Proptosis and Diplopia Response With Teprotumumab and Placebo vs the Recommended Treatment Regimen With Intravenous Methylprednisolone in Moderate to Severe Thyroid Eye Disease: A Meta-analysis and Matching-Adjusted Indirect Comparison.

IMPORTANCE: Thyroid eye disease can be a debilitating autoimmune disorder characterized by progressive proptosis or diplopia. Teprotumumab has been compared with placebo in randomized clinical trials, but not with intravenous methylprednisolone (IVMP), which sometimes is used in clinical practice for this condition. OBJECTIVE: To conduct a matching-adjusted indirect comparison of teprotumumab vs IVMP vs placebo. DATA SOURCES: Deidentified patient-level data from teprotumumab trials and aggregate-level data from literature on the most recommended regimen of IVMP. STUDY SELECTION: PubMed and Embase were searched for randomized/observational studies using key terms and controlled vocabulary. Full texts of eligible articles were reviewed and cataloged. DATA EXTRACTION AND SYNTHESIS: Conducted by 1 reviewer (R.A.Q.) and 1 verifier (R.B.), including study characteristics, eligibility criteria, baseline characteristics, and outcomes. MAIN OUTCOMES AND MEASURES: Changes in proptosis by millimeter and diplopia response (percentage with ≥1 grade reduction) from baseline to week 12 in patients receiving IVMP and placebo, and to week 24 in patients receiving teprotumumab. RESULTS: The search identified 1019 records, and 6 through manual searches, alerts, and secondary references. After excluding duplicates and screening full-text records, 12 IVMP studies were included in the matching-adjusted indirect comparison (11 for proptosis change [n = 419], 4 for diplopia response [n = 125], and 2 teprotumumab [n = 79] and placebo [n = 83] comparator studies). Treatment with IVMP resulted in a proptosis difference of -0.16 mm (95% CI, -1.55 to 1.22 mm) from baseline to week 12 vs placebo. The proptosis treatment difference between IVMP and teprotumumab of -2.31 mm (95% CI, -3.45 to -1.17 mm) favored teprotumumab. Treatment with IVMP (odds ratio, 2.69; 95% CI, 0.94-7.70) was not favored over placebo in odds of diplopia response; however, teprotumumab was favored over IVMP (odds ratio, 2.32; 95% CI, 1.07-5.03). CONCLUSIONS AND RELEVANCE: This meta-analysis suggests that use of IVMP is associated with a small, typically not clinically relevant, change from baseline in proptosis vs placebo, with modest changes in diplopia. While this nonrandomized comparison suggests that use of teprotumumab, compared with IVMP, is associated with greater improvements in proptosis and may be twice as likely to have a 1 grade or higher reduction in diplopia, randomized trials comparing these 2 treatments would be warranted to determine if 1 treatment is superior to the other to a clinically relevant degree.

Comparative Assessment of Ergonomic Experience with Heads-Up Display and Conventional Surgical Microscope in the Operating Room.

PURPOSE: Musculoskeletal pain issues are prevalent in ophthalmic surgeons and can impact surgeon well-being and productivity. Heads-up displays (HUD) can improve upon conventional microscopes by reducing ergonomic stress. This study compared ergonomic outcomes between HUD and a conventional optical microscope in the operating room, as reported by ophthalmic surgeons in the US. METHODS: An online questionnaire was distributed to a sample of surgeons who had experience operating with HUD. The questionnaire captured surgeon-specific variables, the validated Nordic Musculoskeletal Questionnaire, and custom questions to compare HUD and conventional microscope. A multivariable model was built to identify variables that were likely to predict improvement in pain-related issues. RESULTS: Analysis was conducted on 64 surgeons (37 posterior-segment, 25 anterior-segment, and two mixed) with a mean 14.9 years of practice and 2.3 years using HUD. Most surgeons agreed or strongly agreed that HUD reduced the severity (64%) and frequency (63%) of pain and discomfort, improved posture (73%), and improved overall comfort (77%). Of respondents who experienced headaches, or pain and discomfort during operation, 12 (44%) reported their headaches improved and 45 (82%) reported feeling less pain and discomfort since they started using HUD. The multivariable model indicated the odds of reporting an improvement in pain since introducing the HUD in the operating room were 5.12-times greater for those who used HUD in >50% of their cases (P=0.029). CONCLUSION: This study indicates that heads-up display may be an important tool for wellness in the operating room as it can benefit ophthalmic surgeons across several ergonomic measures.

