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1.
Diabetes Res Clin Pract ; 205: 110983, 2023 Nov.
Article in English | MEDLINE | ID: mdl-37890702

ABSTRACT

AIMS: 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. METHODS: 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. RESULTS: 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 %). CONCLUSIONS: 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.


Subject(s)
Diabetes Mellitus, Type 1 , Diabetes Mellitus, Type 2 , Humans , United States/epidemiology , Diabetes Mellitus, Type 2/drug therapy , Diabetes Mellitus, Type 1/therapy , Health Care Costs , Health Services , Drug Costs , Retrospective Studies
2.
Ann Clin Transl Neurol ; 10(10): 1891-1898, 2023 10.
Article in English | MEDLINE | ID: mdl-37518982

ABSTRACT

We performed a cross-sectional study to determine associations between cognition and MRI-derived brain outcomes, with obesity, diabetes duration, and metabolic risk factors in 51 Pima American Indians with longstanding type 2 diabetes (T2d) (mean [SD] age: 48.4 [11.3] years, T2d duration: 20.1 [9.1] years). Participants had similar cognition (NIH Toolbox Cognition Battery composite: 45.3 [9.8], p = 0.64, n = 51) compared to normative data. T2d duration, but not other metabolic risk factors, associated with decreased cortical thickness (Point Estimate (PE): -0.0061, 95%CI: -0.0113, -0.0009, n = 45), gray matter volume (PE: -830.39, 95%CI: -1503.14, -157.64, n = 45), and increased white matter hyperintensity volume (PE: 0.0389, 95%CI: 0.0049, 0.0729, n = 45).


Subject(s)
Diabetes Mellitus, Type 2 , Humans , United States , Middle Aged , Diabetes Mellitus, Type 2/complications , Brain/diagnostic imaging , Brain/metabolism , Cross-Sectional Studies , Risk Factors , Outcome Assessment, Health Care
3.
Diabetologia ; 66(7): 1192-1207, 2023 07.
Article in English | MEDLINE | ID: mdl-36917280

ABSTRACT

AIMS/HYPOTHESIS: The aim of this study was to determine the effect of bariatric surgery on diabetes complications in individuals with class II/III obesity (BMI > 35 kg/m2). METHODS: We performed a prospective cohort study of participants with obesity who underwent bariatric surgery. At baseline and 2 years following surgery, participants underwent metabolic phenotyping and diabetes complication assessments. The primary outcomes for peripheral neuropathy (PN) were a change in intra-epidermal nerve fibre density (IENFD, units = fibres/mm) at the distal leg and proximal thigh, the primary outcome for cardiovascular autonomic neuropathy (CAN) was a change in the expiration/inspiration (E/I) ratio, and the primary outcome for retinopathy was a change in the mean deviation on frequency doubling technology testing. RESULTS: Among 127 baseline participants, 79 completed in-person follow-up (age 46.0 ± 11.3 years [mean ± SD], 73.4% female). Participants lost a mean of 31.0 kg (SD 18.4), and all metabolic risk factors improved except for BP and total cholesterol. Following bariatric surgery, one of the primary PN outcomes improved (IENFD proximal thigh, +3.4 ± 7.8, p<0.01), and CAN (E/I ratio -0.01 ± 0.1, p=0.89) and retinopathy (deviation -0.2 ± 3.0, p=0.52) were stable. Linear regression revealed that a greater reduction in fasting glucose was associated with improvements in retinopathy (mean deviation point estimate -0.7, 95% CI -1.3, -0.1). CONCLUSIONS/INTERPRETATION: Bariatric surgery may be an effective approach to reverse PN in individuals with obesity. The observed stability of CAN and retinopathy may be an improvement compared with the natural progression of these conditions; however, controlled trials are needed.


