Cost-effectiveness of noninvasive fetal RhD blood group genotyping in nonalloimmunized and alloimmunized pregnancies.

BACKGROUND: We sought to determine the cost-effectiveness of noninvasive fetal RhD blood group genotyping in nonalloimmunized and alloimmunized pregnancies in Canada. STUDY DESIGN AND METHODS: We developed two probabilistic state-transition (Markov) microsimulation models to compare fetal genotyping followed by targeted management versus usual care (i.e., universal Rh immunoglobulin [RhIG] prophylaxis in nonalloimmunized RhD-negative pregnancies, or universal intensive monitoring in alloimmunized pregnancies). The reference case considered a healthcare payer perspective and a 10-year time horizon. Sensitivity analysis examined assumptions related to test cost, paternal screening, subsequent pregnancies, other alloantibodies (e.g., K, Rh c/C/E), societal perspective, and lifetime horizon. RESULTS: Fetal genotyping in nonalloimmunized pregnancies (at per-sample test cost of C$247/US$311) was associated with a slightly higher probability of maternal alloimmunization (22 vs. 21 per 10,000) and a reduced number of RhIG injections (1.427 vs. 1.795) than usual care. It was more expensive (C$154/US$194, 95% Credible Interval [CrI]: C$139/US$175-C$169/US$213) and had little impact on QALYs (0.0007, 95%CrI: -0.01-0.01). These results were sensitive to the test cost (threshold achieved at C$88/US$111), and inclusion of paternal screening. Fetal genotyping in alloimmunized pregnancies (at test cost of C$328/US$413) was less expensive (-C$6280/US$7903, 95% CrI: -C$6325/US$7959 to -C$6229/US$7838) and more effective (0.19 QALYs, 95% CrI 0.17-0.20) than usual care. These cost savings remained robust in sensitivity analyses. DISCUSSION: Noninvasive fetal RhD genotyping saves resources and represents good value for the management of alloimmunized pregnancies. If the cost of genotyping is substantially decreased, the targeted intervention can become a viable option for nonalloimmunized pregnancies.

Noninvasive Fetal RhD Blood Group Genotyping: A Systematic Review of Economic Evaluations.

OBJECTIVE: Noninvasive fetal rhesus D (RhD) blood group genotyping may prevent unnecessary use of anti-D immunoglobulin (RhIG) in non-alloimmunized RhD-negative pregnancies and can guide management of alloimmunized pregnancies. We conducted a systematic review of the economic literature to determine the cost-effectiveness of this intervention over usual care. DATA SOURCES: Systematic literature searches of bibliographic databases (Ovid MEDLINE, Embase, and Cochrane) until February 26, 2019, and auto-alerts until October 30, 2020, and of grey literature sources were performed to retrieve all English-language studies. STUDY SELECTION: We included studies done in serologically confirmed non-alloimmunized or alloimmunized RhD-negative pregnancies, comparing costs and effectiveness of the intervention versus usual care. DATA EXTRACTION AND SYNTHESIS: Two reviewers extracted data from the eligible studies and assessed their methodological quality (risk of bias) using the Quality of Health Economic Studies (QHES) and Drummond tools. We narratively synthesized findings. Our review included 8 economic studies that evaluated non-invasive fetal RhD genotyping followed by targeted RhIG prophylaxis in non-alloimmunized pregnancies. Five studies further considered a subsequent alloimmunized pregnancy. The cost-effectiveness of the intervention versus usual care (e.g., universal RhIG or prophylaxis conditional on results of paternal testing) for non-alloiummunized pregnancies was inconsistent. Two studies indicated greater benefits and lower costs for the intervention, and another 2 suggested a trade-off. In 4 studies, the intervention was less effective and costlier than alternatives. Three studies were determined to be of high quality by both tools. Two of these studies favoured the intervention, and one assessed benefits in quality-adjusted life-years. No study clearly examined the cost-effectiveness of repetitive use of fetal genotyping in multiple non-alloimmunized or alloimmunized pregnancies. The cost of genotyping was the most influential parameter. CONCLUSION: The cost-effectiveness of noninvasive fetal RhD genotyping for non-alloimmunized pregnancies varies between studies. Potential savings from targeted management of alloimmunized pregnancies requires further research.

