Increasing COVID-19 vaccination in the United States: projected impact on cases, hospitalizations, and deaths by age and racial group.

OBJECTIVES: Minority populations in the United States face a disproportionate burden of illness from COVID-19 infection and have lower vaccination rates compared with other groups. This study estimated the equity implications of increased COVID-19 vaccination in the United States, with a focus on the number of cases, hospitalizations, and deaths avoided. STUDY DESIGN: This was an observational real-world modeling study. METHODS: Data from the Centers for Disease Control and Prevention (CDC) were used to identify the remaining unvaccinated US population by county, age, and race as of October 22, 2021. The number of COVID-19 cases, hospitalizations, and deaths avoided were calculated based on case incidence and death data from the CDC, along with data on race- and age-specific hospitalization multipliers, under a scenario in which half of the remaining unvaccinated population per county, race, and age group obtained a full vaccine regimen. RESULTS: Vaccinating half of the remaining unvaccinated population in each age and race subgroup within counties would result in an estimated 22.09 million COVID-19 cases avoided, 1.38 million hospitalizations avoided, and 150,000 deaths avoided over 12 months. Some minority groups, particularly Black and Hispanic/Latino populations, were projected to experience substantial benefits from increased vaccination rates as they face both lower vaccination rates and worse outcomes if infected with COVID-19. CONCLUSIONS: Increasing COVID-19 vaccination in the United States not only benefits the population as a whole but also serves as a potentially useful lever to reduce the disproportionate burden of COVID-19 illness among minority populations.

Parathyroid suppression therapy normalizes chronic kidney disease-induced elevations in cortical bone vascular perfusion: a pilot study.

Interventions that alter PTH levels in an animal model of chronic kidney disease have effects on the perfusion of bone and bone marrow. INTRODUCTION: Patients with chronic kidney disease (CKD) have accelerated bone loss, vascular calcification, and abnormal biochemistries, together contributing to an increased risk of cardiovascular disease and fracture-associated mortality. Despite evidence of vascular pathologies and dysfunction in CKD, our group has shown that cortical bone tissue perfusion is higher in a rat model of high-turnover CKD. The goal of the present study was to test the hypothesis that parathyroid hormone (PTH) suppressive interventions would normalize cortical bone vascular perfusion in the setting of CKD. METHODS: In two separate experiments, 35-week-old CKD animals and their normal littermates underwent intra-cardiac fluorescent microsphere injection to assess the effect of 10 weeks of PTH suppression (Experiment 1: calcium supplementation, Experiment 2: calcimimetic treatment) on alterations in bone tissue perfusion. RESULTS: In Experiment 1, CKD animals had serum blood urea nitrogen (BUN) and PTH levels significantly higher than NL (+ 182% and + 958%; p < 0.05). CKD+Ca animals had BUN levels that were similar to CKD, while PTH levels were significantly lower and comparable to NL. Both femoral cortex (+ 220%, p = 0.003) and tibial cortex (+ 336, p = 0.005) tissue perfusion were significantly higher in CKD animals when compared to NL; perfusion was normalized to those of NL in CKD+Ca animals. MicroCT analysis of the proximal tibia cortical porosity showed a trend toward higher values in CKD (+ 401%; p = 0.017) but not CKD+Ca (+ 111%; p = 0.38) compared to NL. Experiment 2, using an alternative method of PTH suppression, showed similar results as those of Experiment 1. CONCLUSIONS: These data demonstrate that PTH suppression-based interventions normalize cortical bone perfusion in the setting of CKD.

Skeletal accumulation of fluorescently tagged zoledronate is higher in animals with early stage chronic kidney disease.

