Does mothers' and caregivers' access to information on their child's vaccination card impact the timing of their child's measles vaccination in Uganda?

INTRODUCTION: On-time measles vaccination is essential for preventing measles infection among children as early in life as possible, especially in areas where measles outbreaks occur frequently. Characterizing the timing of routine measles vaccination (MCV1) among children and identifying risk factors for delayed measles vaccination is important for addressing barriers to recommended childhood vaccination and increasing on-time MCV1 coverage. We aim to assess the timing of children's MCV1 vaccination and to investigate the association between demographic and healthcare factors, mothers'/caregivers' ability to identify information on their child's vaccination card, and achieving on-time (vs. delayed) MCV1 vaccination. METHODS: We conducted a population-based, door-to-door survey in Kampala, Uganda, from June-August of 2019. We surveyed mothers/caregivers of children aged one to five years to determine how familiar they were with their child's vaccination card and to determine their child's MCV1 vaccination status and timing. We assessed the proportion of children vaccinated for MCV1 on-time and delayed, and we evaluated the association between mothers'/caregivers' ability to identify key pieces of information (child's birth date, sex, and MCV1 date) on their child's vaccination card and achieving on-time MCV1 vaccination. RESULTS: Of the 999 mothers/caregivers enrolled, the median age was 27 years (17-50), and median child age was 29 months (12-72). Information on vaccination status was available for 66.0% (n = 659) of children. Of those who had documentation of MCV1 vaccination (n = 475), less than half (46.5%; n = 221) achieved on-time MCV1 vaccination and 53.5% (n = 254) were delayed. We found that only 47.9% (n = 264) of the 551 mothers/caregivers who were asked to identify key pieces of information on their child's vaccination card were able to identify the information, but ability to identify the key pieces of information on the card was not independently associated with achieving on-time MCV1 vaccination. CONCLUSION: Mothers'/caregivers' ability to identify key pieces of information on their child's vaccination card was not associated with achieving on-time MCV1 vaccination. Further research can shed light on interventions that may prompt or remind mothers/caregivers of the time and age when their child is due for measles vaccine to increase the chance of the child receiving it at the recommended time.

When and what to test for: A cost-effectiveness analysis of febrile illness test-and-treat strategies in the era of responsible antibiotic use.

BACKGROUND: Febrile illness caused by viral and bacterial diseases (e.g., dengue and leptospirosis) often have similar symptoms and are difficult to differentiate without diagnostic tests. If not treated appropriately, patients may experience serious complications. The question of what diagnostic tests to make available to providers in order to inform antibiotic therapy remains an open problem for health services facing limited resources. METHODS AND FINDINGS: We formulated the problem of minimizing the weighted average of antibiotic underuse and overuse to inform the optimal diagnostic test and antibiotic treatment options for given occurrence probabilities of several bacterial and viral infections. We modeled the weight of antibiotic overuse as a monetary penalty per unnecessarily administered course, which we varied in both the base case and sensitivity analysis. Detailed Markov cohort models of febrile illness progression were used to estimate the weight of antibiotic underuse. The model accounted for multiple infections simultaneously and incorporated test, treatment, and other direct and indirect costs, as well as the effect of delays in seeking care and test turnaround times. We used the Markov models to numerically estimate disability-adjusted life years (DALYs), pre-penalty costs, and likelihood of antibiotics overuse per patient for fifteen different strategies in two example settings in Thailand, one with a higher probability of bacterial infections (Northern Thailand, Scenario A) and one with a higher probability of viral infections (Bangkok, Scenario B). We found that empirical antibiotic treatment to all patients always incurs the lowest pre-penalty cost (Scenario A: $47.5/patient, $100.6/patient, $149.5/patient for patients seeking care on day one, day four, and day ten respectively; Scenario B: $94.1/patient, $108.7/patient, $122.1/patient on day one, day four, and day ten respectively), and the lowest DALYs, (Scenario A: 0.2 DALYs/patient, 0.9 DALYs/patient, 1.7 DALYs/patient on day one, day four, and day ten, respectively; Scenario B: 0.5 DALYs/patient, 0.7 DALYs/patient, 0.9 DALYs/patient on day one, day four, and day ten, respectively). However, such strategy resulted in the highest proportion of antibiotic overuse per patient (Scenario A: 38.1%, 19.3%, 7.5% on day one, day four, and day ten, respectively; Scenario B: 82.9%, 42.1%, 16.3% on day one, day four, and day ten, respectively). Consequently, empirical antibiotic treatment became suboptimal with antibiotic overuse penalties above $12,800/course, $18,400/course, $23,900/course for patients presenting on day one, day four, and day ten in Scenario A and above $1,100/course, $1,500/course, $1,600/course for patients presenting on day one, day four, and day ten in Scenario B. CONCLUSIONS: Empirical antibiotic treatment to all patients provided the best outcomes if antibiotic overuse was not the primary concern or if presenting with viral disease (such as dengue) was unlikely. Empirical antibiotic treatment to severe patients only was in most cases not beneficial. Otherwise, strategies involving diagnostic tests became optimal. In particular, our results indicated that single test strategies (bacterial RDT or viral PCR) were optimal in regions with a greater probability of presenting with viral infection. PCR-led strategies (e.g., parallel bacterial PCR, or multiplex PCR) are robust under parameter uncertainty (e.g., with uncertain disease occurrence probabilities).

