A systematic literature review of the global seroprevalence of cytomegalovirus: possible implications for treatment, screening, and vaccine development.

BACKGROUND: Cytomegalovirus (CMV) is a common pathogen that affects individuals of all ages and establishes lifelong latency. Although CMV is typically asymptomatic in healthy individuals, infection during pregnancy or in immunocompromised individuals can cause severe disease. Currently, treatments are limited, with no prophylactic vaccine available. Knowledge of the current epidemiologic burden of CMV is necessary to understand the need for treatment and prevention. A systematic literature review (SLR) was conducted to describe the most recent epidemiologic burden of CMV globally. METHODS: Medline, Embase, and LILACS were searched to identify data on CMV prevalence, seroprevalence, shedding, and transmission rates. The SLR covered the time period of 2010-2020 and focused geographically on Australia, Europe, Israel, Japan, Latin America (LATAM), and North America. Studies were excluded if they were systematic or narrative reviews, abstracts, case series, letters, or correspondence. Studies with sample sizes < 100 were excluded to focus on studies with higher quality of data. RESULTS: Twenty-nine studies were included. Among adult men, CMV immunoglobulin G (IgG) seroprevalence ranged from 39.3% (France) to 48.0% (United States). Among women of reproductive age in Europe, Japan, LATAM, and North America, CMV IgG seroprevalence was 45.6-95.7%, 60.2%, 58.3-94.5%, and 24.6-81.0%, respectively. Seroprevalence increased with age and was lower in developed than developing countries, but data were limited. No studies of CMV immunoglobulin M (IgM) seroprevalence among men were identified. Among women of reproductive age, CMV IgM seroprevalence was heterogenous across Europe (1.0-4.6%), North America (2.3-4.5%), Japan (0.8%), and LATAM (0-0.7%). CMV seroprevalence correlated with race, ethnicity, socioeconomic status, and education level. CMV shedding ranged between 0% and 70.2% depending on age group. No findings on CMV transmission rates were identified. CONCLUSIONS: Certain populations and regions are at a substantially higher risk of CMV infection. The extensive epidemiologic burden of CMV calls for increased efforts in the research and development of vaccines and treatments. TRIAL REGISTRATION: N/A.

Factors influencing series completion rates of recombinant herpes zoster vaccine in the United States: A retrospective pharmacy and medical claims analysis.

BACKGROUND/OBJECTIVES: Vaccination against herpes zoster (HZ) is an effective strategy in protecting the population against consequences of varicella zoster virus reactivation. Optimal immunogenicity with recombinant zoster vaccine (RZV) relies on completion of the 2-dose series within 2-6 months from the first dose. The objectives of this study were to estimate RZV completion rates and adherence with the recommended administration schedule in the general United States population aged at least 50 years and to evaluate factors influencing completion rates. METHODS: Longitudinal, open-source pharmacy and medical claims databases were analyzed for adults aged at least 50 years with a first RZV prescription filled between October 2017 and September 2019. The data were linked to Experian Marketing Services Consumer View data to obtain information regarding race. Completion rates and adherence were calculated overall and stratified according to claim source, age class, sex, and payer type. Logistic regression models were built for each subpopulation of interest to identify factors correlating with completion rates. RESULTS: Overall, cumulative completion rates were 70.41% and 81.80% at 6 and 12 months, respectively. Median time to second dose was approximately 4 months (4.08-5.13 months) and adherence 67.62%. Completion rates were lower in the medical claims database compared with the pharmacy claims database (48.98% vs. 73.23% at 6 months). Regression models confirmed that pharmacy claim was an independent factor for higher completion rates, while African American race and Medicaid status were associated with lower completion rates. Most comorbidities, including chronic obstructive pulmonary disease and type 2 diabetes mellitus, were associated with lower completion rates. CONCLUSION: Pharmacists contribute substantially to the overall high RZV completion rates in the United States. However, completion rates can be improved, especially in people receiving their first RZV dose at a physician's office. Future strategies should aim at lowering barriers to completing vaccination series in African Americans, Medicaid beneficiaries, and people with comorbidities.

