Timing and severity of inhibitor development in recombinant versus plasma-derived factor VIII concentrates: a SIPPET analysis

Essentials Recombinant factor VIII (rFVIII) was contrasted with plasma-derived FVIII (pdFVIII). In previously untreated patients with hemophilia A, rFVIII led to more inhibitors than pdFVIII. Inhibitors with rFVIII developed earlier, and the peak rate was higher than with pdFVIII. Inhibitors with rFVIII were more severe (higher titre) than with pdFVIII. Summary: Background The development of neutralizing antibodies (inhibitors) against factor VIII (FVIII) is the most severe complication in the early phases of treatment of severe hemophilia A. Recently, a randomized trial, the Survey of Inhibitors in Plasma-Product Exposed Toddlers (SIPPET) demonstrated a 2-fold higher risk of inhibitor development in children treated with recombinant FVIII (rFVIII) products than with plasma-derived FVIII (pdFVIII) during the first 50 exposure days (EDs). Objective/Methods In this post-hoc SIPPET analysis we evaluated the rate of inhibitor incidence over time by every 5 EDs (from 0 to 50 EDs) in patients treated with different classes of FVIII product, made possible by a frequent testing regime. Results The highest rate of inhibitor development occurred in the first 10 EDs, with a large contrast between rFVIII and pdFVIII during the first 5 EDs: hazard ratio 3.14 (95% confidence interval [CI], 1.01\ue2\u80\u939.74) for all inhibitors and 4.19 (95% CI, 1.18\ue2\u80\u9314.8) for high-titer inhibitors. For patients treated with pdFVIII, the peak of inhibitor development occurred later (6\ue2\u80\u9310 EDs) and lasted for a shorter time. Conclusion These results emphasize the high immunologic vulnerability of patients during the earliest exposure to FVIII concentrates, with the strongest response to recombinant FVIII products

A population-based exposure assessment methodology for carbon monoxide: Development of a carbon monoxide passive sampler and occupational dosimeter

Two devices, an occupational carbon monoxide (CO) dosimeter (LOCD), and an indoor air quality (IAQ) passive sampler were developed for use in population-based CO exposure assessment studies. CO exposure is a serious public health problem in the U.S., causing both morbidity and mortality (lifetime mortality risk approximately 10{sup -4}). Sparse data from population-based CO exposure assessments indicate that approximately 10% of the U.S. population is exposed to CO above the national ambient air quality standard. No CO exposure measurement technology is presently available for affordable population-based CO exposure assessment studies. The LOCD and IAQ Passive Sampler were tested in the laboratory and field. The palladium-molybdenum based CO sensor was designed into a compact diffusion tube sampler that can be worn. Time-weighted-average (TWA) CO exposure of the device is quantified by a simple spectrophotometric measurement. The LOCD and IAQ Passive Sampler were tested over an exposure range of 40 to 700 ppm-hours and 200 to 4200 ppm-hours, respectively. Both devices were capable of measuring precisely (relative standard deviation <20%), with low bias (<10%). The LOCD was screened for interferences by temperature, humidity, and organic and inorganic gases. Temperature effects were small in the range of 10{degrees}C to 30{degrees}C. Humidity effects were low between 20% and 90% RH. Ethylene (200 ppm) caused a positive interference and nitric oxide (50 ppm) caused a negative response without the presence of CO but not with CO

A population-based exposure assessment methodology for carbon monoxide: Development of a carbon monoxide passive sampler and occupational dosimeter

Two devices, an occupational carbon monoxide (CO) dosimeter (LOCD), and an indoor air quality (IAQ) passive sampler were developed for use in population-based CO exposure assessment studies. CO exposure is a serious public health problem in the U.S., causing both morbidity and mortality (lifetime mortality risk approximately 10{sup -4}). Sparse data from population-based CO exposure assessments indicate that approximately 10% of the U.S. population is exposed to CO above the national ambient air quality standard. No CO exposure measurement technology is presently available for affordable population-based CO exposure assessment studies. The LOCD and IAQ Passive Sampler were tested in the laboratory and field. The palladium-molybdenum based CO sensor was designed into a compact diffusion tube sampler that can be worn. Time-weighted-average (TWA) CO exposure of the device is quantified by a simple spectrophotometric measurement. The LOCD and IAQ Passive Sampler were tested over an exposure range of 40 to 700 ppm-hours and 200 to 4200 ppm-hours, respectively. Both devices were capable of measuring precisely (relative standard deviation <20%), with low bias (<10%). The LOCD was screened for interferences by temperature, humidity, and organic and inorganic gases. Temperature effects were small in the range of 10{degrees}C to 30{degrees}C. Humidity effects were low between 20% and 90% RH. Ethylene (200 ppm) caused a positive interference and nitric oxide (50 ppm) caused a negative response without the presence of CO but not with CO

Associations of indoor carbon dioxide concentrations, VOCS, environmental susceptibilities with mucous membrane and lower respiratory sick building syndrome symptoms in the BASE study: Analyses of the 100 building dataset

Using the 100 office-building Building Assessment Survey and Evaluation (BASE) Study dataset, we performed multivariate logistic regression analyses to quantify the associations between indoor minus outdoor CO{sub 2} (dCO{sub 2}) concentrations and mucous membrane (MM) and lower respiratory system (Lresp) Sick Building Syndrome (SBS) symptoms, adjusting for age, sex, smoking status, presence of carpet in workspace, thermal exposure, relative humidity, and a marker for entrained automobile exhaust. Using principal components analysis we identified a number of possible sources of 73 measured volatile organic compounds in the office buildings, and assessed the impact of these VOCs on the probability of presenting the SBS symptoms. Additionally we included analysis adjusting for the risks for predisposition of having SBS symptoms associated with the allergic, asthmatic, and environmentally sensitive subpopulations within the office buildings. Adjusted odds ratios (ORs) for statistically significant, dose-dependant associations (p&lt;0.05) for dry eyes, sore throat, nose/sinus congestion, and wheeze symptoms with 100-ppm increases in dCO{sub 2} ranged from 1.1 to 1.2. These results suggest that increases in the ventilation rates per person among typical office buildings will, on average significantly reduce the prevalence of several SBS symptoms, up to 80%, even when these buildings meet the existing ASHRAE ventilation standards for office buildings. VOC sources were observed to play an role in direct association with mucous membrane and lower respiratory irritation, and possibly to be indirectly involved in indoor chemical reactions with ozone that produce irritating compounds associated with SBS symptoms. O-xylene, possibly emitted from furniture coatings was associated with shortness of breath (OR at the maximum concentration = 8, p &lt; 0.05). The environmental sensitivities of a large subset of the office building population add to the overall risk of SBS symptoms (ORs ranging from 2 to above 11) within the buildings

Air Filter Materials and Building Related Symptoms in the BASE Study

This analysis uses existing data on U.S office buildings, collected in the US Environmental Protection Agency's building assessment, Survey and Evaluations (BASE) study to investigate in greater detail the effects of air filters on BRS: specifically, the possibility that certain air filter materials contribute more than others to the burden of BRS among building occupants