Trial of Globus Pallidus Focused Ultrasound Ablation in Parkinson's Disease.

BACKGROUND: Unilateral focused ultrasound ablation of the internal segment of globus pallidus has reduced motor symptoms of Parkinson's disease in open-label studies. METHODS: We randomly assigned, in a 3:1 ratio, patients with Parkinson's disease and dyskinesias or motor fluctuations and motor impairment in the off-medication state to undergo either focused ultrasound ablation opposite the most symptomatic side of the body or a sham procedure. The primary outcome was a response at 3 months, defined as a decrease of at least 3 points from baseline either in the score on the Movement Disorders Society-Unified Parkinson's Disease Rating Scale, part III (MDS-UPDRS III), for the treated side in the off-medication state or in the score on the Unified Dyskinesia Rating Scale (UDysRS) in the on-medication state. Secondary outcomes included changes from baseline to month 3 in the scores on various parts of the MDS-UPDRS. After the 3-month blinded phase, an open-label phase lasted until 12 months. RESULTS: Of 94 patients, 69 were assigned to undergo ultrasound ablation (active treatment) and 25 to undergo the sham procedure (control); 65 patients and 22 patients, respectively, completed the primary-outcome assessment. In the active-treatment group, 45 patients (69%) had a response, as compared with 7 (32%) in the control group (difference, 37 percentage points; 95% confidence interval, 15 to 60; P = 0.003). Of the patients in the active-treatment group who had a response, 19 met the MDS-UPDRS III criterion only, 8 met the UDysRS criterion only, and 18 met both criteria. Results for secondary outcomes were generally in the same direction as those for the primary outcome. Of the 39 patients in the active-treatment group who had had a response at 3 months and who were assessed at 12 months, 30 continued to have a response. Pallidotomy-related adverse events in the active-treatment group included dysarthria, gait disturbance, loss of taste, visual disturbance, and facial weakness. CONCLUSIONS: Unilateral pallidal ultrasound ablation resulted in a higher percentage of patients who had improved motor function or reduced dyskinesia than a sham procedure over a period of 3 months but was associated with adverse events. Longer and larger trials are required to determine the effect and safety of this technique in persons with Parkinson's disease. (Funded by Insightec; ClinicalTrials.gov number, NCT03319485.).

Economic impact on local businesses of road safety improvements in Seattle: implications for Vision Zero projects.

BACKGROUND: Local transportation agencies implementing Vision Zero road safety improvement projects often face opposition from business owners concerned about the potential negative impact on their sales. Few studies have documented the economic impact of these projects. METHODS: We examined baseline and up to 3 years of postimprovement taxable sales data for retail, food and service-based businesses adjacent to seven road safety projects begun between 2006 and 2014 in Seattle. We used hierarchical linear models to test whether the change in annual taxable sales differed between the 7 intervention sites and 18 nearby matched comparison sites that had no road safety improvements within the study time frame. RESULTS: Average annual taxable sales at baseline were comparable at the 7 intervention sites (US$44.7 million) and the 18 comparison sites (US$56.8 million). Regression analysis suggests that each additional year following baseline was associated with US$1.20 million more in taxable sales among intervention sites and US$1.14 million more among comparison sites. This difference is not statistically significant (p=0.64). Sensitivity analyses including a random slope, using a generalised linear model and an analysis of variance did not change conclusions. DISCUSSION: Results suggest that road safety improvement projects such as those in Vision Zero plans are not associated with adverse economic impacts on adjacent businesses. The absence of negative economic impacts associated with pedestrian and bicycle road safety projects should reassure local business owners and may encourage them to work with transportation agencies to implement Vision Zero road safety projects designed to eliminate traffic-related injuries.

Cost of Implementing an Evidence-Based Intervention to Support Safer Use of Antipsychotics in Youth.

