Paramedic-Assisted Community Evaluation After Discharge: The PACED Intervention.

OBJECTIVES: Early rehospitalization of frail older adults after hospital discharge is harmful to patients and challenging to hospitals. Mobile integrated health (MIH) programs may be an effective solution for delivering community-based transitional care. The objective of this study was to assess the feasibility and implementation of an MIH transitional care program. DESIGN: Pilot clinical trial of a transitional home visit conducted by MIH paramedics within 72 hours of hospital discharge. SETTING AND PARTICIPANTS: Patients aged ≥65 years discharged from an urban hospital with a system-adapted eFrailty index ≥0.24 were eligible to participate. METHODS: Participants were enrolled after hospital discharge. Demographic and clinical information were recorded at enrollment and 30 days after discharge from the electronic health record. Data from a comparison group of patients excluded from enrollment due to geographical location was also abstracted. Primary outcomes were intervention feasibility and implementation, which were reported descriptively. Exploratory clinical outcomes included emergency department (ED) visits and rehospitalization within 30 days. Categorical and continuous group comparisons were conducted using χ2 tests and Kruskal-Wallis testing. Binomial regression was used for comparative outcomes. RESULTS: One hundred of 134 eligible individuals (74.6%) were enrolled (median age 81, 64% female). Forty-seven participants were included in the control group (median age 80, 55.2% female). The complete protocol was performed in 92 (92.0%) visits. Paramedics identified acute clinical problems in 23 (23.0%) visits, requested additional services for participants during 34 (34.0%) encounters, and detected medication errors during 34 (34.0%). The risk of 30-day rehospitalization was lower in the Paramedic-Assisted Community Evaluation after Discharge (PACED) group compared with the control (RR, 0.40; CI, 0.19-0.84; P = .03); there was a trend toward decreased risk of 30-day ED visits (RR, 0.61; CI, 0.37-1.37; P = .23). CONCLUSIONS AND IMPLICATIONS: This pilot study of an MIH transition care program was feasible with high protocol fidelity. It yields preliminary evidence demonstrating a decreased risk of rehospitalization in frail older adults.

Cognitively enhanced tai chi improved cognition vs. tai chi or stretching at 24 wk in older adults with MCI or memory concerns.

SOURCE CITATION: Li F, Harmer P, Eckstrom E, et al. Clinical effectiveness of cognitively enhanced tai ji quan training on global cognition and dual-task performance during walking in older adults with mild cognitive impairment or self-reported memory concerns: a randomized controlled trial. Ann Intern Med. 2023;176:1498-1507. 37903365.

CTFPHC recommends risk assessment-first screening to prevent fragility fractures in women aged ≥65 y.

SOURCE CITATION: Thériault G, Limburg H, Klarenbach S, et al; Canadian Task Force on Preventive Health Care. Recommendations on screening for primary prevention of fragility fractures. CMAJ. 2023;195:E639-E649. 37156553.

Advancing clinical trials in nursing homes: A proposed roadmap to success.

An effective clinical research effort in nursing homes to address prevention and treatment of COVID-19 faced overwhelming challenges. Under the Health Care Systems Research Network-Older Americans Independence Centers AGING Initiative, a multidisciplinary Stakeholder Advisory Panel was convened to develop recommendations to improve the capability of the clinical research enterprise in US nursing homes. The Panel considered the nursing home as a setting for clinical trials, reviewed the current state of clinical trials in nursing homes, and ultimately developed recommendations for the establishment of a nursing home clinical trials research network that would be centrally supported and administered. This report summarizes the Panel's recommendations, which were developed in alignment with the following core principles: build on available research infrastructure where appropriate; leverage existing productive partnerships of researchers with groups of nursing homes and nursing home corporations; encompass both efficacy and effectiveness clinical trials; be responsive to a broad range of stakeholders including nursing home residents and their care partners; be relevant to an expansive range of clinical and health care delivery research questions; be able to pivot as necessary to changing research priorities and circumstances; create a pathway for industry-sponsored research as appropriate; invest in strategies to increase diversity in study populations and the research workforce; and foster the development of the next generation of nursing home researchers.

Stakeholders' views on priorities essential for establishing a supportive environment for clinical trials in nursing homes.