This work examines the skeletal accumulation of fluorescently tagged zoledronate in an animal model of chronic kidney disease. The results show higher accumulation in 24-h post-dose animals with lower kidney function due to greater amounts of binding at individual surfaces. INTRODUCTION: Chronic kidney disease (CKD) patients suffer from increased rates of skeletal-related mortality from changes driven by biochemical abnormalities. Bisphosphonates are commonly used in reducing fracture risk in a variety of diseases, yet their use is not recommended in advanced stages of CKD. This study aimed to characterize the accumulation of a single dose of fluorescently tagged zoledronate (FAM-ZOL) in the setting of reduced kidney function. METHODS: At 25 weeks of age, FAM-ZOL was administered to normal and CKD rats. Twenty-four hours later, multiple bones were collected and assessed using bulk fluorescence imaging, two-photon imaging, and dynamic histomorphometry. RESULTS: CKD animals had significantly higher levels of FAM-ZOL accumulation in the proximal tibia, radius, and ulna, but not in lumbar vertebral body or mandible, based on multiple measurement modalities. Although a majority of trabecular bone surfaces were covered with FAM-ZOL in both normal and CKD animals, the latter had significantly higher levels of fluorescence per unit bone surface in the proximal tibia. CONCLUSIONS: These results provide new data regarding how reduced kidney function affects drug accumulation in rat bone.

Economic burden of privately insured non-vertebral fracture patients with osteoporosis over a 2-year period in the US.

UNLABELLED: This study assesses the costs of non-vertebral osteoporosis-related fractures patients compared with osteoporosis patients without fractures, focusing on the second year following a fracture. Since fracture patients remained more costly in the second year, their economic burden extends beyond the year in which the fracture occurs. INTRODUCTION: The purpose of this study is to examine the comorbidity profile, resource use, and direct costs of patients who incur osteoporosis-related non-vertebral (NV) fractures in the United States during the 2 years following an incident fracture, focusing on the second year following a fracture. METHODS: Osteoporosis patients (ICD-9-CM: 733.0) with a NV fracture (hip, femur, pelvis, lower leg, upper arm, forearm, rib, and multiple sites) were selected from a privately insured health insurance claims database (>8 million lives, ages 18-64, 1999-2006). These NV fracture patients were randomly matched 1:1 on age, gender, employment status, and geographic region to controls with osteoporosis but without a fracture history. Year-by-year and month-by-month rates of comorbidities, resource use, and direct costs were calculated for the matched sample (N = 3,781). RESULTS: Comorbidity rates and resource use remained significantly higher among NV fracture patients during second year following an NV fracture compared with controls, although absolute rates of comorbidities and service utilization declined. Mean direct excess costs for NV fracture patients fell from $5,267 in the first year to $2,072 in the second year after a fracture, but remained statistically significant (p < 0.01). Patients with fractures of the pelvis, hip, and femur had the highest excess costs in the second year ($5,121, $3,930, and $3,828, respectively). Although hip fractures had highest excess costs over both years, non-vertebral, non-hip fracture patients made up a larger proportion of the sample and were significantly more costly than controls. CONCLUSIONS: Patients with osteoporosis-related NV fractures have substantial excess costs beyond the first year in which the fracture occurs.

Prevalence and costs of osteoporotic patients with subsequent non-vertebral fractures in the US.

UNLABELLED: This study assesses prevalence of subsequent fractures during the year after incident osteoporosis-related non-vertebral fractures among privately insured and Medicare populations and compares costs between patients with and without subsequent fractures. Many non-vertebral fracture patients incur subsequent fractures, and those who do are significantly more costly during the year after incident fracture. INTRODUCTION: To estimate the prevalence of subsequent osteoporosis-related non-vertebral (NV) fractures during the year following an incident NV fracture and compare costs between NV fracture patients with and without subsequent fractures. METHODS: Using insurance claims data (1999-2006), privately-insured (ages 18-64 years) and Medicare (ages 65+ years) patients with ≥1 subsequent osteoporosis-related NV fracture within a year of an incident osteoporosis-related NV fracture were matched to controls with incident NV fractures but no subsequent fractures. Subsequent fractures were identified as any claim for an NV fracture occurring >3 months after the incident NV fracture (>6 months were required for fractures occurring at the same site as the incident fracture). The study assessed prevalence of subsequent fractures and compared costs (from the payer's perspective) between patients with and without subsequent fractures over the year following an incident NV fracture. RESULTS: Among privately insured NV fracture patients, 14.1% had any subsequent NV fractures, 1.6% had subsequent hip fractures, and 13.0% had subsequent non-vertebral, non-hip (NVNH) fractures, while 22.6% of Medicare NV fracture patients had subsequent NV fractures, 9.4% had subsequent hip fractures, and 15.5% had subsequent NVNH fractures. Mean excess health care costs per privately insured subsequent fracture patient were $9,789 ($19,072 vs. $9,914, p < 0.01), while excess medical costs per Medicare subsequent fracture patient were $12,527 ($31,904 vs. $19,377, p < 0.01). CONCLUSIONS: NV fracture patients are at substantial risk for subsequent NV fractures within 1 year, and patients who incur subsequent fractures are significantly more costly than those who do not during the year following an incident fracture.

