Association between upper limb movements during drumming and cognition in older adults with cognitive impairment and dementia at a nursing home: a pilot study.

Background: Despite the association between motor dysfunction and dementia, quantitative assessment of dementia-related specific motor dysfunction in patients with severe dementia is difficult. Thus, this study aimed to develop a new method to measure upper limb motor function in people with dementia. Methods: We examined the relationship between dementia severity and dementia-related specific motor dysfunction using the Mini-Mental State Examination (MMSE), a dementia screening test. Participants comprised 16 nursing home residents with a mean age of 86 years and MMSE score of 14.56 (range, 1-23) Points. Participants were seated in a circle and instructed to play a drum that was placed in their lap using mallets (drumsticks) in their dominant hand. Acceleration and gyroscopic sensors were attached to their wrists to collect data on arm movements while drumming. Upper limb motor characteristics were confirmed by recording acceleration and arm movement during drumming and analyzing the correlation with handgrip strength. Results: Handgrip strength was correlated with arm elevation angle during drumming. The arm elevation angle displayed a significant regression equation with the MMSE score and showed the best regression equation along with handgrip strength (adjusted R2 = 0.6035, p = 0.0009). Conclusion: We developed a new method using drums to measure upper limb motor function in people with dementia. We also verified that the average arm elevation angle during drumming could predict cognitive dysfunction. This system may be used to monitor people with dementia in a simple and safe way.

Clinical and Serological Follow-Up of 216 Patients with Hematological Malignancies after Vaccination with Pfizer-BioNT162b2 mRNA COVID-19 in a Real-World Study.

Hematological malignancies (HMs) have heterogeneous serological responses after vaccination due to disease or treatment. The aim of this real-world study was to analyze it after Pfizer-BioNT162b2 mRNA vaccination in 216 patients followed up for 1 year. The first 43 patients had an initial follow-up by a telemedicine (TM) system with no major events reported. The anti-spike IgG antibodies were checked 3-4 weeks post-first vaccination and every 3-4 months, by two standard bioassays and a rapid serological test (RST). Vaccine boosts were given when the level was <7 BAU/mL. Patients who did not seroconvert after 3-4 doses received tixagevimab/cilgavimab (TC). Fifteen results were discordant between two standard bioassays. Good agreement was observed between the standard and RST in 97 samples. After two doses, 68% were seroconverted (median = 59 BAU/mL) with a median of 162 BAU/mL and 9 BAU/mL, respectively, in untreated and treated patients (p < 0.001), particularly for patients receiving rituximab. Patients with gammaglobulin levels < 5 g/L had reduced seroconversion compared to higher levels (p = 0.019). The median levels were 228 BAU/mL post-second dose if seroconverted post-first and second, or if seroconverted only post-second dose. A total of 68% of post-second dose negative patients were post-third dose positive. A total of 16% received TC, six with non-severe symptomatic COVID-19 within 15-40 days. Personalized serological follow-up should apply particularly to patients with HMs.

The Effect of Cognitive Training with Neurofeedback on Cognitive Function in Healthy Adults: A Systematic Review and Meta-Analysis.

BACKGROUND: Cognitive training aims to improve cognitive function through cognitive tasks or training games. Neurofeedback is a technique to monitor brain signals with either visual or auditory feedback. Previous studies suggest that a combination of cognitive training and neurofeedback has a superior effect on cognitive functions compared with cognitive training alone. However, no systematic reviews and meta-analyses of the benefits of cognitive training with neurofeedback (CTNF) exist. The purpose of this study was to examine the beneficial effects of CTNF in healthy adults using a systematic review and multilevel meta-analysis. METHODS: PubMed, Scopus, PsychoINFO, and MEDLINE were searched for research papers reporting the results of interventions using CTNF. RESULTS: After an initial screening of 234 records, three studies using near-infrared spectroscopy (NIRS) and one study using electroencephalography were extracted from the database. We performed a multi-level meta-analysis with three NIRS studies including 166 participants (mean ages ranged from 21.43 to 65.96 years). A multi-level meta-analysis revealed that CTNF has a beneficial effect on the episodic, long-term, and working memory domains. CONCLUSIONS: Although three studies were included in the systematic review and meta-analysis, our results indicate that CTNF using NIRS would lead to improvements in memory functioning.