Subject(s)
Bariatric Surgery , Diabetes Complications , Diabetes Mellitus, Type 2 , Obesity, Morbid , Humans , Female , Adult , Middle Aged , Male , Prospective Studies , Obesity/complications , Obesity/surgery , Bariatric Surgery/adverse effects , Weight Loss , Diabetes Complications/complications , Obesity, Morbid/surgery , Diabetes Mellitus, Type 2/complications , Diabetes Mellitus, Type 2/surgery
5.
Neurology ; 100(9): e884-e898, 2023 02 28.
Article in English | MEDLINE | ID: mdl-36450601

ABSTRACT

BACKGROUND AND OBJECTIVES: The objective of this study was to compare the utilization and costs (total and out-of-pocket) of new-to-market neurologic medications with existing guideline-supported neurologic medications over time. METHODS: We used a healthcare pharmaceutical claims database (from 2001 to 2019) to identify patients with both a diagnosis of 1 of 11 separate neurologic conditions and either a new-to-market medication or an existing guideline-supported medication for that condition. Neurologic conditions included orthostatic hypotension, spinal muscular atrophy, Duchenne disease, Parkinson disease, multiple sclerosis, amyotrophic lateral sclerosis, myasthenia gravis, Huntington disease, tardive dyskinesia, transthyretin amyloidosis, and migraine. New-to-market medications were defined as all neurologic medications approved by the US Food and Drug Administration (FDA) between 2014 and 2018. In each year, we determined the median out-of-pocket and standardized total costs for a 30-day supply of each medication. We also measured the proportion of patients receiving new-to-market medications compared with all medications specific for the relevant condition. RESULTS: We found that the utilization of most new-to-market medications was small (<20% in all but 1 condition), compared with existing, guideline-supported medications. The out-of-pocket and standardized total costs were substantially larger for new-to-market medications. The median (25th percentile, 75th percentile) out-of-pocket costs for a 30-day supply in 2019 were largest for edaravone ($712.8 [$59.8-$802.0]) and eculizumab ($91.1 [$3.0-$3,216.4]). For new-to-market medications, the distribution of out-of-pocket costs was highly variable and the trends over time were unpredictable compared with existing guideline-supported medications. DISCUSSION: Despite the increasing number of FDA-approved neurologic medications, utilization of newly approved medications in the privately insured population remains small. Given the high costs and similar efficacy for most of the new medications, limited utilization may be appropriate. However, for new medications with greater efficacy, future studies are needed to determine whether high costs are a barrier to utilization.


Subject(s)
Central Nervous System Depressants , Nervous System Diseases , Parkinson Disease , Humans , Costs and Cost Analysis , Health Expenditures , Pharmaceutical Preparations , Retrospective Studies , Health Care Costs
6.
Muscle Nerve ; 67(1): 45-51, 2023 01.
Article in English | MEDLINE | ID: mdl-36367146

ABSTRACT

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.


Subject(s)
Peripheral Nervous System Diseases , Polyneuropathies , Humans , Neural Conduction/physiology , Nerve Conduction Studies , Case-Control Studies , Peripheral Nervous System Diseases/diagnosis , Polyneuropathies/diagnosis
7.
Clin Transl Med ; 12(9): e1046, 2022 09.
Article in English | MEDLINE | ID: mdl-36101963

ABSTRACT

BACKGROUND: As the field of stem cell therapy advances, it is important to develop reliable methods to overcome host immune responses in animal models. This ensures survival of transplanted human stem cell grafts and enables predictive efficacy testing. Immunosuppressive drugs derived from clinical protocols are frequently used but are often inconsistent and associated with toxic side effects. Here, using a molecular imaging approach, we show that immunosuppression targeting costimulatory molecules CD4 and CD40L enables robust survival of human xenografts in mouse brain, as compared to conventional tacrolimus and mycophenolate mofetil. METHODS: Human neural stem cells were modified to express green fluorescent protein and firefly luciferase. Cells were implanted in the fimbria fornix of the hippocampus and viability assessed by non-invasive bioluminescent imaging. Cell survival was assessed using traditional pharmacologic immunosuppression as compared to monoclonal antibodies directed against CD4 and CD40L. This paradigm was also implemented in a transgenic Alzheimer's disease mouse model. RESULTS: Graft rejection occurs within 7 days in non-immunosuppressed mice and within 14 days in mice on a traditional regimen. The addition of dual monoclonal antibody immunosuppression extends graft survival past 7 weeks (p < .001) on initial studies. We confirm dual monoclonal antibody treatment is superior to either antibody alone (p < .001). Finally, we demonstrate robust xenograft survival at multiple cell doses up to 6 months in both C57BL/6J mice and a transgenic Alzheimer's disease model (p < .001). The dual monoclonal antibody protocol demonstrated no significant adverse effects, as determined by complete blood counts and toxicity screen. CONCLUSIONS: This study demonstrates an effective immunosuppression protocol for preclinical testing of stem cell therapies. A transition towards antibody-based strategies may be advantageous by enabling stem cell survival in preclinical studies that could inform future clinical trials.


