Clinical outcomes of chikungunya: A systematic literature review and meta-analysis.

BACKGROUND: Chikungunya is a viral disease caused by a mosquito-borne alphavirus. The acute phase of the disease includes symptoms such as fever and arthralgia and lasts 7-10 days. However, debilitating symptoms can persist for months or years. Despite the substantial impact of this disease, a comprehensive assessment of its clinical picture is currently lacking. METHODS: We conducted a systematic literature review on the clinical manifestations of chikungunya, their prevalence and duration, and related hospitalization. Embase and MEDLINE were searched with no time restrictions. Subsequently, meta-analyses were conducted to quantify pooled estimates on clinical outcomes, the symptomatic rate, the mortality rate, and the hospitalization rate. The pooling of effects was conducted using the inverse-variance weighting methods and generalized linear mixed effects models, with measures of heterogeneity reported. RESULTS: The systematic literature review identified 316 articles. Out of the 28 outcomes of interest, we were able to conduct 11 meta-analyses. The most prevalent symptoms during the acute phase included arthralgia in 90% of cases (95% CI: 83-94%), and fever in 88% of cases (95% CI: 85-90%). Upon employing broader inclusion criteria, the overall symptomatic rate was 75% (95% CI: 63-84%), the chronicity rate was 44% (95% CI: 31-57%), and the mortality rate was 0.3% (95% CI: 0.1-0.7%). The heterogeneity between subpopulations was more than 92% for most outcomes. We were not able to estimate all predefined outcomes, highlighting the existing data gap. CONCLUSION: Chikungunya is an emerging public health concern. Consequently, a thorough understanding of the clinical burden of this disease is necessary. Our study highlighted the substantial clinical burden of chikungunya in the acute phase and a potentially long-lasting chronic phase. Understanding this enables health authorities and healthcare professionals to effectively recognize and address the associated symptoms and raise awareness in society.

Cost-effectiveness model of trastuzumab deruxtecan as second-line treatment in HER2-positive unresectable and/or metastatic breast cancer in Finland.

OBJECTIVES: Trastuzumab deruxtecan (T-DXd) was recently recommended by the Committee for Medicinal Products for Human Use as a treatment for adult patients with unresectable or metastatic HER2-positive breast cancer, who had received a prior anti-HER2-based regimen. In our study, we evaluated the cost-effectiveness of T-DXd compared with ado-trastuzumab emtansine (T-DM1) for this indication in Finland. METHODS: A three-state partitioned survival analysis model was developed with a payer's perspective. Time to event data from the DESTINY-Breast03 (DB-03) trial were extrapolated over a lifetime horizon either directly-for progression-free survival and time to treatment discontinuation-or using an alternative approach utilizing long-term T-DM1 survival data and DB-03 data-for overall survival. Discount rates of 3% were applied for costs and effects. Inputs were sourced from the Medicinal Products Database from Kela, Helsinki University Hospital service price list, Finnish Medicines Agency assessments, clinical experts, and DB-03. Sensitivity analyses were performed to characterize and demonstrate parameter uncertainties in the model. RESULTS: Total quality-adjusted life years (QALYs) and life years (LYs) gained for T-DXd compared with T-DM1 were 1.93 and 2.56, respectively. Incremental costs for T-DXd compared with T-DM1 were €106,800, resulting in an ICER of €55,360 per QALY gained and an ICER of €41,775 per LY gained. One-way sensitivity analysis showed the hazard ratio of T-DXd vs T-DM1 for OS was the most influential parameter. The probabilistic sensitivity analysis showed similar results to the base case. CONCLUSIONS: T-DXd is cost-effective based on surrogate WTP thresholds of €72,000 and €139,000 per QALY.

Evaluating the reactogenicity of COVID-19 vaccines from network-meta analyses.