The Effect of Music-Based Intervention on General Cognitive and Executive Functions, and Episodic Memory in People with Mild Cognitive Impairment and Dementia: A Systematic Review and Meta-Analysis of Recent Randomized Controlled Trials.

BACKGROUND: Music-based intervention has been used as first-line non-pharmacological treatment to improve cognitive function for people with mild cognitive impairment (MCI) or dementia in clinical practice. However, evidence regarding the effect of music-based intervention on general cognitive function as well as subdomains of cognitive functions in these individuals is scarce. OBJECTIVE: To evaluate the efficacy of music-based interventions on a wide range of cognitive functions in people with MCI or dementia. METHOD: We searched the effect of various music therapies using randomized controlled trials on cognitive function using several databases. Studies based on any type of dementia or MCI were combined. The effects of music-based intervention on each cognitive function were pooled by meta-analysis. RESULTS: A total of 19 studies involving n = 1024 participants (mean age ranged from 60 to 87 years old) were included. We found statistically significant improvements in MMSE (general cognitive function), the Frontal Assessment Battery (executive function), and the Auditory Verbal Learning Test (episodic memory). CONCLUSIONS: This study provides positive evidence to support music-based interventions for improving a wide range of cognitive functions in older adults with MCI and dementia. Therefore, we recommend increased use of music in people's homes, day care centers and nursing homes. This study was registered with PROSPERO, number 250383.

Benefits of VR Physical Exercise on Cognition in Older Adults with and without Mild Cognitive Decline: A Systematic Review of Randomized Controlled Trials.

It is well known that physical exercise has beneficial effects on cognitive function in older adults. Recently, several physical exercise programs with virtual reality (VR) have been proposed to support physical exercise benefits. However, it is still unclear whether VR physical exercise (VR-PE) has positive effects on cognitive function in older adults. The purpose of this study was to conduct a systematic review (SR) of the effects of VR-PE on cognitive function in older adults with and without cognitive decline. We used academic databases to search for research papers. The criteria were intervention study using any VR-PE, participants were older adults with and without mild cognitive decline (not dementia), and cognitive functions were assessed. We found that 6 of 11 eligible studies reported the significant benefits of the VR-PE on a wide range of cognitive functions in aging populations. The SR revealed that VR-PE has beneficial effects on the inhibition of executive functions in older adults with and without mild cognitive decline. Moreover, VR-PE selectively leads to improvements in shifting and general cognitive performance in healthy older adults. The SR suggests that VR-PE could be a successful approach to improve cognitive function in older adults with and without cognitive decline.

Cognitive Training with Neurofeedback Using NIRS Improved Cognitive Functions in Young Adults: Evidence from a Randomized Controlled Trial.

(1) Background: A previous study has shown that cognitive training with neurofeedback (CT-NF) using down-regulation improves cognitive functions in young adults. Neurofeedback has two strategies for manipulating brain activity (down-regulation and upregulation). However, the benefit of CT-NF with the upregulation of cognitive functions is still unknown. In this study, we investigated whether the upregulation of CT-NF improves a wide range of cognitive functions compared to cognitive training alone. (2) Methods: In this double-blinded randomized control trial (RCT), 60 young adults were randomly assigned to one of three groups: CT-NF group, CT alone group, and an active control (ACT) group who played a puzzle game. Participants in the three groups used the same device (tablet PC and 2ch NIRS (near-infrared spectroscopy)) and performed the training game for 20 min every day for four weeks. We measured brain activity during training in all groups, but only CT-NFs received NF. We also measured a wide range of cognitive functions before and after the intervention period. (3) Results: The CT-NF groups showed superior beneficial effects on episodic memory, working memory, and attention compared to the CT alone and ACT groups. In addition, the CT-NF group showed an increase in brain activity during CT, which was associated with improvements in cognitive function. (4) Discussion: This study first demonstrated that the CT-NF using the upregulation strategy has beneficial effects on cognitive functions compared to the CT alone. Our results suggest that greater brain activities during CT would enhance a benefit from CT.