Burden of asthma with elevated blood eosinophil levels.

BACKGROUND: Asthma is a common chronic condition with an economic burden of almost $56 billion annually in the US. Biologic markers like blood eosinophils, that help predict the risk of exacerbation could help guide more optimal treatment plans and reduce cost. The purpose of this study was to determine whether healthcare resource use and expenditures vary by eosinophil level among patients with asthma. METHODS: Patients with a diagnosis of asthma defined by ICD-9-CM code 493.xx between January 2004 and July 2011 were extracted from EMRClaims + database (eMAX Health, White Plains NY). Patients were classified as mild, moderate, or severe by medication use following diagnosis, based on recommendations of National Institutes of Health Expert Panel Report 3. Patients were classified as those with elevated eosinophils (≥400 cells/µL) and normal eosinophil level (<400 cells/µL). Patients were followed for resource use, defined as hospitalizations, ER visits and outpatient visit and associated costs were calculated to assess whether an economic difference exists between eosinophil groups. Non-parametric tests were used to compare resource use and associated cost between elevated and normal eosinophil groups. Multivariate modeling was performed to assess the contribution of eosinophil level on the likelihood of study outcomes among patients with severe asthma. RESULTS: Among the 2,164 patients meeting eligibility criteria, 1,144 had severity designations. Of these, 179(16 %) of patients had severe asthma of which 20 % (n = 35) had elevated eosinophils. Seventeen percent of patients with elevated eosinophils were admitted to the hospital during the follow-up period, significantly greater than patients with normal eosinophil levels (12 %; p = 0.011). Overall, compared to patients with normal eosinophil levels (n = 1734), patients with elevated eosinophil levels (n = 430) had significantly greater mean annual hospital admissions (0.51 vs. 0.21/year, p = 0.006) and hospital costs (2,536 vs. $1,091, p = 0.011). Logistic regressions showed that elevated eosinophil level was associated with 5.14 times increased odds of all cause admissions (95 % CI:1.76-14.99, p = 0.003) and 4.07 times increased odds of asthma related admissions (95 % CI: 1.26-13.12, p = 0.019). CONCLUSION: Eosinophil elevation was associated with greater healthcare resource use in patients with asthma.

Value of peripheral blood eosinophil markers to predict severity of asthma.

BACKGROUND: Asthma represents a significant clinical and economic burden to the US healthcare system. Along with other clinical manifestations of the disease, elevated sputum and blood eosinophil levels are observed in patients experiencing asthma exacerbations. The aim of this study was to evaluate the association between blood eosinophil levels and asthma severity defined using Expert Panel Report 3 guidelines. METHODS: Patients with asthma diagnosis between 2004 and 2011 were extracted from the EMRClaims+ database (eMAX Health, White Plains, NY) containing electronic medical records linked to insurance claims for over 675,000 patients. The date of first asthma diagnosis was defined as the 'index date'. Patients were required to have at least 1 peripheral eosinophil test (elevated defined as ≥ 400 cells/µL) in the 12 month 'assessment' period following the index date. We classified patients as those with mild asthma and moderate-to-severe asthma based on the pattern of medication use, as recommended by the 2007 National Institutes of Health Expert Panel Report. Logistic regression models were used to determine if patients with moderate-to-severe asthma had increased likelihood of an elevated peripheral eosinophil count, after accounting for demographics and comorbidities. RESULTS: Among 1,144 patients with an asthma diagnosis, 60 % were classified as having moderate-to-severe asthma. Twenty four percent of patients with moderate-to-severe asthma and 19 % of patients with mild asthma had an elevated peripheral eosinophil count (p = 0.053). Logistic regression showed that moderate-to-severe asthma was associated with 38 % increased odds of elevated eosinophil level (OR 1.38, 95 % CI: 1.02 to 1.86, p = 0.04). CONCLUSION: Patients with moderate-severe asthma are significantly more likely to have an elevated peripheral eosinophil count than patients with mild asthma.

