Search

This study aimed to estimate the epidemiologic and economic impact of a nonavalent human papillomavirus (HPV) vaccination program for 13- to 14-year-old females compared with that of the bivalent vaccine in Taiwan.A previously developed dynamic transmission model for the nonavalent HPV vaccine was adapted to the Taiwan setting. The natural history of cervical cancer and genital warts was simulated by the HPV model assuming an 80% vaccination coverage rate in girls aged 13 to 14 years of age with a 2-dose schedule for the nonavalent and bivalent HPV vaccines. A lifetime duration of vaccine protection was assumed for the HPV vaccine types.The model estimated that the nonavalent HPV vaccine would prevent an additional 15 951 cervical cancer cases, 6600 cervical cancer-related deaths, 176 702 grade 2 or grade 3 cervical intraepithelial neoplasia cases, 103 959 grade 1 cervical intraepithelial neoplasia cases, and 1 115 317 genital warts cases compared with the bivalent HPV vaccine. The nonavalent HPV vaccination program was projected to cost an additional New Taiwan dollars (NTD) 675.21 per person and to produce an additional 0.00271 quality-adjusted life-year per person over 100 years compared with the bivalent HPV vaccine. Thus, the incremental cost-effectiveness ratio of the nonavalent HPV vaccine versus the bivalent HPV vaccine was NTD 249 462/quality-adjusted life-year.A nonavalent HPV vaccination program for 13- to 14-year-old girls would have additional public health and economic impacts and would be highly cost-effective compared with the bivalent HPV vaccine, relative to per capita gross domestic product, which is estimated at NTD 746 526 for Taiwan.

Although no human papillomavirus (HPV) vaccine is indicated for single-dose administration, some observational evidence suggests that a 1-dose regimen might reduce HPV infection risk to that achieved with 2 doses. This study estimated the potential health and economic outcomes associated with switching from a 2-dose HPV vaccination program for girls and boys aged 13-14 years to an off-label 9-valent (9vHPV), 1-dose regimen, accounting for the uncertainty of the effectiveness and durability of a single dose. A dynamic HPV transmission infection and disease model was adapted to the United Kingdom and included a probabilistic sensitivity analysis using estimated distributions for duration of protection of 1-dose and degree of protection of 1 relative to 2 doses. One-way sensitivity analyses of key inputs were performed. Outcomes included additional cancer and disease cases and the difference in net monetary benefit (NMB). The 1-dose program was predicted to result in 81,738 additional HPV-related cancer cases in males and females over 100 years compared to the 2-dose program, ranging from 36,673 to 134,347 additional cases (2.5% and 97.5% quantiles, respectively), and had a 7.8% probability of being cost-effective at the £20,000/quality-adjusted life years willingness-to-pay (WTP) threshold. In one-way sensitivity analyses, the number of additional cancer cases was sensitive to the median of the duration of protection distribution and coverage rates. The differences in NMBs were sensitive to the median of the duration of protection distribution, dose price and discount rate, but not coverage variations. Across sensitivity analyses, the probability of 1 dose being cost-effective vs 2 doses was 50% at the standard WTP threshold. Adoption of a 1-dose 9vHPV vaccination program resulted in more vaccine-preventable HPV-related cancer and disease cases in males and females, introduced substantial uncertainty in health and economic outcomes, and had a low probability of being cost-effective compared to the 2-dose program.

OBJECTIVE: The COVID-19 pandemic has led to significant reductions in the administration of routinely recommended vaccines among adolescents in the US including tetanus, diphtheria, and acellular pertussis (Tdap); meningococcal (ACWY); and human papillomavirus (HPV) vaccines. The extent to which these deficits could persist in 2021 and beyond is unclear. To address this knowledge gap, this study estimated the cumulative deficits of routine vaccine doses among US adolescents during the COVID-19 pandemic and estimated the time and effort needed to recover from those deficits. METHODS: Monthly reductions in Tdap, meningococcal, and HPV doses administered to US adolescents during the COVID-19 pandemic were quantified using MarketScan Commercial Claims and Encounters data. The time and effort required to reverse the vaccination deficit under various catch-up scenarios were estimated. RESULTS: Annual doses administered of Tdap, meningococcus, and HPV vaccines decreased by 21.2%, 20.8%, and 24.0%, respectively, in 2020 compared to 2019. For 2021, the reduction in doses administered is projected to be 6%-21% compared to 2019 under different scenarios. The projected deficit of missed doses is expected to be cleared between winter 2023 and fall 2031. CONCLUSIONS: Administration rates of routine vaccines decreased significantly among US adolescents during COVID-19. Reversing these deficits to mitigate long-term health and economic consequences will require a sustained increase in vaccination rates over multiple years.