To estimate the cost of implementing a clinical program designed to support safer use of antipsychotics in children and adolescents (youth) age 3-17 years at the time of initiating an antipsychotic medication. We calculate the costs of implementing a psychiatric consultation and navigation program for youth prescribed antipsychotic medications across 4 health systems, which included an electronic health record (EHR) decision support tool, consultation with a child and adolescent psychiatrist, and up to 6 months of behavioral health care navigation, as well as telemental health for patients (n = 348). Cost data were collected for both start-up and ongoing intervention phases and are estimated over a 1-year period. Data sources included study records and time-in-motion reports, analyzed from a health system perspective. Costs included both labor and nonlabor costs (2019 US dollars). The average total start-up and ongoing costs per health system were $34,007 and $185,174, respectively. The average total cost per patient was $2,128. The highest average ongoing labor cost components were telemental health ($901 per patient), followed by child and adolescent psychiatrist consultation ($659), and the lowest cost component was primary care/behavioral health provider time to review/respond to the EHR decision support tool and case consultation ($24). For health systems considering programs to promote safer and targeted use of antipsychotics among youth, this study provides estimates of the full start-up and ongoing costs of an EHR decision support tool, psychiatric consultation service, and psychotherapeutic services for patients and families.Trial registration: Clinicaltrials.gov, NCT03448575.

Observational study of patient characteristics associated with a timely diagnosis of dementia and mild cognitive impairment without dementia.

BACKGROUND: Timely diagnosis of cognitive impairment is a key goal of the National Plan to Address Alzheimer's Disease, but studies of factors associated with a timely diagnosis are limited. OBJECTIVE: To identify patient characteristics associated with a timely diagnosis of dementia and mild cognitive impairment (MCI). DESIGN: Retrospective observational study using survey data from the Health and Retirement Study (HRS) from 1995-2016 (interview waves 3-13). PARTICIPANTS: 4,760 respondents with incident dementia and 1,864 with incident MCI identified using longitudinal measures of cognitive functioning. MAIN MEASURES: Timely or delayed diagnosis based on the timing of a self or proxy report of a healthcare provider diagnosis in relation to respondents first dementia or MCI-qualifying cognitive score, sociodemographic characteristics, health status, health care utilization, insurance provider, and year of first qualifying score. KEY RESULTS: Only 26.0% of the 4,760 respondents with incident dementia and 11.4% of the 1,864 respondents with incident MCI received a timely diagnosis. Non-Hispanic Black respondents and respondents with less than a college degree were significantly less likely to receive a timely diagnosis of either dementia or MCI than Non-Hispanic White respondents (dementia odds ratio (OR): 0.61, 95% CI: 0.50, 0.75; MCI OR: 0.40, 95% CI: 0.23, 0.70) and those with a college degree (dementia OR for less than high school degree: 0.30, 95% CI: 0.23, 0.38; MCI OR: 0.36, 95% CI: 0.22, 0.60). Respondents that lived alone were also less likely to receive a timely diagnosis of dementia (OR: 0.69, 95% CI: 0.59, 0.81), though not MCI. Timely diagnosis of both conditions increased over time. CONCLUSIONS: Targeting resources for timely diagnosis of cognitive impairment to individuals from racial and ethnic minorities, lower educational attainment, and living alone may improve detection and reduce disparities around timely diagnosis of dementia and MCI.

Patterns of Medical Care Cost by Service Type for Patients With Recurrent and De Novo Advanced Cancer.

OBJECTIVES: There is limited knowledge about the cost patterns of patients who receive a diagnosis of de novo and recurrent advanced cancers in the United States. METHODS: Data on patients who received a diagnosis of de novo stage IV or recurrent breast, colorectal, or lung cancer between 2000 and 2012 from 3 integrated health systems were used to estimate average annual costs for total, ambulatory, inpatient, medication, and other services during (1) 12 months preceding de novo or recurrent diagnosis (preindex) and (2) diagnosis month through 11 months after (postindex), from the payer perspective. Generalized linear regression models estimated costs adjusting for patient and clinical factors. RESULTS: Patients who developed a recurrence <1 year after their initial cancer diagnosis had significantly higher total costs in the preindex period than those with recurrence ≥1 year after initial diagnosis and those with de novo stage IV disease across all cancers (all P < .05). Patients with de novo stage IV breast and colorectal cancer had significantly higher total costs in the postindex period than patients with cancer recurrent in <1 year and ≥1 year (all P < .05), respectively. Patients in de novo stage IV and those with recurrence in ≥1 year experienced significantly higher postindex costs than the preindex period (all P < .001). CONCLUSIONS: Our findings reveal distinct cost patterns between patients with de novo stage IV, recurrent <1-year, and recurrent ≥1-year cancer, suggesting unique care trajectories that may influence resource use and planning. Future cost studies among patients with advanced cancer should account for de novo versus recurrent diagnoses and timing of recurrence to obtain estimates that accurately reflect these care pattern complexities.

