Estimating the Cost-Effectiveness of Switching to Higher-Valency Pediatric Pneumococcal Conjugate Vaccines in the United Kingdom.

Currently, the 13-valent pneumococcal conjugate vaccine (PCV13) is administered under a 1+1 (1 primary dose) pediatric schedule in the United Kingdom (UK). Higher-valency PCVs, 15-valent PCV (PCV15), or 20-valent PCV (PCV20) might be considered to expand serotype coverage. We evaluated the cost-effectiveness of PCV20 or PCV15 using either a 2+1 (2 primary doses) or 1+1 schedule for pediatric immunization in the UK. Using a dynamic transmission model, we simulated future disease incidence and costs under PCV13 1+1, PCV20 2+1, PCV20 1+1, PCV15 2+1, and PCV15 1+1 schedules from the UK National Health Service perspective. We prospectively estimated disease cases, direct costs, quality-adjusted life-years (QALYs), and incremental cost-effectiveness ratio. Scenario analyses were performed to estimate the impact of model assumptions and parameter uncertainty. Over a five-year period, PCV20 2+1 averted the most disease cases and gained the most additional QALYs. PCV20 2+1 and 1+1 were dominant (cost-saving and more QALYs gained) compared with PCV15 (2+1 or 1+1) and PCV13 1+1. PCV20 2+1 was cost-effective (GBP 8110/QALY) compared with PCV20 1+1. PCV20 was found cost-saving compared with PCV13 1+1, and PCV20 2+1 was cost-effective compared with PCV20 1+1. Policymakers should consider the reduction in disease cases with PCV20, which may offset vaccination costs.

Quantifying the Value of Introducing an Oral Drug Delivery Option for Edaravone: A Review of Analyses Evaluating the Economic Impact of Oral versus Intravenous Formulations.

Background: Drug formulation and route of administration can have an impact on not only patients' quality of life and disease outcomes but also costs of care. It is essential for decision makers to use appropriate economic modeling methods to guide drug coverage policies and to support patients' decision-making. Purpose: To illustrate key cost considerations for decision makers in economic evaluation of innovative oral formulations as alternatives to intravenous medication. Materials and Methods: A structured literature review was conducted using the PubMed database to examine methods used for quantifying the economic impact of introducing a new oral pharmaceutical formulation as an alternative to intravenous medication. To illustrate the methods described in this review, a cost-minimization analysis was conducted to quantify the impact of introducing an oral formulation of a medication originally developed as an intravenous treatment for amyotrophic lateral sclerosis. Results: We identified 14 published evaluations of oral and intravenous formulations from 10 countries across a variety of disease areas. The identified studies used cost-effectiveness (n=10), cost-minimization (n=2), and cost-calculation (n=2) modeling approaches. All but one (13/14) reported outcomes from payers' perspective, while societal perspectives were also incorporated in 3 of the reviewed evaluations. One study estimated costs from a public hospital's perspective. Only a subset of the identified studies accounted for the effects of safety (n=6) or efficacy (n=8) differences on treatment costs when estimating the costs of a formulation choice. Many studies that omitted these aspects did not include rationales for their decisions. Conclusion: We found significant design variations in published models that estimated the impact of an additional formulation option on the treatment costs to payers and the society. Models need to be accompanied with clear descriptions on rationales for their time horizons and assumptions on how different formulations may affect healthcare costs from the selected perspectives.

Detection of Vancomycin-Resistant Enterococcus faecium Endocarditis After Clearance of Vancomycin-Sensitive Enterococcus faecium Bacteremia.

Vancomycin-resistant enterococcal (VRE) bacteremia is associated with higher mortality rates and longer hospitalizations than vancomycin-sensitive enterococcal (VSE) bacteremia. A 67-year-old man with a right psoas abscess and pacemaker-associated tricuspid valve endocarditis in September 2020 grew VSE Enterococcus faecium from blood cultures that cleared after administration of intravenous vancomycin and gentamicin. Subsequently, he underwent tricuspid valve repair, pacemaker removal, and partial lead extraction. Valve and postoperative blood cultures grew VRE E. faecium, which cleared after administration of intravenous daptomycin. One VSE and two VRE isolates were collected and sequenced. All isolates belonged to E. faecium multilocus sequence type ST17 and were closely related, having <20 mutations in pairwise genome comparisons. Vancomycin resistance was due to the acquisition of a plasmid-encoded VanA operon. None of the isolates encoded the virulence factors asa1, gelE, cylA, or hyl; all encoded a homologue of efaAfm. VSE E. faecium, but not VRE E. faecium isolates, encoded a glucose transporter gene mutation. Two VRE E. faecium isolates formed more robust biofilms than the VSE E. faecium isolate (p < 0.001). The VRE E. faecium isolates, which generated larger biofilms than the VSE E. faecium isolate, could have remained protected in the heart valve and only caused bacteremia when disrupted during cardiac surgery. This study demonstrates that bacteria detected in the bloodstream of patients with endocarditis may not fully represent the organisms adherent to the cardiac valves or indwelling devices.