Treatment Patterns and Health Resource Use Among Patients with Metastatic Gastroenteropancreatic Neuroendocrine Tumors Treated at a Tertiary Referral Center.

BACKGROUND: Although an increasing number of treatments have become available for patients with advanced gastroenteropancreatic neuroendocrine tumors (GEP-NETs), there remains little consensus on treatment sequence and its impact on health care resource use (HRU). We sought to describe treatment patterns and HRU, in a cohort of patients with metastatic GEP-NETs treated at a tertiary referral center in the U.S. MATERIALS AND METHODS: We identified patients with a well-differentiated, metastatic GEP-NET evaluated at Dana-Farber Cancer Institute between July 2003 and May 2015. For these patients, we describe the sequence of treatment regimens received for their disease, together with associated HRU. RESULTS: We identified 682 patients with advanced GEP-NETs. Of these patients, 597 (87.0%) initiated ≥1 treatment over the follow-up period. The mean age at diagnosis was 58.5 years, 50.2% were men, and 94.0% were white. A total of 83.1% initiated a somatostatin analog (SSA) as their first-line treatment, with 55% and 31% of patients continuing with second- and third-line therapies. A total of 31.2% of patients with SSAs underwent dose escalation to above standard dose. In this setting, patients with pancreatic neuroendocrine tumors were more commonly treated with cytotoxic regimens than other NET tumor types and also had higher HRU. CONCLUSION: Our study suggests that, at a tertiary referral center, patients with advanced NETs commonly received multiple courses of treatments. Our data suggest a clear preference for use of SSAs as a first-line treatment for patients with advanced NETs, with SSAs commonly escalated and continued throughout the course of treatment in combination with other regimens. IMPLICATIONS FOR PRACTICE: The current study demonstrates the common use of somatostatin analog as a first-line therapy for patients with advanced gastroenteropancreatic neuroendocrine tumors as well as the incorporation of multiple different treatment regimens in the treatment course of patients with this disease.

Cost effectiveness and impact on quality of life of abobotulinumtoxinA and onabotulinumtoxinA in the treatment of children with lower limb spasticity in Canada.

Background: Injectable botulinum neurotoxins are a mainstay of treatment for pediatric spasticity. AbobotulinumtoxinA and onabotulinumtoxinA are both injectable toxin therapies used to treat pediatric lower limb (PLL) spasticity in Canada. The objective of this study was to assess the cost-effectiveness of abobotulinumtoxinA vs. onabotulinumtoxinA in the treatment of PLL spasticity in Canada.Methods: A probabilistic Markov cohort model with a 2-year time horizon was developed, with health states defined by response to therapy, as characterized by the goal attainment scale (GAS). Based on randomized controlled trial evidence, response to therapy was similar or higher for abobotulinumtoxinA relative to onabotulinumtoxinA; uncertainty was incorporated into model parameters, however, as the two therapies have not been compared head-to-head. Canadian resource use and cost data were incorporated.Results: In the base case, abobotulinumtoxinA generated 1.48 quality-adjusted life years over the model time horizon, compared to 1.47 for onabotulinumtoxinA. AbobotulinumtoxinA was associated with cost savings of $123 CAD, reflecting lower costs in both medication acquisition and health services. The estimated improvement to quality of life and reduced costs result in an estimate of economic dominance for abobotulinumtoxinA over onabotulinumtoxinA. This dominant result persisted across probabilistic and scenario analyses.Key points for decision makersBased on a review of available clinical evidence, abobotulinumtoxinA was found to have significant and/or numerical efficacy benefits to onabotulinumtoxinA on functional outcomes (Goal Attainment Scale) and tone (Modified Ashworth Scale) and in the treatment of pediatric lower limb spasticityIn this cost-effectiveness analysis, abobotulinumtoxinA was found to be associated with greater quality-adjusted life years and lower costs than onabotulinumtoxinA (economically dominant)A limitation of this analysis was the uncertainty around key parameters. Specifically, the lack of head-to-head comparison data for the two therapies, and variable data regarding likely onabotulinumtoxinA dosing in PLL in clinical practice. However, across a range of plausible scenarios, the economic dominant result remained.