Proactive Vs Reactive Therapeutic Drug Monitoring of Infliximab in Crohn's Disease: A Cost-Effectiveness Analysis in a Simulated Cohort.

BACKGROUND: Therapeutic drug monitoring (TDM) is increasingly performed for Infliximab (IFX) in patients with Crohn's disease (CD). Reactive TDM is a cost-effective strategy to empiric IFX dose escalation. The cost-effectiveness of proactive TDM is unknown. The aim of this study is to assess the cost-effectiveness of proactive vs reactive TDM in a simulated population of CD patients on IFX. METHODS: We developed a stochastic simulation model of CD patients on IFX and evaluated the expected health costs and outcomes of a proactive TDM strategy compared with a reactive strategy. The proactive strategy measured IFX concentration and antibody status every 6 months, or at the time of a flare, and dosed IFX to a therapeutic window. The reactive strategy only did so at the time of a flare. RESULTS: The proactive strategy led to fewer flares than the reactive strategy. More patients stayed on IFX in the proactive vs reactive strategy (63.4% vs 58.8% at year 5). From a health sector perspective, a proactive strategy was marginally cost-effective compared with a reactive strategy (incremental cost-effectiveness ratio of $146,494 per quality-adjusted life year), assuming a 40% of the wholesale price of IFX. The results were most sensitive to risk of flaring with a low IFX concentration and the cost of IFX. CONCLUSIONS: Assuming 40% of the average wholesale acquisition cost of biologic therapies, proactive TDM for IFX is marginally cost-effective compared with a reactive TDM strategy. As the cost of infliximab decreases, a proactive monitoring strategy is more cost-effective.

Dynamic Learning of Patient Response Types: An Application to Treating Chronic Diseases.

Currently available medication for treating many chronic diseases is often effective only for a subgroup of patients, and biomarkers accurately assessing whether an individual belongs to this subgroup typically do not exist. In such settings, physicians learn about the effectiveness of a drug primarily through experimentation, i.e., by initiating treatment and monitoring the patient's response. Precise guidelines for discontinuing treatment are often lacking or left entirely to the physician's discretion. We introduce a framework for developing adaptive, personalized treatments for such chronic diseases. Our model is based on a continuous-time, multi-armed bandit setting where drug effectiveness is assessed by aggregating information from several channels: by continuously monitoring the state of the patient, but also by (not) observing the occurrence of particular infrequent health events, such as relapses or disease flare-ups. Recognizing that the timing and severity of such events provides critical information for treatment decisions is a key point of departure in our framework compared with typical (bandit) models used in healthcare. We show that the model can be analyzed in closed form for several settings of interest, resulting in optimal policies that are intuitive and may have practical appeal. We illustrate the effectiveness of the methodology by developing a set of efficient treatment policies for multiple sclerosis, which we then use to benchmark several existing treatment guidelines.

Differentiated Human Immunodeficiency Virus RNA Monitoring in Resource-Limited Settings: An Economic Analysis.