Human papillomavirus (HPV) cause cancers in a variety of anatomic sites presenting at various stages of disease. Current economic assessments rely on HPV-related cancer cost estimates from data prior to the launch of the nonavalent HPV vaccine (2014). The goal of the present study was to assess and describe the current direct medical care burden of HPV-related cancers in the US.Using Clinformatics Data Mart, patients in the US who were newly diagnosed with cervical, vulvar, vaginal, anal, and oropharyngeal cancers between 2012 and 2015 were compared to non-cancer matched (propensity score) controls. Health care resource utilization and direct medical cost (2020 USD) were assessed over a 2-year follow-up period following index diagnosis from a payer perspective. The cost for censored time was estimated using generalized linear model while adjusting for survival probability using cox-proportional hazard model. Confidence intervals were calculated with bootstrapping technique.The analyses included 4128 cervical, 1580 vulvar, 538 vaginal, 1827 anal, and 6106 oropharyngeal cancers and matched controls. Cases and controls had similar baseline clinical characteristics and length of follow-up. The 2-year incremental direct medical costs were $93,272, $81,676, $141,096, $129,366, and $134,045 for cervical, vulvar, vaginal, anal, and oropharyngeal cancers respectively. Outpatient care costs was the biggest driver of the total incremental medical costs. Most cancer costs were incurred during the first 6 months of follow-up and then stabilized during follow-up.HPV-related cancers are responsible for substantial health care expenditure each year.

Human papillomavirus (HPV) is one of the most common sexually transmitted infection in the United States and can lead to cervical, vulvovaginal, anal, penile, and oropharyngeal cancers. Compared with the general population, US military members are at a higher risk of HPV-related conditions, yet vaccination rates are relatively low in this population. As many service members may not be diagnosed with HPV-related cancers until after they leave active service, the objective of this study was to determine the incidence, prevalence, and economic burden of HPV-related cancers among US veterans. The study used the 2014���2018 Veterans Health Administration (VHA) database to identify newly diagnosed adult patients (cases) with HPV-related cancers, including cervical, vulvovaginal, anal, penile, and oropharyngeal cancers. Cases were matched by age, race, and sex to patients without HPV related cancer (controls). Outcome measures included annual incidence, prevalence, health care resource utilization (HCRU), and costs. These outcomes were calculated from the index date (first cancer diagnosis) through the earliest of 24 months, death, or end of study period. Adjusted results were examined using generalized linear models. The annual prevalence and incidence rates of HPV-related cancers ranged from 43 (anal) to 790 (oropharyngeal) cases per million (CPM), and four (anal) to 131 (cervical) CPM, respectively. Compared with controls, cases had significantly higher annual HCRU. Mean numbers of annual inpatient hospitalizations were several times higher compared to controls (cervical: 6.7-times (��); vulvovaginal: 2.7��; penile: 6.6��; oropharyngeal: 10.2��; and anal: 14.9��; all p p HPV-related cancers may cause significant clinical and economic burden within the VHA system. Given the consequences of HPV-related cancers among veterans who did not have access to the vaccine, HPV vaccination of active military and eligible veterans should be considered a healthcare priority.

Introduction In Hong Kong (HK), a single-cohort vaccination program for 10–12-year-old girls with the 9-valent human papillomavirus (HPV) vaccine (9vHPV; types 6/11/16/18/31/33/45/52/58) has been launched. This study assessed the public health impact and cost-effectiveness of implementing routine 9vHPV vaccination (12-year-olds) with or without catch-up 9vHPV vaccination (13–18-year-olds) in HK. Methods The health impact and costs of implementing routine 9vHPV vaccination with or without catch-up vaccination over a 100-year time horizon were evaluated using a validated HPV-type transmission dynamic model adapted to the HK population; analyses were performed from a healthcare payer perspective. Routine vaccination (12-year-old girls) and catch-up vaccination (13–18 years) assumed vaccine coverage rates of 70% (base case) and 30%, respectively. The model also assumed herd immunity, lifelong vaccine protection, a discount rate of 3%, and a cost per dose of HK dollars (HKD) 858 [United States dollars (USD) 110] and HKD 1390 (USD 179) for the 2-valent HPV (2vHPV) and 9vHPV vaccines, respectively. HPV disease-related incidence and the incremental cost-effectiveness ratio (ICER) per quality-adjusted-life-year (QALY) were estimated. Cost-effectiveness was determined at a ceiling threshold of HK dollars (HKD) 382,046 (USD 49,142) or 1.0 times the gross domestic product per capita of HK. Results Compared with routine 9vHPV alone, routine plus catch-up 9vHPV is projected to reduce cervical cancer incidence by 3.4%. Routine plus catch-up 9vHPV will also reduce genital warts incident cases for males/females by 2.6%/5.4%. The incremental cost-effectiveness ratios were HKD 29,911 (USD 3847)/quality-adjusted life-year (QALY) for routine plus catch-up 9vHPV versus routine 9vHPV alone and HKD 25,524 (USD 3283)/QALY for routine 9vHPV alone versus screening only. Sensitivity analyses indicated that routine plus catch-up 9vHPV compared with routine 9vHPV alone remained cost-effective at coverage rates of 30% and 90%. Conclusions This analysis predicts that the current HK vaccination strategy can be considered cost-effective and will provide maximum health benefit. These results support addition of the routine 9vHPV vaccine with or without catch-up 9vHPV vaccination to the regional vaccination program in HK.