Treatment Patterns and Survival among Patients with Metastatic Gastroenteropancreatic Neuroendocrine Tumours in Sweden - a Population-based Register-linkage and Medical Chart Review Study.

Background: Gastroenteropancreatic neuroendocrine tumours (GEP-NETs) are neoplasms derived from the endocrine system in the gastrointestinal tract and pancreas. Treatment options include surgery; pharmacological treatments like somatostatin analogues (SSA), interferon alpha, molecular targeted therapy and chemotherapy; and peptide receptor radionuclide therapy. The objective of this study was to describe treatment patterns and survival among patients with metastatic GEP-NET grade 1 or 2 in Sweden. Methods: Data was obtained via linkage of nationwide registers. Patients diagnosed with metastatic GEP-NET grade 1 or 2 in Sweden between 2005 and 2013 were included (n=811; National population). In addition, medical chart review was performed for the subpopulation diagnosed at Sahlgrenska University Hospital, Gothenburg (n=127; Regional population). Treatment patterns, including treatment sequences, and overall survival were assessed. Results: Most patients had small intestinal NET (76%). In the regional population, 72% had grade 1 tumours; 50% had functioning tumours. The two most common first-line treatments were surgery (57%) and SSA (25%). After first-line surgery, 46% received SSA, while 40% had no further treatment. After first-line SSA, 52% received surgery, while 27% had no further treatment. Overall median survival time from date of diagnosis was 7.0 years (95% CI 6.2-not reached). Among patients with distant metastases, pancreatic NET (vs. small intestinal NET) was associated with poorer survival (HR 1.9; 95% CI 1.1-3.3), as were liver metastases (HR 3.2; 95% CI 1.5-7.0). Conclusions: First-line surgery was typically followed by SSA or no further treatment. Among patients with distant metastases, pancreatic NET or liver metastases were associated with a poorer survival.

Cost-of-illness of metastatic gastroenteropancreatic neuroendocrine tumours in Sweden-A population-based register-linkage study.

The objective was to estimate the cost-of-illness of grades 1 and 2 metastatic gastroenteropancreatic neuroendocrine tumours (GEP-NETs) in Sweden in 2013 in a population-based study including all patients diagnosed between 2005 and 2013. Data were obtained from national registers, and patients who utilised healthcare resources due to metastatic GEP-NETs in 2013 were included. The study included 478 patients (mean age 64 [SD=11] years, 51% men). The majority (80%) had small intestinal NET, 10% had pancreatic NET, and 41% had carcinoid syndrome. The total cost-of-illness was €12,189,000 in 2013, of which direct costs constituted 77% and costs from production loss constituted 22%. The largest contributor to the direct medical costs was prescription drugs (54%; primarily somatostatin analogues [91% of the total drug cost]). Production loss due to sickness absence constituted 52% of the total costs of production loss. The total annual cost per patient was €25,500. By patient group, the cost was €24,800 (95% CI €21,600-€28,100) for patients with small intestinal NET, €37,300 (95% CI €23,300-€51,300) for those with pancreatic NET and €18,600 (95% CI €12,600-€24,500) for patients with other GEP-NETs. To conclude, the total annual cost of grades 1 and 2 metastatic GEP-NETs in Sweden was €25,500 per patient and year.

Second-line cabozantinib versus nivolumab in advanced renal cell carcinoma: Systematic review and indirect treatment comparison.

BACKGROUND: Nivolumab and cabozantinib, two new treatment options for previously-treated advanced/metastatic renal cell carcinoma (aRCC), have recently been approved. METHODS: Two independent reviewers performed study selection, data extraction, and risk of bias assessment. Indirect treatment comparisons were carried out by directly assessing HR differences and statistical modeling of Kaplan-Meier curves from these two trials. RESULTS: Publications identified showed that no head-to-head comparisons had been carried out. Two indirect treatment comparisons used agreed that there was no significant difference in OS between cabozantinib and nivolumab and that cabozantinib significantly improved PFS compared to nivolumab. CONCLUSIONS: The field of aRCC treatments is evolving rapidly, creating opportunities for individualized treatments and challenges for clinicians to keep up with the evidence. In lieu of availability of direct comparisons of all options, advanced modeling results presented herein can help to inform and improve personalized treatments.

