bluuebunny/crossref_metadata_2025 huggingface dataset:
Rating the Impact of Visual Impairment
Authors: Colenbrander August
Published: December 2020

The AMA Guides to the Evaluation of Permanent Impairment (AMA Guides) used the Snell Visual Efficiency Scale (1925). Following scientific progress, the Vision chapter in the fifth and sixth editions of the AMA Guides began using the Functional Vision Score (FVS) that is endorsed by the International Council of Ophthalmology and the International Society for Low Vision Research and Rehabilitation. Use of the FVS provided an opportunity to correct many inconsistencies in the VES system and also is better integrated with modern measurement methods and the ratings used for other organ systems. The FVS score is obtained by combining the Functional Acuity Score and the Functional Field Score; if any adjustments are introduced in this combination, they must be completely justified and cannot be based on subjective arguments. The disability is rated on the basis of functional considerations and is not influenced by nonfunctional factors. Combining visual acuity loss and visual field loss into a single number is attractive for administrative and legal purposes, but this step is meaningless in the context of rehabilitation because rehabilitation for visual acuity loss is entirely different from rehabilitation for visual field loss. The FVS system provides internationally endorsed statistical estimates of the effects of visual impairment on the ability to perform activities of daily living.
Subjective, Objective, or Both?
Authors: Brooks Charles N. , Talmage James B. , Mueller Kathryn
Published: December 2020

The terms subjective and objective often appear in health care records, and one commonly hears about “subjective symptoms” and “objective complaints”—yet the former is redundant and the latter an oxymoron. Objectively verifiable pathology may explain a patient's symptoms, but complaints themselves are never objective but rather, by definition, subjective. The AMA Guides to the Evaluation of Permanent Impairment (AMA Guides), Sixth Edition, defines the terminology: Subjective information is more open to interpretation, but objective data are factual, reproducible, and often measurable or quantifiable. Objective findings generally have much higher inter-examiner reliability than subjective findings. Symptoms and most findings on physical (particularly neuromusculoskeletal) examination are subjective. Diagnostic study results and a minority of physical findings are objective. Some physical findings, such as strength and range of motion measurements, are both subjective and objective. Repeat testing, assessment of plausibility, and use of confirmatory physical findings can be used to validate or “objectify” subjective findings (eg, by determining if a weakness is corroborated by other neurologic or physical findings, imaging study results, and/or electrodiagnostic testing). The use of objective, or at least less subjective, findings in impairment rating should improve interrater reliability. Thus, evaluating physicians should not regard subjective complaints and findings, and they should lend greater weight to objective findings.
Chronic Pain: Fundamental Scientific Considerations, Specifically for Legal Claims
Authors: Barth Robert J.
Published: December 2020

Scientific findings have indicated that psychological and social factors are the driving forces behind most chronic benign pain presentations, especially in a claim context, and are relevant to at least three of the AMA Guides publications: AMA Guides to Evaluation of Disease and Injury Causation, AMA Guides to Work Ability and Return to Work, and AMA Guides to the Evaluation of Permanent Impairment. The author reviews and summarizes studies that have identified the dominant role of financial, psychological, and other non–general medicine factors in patients who report low back pain. For example, one meta-analysis found that compensation results in an increase in pain perception and a reduction in the ability to benefit from medical and psychological treatment. Other studies have found a correlation between the level of compensation and health outcomes (greater compensation is associated with worse outcomes), and legal systems that discourage compensation for pain produce better health outcomes. One study found that, among persons with carpal tunnel syndrome, claimants had worse outcomes than nonclaimants despite receiving more treatment; another examined the problematic relationship between complex regional pain syndrome (CRPS) and compensation and found that cases of CRPS are dominated by legal claims, a disparity that highlights the dominant role of compensation. Workers’ compensation claimants are almost never evaluated for personality disorders or mental illness. The article concludes with recommendations that evaluators can consider in individual cases.
To Spinal Image or Not To Spinal Image, That is the Question
Authors: Auerbach Marjorie Eskay
Published: December 2020

Although back pain is the most common and expensive cause of work disability in the United States, our understanding of low back pain (LBP) is limited despite the advantages of advanced imaging technologies. Diagnostic studies often are requested for fear of missing serious or occult pathology or to reassure patients but have a low likelihood of identifying a specific cause for the reported symptoms in patients who present with nonspecific LBP. From a clinical perspective, the information provided in lumbar imaging, whether plain X rays or magnetic resonance imaging (MRI), has not been found either to influence treatment recommendations or improve outcomes. Further, routine advanced imaging is not associated with improved outcomes and identifies many radiographic findings that correlate poorly with symptoms; imaging is recommended when severe or progressive neurologic deficit is present or if serious underlying disease is suspected. Surgery rates are highest where imaging rates are highest, and a significant proportion of the variation in rates of spine surgery can be explained by differences in the rates of advanced spinal imaging. Because imaging has no role in the impairment rating of nonspecific LBP, an individual's having a work injury that requires an impairment rating is not a reason to order spinal imaging. To answer the question in this article's title, the answer usually is not to order a spinal image.
Maximum Medical Improvement
Authors: Brooks Charles N. , Brigham Christopher R.
Published: December 2020

