Objective: To examine the direct and indirect costs of hemophilia care among persons with hemophilia A in the US. Methods:Observational data were obtained from HUGS-Va, a multi-center study from six federally supported hemophilia treatment centers (HTCs). Eligible individuals completed a standardized initial questionnaire and were followed regularly for 2 years to obtain information on work or school absenteeism, time spent arranging hemophilia care, and unpaid hemophilia-related support from caregivers. Data from 1-year healthcare utilization records and 2-year clotting factor dispensing records measured direct medical costs. Indirect costs were imputed using the human capital approach, which uses wages as a proxy measure of work time output. Results:A total of 222 patients with complete data were included in the analysis. Two-thirds had severe hemophilia and the mean age was 21.1 years. The use of prophylaxis in severe hemophilia patients is associated with statistically significant reduction in the numbers of emergency department (ED) visits and bleeding episodes compared with those who were treated episodically. From the societal perspective, mild hemophilia costs $59,101 (median: $7519) annually per person, $84,363 (median: $61,837) for moderate hemophilia, $201,471 (median: $143,431) for severe hemophilia using episodic treatment, and $301,392 (median: $286,198) for severe hemophilia receiving prophylaxis. Clotting factor contributed from 54% of total costs in mild hemophilia to a maximum of 94% for patients with severe hemophilia receiving prophylaxis. Conclusion:Hemophilia is a costly disorder not only because of its high medical expenses, but also due to the high indirect costs incurred.

PURPOSE The aim of the current study was to assess the economic impact of using next-generation sequencing (NGS) versus single-gene testing strategies among patients with metastatic non–small-cell lung cancer (mNSCLC) from the perspective of the Centers for Medicare & Medicaid Services (CMS) and US commercial payers. METHODS A decision analytic model considered patients who were newly diagnosed with mNSCLC who received programmed death ligand 1 and genomic alteration tests— EGFR, ALK, ROS1, BRAF, MET, HER2, RET, and NTRK1—using upfront NGS (all alterations tested simultaneously plus KRAS), sequential testing (sequence of single-gene tests), exclusionary testing ( KRAS plus sequential testing), and hotspot panels ( EGFR, ALK, ROS1, and BRAF tested simultaneously plus single-gene tests or NGS for MET, HER2, RET, and NTRK1). Model outcomes for each strategy were time-to-test results, the proportion of patients identified harboring alterations with or without US Food and Drug Administration–approved therapies, and total testing costs. A budget impact analysis assessed the economic effects of increasing the proportion of NGS-tested patients. RESULTS In a hypothetical 1,000,000-member health plan, 2,066 Medicare-insured patients and 156 commercially insured patients were estimated to have mNSCLC and to be eligible for testing. Time-to-test results were 2.0 weeks for NGS and the hotspot panel, faster than exclusionary and sequential testing by 2.7 and 2.8 weeks, respectively. NGS was associated with cost savings for both CMS ($1,393,678; $1,530,869; and $2,140,795 less than exclusionary, sequential testing, and hotspot panels, respectively) and commercial payers ($3,809; $127,402; and $250,842 less than exclusionary, sequential testing, and hotspot panels, respectively). Increasing the proportion of NGS-tested patients translated into substantial cost savings for both CMS and commercial payers. CONCLUSION Use of upfront NGS testing in patients with mNSCLC was associated with substantial cost savings and shorter time-to-test results for both CMS and commercial payers.

This study describes health-related quality of life (HRQoL) of persons with haemophilia A in the United States (US) and determines associations between self-reported joint pain, motion limitation and clinically evaluated joint range of motion (ROM), and between HRQoL and ROM. As part of a 2-year cohort study, we collected baseline HRQoL using the SF-12 (adults) and PedsQL (children), along with self-ratings of joint pain and motion limitation, in persons with factor VIII deficiency recruited from six Haemophilia Treatment Centres (HTCs) in geographically diverse regions of the US. Clinically measured joint ROM measurements were collected from medical charts of a subset of participants. Adults (N = 156, mean age: 33.5 ± 12.6 years) had mean physical and mental component scores of 43.4 ± 10.7 and 50.9 ± 10.1, respectively. Children (N = 164, mean age: 9.7 ± 4.5 years) had mean total PedsQL, physical functioning, and psychosocial health scores of 85.9 ± 13.8, 89.5 ± 15.2, and 84.1 ± 15.3, respectively. Persons with more severe haemophilia and higher self-reported joint pain and motion limitation had poorer scores, particularly in the physical aspects of HRQoL. In adults, significant correlations (P < 0.01) were found between ROM measures and both self-reported measures. Except among those with severe disease, children and adults with haemophilia have HRQoL scores comparable with those of the healthy US population. The physical aspects of HRQoL in both adults and children with haemophilia A in the US decrease with increasing severity of illness. However, scores for mental aspects of HRQoL do not differ between severity groups. These findings are comparable with those from studies in European and Canadian haemophilia populations.

Reconfigurable intelligent surfaces (RISs), consisting of many low-cost elements that reflect the incident waves by an adjustable phase shift, have attracted sudden attention for their potential of reconfiguring the signal propagation environment and enhancing the performance of wireless networks. The passive nature of RISs is indeed beneficial, but the lack of radio frequency (RF) chains at the RIS has made channel estimation extremely challenging. We face this challenge by proposing a joint channel estimation and transmit precoding framework for RIS-aided multiple-input multiple-output (MIMO) systems. Specifically, the effective cascaded channel of the reflected transmitter-RISreceiver link is decomposed into multiple subchannels, each of which corresponds to a single RIS element. Then our joint RIStransmitter precoding model is formulated for the individual subchannels of each reflecting element. Finally, we develop a twostage precoding design for successively determining the required phase shifts of each reflecting element of the RIS and the digital baseband precoder of the transmitter, only relying on the channel state information (CSI) of the subchannels. The performance of the proposed subchannel estimation and joint precoding method is evaluated by extensive simulations. Our numerical results show that the proposed designs provide an attractive solution to RISaided MIMO systems.

SUMMARY BackgroundChronic constipation (CC) is a highly prevalent health problem, potentially associated with increased risk of colorectal cancer (CRCancer).