Cost-effectiveness comparison of cabozantinib with everolimus, axitinib, and nivolumab in the treatment of advanced renal cell carcinoma following the failure of prior therapy in England.

PURPOSE: The aim of this study was to compare the cost-effectiveness of cabozantinib with the standard of care in England in adult patients with advanced renal cell carcinoma (aRCC), following prior vascular endothelial growth factor receptor (VEGFR)-targeted therapy. METHODS: We developed a partitioned-survival model with three health states to assess the cost-effectiveness of cabozantinib and its comparators. The model time horizon was 30 years. Efficacy and safety data were derived from pivotal clinical trials (METEOR: NCT01865747, CheckMate025: NCT01668784, and AXIS: NCT00678392). METEOR data were used for a direct comparison of cabozantinib and everolimus. Cabozantinib and nivolumab were compared indirectly, whereas equal efficacy for axitinib and everolimus was assumed based on a previously published expert opinion. For all efficacy endpoints, the best-fitting log-logistic or fractional polynomial curves were used to estimate outcomes. Utilities were converted from the 5-level EQ-5D version instrument applied during the METEOR study for specific health states. Reductions in utility scores due to adverse events were applied. English costs (eg, drug prices) and resource use (eg, visit to consultant) data were used. RESULTS: The total treatment cost was estimated to be 84,136 Great British Pounds (GBP) per patient treated with cabozantinib. The health gains were 2.26 life-years (LYs) and 1.78 quality-adjusted LYs (QALYs). The incremental cost-effectiveness ratios (ICERs) versus axitinib and everolimus were 98,967 GBP/QALY and 137,450 GBP/QALY, respectively. Cabozantinib was less costly and more effective than nivolumab; the incremental cost was -6,742 GBP and the QALY difference was 0.18. CONCLUSION: Treatment with cabozantinib was more effective than treatment with axitinib or everolimus but was associated with higher total costs. When compared with nivolumab, cabozantinib represents an efficient option with nominally better efficacy and lower costs.

A retrospective study to assess resource utilization and costs in patients with post-stroke spasticity in the United Kingdom.

OBJECTIVE: Post-stroke spasticity (PSS) is a common complication following stroke. This study describes the differences in healthcare resource utilization between patients who do and do not develop PSS in the UK. METHODS: Adults registered in The Health Improvement Network database with a recorded stroke between 2007 and 2011 were included. PSS was identified through Read codes; machine learning was used to retrospectively identify unrecorded PSS events. Patients with diagnosed or predicted PSS in the 12 months after stroke were matched to those with no PSS on age, sex, number of strokes, socioeconomic status, and comorbidities using the nearest neighbor algorithm. Utilization and costs associated with general practitioner visits, nurse visits, hospitalizations, referrals to specialists, laboratory tests, and medications in the 12 months after stroke were compared. RESULTS: Overall, 2,951 PSS cases were matched to 37,753 controls. During the first year, more PSS cases visited a physiotherapist (19% vs 7%) and occupational therapist (12% vs 5%) compared to controls. A greater proportion of cases were also referred to specialists (76% vs 64%) and hospitalized (33% vs 9%) compared to controls. Medication for spasticity was, on average, 14.68 prescriptions for cases and 5.64 for controls. Total mean costs per patient were £1,270 (standard deviation [SD] = 772) and £635 (SD = 273) for cases and controls, respectively. CONCLUSION: Costs after stroke for patients developing PSS are twice as high compared to patients who do not develop it, with the major driver being the number of hospital admissions. This highlights the need for better recording and closer management of PSS.

Patient-reported health state utilities in metastatic gastroenteropancreatic neuroendocrine tumours - an analysis based on the CLARINET study.