Most acute injuries and illnesses resolve, ie, reach maximum medical improvement (MMI), within days or weeks and without permanent impairment. Fractures, more severe soft tissue injuries and illness, and conditions that require surgery take longer to reach MMI, often about a year, with a range of six months to two years. Serious head, spinal cord, and other catastrophic injuries commonly take two or more years to reach MMI. These more severe injuries and illnesses understandably are more likely to result in permanent impairment. However, various parties to the claim process may request impairment rating prematurely: The claimant or plaintiff whose injury or illness has resulted in loss of income and financial hardship may push for an early impairment award or settlement. The surgeon who has operated and is done with postoperative follow-up may want to be rid of claim forms and move on to other patients. The overburdened adjuster may want to get the claim closed, thereby diminishing their workload. But rating impairment prior to MMI, ie, before it is permanent, often results in erroneously inflated ratings. In general, functional status, physical findings, and/or clinical study results improve over time, sometimes with and sometimes without treatment. This usually results in a concurrent decrease in, and sometimes even resolution of, impairment. With knowledge of the appropriate terminology and definitions, the evaluating physician should be able to render an opinion regarding MMI that is both understandable and legally sustainable in the applicable jurisdiction.
AMA Guides, Sixth Edition: Spinal Impairment Case Examples
Authors: Hazlewood Jeffrey , Talmage James B. , Eskay-Auerbach Marjorie
Published: December 2020

Chapter 17, The Spine and Pelvis, of the AMA Guides to the Evaluation of Permanent Impairment (AMA Guides), Sixth Edition, is used frequently when determining an individual's permanent impairment rating at maximum medical improvement (MMI). Frequently, ratings for diagnoses of “nonverifiable back pain,” herniated discs, nonverifiable radicular pain, and radiculopathy are requested. Definitions of terminology used in the AMA Guides may differ from those used by some physicians when they see patients, and evaluators should use terminology that is consistent with that of the AMA Guides. For example, for the purposes of the AMA Guides, radiculopathy is defined as “significant alteration in the function of a single or multiple nerve roots and is usually caused by mechanical or chemical irritation of one or several nerves.” This article presents fifteen cases, the whole person impairment associated with each case, and a discussion of the process whereby the rating was obtained. Accurate and fair ratings of common cases of injury-related back and leg pain require a thorough knowledge of the definitions outlined in the AMA Guides, Sixth Edition, as well as thorough knowledge of the peripheral nervous system. Also, an accurate and detailed subjective history of pain reports (including true “radicular” referral patterns) and objective physical examination, as well as a review of the medical records and previous documentations, are essential.
The Historical Development of Burden of Treatment Compliance
Authors: Demeter Stephen L.
Published: December 2020

A long-standing criticism of the AMA Guides to the Evaluation of Permanent Impairment (AMA Guides) has been the inequity between the internal medicine ratings and the orthopedic ratings; in the comparison, internal medicine ratings appear inflated. A specific goal of the AMA Guides, Sixth Edition, was to diminish, where possible, those disparities. This led to the use of the International Classification of Functioning, Disability, and Health from the World Health Organization in the AMA Guides, Sixth Edition, including the addition of the burden of treatment compliance (BOTC). The BOTC originally was intended to allow rating internal medicine conditions using the types and numbers of medications as a surrogate measure of the severity of a condition when other, more traditional methods, did not exist or were insufficient. Internal medicine relies on step-wise escalation of treatment, and BOTC usefully provides an estimate of impairment based on the need to be compliant with treatment. Simplistically, the need to take more medications may indicate a greater impairment burden. BOTC is introduced in the first chapter of the AMA Guides, Sixth Edition, which clarifies that “BOTC refers to the impairment that results from adhering to a complex regimen of medications, testing, and/or procedures to achieve an objective, measurable, clinical improvement that would not occur, or potentially could be reversed, in the absence of compliance.
Commentary on Two-Point Discrimination in the Use of Upper Extremity Nerve Function in the AMA Guides
Authors: Talmage James B. , Melhorn J. Mark
Published: December 2020

This article responds to the previous article in this issue of The Guides Newsletter (Two-point Discrimination in the Use of Upper Extremity Nerve Function in the AMA Guides) and discusses why the AMA Guides to the Evaluation of Permanent Impairment (AMA Guides), Sixth Edition, has chosen to retain the use of static two-point discrimination for both acute single incident digital nerve injury and for upper extremity focal entrapment neuropathy. The authors clarify that the AMA Guides, Sixth Edition does not use two-point discrimination as a diagnostic criterion for entrapment neuropathy such as carpal tunnel syndrome. Instead, it uses two-point discrimination as a criterion to judge severity, specifically to help select the proper integer for the rating to be assigned for the diagnosis determined by other criteria. Two-point testing is not sensitive but is specific to significant nerve impairment (ie, severity, not diagnosis), and the authors note its advantages of being familiar to most impairment examiners, having a basis in published literature, having variations of the testing protocol that help “objectify” the apparent sensory deficit, and correlating with severity. Thus, if a rating is to be done “according to the AMA Guides,” two-point discrimination remains a required and important part of assessment of the upper extremity neurologic impairment of the hand.
Q&A: Rating Multiple Pelvic Fractures
Authors: Talmage James B.
Published: December 2020

