Citations

Abstract Objective The aim of this study was to evaluate the efficacy and safety of the dopaminergic‐enhancing agent modafinil/armodafinil (MoArm) as adjunctive treatment for bipolar depression. Methods A comprehensive search of major electronic databases was conducted to identify randomized controlled trials (RCTs) of adjunctive MoArm that included patients with bipolar I (BP‐I) or bipolar II (BP‐II) depression. Data for response/remission and all‐cause discontinuation were analyzed. Effect size was summarized by relative risk (RR) using a random effect model. Results Of 58 studies, five RCTs (N = 795 drug, N = 792 placebo) met inclusion criteria. Four armodafinil studies included only BP‐I patients and one modafinil study included both bipolar subtypes with limited heterogeneity ( I 2 = 34%, P = .19; I 2 = 18%, P = .30). Compared to placebo, augmentation with MoArm was associated with significantly greater rates of treatment response (RR, 1.18; 95% CI, 1.01‐1.37; P = .03) and remission (RR, 1.38; 95% CI, 1.10‐1.73; P = .005). All‐cause discontinuation was not different than placebo (RR, 1.08; 95% CI, 0.89‐1.30; P = .45) with no evidence of increased risk of mood switch or suicide attempts with MoArm (RR, 0.99; 95% CI, 0.39‐2.5; P = .98; RR, 1.02; 95% CI, 0.37‐2.85; P = .97). Conclusion This narrower scope meta‐analysis of one drug for one disease suggests that adjunctive MoArm may represent a novel therapeutic intervention. Further studies delineating the subtypes of bipolar depression responsive to these novel dopaminergic‐enhancing agents are encouraged.

AbstractPurposeHistorical trends and factors likely to influence future pharmaceutical expenditures are discussed, and projections are made for drug spending in 2019 in nonfederal hospitals, clinics, and overall (all sectors).MethodsDrug expenditure data through calendar year 2018 were obtained from the IQVIA National Sales Perspectives database and analyzed. New drug approvals, patent expirations, and other factors that may influence drug spending in hospitals and clinics in 2019 were also reviewed. Expenditure projections for 2019 for nonfederal hospitals, clinics, and overall (all sectors) were made through a combination of quantitative analyses and expert opinion.ResultsU.S. prescription sales in calendar year 2018 totaled $476.2 billion, a 5.5% increase from 2017 spending. The top 3 drugs by expenditures were adalimumab ($19.1 billion), insulin glargine ($9.3 billion), and etanercept ($8.0 billion). Prescription expenditures in nonfederal hospitals totaled $35.8 billion, a 4.8% increase from 2017. Expenditures in clinics in 2018 increased by 13.0% to $80.5 billion. The increase in spending in nonfederal hospitals was largely driven by new products and increased utilization of existing products. The list of the top 25 drugs by expenditures in nonfederal hospitals and clinics was dominated by specialty drugs.ConclusionWe predict continued moderate growth of 4–6% in overall drug expenditures (across the entire U.S. market). We expect the clinic sector to continue to experience high (11–13%) growth in drug spending in 2019. Finally, for nonfederal hospitals we anticipate growth in the range of 3–5%. These estimates are at the national level. Health-system pharmacy leaders should carefully examine local drug utilization patterns to determine their own organization’s anticipated spending in 2019.

SummaryDue to the introduction of newer, more efficacious treatment options, there is a pressing need for policy makers and public health officials to develop or adapt national hepatitis C virus (HCV) control strategies to the changing epidemiological landscape. To do so, detailed, country‐specific data are needed to characterize the burden of chronic HCV infection. In this study of 17 countries, a literature review of published and unpublished data on HCV prevalence, viraemia, genotype, age and gender distribution, liver transplants and diagnosis and treatment rates was conducted, and inputs were validated by expert consensus in each country. Viraemic prevalence in this study ranged from 0.2% in Hong Kong to 2.4% in Taiwan, while the largest viraemic populations were in Nigeria (2 597 000 cases) and Taiwan (569 000 cases). Diagnosis, treatment and liver transplant rates varied widely across the countries included in this analysis, as did the availability of reliable data. Addressing data gaps will be critical for the development of future strategies to manage and minimize the disease burden of hepatitis C.

SummaryFactors influencing the morbidity and mortality associated with viremic hepatitis C virus (HCV) infection change over time and place, making it difficult to compare reported estimates. Models were developed for 17 countries (Bahrain, Bulgaria, Cameroon, Colombia, Croatia, Dominican Republic, Ethiopia, Ghana, Hong Kong, Jordan, Kazakhstan, Malaysia, Morocco, Nigeria, Qatar and Taiwan) to quantify and characterize the viremic population as well as forecast the changes in the infected population and the corresponding disease burden from 2015 to 2030. Model inputs were agreed upon through expert consensus, and a standardized methodology was followed to allow for comparison across countries. The viremic prevalence is expected to remain constant or decline in all but four countries (Ethiopia, Ghana, Jordan and Oman); however, HCV‐related morbidity and mortality will increase in all countries except Qatar and Taiwan. In Qatar, the high‐treatment rate will contribute to a reduction in total cases and HCV‐related morbidity by 2030. In the remaining countries, however, the current treatment paradigm will be insufficient to achieve large reductions in HCV‐related morbidity and mortality.