A Review of Treatment and Prevention of Coronavirus Disease 2019 among Solid Organ Transplant Recipients.

Therapeutic management of solid organ transplant (SOT) recipients infected with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the cause of coronavirus disease 2019 (COVID-19), may challenge healthcare providers given a paucity of clinical data specific to this cohort. Herein, we summarize and review the studies that have formed the framework for current COVID-19 consensus management guidelines. Our review focuses on COVID-19 treatment options including monoclonal antibody products, antiviral agents such as remdesivir, and immunomodulatory agents such as corticosteroids, interleukin inhibitors, and kinase inhibitors. We highlight the presence or absence of clinical data of these therapeutics related to the SOT recipient with COVID-19. We also describe data surrounding COVID-19 vaccination of the SOT recipient. Understanding the extent and limitations of observational and clinical trial data for the prevention and treatment of COVID-19 specific to the SOT population is crucial for optimal management. Although minimal data exist on clinical outcomes among SOT recipients treated with varying COVID-19 therapeutics, reviewing these agents and the studies that have led to their inclusion or exclusion in clinical management of COVID-19 highlights the need for further studies of these therapeutics in SOT patients with COVID-19.

Introduction of the BNT162b2 vaccine during a COVID-19 nursing home outbreak.

BACKGROUND: Coronavirus disease 2019 (COVID-19) outbreaks often occur in nursing homes and prompt frequent surveillance testing for SARS-CoV-2. A single dose of the BNT162b2 vaccine reduces viral load and transmission. In this study, we describe the real-world efficacy of BNT162b2 single-dose vaccination during a COVID-19 outbreak at a Veterans Affairs Community Living Center (CLC). METHODS: From 12/2/20 to 5/14/21, twice weekly antigen testing was used to detect COVID-19 among 146 residents at the CLC. Residents without a prior history of COVID-19 who agreed to immunization were vaccinated with the BNT162b2 vaccine on 12/16/20 and 1/6/21. Single-dose vaccine efficacy was determined for days 1-21 and days 14-21 after the first vaccine dose. RESULTS: The outbreak occurred from 12/2/20 to 1/7/21 with an attack rate of 30.8% (45/146); 46.7% (21/45) of the cases were due to asymptomatic COVID-19. One unit accounted for 77.8% (35/45) of the cases. In the vaccine analysis, 116 residents were a median age of 74.5 years and 93.1% (108/116) had ≥ 1 comorbid condition. Between the first and second dose, 15.5% (15/97) of vaccinated residents, and 21.2% (4/19) of unvaccinated residents developed COVID-19 (P = .81). One week after the second dose, no cases of COVID-19 occurred. CONCLUSIONS: Albeit limited by the small numbers, a single dose of the BNT162b2 vaccine was not efficacious at preventing COVID-19 during this nursing home outbreak.

Single Dose of an mRNA Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-Cov-2) Vaccine Is Associated With Lower Nasopharyngeal Viral Load Among Nursing Home Residents With Asymptomatic Coronavirus Disease 2019 (COVID-19).

In nursing home residents with asymptomatic COVID-19 diagnosed through twice-weekly surveillance testing, single-dose BNT162b2 vaccination (Pfizer-BioNTech) was associated with -2.4 mean log10 lower nasopharyngeal viral load than detected in absence of vaccination (P = .004). Since viral load is linked to transmission, single-dose mRNA SARS-CoV-2 vaccination may help control outbreaks.

SARS-CoV-2 is associated with high viral loads in asymptomatic and recently symptomatic healthcare workers.