Part 1 of this series examined many of the rules in the AMA Guides to the Evaluation of Permanent Impairment (AMA Guides), Sixth Edition, regarding rating nerve entrapment or focal neuropathies; the current article, part 2, examines how to read and match the findings in an electrodiagnostic report to the criteria in Appendix 15-B, Electrodiagnostic Evaluation of Entrapment, as explained in Section 15.4f, and determine the severity of the test findings as listed in Table 15-23. Physicians who perform nerve conduction studies often use their own definitions of mild, moderate, and severe; these definitions are not standardized and frequently differ from the electrophysiologic definitions used in the AMA Guides, Sixth Edition. When examiners rate focal entrapment neuropathy, they must match data from the electrodiagnostic report to the criteria in Appendix 15-B, and a figure shows a hypothetical motor nerve conduction report for a case that shows both mild neuropathy (conduction delay) of the median nerve at the wrist (carpal tunnel syndrome) and severe neuropathy (axon loss) of the ulnar nerve at the elbow (cubital tunnel syndrome). If both fibrillations and positive waves are seen in the same muscle, the reviewer can be more confident that other electromyographic potentials were not misinterpreted as fibrillations. Prepared with the results of electrodiagnostic studies, the evaluator can work through the steps of history, physical findings, and functional scale to determine the final upper limb impairment according to the AMA Guides.
GUEST EDITORIAL: In the Line of Fire: IME Burnout
Authors: Pinsky Tim
Published: December 2020

Physicians suffer more burnout than many other American workers and rank near the top of all professions in burnout. Physicians who perform independent medical evaluations (IME) face the usual challenges (too many bureaucratic tasks, too many hours of work, insufficient income, and loss of status) that contribute to burnout among all physicians. Both “innate personality traits” and external factors (circumstances, examinees, time, performance, and risk) contribute to burnout among physicians who perform IME. Stressed because of multilayered litigation, insurance, and bureaucratic processes, IME physicians face a high concentration of difficult patients who are disgruntled with their jobs and, often, their lives. Examinees’ negative attitudes and outlooks contribute to pessimism and depression that can be contagious to the examiner, and because IMEs are one-time evaluations with no longitudinal care, the opportunity to establish rapport is limited. Physicians who are coping with the pressures of the IME milieu may need to realize that they have a greater sphere of positive influence than they realize: By conducting oneself in a professional and ethical fashion, writing fair reports, relying on evidence-based medicine, and applying the AMA Guides to the Evaluation of Permanent Impairment in a proficient manner, physicians who conduct IMEs can recognize and, one hopes, avoid IME burnout.
The Effects of Functional Restoration on Disability and Impairment
Authors: Feinberg Steven
Published: December 2020

The treatment of chronic pain conditions is difficult, time consuming, expensive, and, all too often, unsuccessful. An effective alternative is chronic pain rehabilitation or functional restoration (FR). An FR team works together to help patients achieve better outcomes with reduced disability. The basic treatment goals of early and chronic FR rehabilitation programs are functional improvement; improved abilities in performance of activities of daily living (ADL); a return to leisure, sport, and vocational activities; and improved pharmacologic management of pain and related affective distress. Individuals at risk of developing chronic pain conditions may benefit from an FR program because physical and psychological interventions can be used before the disability becomes chronic. FR programs emphasize a multidisciplinary, biopsychosocial approach in which physicians, psychologists, and occupational, physical, and relaxation therapists work in concert. FR treatment includes quantification of physical deficits, psychosocial and socioeconomic assessment, and an emphasis on reconditioning the injured area or body part. The team-centered approach includes simulation of work or activity; disability management using cognitive–behavioral approaches; psychopharmacologic management that focuses on improving analgesia, sleep, and affective distress; and, in appropriate cases, detoxification. FR is a patient-centered, whole-person, team approach that focuses on helping patients achieve individual goals that enable them to improve physical and psychosocial function, decrease pain, lessen disability, and improve quality of life, including return to work.
Apportionment of Musculoskeletal Injuries
Authors: Demeter Stephen L. , Brigham Christopher , Talmage James B. , Melhorn J. Mark , Feinberg Steven D.
Published: December 2020

When they apportion impairment in musculoskeletal cases, evaluators encounter a variety of unique issues and problems. The first step in apportionment is scientifically based causation analysis. Arbitrary or opinion-based unscientific apportionment estimates that amount to little more than speculation should be avoided. The AMA Guides to the Evaluation of Permanent Impairment (AMA Guides), Fourth and Fifth Editions, are similar in their assessment of orthopedic impairment, but significant differences exist between these and the Sixth Edition. Individuals may experience impairments on several occasions. For example, if the first injury was rated using an earlier edition of the AMA Guides and a second injury occurs and is rated using a more current edition, then the most recent edition in the current jurisdiction is used to recalculate the rating for the first injury. Regarding which edition of the AMA Guides to use, evaluators should be aware of the jurisdictional requirements and also the timing to ensure that the individual is at maximum medical improvement. If the issue to be determined is apportioning the cause of the injury and not the impairment rating, then different criteria are used and the AMA Guides to the Evaluation of Disease and Injury Causation, Second Edition, is an invaluable resource. Extensive sidebars discuss qualitative vs qualitative apportionment and steps that evaluators can take to ensure that body regions and conditions are not confused (ie, that an apples-to-apples comparison is taking place).
Job Validation Studies and Physical Agility Testing: Is the Vendor Telling You What They Think You Want or Are You Telling Them What You Need?
Authors: Soo Hoo E. Randolph , Demeter Stephen L.
Published: December 2020