Noninvasive Prenatal Testing for Trisomies 21, 18, and 13, Sex Chromosome Aneuploidies, and Microdeletions in Average-Risk Pregnancies: A Cost-Effectiveness Analysis.

OBJECTIVE: The cost effectiveness of noninvasive prenatal testing (NIPT) has been established for high-risk pregnancies but remains unclear for pregnancies at other risk levels. The aim was to assess the cost effectiveness of NIPT in average-risk pregnancies from the perspective of a provincial public payer in Canada. METHODS: A model was developed to compare traditional prenatal screening (TPS), NIPT as a second-tier test (performed only after a positive TPS result), and NIPT as a first-tier test (performed instead of TPS) for trisomies 21, 18, and 13; sex chromosome aneuploidies; and microdeletions in a hypothetical annual population cohort of average-risk pregnancies (142 000 to 148,000) in Ontario, Canada. A probabilistic analysis was conducted with 5000 repetitions. RESULTS: Compared with TPS, NIPT as a second-tier test detected more affected fetuses with trisomies 21, 18, and 13 (188 vs. 158), substantially reduced the number of diagnostic tests (i.e., chorionic villus sampling and amniocentesis) performed (660 vs. 3107), and reduced the cost of prenatal screening ($26.7 million vs. $27.6 million) annually. Compared with second-tier NIPT, first-tier NIPT detected an additional 80 cases of trisomies 21, 18, and 13 at an additional cost of $33 million. The incremental cost per additional affected fetus detected was $412 411. Extending first-tier NIPT to include testing for sex chromosome aneuploidies and 22q11.2 deletion would increase the total screening cost. CONCLUSIONS: NIPT as a second-tier test is cost-saving compared with TPS alone. Compared with second-tier NIPT, first-tier NIPT detects more cases of chromosomal anomalies but at a substantially higher cost.

Facilitating informed choice about non-invasive prenatal testing (NIPT): a systematic review and qualitative meta-synthesis of women's experiences.

BACKGROUND: Non-invasive prenatal testing (NIPT) can be used to accurately detect fetal chromosomal anomalies early in pregnancy by assessing cell-free fetal DNA present in maternal blood. The rapid diffusion of NIPT, as well as the ease and simplicity of the test raises concerns around informed decision-making and the potential for routinization. Introducing NIPT in a way that facilitates informed and autonomous decisions is imperative to the ethical application of this technology. We approach this imperative by systematically reviewing and synthesizing primary qualitative research on women's experiences with and preferences for informed decision-making around NIPT. METHODS: We searched multiple bibliographic databases including Ovid MEDLINE, EBSCO Cumulative Index to Nursing & Allied Health Literature (CINAHL), and ISI Web of Science Social Sciences Citation Index (SSCI). Our review was guided by integrative qualitative meta-synthesis, and we used a staged coding process similar to that of grounded theory to conduct our analysis. RESULTS: Thirty empirical primary qualitative research studies were eligible for inclusion. Women preferred to learn about NIPT from their clinicians, but they expressed dissatisfaction with the quality and quantity of information provided during counselling and often sought information from a variety of other sources. Women generally had a good understanding of test characteristics, and the factors of accuracy, physical risk, and test timing were the critical information elements that they used to make informed decisions around NIPT. Women often described NIPT as easy or just another blood test, highlighting threats to informed decision-making such as routinization or a pressure to test. CONCLUSIONS: Women's unique circumstances modulate the information that they value and require most in the context of making an informed decision. Widened availability of trustworthy information about NIPT as well as careful attention to the facilitation of counselling may help facilitate informed decision-making. TRIAL REGISTRATION: PROSPERO 2018 CRD42018086261 .

