Prominent Mutation of Intron 22 Inversion in Sporadic Hemophilia: Is It Worth the Antenatal Screening?

Background: Adequate replacement for patients with hemophilia is costly, especially in countries with limited resources. Objective: Factor VIII gene mutations among Thai patients with hemophilia A were analyzed for the most common mutation. The cost-effectiveness of finding one female without family history of hemophilia possessing the most common factor VIII mutation was compared with the cost of treating one patient with hemophilia. Methods: In all, 109 unrelated patients with hemophilia A, defined as sporadic cases (n=58) and hereditary cases (n=51), were enrolled for genotypic analysis. Results: Intron 22 inversion was prominently found in 34 sporadic (58.6%) and 27 hereditary (51.9%) cases. The screening for intron 22 inversion among females without family history of hemophilia at antenatal care has been optionally suggested. A female with a positive result will undergo further prenatal diagnosis of hemophilia in her male offspring. On the contrary, a female with a negative test result remains at risk to have a hemophiliac son caused by other factor VIII gene mutations not included in the screening but the risk is not as high as intron 22 inversion. Although the screening of factor VIII mutation among females without family history of hemophilia is against the current practice, it has been initiated due to the inadequate treatment provided to patients with hemophilia in countries with limited resources. The study calculated approximately one female with intron 22 inversion would exist among 17,064 females without family history of hemophilia. The cost of screening (194,870 USD) was much less than that of treating one patient with hemophilia from birth to 40 years of age by the current regimen (378,000 USD). Conclusion: Implementing antenatal screening of intron 22 inversion among females without family history of hemophilia is optionally suggested, especially in economically less-developed countries with inadequate treatment service for patients with hemophilia.

A late sharp increase in influenza detections and low interim vaccine effectiveness against the circulating A(H3N2) strain, Denmark, 2021/22 influenza season up to 25 March 2022.

We estimated interim influenza A vaccine effectiveness (VE) following a late sharp rise in cases during an influenza A(H3N2)-dominated 2021/22 season, after lifting COVID-19 restrictions. In children aged 2-6 years offered a live attenuated influenza vaccine, adjusted VE was 62.7% (95% CI: 10.9-84.4) in hospitalised and 64.2% (95% CI: 50.5-74.1) in non-hospitalised children. In non-hospitalised patients aged 7-44 years, VE was 24.8% (95% CI: 12.8-35.2); VE was non-significant in remaining age groups and hospital/non-hospital settings.

Fiscal policy, inequality, and poverty in Iran: assessing the impact and effectiveness of taxes and transfers.

Using the Iranian Household Expenditure and Income Survey for 2011/12, we estimate the impact and effectiveness of various components of Iran's fiscal system on reducing inequality and poverty. We utilize the marginal contribution analysis to determine the impact of each component, and we introduce newly developed indicators of effectiveness to calculate how well various taxes and transfers are operating to reduce inequality and poverty. We find that the fiscal system reduces the poverty-head-count-ratio by 10.5 percentage points and inequality by 0.0854 Gini points. Transfers are generally more effective in reducing inequality than taxes while taxes are especially effective in raising revenue without causing poverty to rise. Although transfers are not targeted toward the poor, they reduce poverty significantly. The main driver is the Targeted Subsidy Program (TSP), and we show through simulations that the poverty reducing impact of TSP could be enhanced if resources were more targeted to the bottom deciles.

The minimum detectable measurement difference for the Scoliosis Research Society-22r in adolescent idiopathic scoliosis: a comparison with the minimum clinically important difference.