Subject(s)
Alzheimer Disease , Neural Stem Cells , Animals , Antibodies, Monoclonal/pharmacology , Antibodies, Monoclonal/therapeutic use , Brain , CD40 Ligand , Humans , Immunosuppression Therapy , Mice , Mice, Inbred C57BL
8.
Ann Clin Transl Neurol ; 9(9): 1392-1404, 2022 09.
Article in English | MEDLINE | ID: mdl-35923113

ABSTRACT

OBJECTIVE: The serum lipidomic profile associated with neuropathy in type 2 diabetes is not well understood. Obesity and dyslipidemia are known neuropathy risk factors, suggesting lipid profiles early during type 2 diabetes may identify individuals who develop neuropathy later in the disease course. This retrospective cohort study examined lipidomic profiles 10 years prior to type 2 diabetic neuropathy assessment. METHODS: Participants comprised members of the Gila River Indian community with type 2 diabetes (n = 69) with available stored serum samples and neuropathy assessment 10 years later using the combined Michigan Neuropathy Screening Instrument (MNSI) examination and questionnaire scores. A combined MNSI index was calculated from examination and questionnaire scores. Serum lipids (435 species from 18 classes) were quantified by mass spectrometry. RESULTS: The cohort included 17 males and 52 females with a mean age of 45 years (SD = 9 years). Participants were stratified as with (high MNSI index score > 2.5407) versus without neuropathy (low MNSI index score ≤ 2.5407). Significantly decreased medium-chain acylcarnitines and increased total free fatty acids, independent of chain length and saturation, in serum at baseline associated with incident peripheral neuropathy at follow-up, that is, participants had high MNSI index scores, independent of covariates. Participants with neuropathy also had decreased phosphatidylcholines and increased lysophosphatidylcholines at baseline, independent of chain length and saturation. The abundance of other lipid classes did not differ significantly by neuropathy status. INTERPRETATION: Abundance differences in circulating acylcarnitines, free fatty acids, phosphatidylcholines, and lysophosphatidylcholines 10 years prior to neuropathy assessment are associated with neuropathy status in type 2 diabetes.


Subject(s)
Diabetes Mellitus, Type 2 , Diabetic Neuropathies , Diabetes Mellitus, Type 2/complications , Diabetic Neuropathies/etiology , Fatty Acids, Nonesterified , Female , Humans , Lipidomics , Lysophosphatidylcholines , Male , Middle Aged , Phosphatidylcholines , Retrospective Studies
10.
Front Endocrinol (Lausanne) ; 13: 834978, 2022.
Article in English | MEDLINE | ID: mdl-35317223