A sub-group evaluation of the multi-month dispensing strategy for differentiated HIV care: is personalization of care guidelines warranted in Haiti?

BACKGROUND: Differentiated care strategies are rapidly becoming the norm for HIV care delivery globally. Building upon an interest in tailoring antiretroviral therapy (ART) delivery for client-centered needs, the Ministry of Health and Population in Haiti formally endorsed multiple-month dispenses (MMD) in the 2016 national ART guidelines This study explores heterogeneity in retention in care with MMD for specific Haitian populations living with HIV and evaluates if a targeted algorithm for optimal ART prescription intervals is warranted in Haiti. METHODS: This study included ART-naïve individuals who started ART on or after January 1st, 2017 in Haiti. To identify subgroups in which to explore heterogeneity of retention, we implemented a double-lasso regression method to determine which individual characteristics would define the subgroups. Characteristics evaluated for potential subgroup definition included: sex, age category, WHO clinical stage, and body mass index category. We employed instrumental variable models to estimate the causal effect of increasing ART dispensing length on ART retention, by client subgroup. The outcome of interest was retention in care after one year in treatment. We then estimated the marginal effect of a 30-day increase to ART dispensing length to retention in care for each of these subgroups. RESULTS: There was evidence for heterogeneity in the effect of extending ART dispensing intervals on retention by WHO clinical stage. We observed significant improvements to retention in care at one year with a 30-day increase in ART dispense length for all subgroups defined by WHO clinical stages 1-4. The effects ranged from a 14.7% increase (95% CI: 12.4-17.0) to the likelihood of retention for people with HIV in WHO stage 1 to a 21.6% increase (95% CI: 18.7-24.5) to the likelihood of retention for those in WHO stage 3. CONCLUSIONS: All the subgroups defined by WHO clinical stage experienced a benefit of extending ART intervals to retention in care at one year. Though the effect did differ slightly by WHO stage, the effects went in the same direction and were of similar magnitude. Therefore, a standardized recommendation for MMD among those living with HIV and new on ART is appropriate for Haiti treatment guidelines.

Racial Disparities in Avoidable Hospitalizations in Traditional Medicare and Medicare Advantage.

IMPORTANCE: Compared with traditional Medicare (TM), Medicare Advantage (MA) has the potential to reduce racial disparities in hospitalizations for ambulatory care sensitive conditions (ACSC). As racial disparities may be partly attributable to unequal treatment based on where people live, this suggests the need of examining geographic variations in racial disparities. OBJECTIVE: The aim of this study was to examine differences in ACSC hospitalizations between White and Black beneficiaries in TM and MA and examine geographic variations in racial differences in ACSC hospitalizations in TM and MA. METHODS: We analyzed the 2015-2016 Medicare Provider Analysis and Review files. We used propensity score matching to account for differences in characteristics between TM and MA beneficiaries. Then, we conducted linear regression and estimated adjusted outcomes for TM and MA beneficiaries by race. Also, we estimated racial differences in adjusted outcomes by insurance and hospital referral region (HRR). RESULTS: While White beneficiaries in TM and MA had similar rates of ACSC hospitalizations (163.7 vs. 162.2/10,000 beneficiaries), Black beneficiaries in MA had higher rates of ACSC hospitalizations than Black beneficiaries in TM (221.2 vs. 209.3/10,000 beneficiaries). However, the racial differences were greater in MA than TM (59.0 vs. 45.6/10,000 beneficiaries). Racial differences in ACSC hospitalizations in MA were prevalent across almost all HRRs. 95.5% of HRRs had higher rates of ACSC hospitalizations among Black beneficiaries than White beneficiaries in MA relative to just 54.2% of HRRs in TM. CONCLUSION: Our findings provide evidence of racial disparities in access to high-quality primary care, especially in MA.

Differences in Health Care Utilization, Process of Diabetes Care, Care Satisfaction, and Health Status in Patients With Diabetes in Medicare Advantage Versus Traditional Medicare.