New Vaccine Platforms-Novel Dimensions of Economic and Societal Value and Their Measurement.

The COVID-19 pandemic's dramatic impact has been a vivid reminder that vaccines-especially in the context of infectious respiratory viruses-provide enormous societal value, well beyond the healthcare system perspective which anchors most Health Technology Assessment (HTA) and National Immunization Technical Advisory Group (NITAG) evaluation frameworks. Furthermore, the development of modified ribonucleic acid-based (mRNA-based) and nanoparticle vaccine technologies has brought into focus several new value drivers previously absent from the discourse on vaccines as public health interventions such as increased vaccine adaptation capabilities, the improved ability to develop combination vaccines, and more efficient vaccine manufacturing and production processes. We review these novel value dimensions and discuss how they might be measured and incorporated within existing value frameworks using existing methods. To realize the full potential of next-generation vaccine platforms and ensure their widespread availability across populations and health systems, it is important that value frameworks utilized by HTAs and NITAGs properly reflect the full range of benefits for population health and well-being and cost efficiencies that these new vaccines platforms provide.

Improving asthma management: the case for mandatory inclusion of dose counters on all rescue bronchodilators.

BACKGROUND: Asthma remains a serious global health challenge. Poor control of asthma symptoms is due in part to incorrect use of oral inhaler devices that deliver asthma medications, such as poor inhalation technique or use of a metered dose inhaler (MDI) after the recommended number of doses is expelled. OBJECTIVE: To review published research on the potential for patients to overestimate or underestimate the amount of asthma rescue medication in MDIs without integrated dose-counting mechanisms. METHODS: We searched PubMed and EMBASE using search terms "dose counter and asthma" and "dose counter and metered dose inhaler" for English language publications up to July, 2012, with a manual search of references from relevant articles. RESULTS: Up to 40% of patients believe they are taking their asthma medication when they actually are activating an empty or nearly empty MDI. Device design makes it impossible for an MDI to cease delivering drug doses at an exact point, and the number of actuations in an MDI may be twice the nominal number of recommended medication doses. Once the recommended number of medication doses is expelled, remaining actuations deliver decreasing concentrations of active medication and increasing concentrations of propellants and excipients. This phenomenon, called "tail-off," is particularly problematic when medications are formulated as suspensions, as are rescue medications to control acute bronchospasm. Reliable inhalation of rescue medication could reduce asthma-related morbidity. CONCLUSION: By helping to ensure that patients receive accurate metered doses of asthma rescue medication to relieve bronchoconstriction, dose counters may help to improve asthma management.

Factors associated with receipt of mRNA-1273 vaccine at a United States national retail pharmacy during the COVID-19 pandemic.

INTRODUCTION: The emergence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) prompted accelerated vaccine development of novel messenger RNA (mRNA)-based vaccines by Moderna and Pfizer, which received FDA Emergency Use Authorization in December 2020. The purpose of this study was to examine trends in primary series administration and multi-dose completion rates with Moderna's mRNA-1273 vaccine administered at a United States retail pharmacy. METHODS: Walgreens pharmacy data were joined to publicly available data sets to examine trends in mRNA-1273 primary series and multi-dose completion across patient race/ethnicity, age, gender, distance to first vaccination, and community characteristics. Eligible patients received their first dose of mRNA-1273 administered by Walgreens between December 18, 2020 and February 28, 2022. Variables significantly associated with on-time second dose (all patients) and third dose (immunocompromised patients) in univariate analyses were included in linear regression models. A subset of patients in selected states were studied to identify differences in early and late vaccine adoption. RESULTS: Patients (N = 4,870,915) who received ≥ 1 dose of mRNA-1273 were 57.0% White, 52.6% female, and averaged 49.4 years old. Approximately 85% of patients received a second dose during the study period. Factors associated with on-time second dose administration included older age, race/ethnicity, traveling ≤ 10 miles for the first dose, higher community-level health insurance, and residing in areas with low social vulnerability. Only 51.0% of immunocompromised patients received the third dose as recommended. Factors associated with third dose administration included older age, race/ethnicity, and small-town residence. Early adopters accounted for 60.6% of patients. Factors associated with early adoption included older age, race/ethnicity, and metropolitan residence. CONCLUSION: Over 80% of patients received their on-time second dose of mRNA-1273 vaccine per CDC recommendations. Patient demographics and community characteristics were associated with vaccine receipt and series completion. Novel approaches to facilitate series completion during a pandemic should be further studied.

