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Objective: Compare the diagnostic characteristics of intraepidermal nerve fiber density (IENFD) and confocal corneal microscopy (CCM) for distal symmetric polyneuropathy (DSP) and small fiber neuropathy (SFN). Methods: Participants with obesity were recruited from bariatric surgery clinics and testing was performed prior to surgery. DSP and SFN were determined using the Toronto consensus definitions of probable neuropathy. IENFD was assessed from 3 mm punch biopsies of the distal leg and proximal thigh. CCM was performed on both eyes with manual and automated counting. The Michigan Neuropathy Screening Instrument questionnaire (MNSIq) was also completed. Diagnostic capability was determined using areas under the receiver operating characteristics curve (AUC) from logistic regression. Results: We enrolled 140 participants (mean [standard deviation [SD]] age: 50.3 years [7.1], 77.1% female, BMI: 44.4 kg/m2 [6.7]). In this population, 22.9% had DSP and 14.3% had SFN. Distal leg IENFD had the largest AUC (95% confidence interval) for DSP (0.78, 0.68–0.89) and SFN (0.85, 0.75–0.96). Proximal thigh IENFD (DSP: AUC: 0.59, 0.48–0.69, SFN: AUC: 0.59, 0.46–0.73) and CCM metrics (DSP: AUC range: 0.55–0.60, SFN: AUC range: 0.45–0.62) had poorer diagnostic capability than distal leg IENFD for DSP/SFN (P < 0.05). MNSIq had similar diagnostic capability to distal leg IENFD for both DSP/SFN (DSP: AUC: 0.76, 0.68–0.85, SFN: AUC: 0.81, 0.73–0.88). More participants (52%) preferred skin biopsies to CCM. Interpretation: Distal leg IENFD was the best quantitative measure of DSP/SFN. CCM had poor diagnostic characteristics and fewer patients preferred this test to IENFD. The MNSIq had similar diagnostic characteristics to distal leg IENFD, indicating its value as a diagnostic tool in the clinical setting. Clinical Trial Registration: clinicaltrials.gov: NCT03617185. [ABSTRACT FROM AUTHOR]

Introduction/Aims: Randomized controlled trials show that repeat intravenous immunoglobulin (IVIG) dosing and plasma exchange (PLEX) followed by IVIG (combination therapy) have no additional therapeutic benefit in Guillain‐Barre Syndrome (GBS) non‐responders. Furthermore, the delineation between GBS and Acute Onset CIDP (A‐CIDP) can be particularly challenging and carries therapeutic implications. We aimed to evaluate the presence of repeat IVIG, combination therapy, and diagnostic reclassification from GBS to CIDP. Methods: We performed a retrospective study of a large healthcare database for patients with GBS in the US from 2001 to 2018. We identified individuals initially diagnosed with GBS and later re‐classified as CIDP. Multivariable logistic regression models were developed to determine associations between patient factors and repeat IVIG dosing, combination therapy, and diagnostic re‐classification from GBS to CIDP. Results: We identified 2325 patients with GBS. A total of 39.7% received repeat IVIG and 6.1% received combination therapy. The proportion of individuals initially diagnosed with GBS and then re‐classified as CIDP was 32.0%. Repeat IVIG, combination therapy, and diagnostic reclassification remained stable over time. Female sex (OR 0.79, 95% CI 0.65–0.96) and medium‐high net worth (OR 0.64, 95% CI 0.45–0.90) associated with repeat IVIG therapy, while Asian ethnicity associated with diagnostic re‐classification from GBS to CIDP (OR 1.77, 95% CI 1.09–2.86). Discussion: Repeat IVIG dosing was quite common in GBS before newer trials suggesting harm in non‐responders, and IVIG/PLEX combination therapy continues to persist despite strong evidence against use in non‐responders. Further, nearly one in three patients initially diagnosed with GBS is subsequently diagnosed with CIDP, but the reasons are unclear. [ABSTRACT FROM AUTHOR]

