SQ liposome) prepared from squid-skin phospholipids can explore the suppressive osteoclastogenesis.

Methods:

The intermolecular fatty-acid composition in the phospholipid of squid-skin extract was analyzed by GC-FID. The SQ liposome structure was characterized by size distribution and zeta potential (ζ). RAW 264.7 cell is used to study the effect of SQ liposomes on osteoclast differentiation. Secretion of prostaglandin E2 (PGE2) and transforming growth factor-β (TGF-β) from RAW 264.7 cells were assayed. Antiosteoclastogenesis effects were performed via the tartrate-resistant acid phosphatase (TRAP)-positive multinucleated cell (MNC) counting, bone resorption pit assay, and TRAP activity analysis. The specific gene expressions related to antiosteoclastogenesis were also detected.

Results:

An apoptotic mimicry through the use of a single-layer liposome (SQ liposome) with phosphatidylserine exposure contains DHA (28.7%) and eicosapentaenoic acid (EPA, 11.8%). Co-treatment with receptor activator of nuclear factor kappa B ligand (RANKL)/macrophage colony-stimulating factor induced RAW 264.7-cell differentiation into mature osteoclasts, thus enhancing PGE2 and TGF-β secretion. However, cotreatment with 1 mg/mL of SQ liposome restored (p < 0.05) the cell viabilities under the RANKL stress. Increased PGE2 levels was downregulated (p < 0.05) in cotreatments with 0.11 and 0.33 mg/mL of SQ liposome, but on the TGF-β levels were not (p > 0.05) influenced in SQ liposome cotreatments. Cotreatments with 0.33–1 mg/mL of SQ liposome suppressed (p < 0.05) the osteoclast maturation (such as decreased MNCs and bone pit formation), inhibited TRAP activities, and downregulated the osteoclastogenesis-related gene expressions.

Conclusion:

In summary, current data support that a possible prevention of our prepared SQ liposomes which are rich in DHA and EPA on bone loss is through the suppression of osteoclastogenesis. Moreover, based on the results from this study an in vivo study warrants a further investigation.
Identification of a de novo TSC2 variant in a Han-Chinese family with tuberous sclerosis complex
Authors: Wu Shan , Guo Yi , Liu Chun , Liu Qingxiang , Deng Hao , Yuan Lamei
Published: November 2020

Background:

Tuberous sclerosis complex (TSC) is an autosomal dominant disorder with a variety of clinical findings. Variants in the TSC complex subunit 1 gene (TSC1) or the TSC complex subunit 2 gene (TSC2) are responsible for TSC.

Methods:

Physical examinations, computed tomography scans, and light microscopy analyses were performed on the TSC patient from a Han-Chinese pedigree. Whole-exome sequencing combined with Sanger sequencing were performed on the family members.

Results:

The TSC patient showed typical clinical features, including facial angiofibromas, gingival fibromas, a shagreen patch, hypomelanotic macules, ungual fibromas, subependymal nodules, multiple pulmonary cysts, and renal hamartomas. A de novo heterozygous c.5146delG (p.Ala1716Profs*110) variant in the TSC2 gene was identified in the TSC patient of the Han-Chinese family. To our knowledge, this is the first report of the TSC2 c.5146delG variant associated with TSC.

Conclusion:

The study expanding the disease-causing variant spectrum, suggests that whole-exome sequencing combined with Sanger sequencing may be a method for TSC diagnosis and differential diagnosis, and may facilitate the development of genetic counseling and targeted gene therapy for this disease.
Enhancing POLST Completion in a Hospital Setting: An Interdisciplinary Approach
Authors: R. Reed Margaret , Stewart Samantha , Meyer Stephanie A. , Seferian Edward G. , Sax Harry C.
Published: November 2020

EXECUTIVE SUMMARY

With increased therapeutic capabilities in healthcare today, many patients with multiple progressive comorbidities are living longer. They experience recurrent hospitalizations and often undergo procedures that are not aligned with their personal goals. That is why it is essential to discuss and document healthcare preferences prior to an acute event when significant interventions could occur, especially for patients with serious and progressive illness. Completion of an advance directive and a physician order for life-sustaining treatment (POLST) supports provision of goal-concordant care. Further, for patients who have do not attempt resuscitation (DNAR) orders or are diagnosed with advanced dementia, having a POLST is essential. This may be best accomplished with hospitalization discharge plans.

Our 896-bed academic medical center, Cedars-Sinai Medical Center, launched a quality initiative in 2015 to complete POLSTs for patients being discharged with DNAR status or with dementia returning to a skilled nursing facility. As part of interdisciplinary progression of care rounds, emphasis was placed on those patients for whom POLST completion was indicated. Proactive, facilitated discussions with patients, family members, and attending physicians were initiated to support POLST completion. The completed forms were then uploaded to the electronic health record. Individual units and physicians received regular feedback on POLST completion rates, and the data were later shared at medical staff quality improvement meetings.

