Cost-effectiveness of maribavir versus conventional antiviral therapies for post-transplant refractory cytomegalovirus infection with or without genotypic resistance: A US perspective.

This study evaluated the cost-effectiveness of maribavir versus investigator-assigned therapy (IAT; valganciclovir/ganciclovir, foscarnet, or cidofovir) for post-transplant refractory cytomegalovirus (CMV) infection with or without resistance. A two-stage Markov model was designed using data from the SOLSTICE trial (NCT02931539), real-world multinational observational studies, and published literature. Stage 1 (0-78 weeks) comprised clinically significant CMV (csCMV), non-clinically significant CMV (n-csCMV), and dead states; stage 2 (78 weeks-lifetime) comprised alive and dead states. Total costs (2022 USD) and quality-adjusted life years (QALYs) were estimated for the maribavir and IAT cohorts. An incremental cost-effectiveness ratio was calculated to determine cost-effectiveness against a willingness-to-pay threshold of $100 000/QALY. Compared with IAT, maribavir had lower costs ($139 751 vs $147 949) and greater QALYs (6.04 vs 5.83), making it cost-saving and more cost-effective. Maribavir had higher acquisition costs compared with IAT ($80 531 vs $65 285), but lower costs associated with administration/monitoring ($16 493 vs $27 563), adverse events (AEs) ($11 055 vs $16 114), hospitalization ($27 157 vs $33 905), and graft loss ($4516 vs $5081), thus making treatment with maribavir cost-saving. Maribavir-treated patients spent more time without CMV compared with IAT-treated patients (0.85 years vs 0.68 years), leading to lower retreatment costs for maribavir (cost savings: -$42 970.80). Compared with IAT, maribavir was more cost-effective for transplant recipients with refractory CMV, owing to better clinical efficacy and avoidance of high costs associated with administration, monitoring, AEs, and hospitalizations. These results can inform healthcare decision-makers on the most effective use of their resources for post-transplant refractory CMV treatment.

Systematic reviews of machine learning in healthcare: a literature review.

INTRODUCTION: The increasing availability of data and computing power has made machine learning (ML) a viable approach to faster, more efficient healthcare delivery. METHODS: A systematic literature review (SLR) of published SLRs evaluating ML applications in healthcare settings published between1 January 2010 and 27 March 2023 was conducted. RESULTS: In total 220 SLRs covering 10,462 ML algorithms were reviewed. The main application of AI in medicine related to the clinical prediction and disease prognosis in oncology and neurology with the use of imaging data. Accuracy, specificity, and sensitivity were provided in 56%, 28%, and 25% SLRs respectively. Internal and external validation was reported in 53% and less than 1% of the cases respectively. The most common modeling approach was neural networks (2,454 ML algorithms), followed by support vector machine and random forest/decision trees (1,578 and 1,522 ML algorithms, respectively). EXPERT OPINION: The review indicated considerable reporting gaps in terms of the ML's performance, both internal and external validation. Greater accessibility to healthcare data for developers can ensure the faster adoption of ML algorithms into clinical practice.

Investigating Tetanus, Diphtheria, Acellular Pertussis Vaccination During Pregnancy and Risk of Congenital Anomalies.

INTRODUCTION: This observational retrospective matched cohort study evaluated the safety of a prenatal tetanus, diphtheria, acellular pertussis (Tdap) vaccination, Boostrix. We previously reported on the risk of maternal and neonatal outcomes; here we report on the risk of congenital anomalies in infants at birth through 6 months of age. METHODS: The study included pregnant Kaiser Permanente Southern California members. Women who received the Tdap vaccine on or after the 27th week of pregnancy between January 2018 and January 2019 were matched to women who were pregnant between January 2012 and December 2014 and were not vaccinated with Tdap during pregnancy. Unadjusted and adjusted relative risks (aRRs) with 95% confidence intervals were estimated by Poisson regression. Quantitative secular trend analyses, from 2011 to 2017, were conducted on congenital anomalies with a statistically significant aRR > 1. RESULTS: The analysis consisted of 16,350 and 16,088 live-born infants in the Tdap-exposed and unexposed cohorts, respectively. Of the 14 congenital anomaly body systems evaluated, 8 (eye, ear/face/neck, respiratory, upper gastrointestinal, genital, renal, musculoskeletal, integument) had statistically significant elevated aRRs, with point estimates ranging from 1.17 to 2.02. The observed elevated aRRs were consistent with their respective secular increases over time. CONCLUSION: Cautious interpretation of these findings is warranted as these increases may have resulted from improved identification and diagnosis. Furthermore, the biological plausibility of an association between maternal vaccine exposure in the third trimester of pregnancy and birth defects is low. The overall study findings support the safety of maternal immunization with Boostrix during the third trimester of pregnancy. TRIAL REGISTRATION: ClinicalTrials.gov identifier, NCT03463577.