Cost-Effectiveness of Magnetic Resonance-Guided Focused Ultrasound for Essential Tremor.

BACKGROUND: Radiofrequency thalamotomy and deep brain stimulation are current treatments for moderate to severe medication-refractory essential tremor. However, they are invasive and thus carry risks. Magnetic resonance-guided focused ultrasound is a new, less invasive surgical option. The objective of the present study was to determine the cost-effectiveness of magnetic resonance-guided focused ultrasound compared with standard treatments in Canada. METHODS: We conducted a cost-utility analysis using a Markov cohort model. We compared magnetic resonance-guided focused ultrasound with no surgery in people ineligible for invasive neurosurgery and with radiofrequency thalamotomy and deep brain stimulation in people eligible for invasive neurosurgery. In the reference case analysis, we used a 5-year time horizon and a public payer perspective and discounted costs and benefits at 1.5% per year. RESULTS: Compared with no surgery in people ineligible for invasive neurosurgery, magnetic resonance-guided focused ultrasound cost $21,438 more but yielded 0.47 additional quality-adjusted life years, producing an incremental cost-effectiveness ratio of $45,817 per quality-adjusted life year gained. In people eligible for invasive neurosurgery, magnetic resonance-guided focused ultrasound was slightly less effective but much less expensive compared with the current standard of care, deep brain stimulation. The results were sensitive to assumptions regarding the time horizon, cost of magnetic resonance-guided focused ultrasound, and probability of recurrence. CONCLUSIONS: In people ineligible for invasive neurosurgery, the incremental cost-effectiveness ratio of magnetic resonance-guided focused ultrasound versus no surgery is comparable to many other tests and treatments that are widely adopted in high-income countries. In people eligible for invasive neurosurgery, magnetic resonance-guided focused ultrasound is also a reasonable option. © 2018 International Parkinson and Movement Disorder Society.

Prospective observational cohort study of 'treatment as usual' over four years for patients with schizophrenia in a national forensic hospital.

BACKGROUND: We evaluated change in response to multi-modal psychosocial 'treatment as usual' programs offered within a forensic hospital. METHODS: Sixty nine patients with a diagnosis of schizophrenia or schizoaffective disorder were followed for up to four years. Patient progress was evaluated using the DUNDRUM-3, a measure of patient ability to participate and benefit from multi-modal psychosocial programs and the HCR-20 dynamic items, a measure of violence proneness. We report reliable change index (RCI) and reliable and clinically meaningful change (RMC). We assessed patients' cognition using the MCCB, psychopathology using the PANSS. The effect of cognition and psychopathology on change in DUNDRUM-3 was examined using hierarchical multiple regression with age, gender, and baseline DUNDRUM-3 scores. RESULTS: The DUNDRUM-3 changed significantly (p < 0.004, d = 0.367, RCI 32% of 69 cases, RMC 23%) and HCR-20-C (p < 0.003, d = 0.377, RCI 10%). Both cognition and psychopathology accounted for significant variance in DUNDRUM-3 at follow up. Those hospitalized for less than five years at baseline changed more than longer stay patients. Mediation analysis demonstrated that the relationship between cognition and change in violence proneness (HCR-20-C) was both directly affected and indirectly mediated by change in DUNDRUM-3. CONCLUSIONS: Change in response to multi-modal psychosocial programs (DUNDRUM-3) reduced a measure of violence proneness over four years. Forensic in-patients' ability to benefit from psychosocial treatment appears to be a function of the outcome measure used, unit of measurement employed, degree of cognitive impairment, psychopathology, and length of stay. Lower risk of re-offending may be partially attributable to participation and engagement in psychosocial interventions.

Robot-assisted hysterectomy for endometrial and cervical cancers: a systematic review.

