Emergence and rapid transmission of SARS-CoV-2 B.1.1.7 in the United States.

The highly transmissible B.1.1.7 variant of SARS-CoV-2, first identified in the United Kingdom, has gained a foothold across the world. Using S gene target failure (SGTF) and SARS-CoV-2 genomic sequencing, we investigated the prevalence and dynamics of this variant in the United States (US), tracking it back to its early emergence. We found that, while the fraction of B.1.1.7 varied by state, the variant increased at a logistic rate with a roughly weekly doubling rate and an increased transmission of 40%-50%. We revealed several independent introductions of B.1.1.7 into the US as early as late November 2020, with community transmission spreading it to most states within months. We show that the US is on a similar trajectory as other countries where B.1.1.7 became dominant, requiring immediate and decisive action to minimize COVID-19 morbidity and mortality.

Genomic epidemiology identifies emergence and rapid transmission of SARS-CoV-2 B.1.1.7 in the United States.

As of January of 2021, the highly transmissible B.1.1.7 variant of SARS-CoV-2, which was first identified in the United Kingdom (U.K.), has gained a strong foothold across the world. Because of the sudden and rapid rise of B.1.1.7, we investigated the prevalence and growth dynamics of this variant in the United States (U.S.), tracking it back to its early emergence and onward local transmission. We found that the RT-qPCR testing anomaly of S gene target failure (SGTF), first observed in the U.K., was a reliable proxy for B.1.1.7 detection. We sequenced 212 B.1.1.7 SARS-CoV-2 genomes collected from testing facilities in the U.S. from December 2020 to January 2021. We found that while the fraction of B.1.1.7 among SGTF samples varied by state, detection of the variant increased at a logistic rate similar to those observed elsewhere, with a doubling rate of a little over a week and an increased transmission rate of 35-45%. By performing time-aware Bayesian phylodynamic analyses, we revealed several independent introductions of B.1.1.7 into the U.S. as early as late November 2020, with onward community transmission enabling the variant to spread to at least 30 states as of January 2021. Our study shows that the U.S. is on a similar trajectory as other countries where B.1.1.7 rapidly became the dominant SARS-CoV-2 variant, requiring immediate and decisive action to minimize COVID-19 morbidity and mortality.

Genetic testing costs and compliance with clinical best practices.

We sought to determine the costs of genetic testing and compliance with published guidelines and clinical best practices at our institution. A cost analysis was performed comparing the costs of ordered tests to the cost of the recommended testing. This was an approved quality improvement project at a tertiary teaching hospital in California. We identified charts associated with the genetic testing billing codes for common genetic tests through our contracted laboratory (cystic fibrosis genotyping, Breast cancer susceptibility gene (BRCA 1&2), Methylenetetrahydrofolate reductase (MTHFR), factor V Leiden (FVL), prothrombin gene pathogenic variant, alpha-thalassemia, hemochromatosis, and cell-free fetal DNA). Charts were reviewed retrospectively by a licensed, certified genetic counselor to assess the compliance with published clinical practice guidelines identified on GeneReviews and the American College of Obstetricians and Gynecologists (ACOG). Tests were classified as: appropriate, misordered/not indicated, misordered/false reassurance, and misordered/inadequate. We performed a cost analysis for the recommended test changes. We reviewed 114 charts over a three-month period. Forty-four (38.6%) of the tests were misordered based on published clinical practice guidelines: 24 (21%) were misordered/not indicated, 8 (7%) were misordered/false reassurance, and 12 (10.5%) were misordered/inadequate. Costs of ordered testing ($75,177) were compared to recommended testing after review ($54,265), with a total cost savings of $20,912. In clinical practice, over one-third of genetic tests reviewed were misordered. As these tests are a small fraction of all genetic tests at our institution, future studies should broaden the scope of testing evaluated to understand the magnitude of this problem and potential cost savings. Genetic counselor review and involvement in genetic test ordering can decrease inappropriate healthcare expenditures and improve patient care.

Microtensile bond strength of lithium disilicate to zirconia with the CAD-on technique.