BACKGROUND: Evidence-based reassurances addressing vaccine-related concerns are crucial to promoting primary vaccination, completion of the primary series, and booster vaccination. By summarizing and comparing the reactogenicity of COVID-19 vaccines authorized by the European Medicines Agency, this analysis aims to support in-formed decision-making by the lay public and help overcome vaccine hesitancy. RESEARCH DESIGN AND METHODS: A systematic literature review identified 24 records reporting solicited adverse events for AZD1222, BNT162b2, mRNA-1273, NVX-Cov2373, and VLA2001 in individuals aged 16 or older. Network meta-analyses were conducted for each solicited adverse events reported for at least two vaccines that were not compared head-to-head but could be connected through a common comparator. RESULTS: A total of 56 adverse events were investigated through network meta-analyses within a Bayesian framework with random-effects models. Overall, the two mRNA vaccines were found to be the most reactogenic vaccines. VLA2001 had the highest likelihood of being the least reactogenic vaccine after the first and second vaccine dose, especially for systemic adverse events after the first dose. CONCLUSIONS: The reduced chance of experiencing an adverse event with some COVID-19 vaccines may help to overcome vaccine hesitancy in population groups with concerns about the side effects of vaccines.

Association between socioeconomic status and self-reported, tested and diagnosed COVID-19 status during the first wave in the Northern Netherlands: a general population-based cohort from 49 474 adults.

OBJECTIVES: Studies in clinical settings showed a potential relationship between socioeconomic status (SES) and lifestyle factors with COVID-19, but it is still unknown whether this holds in the general population. In this study, we investigated the associations of SES with self-reported, tested and diagnosed COVID-19 status in the general population. DESIGN, SETTING, PARTICIPANTS AND OUTCOME MEASURES: Participants were 49 474 men and women (46±12 years) residing in the Northern Netherlands from the Lifelines cohort study. SES indicators and lifestyle factors (i.e., smoking status, physical activity, alcohol intake, diet quality, sleep time and TV watching time) were assessed by questionnaire from the Lifelines Biobank. Self-reported, tested and diagnosed COVID-19 status was obtained from the Lifelines COVID-19 questionnaire. RESULTS: There were 4711 participants who self-reported having had a COVID-19 infection, 2883 participants tested for COVID-19, and 123 positive cases were diagnosed in this study population. After adjustment for age, sex, lifestyle factors, body mass index and ethnicity, we found that participants with low education or low income were less likely to self-report a COVID-19 infection (OR [95% CI]: low education 0.78 [0.71 to 0.86]; low income 0.86 [0.79 to 0.93]) and be tested for COVID-19 (OR [95% CI]: low education 0.58 [0.52 to 0.66]; low income 0.86 [0.78 to 0.95]) compared with high education or high income groups, respectively. CONCLUSION: Our findings suggest that the low SES group was the most vulnerable population to self-reported and tested COVID-19 status in the general population.

The persistence of child and adolescence mental healthcare: results from registry data.

BACKGROUND: Previous studies on the persistence of child and adolescent mental healthcare do not consider the role of time-invariant individual characteristics. Estimating persistence of healthcare using standard linear models yields biased estimates due to unobserved heterogeneity and the autoregressive structure of the model. This study provides estimates of the persistence of child and adolescent mental healthcare taking these statistical issues into account. METHODS: We use registry data of more than 80,000 Dutch children and adolescents between 2000 and 2012 from the Psychiatric Case Registry Northern Netherlands (PCR-NN). In order to account for autocorrelation due to the presence of a lagged dependent variable and to distinguish between persistence caused by time-invariant individual characteristics and a direct care effect we use difference GMM-IV estimation. In further analyses we assess the robustness of our results to policy reforms, different definitions of care and diagnosis decomposition. RESULTS: All estimation results for the direct care effect (true state-dependence) show a positive coefficient smaller than unity with a main effect of 0.215 (p<0.01), which indicates that the process is stable. Persistence of care is found to be 0.065 (p<0.05) higher for females. Additionally, the majority of persistence of care appears to be associated with time-invariant characteristics. Further analyses indicate that (1) results are robust to different definitions of care and (2) persistence of care does not differ significantly across subgroups. CONCLUSIONS: The results indicate that the majority of mental healthcare persistence for children and adolescents is due to time-invariant individuals characteristics. Additionally, we find that in the absence of further shocks a sudden increase of 10 care contacts in the present year is associated with an average of less than 3 additional care contacts at some point in the future. This result provides essential information about the necessity of budget increases for future years in the case of exogenous increases in healthcare use.