BACKGROUND: Healthcare workers (HCW) are at increased risk of SARS-CoV-2 infection from both patients and other HCW with coronavirus disease 2019 (COVID-19). RT-PCR cycle threshold (Ct) values of SARS-CoV-2 ≤ 34 and the first 7-9 days of symptoms are associated with enhanced infectivity. We determined Ct values and duration of symptoms of HCW with a positive SARS-CoV-2 test. As HCW often assume their greatest risk of acquiring SARS-CoV-2 is working on a COVID-19 unit, we also determined Ct values and symptom duration of inpatients with a positive SARS-CoV-2 test. METHODS: From 6/24/2020-8/23/2020, Ct values and duration of symptoms from 13 HCW, 12 outpatients, and 28 inpatients who had a positive nasopharyngeal swab for SARS-CoV-2 were analyzed. RESULTS: Among HCW with a positive SARS-CoV-2 test, 46.2% (6/13) were asymptomatic and requested testing due to an exposure to someone with COVID-19; 83.3% (5/6) of those exposures occurred in the community rather than in the hospital. The median Ct value of HCW was 23.2, and 84.6% (11/13) had a Ct value ≤ 34. The median Ct value of 29.0 among outpatients with COVID-19 did not significantly differ from HCW. In contrast, inpatients with a positive SARS-CoV-2 test had a median Ct value of 34.0 (p = 0.003), which translated into a median ~1,000-fold lower viral load than observed in HCW. Among those with symptoms related to COVID-19, no (0/6) HCW compared to 50% (6/12) of inpatients had symptoms for at least one week (p = 0.04). CONCLUSIONS: At our institution, asymptomatic COVID-19 accounted for nearly half of the cases among HCW. Symptomatic HCW had high viral loads and short duration of symptoms, both of which are associated with peak infectivity. Infection prevention programs should educate HCW on these findings in an effort to increase adherence to the requirement to maintain six feet separation in workspaces and breakrooms, in addition to consistently wearing personal protection equipment.

A framework for assessing the lifetime economic burden of congenital cytomegalovirus in the United States.

BACKGROUND: In the United States (US), congenital cytomegalovirus infection (cCMVi) is a major cause of permanent disabilities and the most common etiology of non-genetic sensorineural hearing loss. Evaluations of prevention strategies will require estimates of the economic implications of cCMVi. We aimed to develop a conceptual framework to characterize the lifetime economic burden of cCMVi in the US and to use that framework to identify data gaps. METHODS: Direct health care, direct non-health care, indirect, and intangible costs associated with cCMVi were considered. An initial framework was constructed based on a targeted literature review, then validated and refined after consultation with experts. Published costs were identified and used to populate the framework. Data gaps were identified. RESULTS: The framework was constructed as a chance tree, categorizing clinical event occurrence to form patient profiles associated with distinct economic trajectories. The distribution and magnitude of costs varied by patient life stage, cCMVi diagnosis, severity of impairment, and developmental delays/disabilities. Published studies could not fully populate the framework. The literature best characterized direct health care costs associated with the birth period. Gaps existed for direct non-health care, indirect, and intangible costs, as well as health care costs associated with adult patients and those severely impaired. CONCLUSIONS: Data gaps exist concerning the lifetime economic burden of cCMVi in the US. The conceptual framework provides the basis for a research agenda to address these gaps. Understanding the full lifetime economic burden of cCMVi would inform clinicians, researchers, and policymakers, when assessing the value of cCMVi interventions.

Budget Impact of Adding Vedolizumab to a Health Plan Formulary as Another First-Line Biologic Option for Ulcerative Colitis and Crohn's Disease.

BACKGROUND: Vedolizumab is a biologic drug approved by the US Food and Drug Administration (FDA) for the treatment of adults with moderately to severely active Crohn's disease (CD) or ulcerative colitis (UC) who have had inadequate response to, lost response to, or were intolerant of immunomodulators or tumor necrosis factor (TNF) blocker therapy, or who had an inadequate response with, were intolerant to, or demonstrated dependence on corticosteroid therapy. The biologics approved by the FDA for CD and/or UC include adalimumab, infliximab, golimumab, certolizumab, and ustekinumab. OBJECTIVE: To assess the budget impact of including vedolizumab in a health plan formulary among current options as a preferred first-line biologic therapy for UC and CD rather than only for patients who failed anti-TNF therapy. METHODS: We developed a 3-year budget impact model for a 1-million-member health plan. Comparators included all currently approved brand-name biologic and biosimilar agents for the treatment of UC (ie, adalimumab, infliximab, and golimumab) and CD (ie, adalimumab, certolizumab, infliximab, and ustekinumab). Clinical inputs included therapy response probabilities, disease remission, and surgery risk. Given the lack of head-to-head clinical trials, we estimated indirect comparisons of treatment efficacy based on clinical trial data using the Bucher method. The drug and medical costs were obtained from published literature. The model compared hypothetical health plan costs for 2 scenarios-(1) a market mix with vedolizumab included on the formulary with currently existing first- and second-line preferred treatments, and (2) vedolizumab included only with existing preferred second-line treatments on the hypothetical formulary. These scenarios were compared in the context of 3 hypothetical health plan formulary cases. RESULTS: Including vedolizumab in a hypothetical formulary with currently preferred first-line biologic treatment options (Scenario 1) resulted in cost-savings compared with vedolizumab as a preferred second-line biologic option (Scenario 2). The total cost-savings were from $0.13 million to $1.63 million in year 1, and from $0.38 million to $4.68 million in year 3. The per-member per-month cost-savings were from $0.01 to $0.14 in year 1 and from $0.03 to $0.39 in year 3. CONCLUSION: Based on our model's results, including vedolizumab among the current health plan formulary biologic options as a preferred first-line treatment for UC and CD can result in substantial cost-savings compared with including vedolizumab as a preferred second-line treatment only.