Herpes Zoster Incidence and Burden in Adults With Type 2 Diabetes in the U.S.: A Retrospective Database Analysis.

OBJECTIVE: Data on the real-world burden of herpes zoster (HZ) in adults with type 2 diabetes (T2D) in the U.S. are limited. We assessed HZ in patients with and without T2D and measured the impact of HZ on health care resource use (HCRU) and costs. RESEARCH DESIGN AND METHODS: This retrospective cohort analysis used U.S. commercial claims data (sourced from claims incurred between 1 January 2012 and 31 July 2018). HZ incidence rates/1,000 person-years (PYs) were calculated in patients with and without T2D. HZ risk was evaluated using Poisson regression to generate adjusted incidence rate ratios (aIRRs). Patients with T2D with HZ were propensity score matched to patients with T2D only and to patients with HZ without T2D. HCRU and costs were compared across cohorts during a 1-year follow-up period. Cox proportional hazards analyses evaluated factors associated with HZ-related complications. RESULTS: Crude HZ incidence rates in patients with and without T2D were 9.8/1,000 PY and 2.6/1,000 PY, respectively. T2D patients were almost twice as likely to be diagnosed with HZ (aIRR 1.84; 95% CI 1.82-1.85). HZ was associated with increased HCRU and health care costs. At 12 months, unadjusted incremental all-cause health care costs for patients with T2D with HZ versus patients with T2D without HZ were $5,216. The unadjusted incremental HZ-related health care costs for patients with T2D with HZ versus patients with HZ without T2D were $2,726. Age was the most important predictor for HZ-related complications. CONCLUSIONS: Given the increased risk of HZ and HCRU and cost burden in patients with T2D, HZ prevention in patients with T2D may be beneficial.

Safety of tetanus, diphtheria, acellular pertussis (Tdap) vaccination during pregnancy.

The objective of this study was to evaluate the safety of prenatal tetanus, diphtheria, acellular pertussis (Tdap) vaccination. This cohort study was conducted among pregnant members at Kaiser Permanente Southern California (KPSC). The exposed cohort consisted of women who received Tdap vaccine on or after the 27th week of pregnancy between January 2018 and January 2019. The unexposed cohort consisted of matched women who were pregnant between January 2012 and December 2014 and were not vaccinated with any Tdap vaccine throughout their pregnancy. Maternal and infant characteristics and pre-specified endpoints were collected through automated data and review of the electronic health records. Unadjusted and adjusted relative risks (aRRs) with confidence intervals (CIs) were estimated by Poisson regression. Non-inferiority testing (i.e., to rule out a two-fold increase) was conducted for primary endpoints with adjustment for multiplicity. Superiority testing was conducted without multiplicity adjustment for secondary endpoints. The analysis consisted of 16,606 pairs of Tdap recipients and unexposed pregnant women. For the primary endpoints, the aRR for preeclampsia/eclampsia was 1.38 (98.75% CI:1.21-1.58) and the aRR for intrauterine infection was 1.28 (98.75% CI:1.12-1.47). These increases were consistent with the background increasing trend of these diagnoses among all pregnant women at KPSC since 2011, and the upper limit of the 98.75% CI of both aRRs did not exceed the pre-specified threshold of 2. No increased risks of small for gestational age (aRR = 1.04, 98.75% CI:0.94-1.16) or preterm delivery (aRR = 0.71, 98.75% CI:0.64-0.78) were observed. No evidence of increased risks for secondary endpoints, including poor fetal growth, preterm pre-labor rupture of membranes, stillbirth/fetal death, placental abruption, transfusion during delivery hospitalization, and neonatal death, was observed. Prenatal Tdap vaccination after the 27th week of pregnancy was not associated with increased risks of pre-specified maternal and infant outcomes, supporting the safety of Tdap vaccination during pregnancy.