The coronavirus disease 2019 (COVID-19) pandemic has significantly affected utilization of preventative health care, including vaccines. We aimed to assess HPV vaccination rates during the pandemic, and conduct a simulation model-based analysis to estimate the impact of current coverage and future pandemic recovery scenarios on disease outcomes. The model population included females and males of all ages in the US. The model compares pre-COVID vaccine uptake to 3 reduced coverage scenarios with varying recovery speed. Vaccine coverage was obtained from Truven Marketscan™. Substantially reduced coverage between March- August 2020 was observed compared to 2018-2019. The model predicted that 130,853 to 213,926 additional cases of genital warts; 22,503 to 48,157 cases of CIN1; 48,682 to 110,192 cases of CIN2/3; and 2,882 to 6,487 cases of cervical cancer will occur over the next 100 years, compared to status quo. Providers should plan efforts to recover HPV vaccination and minimize potential long-term consequences.

Consumption of ethanol is a considerable risk factor for death in heroin overdose. We sought to determine whether a mildly intoxicating concentration of ethanol could alter morphine tolerance at the cellular level. In rat locus coeruleus (LC) neurons, tolerance to morphine was reversed by acute exposure of the brain slice to ethanol (20 mM). Tolerance to the opioid peptide [d-Ala(2),N-MePhe(4),Gly-ol]-enkephalin was not reversed by ethanol. Previous studies in LC neurons have revealed a role for protein kinase C (PKC)α in μ-opioid receptor (MOPr) desensitization by morphine and in the induction and maintenance of morphine tolerance, but we have been unable to demonstrate that 20 mM ethanol produces significant inhibition of PKCα. The ability of ethanol to reverse cellular tolerance to morphine in LC neurons was absent in the presence of the phosphatase inhibitor okadaic acid, indicating that dephosphorylation is involved. In human embryonic kidney 293 cells expressing the MOPr, ethanol reduced the level of MOPr phosphorylation induced by morphine. Ethanol reversal of tolerance did not appear to result from a direct effect on MOPr since acute exposure to ethanol (20 mM) did not modify the affinity of binding of morphine to the MOPr or the efficacy of morphine for G-protein activation as measured by guanosine 5'-O-(3-[(35)S]thio)triphosphate binding. Similarly, ethanol did not affect MOPr trafficking. We conclude that acute exposure to ethanol enhances the effects of morphine by reversing the processes underlying morphine cellular tolerance.

Potential long-term health effects from tobacco products can be estimated by measuring changes in biochemical indicators of disease mechanisms like inflammation. This study assesses the potential relationships between biomarkers of potential harm (BOPH) and biomarkers of cigarette smoke exposure (BOE) based on data from the NHANES (2007–2012, n = 17,293 respondents). Statistically significant relationships were observed between white blood cells (WBC) and high-density lipoprotein (HDL) and BOE; between WBC and high-sensitivity C-reactive protein and smoking status; and between WBC and HDL and smoking intensity. This analysis suggests that WBC and HDL are useful BOPH in studies assessing the health risks of cigarette smoking.