Health economic impact of first-pass success among patients with acute ischemic stroke treated with mechanical thrombectomy: a United States and European perspective.

BACKGROUND: First-pass effect (FPE), restoring complete or near complete reperfusion (modified Thrombolysis in Cerebral Infarction (mTICI) 2c-3) in a single pass, is an independent predictor for good functional outcomes in the endovascular treatment of acute ischemic stroke. The economic implications of achieving FPE have not been assessed. OBJECTIVE: To assess the economic impact of achieving complete or near complete reperfusion after the first pass. METHODS: Post hoc analyses were conducted using ARISE II study data. The target population consisted of patients in whom mTICI 2c-3 was achieved, stratified into two groups: (1) mTICI 2c-3 achieved after the first pass (FPE group) or (2) after multiple passes (non-FPE group). Baseline characteristics, clinical outcomes, and healthcare resource use were compared between groups. Costs from peer-reviewed literature were applied to assess cost consequences from the perspectives of the United States (USA), France, Germany, Italy, Spain, Sweden, and United Kingdom (UK). RESULTS: Among patients who achieved mTICI 2c-3 (n=172), FPE was achieved in 53% (n=91). A higher proportion of patients in the FPE group reached good functional outcomes (90-day modified Rankin Scale score 0-2 80.46% vs 61.04%, p<0.01). The patients in the FPE group had a shorter mean length of stay (6.10 vs 9.48 days, p<0.01) and required only a single stent retriever, whereas 35% of patients in the non-FPE group required at least one additional device. Driven by improvement in clinical outcomes, the FPE group had lower procedural/hospitalization-related (24-33% reduction) and annual care (11-27% reduction) costs across all countries. CONCLUSIONS: FPE resulted in improved clinical outcomes, translating into lower healthcare resource use and lower estimated costs.

Substance use disorders among youth with chronic physical illness.

This study estimated prevalence of substance use disorder in youth with chronic physical illness; quantified magnitudes of association between different chronic physical illnesses with substance use disorder; and, tested whether mental disorder moderates these associations. Data come from 6,377 individuals aged 15-30 years in the Canadian Community Health Survey-Mental Health. Alcohol, cannabis, or other drug use disorder measured using the WHO Composite International Diagnostic Interview 3.0. Individuals with chronic physical illness were more likely to have other drug use disorder compared to healthy controls (2.4% vs. 1.3%; p < .001), but not more likely to have alcohol (7.8% vs. 6.8%) or cannabis use disorder (5.0% vs. 3.6%). Odds of alcohol use disorder were higher among individuals with musculoskeletal conditions, OR = 1.41 (1.03-1.93), but lower among individuals with neurological conditions, OR = 0.49 (0.33-0.72), compared to healthy controls. No associations were found for cannabis use disorder. Odds of other drug use disorder were higher among individuals with endocrine conditions, OR = 2.88 (1.37-6.06). In the presence vs. absence of major depressive disorder, odds for substance use disorder were higher among individuals with respiratory or endocrine conditions. However, odds were lower among individuals with comorbid neurological and major depressive disorders or comorbid respiratory and generalized anxiety disorders. The complexity of the association between chronic physical illness and substance use disorder is compounded when accounting for the moderating effect of mental disorder, which in some contexts, results in a reduced likelihood of substance use disorder in youth with chronic physical illness.

A budget impact analysis of a magnetic sphincter augmentation device for the treatment of medication-refractory mechanical gastroesophageal reflux disease: a United States payer perspective.

BACKGROUND: Medication-refractory gastroesophageal reflux disease (GERD) is sometimes treated with laparoscopic Nissen fundoplication (LNF); however, this is a non-reversible procedure associated with important side effects and the need for repeat surgery. Removable magnetic sphincter augmentation (MSA) devices are an alternative, effective, and safe treatment option for such patients who have some lower esophageal sphincter function. The objective of this study was to assess the economic impact of introducing MSA technology (i.e., LINX Reflux Management System) into current practice from a US-payer perspective. METHODS: An economic budget impact model was developed over a 1-year time horizon that compared current treatment of GERD patients who are medically managed (but refractory) or receiving LNF to future treatment of GERD patients that included a mix of patients treated with medical management only, LNF, or MSA. Resources included within the analyses were index procedures (inpatient and outpatient use), reoperations (revisions and removals), readmissions, healthcare visits, diagnostic tests, procedures, and medications. Medicare payment rates were typically used to inform unit costs. RESULTS: Assuming a hypothetical commercial insurance population of 1 million members, the base-case analysis estimated a net cost savings of $111,367 with introduction of the MSA. This translates to a savings of $0.01 per member per month. Results were largely driven by avoided inpatient procedures with use of the MSA device. Alternative analyses exploring the potential impact of increasing surgical volumes predicted that results would remain cost saving if the proportion of MSA market share taken from LNF was ≥ 90%. CONCLUSIONS: This study predicts that the introduction of the MSA device would lead to favorable budget impact results for the treatment of medication-refractory mechanical GERD for commercial payers. Future analyses will benefit from inclusion of middle-ground treatments as well as longer time horizons.

