Metabolic syndrome, number of risk factors, and specific combinations of risk factors are markers for high utilization and costs among patients receiving medical care. Diabetes and certain risk clusters are major drivers of utilization and costs.

Background: The recognition of distinct molecular subgroups within cholangiocarcinoma (CC), along with the increasing availability of targeted therapies, suggests that further characterization of the prevalence and prognosis of frequently occurring subgroups may assist with the development of more effective treatment approaches for the management of CC. A systematic review was performed to investigate the prevalence of isocitrate dehydrogenase 1 (IDH1) mutations (mIDH1) in patients with CC, the possible clinical and prognostic significance of mIDH1, and the presence of co-mutations in tumors with mIDH1. Methods: This review was conducted using the Cochrane dual-reviewer methodology and the Preferred Reporting Items for Systematic Reviews and Meta-Analyses protocol (PRISMA-P) guidelines. Searches were performed in Embase, MEDLINE, the Cochrane Central Trials Register and Database of Systematic Reviews, and other Cochrane Library assets using terms for CC and mIDH1 with no language or date restrictions for articles published up to December 31, 2017. Searches were also performed of abstracts presented at the following conferences in 2016 and 2017: American Society of Clinical Oncology (ASCO), ASCO-Gastrointestinal Cancers Symposium (ASCO-GI), the European Society for Medical Oncology (ESMO), and ESMO-Asia. Screening was performed separately by two reviewers and cross-checked. Any discrepancies between reviewers were resolved by a senior researcher. Data from all selected references were recorded in a data extraction grid. Results: A total of 46 publications met the inclusion criteria and were included in the systematic review.Of these publications, 45 reported the frequency of mIDH1 among a total sample of 5,393 patients with CC. mIDH1 was enriched in intrahepatic CC (ICC), with 552 (13.1%; 95% CI, 12.1-14.2) of the 4,214 patients with ICC having the mutation compared with 9 (0.8%; 95% CI, 0.4-1.5%) of the 1,123 patients with extrahepatic CC (ECC). The percentage of females with mIDH1 CC (66.2%; 95% CI, 57.7-73.7%) was higher than in the overall CC population (44.4%). The frequency of mIDH1 in patients with ICC reported in individual studies ranged from 4.5-55.6%, and a significantly higher frequency was reported in non-Asian centers compared with Asian centers (weighted mean, 16.5% vs. 8.8%; P<0.001). The prevalence of mIDH1 in patients with ICC at USA centers was 18.0% (95% CI, 16.4-19.8%). Eleven publications reported the prevalence of co-mutations in patients with mIDH1 ICC, with the most frequent being AT-rich interactive domain-containing protein 1A (ARID1A) (22.0%), BRCA1-associated protein 1 (BAP1) (15.5%), and PBRM1 (13.3%). Eight publications investigated the possible prognostic significance of mIDH1. None of the studies reported a statistically significant association between mIDH1 and overall survival (OS), progression-free survival (PFS), or time to progression. Conclusions: This systematic review substantiates the prevalence of mIDH1 in CC and further 752 Boscoe et al. A systematic review of mIDH1 in CC

Refractory MG patients have significantly greater clinical burden and are more likely to utilize intensive healthcare resources than nonrefractory patients. Furthermore, refractory patients may be at greater risk of crises throughout the disease course than previous studies have suggested. Muscle Nerve, 2018.

For the COMPANION trial patients, the use of CRT-P and CRT-D was associated with a cost-effectiveness ratio below generally accepted benchmarks for therapeutic interventions of 50,000 dollars per QALY to 100,000 dollars per QALY. This suggests that the clinical benefits of CRT-P and CRT-D can be achieved at a reasonable cost.

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Objectives: Myasthenia gravis (MG) may be refractory to traditional therapies. Quality of life (QOL) and disease burden in patients with refractory and nonrefractory MG were compared using Myasthenia Gravis Foundation of America MG Patient Registry data. Methods: Adults aged 18 years or older with MG diagnosed ≥2 years before enrollment were included. Participants with refractory MG had received ≥2 previous and 1 current MG treatment and had MG Activities of Daily Living Scale total score ≥6 at enrollment; other participants had nonrefractory MG. MG QOL 15-item scale (MG-QOL15) scores were compared. Results: In total, 56 participants with refractory and 717 participants with nonrefractory MG enrolled. Participants with refractory MG had significantly higher mean (SD) MG-QOL15 total scores [31.4 (11.1) vs. 20.8 (15.0), P < 0.0001] and were more likely to have had exacerbations, emergency department visits, and recent hospitalizations. Conclusions: Participants with refractory MG experience worse QOL and greater clinical burden than those with nonrefractory disease.

Background: Qualitative data are lacking on decision making and factors surrounding changes in employment for patients with multiple sclerosis (MS). This study aimed to increase our understanding of the key symptoms and factors leading patients with MS to leave work or reduce employment. Methods: Adults with MS who reported leaving the workforce, reducing work hours, or changing jobs due to MS in the past 6 months were recruited from four US clinical sites. Patients participated in semistructured interviews to discuss MS symptoms and reasons for changing employment status. All interviews were transcribed and coded for descriptive analyses. Results: Twenty-seven adults (mean age = 46.3 years, mean duration of MS diagnosis = 10.9 years) with a range of occupations participated; most were white (81.5%) and female (70.4%). Physical symptoms (eg, fatigue, visual deficits) (77.8%) were the most common reasons for employment change; 40.7% of patients reported at least one cognitive symptom (eg, memory loss). Fatigue emerged as the most pervasive symptom and affected physical and mental aspects of patients' jobs. Most patients (85.2%) reported at least two symptoms as drivers for change. Some patients reported a significant negative impact of loss of employment on their mental status, family life, and financial stability. Conclusions: Fatigue was the most common symptom associated with the decision to leave work or reduce employment and can lead to a worsening of other MS symptoms. Comprehensive symptom management, especially fatigue management, may help patients preserve their employment status.

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