Introduction/Aims: Given the importance of early diagnosis and treatment of myasthenia gravis (MG), it is critical to understand disparities in MG care. We aimed to determine if there are any differences in testing, treatment, and/or access to neurologists for patients of varying sex and race/ethnicity with MG. Methods: We used a nationally representative healthcare claims database of privately insured individuals (2001–2018) to identify incident cases of MG using a validated definition. Diagnostic testing, steroid‐sparing agents, intravenous immunoglobulin (IVIG), plasma exchange (PLEX), and thymectomy were defined using drug names or CPT codes. Steroid use was defined using AHFS class codes. We also determined whether an individual had a visit to a neurologist and the time between primary care and neurologist visits. Logistic regression determined associations between sex and race/ethnicity and testing, treatments, and access to neurologists. Results: Female patients were less likely to get a computed tomography (CT) chest (odds ratio (OR) 0.73, 95% confidence interval (CI): 0.64–0.83), receive steroids (OR: 0.85, 95% CI: 0.75–0.97), steroid‐sparing agents (OR: 0.84, 95% CI: 0.72–0.97), and IVIG or PLEX (OR: 0.80, 95% CI: 0.67–0.95). Black patients were less likely to receive steroids (OR: 0.78, 95% CI: 0.63–0.96). No significant disparities were seen in access to neurologists. Discussion: We found healthcare disparities in MG treatment with female and Black patients receiving less treatment than men and those of other races/ethnicities. Further research and detailed assessments accounting for individual patient factors are needed to confirm these apparent disparities. [ABSTRACT FROM AUTHOR]

OBJECTIVE: To determine bidirectional associations between the timing of chronic diabetes complications (CDCs) and mental health disorders (MHDs) in individuals with type 1 or type 2 diabetes. RESEARCH DESIGN AND METHODS: We used a nationally representative health care claims database to identify matched individuals with type 1 or 2 diabetes or without diabetes using a propensity score quasirandomization technique stratified by age (0–19, 20–39, 40–59, and ≥60 years). CDCs and MHDs were identified using ICD-9/10 codes. We fit Cox proportional hazards models with time-varying diagnoses of CDCs or MHDs to investigate their association with the hazard of developing MHDs or CDCs, respectively. RESULTS: From 2001 to 2018, a total of 553,552 individuals were included (44,735 with type 1 diabetes, 152,187 with type 2 diabetes, and 356,630 without diabetes). We found that having a CDC increased the hazard of developing an MHD (hazard ratio [HR] 1.9–2.9; P < 0.05, with higher HRs in older age strata), and having an MHD increased the hazard of developing a CDC (HR 1.4–2.5; P < 0.05, with the highest HR in age stratum 0–19 years). In those aged <60 years, individuals with type 1 diabetes were more likely to have CDCs, whereas individuals with type 2 diabetes were more likely to have MHDs. However, the relationship between CDCs and MHDs in either direction was not affected by diabetes type (P > 0.05 for interaction effects). CONCLUSIONS: We found a consistent bidirectional association between CDCs and MHDs across the life span, highlighting the important relationship between CDCs and MHDs. Prevention and treatment of either comorbidity may help reduce the risk of developing the other. [ABSTRACT FROM AUTHOR]

Introduction/aims: In vasculitic neuropathy (VN), a 50% side‐to‐side difference in the amplitude of compound muscle action potentials and sensory nerve action potentials is considered meaningful, but unequivocal evidence is lacking. The aim of this study is to characterize electrodiagnostic features that best distinguish VN from other axonal polyneuropathies. Methods: We conducted a case–control study between January 2000 and April 2021. We reviewed the records of patients with VN who had bilateral nerve conduction studies (NCS) and evaluated different electrodiagnostic models to help distinguish VN from non‐inflammatory axonal polyneuropathies. Results: We identified 82 cases, and 174 controls with non‐inflammatory axonal neuropathies. The amplitude percent difference Z‐score model showed the best discriminatory capability between cases and controls (area under the curve [AUC] 0.87; 95% confidence interval [CI] 0.82, 0.93), and the number of nerves tested did not significantly influence the model. Individually, the ulnar motor nerve (AUC 0.86; 95% CI 0.77, 0.94) and median motor nerve (AUC 0.85; 95% CI 0.77, 0.94) showed the best discriminatory capability. A 50% amplitude difference between at least two bilateral nerves, either in the upper (AUC 0.85; 95% CI 0.77, 0.93) or lower (AUC 0.79; 95% CI 0.71, 0.87) extremity showed good discriminatory threshold for detecting VN. Discussion: The best electrodiagnostic criteria for VN utilizes z‐scores of percent differences in nerve amplitudes, but this approach may be difficult to implement at the bedside. Alternately, a 50% amplitude difference in at least two nerves is a reasonable approximation. [ABSTRACT FROM AUTHOR]