During the initiative, POLST completion rates for DNAR patients discharged alive rose from 41% in fiscal year (FY) 2014 to 75% in FY 2019. Similar improvement was seen for patients with dementia discharged to skilled nursing facilities, regardless of code status (rising from 14% in FY 2014 to 54% in FY 2019). Subsequently, we have expanded our efforts to include early discussion and completion of these advanced care planning documents for patients recently diagnosed with high mortality cancers (ovarian, pancreatic, lung, glioblastoma), focusing on the completion of advanced care planning documentation and palliative care referrals.
Time-Driven Activity-Based Costing of Emergency Department Postdischarge Nurse Calls
Authors: Liu Yingna , Luciani-Mcgillivray Ines , Hughes Maryfran , Raja Ali S. , Kaplan Robert S. , Yun Brian J.
Published: November 2020

EXECUTIVE SUMMARY

Postdischarge telephone calls by nurses can decrease patient return rates to healthcare systems. To date, call program costs have not been compared with patient return rates to determine cost-effectiveness. We used time-driven activity-based costing to determine the costs associated with such programs. We developed process maps for a postdischarge nurse call program in the emergency department of an urban, quaternary care, academic, Level 1 trauma center. Our primary outcome was the total cost of calls, which is based on the length of the calls (after 8 hours of observation) and the total capacity rate cost based on national registered nurse salary and space costs. Seven-day return rate differences between patients reached and those not reached from July 2018 to March 2019 were determined with a Z-test. We observed 113 postdischarge calls for 79 patients. The mean (SD) length of calls for patients reached was 4.3 minutes (1.8) compared with 2.6 minutes (0.6) for those not reached. The total capacity rate cost for calls was $1.09/minute, or $4.69 per patient reached and $2.83 per patient not reached. A retrospective analysis of 6,698 patients reached and 6,519 patients not reached showed hospital return rates of 3.5% and 6.3% (p < .0001), respectively. The study findings show that postdischarge calls were associated with decreased return rates to the emergency department and a savings of $134.89 per prevention of one return. In deciding whether to use postdischarge call programs, healthcare systems should also consider the effects on specific demographics and the potential benefits of greater patient satisfaction and increased treatment adherence.
Weather Parameters and COVID-19
Authors: Pahuja Sourabh , Madan Manu , Mittal Saurabh , Pandey Ravindra Mohan , Nilima  , Madan Karan , Mohan Anant , Hadda Vijay , Tiwari Pawan , Guleria Randeep
Published: November 2020

Objectives:

To assess the effect of ambient temperature, humidity and wind speed on disease occurrence in Delhi, India.

Data and Methods:

Data regarding daily corona cases, temperature, humidity, wind speed, doubling time and basic reproduction number (R
0) was retrieved from online sources. Pearson's coefficient was used to assess the correlation between daily as well as weekly corona cases and various environmental factors.

Results:

During the study period of 97 days, there was a steady rise in number of corona cases with median (interquartile range) cases per day being 224 (58 to 635). The doubling time demonstrated a strong positive correlation with temperature while R
0 had strong negative correlation with temperature (correlation coefficients 0.814 and −0.78, respectively). No significant correlation with humidity or wind speed was observed.

Conclusion:

Increasing temperature decreases COVID-19 infectivity; however, actual role of environmental factors in expansion of pandemic needs further evaluation globally.
Prospective evaluation of variables affecting platelet function in patients with newly diagnosed chronic myeloid leukemia
Authors: Jain Ankur , Arora Anupma , Singh Jyoti , Patarwal Ram N. , Prasad Pooja , Chaudhry Sumita , Sharma Monica , Khunger Jitender Mohan , Gupta Dipender Kumar , Saluja Sumita
Published: November 2020

Platelet function in chronic myeloid leukemia (CML) could be affected by either hyperleucocytosis, clonal megakaryopoiesis, or tyrosine kinase inhibitors. However, these variables have never been prospectively evaluated. We conducted a prospective study over a period of 1.5 years in a tertiary care center of north India. Patients with CML in chronic phase, more than 18 years, and treated with imatinib were enrolled (n = 32). Age, and sex-matched controls were also included. Platelet function test was performed using two-channel Chrono-Log aggregometer 490 at four time-points: first, at diagnosis; second, after leucoreduction (total leucocyte count, <10 × 109/l) achieved with hydroxycarbamide; third, on-imatinib at BCR-ABL less than 1%; and fourth, in an independent cohort (off-imatinib) at deep molecular response (DMR) (BCR-ABL < 0.01%). Statistical analysis was performed using IBM SPSS statistics (version 22.0). Median age of patients was 42 years (15–65), and M : F ratio was 1 : 1. At diagnosis, platelet function correlated negatively with total leucocyte count, but not with platelet count. As compared with baseline, platelet aggregation with ADP (2.5 μl), and collagen (2.5 μl) improved significantly after leucoreduction (P = 0.05 and 0.009, respectively). Imatinib further caused significant impairment of aggregation with ADP (2.5 μl), collagen (2.5 μl), and collagen (1 μl) (P = 0.04, 0.008, and 0.02, respectively). Patients in DMR also demonstrated a significant impairment of platelet aggregation with all the agonists as compared with controls. While leucoreduction alone can improve the baseline platelet function derangement in CML, imatinib further impairs it. Residual CML stem cells, or effect of imatinib on normal common myeloid progenitors might account for platelet function derangement at DMR.