WIN‐R revisited

Abstract

We thank Drs. Han and Smith for their thoughtful editorial 1 that accompanied our 2 papers describing results of the WIN-R (WeightBased Dosing of Peginterferon alfa-2b and Ribavirin) trial, 2,3 in which patients with chronic hepatitis C were treated with peginterferon (PEG-IFN) alfa-2b 1.5 g/kg/week plus flat-dose (FD; 800 mg/day) or weight-based dose (WBD; 800-1400 mg/day) ribavirin (RBV). The authors appropriately focused on the importance and superiority of WBD RBV in hepatitis C virus genotype 1-infected patients and provided an excellent review of the treatment of African Americans. However, several points require correction or clarification.The authors state that before 2001, the accepted dose of RBV was 800 mg. Actually, RBV was approved for use with standard, unmodified interferon alfa-2b at doses of 1000-1200 mg in the late 1990s. Later, RBV was approved in the United States for use with PEG-IFN alfa-2b at a dose of 800 mg; currently, the approved dose is 800-1200 mg, based on body weight, in the rest of the world. When using PEG-IFN alfa-2a, the approved RBV dose is 1000-1200 mg in the United States and abroad. Therefore, the statement "currently approved therapies recommend 'standard' WBD RBV in combination with PEG-IFN alfa-2a or 2b" is inaccurate. In fact, there is no "standard" WBD of RBV. A main objective of the WIN-R trial was to evaluate whether the regimen approved in many countries-PEG-IFN alfa-2b 1.5 g/kg/week plus WBD RBV (800-1200 mg/day)-was superior to the U.S.-approved regimen of PEG-IFN alfa-2b 1.5 g/ kg/week plus RBV 800 mg/day. Further, because there are many heavy (Ͼ105 kg) patients in the United States, WIN-R also evaluated a novel, 1400-mg/day RBV dosage, which is not approved anywhere. Although not mentioned in the editorial, we reported equivalent sustained virologic response (SVR) rates in patients weighing Ͼ105 kg and receiving RBV 1400 mg/day compared with patients weighing Յ105 kg and receiving RBV 800-1200 mg/day, as well as equivalent hematologic safety across weight categories. We regard this as an important additional finding of the study that should lead to consideration of RBV 1400 mg in heavy patients weighing Ͼ105 kg.The authors of the editorial ascribed to us a suggestion, which we did not make, that the WBD range of RBV used in our study was superior to that used in the study of Hadziyannis et al.,4 in which RBV 800 mg/day was compared with RBV 1000-1200 mg/day (both in combination with flat-dose PEG-IFN alfa-2a [180 g/week]), based on a greater relative difference in SVR rates between the FD and WBD groups in our study. We made this comparison only with regard to African Americans with genotype 1 infection in the WIN-R trial, 3 in whom the increment in SVR with WBD RBV was greater than in the overall patient cohorts of either study. [2][3][4] The intent in our primary paper 2 in citing the study by Hadziyannis et al. 4 was to underscore the demonstration in the WIN-R trial that a broad WBD range of RBV, combined with weight-based PEG-IFN alfa-2b, produces equivalen...

Assessing Impacts of Atmospheric Conditions on Efficiency and Siting of Large-Scale Direct Air Capture Facilities

“…Meteorological data at 1 × 1° latitude/longitude grid spacing was obtained from the National Oceanic and Atmospheric Administration CarbonTracker measurement and modeling system . CarbonTracker is an inverse model of atmospheric CO 2 .…”

“…Meteorological data at 1 × 1° latitude/longitude grid spacing was obtained from the National Oceanic and Atmospheric Administration CarbonTracker measurement and modeling system. 13 CarbonTracker is an inverse model of atmospheric CO 2 . That is CarbonTracker models gridded atmospheric CO 2 by adjusting inputs and removals of CO 2 at the surface of the Earth until they show the best agreement with observations.…”

“… Average annual CO 2 concentration (ppm) of the lowest atmospheric layer in each 1 × 1° grid cell for the contiguous US for calendar year 2018 using data from CarbonTracker. 13 …”

“…In addition to the well-known local variations in temperature and humidity, the CO 2 available in ambient air also varies spatially and temporally. General circulation models have shown that the spatial distribution of global CO 2 concentration is nonuniform, and measurements show that some locations record larger annual amplitudes of the CO 2 cycle than others. , These inhomogeneities and variations in atmospheric pressure among locations on continental scales mean that the amount of CO 2 available for a fixed volume of ambient air is far from uniform among geographic locations. Previous analyses of DAC process efficiency have not considered these effects in a systematic way …”