A systematic literature review on the humanistic burden of cytomegalovirus.

OBJECTIVE: Cytomegalovirus (CMV) infection is typically asymptomatic in healthy individuals; however, certain populations are vulnerable to infection and may develop serious sequelae. CMV infection may also have a broad impact on humanistic outcomes, including patient health status and quality of life (QoL). We conducted a systematic literature review (SLR) to describe the global humanistic burden of CMV and congenital CMV (cCMV) infections across all age groups. METHODS: Medline, Embase, and LILACS were searched to identify studies on humanistic outcomes following CMV infection, including health status/QoL and any outcomes in domains such as auditory performance, cognitive ability, developmental status, intelligence, language, memory, mental health, motor performance, social communication, speech, and vocabulary. The SLR included articles published from 2000 to 2020 and focused geographically on Australia, Europe, Israel, Japan, Latin America, and North America. RESULTS: Sixty-three studies met the inclusion criteria. In general, individuals with symptomatic cCMV infection experience a greater burden of disease and more substantial impact on QoL versus those with asymptomatic cCMV infection. Children with hearing loss due to cCMV infection, both symptomatic and asymptomatic, showed improved auditory outcomes following cochlear implantation. Newborns, infants, and children with cCMV infections had worse cognitive outcomes in psychological development, sequential and simultaneous processing, phonological working memory, and attention control versus age-matched controls without cCMV infection. CMV infection was also associated with cognitive decline in elderly populations. CONCLUSIONS: CMV infection can have substantial, lifelong, heterogenous impacts on humanistic outcomes, including health status and QoL, which should be considered when developing and implementing treatment and prevention strategies.

A systematic literature review of the economic and healthcare resource burden of cytomegalovirus.

OBJECTIVE: Cytomegalovirus (CMV) can infect individuals at any age, including infants, who may contract it from infected mothers (congenital CMV [cCMV]). Whereas CMV infection is typically asymptomatic or causes mild illness in healthy individuals, infection can result in severe outcomes in immunocompromised individuals and in infants with cCMV. This systematic review aims to characterize the economic impact of CMV and cCMV infections. METHODS: Medline, Embase, and LILACS databases were searched for publications reporting the economic impact of cCMV and CMV infections across all age groups. Manuscripts published between 2010 and 2020 from Australia, Latin America, Canada, Europe, Israel, Japan, the United States, and global (international, worldwide) studies were included; congress materials were excluded. Outcomes of interest included cCMV- and CMV-attributable direct costs/charges, resource utilization, and indirect/societal costs. RESULTS: Of 751 records identified, 518 were excluded based on duplication, population, outcome, study design, or country. Overall, 55 articles were eligible for full-text review; 25 were further excluded due to population, outcome, study design, or congress abstract. Two publications were additionally identified, resulting in economic impact data compiled from 32 publications. Of these, 24 publications reported cost studies of cCMV or CMV, including evaluation of direct costs/charges, healthcare resource utilization, and indirect/societal costs, and 7 publications reported economic evaluations of interventions. The populations, methods and outcomes used across these studies varied widely. CONCLUSIONS: CMV and cCMV infections impose a considerable economic impact on different countries, populations, and outcomes. There are substantial evidence gaps where further research is warranted.

Medical costs and adherence in patients receiving aqueous versus pressurized aerosol formulations of intranasal corticosteroids.