BACKGROUND: Gastroenteropancreatic neuroendocrine tumours (GEP-NETs) are rare cancers most often found in the gastrointestinal system or the pancreas. However, patient-reported health state utilities based on clinical trials have not been previously reported in this disease area. METHODS: The CLARINET study collected EORTC QLQ-C30 data from patients in both stable and progressive disease states, although data for the latter were only available during the early stage of progression due to trial design. Using published algorithms, data were mapped to EQ-5D utility values. Random-effects generalised least squares models were used to investigate the impacts of progression status, tumour site and other patient characteristics on mapped utility values. RESULTS: In total, 1053 observations from 204 patients were mapped to EQ-5D utilities using the McKenzie mapping algorithm. The final random-effects model included age, gender, baseline utility and progression status as covariates; it was not feasible to investigate time-to-death utility due to a limit number of deaths in the CLARINET study. Tumour location (midgut vs pancreas) does not seem to affect utility. However, the difference in utilities based on progression status is statistically significant (p < 0.05) in the base case analysis, and the estimated utilities for stable and progressive disease are 0.776 and 0.726, respectively. Furthermore, scenario analyses showed that utility for progressive disease is numerically lower than for stable disease, but this may not be statistically significant in scenarios where alternative Longworth mapping algorithm was used. CONCLUSIONS: Patients with GEP-NETs experience worse utility values in the progressive disease state compared to the stable disease state, based on patient-reported health-related quality of life (HRQL) data from the CLARINET study. The decline of utility in the progressive disease state may be underestimated because progressive HRQL data were only collected shortly after the progression event in the trial. The estimated trial-based utilities can be used in future economic evaluations for GEP-NET treatments and to provide more insights to physicians on patient-reported quality of life outcomes in GEP-NETs. TRIAL REGISTRATION: CLARINET EU Clinical Trials Register Number, 2005-004904-35 .

Cost-effectiveness analysis of abobotulinumtoxinA for the treatment of cervical dystonia in the United Kingdom.

BACKGROUND: Cervical dystonia (CD) involves painful involuntary contraction of the neck and shoulder muscles and abnormal posture in middle-aged adults. Botulinum neurotoxin type A (BoNT-A) is effective in treating CD but little is known about its associated cost-effectiveness. OBJECTIVE: To evaluate the cost-effectiveness of abobotulinumtoxinA for treating CD from the UK payer perspective. METHODS: A Markov model was developed to evaluate the cost-effectiveness of abobotulinum-toxinA versus best supportive care (BSC) in CD, with a lifetime horizon and health states for response, nonresponse, secondary nonresponse, and BSC in patients with CD (mean age: 53 years; 37% male). Clinical improvement measured using Toronto Western Spasmodic Torticollis Rating Scale (TWSTRS) was mapped to utility using data from a randomized trial of abobotulinumtoxinA. Health care resource use, costs, and other inputs were from the British National Formulary, Personal Social Services Research Unit, published literature, or expert opinion. Costs and outcomes were discounted at 3.5% per annum. RESULTS: In the base case, the incremental lifetime quality-adjusted life-years (QALYs) gained from abobotulinumtoxinA arm versus BSC was 0.253 per patient, whereas the incremental cost was £7,160, leading to an incremental cost-effectiveness ratio (ICER) of £30,468 per QALY. One-way sensitivity analyses showed that these results were sensitive to the proportion of responders to abobotulinumtoxinA at first injection, duration between injections, the number of reinjections allowed among primary nonresponders, and any difference in baseline TWSTRS value between the BSC and abobotulinumtoxinA arms. Probabilistic sensitivity analysis showed that abobotulinumtoxinA was cost-effective 46% and 49% of times at thresholds of £20,000 and £30,000 per QALY, respectively. Scenarios are considered including vial-sharing, productivity losses, secondary response/nonresponse at subsequent injections, 5-year time horizon, and alternative reinjection intervals for BoNT-As produced ICERs ranging from cost-saving to £40,777 per QALY, versus BSC. CONCLUSION: AbobotulinumtoxinA was found to be cost-effective in treating adults with CD, at acceptable willingness-to-pay thresholds in the UK.

Association Between Tumor Progression Endpoints and Overall Survival in Patients with Advanced Neuroendocrine Tumors.