Search for the rare decays K(L)→π0π0µ+µ- and K(L)→π0π0X0→π0π0µ+µ-.

The KTeV E799 experiment has conducted a search for the rare decays, K(L)→π(0)π(0)µ(+)µ(-) and K(L)→π(0)π(0)X(0)→π(0)π(0)µ(+)µ(-), where the X(0) is a possible new neutral boson that was reported by the HyperCP experiment with a mass of (214.3 ± 0.5) MeV/c(2). We find no evidence for either decay. We obtain upper limits of Br(K(L)→π(0)π(0)X(0)→π(0)π(0)µ(+)µ(-)) < 1.0 × 10(-10) and Br(K(L)→π(0)π(0)µ(+)µ(-)) < 9.2 × 10(-11) at the 90% confidence level. This result rules out the pseudoscalar X(0) as an explanation of the HyperCP result under the scenario that the dsX(0) coupling is completely real.

Quadriceps muscle strength in scoliosis.

Quadriceps muscle weakness is an important component of chronic obstructive pulmonary disease (COPD). We hypothesised that quadriceps weakness would also be a feature of restrictive lung disease due to scoliosis. We studied 10 patients with severe scoliosis (median (interquartile range (IQR)) forced expiratory volume in 1 s (FEV(1))() 35.3 (11)% predicted), 10 patients with severe COPD (FEV(1) 26.5 (9.0)% pred) and 10 healthy age-matched adults. We measured quadriceps strength, exercise capacity and analysed quadriceps muscle biopsies for myosin heavy-chain (MyHC) isoform expression and the presence of oxidative stress. Both groups exhibited quadriceps weakness with median (IQR) maximal voluntary contraction force being 46.0 (17.0) kg, 21.5 (21.0) kg and 31.5 (11.0) kg, respectively (p = 0.02 and 0.04, respectively, for each patient group against controls). Oxidative stress was significantly greater in the quadriceps of both restrictive and COPD patients. The scoliosis patients exhibited a decrease in the proportion of MyHC type I compared with controls; median (IQR) 35.3 (18.5)% compared with 47.7 (9.3)%, p = 0.028. The scoliosis patients also showed an increase in MyHC IIx (26.3 (15.5)% compared with 11.3 (13.0)%, p = 0.01. Quadriceps weakness is a feature of severe scoliosis; the similarities between patients with scoliosis and patients with COPD suggest a common aetiology to quadriceps weakness in both conditions.

Cytokine profile in quadriceps muscles of patients with severe COPD.

BACKGROUND: Systemic proinflammatory cytokines and oxidative stress have been described in association with peripheral muscle wasting and weakness of patients with severe chronic obstructive pulmonary disease (COPD), but their expression in skeletal muscle is unknown. The objectives of the present study were to determine muscle protein levels of selected cytokines in patients with COPD and to study their relationships with protein carbonylation as a marker of oxidative stress, quadriceps function and exercise capacity. METHODS: We conducted a cross sectional study in which 36 cytokines were detected using a human antibody array in quadriceps specimens obtained from 19 patients with severe COPD and seven healthy controls. Subsequently, selected cytokines (tumour necrosis factor (TNF)alpha, TNFalpha receptors I and II, interleukin (IL) 6, interferon gamma, transforming growth factor (TGF) beta and vascular endothelial growth factor (VEGF)), as well as protein carbonylation (oxidative stress index) were determined using an enzyme linked immunosorbent assay (ELISA) in all muscles. RESULTS: Compared with controls, the vastus lateralis of patients with COPD showed significantly lower protein ELISA levels of TNFalpha, which positively correlated with their quadriceps function, TNFalpha receptor II and VEGF. Protein ELISA levels of IL6, interferon gamma and TGFbeta did not differ between patients and controls. Quadriceps protein carbonylation was greater in patients and inversely correlated with quadriceps strength among them. CONCLUSIONS: These findings do not support the presence of a proinflammatory environment within the quadriceps muscles of clinically and weight stable patients with severe COPD, despite evidence for increased oxidative stress and the presence of muscle weakness.