Intranasal corticosteroid (INS) formulations have different sensory attributes that influence patient preferences, and thereby possibly adherence and health outcomes. This study compares health care use and costs and medication adherence in matched cohorts of patients with allergic rhinitis (AR) using a chlorofluorocarbon-propelled pressurized metered-dose inhaler (pMDI) or aqueous intranasal corticosteroid (A-INS). Florida Medicaid retrospective claims analysis was performed of enrollees aged ≥12 years with at least 1 year of continuous enrollment before their initial AR diagnosis, 1 year for continuous enrollment before their index INS claim, and 18 months of continuous enrollment after their index INS claim during which they received either pMDI or A-INS. pMDI and A-INS patients were matched 1:2 using propensity scores. Nonparametric analyses compared outcomes between matched cohorts at 6, 12, and 18 months of follow-up. A total of 585 patients were matched (pMDI = 195, A-INS = 390). pMDI patients were more adherent to INS, as reflected in their higher median medication possession ratio (53.2% versus 32.7%; p < 0.0001) and fewer median days between fills (73 days versus 111 days; p = 0.0003). Significantly lower median per patient pharmacy fills (34.0 versus 50.5; p < 0.05) and costs ($1282 versus $2178; p < 0.01) were observed among pMDI patients versus A-INS patients 18 months after INS initiation and were maintained when analyses excluded INS fills. Adherence to INS and health care utilization and costs following INS initiation for AR differed by type of formulation received. Our findings suggest patient preferences for INS sensory attributes can drive adherence and affect disease control, and ultimately impact health care costs.

Hepatitis A and B vaccination in adults at risk: A survey of US healthcare providers' attitudes and practices.

This study aimed to evaluate the attitudes and practices of US healthcare professionals (HCPs) regarding the Advisory Committee on Immunization Practices (ACIP) vaccination recommendations on HepA and HepB for adult patients at risk of contracting these infections or experiencing complications of hepatitis disease. This cross-sectional, web-based survey of 400 US HCPs, which included nurse practitioners and family medicine, internal medicine, infectious disease, emergency department, and gastroenterology physicians, assessed HCPs' attitudes and practices regarding the ACIP recommendations for adult patients at risk for hepatitis disease. HCP participants were identified via a survey research panel. A recruitment quota of 400 HCPs was set, including 50 NPs, 100 FMs, 100 IMs, 50 GIs, 50 EDs, and 50 IDs. The most frequently reported reasons for not recommending either HepA or HepB vaccines were "I think the risk of HepA infection is low in this patient population" and "I am uncertain about what the guidelines say about vaccinating this population." The most reported factors considered when determining eligibility for either vaccine were medical history and the patient's willingness/motivation to be vaccinated. Most reported it was extremely or moderately important to prevent hepatitis disease by vaccinating adult patients at risk, and most also reported recommending a HepA vaccine or HepB vaccine to patients at risk. Although most HCPs reported recommending HepA and HepB vaccines to patients at risk, these findings contrast with the low reported vaccination rates among these populations, and improved awareness of the ACIP recommendations among HCPs is needed.

Although hepatitis A and hepatitis B are vaccine-preventable diseases, not enough adults at risk are vaccinated in the United States (US). The Advisory Committee on Immunization Practices (ACIP) makes recommendations on the use of vaccines in the US. The ACIP recommendations identify groups of people at risk of contracting hepatitis A infection or experiencing complications of hepatitis A disease (e.g., people with chronic liver disease) and hepatitis B infection or its related complications (e.g., people with diabetes).To identify potential barriers to vaccination, we surveyed 400 US healthcare professionals to evaluate their views about the ACIP recommendations on hepatitis A and hepatitis B vaccination for patients at risk of infection or complications. Most reported it was extremely or moderately important to prevent hepatitis A or hepatitis B infection by vaccinating these adult patients. The most commonly reported reasons for not recommending either vaccine were "I am uncertain about what the guidelines say about vaccinating this population" and "I think the risk of hepatitis A or hepatitis B infection is low in this patient population".Our findings show that improved awareness of the guidelines among healthcare professionals is needed, particularly of the importance of hepatitis A vaccination, and hepatitis B vaccination in adults with diabetes. In addition to helping the ongoing multi-state hepatitis A outbreaks, this could aid in the successful implementation of the recent ACIP recommendation for hepatitis B vaccination in all adults that is expected to reduce barriers to vaccination.