BACKGROUND: The U.S. clinical research enterprise in nursing homes was unprepared to mount clinical trials in nursing homes to address urgent questions relevant to prevention and treatment during the COVID-19 pandemic. We identify priorities essential for establishing a supportive environment for future clinical trials in nursing homes. METHODS: Two cross-sectional online questionnaires were administered between January and February 2021. One was administered to nursing home providers, researchers, and policymakers; respondents rated the importance of attributes of researchers, facilities, leaders and staff for conducting clinical trials in nursing homes. Because importance may depend on trial type, respondents rated each attribute for efficacy trials (testing an intervention in ideal circumstances) and effectiveness trials (testing an intervention in "real world" circumstances). We calculated the attribute rating means and standard deviations, and used content analysis to characterize open-ended responses. The second questionnaire for resident family members and advocates included open-ended questions about nursing home research, and factors influencing willingness to participate. RESULTS: The attributes rated as most essential for conducting efficacy and effectiveness trials in nursing homes are research team attributes, that is, that researchers recognize regulatory constraints; understand and adapt to nursing home workflow; and work collaboratively with nursing home leaders to identify priorities. Resident and facility diversity emerged as essential for effectiveness trials; important dimensions included resident race, ethnicity and income, as well as nursing home urban/rural location, quality ratings, geography, staffing ratios, size, and profit status. Caregivers and resident advocates stressed the importance of communication among participants, researchers, and nursing home leadership and staff at all stages of a trial. CONCLUSION: Developing a robust U.S. clinical research enterprise capable of efficiently mounting future clinical trials in nursing homes will require a reimagining of the relationships that exist between researchers, facilities, nursing home leaders, and residents, with a research infrastructure specifically focused on supporting and fostering these connections.

Advancing Clinical Trials in Nursing Homes: A Proposed Roadmap to Success.

An effective clinical research effort in nursing homes to address prevention and treatment of COVID-19 faced overwhelming challenges. Under the Health Care Systems Research Network-Older Americans Independence Centers AGING Initiative, a multidisciplinary Stakeholder Advisory Panel was convened to develop recommendations to improve the capability of the clinical research enterprise in US nursing homes. The Panel considered the nursing home as a setting for clinical trials, reviewed the current state of clinical trials in nursing homes, and ultimately developed recommendations for the establishment of a nursing home clinical trials research network that would be centrally supported and administered. This report summarizes the Panel's recommendations, which were developed in alignment with the following core principles: build on available research infrastructure where appropriate; leverage existing productive partnerships of researchers with groups of nursing homes and nursing home corporations; encompass both efficacy and effectiveness clinical trials; be responsive to a broad range of stakeholders including nursing home residents and their care partners; be relevant to an expansive range of clinical and health care delivery research questions; be able to pivot as necessary to changing research priorities and circumstances; create a pathway for industry-sponsored research as appropriate; invest in strategies to increase diversity in study populations and the research workforce; and foster the development of the next generation of nursing home researchers.

Advancing Clinical Trials in Nursing Homes: A Proposed Roadmap to Success.

An effective clinical research effort in nursing homes to address prevention and treatment of COVID-19 faced overwhelming challenges. Under the Health Care Systems Research Network-Older Americans Independence Centers AGING Initiative, a multidisciplinary Stakeholder Advisory Panel was convened to develop recommendations to improve the capability of the clinical research enterprise in US nursing homes. The Panel considered the nursing home as a setting for clinical trials, reviewed the current state of clinical trials in nursing homes, and ultimately developed recommendations for the establishment of a nursing home clinical trials research network that would be centrally supported and administered. This report summarizes the Panel's recommendations, which were developed in alignment with the following core principles: build on available research infrastructure where appropriate; leverage existing productive partnerships of researchers with groups of nursing homes and nursing home corporations; encompass both efficacy and effectiveness clinical trials; be responsive to a broad range of stakeholders including nursing home residents and their care partners; be relevant to an expansive range of clinical and health care delivery research questions; be able to pivot as necessary to changing research priorities and circumstances; create a pathway for industry-sponsored research as appropriate; invest in strategies to increase diversity in study populations and the research workforce; and foster the development of the next generation of nursing home researchers.

Evaluation of the Cost-effectiveness of Drug Treatment for Alzheimer Disease in a Simulation Model That Includes Caregiver and Societal Factors.