Referring agents may ask independent medical evaluators if the examinee can return to work in either a normal or a restricted capacity; similarly, employers may ask external parties to conduct this type of assessment before a hire or after an injury. Functional capacity evaluations (FCEs) are used to measure agility and strength, but they have limitations and use technical jargon or concepts that can be confusing. This article clarifies key terms and concepts related to FCEs. The basic approach to a job analysis is to collect information about the job using a variety of methods, analyze the data, and summarize the data to determine specific factors required for the job. No single, optimal job analysis or validation method is applicable to every work situation or company, but the Equal Employment Opportunity Commission offers technical standards for each type of validity study. FCEs are a systematic method of measuring an individual's ability to perform various activities, and results are matched to descriptions of specific work-related tasks. Results of physical abilities/agilities tests are reported as “matching” or “not matching” job demands or “pass” or “fail” meeting job criteria. Individuals who fail an employment physical agility test often challenge the results on the basis that the test was poorly conducted, that the test protocol was not reflective of the job, or that levels for successful completion were inappropriate.
The AMA Guides, Fifth Edition—the California Experience
Authors: Feinberg Steven , Kingdon Kenneth , Rassp Robert
Published: December 2020

Over the past thirteen years, physicians have experienced a learning curve regarding how to use the AMA Guides to the Evaluation of Permanent Impairment (AMA Guides) with a “California flavor.” Physicians are mandated by law to provide the court with the “most accurate” ratings that apply in a given case based on permanent objective medical evidence and the education, skills, knowledge, and experience of the physician. Two cases, commonly known as Almaraz–Guzman, profoundly changed how California interprets and uses the AMA Guides, Fifth Edition. Under Almaraz–Guzman, the evaluating physician is tasked with first providing a whole person impairment using a “standard” AMA Guides impairment rating. If the physician believes that this rating “is not the most accurate” and does not adequately reflect the extend of the disability, an alternative rating “within the four corners” of the AMA Guides can be provided based on “reasonable medical probability.” In many cases, this has resulted in the use of tables, charts, methods, measurements, and descriptions from chapters and text materials that were not originally intended to apply to other parts of the body. The AMA Guides tells us that when there is no clear impairment rating, rating by analogy or use of other impairments that create a similar effect on ADLs should be considered, and the opinion must reach the level of substantial evidence.
Medical and Legal Issues Raised by the Protz Decision Issued by the Pennsylvania Supreme Court
Authors: Haley LuAnn , Eskay-Auerbach Marjorie
Published: December 2020

Pennsylvania adopted the impairment rating provisions described in the AMA Guides to the Evaluation of Permanent Impairment (AMA Guides) in 1996 as an exposure cap for employers seeking predictability and cost control in workers’ compensation claims. In 2017, the Supreme Court of Pennsylvania handed down the Protz decision, which held that requiring physicians to apply the methodology set forth in the most recent edition of the AMA Guides reflected an unconstitutional delegation of legislative power to the American Medical Association. The decision eliminates the impairment-rating evaluation (IRE) mechanism under which claimants were assigned an impairment rating under the most recent edition of the AMA Guides. The AMA Guides periodically are revised to include the most recent scientific evidence regarding impairment ratings, and the AMA Guides, Sixth Edition, acknowledges that impairment is a complex concept that is not yet defined in a way that readily permits an evidence-based definition of assessment. The AMA Guides should not be considered standards frozen in time simply to withstand future scrutiny by the courts; instead, workers’ compensation acts could state that when a new edition of the AMA Guides is published, the legislature shall review and consider adopting the new edition. It appears unlikely that the Protz decision will be followed in other jurisdictions: Challenges to using the AMA Guides in assessing workers’ compensation claims have been attempted in three states, and all attempts failed.
Peripheral Nerve and Brachial Plexus Impairment, AMA Guides, Sixth Edition
Authors: Talmage James B. , Blaisdell Jay
Published: December 2020

Physicians use a variety of methodologies within the AMA Guides to the Evaluation of Permanent Impairment (AMA Guides), Sixth Edition, to rate nerve injuries depending on the type of injury and location of the nerve. Traumatic injuries that cause impairment to the peripheral or brachial plexus nerves are rated using Section 15.4e, Peripheral Nerve and Brachial Plexus Impairment, for upper extremities and Section 16.4c, Peripheral Nerve Rating Process, for lower extremities. Verifiable nerve lesions that incite the symptoms of complex regional pain syndrome, type II (similar to the former concept of causalgia), also are rated in these sections. Nerve entrapments, which are not isolated traumatic events, are rated using the methodology in Section 15.4f, Entrapment Neuropathy. Type I complex regional pain syndrome is rated using Section 15.5, Complex Regional Pain Syndrome for upper extremities or Section 16.5, Complex Regional Pain Syndrome for lower extremities. The method for grading the sensory and motor deficits is analogous to the method described in previous editions of AMA Guides. Rating the permanent impairment of the peripheral nerves or brachial plexus is similar to the methodology used in the diagnosis-based impairment scheme with the exceptions that the physical examination grade modifier is never used to adjust the default rating and the names of individual nerves or plexus trunks, as opposed to the names of diagnoses, appear in the far left column of the rating grids.
Life Expectancy: A Primer with a Focus on Neurological and Psychiatric Conditions
Authors: Katz Richard T. , Katz Robert B.
Published: December 2020