Microwave ablation compared with radiofrequency ablation for treatment of hepatocellular carcinoma and liver metastases: a systematic review and meta-analysis.

PURPOSE: Percutaneous ablation techniques, including microwave ablation (MWA) and radiofrequency ablation (RFA), have become important minimally invasive treatment options for liver cancer. This systematic review compared MWA with RFA for treatment of liver cancer. METHODS: The systematic review and meta-analysis followed the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. A systematic search of MEDLINE, EMBASE, and Cochrane Central Register of Controlled Trials was conducted for randomized and observational studies published from 2006 onwards. A random-effects model was used for meta-analyses and local tumor progression (LTP), technique efficacy, overall survival (OS), disease-free survival (DFS), intrahepatic de novo lesions (IDL), extrahepatic metastases (EHM), length of stay (LOS), and complications were analyzed. Subgroup and sensitivity analyses were also conducted. RESULTS: Of 1379 studies identified, 28 randomized and observational studies met inclusion criteria. The main analysis demonstrated that LTP was significantly reduced by 30% with MWA versus RFA (RR=0.70; P=0.02) (all studies) and by 45% with MWA versus RFA (RR=0.55; P=0.007) (randomized studies only). There were no significant differences between MWA and RFA for other efficacy and safety outcomes. Higher frequency (2450 MHz) and larger tumor size (≥2.5 cm) are amongst variables that may be associated with improved outcomes for MWA. Sensitivity analyses were generally congruent with the main results. CONCLUSION: MWA is at least as safe and effective as RFA for treating liver cancer and demonstrated significantly reduced LTP rates. Future studies should assess time and costs associated with these two treatment modalities.

An Epidemiological Study of Substance Use Disorders Among Emerging and Young Adults.

OBJECTIVES: We investigated the prevalence of substance use disorders (SUDs) among emerging adults and quantified the extent to which emerging adults, compared with young adults, have increased odds for SUDs. METHODS: Data were from the 2012 Canadian Community Health Survey-Mental Health (CCHS-MH). Respondents were 15 to 39 y of age ( n = 9228) and were categorized as: early emerging adults (15 to 22 y); late emerging adults (23 to 29 y); and, young adults (30 to 39 y). SUDs [alcohol or drug abuse/dependence (AAD or DAD)] were measured using the WHO Composite International Diagnostic Interview 3.0. The prevalence of SUDs was compared across age groups, and odds ratios (OR) and 95% confidence intervals (CI) were computed from logistic regression models adjusting for sociodemographic and health covariates. Analyses were weighted to maintain representativeness to the Canadian population. RESULTS: The prevalence of AAD was 8.0%, 6.6%, and 2.7% for early emerging adults, late emerging adults, and young adults, respectively. For DAD, the prevalence was 6.4%, 3.6%, and 1.3%. After covariate adjustment, early and late emerging adults had greater odds of reporting AAD (OR = 3.2, 95% CI = 2.2 to 4.9 and OR = 2.4, 95% CI = 1.6 to 3.4, respectively) or DAD (OR = 4.2, 95% CI = 2.5 to 7.0 and OR = 2.5, 95% CI = 1.6 to 4.1, respectively) compared with young adults. Differences between early and late emerging adults were not significant. CONCLUSION: Emerging adults are at increased odds for SUDs. Lack of differences between early and late emerging adults provide evidence of the extension of emerging adulthood into the late 20s. Findings have implications for the provision of screening and treatment of SUDs during this developmental period.

Procedure costs associated with the use of Harmonic devices compared to conventional techniques in various surgeries: a systematic review and meta-analysis.