Endpoints related to tumor progression are commonly used in clinical trials of novel therapeutic agents for neuroendocrine tumors (NETs). Whether improved tumor control translates into improved overall survival (OS), however, is uncertain. We assessed associations between tumor progression endpoints and OS in observational cohorts of patients with advanced neuroendocrine tumors treated with somatostatin analogs or with everolimus. We identified 440 patients with advanced NET who had received treatment with single-agent somatostatin analogs and 109 patients treated with everolimus, all of whom were treated at our institution and were evaluable for both tumor progression and survival. We assessed associations between progression-free survival (PFS) and OS by using the Kendall tau test, and we assessed associations between tumor progression and OS by using a landmark analysis. In the 440 patients treated with somatostatin analogs, we observed a significant correlation between PFS and OS by using the Kendall tau test (0.31; p < .0001). Additionally, the development of progressive disease was associated with OS in a landmark analysis, at landmark times of 6, 12, 18, and 24 months. In the 109 patients treated with everolimus, we similarly observed a significant correlation between PFS and OS by using the Kendall tau test (0.44; p < .0001) and associations between progressive disease and OS by using a landmark analysis at 3, 6, and 12 months. In these observational cohorts of patients with metastatic NET treated with single-agent somatostatin analogs or everolimus, longer times to disease progression and longer PFS were both associated with improved OS. Our findings support the continued use of disease progression endpoints in NET clinical trials. The Oncologist 2017;22:165-172Implications for Practice: Clinical trials in patients with advanced neuroendocrine tumors have used progression-free survival as a primary endpoint. While there is a general assumption that slowing or halting tumor growth is beneficial, little direct evidence links improvements in progression endpoints to improvements in overall survival. This study assessed associations between tumor progression endpoints and overall survival in observational cohorts of patients with advanced neuroendocrine tumor treated with somatostatin analogs or everolimus. Longer times to disease progression and improved progression-free survival were both associated with improved overall survival. The findings support the continued use of tumor progression endpoints in clinical trials for neuroendocrine tumors.

Comorbidities, treatment patterns and cost-of-illness of acromegaly in Sweden: a register-linkage population-based study.

OBJECTIVE: Acromegaly is a complex endocrine disease with multiple comorbidities. Treatment to obtain biochemical remission includes surgery, medical therapy and radiation. We aimed to describe comorbidities, treatment patterns and cost-of-illness in patients with acromegaly in Sweden. DESIGN: A nationwide population-based study. METHODS: Patients with acromegaly were identified and followed in national registers in Sweden. Longitudinal treatment patterns were assessed in patients diagnosed between July 2005 and December 2013. The cost-of-illness during 2013 was estimated from a societal perspective among patients diagnosed between 1987 and 2013. RESULTS: Among 358 patients with acromegaly (48% men, mean age at diagnosis 50.0 (s.d. 15.3) years) at least one comorbidity was reported in 81% (n = 290). The most common comorbidities were hypertension (40%, n = 142), neoplasms outside the pituitary (30%, n = 109), hypopituitarism (22%, n = 80) and diabetes mellitus (17%, n = 61). Acromegaly treatment was initiated on average 3.7 (s.d. 6.9) months after diagnosis. Among the 301 treated patients, the most common first-line treatments were surgery (60%, n = 180), somatostatin analogues (21%, n = 64) and dopamine agonists (14%, n = 41). After primary surgery, 24% (n = 44) received somatostatin analogues. The annual per-patient cost was €12 000; this was €8700 and €16 000 if diagnosed before or after July 2005, respectively. The cost-of-illness for acromegaly and its comorbidities was 77% from direct costs and 23% from production loss. CONCLUSIONS: The prevalence of comorbidity is high in patients with acromegaly. The most common first-line treatment in acromegalic patients was surgery followed by somatostatin analogues. The annual per-patient cost of acromegaly and its comorbidities was €12 000.

Anxious and depressive symptoms in the French Asbestos-Related Diseases Cohort: risk factors and self-perception of risk.