Frequency and Mechanisms of Spontaneous Fosfomycin Nonsusceptibility Observed upon Disk Diffusion Testing of Escherichia coli.

Fosfomycin maintains activity against most Escherichia coli clinical isolates, but the growth of E. coli colonies within the zone of inhibition around the fosfomycin disk is occasionally observed upon susceptibility testing. We aimed to estimate the frequency of such nonsusceptible inner colony mutants and identify the underlying resistance mechanisms. Disk diffusion testing of fosfomycin was performed on 649 multidrug-resistant E. coli clinical isolates collected between 2011 and 2015. For those producing inner colonies inside the susceptible range, the parental strains and their representative inner colony mutants were subjected to MIC testing, whole-genome sequencing, reverse transcription-quantitative PCR (qRT-PCR), and carbohydrate utilization studies. Of the 649 E. coli clinical isolates, 5 (0.8%) consistently produced nonsusceptible inner colonies. Whole-genome sequencing revealed the deletion of uhpT encoding hexose-6-phosphate antiporter in 4 of the E. coli inner colony mutants, while the remaining mutant contained a nonsense mutation in uhpA The expression of uhpT was absent in the mutant strains with uhpT deletion and was not inducible in the strain with the uhpA mutation, unlike in its parental strain. All 5 inner colony mutants had reduced growth on minimal medium supplemented with glucose-6-phosphate. In conclusion, fosfomycin-nonsusceptible inner colony mutants can occur due to the loss of function or induction of UhpT but are rare among multidrug-resistant E. coli clinical strains. Considering that these mutants carry high biological costs, we suggest that fosfomycin susceptibility of strains that generate inner colony mutants can be interpreted on the basis of the zone of inhibition without accounting for the inner colonies.

The SIGN nail for knee fusion: technique and clinical results.

PURPOSE: Evaluate the efficacy of using the SIGN nail for instrumented knee fusion. METHODS: Six consecutive patients (seven knees, three males) with an average age of 30.5 years (range, 18-50 years) underwent a knee arthrodesis with SIGN nail (mean follow-up 10.7 months; range, 8-14 months). Diagnoses included tuberculosis (two knees), congenital knee dislocation in two knees (one patient), bacterial septic arthritis (one knee), malunited spontaneous fusion (one knee), and severe gout with 90° flexion contracture (one knee). The nail was inserted through an anteromedial entry point on the femur and full weightbearing was permitted immediately. RESULTS: All knees had clinical and radiographic evidence of fusion at final follow-up and none required further surgery. Four of six patients ambulated without assistive device, and all patients reported improved overall physical function. There were no post-operative complications. CONCLUSION: The technique described utilizing the SIGN nail is both safe and effective for knee arthrodesis and useful for austere environments with limited fluoroscopy and implant options.

A study of the level and dynamics of Eimeria populations in naturally infected, grazing beef cattle at various stages of production in the Mid-Atlantic USA.

There is little information available on the species dynamics of eimerian parasites in grazing cattle in the central Appalachian region of the United States. Therefore, the objective of this study was to describe the level of infection and species dynamics of Eimeria spp. in grazing beef cattle of various age groups over the course of a year in the central Appalachian region. Rectal fecal samples were collected from male and female calves (n=72) monthly from May through October 2005, heifers only (n=36) monthly from November 2005 to April 2006, and cows (n=72) in May, July, and September, 2005. Eimeria spp. oocysts were seen in 399 of 414 (96%) fecal samples collected from the calves from May through October. Fecal oocysts counts (FOC) in the calves were lower (P<0.05) in May than all other months and no significant differences were detected from June through September. Eimeria spp. oocysts were detected in 198 of 213 (92%) of fecal samples collected from the 36 replacement heifers monthly from November to April and monthly mean FOC did not differ during this time period. The prevalence of oocyst shedding increased to 100% in calves in September and remained near 100% in the replacement heifers during the sampling period. Eimeria spp. oocysts were also detected in 150 of 200 (75%) samples collected in May, July, and September from the cows and mean FOC did not differ significantly over the sampling period. Eimeria spp. composition was dominated by Eimeria bovis in fecal samples collected from calves, replacement heifers and cows. Mixed Eimeria spp. infections were, however, common in all groups and 13 Eimeria spp. oocysts were identified throughout the sampling period.