BACKGROUND: As compared to conventional techniques, recent meta-analyses have reported cost savings with Harmonic devices; however, only in thyroidectomy. Thus, the aim of this study was to evaluate the costs associated with Harmonic devices versus conventional techniques across a range of surgical procedures. METHODS: A systematic search of MEDLINE, EMBASE, and Cochrane Library was conducted from inception to October 01, 2016 without language restrictions to identify randomized controlled trials comparing Harmonic devices to conventional techniques and reporting procedure costs (operating time plus operating equipment/consumables/device costs). Costs were pooled using the ratio of geometric means, and a random effects model was applied. Sensitivity analyses varying statistical methods, number of included studies, and cost outcomes were completed to test the robustness of the results. RESULTS: Thirteen studies met the inclusion criteria. A total of 561 and 540 participants had procedures performed with Harmonic devices and conventional methods, respectively, with procedures including gastrectomy, thyroidectomy, colectomy, cholecystectomy, Nissen fundoplication, and pancreaticoduodenectomy. As compared to conventional methods, Harmonic devices reduced total procedure costs by 8.7% (p=0.029), resulting in an absolute reduction of US$227.77 from mean conventional technique costs, derived primarily from a reduction in operating time costs. When operating time costs, excluding operating equipment/consumables/device costs, were analyzed, costs were reduced by $544 per procedure with the use of Harmonic devices. The results from all sensitivity analyses demonstrated cost reductions with Harmonic devices. CONCLUSION: This systematic review and meta-analysis showed that despite a higher device cost, Harmonic devices provide a statistically significant reduction in procedure costs, derived primarily from a reduction in operating time costs, across surgical procedures. In addition to functionality benefits, Harmonic devices may represent a potentially cost saving method to reduce overall hospital resource use. Future research should focus on potential costs and benefits from use of Harmonic devices in procedures not covered here.

Chronic disruptive pain in emerging adults with and without chronic health conditions and the moderating role of psychiatric disorders: Evidence from a population-based cross-sectional survey in Canada.

BACKGROUND AND AIMS: There has been a growth in the proportion of emerging adults vulnerable to pain-related sequelae of chronic health conditions (CHCs). Given the paucity of research during this important developmental period, this study investigated the association between CHCs and chronic disruptive pain among emerging adults and the extent to which psychiatric disorders moderate this association. METHODS: Data come from the 2012 Canadian Community Health Survey - Mental Health (CCHS-MH). This cross-sectional survey included 5987 participants that were 15-30 years of age and self-reported their CHCs (n=2460, 41%) and the extent to which pain impacted daily functioning using items from the Health Utilities Index Mark 3 (HUI 3). Group comparisons between respondents with CHCs and healthy controls were made using chi-square tests. Odds ratios (OR) and 95% confidence intervals (CI) were computed from ordinal logistic regression models adjusting for sociodemographic covariates. Product-term interactions between CHCs and psychiatric disorders were included in the models to explore moderating effects. All analyses were weighted to maintain representativeness of the study sample to the Canadian population. RESULTS: The mean age of participants was 23.5 (SE 0.1) years and 48% were female. Compared to healthy controls, a greater proportion of participants with CHCs reported having chronic pain (20.3% vs. 4.5%, p<0.001). Among those with chronic pain, respondents with CHCs reported a greater number of activities prevented because of chronic disruptive pain (χ2=222.28, p<0.001). Similarly, in logistic regression models, participants with CHCs had greater odds of reporting chronic disruptive pain (OR=4.94, 95% CI=4.08-5.99). Alcohol (ß=-0.66; p=0.025) and drug abuse/dependence disorders (ß=-1.24; p=0.012) were found to moderate the association between CHCs and chronic disruptive pain. Specifically, the probability of chronic disruptive pain was higher for emerging adults without CHCs and with alcohol or drug disorders; however, among participants with CHCs, probability was higher for those without these disorders. CONCLUSIONS: There is a robust association between CHCs and chronic disruptive pain. The moderating effects suggest that alcohol or drug disorders are especially harmful for emerging adults without CHCs and contribute to higher levels of chronic disruptive pain; however, among those with CHCs, alcohol and illicit drugs may be used as a numbing agent to blunt chronic disruptive pain. IMPLICATIONS: Findings from this study have implications for the integration and coordination of services to design strategies aimed at managing chronic disruptive pain and preventing pain-related disabilities later in life. Within the health system, healthcare providers should engage in dialogues about mental health and substance use regularly with emerging adults, be proactive in screening for psychiatric disorders, and continue to monitor the impact of pain on daily functioning. Given the age range of emerging adults, there is tremendous opportunity for clinicians to work cooperatively with colleagues in the education system to support emerging adults with and without CHCs. Overall, clinicians, researchers, educators, and those in social services should continue to be mindful of the complex interrelationships between physical and mental health and chronic disruptive pain and work cooperatively to optimize health outcomes and prevent pain-related disabilities among emerging adults.