SummaryThe hepatitis C virus (HCV) epidemic was forecasted through 2030 for 17 countries in Africa, Asia, Europe, Latin America and the Middle East, and interventions for achieving the Global Health Sector Strategy on viral hepatitis targets—“WHO Targets” (65% reduction in HCV‐related deaths, 90% reduction in new infections and 90% of infections diagnosed by 2030) were considered. Scaling up treatment and diagnosis rates over time would be required to achieve these targets in all but one country, even with the introduction of high SVR therapies. The scenarios developed to achieve the WHO Targets in all countries studied assumed the implementation of national policies to prevent new infections and to diagnose current infections through screening.

ObjectivesBipolar disorder (BD) is a complex disease associated with various hereditary traits, including a higher body mass index (BMI). In a prior genome‐wide association study, we found that BMI modified the association of rs12772424 – a common variant in the gene encoding transcription factor 7‐like 2 (TCF7L2) – with risk for BD. TCF7L2 is a transcription factor in the canonical Wnt pathway, involved in multiple disorders, including diabetes, cancer and psychiatric conditions. Here, using an independent sample, we evaluated 26 TCF7L2 single nucleotide polymorphisms (SNPs) to explore further the association of BD with the TCF7L2–BMI interaction.MethodsUsing a sample of 662 BD cases and 616 controls, we conducted SNP‐level and gene‐level tests to assess the evidence for an association between BD and the interaction of BMI and genetic variation in TCF7L2. We also explored the potential mechanism behind the detected associations using human brain expression quantitative trait loci (eQTL) analysis.ResultsThe analysis provided independent evidence of an rs12772424–BMI interaction (p = 0.011). Furthermore, while overall there was no evidence for SNP marginal effects on BD, the TCF7L2–BMI interaction was significant at the gene level (p = 0.042), with seven of the 26 SNPs showing SNP–BMI interaction effects with p < 0.05. The strongest evidence of interaction was observed for rs7895307 (p = 0.006). TCF7L2 expression showed a significant enrichment of association with the expression of other genes in the Wnt canonical pathway.ConclusionsThe current study provides further evidence suggesting that TCF7L2 involvement in BD risk may be regulated by BMI. Detailed, prospective assessment of BMI, comorbidity, and other possible contributing factors is necessary to explain fully the mechanisms underlying this association.

Background and purpose The use of computed tomography angiography (CTA) as the sole vascular imaging study for preoperative planning for clipping of aneurysms is well described in the literature. CTA is widely available, provides quick acquisition, has low morbidity, and low cost. In this study, we describe the accuracy of CTA in determining the blood supply dominance in comparison to standard digital subtraction angiography. Materials and methods Sixty-six patients, with both CTAs and angiograms, were reviewed by two independent neuroradiologists. The posterior cerebral artery was determined to have dominant supply from the posterior communicating artery if it was of similar size to the P2 segment and the P1 segment was smaller by approximately 50%. If the posterior communicating artery and P1 segment were the same size, it was considered to have a dual supply. If P1 and P2 segments were the same caliber and the posterior communicating artery was smaller by 50%, it was deemed to have posterior circulation dominance. Results Based on the findings of our reviewers, CTA had a sensitivity and specificity of 69% and 96%, respectively, in predicting the presence of a fetal PCA. The positive predictive value was found to be 82% while a negative predictive value was estimated as 93%. A small-caliber P1 segment and large-caliber posterior communicating artery led to inaccurate interpretations of the CTAs. Conclusion This study shows that one cannot accurately predict blood supply dominance of the posterior cerebral artery. Knowledge of the blood flow dominance is essential when clipping a posterior communicating artery aneurysm to avoid compromise in posterior circulation.

OBJECT The authors sought to determine whether flow diversion with the Pipeline Embolization Device (PED) can approximate microsurgical decompression in restoring function after cranial neuropathy following carotid artery aneurysms. METHODS This multiinstitutional retrospective study involved 45 patients treated with PED across the United States. All patients included presented between November 2009 and October 2013 with cranial neuropathy (cranial nerves [CNs] II, III, IV, and VI) due to intracranial aneurysm. Outcome analysis included clinical and procedural variables at the time of treatment as well as at the latest clinical and radiographic follow-up. RESULTS Twenty-six aneurysms (57.8%) were located in the cavernous segment, while 6 (13.3%) were in the clinoid segment, and 13 (28.9%) were in the ophthalmic segment of the internal carotid artery. The average aneurysm size was 18.6 mm (range 4–35 mm), and the average number of flow diverters placed per patient was 1.2. Thirty-eight patients had available information regarding duration of cranial neuropathy prior to treatment. Eleven patients (28.9%) were treated within 1 month of symptom onset, while 27 (71.1%) were treated after 1 month of symptoms. The overall rate of cranial neuropathy improvement for all patients was 66.7%. The CN deficits resolved in 19 patients (42.2%), improved in 11 (24.4%), were unchanged in 14 (31.1%), and worsened in 1 (2.2%). Overtime, the rate of cranial neuropathy improvement was 33.3% (15/45), 68.8% (22/32), and 81.0% (17/21) at less than 6, 6, and 12 months, respectively. At last follow-up, 60% of patients in the isolated CN II group had improvement, while in the CN III, IV, or VI group, 85.7% had improved. Moreover, 100% (11/11) of patients experienced improvement if they were treated within 1 month of symptom onset, whereas 44.4% (12/27) experienced improvement if they treated after 1 month of symptom onset; 70.4% (19/27) of those with partial deficits improved compared with 30% (3/10) of those with complete deficits. CONCLUSIONS Cranial neuropathy caused by cerebral aneurysm responds similarly when the aneurysm is treated with the PED compared with open surgery and coil embolization. Lower morbidity and higher occlusion rates obtained with the PED may suggest it as treatment of choice for some of these lesions. Time to treatment is an important consideration regardless of treatment modality.