ABSTRACT

Objective: To determine the prevalence of neuropsychological outcomes in individuals with type 1 diabetes compared to individuals with type 2 diabetes or without diabetes, and to evaluate the association of diabetes status and microvascular/macrovascular complications with neuropsychological outcomes. Patients and Methods: We used a nationally representative healthcare claims database of privately insured individuals (1/1/2001-12/31/2018) to identify individuals with type 1 diabetes. Propensity score matching was used as a quasi-randomization technique to match type 1 diabetes individuals to type 2 diabetes individuals and controls. Diabetes status, microvascular/macrovascular complications (retinopathy, neuropathy, nephropathy, stroke, myocardial infarction, peripheral vascular disease, amputations), and neuropsychological outcomes (mental health, cognitive, chronic pain, addiction, sleep disorders) were defined using ICD-9/10 codes. Logistic regression determined associations between diabetes status, microvascular/macrovascular complications, and neuropsychological outcomes. Results: We identified 184,765 type 1 diabetes individuals matched to 524,602 type 2 diabetes individuals and 522,768 controls. With the exception of cognitive disorders, type 2 diabetes individuals had the highest prevalence of neuropsychological outcomes, followed by type 1 diabetes, and controls. After adjusting for the presence of microvascular/macrovascular complications, type 1 diabetes was not significantly associated with a higher risk of neuropsychological outcomes; however, type 2 diabetes remained associated with mental health, cognitive, and sleep disorders. The presence of microvascular/macrovascular complications was independently associated with each neuropsychological outcome regardless of diabetes status. Conclusion: Microvascular/macrovascular complications are associated with a high risk of neuropsychological outcomes regardless of diabetes status. Therefore, preventing microvascular and macrovascular complications will likely help reduce the likelihood of neuropsychological outcomes either as the result of similar pathophysiologic processes or by preventing the direct and indirect consequences of these complications. For individuals with type 2 diabetes, risk factors beyond complications (such as obesity) likely contribute to neuropsychological outcomes.


Subject(s)
Diabetes Mellitus, Type 1 , Diabetes Mellitus, Type 2 , Sleep Wake Disorders , Diabetes Mellitus, Type 1/complications , Diabetes Mellitus, Type 1/epidemiology , Diabetes Mellitus, Type 2/complications , Diabetes Mellitus, Type 2/epidemiology , Humans , Obesity/complications , Risk Factors
11.
Headache ; 62(1): 36-56, 2022 Jan.
Article in English | MEDLINE | ID: mdl-35041218

ABSTRACT

OBJECTIVE: The objective of this study was to understand current practice, clinician understanding, attitudes, barriers, and facilitators to optimal headache neuroimaging practices. BACKGROUND: Headaches are common in adults, and neuroimaging for these patients is common, costly, and increasing. Although guidelines recommend against routine headache neuroimaging in low-risk scenarios, guideline-discordant neuroimaging is still frequently performed. METHODS: We administered a 60-item survey to headache clinicians at the Veterans Affairs health system to assess clinician understanding and attitudes on headache neuroimaging and to determine neuroimaging practice patterns for three scenarios describing hypothetical patients with headaches. Descriptive statistics were used to summarize responses, stratified by clinician type (physicians or advanced practice clinicians [APCs]) and specialty (neurology or primary care). RESULTS: The survey was successfully completed by 431 of 1426 clinicians (30.2% response rate). Overall, 317 of 429 (73.9%) believed neuroimaging was overused for patients with headaches. However, clinicians would utilize neuroimaging a mean (SD) 30.9% (31.7) of the time in a low-risk scenario without red flags, and a mean 67.1% (31.9) of the time in the presence of minor red flags. Clinicians had stronger beliefs in the potential benefits (268/429, 62.5%) of neuroimaging compared to harms (181/429, 42.2%) and more clinicians were bothered by harms stemming from the omission of neuroimaging (377/426, 88.5%) compared to commission (329/424, 77.6%). Additionally, APCs utilized neuroimaging more frequently than physicians and were more receptive to potential interventions to improve neuroimaging utilization. CONCLUSIONS: Although a majority of clinicians believed neuroimaging was overused for patients with headaches, many would utilize neuroimaging in low-risk scenarios with a small probability of changing management. Future studies are needed to define the role of currently used red flags given their importance in neuroimaging decisions. Importantly, APCs may be an ideal target for future optimization efforts.


Subject(s)
Attitude of Health Personnel , Facilities and Services Utilization , Headache Disorders/diagnostic imaging , Headache/diagnostic imaging , Magnetic Resonance Imaging , Neuroimaging , Health Care Surveys , Humans , Nurse Practitioners , Physician Assistants , Physicians , United States , United States Department of Veterans Affairs
12.
Oral Dis ; 28(1): 193-201, 2022 Jan.
Article in English | MEDLINE | ID: mdl-33274559

ABSTRACT

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.