In the interface between medicine and law, physicians may be asked to comment on a patient's life expectancy. Life expectancy is based on life tables, eg, from the US census, and are published in National Vital Statistics reports. The life expectancy for a particular patient with a serious medical illness or disability cannot be determined from such tables; rather one must investigate the life expectancies associated with the patient's particular disease or condition. Standardized mortality ratios have a complex relationship to life expectancy, depending on the patient's age and specific conditions. For example, excellent data are available regarding life expectancy for individuals with spinal cord injury (SCI) and are sorted in various ways, eg conditional life expectancy calculated for persons who have survived the first year after an SCI. Major depressive disorder is associated with increased mortality due to suicidality and other causes (eg, cardiovascular disease or respiratory disease); men with mental disorders live twenty years less and women live fifteen years less compared with the general population. To testify about life expectancy in a person with neurological or psychiatric disability, the experience of a personal physician is not adequate—familiarity with epidemiological data is a prerequisite. This article is based on a wide and recent body of literature concerning life expectancy and gives an indication of some of the complexities regarding life expectancy.
Somatization
Authors: Ensalada Leon , Brigham Christopher R. , Kertay Les
Published: December 2020

An evaluator's failure to recognize illness behavior and to adjust for its effect on symptom presentation can lead to erroneous conclusions regarding impairment or disability; here the authors review the associated phenomena of somatization, disorders that arise from it, and factors that contribute to somatization. Somatization is an individual's unconscious use of the body or bodily symptoms for psychological purposes or psychological gain. As the AMA Guides to the Evaluation of Permanent Impairment (AMA Guides), Sixth Edition, notes, somatization is a “tendency to experience and report somatic complaints (physical symptoms) in response to psychosocial stress and seek health care services for them.” The AMA Guides also advises evaluators that “exclusion or inclusion of somatization disorder, factitious disorder, and/or malingering must be done with care.” A table lists developmental factors that may dispose to somatization (eg, somatizers are present in the family of origin, or coping mechanisms other than illness behavior are absent or unacceptable); a second table compares disorders that may involve somatization. Somatization is prevalent in clinical practice and is likely to occur with equal, or higher, frequency in the evaluation setting. The presence of somatization distorts symptom presentation and can exert a confounding effect on impairment assessment methodologies that rely on the accuracy of patients’ self-presentations.
Longshore and Harbor Workers' Compensation Act: Use of the AMA Guides1
Authors: Brigham Christopher R. , Richardson Eric
Published: December 2020

The US Congress passed the Longshore and Harbor Workers’ Compensation Act (LHWCA) in 1927; it is administered by the US Department of Labor, Division of Longshore and Harbor Workers’ Compensation (DLHWC), and provides medical benefits, compensation for lost wages, and rehabilitation services to longshoremen, harbor workers, and other maritime workers such as pier, wharf, dock, or terminal workers who are injured during employment or suffer diseases caused or worsened by employment conditions. The LHWCA and the AMA Guides to the Evaluation of Permanent Impairment (AMA Guides) similarly define many terms (eg, injury, disability, impairment, permanent). Under the LHWCA, impairment ratings are performed for “scheduled injuries,” and disability benefits are determined by multiplying the percentage of “permanent disability” (eg, “permanent impairment”) for a specific body part by a specified number of weeks. For DLHWC impartial medical specialty evaluations, specific steps are taken to avoid prejudgment of a case, and contested cases are heard before administrative law judges. Physicians who perform impairment ratings should understand not only how to fairly rate permanent impairment according to the AMA Guides but also the specific needs of the groups that request these evaluations. Impairment ratings are required for scheduled injuries, hearing loss, and occupational disease cases covered by the LHWCA; physicians must express extremity ratings as the most distal body part applicable, not as a whole person impairment.
Shoulder Impairment Rating: Sixth Edition Clarifications (Authoritative Article*)
Authors: Melhorn J. Mark
Published: December 2020

A request for an impairment rating using both the fourth and sixth editions of the AMA Guides to the Evaluation of Permanent Impairment (AMA Guides) demonstrated two interesting facts: In the sixth edition, Table 15-34, Shoulder Range of Motion has two typographical errors. First, Grade Modifier 3 (column 6) and the Internal Rotation (IR) (row 12) lists ≤20° ER = 8% UEI; this should be ≥20° ER = 8% UEI; and Grade Modifier 4 (column 7) and IR (row 12) lists: 20° to 50° IR = 6% UEI, ≥60° IR or 10° IR to ER = 0% UEI; this should be ≥60° IR or 10° IR to ER = 10% UEI. Second, the impairment rating using the fourth and sixth editions resulted in the same total impairment. A case example presents a 54-year-old male who experienced a right shoulder strain that was determined to be a right shoulder rotator cuff tear of the supraspinatus and infraspinatus muscles. The patient was evaluated for impairment based on the range-of-motion method in the fourth edition of the AMA Guides, and 13% upper extremity impairment was determined. Using the sixth edition produced similar results, demonstrating how similar impairment ratings can be based on the fourth and sixth editions.
Impairment of Face-, Nose-, and Throat-related Structures Sixth Edition Approaches
Authors: Blaisdell Jay , Talmage James B.
Published: December 2020