Phosphorylation is considered a key event in the signalling and regulation of the μ opioid receptor (MOPr). Here, we used mass spectroscopy to determine the phosphorylation status of the C-terminal tail of the rat MOPr expressed in human embryonic kidney 293 (HEK-293) cells. Under basal conditions, MOPr is phosphorylated on Ser(363) and Thr(370), while in the presence of morphine or [D-Ala2, NMe-Phe4, Gly-ol5]-enkephalin (DAMGO), the COOH terminus is phosphorylated at three additional residues, Ser(356) , Thr(357) and Ser(375). Using N-terminal glutathione S transferase (GST) fusion proteins of the cytoplasmic, C-terminal tail of MOPr and point mutations of the same, we show that, in vitro, purified G protein-coupled receptor kinase 2 (GRK2) phosphorylates Ser(375), protein kinase C (PKC) phosphorylates Ser(363), while CaMKII phosphorylates Thr(370). Phosphorylation of the GST fusion protein of the C-terminal tail of MOPr enhanced its ability to bind arrestin-2 and -3. Hence, our study identifies both the basal and agonist-stimulated phospho-acceptor sites in the C-terminal tail of MOPr, and suggests that the receptor is subject to phosphorylation and hence regulation by multiple protein kinases.

Objective: Assess the newspaper coverage of off-label drug use from the years 1990 to 2010.Methods: News articles from the top six selling national newspapers were studied. Variables of interest were the number of articles published, article themes, headline and content tone, concerns and benefits discussed with offlabel use, drugs discussed, and primary individuals interviewed for the article.Results: The number of articles published on off-label drug and device use steadily increased over the period of the study. The key themes discussed in these articles were concerns over safety and efficacy (45.8%) and benefits of off-label prescribing (25.9%). The overall tone of the articles was often negative toward offlabel use (40.4% of articles).Conclusion: Overall, the tone and coverage of off-label medication and device usage was more negative than positive, focusing more on concerns than on benefits. Nevertheless, there did not appear to be any impartial or systematic media bias against the practice.

Current technologies for overcoming lower extremity weakness are expensive and restricting. The Intuitive Leg Assist Device 2 (ILAD-2), a second-generation device, will feature a lightweight, comfortable, and affordable alternative. The ILAD-2 will incorporate two degrees of freedom at the hip joint, adjustable components for a variety of user heights, and a more efficient motor and gear design. The motor (Industrial Torxis Servo i01855) will have a torque of 22.6 N*m, connected to a gear reduction system that will achieve a desired 30 N*m output torque. The ILAD-2 will mimic the natural gait cycle using both force sensors and accelerometers as a feedback system. In addition, a dorsiflexion assist device incorporating a spring will be used at the ankle to ease the effort input by the user throughout the gait cycle. Using aluminum alloy components, along with a new motor and gear system, the overall weight of the device will be decreased as well. The user effort will be evaluated with and without the device using electromyography (EMG), in addition to video analysis of the gait cycle.

Appointment-based medication synchronization (ABMS) has been associated with greater patient adherence and persistence when patients begin taking chronic medications. It is not known whether similar results will be seen for patients who have been taking chronic medications for 6 months or more.To compare the impact of a community pharmacy chain's ABMS program on medication adherence and persistence of existing users of chronic medications with individuals who are not enrolled in the program.A retrospective cohort study compared patients receiving ABMS with matched comparison groups receiving usual care. ABMS consisted of synchronizing a patient's medications to be dispensed on a single appointment day every month, a call to the patient prior to the appointment day to address any prescription changes and to remind the patient, and a patient visit to the pharmacy to pick up the medications. Outcomes were 1-year adherence rates using proportion of days covered (PDC) and 1-year nonpersistence rates. Data for this study came from prescription claims records of patients taking 1 of 6 chronic medication classes during the period of December 1, 2011, to February 28, 2014. ABMS patients were matched with comparison groups according to prior adherence behavior, medication class, age, gender, and geographic region.Mean PDC scores ranged from 0.73 to 0.91 for ABMS patients (n = 205 to 716) and from 0.57 to 0.71 for usual care depending on the medication class. The percentage of adherent individuals (i.e., PDC ≥ 0.80) was 55% to 84% for ABMS participants and 37% to 62% for usual care. Odds of adherence was 2.3 to 3.6 times greater with ABMS. Usual care patients became nonpersistent (61% to 74%) more often than ABMS patients (33% to 44%) with hazard ratios of nonpersistence being 0.39 to 0.67 for individuals in the program.An ABMS program in a community pharmacy setting was associated with higher rates of adherence and persistence for patients who had been taking chronic medications for at least 6 months. Approximately 18 to 35 additional ABMS participants were adherent for every 100 patients enrolled when compared with usual care. For every 100 patients receiving usual care, 17 to 40 additional patients in the ABMS group were persistent. This study shows that ABMS programs can improve medication adherence and persistence for patients who are newly prescribed or currently taking chronic medications.