The Population-Wide Risk-Benefit Profile of Extending the Primary COVID-19 Vaccine Course Compared with an mRNA Booster Dose Program.

The vaccination program is reducing the burden of COVID-19. However, recently, COVID-19 infections have been increasing across Europe, providing evidence that vaccine efficacy is waning. Consequently, booster doses are required to restore immunity levels. However, the relative risk-benefit ratio of boosters, compared to pursuing a primary course in the unvaccinated population, remains uncertain. In this study, a susceptible-exposed-infectious-recovered (SEIR) transmission model of SARS-CoV-2 was used to investigate the impact of COVID-19 vaccine waning on disease burden, the benefit of a booster vaccine program compared to targeting the unvaccinated population, and the population-wide risk-benefit profile of vaccination. Our data demonstrates that the rate of vaccine efficacy waning has a significant impact on COVID-19 hospitalisations with the greatest effect in populations with lower vaccination coverage. There was greater benefit associated with a booster vaccination strategy compared to targeting the unvaccinated population, once >50% of the population had received their primary vaccination course. The population benefits of vaccination (reduced hospitalisations, long-COVID and deaths) outweighed the risks of myocarditis/pericarditis by an order of magnitude. Vaccination is important in ending the COVID-19 pandemic sooner, and the reduction in hospitalisations, death and long-COVID associated with vaccination significantly outweigh any risks. Despite these obvious benefits some people are vaccine reluctant, and as such remain unvaccinated. However, when most of a population have been vaccinated, a focus on a booster vaccine strategy for this group is likely to offer greater value, than targeting the proportion of the population who choose to remain unvaccinated.

The potential clinical impact of implementing different COVID-19 boosters in fall 2022 in the United States.

OBJECTIVE: Emerging SARS-COV-2 variants are spurring the development of adapted vaccines as public health authorities plan for fall vaccinations. This study estimated the number of infections and hospitalizations prevented by three potential booster strategies for adults (≥18 years) in the United States: boosting with either Moderna's (1) licensed first generation monovalent vaccine mRNA-1273 (ancestral strain) or (2) candidate bivalent vaccine mRNA-1273.214 (ancestral + BA.1 variant of concern [VOC]) starting in September 2022, or (3) Moderna's updated candidate bivalent vaccine mRNA-1273.222 (ancestral + BA.4/5 VOC) starting November 2022 due to longer development time. METHODS: An age-stratified, transmission dynamic, Susceptible-Exposed-Infection-Recovered (SEIR) model, adapted from previous literature, was used to estimate infections over time; the model contains compartments defined by SEIR and vaccination status. A decision tree was used to estimate clinical consequences of infections. Calibration was performed so the model tracks the actual course of the pandemic to present time. RESULTS: Vaccinating with mRNA-1273(Sept), mRNA-1273.214(Sept), and mRNA-1273.222(Nov) is predicted to reduce infections by 34%, 40%, and 18%, respectively, and hospitalizations by 42%, 48%, and 25%, respectively, over 6 months compared to no booster. Sensitivity analyses around transmissibility, vaccine coverage, masking, and waning illustrate that boosting with mRNA-1273.214 in September prevented more cases of infection and hospitalization than the other vaccines. LIMITATIONS AND CONCLUSIONS: With the emergence of new variants, key characteristics of the virus that affect estimates of spread and clinical impact also evolve, making parameter estimation difficult. Our analysis demonstrated that boosting with mRNA-1273.214 was more effective over 6 months in preventing infections and hospitalizations with a BA.4/5 subvariant than the tailored vaccine, simply because it could be deployed 2 months earlier. We conclude that there is no advantage to delay boosting until a more effective BA.4/5 vaccine is available; earlier boosting with mRNA-1273.214 will prevent the most infections and hospitalizations.