PURPOSE: Recently, a novel technique was introduced to combine lithium disilicate and zirconia into one restoration. The purpose of this study was to compare the microtensile bond strength of veneering ceramic to a zirconia core in two techniques: the e.max® CAD-on technique and the Press-on technique. MATERIALS AND METHODS: Group A was prepared by veneering sintered zirconia blocks (e.max® ZirCAD) with lithium disilicate blocks (e.max® CAD) using the CAD-on technique according to manufacturer's instructions. Group B was prepared by taking sintered e.max® ZirCAD blocks and veneering them with fluorapatite glass-ceramic (e.max® ZirPress) using the Press-on technique according to manufacturer's instructions. Each block was loaded in a dynamic cyclic loading machine. The blocks were then sectioned into 1 × 1 mm(2) beams (n = 43) using a precision saw, thermocycled, and loaded in tension until failure on a universal testing machine. A mean and standard deviation were determined per group. Data were analyzed using an unpaired t-test (α = 0.05). RESULTS: The mean microtensile bond strengths were 44.0 ± 13.8 MPa for the CAD-on technique and 14.9 ± 8.8 MPa for the Press-on technique. Significant differences were found between the two groups (p = 2.7E-19). CONCLUSIONS: The CAD-on technique (lithium disilicate/zirconia) resulted in greater microtensile bond strength than the Press-on technique (fluorapatite glass-ceramic/zirconia).

Transfusion-transmitted human T-lymphotropic virus Type I infection in a United States military emergency whole blood transfusion recipient in Afghanistan, 2010.

BACKGROUND: The United States introduced human T-lymphotropic virus Type I (HTLV-I) screening of blood donors in 1988. The US military uses freshly collected blood products for life-threatening injuries when available stored blood components in theater have been exhausted or when these components are unsuccessful for resuscitation. These donors are screened after donation by the Department of Defense (DoD) retrospective testing program. All recipients of blood collected in combat are tested according to policy soon after and at 3, 6, and 12 months after transfusion. CASE REPORT: A 31-year-old US Army soldier tested positive for HTLV-I 44 days after receipt of emergency blood transfusions for severe improvised explosive device blast injuries. One donor's unit tested HTLV-I positive on the DoD-mandated retrospective testing. Both the donor and the recipient tested reactive with enzyme immunoassay and supplemental confirmation by HTLV-I Western blot. The donor and recipient reported no major risk factors for HTLV-I. Phylogenetic analysis of HTLV-I sequences indicated Cosmopolitan subtype, Subgroup B infections. Comparison of long terminal repeat and env sequences revealed molecular genetic linkage of the viruses from the donor and recipient. CONCLUSION: This case is the first report of transfusion transmission of HTLV-I in the US military during combat operations. The emergency fresh whole blood policy enabled both the donor and the recipient to be notified of their HTLV-I infection. While difficult in combat, predonation screening of potential emergency blood donors with Food and Drug Administration-mandated infectious disease testing as stated by the DoD Health Affairs policy should be the goal of every facility engaged with emergency blood collection in theater.

The Armed Services Blood Program: blood support to combat casualty care 2001 to 2011.

BACKGROUND: The Armed Services Blood Program (ASBP) provides the farthest-reaching blood supply in the world. This article provides statistics and a review of blood operations in support of combat casualty care during the last 10 years. It also outlines changes in blood doctrine in support of combat casualty care. METHODS: This is a descriptive overview and review of blood product use and transfusions used by ASBP personnel to support combat operations in Iraq and Afghanistan between October 2001 and November 2011. RESULTS: The ASBP initiated major changes in blood availability and age of blood in theater. In support of data published by physicians in theater, showing improved patient survival when a higher ratio of fresh frozen plasma and red blood cells (RBCs) is achieved, plus the use of platelets, the ASBP increased availability of plasma and established platelet collection facilities in theater. New capabilities included emergency collection of apheresis platelets in the battlefield, availability and transfusion of deglycerolized red cells, rapid diagnostic donor screening, and a new modular blood detachment. Forward surgical facilities that were at one time limited to a blood inventory consisting of RBCs now have a complete arsenal of products at their fingertips that may include fresher RBCs, fresh frozen plasma, cryoprecipitate, and platelets. A number of clinical practice guidelines are in place to address these processes. Changes in blood doctrine were made to support new combat casualty care and damage-control resuscitation initiatives. CONCLUSION: Despite the challenges of war in two theaters of operation, a number of improvements and changes to blood policy have been developed during the last 10 years to support combat casualty care. The nature of medical care in combat operations will continue to be dynamic and constantly evolving. The ASBP needs to be prepared to meet future challenges. LEVEL OF EVIDENCE: Epidemiologic study, level IV.