Importance: The possibility of widespread use of a novel effective therapy for Alzheimer disease (AD) will present important clinical, policy, and financial challenges. Objective: To describe how including different patient, caregiver, and societal treatment-related factors affects estimates of the cost-effectiveness of a hypothetical disease-modifying AD treatment. Design, Setting, and Participants: In this economic evaluation, the Alzheimer Disease Archimedes Condition Event Simulator was used to simulate the prognosis of a hypothetical cohort of patients selected from the Alzheimer Disease Neuroimaging Initiative database who received the diagnosis of mild cognitive impairment (MCI). Scenario analyses that varied costs and quality of life inputs relevant to patients and caregivers were conducted. The analysis was designed and conducted from June 15, 2019, to September 30, 2020. Exposures: A hypothetical drug that would delay progression to dementia in individuals with MCI compared with usual care. Main Outcomes and Measures: Incremental cost-effectiveness ratio (ICER), measured by cost per quality-adjusted life-year (QALY) gained. Results: The model included a simulated cohort of patients who scored between 24 and 30 on the Mini-Mental State Examination and had a global Clinical Dementia Rating scale of 0.5, with a required memory box score of 0.5 or higher, at baseline. Using a health care sector perspective, which included only individual patient health care costs, the ICER for the hypothetical treatment was $192 000 per QALY gained. The result decreased to $183 000 per QALY gained in a traditional societal perspective analysis with the inclusion of patient non-health care costs. The inclusion of estimated caregiver health care costs produced almost no change in the ICER, but the inclusion of QALYs gained by caregivers led to a substantial reduction in the ICER for the hypothetical treatment, to $107 000 per QALY gained in the health sector perspective. In the societal perspective scenario, with the broadest inclusion of patient and caregiver factors, the ICER decreased to $74 000 per added QALY. Conclusions and Relevance: The findings of this economic evaluation suggest that policy makers should be aware that efforts to estimate and include the effects of AD treatments outside those on patients themselves can affect the results of the cost-effectiveness analyses that often underpin assessments of the value of new treatments. Further research and debate on including these factors in assessments that will inform discussions on fair pricing for new treatments are needed.

Cost-effectiveness of Screening for Osteoporosis in Older Men With a History of Falls.

Importance: Falls and osteoporosis share the potential clinical end point of fractures among older patients. To date, few fall prevention guidelines incorporate screening for osteoporosis to reduce fall-related fractures. Objective: To assess the cost-effectiveness of screening for osteoporosis using dual-energy x-ray absorptiometry (DXA) followed by osteoporosis treatment in older men with a history of falls. Design, Setting, and Participants: In this economic evaluation, a Markov model was developed to simulate the incidence of major osteoporotic fractures in a hypothetical cohort of community-dwelling men aged 65 years who had fallen at least once in the past year. Data sources included literature published from January 1, 1946, to July 31, 2020. The model adopted a societal perspective, a lifetime horizon, a 1-year cycle length, and a discount rate of 3% per year for both health benefits and costs. The analysis was designed and conducted from October 1, 2019, to September 30, 2020. Interventions: Screening with DXA followed by treatment for men diagnosed with osteoporosis compared with usual care. Main Outcomes and Measures: Incremental cost-effectiveness ratio (ICER), measured by cost per quality-adjusted life-year (QALY) gained. Results: Among the hypothetical cohort of men aged 65 years, the screening strategy had an ICER of $33 169/QALY gained and was preferred over usual care at the willingness-to-pay threshold of $100 000/QALY gained. The number needed to screen to prevent 1 hip fracture was 1876; to prevent 1 major osteoporotic fracture, 746. The screening strategy would become more effective and less costly than usual care for men 77 years and older. The ICER for the screening strategy did not substantially change across a wide range of assumptions tested in all other deterministic sensitivity analyses. At a willingness-to-pay threshold of $50 000/QALY gained, screening was cost-effective in 56.0% of simulations; at $100 000/QALY gained, 90.8% of simulations; and at $200 000/QALY gained, 99.6% of simulations. Conclusions and Relevance: These findings suggest that for older men who have fallen at least once in the past year, screening with DXA followed by treatment for those diagnosed with osteoporosis is a cost-effective use of resources. Fall history could be a useful cue to trigger assessment for osteoporosis in men.

Cost-effectiveness of single-dose zoledronic acid for nursing home residents with osteoporosis in the USA.