Subject(s)
Bone Density Conservation Agents , Neoplasms , Osteonecrosis , Bone Density Conservation Agents/adverse effects , Case-Control Studies , Diphosphonates/adverse effects , Humans , Risk Factors
13.
Cardiol Young ; 32(10): 1649-1656, 2022 Oct.
Article in English | MEDLINE | ID: mdl-34924086

ABSTRACT

BACKGROUND: Cardiac intensivists frequently assess patient readiness to wean off mechanical ventilation with an extubation readiness trial despite it being no more effective than clinician judgement alone. We evaluated the utility of high-frequency physiologic data and machine learning for improving the prediction of extubation failure in children with cardiovascular disease. METHODS: This was a retrospective analysis of clinical registry data and streamed physiologic extubation readiness trial data from one paediatric cardiac ICU (12/2016-3/2018). We analysed patients' final extubation readiness trial. Machine learning methods (classification and regression tree, Boosting, Random Forest) were performed using clinical/demographic data, physiologic data, and both datasets. Extubation failure was defined as reintubation within 48 hrs. Classifier performance was assessed on prediction accuracy and area under the receiver operating characteristic curve. RESULTS: Of 178 episodes, 11.2% (N = 20) failed extubation. Using clinical/demographic data, our machine learning methods identified variables such as age, weight, height, and ventilation duration as being important in predicting extubation failure. Best classifier performance with this data was Boosting (prediction accuracy: 0.88; area under the receiver operating characteristic curve: 0.74). Using physiologic data, our machine learning methods found oxygen saturation extremes and descriptors of dynamic compliance, central venous pressure, and heart/respiratory rate to be of importance. The best classifier in this setting was Random Forest (prediction accuracy: 0.89; area under the receiver operating characteristic curve: 0.75). Combining both datasets produced classifiers highlighting the importance of physiologic variables in determining extubation failure, though predictive performance was not improved. CONCLUSION: Physiologic variables not routinely scrutinised during extubation readiness trials were identified as potential extubation failure predictors. Larger analyses are necessary to investigate whether these markers can improve clinical decision-making.


Subject(s)
Airway Extubation , Ventilator Weaning , Humans , Child , Ventilator Weaning/methods , Retrospective Studies , Intensive Care Units, Pediatric , Machine Learning
14.
Obesity (Silver Spring) ; 29(12): 2108-2118, 2021 12.
Article in English | MEDLINE | ID: mdl-34747574

ABSTRACT

OBJECTIVE: The aim of this study was to determine the effect of dietary weight loss on neuropathy outcomes in people with severe obesity. METHODS: A prospective cohort study of participants attending a medical weight-management program was followed. Weight loss was achieved with meal replacement of 800 kcal/d for 12 weeks and then transitioning to 1,200 to 1,500 kcal/d. The coprimary outcomes were changes in intraepidermal nerve fiber density (IENFD) at the distal leg and proximal thigh. Secondary outcomes included nerve conduction studies, Michigan Neuropathy Screening Instrument questionnaire and exam, Quality of Life in Neurological Disorders, and quantitative sensory testing. RESULTS: Among 131 baseline participants, 72 (mean [SD] age: 50.1 [10.5] years, 51.4% female) completed 2 years of follow-up. Participants lost 12.4 (11.8) kg. All metabolic syndrome components improved with the exception of blood pressure. IENFD in the distal leg (0.4 [3.3], p = 0.29), and proximal thigh (0.3 [6.3], p = 0.74) did not significantly change. Improvements were observed on the Michigan Neuropathy Screening Instrument questionnaire, two Quality of Life in Neurological Disorders subdomains, and quantitative sensory testing cold threshold. CONCLUSIONS: Dietary weight loss was associated with improvements in all metabolic parameters except blood pressure, and both IENFD outcomes remained stable after 2 years. Given that natural history studies reveal decreases in IENFD over time, dietary weight loss may halt this progression, but randomized controlled trials are needed.