BACKGROUND CONTEXT: The minimal clinically important difference (MCID) is the smallest change in an outcomes instrument deemed relevant to a patient. MCID values proposed in spine research are limited by poor discriminative abilities to accurately classify patients as "improved" or "not improved." Furthermore, the MCID should not compare relative effectiveness between two groups of patients, though it is frequently used for this. The minimum detectable measurement difference (MDMD) is an alternative to the MCID in outcomes research. The MDMD must be greater than the MCID for the latter to be of value and the MDMD can compare change between groups. PURPOSE: The purpose of this study was to determine the MDMD for the Scoliosis Research Society-22r (SRS-22r) in adolescent idiopathic scoliosis (AIS) patients treated with surgery. STUDY DESIGN: Retrospective cohort study from multi-center registry. PATIENT SAMPLE: Patients treated surgically for AIS. OUTCOME MEASURES: Self-reported SRS-22r. METHODS: An observational cohort of surgically treated AIS patients was queried for patients with complete baseline, 1-year, and 2-year SRS-22r data. The MDMD was calculated for SRS-22r domain and subscores. Effect size (ES) and standardized response mean were calculated to measure responsiveness of the SRS-22r to change. MDMD values were compared with MCID values. Research grants were received from DePuy Synthes Spine, EOS imaging, K2M, Medtronic, NuVasive, and Zimmer Biomet to Setting Scoliosis Straight Foundation. RESULTS: One thousand two hundred and eighty-one AIS patients (1,034 female, 247 male, mean age 14.6 years) were analyzed. MDMD values were between 0.23 and 0.31. SRS-Pain MDMD was 0.3, greater than the MCID of 0.2. SRS-Activity MDMD was 0.24, greater than the MCID of 0.08. SRS-self-image MDMD was 0.3, less than the MCID of 0.98. Sixty-four percent of those with baseline SRS-self-image>4.0 improved MDMD or more, whereas only 14% improved beyond the MCID. ES and standardized response mean were highest for subscore and self-image. CONCLUSIONS: The MDMD can compare the relevance of change in SRS-22r scores between groups of AIS patients. SRS-pain and SRS-activity MDMD values are greater than the MCID and should serve as the threshold for clinically relevant improvement. MDMD may help evaluate change in patients with baseline self-image>4.0.

Cost-effectiveness analysis of sequential biologic therapy with ixekizumab versus secukinumab as first-line treatment of moderate-to-severe psoriasis in the UK.

AIMS: Patients with psoriasis often undergo treatment with a sequence of biologic agents because of poor/loss of response to initial therapy. With the availability of newer agents like ixekizumab and secukinumab, there is a need for cost-effectiveness analyses to better reflect current clinical practice. This study aimed to assess the cost-effectiveness of a sequence of biologic therapies containing first-line ixekizumab vs first-line secukinumab in patients with moderate-to-severe plaque psoriasis in the UK. MATERIALS AND METHODS: A Markov model with a lifetime horizon was developed to compare the cost-effectiveness of ixekizumab and secukinumab treatment sequences: ixekizumab → ustekinumab → infliximab → best supportive care (BSC) vs secukinumab → ustekinumab → infliximab → BSC. The model used monthly cycles, and included four health states: trial period, treatment maintenance, BSC, and death. At the end of the trial period, responders transitioned to maintenance therapy; non-responders transitioned to the next biologic in the sequence. An annual discontinuation rate of 20% was assumed for maintenance therapy. RESULTS: The ixekizumab sequence provided cost savings of £898 (£176,203 vs 177,101) [year 2015 values] and gained 0.03 more quality-adjusted life-years (QALYs: 1.45 vs 1.42) vs the secukinumab sequence over the lifetime horizon. Probabilistic sensitivity analysis showed an 89.8% likelihood that the ixekizumab sequence would be cost-effective at a threshold of £20,000 per QALY gained. LIMITATIONS: The analysis used list prices for drugs rather than confidential, preferentially priced Patient Access Scheme costs. In addition, efficacy input data were based on a network meta-analysis, as there were no head-to-head trials comparing ixekizumab and secukinumab. CONCLUSION: First-line treatment with ixekizumab as part of a specific sequential biologic therapy for moderate-to-severe plaque psoriasis in the UK provided slight advantages in cost savings and QALYs gained over a similar treatment sequence initiated with secukinumab. In view of the small magnitude of these differences, factors such as patient preferences (e.g. for number of injections) and long-term safety (e.g. related to time on the market) may also be important for clinical decision-making.

Environmental cost-effectiveness analysis in intertemporal natural resource policy: evaluation of selective fishing gear.

In most decision-making involving natural resources, the achievements of a given policy (e.g., improved ecosystem or biodiversity) are rather difficult to measure in monetary units. To address this problem, the current paper develops an environmental cost-effectiveness analysis (ECEA) to include intangible benefits in intertemporal natural resource problems. This approach can assist managers in prioritizing management actions as least cost solutions to achieve quantitative policy targets. The ECEA framework is applied to a selective gear policy case in Danish mixed trawl fisheries in Kattegat and Skagerrak. The empirical analysis demonstrates how a policy with large negative net benefits might be justified if the intangible benefits are included.