BACKGROUND.: Viral load (VL) monitoring for patients receiving antiretroviral therapy (ART) is recommended worldwide. However, the costs of frequent monitoring are a barrier to implementation in resource-limited settings. The extent to which personalized monitoring frequencies may be cost-effective is unknown. METHODS.: We created a simulation model parameterized using person-level longitudinal data to assess the benefits of flexible monitoring frequencies. Our data-driven model tracked human immunodeficiency virus (HIV)-infected individuals for 10 years following ART initiation. We optimized the interval between viral load tests as a function of patients' age, gender, education, duration since ART initiation, adherence behavior, and the cost-effectiveness threshold. We compared the cost-effectiveness of the personalized monitoring strategies to fixed monitoring intervals every 1, 3, 6, 12, and 24 months. RESULTS.: Shorter fixed VL monitoring intervals yielded increasing benefits (6.034 to 6.221 discounted quality-adjusted life-years [QALYs] per patient with monitoring every 24 to 1 month over 10 years, respectively, standard error = 0.005 QALY), at increasing average costs: US$3445 (annual monitoring) to US$5393 (monthly monitoring) per patient, respectively (standard error = US$3.7). The adaptive policy optimized for low-income contexts achieved 6.142 average QALYs at a cost of US$3524, similar to the fixed 12-month policy (6.135 QALYs, US$3518). The adaptive policy optimized for middle-income resource settings yields 0.008 fewer QALYs per person, but saves US$204 compared to monitoring every 3 months. CONCLUSIONS.: The benefits from implementing adaptive vs fixed VL monitoring policies increase with the availability of resources. In low- and middle-income countries, adaptive policies achieve similar outcomes to simpler, fixed-interval policies.

Screening and rapid molecular diagnosis of tuberculosis in prisons in Russia and Eastern Europe: a cost-effectiveness analysis.

BACKGROUND: Prisons of the former Soviet Union (FSU) have high rates of multidrug-resistant tuberculosis (MDR-TB) and are thought to drive general population tuberculosis (TB) epidemics. Effective prison case detection, though employing more expensive technologies, may reduce long-term treatment costs and slow MDR-TB transmission. METHODS AND FINDINGS: We developed a dynamic transmission model of TB and drug resistance matched to the epidemiology and costs in FSU prisons. We evaluated eight strategies for TB screening and diagnosis involving, alone or in combination, self-referral, symptom screening, mass miniature radiography (MMR), and sputum PCR with probes for rifampin resistance (Xpert MTB/RIF). Over a 10-y horizon, we projected costs, quality-adjusted life years (QALYs), and TB and MDR-TB prevalence. Using sputum PCR as an annual primary screening tool among the general prison population most effectively reduced overall TB prevalence (from 2.78% to 2.31%) and MDR-TB prevalence (from 0.74% to 0.63%), and cost US$543/QALY for additional QALYs gained compared to MMR screening with sputum PCR reserved for rapid detection of MDR-TB. Adding sputum PCR to the currently used strategy of annual MMR screening was cost-saving over 10 y compared to MMR screening alone, but produced only a modest reduction in MDR-TB prevalence (from 0.74% to 0.69%) and had minimal effect on overall TB prevalence (from 2.78% to 2.74%). Strategies based on symptom screening alone were less effective and more expensive than MMR-based strategies. Study limitations included scarce primary TB time-series data in FSU prisons and uncertainties regarding screening test characteristics. CONCLUSIONS: In prisons of the FSU, annual screening of the general inmate population with sputum PCR most effectively reduces TB and MDR-TB prevalence, doing so cost-effectively. If this approach is not feasible, the current strategy of annual MMR is both more effective and less expensive than strategies using self-referral or symptom screening alone, and the addition of sputum PCR for rapid MDR-TB detection may be cost-saving over time.

Balancing immunological benefits and cardiovascular risks of antiretroviral therapy: when is immediate treatment optimal?

We developed a mathematical model to identify the timing of antiretroviral therapy (ART) initiation that optimizes patient outcomes as a function of patient CD4 count, age, cardiac mortality risk, sex, and personal preferences. Our goal was to find the conditions that maximize patient quality-adjusted life expectancy (QALE) in the context of our model. Under the assumption that ART confers disease progression and mortality benefits at any CD4 count, immediate treatment initiation yields the greatest remaining QALE for young patients under most circumstances. The timing of ART initiation depends on the magnitude of benefit from ART at high CD4 counts, the magnitude of increases in cardiac risk, and patients' preferences. If ART reduces HIV progression at high CD4 counts, immediate ART is preferable for most newly infected individuals <35 years even if ART doubles age- and sex-specific cardiac risk.