OBJECTIVE: The objective of this study was to determine differences in health care utilization, process of diabetes care, care satisfaction, and health status for Medicare Advantage (MA) and traditional Medicare (TM) beneficiaries with and without diabetes. METHODS: Using the 2010-2016 Medicare Current Beneficiary Survey, we identified MA and TM beneficiaries with and without diabetes. To address the endogenous plan choice between MA and TM, we used an instrumental variable approach. Using marginal effects, we estimated differences in the outcomes between MA and TM beneficiaries with and without diabetes. RESULTS: Our instrumental variable analysis showed that compared with TM beneficiaries with diabetes, MA beneficiaries with diabetes had less annual health care utilization, including -22.4 medical provider visits [95% confidence interval (CI): -23.6 to -21.1] and -3.4 outpatient hospital visits (95% CI: -3.8 to -3.0). A significant difference between MA and TM beneficiaries without diabetes was only observed in medical provider visits and the difference was greater among beneficiaries with diabetes than beneficiaries without diabetes (-12.5 medical provider visits; 95% CI: -15.9 to -9.2). While we did not detect significant differences in 5 measures of the process of diabetes care between MA and TM beneficiaries with diabetes, there were inconsistent results in the other 3 measures. There were no or marginal differences in care satisfaction and health status between MA and TM beneficiaries with and without diabetes. CONCLUSIONS: MA enrollment was associated with lower health care utilization without compromising care satisfaction and health status, particularly for beneficiaries with diabetes. MA may have a more efficient care delivery system for beneficiaries with diabetes.

Health Care Costs of Alzheimer's and Related Dementias Within a Medicare Managed Care Provider.

BACKGROUND: Although one third of Medicare beneficiaries are enrolled in Medicare Advantage (MA) plans, there is limited information about the cost of treating Alzheimer disease and related dementias (ADRD) in these settings. OBJECTIVE: The objective of this study was to estimate direct health care costs attributable to ADRD among older adults within a large MA plan. RESEARCH DESIGN: A retrospective cohort design was used to estimate direct total, outpatient, inpatient, ambulatory pharmacy, and nursing home costs for 3 years before and after an incident ADRD diagnosis for 927 individuals diagnosed with ADRD relative to a sex-matched and birth year-matched set of 2945 controls. SUBJECT: Adults 65 years of age and older enrolled in the Kaiser Permanente Washington MA plan and the Adult Changes in Thought (ACT) Study, a prospective longitudinal cohort study of ADRD and brain aging. MEASURES: Data on monthly health service use obtained from health system electronic medical records for the period 1992-2012. RESULTS: Total monthly health care costs for individuals with ADRD are statistically greater (P<0.05) than controls beginning in the third month before diagnosis and remain significantly greater through the eighth month following diagnosis. Greater total health costs are driven by significantly (P<0.05) greater nursing home costs among individuals diagnosed with ADRD beginning in the third month prediagnosis. Although total costs were no longer significantly greater at 8 months following diagnosis, nursing home costs remained higher for the people with dementia through the 3 years postdiagnosis we analyzed. CONCLUSION: Greater total health care costs among individuals with ADRD are primarily driven by nursing home costs.

A Randomized Trial of Focused Ultrasound Thalamotomy for Essential Tremor.

BACKGROUND: Uncontrolled pilot studies have suggested the efficacy of focused ultrasound thalamotomy with magnetic resonance imaging (MRI) guidance for the treatment of essential tremor. METHODS: We enrolled patients with moderate-to-severe essential tremor that had not responded to at least two trials of medical therapy and randomly assigned them in a 3:1 ratio to undergo unilateral focused ultrasound thalamotomy or a sham procedure. The Clinical Rating Scale for Tremor and the Quality of Life in Essential Tremor Questionnaire were administered at baseline and at 1, 3, 6, and 12 months. Tremor assessments were videotaped and rated by an independent group of neurologists who were unaware of the treatment assignments. The primary outcome was the between-group difference in the change from baseline to 3 months in hand tremor, rated on a 32-point scale (with higher scores indicating more severe tremor). After 3 months, patients in the sham-procedure group could cross over to active treatment (the open-label extension cohort). RESULTS: Seventy-six patients were included in the analysis. Hand-tremor scores improved more after focused ultrasound thalamotomy (from 18.1 points at baseline to 9.6 at 3 months) than after the sham procedure (from 16.0 to 15.8 points); the between-group difference in the mean change was 8.3 points (95% confidence interval [CI], 5.9 to 10.7; P<0.001). The improvement in the thalamotomy group was maintained at 12 months (change from baseline, 7.2 points; 95% CI, 6.1 to 8.3). Secondary outcome measures assessing disability and quality of life also improved with active treatment (the blinded thalamotomy cohort)as compared with the sham procedure (P<0.001 for both comparisons). Adverse events in the thalamotomy group included gait disturbance in 36% of patients and paresthesias or numbness in 38%; these adverse events persisted at 12 months in 9% and 14% of patients, respectively. CONCLUSIONS: MRI-guided focused ultrasound thalamotomy reduced hand tremor in patients with essential tremor. Side effects included sensory and gait disturbances. (Funded by InSightec and others; ClinicalTrials.gov number, NCT01827904.).

