The Adverse Event Unit (AEU): A novel metric to measure the burden of treatment adverse events.

OBJECTIVE: To design a physician and patient derived tool, the Adverse Event Unit (AEU), akin to currency (e.g. U.S. Dollar), to improve AE burden measurement independent of any particular disease or medication class. PATIENTS/METHODS: A Research Electronic Data Capture (REDCap) online survey was administered to United States physicians with board certification or board eligibility in general neurology, subspecialty neurology, primary care internal medicine or family medicine, subspecialty internal medicine, general pediatrics, and subspecialty pediatrics. Physicians assigned value to 73 AE categories chosen from the Common Terminology Criteria of Adverse Events (CTCAE) relevant to neurologic disorder treatments. An online forced choice survey was administered to non-physician, potential patients, through Amazon Mechanical Turk (MTurK) to weight the severity of the same AE categories. Physician and non-physician data was combined to assign value to the AEU. Surveys completed between 1/2017 and 3/2019. RESULTS: 363 physicians rated the 73 AE categories derived from CTCAE. 660 non-physicians completed forced choice experiments comparing AEs. The AEU provides 0-10, weighted values for the AE categories studied that differ from the ordinal 1-4 CTCAE scale. For example, CTCAE severe diabetes (category 4) is assigned an AEU score of 9. Although non-physician input changed physician assigned AEU values, there was general agreement among physicians and non-physicians about severity of AEs. CONCLUSION: The AEU has promise to be a useful, practical tool to add precision to AE burden measurement in the clinic and in comparative efficacy research with neurology patients. AEU utility will be assessed in planned comparative efficacy clinical trials.

Total mercury and methylmercury in river dolphins (Cetacea: Iniidae: Inia spp.) in the Madeira River Basin, Western Amazon.

In the Amazon, mercury (Hg) contamination comes from ASGM operations along with soil remobilization processes associated with deforestation. The objective of this study was to evaluate the exposure to methylmercury (MeHg) and total mercury (THg) in 88 samples of skin and blubber tissue obtained from live captured river dolphins (Inia boliviensis, Inia geoffrensis, and Inia spp.) in the Madeira River Basin. THg and MeHg measurements were performed by CV-AAS and GC-AFS, respectively. We also calculated the daily intake rate (DIR) of THg (wet weight) by Inia spp. THg levels in blubber tissue of adult river dolphins (Inia spp.) ranged from 0.015 to 3.804 mg kg-1, while MeHg concentrations in blubber tissue varied from 0.04 to 2.65 mg kg-1 and in skin tissue from 0.09 to 0.66 mg kg-1. There were no significant differences in MeHg concentration in blubber (p = 0.616) and skin (p = 0.498) tissue samples between adult males and females in the different sampling locations. The adult animals showed differences in THg and MeHg concentrations significantly higher than in the calves. The estimate of the DIR of the genus Inia ranged from 1.17 to 12.35 µg kg-1 day-1 (bw), from the consumption of fish species with herbivorous to piscivorous habits, respectively. More biological and ecological data, such as the precise determination of age, mediated length, weight, and diet of river dolphins, are necessary to verify the Hg biomagnification. However, our data indicate that bioaccumulation is an active process in the dolphins of the Madeira River Basin.

Dynamics of Hg and MeHg in the Madeira River basin (Western Amazon) before and after impoundment of a run-of-river hydroelectric dam.

The impact of a hydroelectric run-of-river (RoR) dam construction on the dynamics of total mercury (THg) and methylmercury (MeHg) is of interest to the environment and health of human and wild life. We monitored (May 2010 to October 2018) THg and MeHg in the waters and in the suspended particulate matter (SPM) of the Madeira River and its tributaries (before and after dam construction) to evaluate changes upstream and downstream from the Santo Antonio Hydroelectric Dam (SAHD). We collected 2826 samples of water and SPM at sampling stations upstream (UPMD-01, UPMD-02 and UPMD-03) and downstream the Madeira River (DWMD-04, DWMD-05 and DWMD-06), and Tributaries upstream (Branco River, Jaci-Parana River, Jatuarana-I Igarapé, Contra River, Caripunas Igarapé, Ceara Igarapé, and Teotonio Igarapé) and downstream (Jatuarana-II Igarapé and Belmont Igarapé) from the SAHD and monitored water and the total load of SPM. SPM was significantly higher in the Madeira River (median: 178.63 mg.L-1) than in upstream and downstream tributaries (median: 15.30 mg.L-1); however, the THg and MeHg concentrations were significantly higher in the tributaries (median: 161.14 ng g-1 and 9.03 ng g-1, respectively) than in the mainstream Madeira River (median = 57.06 ng g-1 and 1.63 ng g-1, respectively). THg concentration in the water was significantly higher in the mainstream Madeira River (median = 6.51 ng.L-1) than in the tributaries (median = 2.57 ng.L-1). However, the percentage of methylation in the tributaries (median = 4.9%) was 4-times higher than in the Madeira River (median: 1.3%). The significantly higher MeHg percentages in the tributaries may indicate natural (hydro-bio-geochemical factors) still predominant in this changing landscape of the Western Amazon. So far, the data suggest that this RoR has not yet impacted the THg and MeHg concentrations.