Facial disfigurements, including those caused by burns (thermal, chemical, or electrical) or trauma, are rated in the AMA Guides to the Evaluation of Permanent Impairment (AMA Guides), Sixth Edition, Chapter 11, which also discusses occupational overexposure to sunlight, airborne chemicals, heavy metals, and allergens that may lead to head and neck cancers and degraded ability to breathe, chew, swallow, smell, or speak. Additional relevant impairments include those of olfaction and taste, chewing and swallowing, voice and speech, and of the upper respiratory passages. For upper air passage defects and voice and speech impairments, the evaluator assigns an impairment rating by selecting the relevant table or grid in Chapter 11 and then assigning the appropriate impairment class, as determined by the key factor. The patient's history is the key factor for upper air passage deficits, and the performance measures of audibility, intelligibility, and functional efficiency collectively act as the key factor for voice and speech impairments. Once they select an impairment class, evaluators can modify the rating within the impairment class by considering remaining variables. When rating the patient's ability to smell and taste or chew and swallow, raters do not use impairment classes or modifiers. Rather, they assign impairment within an allowable range largely based on professional judgment complemented by objective findings and a well-documented rationale.
Catastrophic Central Nervous System Injury Rating
Authors: Demeter Stephen L. , Direnfeld Lorne , Katz Richard , Talmage James B. , Brigham Christopher R.
Published: December 2020

We present a case involving a catastrophic injury that resulted from a completely obstructed airway when an examinee choked on food. She had cardiopulmonary arrest and developed a hypoxic-ischemic encephalopathy associated with profound neurological losses. The evaluation of the consequences of severe central nervous system injury necessitates evaluation and rating of all the sequelae of that injury. The first step is clinical assessment, followed by thoughtful application of these data to the processes and criteria provided in the AMA Guides to the Evaluation of Permanent Impairment (AMA Guides). The approaches discussed in the fifth and sixth editions of the AMA Guides are similar.
Mitochondrial DNA copy number in human disease: the more the better?
Authors: Filograna Roberta , Mennuni Mara , Alsina David , Larsson Nils‐Göran
Published: December 2020

Most of the genetic information has been lost or transferred to the nucleus during the evolution of mitochondria. Nevertheless, mitochondria have retained their own genome that is essential for oxidative phosphorylation (OXPHOS). In mammals, a gene‐dense circular mitochondrial DNA (mtDNA) of about 16.5 kb encodes 13 proteins, which constitute only 1% of the mitochondrial proteome. Mammalian mtDNA is present in thousands of copies per cell and mutations often affect only a fraction of them. Most pathogenic human mtDNA mutations are recessive and only cause OXPHOS defects if present above a certain critical threshold. However, emerging evidence strongly suggests that the proportion of mutated mtDNA copies is not the only determinant of disease but that also the absolute copy number matters. In this review, we critically discuss current knowledge of the role of mtDNA copy number regulation in various types of human diseases, including mitochondrial disorders, neurodegenerative disorders and cancer, and during ageing. We also provide an overview of new exciting therapeutic strategies to directly manipulate mtDNA to restore OXPHOS in mitochondrial diseases.
The Diseased Mitoribosome
Authors: Ferrari Alberto , Del’Olio Samuel , Barrientos Antoni
Published: December 2020

Mitochondria control life and death in eukaryotic cells. Harboring a unique circular genome, a by‐product of an ancient endosymbiotic event, mitochondria maintains a specialized and evolutionary divergent protein synthesis machinery, the mitoribosome. Mitoribosome biogenesis depends on elements encoded in both the mitochondrial genome (the RNA components) and the nuclear genome (all ribosomal proteins and assembly factors). Recent cryo‐EM structures of mammalian mitoribosomes have illuminated their composition and provided hints regarding their assembly and elusive mitochondrial translation mechanisms. A growing body of literature involves the mitoribosome in inherited primary mitochondrial disorders. Mutations in genes encoding mitoribosomal RNAs, proteins, and assembly factors impede mitoribosome biogenesis, causing protein synthesis defects that lead to respiratory chain failure and mitochondrial disorders such as encephalo‐ and cardiomyopathy, deafness, neuropathy, and developmental delays. In this article, we review the current fundamental understanding of mitoribosome assembly and function, and the clinical landscape of mitochondrial disorders driven by mutations in mitoribosome components and assembly factors, to portray how basic and clinical studies combined help us better understand both mitochondrial biology and medicine.
Adhesion‐dependent Caveolin‐1 Tyrosine‐14 phosphorylation is regulated by FAK in response to changing matrix stiffness
Authors: Buwa Natasha , Kannan Nivedhika , Kanade Shaunak , Balasubramanian Nagaraj
Published: December 2020