A prospective trial of magnetic resonance-guided focused ultrasound thalamotomy for essential tremor: Results at the 2-year follow-up.

OBJECTIVE: Magnetic resonance guided focused ultrasound (MRgFUS) has recently been investigated as a new treatment modality for essential tremor (ET), but the durability of the procedure has not yet been evaluated. This study reports results at a 2- year follow-up after MRgFUS thalamotomy for ET. METHODS: A total of 76 patients with moderate-to-severe ET, who had not responded to at least two trials of medical therapy, were enrolled in the original randomized study of unilateral thalamotomy and evaluated using the clinical rating scale for tremor. Sixty-seven of the patients continued in the open-label extension phase of the study with monitoring for 2 years. Nine patients were excluded by 2 years, for example, because of alternative therapy such as deep brain stimulation (n = 3) or inadequate thermal lesioning (n = 1). However, all patients in each follow-up period were analyzed. RESULTS: Mean hand tremor score at baseline (19.8 ± 4.9; 76 patients) improved by 55% at 6 months (8.6 ± 4.5; 75 patients). The improvement in tremor score from baseline was durable at 1 year (53%; 8.9 ± 4.8; 70 patients) and at 2 years (56%; 8.8 ± 5.0; 67 patients). Similarly, the disability score at baseline (16.4 ± 4.5; 76 patients) improved by 64% at 6 months (5.4 ± 4.7; 75 patients). This improvement was also sustained at 1 year (5.4 ± 5.3; 70 patients) and at 2 years (6.5 ± 5.0; 67 patients). Paresthesias and gait disturbances were the most common adverse effects at 1 year-each observed in 10 patients with an additional 5 patients experiencing neurological adverse effects. None of the adverse events worsened over the period of follow-up, and 2 of these resolved. There were no new delayed complications at 2 years. INTERPRETATION: Tremor suppression after MRgFUS thalamotomy for ET is stably maintained at 2 years. Latent or delayed complications do not develop after treatment. Ann Neurol 2018;83:107-114.

The role of high-intensity focused ultrasound as a symptomatic treatment for Parkinson's disease.

MR-guided focused ultrasound is a novel, minimally invasive surgical procedure for symptomatic treatment of PD. With this technology, the ventral intermediate nucleus, STN, and internal globus pallidus have been targeted for therapeutic cerebral ablation, while also minimizing the risk of hemorrhage and infection from more invasive neurosurgical procedures. In a double-blinded, prospective, sham-controlled randomized controlled trial of MR-guided focused ultrasound thalamotomy for treatment of tremor-dominant PD, 62% of treated patients demonstrated improvement in tremor scores from baseline to 3 months postoperatively, as compared to 22% in the sham group. There has been only one open-label trial of MR-guided focused ultrasound subthalamotomy for patients with PD, demonstrating improvements of 71% for rigidity, 36% for akinesia, and 77% for tremor 6 months after treatment. Among the two open-label trials of MR-guided focused ultrasound pallidotomy for patients with PD, dyskinesia and overall motor scores improved up to 52% and 45% at 6 months postoperatively. Although MR-guided focused ultrasound thalamotomy is now approved by the U.S. Food and Drug Administration for treatment of parkinsonian tremor, additional high-quality randomized controlled trials are warranted and are underway to determine the safety and efficacy of MR-guided focused ultrasound subthalamotomy and pallidotomy for treatment of the cardinal features of PD. These studies will be paramount to aid clinicians to determine the ideal ablative target for individual patients. Additional work will be required to assess the durability of MR-guided focused ultrasound lesions, ideal timing of MR-guided focused ultrasound ablation in the course of PD, and the safety of performing bilateral lesions. © 2019 International Parkinson and Movement Disorder Society.

