Scott D. Halpern

Correlated Size Variations in Human Visual Cortex, Lateral Geniculate Nucleus, and Optic Tract

We have examined several components of the human visual system to determine how the dimensions of the optic tract, lateral geniculate nucleus (LGN), and primary visual cortex (V1) vary within the same brain. Measurements were made of the cross-sectional area of the optic tract, the volumes of the magnocellular and parvocellular layers of the LGN, and the surface area and volume of V1 in one or both cerebral hemispheres of 15 neurologically normal human brains obtained at autopsy. Consistent with previous observations, there was a two- to threefold variation in the size of each of these visual components among the individuals studied. Importantly, this variation was coordinated within the visual system of any one individual. That is, a relatively large V1 was associated with a commensurately large LGN and optic tract, whereas a relatively small V1 was associated with a commensurately smaller LGN and optic tract. This relationship among the components of the human visual system indicates that the development of its different parts is interdependent. Such coordinated variation should generate substantial differences in visual ability among humans.

Validation of 6-Minute Walk Distance as a Surrogate End Point in Pulmonary Arterial Hypertension Trials

Background— Nearly all available treatments for pulmonary arterial hypertension have been approved based on change in 6-minute walk distance (&Dgr;6MWD) as a clinically important end point, but its validity as a surrogate end point has never been shown. We aimed to validate the difference in &Dgr;6MWD against the probability of a clinical event in pulmonary arterial hypertension trials. Methods and Results— First, to determine whether &Dgr;6MWD between baseline and 12 weeks mediated the relationship between treatment assignment and development of clinical events, we conducted a pooled analysis of patient-level data from the 10 randomized placebo-controlled trials previously submitted to the US Food and Drug Administration (n=2404 patients). Second, to identify a threshold effect for the &Dgr;6MWD that indicated a statistically significant reduction in clinical events, we conducted a meta-regression among 21 drug/dose-level combinations. &Dgr;6MWD accounted for 22.1% (95% confidence interval, 12.1%– 31.1%) of the treatment effect (P<0.001). The meta-analysis showed an average difference in &Dgr;6MWD of 22.4 m (95% confidence interval, 17.4–27.5 m), favoring active treatment over placebo. Active treatment decreased the probability of a clinical event (summary odds ratio, 0.44; 95% confidence interval, 0.33–0.57). The meta-regression revealed a significant threshold effect of 41.8 m. Conclusions— Our results suggest that &Dgr;6MWD does not explain a large proportion of the treatment effect, has only modest validity as a surrogate end point for clinical events, and may not be a sufficient surrogate end point. Further research is necessary to determine whether the threshold value of 41.8 m is valid for long-term outcomes or whether it differs among trials using background therapy or lacking placebo controls entirely.

Comparison of Site of Death, Health Care Utilization, and Hospital Expenditures for Patients Dying With Cancer in 7 Developed Countries

IMPORTANCE Differences in utilization and costs of end-of-life care among developed countries are of considerable policy interest. OBJECTIVE To compare site of death, health care utilization, and hospital expenditures in 7 countries: Belgium, Canada, England, Germany, the Netherlands, Norway, and the United States. DESIGN, SETTING, AND PARTICIPANTS Retrospective cohort study using administrative and registry data from 2010. Participants were decedents older than 65 years who died with cancer. Secondary analyses included decedents of any age, decedents older than 65 years with lung cancer, and decedents older than 65 years in the United States and Germany from 2012. MAIN OUTCOMES AND MEASURES Deaths in acute care hospitals, 3 inpatient measures (hospitalizations in acute care hospitals, admissions to intensive care units, and emergency department visits), 1 outpatient measure (chemotherapy episodes), and hospital expenditures paid by insurers (commercial or governmental) during the 180-day and 30-day periods before death. Expenditures were derived from country-specific methods for costing inpatient services. RESULTS The United States (cohort of decedents aged >65 years, N = 211,816) and the Netherlands (N = 7216) had the lowest proportion of decedents die in acute care hospitals (22.2.% and 29.4%, respectively). A higher proportion of decedents died in acute care hospitals in Belgium (N = 21,054; 51.2%), Canada (N = 20,818; 52.1%), England (N = 97,099; 41.7%), Germany (N = 24,434; 38.3%), and Norway (N = 6636; 44.7%). In the last 180 days of life, 40.3% of US decedents had an intensive care unit admission compared with less than 18% in other reporting nations. In the last 180 days of life, mean per capita hospital expenditures were higher in Canada (US

Randomized Trial of Four Financial-Incentive Programs for Smoking Cessation

21,840), Norway (US

Delay in recognition of pulmonary arterial hypertension: factors identified from the REVEAL Registry.

19,783), and the United States (US

Randomized trial of

18,500), intermediate in Germany (US

5 versus

16,221) and Belgium (US

10 monetary incentives, envelope size, and candy to increase physician response rates to mailed questionnaires

15,699), and lower in the Netherlands (US

Management of the Potential Organ Donor in the ICU: Society of Critical Care Medicine/American College of Chest Physicians/Association of Organ Procurement Organizations Consensus Statement

10,936) and England (US

Survival Differences Following Lung Transplantation Among US Transplant Centers

9342). Secondary analyses showed similar results. CONCLUSIONS AND RELEVANCE Among patients older than 65 years who died with cancer in 7 developed countries in 2010, end-of-life care was more hospital-centric in Belgium, Canada, England, Germany, and Norway than in the Netherlands or the United States. Hospital expenditures near the end of life were higher in the United States, Norway, and Canada, intermediate in Germany and Belgium, and lower in the Netherlands and England. However, intensive care unit admissions were more than twice as common in the United States as in other countries.