The effect of surface treatment of the interfacial surface on fatigue-related microtensile bond strength of milled zirconia to veneering porcelain.

PURPOSE: The success of zirconia-reinforced all-ceramic crowns depends on the formation of a stable bond between the zirconia core and the veneering porcelain. The purpose of this study was to test the effects of liner application and airborne particle abrasion of a postsintered Y-TZP core on the bond strength between the zirconia core and veneering porcelain with or without cyclic loading. MATERIALS AND METHODS: Kavo Everest® Y-TZP blank disks were sintered and divided into three treatment groups: airborne particle abrasion, IPS e.max® Ceram Zirliner application, or no surface treatment. The disks were then veneered with IPS e.max® ZirPress veneering porcelain. Half the veneered disks from each group were cyclically loaded. This created six experimental groups: three surface treatment groups cyclically loaded and three not loaded. The disks were then sectioned into microbars for microtensile bond strength (MTBS) testing (40 specimens per group). Specimens were luted to a fixture mount and loaded to failure using a universal testing machine (MTS Insight). The maximum force was measured and bond strength computed. Data were analyzed with a two-way ANOVA and Tukey's HSD test (α= 0.05). RESULTS: Airborne particle abrasion significantly decreased MTBS values (p= 0.043), and ZirLiner application did not have a significant effect on MTBS values compared to control. Cyclic loading did not have a significant effect on MTBS values. The predominant failure mode in all groups was mixed. CONCLUSIONS: Airborne particle abrasion of the interfacial surface of the Everest® Y-TZP core significantly decreased the MTBS to ZirPress veneering porcelain when compared to no interfacial surface treatment. Application of ZirLiner to the interfacial surface of the Everest® Y-TZP core did not significantly increase or decrease the MTBS to ZirPress veneering porcelain, compared to the other surface treatments. Cyclic loading did not affect bond strengths in any of the groups, regardless of surface treatment. Neither cyclic loading nor surface treatment affected the failure mode of the specimens.

Nitric oxide and attenuated reflex cutaneous vasodilation in aged skin.

Thermoregulatory cutaneous vasodilation is diminished in the elderly. The goal of this study was to test the hypothesis that a reduction in nitric oxide (NO)-dependent mechanisms contributes to the attenuated reflex cutaneous vasodilation in older subjects. Seven young (23 +/- 2 yr) and seven older (71 +/- 6 yr) men were instrumented with two microdialysis fibers in the forearm skin. One site served as control (Ringer infusion), and the second site was perfused with 10 mM N(G)-nitro-l-arginine methyl ester to inhibit NO synthase (NOS) throughout the protocol. Water-perfused suits were used to raise core temperature 1.0 degrees C. Red blood cell (RBC) flux was measured with laser-Doppler flowmetry over each microdialysis fiber. Cutaneous vascular conductance (CVC) was calculated as RBC flux per mean arterial pressure, with values expressed as a percentage of maximal vasodilation (infusion of 28 mM sodium nitroprusside). NOS inhibition reduced CVC from 75 +/- 6% maximal CVC (CVC(max)) to 53 +/- 3% CVC(max) in the young subjects and from 64 +/- 5% CVC(max) to 29 +/- 2% CVC(max) in the older subjects with a 1.0 degrees C rise in core temperature. Thus the relative NO-dependent portion of cutaneous active vasodilation (AVD) accounted for approximately 23% of vasodilation in the young subjects and 60% of the vasodilation in the older subjects at this level of hyperthermia (P < 0.001). In summary, NO-mediated pathways contributed more to the total vasodilatory response of the older subjects at high core temperatures. This suggests that attenuated cutaneous vasodilation with age may be due to a reduction in, or decreased vascular responsiveness to, the unknown neurotransmitter(s) mediating AVD.