Background: Asbestos is known to be an independent risk factor for lung and pleural cancers. However, to date, little attention has been paid to the psychological effects of asbestos exposure among exposed subjects. The objectives of this study were to estimate the prevalence of anxious and depressive symptoms among >2000 French participants of the Asbestos-Related Diseases Cohort (ARDCO), 6 years after their inclusion, to identify the risk factors associated with those anxious and depressive symptoms and to evaluate the impact of the asbestos-risk perception. Methods: The ARDCO was constituted in four regions of France between October 2003 and December 2005, by including former asbestos workers. Between 2011 and 2012, participants of the ARDCO program were invited to undergo another chest CT scan 6 years after the previous scan. Participants were asked to complete questionnaires including asbestos exposure assessment, Hospital Anxiety and Depression Scale (HADS), asbestos-risk perception and self-perception of asbestos-related diseases. Results: Among the 2225 participants, 2210 fully completed questionnaires were collected and analyzed. The prevalence of symptoms of probable anxiety and probable depression was 19.7% and 9.9%, respectively. The risk of anxious and depressive symptoms was independently associated with self-perception of the intensity of asbestos exposure, asbestos-risk perception and self-perception of asbestos-related diseases. Conclusion: The results obtained in this large study confirm that previously asbestos-exposed subjects are likely to develop anxious and depressive symptoms. Finally, implications related to the prevention of anxiety and depression among asbestos-exposed workers is discussed.

Predictive analysis for identifying potentially undiagnosed post-stroke spasticity patients in United Kingdom.

PURPOSE OF THE RESEARCH: Spasticity is one of the well-recognized complications of stroke which may give rise to pain and limit patients' ability to perform daily activities. The predisposing factors and direct effects of post-stroke spasticity also involve high management costs in terms of healthcare resources, and case-control designs are required for establishing such differences. Using 'The Health Improvement Network' (THIN) database, such a study would not provide reliable estimates since the prevalence of post-stroke spasticity was found to be 2%, substantially below the most conservative previously reported estimates. The objective of this study was to use predictive analysis techniques to determine if there are a substantial number of potentially under-recorded patients with post-stroke spasticity. METHODS: This study used retrospective data from adult patients with a diagnostic code for stroke between 2007 and 2011 registered in THIN. Two algorithm approaches were developed and compared, a statistically validated data-trained algorithm and a clinician-trained algorithm. RESULTS: A data-trained algorithm using Random Forest showed better prediction performance than clinician-trained algorithm, with higher sensitivity and only marginally lower specificity. Overall accuracy was 75% and 72%, respectively. The data-trained algorithm predicted an additional 3912 records consistent with patients developing spasticity in the 12months following a stroke. CONCLUSIONS: Using machine learning techniques, additional unrecorded post-stroke spasticity patients were identified, increasing the condition's prevalence in THIN from 2% to 13%. This work shows the potential for under-reporting of PSS in primary care data, and provides a method for improved identification of cases and control records for future studies.

AbobotulinumtoxinA in the management of cervical dystonia in the United Kingdom: a budget impact analysis.

BACKGROUND: Cervical dystonia (CD) can be effectively managed by a combination of botulinum neurotoxin A (BoNT-A) and conventional therapy (skeletal muscle relaxants and rehabilitative therapy), but the costs of different interventions in the UK vary. METHODS: A budget impact model was developed from the UK payer perspective with a 5-year time horizon to evaluate the effects of changing market shares of abobotulinumtoxinA, onabotulinumtoxinA, and incobotulinumtoxinA, and best supportive care from the UK payer perspective. Epidemiological and resource use data were retrieved from the published literature and clinical expert opinion. Deterministic sensitivity analyses were performed to determine the parameters most influential on the budgetary findings under base case assumptions. RESULTS: Under base case assumptions, an increased uptake of abobotulinumtoxinA showed an accumulated savings of £2,250,992 by year 5. Treatment per patient per year with onabotulinumtoxinA and incobotulinumtoxinA costs more when compared to treatment with abobotulinumtoxinA. One-way sensitivity analyses showed that the prevalence of CD, dose per injection of each of the BoNT-As, and time to reinjection of incobotulinumtoxinA and abobotulinumtoxinA influenced the base case findings most. CONCLUSION: There is potential for cost savings associated with the greater use of abobotulinumtoxinA rather than other BoNT-A treatments, permitting more patients to benefit more from effective BoNT-A treatment with a fixed budget.