The cost-effectiveness of expanded HIV screening in the United States.

OBJECTIVE: The current Centers of Disease Control and Prevention (CDC) guidelines from 2006 recommend a one-time test for low-risk individuals and annual testing for those at high risk. These guidelines may not be aggressive enough, even for those at low risk of infection, due to the earlier initiation of HAART and a movement towards a test-and-treat environment. We evaluated the optimal testing frequencies for various risk groups in comparison to the CDC recommendations. METHODS: We build a deterministic mathematical model optimizing the tradeoff between the societal cost of testing and the benefits over a patient's lifetime of earlier diagnosis. RESULTS: Under a test-and-treat scenario with immediate initiation of HAART, the optimal testing frequency is every 2.4 years for low-risk (0.01% annual incidence) individuals; every 9 months for moderate risk (0.1% incidence) individuals; and every 3 months for high-risk (1.0% incidence) individuals. The incremental cost-effectiveness of the optimal policy is $ 36 ,342/quality-adjusted life-years (QALY) for low-risk individuals and $ 45 ,074/QALY for high-risk individuals compared with 20-year and annual testing, respectively. CONCLUSION: The current CDC guidelines for HIV testing are too conservative, and more frequent testing is cost-effective for all risk groups.

Effectiveness of a no-sex or safe-sex month in reducing HIV transmission.

OBJECTIVE: To build a deterministic compartmental model for exploring the effects on the transmission of human immunodeficiency virus (HIV) of a population abstaining from sex or practising only "safe" sex for one month each year. METHODS: A model of HIV transmission was built to simulate the effects of the intervention (i.e. an annual no-sex or safe-sex month in which no transmission occurred) in three countries, under several optimistic assumptions. The reduction in the modelled annual incidence of transmission that was attributable to this "test" intervention was compared with that seen with an alternative intervention. In the latter, monthly incidences of transmission were each reduced by one twelfth, so that, essentially, the month-long interruption was spread evenly across a full year. FINDINGS: Over the first modelled year, the test intervention averted only 2.5% (Kenya), 3.3% (South Africa) and 1.6% (Swaziland) more HIV infections than the alternative interruption. According to the model, if the test intervention were repeated each January, it would avert only 2% (Kenya), 2% (South Africa) and 1% (Swaziland) more HIV infections over 5 years than the alternative intervention. CONCLUSION: Although it did not appear markedly more effective than the alternative intervention, the test intervention may still be more feasible and therefore worthwhile. Before the test intervention can be recommended, the cost-effectiveness and feasibility of such an annual month-long break in HIV transmission need to be assessed and compared with those of other interventions that may reduce new HIV infections, such as circumcision and concurrency-reduction campaigns.

The effect of weaning method on coccidial infections in beef calves.

Weaning is often cited as a stressful event that can precipitate clinical coccidiosis in cattle. Recently, two-stage weaning methods have been investigated as a means to reduce stress in calves. The objective of this study was to investigate the effect of weaning method on fecal oocyst count (FOC) and Eimeria spp. composition. A group of 108 beef calves (190-240 days of age) were allocated to three treatments on day -7: a fenceline weaned group where calves could see and hear their dams, but were physically separated from them by a fence (FL), a noseclipped group where suckling was prevented (NC), and a group left with their dams to be traditionally weaned (TW) by abrupt separation on day 0. On day 0, noseclips were removed from the NC calves and all groups were completely separated from their dams. The steers (n=50) were transported 172 km to another farm, and heifers (n=58) were taken to distant fields on the same farm. Rectal fecal samples were collected from all calves on days -7, 0, and 14. Steers were also sampled on days 7, 28, and 42. A group of steers (n=24) from each of the treatments previously described were fitted with pedometers and intensively observed on days 1-4. The Modified McMaster's test and Wisconsin sugar flotation test were used for quantification and identification of Eimeria spp. oocysts. Clinical coccidiosis was not observed during the study. Fecal oocyst counts did not differ between treatment groups on any sampling day. Differences between steer and heifer FOC were not detected. Treatment had no effect on species composition, but time effects were detected in the steers. The mean percentage of E. bovis was lower (P<0.05) on days 28 and 42 than all other sampling days. The decrease in the percentage of E. bovis was accompanied by an increase (P<0.05) in the percentage of E. canadensis on days 28 and 42. Behavioral observation showed that TW steers exhibited higher levels of stress related behavior (P<0.05) following complete separation, although this was not reflected in FOC.