OBJECTIVE: To evaluate the cost-effectiveness of routine administration of single-dose zoledronic acid for nursing home residents with osteoporosis in the USA. DESIGN: Markov cohort simulation model based on published literature from a healthcare sector perspective over a lifetime horizon. SETTING: Nursing homes. PARTICIPANTS: A hypothetical cohort of nursing home residents aged 85 years with osteoporosis. INTERVENTIONS: Two strategies were compared: (1) a single intravenous dose of zoledronic acid 5 mg and (2) usual care (supplementation of calcium and vitamin D only). PRIMARY AND SECONDARY OUTCOME MEASURES: Incremental cost-effectiveness ratio (ICER), as measured by cost per quality-adjusted life year (QALY) gained. RESULTS: Compared with usual care, zoledronic acid had an ICER of $207 400 per QALY gained and was not cost-effective at a conventional willingness-to-pay threshold of $100 000 per QALY gained. The results were robust to a reasonable range of assumptions about incidence, mortality, quality-of-life effects and the cost of hip fracture and the cost of zoledronic acid. Zoledronic acid had a potential to become cost-effective if a fracture risk reduction with zoledronic acid was higher than 23% or if 6-month mortality in nursing home residents was lower than 16%. Probabilistic sensitivity analysis showed that the zoledronic acid would be cost-effective in 14%, 27% and 44% of simulations at willingness-to-pay thresholds of $50 000, $100 000 or $200 000 per QALY gained, respectively. CONCLUSIONS: Routine administration of single-dose zoledronic acid in nursing home residents with osteoporosis is not a cost-effective use of resources in the USA but could be justifiable in those with a favourable life expectancy.

Long-term cost-effectiveness of providing full coverage for preventive medications after myocardial infarction.

BACKGROUND: Adherence to drugs that are prescribed after myocardial infarction remains suboptimal. Although eliminating patient cost sharing for secondary prevention increases adherence and reduces rates of major cardiovascular events, the long-term clinical and economic implications of this approach have not been adequately evaluated. METHODS AND RESULTS: We developed a Markov model simulating a hypothetical cohort of commercially insured patients who were discharged from the hospital after myocardial infarction. Patients received ß-blockers, renin-angiotensin system antagonists, and statins without cost sharing (full coverage) or at the current level of insurance coverage (usual coverage). Model inputs were extracted from the Post Myocardial Infarction Free Rx Event and Economic Evaluation trial and other published literature. The main outcome was an incremental cost-effectiveness ratio as measured by cost per quality-adjusted life year gained. Patients receiving usual coverage lived an average of 9.46 quality-adjusted life years after their event and incurred costs of $171,412. Patients receiving full coverage lived an average of 9.60 quality-adjusted life years and incurred costs of $167,401. Compared with usual coverage, full coverage would result in greater quality-adjusted survival (0.14 quality-adjusted life years) and less resource use ($4011) per patient. Our results were sensitive to alterations in the risk reduction for post-myocardial infarction events from full coverage. CONCLUSIONS: Providing full prescription drug coverage for evidence-based pharmacotherapy to commercially insured post-myocardial infarction patients has the potential to improve health outcomes and save money from the societal perspective over the long-term. CLINICAL TRIAL REGISTRATION INFORMATION: https://www.clinicaltrials.gov. Unique identifier: NCT00566774.

Cost-effectiveness of oral anticoagulants for treatment of atrial fibrillation.

BACKGROUND: New anticoagulants may improve health outcomes in patients with atrial fibrillation, but it is unclear whether their use is cost-effective. METHODS AND RESULTS: A Markov state transition was created to compare 4 therapies: dabigatran 150 mg BID, apixaban 5 mg BID, rivaroxaban 20 mg QD, and warfarin therapy. The population included those with newly diagnosed atrial fibrillation who were eligible for treatment with warfarin. Compared with warfarin, apixaban, rivaroxaban, and dabigatran, costs were $93 063, $111 465, and $140 557 per additional quality-adjusted life year gained, respectively. At a threshold of $100 000 per quality-adjusted life year, apixaban provided the greatest absolute benefit while still being cost-effective, although warfarin would be superior if apixaban was 2% less effective than expected. Although apixaban was the optimal strategy in our base case, in probabilistic sensitivity analysis, warfarin was optimal in an equal number of iterations at a cost-effectiveness threshold of $100 000 per quality-adjusted life year. CONCLUSIONS: While at a standard cost-effectiveness threshold of $100 000 per quality-adjusted life year, apixaban seems to be the optimal anticoagulation strategy; this finding is sensitive to assumptions about its efficacy and cost. In sensitivity analysis, warfarin seems to be the optimal choice in an equal number of simulations. As a result, although all the novel oral anticoagulants produce greater quality-adjusted life expectancy than warfarin, they may not represent good value for money.