Background: A case–control study was performed to define clinical and genetic risk factors associated with osteonecrosis of the jaw in patients with metastatic cancer treated with bisphosphonates. Methods: Clinical data and tissues were collected from patients treated with bisphosphonates for metastatic bone disease who were diagnosed with osteonecrosis of the jaw (cases) and matched controls. Clinical data included patient, behavioral, disease, and treatment information. Genetic polymorphisms in CYP2C8 (rs1934951) and other candidate genes were genotyped. Odds ratios from conditional logistic regression models were examined to identify clinical and genetic characteristics associated with case or control status. Results: The study population consisted of 76 cases and 126 controls. In the final multivariable clinical model, patients with osteonecrosis of the jaw were less likely to have received pamidronate than zoledronic acid (odds ratio = 0.18, 95% Confidence interval: 0.03–0.97, p =.047) and more likely to have been exposed to bevacizumab (OR = 5.15, 95% CI: 1.67–15.95, p =.005). The exploratory genetic analyses suggested a protective effect for VEGFC rs2333496 and risk effects for VEGFC rs7664413 and PPARG rs1152003. Conclusions: We observed patients with ONJ were more likely to have been exposed to bevacizumab and zoledronic and identified potential genetic predictors that require validation prior to clinical translation. [ABSTRACT FROM AUTHOR]

Introduction: Despite the existence of guidelines, painful neuropathy is often inappropriately treated. We sought to determine the effectiveness of a clinical decision support system on guideline-recommended medication use.Methods: We randomized neurology providers, stratified by subspecialty, to a best practice alert (BPA) linked to a Smartset or a BPA alone when seeing patients with neuropathy. The primary outcome was the proportion of patients with uncontrolled nerve pain prescribed a guideline-recommended medication. Generalized estimating equations were used to assess effectiveness.Results: Seventy-five neurology providers (intervention 38, control 37) treated 2697 patients with neuropathy (intervention 1026, control 671). Providers did not acknowledge the BPA in 1928 (71.5%) visits. Only four of eight intervention arm neurologists who treated patients with uncontrolled nerve pain opened the Smartset. The intervention was not associated with guideline-recommended medication use (odds ratio 0.52, 0.18-1.48; intervention 52%, control 54.8%).Discussion: Our intervention did not improve prescribing practices for painful neuropathy. Physicians typically ignored the BPAs/Smartset; therefore, future studies should mandate their use or employ alternate strategies. [ABSTRACT FROM AUTHOR]

Describe and compare healthcare costs and utilization for insured persons with type 1 diabetes (T1D), type 2 diabetes (T2D), and without diabetes in the United States. Using a nationally representative healthcare claims database, we identified matched persons with T1D, T2D, and without diabetes using a propensity score quasi-randomization technique. In each year between 2009 and 2018, we report costs (total and out-of-pocket) and utilization for all healthcare services and those specific to medications, diabetes-related supplies, visits to providers, hospitalizations, and emergency department visits. In 2018, we found out-of-pocket costs and total costs were highest for persons with T1D (out-of-pocket: $2,037.2, total: $25,652.0), followed by T2D (out-of-pocket: $1,543.3, total: $22,408.1), and without diabetes (out-of-pocket: $1,122.7, total: $14,220.6). From 2009 to 2018, out-of-pocket costs were increasing for persons with T1D(+6.5 %) but decreasing for T2D (−7.5 %) and without diabetes (−2.3 %). Medication costs made up the largest proportion of out-of-pocket costs regardless of diabetes status (T1D: 51.4 %, T2D: 55.4 %,without diabetes: 51.1 %). Given the substantial out-of-pocket costs for people with diabetes, especially for those with T1D, providers should screen all persons with diabetes for financial toxicity (i.e., wide-ranging problems stemming from healthcare costs). In addition, policies that aim to lower out-of-pocket costs of cost-effective diabetes related healthcare are needed with a particular focus on medications. [ABSTRACT FROM AUTHOR]

Objectives: To observe medication cost trends for 5 common neurologic conditions., Methods: We quantified annual out-of-pocket (OOP) and total medication costs for patients seen by a neurologist with epilepsy, multiple sclerosis (MS), Parkinson disease (PD), peripheral neuropathy (PN), and dementia/Alzheimer's disease in a commercial claims database cross-sectionally from 2012 to 2021., Results: We identified 186,144 patients with epilepsy, 54,676 with MS, 45,909 with PD, 169,127 with PN, and 60,861 with dementia/Alzheimer. OOP costs for MS medications increased each year, by 217% on average. Branded epilepsy medications had higher OOP costs than generics. Decreases ranging from 48% to 80% in annual OOP costs of duloxetine, pregabalin, rasagiline, rivastigmine, and memantine were observed in the years after generic introduction., Discussion: Preferentially selecting generic medications reduces OOP costs, other than for MS where costs continue to increase. Policy solutions, such as cost caps, are needed.