Burden of opioid use for pain management among adult herpes zoster patients in the US and the potential impact of vaccination.

PLAIN LANGUAGE SUMMARYWhat is the context? Herpes zoster or shingles and its complications such as postherpetic neuralgia - a painful condition that affects the nerve fibers and skin - may lead to complex pain that can be addressed using opioids in some patients.The recombinant zoster vaccine (RZV) vaccine prevents shingles and, therefore, may reduce the use of opioids and the negative health outcomes and costs associated with it.What is new? In this retrospective medical claims study, including patients between 2012 and 2017, we evaluated the receipt of pain medication including opioids in herpes zoster patients, and assessed factors associated with opioid prescription.estimated health care resource utilization and costs associated with opioid use among patients with herpes zoster.assessed the impact of vaccination on opioid prescriptions.Among subjects receiving opioids, 78.5% started with a weak opioid dose. Dose escalation was uncommon.Postherpetic neuralgia, immunocompromised status, and comorbidities are the main risk factors associated with opioid prescription.Health care costs are almost double in patients with herpes zoster receiving opioids compared with patients without an opioid prescription.In a population of 1 million adults aged 50 years or older, vaccination with the recombinant zoster vaccine could prevent over 19,000 patients from receiving opioids.What is the impact? Prevention of herpes zoster through vaccination may be a highly effective strategy to reduce opioid prescriptions and costs related to pain management in a susceptible population.Increasing RZV vaccination coverage in adults aged ≥50 years may further reduce potential opioid prescriptions through a decrease in shingles incidence.

Cost-benefit analysis of vaccination against four preventable diseases in older adults: Impact of an aging population.

OBJECTIVE: This exploratory study estimates the economic value of the current vaccination program and increased coverage against four preventable diseases in older adults in the United States (US). METHODS: A population-based, age-structured economic model was used to conduct a cost-benefit analysis of vaccination against influenza, pertussis, herpes zoster, and pneumococcal disease among US adults aged 50 years and older, accounting for aging of the population. The model used separate decision trees for each disease to project the discounted number of vaccinated individuals, number of disease cases, and direct medical and indirect costs (2018 US$) over a 30-year period. Benefit-cost ratios (BCRs) and net present values were calculated for two primary analyses comparing current vaccination coverage versus no vaccination and comparing increased coverage versus current coverage. Key parameter values were varied in deterministic sensitivity analyses. RESULTS: Current adult vaccination coverage (vs. no vaccination) is estimated to result in nearly 65 million averted disease cases, $185 billion averted costs of cases, and $136 billion in incremental vaccination costs over a 30-year period from a societal perspective (BCR = 1.4). Increased vaccination coverage (vs. current coverage) is associated with over 33 million additional averted disease cases, $96 billion additional averted costs of cases, and nearly $83 billion in incremental vaccination costs, resulting in a societal BCR of 1.2 over 30 years. Deterministic sensitivity analyses demonstrated that results were most sensitive to disease incidence, vaccine efficacy, and productivity costs for time required for vaccination. CONCLUSIONS: Study results highlight the economic value of vaccination programs for older adults in the US and indicate that efforts to further increase vaccination coverage may be warranted and economically justifiable.

Impact of population aging on the burden of vaccine-preventable diseases among older adults in the United States.

Despite vaccination recommendations, the burden of vaccine-preventable diseases remains high in older adults in the United States (US), contributing to substantial morbidity, mortality, and health care resource use and costs. To adequately plan for health care resource needs and to help inform vaccination policies, burden of disease projections that account for population aging over the coming decades are needed. As a first step, this exploratory study projects the burden of influenza, pertussis, herpes zoster, and pneumococcal disease in adults aged 50 y and older in the US, using a population-based modeling framework with separate decision trees for each vaccine-preventable disease. The model uses projected population estimates from the US Census Bureau to account for changes in the US population over time and then calculates expected numbers of cases and associated costs for each disease, keeping current estimates of age-specific disease incidence, vaccine coverage, and efficacy constant over time. This approach was used to focus the exploratory analysis on the burden of disease that may be expected due to population changes alone, assuming that all else remains unchanged. Due to population growth and the shifting age distribution over the next 30 y, the annual societal economic burden for the four vaccine-preventable diseases is projected to increase from approximately $35 billion to $49 billion, resulting in cumulative costs of approximately $1.3 trillion, as well as more than 1 million disease-related deaths. Given such notable burden, further efforts to increase vaccination coverage and effectiveness in older adults are needed.