Subject(s)
Obesity, Morbid , Female , Humans , Male , Middle Aged , Nerve Fibers/physiology , Obesity, Morbid/complications , Obesity, Morbid/therapy , Prospective Studies , Quality of Life , Weight Loss
15.
JCI Insight ; 6(10)2021 05 24.
Article in English | MEDLINE | ID: mdl-34027894

ABSTRACT

BACKGROUNDWe aimed to determine whether metabolic syndrome (MetS) affects longitudinal trajectories of diabetic complications, including neuropathy, cardiovascular autonomic neuropathy (CAN), and kidney disease in American Indians with type 2 diabetes.METHODSWe performed a prospective study where participants underwent annual metabolic phenotyping and outcome measurements. The updated National Cholesterol Education Program criteria were used to define MetS and its individual components, using BMI instead of waist circumference. Neuropathy was defined using the Michigan Neuropathy Screening Instrument index, CAN with the expiration/inspiration ratio, and kidney disease with glomerular filtration rate. Mixed-effects models were used to evaluate associations between MetS and these outcomes.RESULTSWe enrolled 141 participants: 73.1% female, a mean (±SD) age of 49.8 (12.3), and a diabetes duration of 19.6 years (9.7 years) who were followed for a mean of 3.1 years (1.7 years). MetS components were stable during follow-up except for declining obesity and cholesterol. Neuropathy (point estimate [PE]: 0.30, 95% CI: 0.24, 0.35) and kidney disease (PE: -14.2, 95% CI: -16.8, -11.4) worsened over time, but CAN did not (PE: -0.002, 95% CI: -0.006, 0.002). We found a significant interaction between the number of MetS components and time for neuropathy (PE: 0.05, 95% CI: 0.01-0.10) but not CAN (PE: -0.003, 95% CI: -0.007, 0.001) or kidney disease (PE: -0.69, 95% CI: -3.16, 1.76). Systolic blood pressure (SBP, unit = 10 mmHg) was associated with each complication: neuropathy (PE: 0.23, 95% CI: 0.07, 0.39), CAN (PE: -0.02, 95% CI: -0.03, -0.02), and kidney disease (PE: -10.2, 95% CI: -15.4, -5.1).CONCLUSIONIn participants with longstanding diabetes, neuropathy and kidney disease worsened during follow-up, despite stable to improving MetS components, suggesting that early metabolic intervention is necessary to prevent complications in such patients. Additionally, the number of MetS components was associated with an increased rate of neuropathy progression, and SBP was associated with each complication.FUNDINGThe following are funding sources: NIH T32NS0007222, NIH R24DK082841, NIH R21NS102924, NIH R01DK115687, the Intramural Program of the NIDDK, the NeuroNetwork for Emerging Therapies, the Robert and Katherine Jacobs Environmental Health Initiative, the Robert E. Nederlander Sr. Program for Alzheimer's Research, and the Sinai Medical Staff Foundation.TRIAL REGISTRATIONClinicalTrials.gov, NCT00340678.


Subject(s)
American Indian or Alaska Native/statistics & numerical data , Diabetes Mellitus, Type 2 , Diabetic Nephropathies , Metabolic Syndrome , Adult , Diabetes Mellitus, Type 2/complications , Diabetes Mellitus, Type 2/epidemiology , Diabetic Nephropathies/complications , Diabetic Nephropathies/epidemiology , Female , Glomerular Filtration Rate/physiology , Humans , Male , Metabolic Syndrome/complications , Metabolic Syndrome/epidemiology , Middle Aged , Prospective Studies , Randomized Controlled Trials as Topic
16.
Ann Clin Transl Neurol ; 8(6): 1292-1307, 2021 06.
Article in English | MEDLINE | ID: mdl-33955722