Guidelines for ethical behavior relating to clinical practice issues in neuromuscular and electrodiagnostic medicine.

The American Association of Neuromuscular & Electrodiagnostic Medicine (AANEM) developed guidelines to formalize the ethical standards that neuromuscular and electrodiagnostic (EDx) physicians should observe in their clinical and scientific activities. Neuromuscular and EDx medicine is a subspecialty of medicine that focuses on evaluation, diagnosis, and comprehensive medical management, including rehabilitation of individuals with neuromuscular disorders. Physicians working in this subspecialty focus on disorders of the motor unit, including muscle, neuromuscular junction, axon, plexus, nerve root, anterior horn cell, and the peripheral nerves (motor and sensory). The neuromuscular and EDx physician's goal is to diagnose and treat these conditions to mitigate their impact and improve the patient's quality of life. The guidelines are consistent with the Principles of Medical Ethics adopted by the American Medical Association and represent a revision of previous AANEM guidelines.

Bortezomib-associated demyelinating neuropathy--clinical and pathologic features.

OBJECTIVES: Bortezomib is a proteasome inhibitor that is frequently used for multiple myeloma and lymphoma. A sensory predominant axonal neuropathy is associated with bortezomib treatment but a demyelinating neuropathy is also described primarily based on electrodiagnostic findings. We report a series of patients treated with bortezomib who developed peripheral neuropathy and were found to have demyelinating features on electrodiagnostic testing. METHODS: Four patients who developed a bortezomib-induced peripheral neuropathy underwent electrophysiological testing, and 1 patient had a nerve biopsy. RESULTS: The four patients with bortezomib-induced peripheral neuropathy had demyelinating features on their electrophysiological testing. The nerve biopsy performed in 1 patient demonstrated a demyelinating component in a background of axonal degeneration. CONCLUSIONS: Although most toxic neuropathies are symmetrical axonal neuropathies, bortezomib is part of a small list of agents that may cause a demyelinating polyneuropathy and axonal degeneration. These findings have been confirmed by nerve biopsy.

Chronic inflammatory demyelinating polyneuropathy: diagnosis and management.

Over the course of 8 weeks, a 50-year-old man developed progressive bilateral leg and arm weakness, with numbness and tingling of the feet and hands. His symptoms persisted for 6 months, with impaired manual dexterity, arm weakness when brushing his teeth, tripping when walking, inability to climb stairs and gait imbalance. On examination, there is mild proximal and distal weakness of the upper and lower extremity muscles, length-dependent sensory loss of vibratory perception and joint position sense, areflexia, positive Romberg test and steppage gait with bilateral foot drop. Motor nerve conduction studies of the arms and legs show partial conduction blocks in several nerves with nonuniform slowing, and sensory responses are absent in the hands, however, normal sural responses are noted. Lumbar puncture reveals acellular cerebrospinal fluid with elevated protein. After 2 months following treatment, his strength and gait improved significantly, and his sensory symptoms resolved.

Demyelinating findings in typical and atypical chronic inflammatory demyelinating polyneuropathy: sensitivity and specificity.

OBJECTIVE: The objective of this study was to evaluate how the number of demyelinating findings (DF) on nerve conductions affects sensitivity and specificity of electrodiagnostic criteria for chronic inflammatory demyelinating polyneuropathy (CIDP). METHODS: Electrodiagnostic findings of 26 consecutive patients with CIDP were compared with amyotrophic lateral sclerosis (ALS) and diabetic polyneuropathy controls. Patients with CIDP were divided into typical and atypical CIDP, as defined elsewhere. RESULTS: Depending on the minimal required number (MRN) of DF on nerve conductions, sensitivities decreased from an arbitrary 100% to 58% and 54%, for an MRN of 1, 2, and 3, respectively, as specificities increased, from 48% to 81% and 95%, respectively. The number of DF per patient was higher in typical CIDP than in atypical CIDP. CONCLUSIONS: The considerable gap between specificity and sensitivity is the reason for controversy regarding the MRN for the diagnosis of CIDP. Requiring 2 or more DFs to identify CIDP increases specificity from 48% to 81% but lowers sensitivity from 100% to 58%. For patients with other potential causes of neuropathy, the requirement of 2 or more DFs could further increase specificity.

When metals compete: a case of copper-deficiency myeloneuropathy and anemia.

BACKGROUND: A 47-year-old woman with an otherwise unremarkable medical history was referred to the multiple sclerosis clinic by her primary neurologist for evaluation of a 2-3 year history of progressive knee and back pain, weakness, paresthesias, sensory loss, ataxia, and falls. During the same period, she had received blood transfusions for unexplained anemia and leukopenia. She had been wearing dentures for many years. INVESTIGATIONS: Physical examination, neurological examinations (assessments of reflexes, gait, proprioception, and sensitivity to temperature, pinprick and vibration), neurophysiological studies (visual and brainstem somatosensory evoked potentials, nerve conduction studies and electromyography), T(2)-weighted MRI of the brain and spine, cerebrospinal fluid analysis and serum evaluations. DIAGNOSIS: Myeloneuropathy and anemia due to copper deficiency, secondary to zinc overload associated with long-term use of denture cream with a high zinc content. MANAGEMENT: Change to a low-zinc denture cream and oral copper replacement.