Psychometric validation of the revised SCOPA-Diary Card: expanding the measurement of non-motor symptoms in Parkinson's disease.

BACKGROUND: To identify key non-motor symptoms of Parkinson's disease (PD) to include in a daily diary assessment for off-time, revise the Scales for Outcomes of Parkinson's disease Diary Card (SCOPA-DC) to include these non-motor symptoms, and investigate the validity, reliability and predictive utility of the Revised SCOPA-DC in a U.S. population. METHODS: A convenience sample was used to recruit four focus groups of PD patients. Based on findings from focus groups, the SCOPA-DC was revised and administered to a sample of 101 PD patients. Confirmatory factor analysis was conducted to test the domain structure of the Revised SCOPA-DC. The reliability, convergent and discriminant validity, and ability to predict off-time of the Revised SCOPA-DC were then assessed. RESULTS: Based on input from PD patients, the Revised SCOPA-DC included several format changes and the addition of non-motor symptoms. The Revised SCOPA-DC was best represented by a three-factor structure: Mobility, Physical Functioning and Psychological Functioning. Correlations between the Revised SCOPA-DC and other Health-Related Quality of Life scores were supportive of convergent validity. Known-groups validity analyses indicated that scores on the Revised SCOPA-DC were lower among patients who reported experiencing off-time when compared to those without off-time. The three subscales had satisfactory predictive utility, correctly predicting off-time slightly over two-thirds of the time. CONCLUSIONS: These findings provide evidence of content validity of the Revised SCOPA-DC and suggest that a three-factor structure is an appropriate model that provides reliable and valid scores to assess symptom severity among PD patients with symptom fluctuations in the U.S.

Determining the efficacy of rasagiline in reducing bradykinesia among Parkinson's disease patients: a review.

BACKGROUND: Bradykinesia has a significant impact on the lives of Parkinson's disease (PD) patients. Consequently, treating this symptom is of particular concern for patients and clinicians. A number of studies have documented the efficacy of rasagiline in reducing the severity of PD symptoms. OBJECTIVE: To summarize studies that specifically examined the impact of rasagiline on bradykinesia symptoms in PD patients across disease severity. METHODS: The EMBASE database was searched for relevant articles published between 2000 and November 2010. RESULTS: Three studies were identified that explicitly examined the effect of rasagiline on the bradykinesia subscale of the Unified Parkinson's Disease Rating Scale (UPDRS) motor examination. In each, 1 mg/day rasagiline significantly reduced bradykinesia scores in patients. CONCLUSION: As a monotherapy or an adjunctive therapy, rasagiline is an effective drug for reducing the severity of bradykinesia in PD patients.

Time and cost of administering COVID-19 mRNA vaccines in the United States.

In early 2020, the World Health Organization (WHO) declared the coronavirus disease 2019 (COVID-19) outbreak a global pandemic. In response, two novel messenger RNA (mRNA)-based vaccines: mRNA-1273 (Moderna) and BNT162b2 (Pfizer-BioNTech) were rapidly developed. A thorough understanding of the differences in workflow requirements between the two vaccines may lead to improved efficiencies and reduced economic burden, both of which are crucial for streamlining vaccine deployment and minimizing wastage. Vaccine administration workflow costs are borne by providers and reimbursed separately from dose acquisition in the United States. Currently, mRNA-1273 and BNT162b2 are the most administered COVID-19 vaccines in the United States. In this study, US-licensed and practicing pharmacists were interviewed to collect data on differences in terms of labor costs associated with the workflows for mRNA-1273 and BNT162b2. Results suggest the cost differential for mRNA-1273 compared to BNT162b2 is -$0.82 (or -$1.01 when assuming volume equivalency). If extrapolated to even just a proportion of the remaining unvaccinated US population, this can amount to significant workflow efficiencies and lower vaccine administration costs. Further, as key differences in the vaccine workflow steps between the two vaccines would be similar in other settings/regions, these findings are likely transferable to health-care systems worldwide.