ABSTRACT

OBJECTIVE: The global rise in type 2 diabetes is associated with a concomitant increase in diabetic complications. Diabetic polyneuropathy is the most frequent type 2 diabetes complication and is associated with poor outcomes. The metabolic syndrome has emerged as a major risk factor for diabetic polyneuropathy; however, the metabolites associated with the metabolic syndrome that correlate with diabetic polyneuropathy are unknown. METHODS: We conducted a global metabolomics analysis on plasma samples from a subcohort of participants from the Danish arm of Anglo-Danish-Dutch study of Intensive Treatment of Diabetes in Primary Care (ADDITION-Denmark) with and without diabetic polyneuropathy versus lean control participants. RESULTS: Compared to lean controls, type 2 diabetes participants had significantly higher HbA1c (p = 0.0028), BMI (p = 0.0004), and waist circumference (p = 0.0001), but lower total cholesterol (p = 0.0001). Out of 991 total metabolites, we identified 15 plasma metabolites that differed in type 2 diabetes participants by diabetic polyneuropathy status, including metabolites belonging to energy, lipid, and xenobiotic pathways, among others. Additionally, these metabolites correlated with alterations in plasma lipid metabolites in type 2 diabetes participants based on neuropathy status. Further evaluating all plasma lipid metabolites identified a shift in abundance, chain length, and saturation of free fatty acids in type 2 diabetes participants. Importantly, the presence of diabetic polyneuropathy impacted the abundance of plasma complex lipids, including acylcarnitines and sphingolipids. INTERPRETATION: Our explorative study suggests that diabetic polyneuropathy in type 2 diabetes is associated with novel alterations in plasma metabolites related to lipid metabolism.


Subject(s)
Diabetes Mellitus, Type 2/blood , Diabetic Neuropathies/blood , Lipids/blood , Metabolome , Aged , Aged, 80 and over , Case-Control Studies , Cholesterol/blood , Cross-Sectional Studies , Diabetes Mellitus, Type 2/complications , Diabetic Neuropathies/etiology , Female , Glycated Hemoglobin , Humans , Male , Waist Circumference
17.
Obes Surg ; 31(6): 2669-2681, 2021 06.
Article in English | MEDLINE | ID: mdl-33660154

ABSTRACT

PURPOSE: Extreme obesity has been associated with cognitive deficits across the lifespan and may be a risk factor for dementia in later life. However, the relationship between obesity and domain-specific cognitive deficits is complicated by a body of literature that often fails to adequately account for medical and psychiatric conditions frequently co-occurring with extreme obesity. MATERIALS AND METHODS: The present study included a cross-sectional evaluation of adults with extreme obesity (n=117) compared to lean control (n=46) participants on a brief cognitive battery using the NIH Toolbox and Rey Auditory Verbal Learning Test. Specifically, this study evaluated measures of executive functioning, attention, processing speed, learning, and memory while accounting for many common obesity-related medical and psychiatric comorbidities with known cognitive effects. RESULTS: Results revealed group differences with lower performances on measures of executive functioning, processing speed, and learning (ps<0.01) for participants with obesity. Reduced executive functioning was associated with abdominal obesity and medication use (ps<0.01) and together contributed significantly to overall modeling of cognition in individuals with obesity. CONCLUSION: Individuals with extreme obesity in this sample showed lower cognitive performance on measures of executive functioning, processing speed, and learning compared to lean controls. Abdominal obesity was associated with executive functioning deficits independent of many common medical and psychiatric factors.


Subject(s)
Obesity, Morbid , Adult , Cognition , Cross-Sectional Studies , Executive Function , Humans , Neuropsychological Tests , Obesity/complications , Obesity/epidemiology , Obesity, Morbid/surgery
18.
J Neuromuscul Dis ; 8(2): 299-303, 2021.
Article in English | MEDLINE | ID: mdl-33459659

ABSTRACT

The prognostic value of cerebrospinal fluid (CSF) protein in Guillain Barré Syndrome (GBS) is unclear. We aimed to explore the potential association between CSF protein level and mechanical ventilation in GBS. We undertook a retrospective study of GBS patients from January 2000 to November 2019 at the University of Michigan. 94 patients were ultimately included for evaluation. After adjusting for the Erasmus GBS Respiratory Insufficiency Scale (EGRIS), we did not find a significant difference in CSF protein between ventilated and non-ventilated patients. Elevated CSF protein level does not appear to portend an increased likelihood of mechanical ventilation in GBS patients.