Total and radical hysterectomies are the most common treatment strategies for early-stage endometrial and cervical cancers, respectively. Surgical modalities include open surgery, laparoscopy, and more recently, minimally invasive robot-assisted surgery. We searched several electronic databases for randomized controlled trials and observational studies with a comparison group, published between 2009 and 2014. Our outcomes of interest included both perioperative and morbidity outcomes. We included 35 observational studies in this review. We did not find any randomized controlled trials. The quality of evidence for all reported outcomes was very low. For women with endometrial cancer, we found that there was a reduction in estimated blood loss between the robot-assisted surgery compared to both laparoscopy and open surgery. There was a reduction in length of hospital stay between robot-assisted surgery and open surgery but not laparoscopy. There was no difference in total lymph node removal between the three modalities. There was no difference in the rate of overall complications between the robot-assisted technique and laparoscopy. For women with cervical cancer, there were no differences in estimated blood loss or removal of lymph nodes between robot-assisted and laparoscopic procedure. Compared to laparotomy, robot-assisted hysterectomy for cervical cancer showed an overall reduction in estimated blood loss. Although robot-assisted hysterectomy is clinically effective for the treatment of both endometrial and cervical cancers, methodologically rigorous studies are lacking to draw definitive conclusions.

Impact of an online medical internet site on knowledge and practice of health care providers: a mixed methods study of the Spinal Cord Injury Rehabilitation Evidence project.

BACKGROUND: It is not known whether ongoing access to a broad-based Internet knowledge resource can influence the practice of health care providers. We undertook a study to evaluate the impact of a Web-based knowledge resource on increasing access to evidence and facilitating best practice of health care providers. OBJECTIVE: The objective of this study was to evaluate (1) the impact of the Spinal Cord Injury Rehabilitation Evidence (SCIRE) project on access to information for health care providers and researchers and (2) how SCIRE influenced health care providers' management of clients. METHODS: A 4-part mixed methods evaluation was undertaken: (1) monitoring website traffic and utilization using Google Analytics, (2) online survey of users who accessed the SCIRE website, (3) online survey of targeted end-users, that is, rehabilitation health care providers known to work with spinal cord injury (SCI) clients, as well as researchers, and (4) focus groups with health care providers who had previously accessed SCIRE. RESULTS: The online format allowed the content for a relatively specialized field to have far reach (eg, 26 countries and over 6500 users per month). The website survey and targeted end-user survey confirmed that health care providers, as well as researchers perceived that the website increased their access to SCI evidence. Access to SCIRE not only improved knowledge of SCI evidence but helped inform changes to the health providers' clinical practice and improved their confidence in treating SCI clients. The SCIRE information directly influenced the health providers' clinical decision making, in terms of choice of intervention, equipment needs, or assessment tool. CONCLUSIONS: A Web-based knowledge resource may be a relatively inexpensive method to increase access to evidence-based information, increase knowledge of the evidence, inform changes to the health providers' practice, and influence their clinical decision making.

T cell activation: in vivo veritas.

Phenotypic changes in CD4(+) T cells undergoing antigen-dependent activation were compared in vivo and in vitro. The most obvious difference was in expression of CD25, the alpha chain of the high affinity receptor for IL-2. High level expression of CD25 in vivo is restricted to a small fraction of the cells at the leading edge of the cell division profile, whereas all activated cells express high levels of CD25 in cultures responding to antigen. Because IL-2 is known to upregulate expression of CD25 in preactivated T cells, this suggests a difference in IL-2 exposure in the two responses. A number of other markers, including CD54, show a similar difference in the pattern of expression in vivo and in vitro. Using 6-colour flow cytometry, it was demonstrated that the small percentage of cells expressing CD25 in vivo coexpresses a very high level of a number of other activation markers, including CD38, CD44 and Ly-6A/E, suggesting that these may also be upregulated by autocrine IL-2.