Measurements of the decay KL-->e+ e- gamma.

The E799-II (KTeV) experiment at Fermilab has collected 83 262 K(L)-->e+ e- gamma(gamma) events above a background of 79 events. We measure a decay width, normalized to the K(L)-->pi0pi0pi(D)0 (pi0-->gammagamma, pi0-->gammagamma, pi(D0-->e+ e- gamma(gamma)) decay width, of Gamma(K(L)-->e+e-gamma(gamma))/Gamma(K(L)-->pi0pi0pi(D)0)=(1.3302+/-0.0046(stat)+/-0.0102(syst)) x 10(-3). We also measure parameters of two K(L)gamma*gamma form factor models. In the Bergström-Massó-Singer parametrization, we find Calpha(K*)= -0.517 +/- 0.030(stat) +/- 0.022(syst). We separately fit for the first parameter of the D'Ambrosio-Isidori-Portolés model and find alpha(DIP)= -1.729 +/- 0.043(stat) +/- 0.028(syst).

A novel technique for nonvolitional assessment of quadriceps muscle endurance in humans.

Assessment of quadriceps endurance is of interest to investigators studying human disease. We hypothesized that repetitive magnetic stimulation (rMS) of the intramuscular branches of the femoral nerve could be used to induce and quantify quadriceps endurance. To test this hypothesis, we used a novel stimulating coil to compare the quadriceps endurance properties in eight normal humans and, to confirm that the technique could be used in clinical practice, in eight patients with advanced chronic obstructive pulmonary disease (COPD). To validate the method, we compared in vivo contractile properties of the quadriceps muscle with the fiber-type composition and oxidative enzyme capacity. We used a Magstim Rapid(2) magnetic nerve stimulator with the coil wrapped around the quadriceps. Stimuli were given at 30 Hz, a duty cycle of 0.4 (2 s on, 3 s off), and for 50 trains. Force generation and the surface electromyogram were measured throughout. Quadriceps twitch force, elicited by supramaximal magnetic stimulation of the femoral nerve, was measured before and after the protocol. Quadriceps muscle biopsies were analyzed for oxidative (citrate synthase, CS) and glycolytic (phosphofructokinase, PFK) enzyme activity and myosin heavy chain isoform protein expression. The time for force to fall to 70% of baseline (T(70)) was shorter in the COPD group than the control group: 55.6 +/- 26.0 vs. 121 +/- 38.7 s (P = 0.0014). Considering patients and controls together, positive correlations were observed between T(70) and the proportion of type I fibers (r = 0.68, P = 0.004) and CS-to-PFK ratio (CS/PFK) (r = 0.67, P = 0.005). We conclude that quadriceps endurance assessed using rMS is feasible in clinical studies.

Right hemi-diaphragm paralysis following cardiac radiofrequency ablation.

Diaphragm paralysis may occur after traumatic phrenic nerve injury. Here we report three patients in whom right hemi-diaphragmatic paralysis developed after cardiac radiofrequency ablation. We hypothesise that local focused thermal energy at the time of the ablation may have caused direct neuronal damage by axonal coagulation necrosis. The prognosis for this type of injury may be reasonably good; two of the three patients fully recovered diaphragm function by 1 year.

Angina pectoris: effects of lidoflazine on exercise tolerance and chest pain.

In a double-blind study involving 24 patients, treatment with lidoflazine in comparison with placebo was associated with a significant improvement in exercise tolerance; the median increase in work performed was 62 percent. This increase was significant at the 6th week of assessment. Ten patients were followed up for a further 2 years. Lidoflazine therapy was associated with a significant improvement in work done over that period. Lidoflazine was well tolerated and apparent adverse effects were minor.