Integrin‐mediated adhesion regulates cellular responses to changes in the mechanical and biochemical properties of the extracellular matrix. Cell–matrix adhesion regulates caveolar endocytosis, dependent on caveolin 1 (Cav1) Tyr14 phosphorylation (pY14Cav1), to control anchorage‐dependent signaling. We find that cell–matrix adhesion regulates pY14Cav1 levels in mouse fibroblasts. Biochemical fractionation reveals endogenous pY14Cav1 to be present in caveolae and focal adhesions (FA). Adhesion does not affect caveolar pY14Cav1, supporting its regulation at FA, in which PF‐228‐mediated inhibition of focal adhesion kinase (FAK) disrupts. Cell adhesion on 2D polyacrylamide matrices of increasing stiffness stimulates Cav1 phosphorylation, which is comparable to the phosphorylation of FAK. Inhibition of FAK across varying stiffnesses shows it regulates pY14Cav1 more prominently at higher stiffness. Taken together, these studies reveal the presence of FAK–pY14Cav1 crosstalk at FA, which is regulated by cell–matrix adhesion.
Evaluation of SORD mutations as a novel cause of Charcot‐Marie‐Tooth disease
Authors: Yuan Ru‐Ying , Ye Zi‐Ling , Zhang Xiao‐Rong , Xu Liu‐Qing , He Jin
Published: December 2020

Biallelic mutations in the sorbitol dehydrogenase (SORD) encoding gene were recently identified as a common genetic cause in autosomal‐recessive CMT patients. Here, we investigated the clinical, genetic, and electrophysiological characteristics of three CMT patients with biallelic SORD mutations from a Chinese cohort. Two patients harbored c.757delG (p.A253Qfs*27) homozygous mutations, and one patient carried both c.757delG (p.A253Qfs*27) and c.625C>T (p.R209X) compound heterozygous mutations. Interestingly, the two patients homozygous for the c.757delG mutation exhibited positive responses for pinprick test. In conclusion, we confirmed SORD mutations as causative for CMT and further expanded the mutational and phenotypic spectrum of SORD‐related CMT.
The Study of Optical Properties of III2–VI3 Defect Semiconductor Group Compounds Ga2S3, Ga2Se3, In2S3, and In2Se3
Authors: Ho Ching-Hwa , Lai Xiang-Ru , Chuang Ching-An , Kuo Wei-Li , Tiong Kwong-Kau
Published: December 2020

Herein, high‐quality III2VI3 (III = Ga, In and VI = S, Se) single crystals are successfully grown by a chemical vapor transport method. X‐ray diffraction and Raman spectroscopy verify crystal structure, crystalline state, and vibration modes of the as‐grown III2VI3 crystals. According to the structure characterization, Ga2S3 is crystallized in a monoclinic structure, whereas Ga2Se3 belongs to the cubic zincblende phase. The crystal structure of In2S3 is tetragonal, whereas that of In2Se3 may come from a hexagonal layered structure. The four crystal structures are the most stable phases crystallized in Ga2S3, Ga2Se3, In2S3, and In2Se3, respectively. All the mostly stable phase in each of Ga2S3, Ga2Se3, In2S3, and In2Se3 is different and changing. This result identifies the crystalline nature of the III–VI group defect crystals. Modulated thermoreflectance (TR) and optical transmission measurements of the series III2VI3 compounds are, respectively, implemented. The results indicate that all defective Ga2S3, Ga2Se3, In2S3, and In2Se3 crystals are direct semiconductors. Photoluminescence of Ga2S3 and photoconductivity of the Ga2Se3, In2S3, and In2Se3 defect compounds are, respectively, carried out, and the experimental results are demonstrated and analyzed herein.
Reactive or transgenic increase in microglial TYROBP reveals a TREM2‐independent TYROBP–APOE link in wild‐type and Alzheimer's‐related mice
Authors: Audrain Mickael , Haure‐Mirande Jean‐Vianney , Mleczko Justyna , Wang Minghui , Griffin Jennifer K. , St George‐Hyslop Peter H. , Fraser Paul , Zhang Bin , Gandy Sam , Ehrlich Michelle E.
Published: December 2020

Introduction

Microglial TYROBP (DAP12) is a network hub and driver in sporadic late‐onset Alzheimer's disease (AD). TYROBP is a cytoplasmic adaptor for TREM2 and other receptors, but little is known about its roles and actions in AD. Herein, we demonstrate that endogenous Tyrobp transcription is specifically increased in recruited microglia.

Methods

Using a novel transgenic mouse overexpressing TYROBP in microglia, we observed a decrease of the amyloid burden and an increase of TAU phosphorylation stoichiometry when crossed with APP/PSEN1 or MAPTP301S mice, respectively. Characterization of these mice revealed Tyrobp‐related modulation of apolipoprotein E (Apoe) transcription. We also showed that Tyrobp and Apoe mRNAs were increased in Trem2‐null microglia recruited around either amyloid beta deposits or a cortical stab injury. Conversely, microglial Apoe transcription was dramatically diminished when Tyrobp was absent.