Maternal Immunization in the U.S.: A Nationwide Retrospective Cohort Study.

INTRODUCTION: At present, pregnant women in the U.S. are recommended to receive tetanus toxoid, reduced diphtheria toxoid, and acellular pertussis (Tdap) and influenza vaccines. This study assessed maternal coverage of these 2 vaccinations. METHODS: Data for this retrospective cohort study were extracted from 2 large administrative claims databases, the MarketScan Commercial and Multi-State Medicaid Databases, for 2009-2017 and analyzed in 2018. Women aged 15-44 years on the date of pregnancy end were included. Pregnancies with gestational age of less than 23 weeks were excluded from the Tdap vaccination endpoint owing to the optimal recommended gestational age for Tdap vaccination. Multivariable logistic regression models identified predictors of vaccination. RESULTS: The Tdap vaccination subpopulation included 1,421,452 Commercial and 523,635 Medicaid pregnancies; the influenza vaccination subpopulation included 1,862,705 Commercial and 628,079 Medicaid pregnancies. There were marked increases in vaccination coverage from 2010 to 2017: from 1.0% to 56.3% (Commercial) and from 0.5% to 31.4% (Medicaid) for Tdap, and from 14.7% to 31.3% (Commercial) and from 9.7% to 17.5% (Medicaid) for influenza. The likelihood of Tdap/influenza vaccination increased significantly with receipt of the other vaccine and more pregnancy-related healthcare visits. CONCLUSIONS: Although maternal Tdap and influenza vaccination coverage increased substantially from 2010 to 2017 among large, geographically diverse U.S. cohorts, coverage remained suboptimal, potentially putting newborns at risk of pertussis and influenza. Strategies to increase maternal vaccination coverage could target women identified to have a reduced likelihood of vaccination: those who are younger, black, residing in rural areas, with multiple gestation, and a prepregnancy inpatient admission.

Evaluation of the cost and length of hospital stays related to the management of an intestinal Clostridium difficile infection.

INTRODUCTION: Intestinal Clostridium difficile Infection (CDI) treated in hospitals may concern patients whose reason for admission is CDI (primary diagnosis) or who have acquired CDI during their stay (secondary diagnosis). OBJECTIVES: The objective of this study is to evaluate the cost for social security and hospitals and the length of hospital stays related to CDIs as the main reason for admission. METHOD: This study was carried out in 2012 in 13 Belgian hospitals. Cases were selected by using diagnosis recorded in minimum discharge summaries. Pediatric stays are not part of the inclusion criteria (n= 86). RESULTS: The average length of stay (standard deviation) was 13.53 days (11.95). The average cost (standard deviation) covered by social security/hospitals was €5,019.51 / €6,286.39 (9,638.42/ 6,368.45). 7% of patients were admitted to the Intensive Care Unit during hospitalization, for an average duration (standard deviation) of 8.18 days (2.93). The mortality rate was 8.1%. 19.8% of patients used vancomycin during the stay, 43% were treated with metronidazole only, 12.8% used vancomycin and metronidazole and 24.4% do not received vancomycin or metronidazole. No patients received fidaxomycin. CONCLUSION: This study made it possible to approach the cost of CDI as the main reason for admission. Such data should allow contributing to optimally assess both the pharmacoeconomic impact of the implementation of prevention strategies and also therapeutic management making use of more expensive medicinal products but associated with decreased risk of recurrence.

Vaccine Timeliness: A Cost Analysis of the Potential Implications of Delayed Pertussis Vaccination in the US.