Centralising acute stroke care within clinical practice in the Netherlands: lower bounds of the causal impact.

BACKGROUND: Authors in previous studies demonstrated that centralising acute stroke care is associated with an increased chance of timely Intra-Venous Thrombolysis (IVT) and lower costs compared to care at community hospitals. In this study we estimated the lower bound of the causal impact of centralising IVT on health and cost outcomes within clinical practice in the Northern Netherlands. METHODS: We used observational data from 267 and 780 patients in a centralised and decentralised system, respectively. The original dataset was linked to the hospital information systems. Literature on healthcare costs and Quality of Life (QoL) values up to 3 months post-stroke was searched to complete the input. We used Synthetic Control Methods (SCM) to counter selection bias. Differences in SCM outcomes included 95% Confidence Intervals (CI). To deal with unobserved heterogeneity we focused on recently developed methods to obtain the lower bounds of the causal impact. RESULTS: Using SCM to assess centralising acute stroke 3 months post-stroke revealed healthcare savings of $US 1735 (CI, 505 to 2966) while gaining 0.03 (CI, - 0.01 to 0.73) QoL per patient. The corresponding lower bounds of the causal impact are $US 1581 and 0.01. The dominant effect remained stable in the deterministic sensitivity analyses with $US 1360 (CI, 476 to 2244) as the most conservative estimate. CONCLUSIONS: In this study we showed that a centralised system for acute stroke care appeared both cost-saving and yielded better health outcomes. The results are highly relevant for policy makers, as this is the first study to address the issues of selection and unobserved heterogeneity in the evaluation of centralising acute stroke care, hence presenting causal estimates for budget decisions.

Cost-Effectiveness of Treatments in Children With Attention-Deficit/Hyperactivity Disorder: A Continuous-Time Markov Modeling Approach.

Objectives. This study aimed to assess the cost-effectiveness of treatments for attention-deficit/hyperactivity disorder (ADHD) in children through prevention of serious delinquent behavior. Cost-effectiveness was assessed in net-monetary benefit (NMB). Methods. To evaluate the three major forms of ADHD treatment (medication management, behavioral treatment, and the combination thereof) relative to community-delivered treatment (control condition), we used data from 448 children, aged 7 to 10, who participated in the National Institute of Mental Health's Multimodal Treatment Study of Children with ADHD. We developed a three-state continuous-time Markov model (no delinquency, minor to moderate delinquency, serious delinquency) to extrapolate the results 10 years beyond the 14-month trial period at a 3% discount rate. Serious delinquency was considered an absorbing state to enable assessment in life-years (LYs) of serious delinquent behavior prevented. The willingness-to-pay (WTP) threshold was set equal to the annual cost associated with serious delinquency in children with ADHD of $12,370. Results. Modeled and observed outcomes matched closely with a mean difference of 6.9% in LYs of serious delinquent behavior prevented. The economic evaluation revealed a NMB of $95,449, $88,553, $90,536 and $98,660 for medication management, behavioral treatment, combined treatment, and routine community care, respectively. Estimates remained stable after linearly increasing the WTP threshold between $0 and $50,000 in the deterministic sensitivity analyses. Conclusions. This study assessed the cost-effectiveness of treatments for ADHD in children using continuous-time Markov modeling. We show that treatment evaluation in broader societal outcomes is essential for policy makers, as the three major forms of ADHD treatment turned out to be inferior to the control condition.