Subject(s)
Cerebrospinal Fluid Proteins/analysis , Guillain-Barre Syndrome/cerebrospinal fluid , Respiration, Artificial/statistics & numerical data , Adult , Aged , Biomarkers/cerebrospinal fluid , Female , Humans , Male , Middle Aged , Prognosis , Respiratory Insufficiency , Retrospective Studies
19.
Neurology ; 96(3): e322-e332, 2021 01 19.
Article in English | MEDLINE | ID: mdl-33361253

ABSTRACT

OBJECTIVE: To measure the out-of-pocket (OOP) costs of evaluation and management (E/M) services and common diagnostic testing for neurology patients. METHODS: Using a large, privately insured health care claims database, we identified patients with a neurologic visit or diagnostic test from 2001 to 2016 and assessed inflation-adjusted OOP costs for E/M visits, neuroimaging, and neurophysiologic testing. For each diagnostic service each year, we estimated the proportion of patients with OOP costs, the mean OOP cost, and the proportion of the total service cost paid OOP. We modeled OOP cost as a function of patient and insurance factors. RESULTS: We identified 3,724,342 patients. The most frequent neurologic services were E/M visits (78.5%), EMG/nerve conduction studies (NCS) (7.7%), MRIs (5.3%), and EEGs (4.5%). Annually, 86.5%-95.2% of patients paid OOP costs for E/M visits and 23.1%-69.5% for diagnostic tests. For patients paying any OOP cost, the mean OOP cost increased over time, most substantially for EEG, MRI, and E/M. OOP costs varied considerably; for an MRI in 2016, the 50th percentile paid $103.10 and the 95th percentile paid $875.40. The proportion of total service cost paid OOP increased. High deductible health plan (HDHP) enrollment was associated with higher OOP costs for MRI, EMG/NCS, and EEG. CONCLUSION: An increasing number of patients pay OOP for neurologic diagnostic services. These costs are rising and vary greatly across patients and tests. The cost sharing burden is particularly high for the growing population with HDHPs. In this setting, neurologic evaluation might result in financial hardship for patients.


Subject(s)
Health Expenditures , Insurance, Health/economics , Nervous System Diseases/diagnosis , Neuroimaging/economics , Neurologic Examination/economics , Neurology/economics , Humans , Nervous System Diseases/economics
20.
Neurology ; 95(7): e930-e935, 2020 08 18.
Article in English | MEDLINE | ID: mdl-32680949

ABSTRACT

OBJECTIVE: To determine whether the 2013 nerve conduction study (NCS) reimbursement reduction changed Medicare use, payments, and patient access to Medicare physicians by performing a retrospective analysis of Medicare data (2012-2016 fee-for-service data from the CMS Physician and Other Supplier Public Use File). METHODS: Individual billable services were identified by Healthcare Common Procedure Coding System Current Procedural Terminology and G codes. Medicare use and payments were stratified by specialty and type of service (electrodiagnostic tests, including NCS and EMG, and other neurologic procedures). We also assessed access to Medicare physicians using the annual number of unique beneficiaries receiving initial Evaluation and Management (E/M) services. RESULTS: We identified 676,113 Medicare providers included in all analysis years from 2012 to 2016 (10,599 neurologists, 5,881 physiatrists, and 659,633 other specialties). Comparing 2016 to 2012 showed that 21.1% fewer neurologists, 28.6% fewer physiatrists, and 69.3% fewer other specialists performed NCS and 3.8% fewer neurologists, 21.7% fewer physiatrists, and 5.6% fewer other specialists performed EMG. For NCS providers in 2012, the mean number of unique Medicare beneficiaries increased for neurologists (1.2%) and physiatrists (4.8%) but decreased for other specialists (-6.5%) by 2016. After the NCS cut, the number of providers performing autonomic and evoked potential testing increased substantially. CONCLUSIONS: The Medicare NCS reimbursement policy resulted in a larger decrease in NCS providers than in EMG providers. Despite fewer neurologists and physiatrists performing NCS, Medicare access to these physicians for E/M services was not affected. Increased autonomic and evoked potential testing may be an unintended consequence of NCS reimbursement change.


Subject(s)
Medicare/legislation & jurisprudence , Policy , Practice Patterns, Physicians'/legislation & jurisprudence , Reimbursement Mechanisms , Humans , Medicare/economics , Physicians/legislation & jurisprudence , Retrospective Studies , United States
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