Vaccinating Adolescents and Children Significantly Reduces COVID-19 Morbidity and Mortality across All Ages: A Population-Based Modeling Study Using the UK as an Example.

Debate persists around the risk-benefit balance of vaccinating adolescents and children against COVID-19. Central to this debate is quantifying the contribution of adolescents and children to the transmission of SARS-CoV-2, and the potential impact of vaccinating these age groups. In this study, we present a novel SEIR mathematical disease transmission model that quantifies the impact of different vaccination strategies on population-level SARS-CoV-2 infections and clinical outcomes. The model employs both age- and time-dependent social mixing patterns to capture the impact of changes in restrictions. The model was used to assess the impact of vaccinating adolescents and children on the natural history of the COVID-19 pandemic across all age groups, using the UK as an example. The base case model demonstrates significant increases in COVID-19 disease burden in the UK following a relaxation of restrictions, if vaccines are limited to those ≥18 years and vulnerable adolescents (≥12 years). Including adolescents and children in the vaccination program could reduce overall COVID-related mortality by 57%, and reduce cases of long COVID by 75%. This study demonstrates that vaccinating adolescents and children has the potential to play a vital role in reducing SARS-CoV-2 infections, and subsequent COVID-19 morbidity and mortality, across all ages. Our results have major global public health implications and provide valuable information to inform a potential pandemic exit strategy.

Estimated Public Health Impact of the Recombinant Zoster Vaccine.

OBJECTIVE: To investigate the potential public health impact of adult herpes zoster (HZ) vaccination with the adjuvanted recombinant zoster vaccine (RZV) in the United States in the first 15 years after launch. METHODS: We used a publicly available model accounting for national population characteristics and HZ epidemiological data, vaccine characteristics from clinical studies, and anticipated vaccine coverage with RZV after launch in 2018. Two scenarios were modeled: a scenario with RZV implemented with 65% coverage after 15 years and a scenario continuing with zoster vaccine live (ZVL) with coverage increasing 10% over the same period. We estimated the numbers vaccinated, and the clinical outcomes and health care use avoided yearly, from January 1, 2018, to December 31, 2032. We varied RZV coverage and investigated the associated impact on HZ cases, complications, and health care resource use. RESULTS: With RZV adoption, the numbers of individuals affected by HZ was predicted to progressively decline with an additional 4.6 million cumulative cases avoided if 65% vaccination with RZV was reached within 15 years. In the year 2032, it was predicted that an additional 1.3 million physicians' visits and 14.4 thousand hospitalizations could be avoided, compared with continuing with ZVL alone. These numbers could be reached 2 to 5 years earlier with 15% higher RZV vaccination rates. CONCLUSION: Substantial personal and health care burden can be alleviated when vaccination with RZV is adopted. The predicted numbers of HZ cases, complications, physicians' visits, and hospitalizations avoided, compared with continued ZVL vaccination, depends upon the RZV vaccination coverage achieved.

Early examination of real-world uptake and second-dose completion of recombinant zoster vaccine in the United States from October 2017 to September 2019.

Shingrix (Recombinant zoster vaccine, RZV) was approved in October 2017 in the United States (US) for the prevention of herpes zoster in adults aged 50 years and older. The vaccine is administered in two doses, with the second dose administration recommended between two and six months after the first dose. Examination of uptake and series completion is important to ensure appropriate use, especially at the time of vaccine introduction. This report provides demographic characteristics of patients receiving RZV between October 2017 and September 2019, first- and second-dose uptake, and a cumulative estimation of second-dose completion by month for US adults aged 50 years and older. Monthly uptake increased rapidly since October 2017; overall, 7,097,441 first doses of RZV were administered along with 4,277,636 second doses during the observed timeframe. Among people with an observed first-dose administration, 70% and 80% completed the two-dose series within six and 12 months post initial dose, respectively. This evidence suggests that RZV has rapidly been adopted by a large population in the US and most are following manufacturer or policy recommendations regarding series completion. Further analyses are needed to explore potential patient, provider, and policy-relevant characteristics associated with second-dose completion that could serve as targets for further improvement.