Conclusions

Our results provide evidence that TYROBP‐APOE signaling does not require TREM2 and could be an initiating step in establishment of the disease‐associated microglia (DAM) phenotype.
A simple and efficient sequential electrokinetic and hydrodynamic injections in micellar electrokinetic chromatography method for quantification of anticancer drug 5‐fluorouracil and its metabolite in human plasma
Authors: Semail Nadhiratul‐Farihin , Noordin Siti Salmah , Keyon Aemi Syazwani Abdul , Waras Maisarah Nasution , Saad Bahruddin , Kamaruzaman Sazlinda , Mohamad Zain Nur Nadhirah , Azizi Juzaili , Aziz Mohd Yusmaidie , Yahaya Noorfatimah
Published: December 2020

A simple and sensitive preconcentration strategy using sequential electrokinetic and hydrodynamic injection modes in micellar electrokinetic chromatography with diode array detection was developed and applied for the separation and determination of anticancer agent, 5‐fluorouracil and its metabolite, 5‐fluoro‐2′‐deoxyuridine, in human plasma. Sequential injection modes with increased analyte loading capacity using the anionic pseudo‐stationary phase facilitated collection of the dispersed neutral and charged analytes into narrow zones and improved sensitivity. Several important parameters affecting sample enrichment performance were evaluated and optimized in this study. Under the optimized experimental conditions, 614‐ and 643‐fold and 782‐ and 803‐fold sensitivity improvement were obtained for 5‐fluorouracil and its metabolite when compared with normal hydrodynamic and electrokinetic injection, respectively. The method has good linearity (1–1,000 ng/ml) with acceptable coefficient of determination (r2 > 0.993), low limits of detection (0.11–0.14 ng/ml) and satisfactory analyte relative recovery (97.4–99.7%) with relative standard deviations of 4.6–9.3% (n = 6). Validation results as well as the application to analysis of human plasma samples from cancer patients demonstrate the applicability of the proposed method to clinical studies.
Determination of selpercatinib, a RET kinase inhibitor, in rat plasma and its application to a pharmacokinetic study
Authors: Wang Wei , Shi Liuhong , Jin Luya , Wang Kun
Published: December 2020

Selpercatinib (LOXO‐292) is a selective and potent RET inhibitor. A highly sensitive, rapid and specific high‐performance liquid chromatography with tandem mass spectrometry (LC–MS/MS) method for quantification of selpercatinib in rat plasma is reported. The method was validated in terms of selectivity, linearity, accuracy and precision, extraction recovery and matrix effect, stability and carryover as per the US Food and Drug Administration guidelines for bioanalytical method validation. Selpercatinib was detected by an electrospray ionization interface under selective reaction monitoring conditions in the positive ion mode. The calibration curve was linear over the concentration range from 1 to 2000 ng/ml with r2 = 0.9951. The intra‐ and inter‐batch accuracy values ranged from 97.45 to 100.97% and from 98.70 to 100.74% with coefficients of variation of 2.45–6.99% and 5.89–7.99%, respectively. The extraction recovery and IS‐normalized matrix factor were acceptable for the bioanalysis of selpercatinib. Additionally, selpercatinib was found to be stable under the detected conditions. It showed linear pharmacokinetic characteristics following oral administration to rats at 2.0–18.0 mg/kg. The results showed that the novel method for detecting selpercatinib in rat plasma could be successfully applied for quantification of selpercatinib in biosamples from nonclinical studies.
Inflammatory markers as independent predictors for stroke outcomes
Authors: Zhang Xiao‐Guang , Xue Jie , Yang Wen‐Hao , Xu Xu‐Shen , Sun Hong‐Xian , Hu Liang , Liu Ling‐Yun , Yue Yun‐Hua
Published: December 2020

Background

Inflammation plays an important role in the pathophysiology of stroke. The aim of the present study was to investigate the association between various inflammatory risk markers and ischemic stroke outcome and subtype.

Methods

A total of 3,013 ischemic stroke patients who were admitted to our hospital from 01/01/2016 to 12/30/2018 were retrospectively studied. Stroke subtypes were defined by the Trial of Org 10172 in Acute Stroke Treatment (TOAST) classification. Levels of five common inflammatory markers including white blood cell (WBC) count, neutrophil, lymphocyte, serum C‐reactive protein (CRP), and interleukin‐6 (IL‐6) were measured, and eleven conventional risk factors were further evaluated in the prediction of overall mortality as well as three functional outcomes defined by the National Institute of Health Stroke Scale (NIHSS), the modified Rankin Scale (mRS), and the Barthel Index (BI). Independent predictors of outcome were identified by multivariate logistic regression, and an importance score measured by the area under the receiver operating characteristics curve for each predictor using a Naive Bayes model was reported.

Results

Neutrophil and WBC were significantly higher in large‐artery atherosclerosis (LAA) and cardioembolism (CE) subtype. In contrast, lymphocyte was significantly higher in small‐artery occlusion (SAO). Neutrophil–lymphocyte ratio and CRP level were the best independent predictors, after adjustment for traditional risk factors and TOAST subtype for all four types of outcomes.

Conclusion

Inflammatory risk markers including neutrophil, lymphocyte, and CRP may have strong independent prediction values for stroke outcome.