Neurological adverse event profile of magnetic resonance imaging-guided focused ultrasound thalamotomy for essential tremor.

BACKGROUND: Magnetic resonance imaging-guided focused ultrasound thalamotomy is approved by the U.S. Food and Drug Administration for treatment of essential tremor. Although this incisionless technology creates an ablative lesion, it potentially avoids serious complications of open stereotactic surgery. OBJECTIVE: To determine the safety profile of magnetic resonance imaging-guided focused ultrasound unilateral thalamotomy for essential tremor, including frequency, and severity of adverse events, including serious adverse events. METHODS: Analysis of safety data for magnetic resonance imaging-guided focused ultrasound thalamotomy (186 patients, five studies). RESULTS: Procedure-related serious adverse events were very infrequent (1.6%), without intracerebral hemorrhages or infections. Adverse events were usually transient and were commonly rated as mild (79%) and rarely severe (1%). As previously reported, abnormalities in sensation and balance were the commonest thalamotomy-related adverse events. CONCLUSION: The overall safety profile of magnetic resonance imaging-guided focused ultrasound thalamotomy supports its role as a new option for patients with medically refractory essential tremor. © 2018 International Parkinson and Movement Disorder Society.

Medical Care Costs Associated With Cancer in Integrated Delivery Systems.

Background: The high economic burden of cancer is projected to continue growing. Cost-of-care estimates are key inputs for comparative effectiveness and economic analyses that aim to inform policies associated with cancer care. Existing estimates are based largely on SEER-Medicare data in the elderly, leaving a knowledge gap regarding costs for patients aged <65 years. Methods: We estimated total and net medical care costs using data on individuals diagnosed with breast, colorectal, lung, or prostate cancer (n=45,522) and noncancer controls (n=314,887) enrolled in 1 of 4 participating health plans. Net costs were defined as the difference in mean total costs between patients with cancer and controls. The phase-of-care approach and Kaplan-Meier Sample Average method were used to estimate mean total and net 1- and 5-year costs (in 2015 US dollars) by cancer site, stage at diagnosis, and age group (<65 and ≥65 years). Results: Total and net costs were consistently highest for lung cancer and lowest for prostate cancer. Net costs were higher across all cancer sites for patients aged <65 years than those aged ≥65 years. Medical care costs for all cancers increased with advanced stage at diagnosis. Conclusions: This study improves understanding of medical care costs for the 4 most common invasive cancers in the United States. Higher costs among patients aged <65 years highlight limitations of relying on SEER-Medicare data alone to understand the national burden of cancer, whereas higher costs for patients with advanced-stage cancer underscore the importance of early detection to curtail high long-term costs. These cost estimates can be used in the development and evaluation of interventions and policies across the cancer care continuum.

Discordance Between Physician Assessment and Patient-Reported Depressive Symptoms in Parkinson Disease.

OBJECTIVE: To assess concordance between physician assessment and patient-reported symptoms when screening for depression in Parkinson disease (dPD). BACKGROUND: Depression in Parkinson disease is highly prevalent (∼40%) and has a significant impact on quality of life and disability, yet physician recognition and treatment remain inadequate. METHODS: One thousand seventy-six patients with PD completed the Brief Symptom Inventory-18 (BSI-18), a screening questionnaire for psychiatric symptoms, which was compared to item #3 (depression) on the Unified Parkinson's Disease Rating Scale (UPDRS). RESULTS: The mean BSI-18 depression score was 51.4 (9.7). Of the 170 (16%) patients screening positive for dPD on the BSI-18, 104 (61%) were not recognized as depressed by neurologists on the UPDRS. Factors associated with lower neurologist recognition included male gender, better mental health quality of life, and lack of antidepressant use. CONCLUSION: More than 60% of patients screening positive for depression on self-report were not recognized by neurologists on the UPDRS. A patient-reported screening tool for depression may improve recognition and management of dPD.