BACKGROUND: Pertussis infection remains an important public health problem, particularly in infants. Despite high coverage, pertussis vaccination delays can leave infants at a vulnerable age with less protection than anticipated. METHODS: Current diphtheria-tetanus-pertussis (DTaP) vaccination timeliness for the first 3 doses in the US was estimated using National Immunization Survey data. A Markov model estimated the potential impact on outcomes and costs of a hypothetical situation of vaccination at exactly 60, 120 and 180 days, compared with current timeliness. Incidence and unit cost data came from published sources. Age-specific incidence (for month of life) of pertussis and the associated probabilities of hospitalization and death for the US, during 2000-2007, were taken from a recently published US DTaP vaccination cost-effectiveness study. The cost analysis was conducted from the healthcare system's perspective over a 1-year time horizon. A regression analysis was conducted to explore the factors associated with vaccination delay. RESULTS: Current DTaP vaccination was estimated to be delayed by 16, 27 and 44 days, for the first, second and third doses, respectively, relative to vaccination at exactly 60, 120 and 180 days. The model estimated that vaccination at exactly age 60, 120 and 180 days could prevent approximately 278 pertussis cases, 103 hospitalizations and 1 death in infants aged <1 year in the US, gaining approximately 38 quality-adjusted life years and saving approximately $1.03 million in healthcare costs. CONCLUSIONS: Timely administration of infant pertussis vaccine doses could potentially reduce subsequent pertussis cases, hospitalizations, deaths and medical costs in infants aged <1 year in the US.

Proteomic changes in rat hippocampus and adrenals following short-term sleep deprivation.

BACKGROUND: To identify the biochemical changes induced by sleep deprivation at a proteomic level, we compared the hippocampal proteome of rats either after 4 hours of sleep or sleep deprivation obtained by gentle handling. Because sleep deprivation might induce some stress, we also analyzed proteomic changes in rat adrenals in the same conditions. After sleep deprivation, proteins from both tissues were extracted and subjected to 2D-DIGE analysis followed by protein identification through mass spectrometry and database search. RESULTS: In the hippocampus, 87 spots showed significant variation between sleep and sleep deprivation, with more proteins showing higher abundance in the latter case. Of these, 16 proteins were present in sufficient amount for a sequencing attempt and among the 12 identified proteins, inferred affected cellular functions include cell metabolism, energy pathways, transport and vesicle trafficking, cytoskeleton and protein processing. Although we did not observe classical, macroscopic effect of stress in sleep-deprived rats, 47 protein spots showed significant variation in adrenal tissue between sleep and sleep deprivation, with more proteins showing higher abundance following sleep. Of these, 16 proteins were also present in sufficient amount for a sequencing attempt and among the 13 identified proteins, the most relevant cellular function that was affected was cell metabolism. CONCLUSION: At a proteomic level, short term sleep deprivation is characterized by a higher expression of some proteins in the hippocampus and a lower abundance of other proteins in the adrenals (compared to normal sleep control). Altogether, this could indicate a general activation of a number of cellular mechanisms involved in the maintenance of wakefulness and in increased energy expenditure during sleep deprivation. These findings are relevant to suggested functions of sleep like energy repletion and the restoration of molecular stocks or a more global homeostasis of synaptic processes.

Gemvid, an open source, modular, automated activity recording system for rats using digital video.

BACKGROUND: Measurement of locomotor activity is a valuable tool for analysing factors influencing behaviour and for investigating brain function. Several methods have been described in the literature for measuring the amount of animal movement but most are flawed or expensive. Here, we describe an open source, modular, low-cost, user-friendly, highly sensitive, non-invasive system that records all the movements of a rat in its cage. METHODS: Our activity monitoring system quantifies overall free movements of rodents without any markers, using a commercially available CCTV and a newly designed motion detection software developed on a GNU/Linux-operating computer. The operating principle is that the amount of overall movement of an object can be expressed by the difference in total area occupied by the object in two consecutive picture frames. The application is based on software modules that allow the system to be used in a high-throughput workflow. Documentation, example files, source code and binary files can be freely downloaded from the project website at http://bioinformatics.org/gemvid/. RESULTS: In a series of experiments with objects of pre-defined oscillation frequencies and movements, we documented the sensitivity, reproducibility and stability of our system. We also compared data obtained with our system and data obtained with an Actiwatch device. Finally, to validate the system, results obtained from the automated observation of 6 rats during 7 days in a regular light cycle are presented and are accompanied by a stability test. The validity of this system is further demonstrated through the observation of 2 rats in constant dark conditions that displayed the expected free running of their circadian rhythm. CONCLUSION: The present study describes a system that relies on video frame differences to automatically quantify overall free movements of a rodent without any markers. It allows the monitoring of rats in their own environment for an extended period of time. By using a low-cost, open source hardware/software solution, laboratories can greatly simplify their data acquisition and analysis pipelines and improve their workload.