Search for lepton-flavor-violating decays of the neutral kaon.

The Fermilab KTeV experiment has searched for lepton-flavor-violating decays of the K(L) meson in three decay modes. We observe no events in the signal region for any of the modes studied, and we set the following upper limits for their branching ratios at the 90% C.L.: BR(K(L) --> pi(0) micro(+/-) e(-/+)) <7.6 x 10(-11); BR(K(L) --> pi(0)pi(0) micro(+/-) e(-/+)) <1.7 x 10(-10); BR(pi(0) --> micro(+/-) e(-/+)) <3.6 x 10(-10). This result represents a factor of 82 improvement in the branching ratio limit for K(L) --> pi(0) micro(+/-) e(-/+) and is the first reported limit for K(L) --> pi(0)pi(0) micro(+/-) e(-/+).

Determination of the parity of the neutral pion via its four-electron decay.

We present a new determination of the parity of the neutral pion via the double Dalitz decay pi0-->e+e-e+e-. Our sample, which consists of 30,511 candidate decays, was collected from KL-->pi0pi0pi0 decays in flight at the KTeV-E799 experiment at Fermi National Accelerator Laboratory. We confirm the negative pi0 parity and place a limit on scalar contributions to the pi0-->e+e-e+e- decay amplitude of less than 3.3% assuming CPT conservation. The pi0gamma*gamma* form factor is well described by a momentum-dependent model with a slope parameter fit to the final state phase-space distribution. Additionally, we have measured the branching ratio of this mode to be B(pi0-->e+e-e+e-)=(3.26+/-0.18)x10(-5).

First observation of K{L}-->pi{+/-}e{-/+}nue{+}e{-}.

This Letter is the first report of the K{L}-->pi{+/-}e{-/+}nue{+}e{-} decay. Based on 19 208+/-144 events, we determine the branching fraction, B(K{L}-->pi{+/-}e{-/+}nue{+}e{-}M_{e{+}e{-}}>5 MeV/c{2},E{e{+}e{-}}{*}>30 MeV)=(1.285+/-0.041)x10{-5}, and Gamma(K{e3ee}M{e{+}e{-}}>5 MeV/c{2})/Gamma(K{e3})=[4.57+/-0.04(stat)+/-0.14(syst)]x10{-5}. This ratio agrees with a theoretical prediction based on chiral perturbation theory (ChPT) calculated to O(p{4}). The measured kinematical distributions agree with those predicted by just ChPT O(p{4}), but show significant disagreement with ones predicted by leading-order ChPT.

Measurement of the K0 charge radius and a CP-violating asymmetry and a search for CP-violating E1 direct photon emission in the rare decay KL--> pi+ pi- e+ e-.

Using the complete KTeV data set of 5,241 candidate K(L)--> pi(+) pi(-) e(+) e(-) decays (including an estimated background of 204 +/- 14 events), we have measured the coupling g(CR)= 0.163 +/- 0.0149(stat) +/- 0.023(syst) of the CP conserving charge radius process and from it determined a K(0) charge radius of = [-0.077 +/- 0.007(stat) +/- 0.011(syst)]fm(2). We have determined a first experimental upper limit of 0.04 (90% C.L.) /g(e1)/ / /g(M1)/ of the couplings for the E1 and M1 direct photon emission processes. We also report the measurement of /g(M1)/ including a vector form factor /g(M1)/(1 + (a(1)/a(2))/((M(2)(p)-(M(2)(k))= 2M(K)E(gamma*)), where vector /g(M1)/= 1.11+/- 0.12(stat) +/- 0.08(syst) and a(1)/a(2) = [-0.744 +/- 0.027(stat) +/- 0.032(syst)] GeV(2)/c(2). Finally, a CP-violating asymmetry of [13.6 +/- 1.4(stat) +/- 1.5(syst)]% in the CP and T odd angle phi between the decay planes of the e(+) e(-) and pi(+) pi(-) pairs in the K(L) center of mass is reported.