Cost-effectiveness of full coverage of aromatase inhibitors for Medicare beneficiaries with early breast cancer.

BACKGROUND: Rates of nonadherence to aromatase inhibitors (AIs) among Medicare beneficiaries with hormone receptor-positive early breast cancer are high. Out-of-pocket drug costs appear to be an important contributor to this and may be addressed by eliminating copayments and other forms of patient cost sharing. The authors estimated the incremental cost-effectiveness of providing Medicare beneficiaries with full prescription coverage for AIs compared with usual prescription coverage under the Medicare Part D program. METHODS: A Markov state-transition model was developed to simulate AI use and disease progression in a hypothetical cohort of postmenopausal Medicare beneficiaries with hormone receptor-positive early breast cancer. The analysis was conducted from the societal perspective and considered a lifetime horizon. The main outcome was an incremental cost-effectiveness ratio, which was measured as the cost per quality-adjusted life-year (QALY) gained. RESULTS: For patients receiving usual prescription coverage, average quality-adjusted survival was 11.35 QALYs, and lifetime costs were $83,002. For patients receiving full prescription coverage, average quality-adjusted survival was 11.38 QALYs, and lifetime costs were $82,728. Compared with usual prescription coverage, full prescription coverage would result in greater quality-adjusted survival (0.03 QALYs) and less resource use ($275) per beneficiary. From the perspective of Medicare, full prescription coverage was cost-effective (incremental cost-effectiveness ratio, $15,128 per QALY gained) but not cost saving. CONCLUSIONS: Providing full prescription coverage for AIs to Medicare beneficiaries with hormone receptor-positive early breast cancer would both improve health outcomes and save money from the societal perspective.

Comparative cost-effectiveness of interventions to improve medication adherence after myocardial infarction.

OBJECTIVE: To evaluate the comparative cost-effectiveness of interventions to improve adherence to evidence-based medications among postmyocardial infarction (MI) patients. DATA SOURCES/STUDY SETTING: Cost-effectiveness analysis. STUDY DESIGN: We developed a Markov model simulating a hypothetical cohort of 65-year-old post-MI patients who were prescribed secondary prevention medications. We evaluated mailed education, disease management, polypill use, and combinations of these interventions. The analysis was performed from a societal perspective over a lifetime horizon. The main outcome was an incremental cost-effectiveness ratio (ICER) as measured by cost per quality-adjusted life year (QALY) gained. DATA COLLECTION/EXTRACTION METHODS: Model inputs were extracted from published literature. PRINCIPAL FINDINGS: Compared with usual care, only mailed education had both improved health outcomes and reduced spending. Mailed education plus disease management, disease management, polypill use, polypill use plus mailed education, and polypill use plus disease management cost were $74,600, $69,200, $133,000, $113,000, and $142,900 per QALY gained, respectively. In an incremental analysis, only mailed education had an ICER of less than $100,000 per QALY and was therefore the optimal strategy. Polypill use, particularly when combined with mailed education, could be cost effective, and potentially cost saving if its price decreased to less than $100 per month. CONCLUSIONS: Mailed education and a polypill, once available, may be the cost-saving strategies for improving post-MI medication adherence.

Cost effectiveness of fracture prevention in postmenopausal women who receive aromatase inhibitors for early breast cancer.

PURPOSE: Aromatase inhibitors (AIs) increase the risk of osteoporosis and related fractures in postmenopausal women who receive adjuvant AIs for hormone receptor (HR) -positive early breast cancer (EBC). We compared the cost effectiveness of alternative screening and treatment strategies for fracture prevention. METHODS: We developed a Markov state transition model to simulate clinical practice and outcomes in a hypothetical cohort of women age 60 years with HR-positive EBC starting a 5-year course of AI therapy after primary surgery for breast cancer. Outcomes were quality-adjusted life-years (QALYs), lifetime cost, and incremental cost-effectiveness ratio (ICER). We compared the following strategies: no intervention; one-time bone mineral density (BMD) screening and selective bisphosphonate therapy in women with osteoporosis or osteopenia; annual BMD screening and selective bisphosphonate therapy in women with osteoporosis or osteopenia; and universal bisphosphonate therapy. RESULTS: ICERs for annual BMD screening followed by oral bisphosphonates for those with osteoporosis, annual BMD screening followed by oral bisphosphonates for those with osteopenia, and universal treatment with oral bisphosphonates were $87,300, $129,300, and $283,600 per QALY gained, respectively. One-time BMD screening followed by oral bisphosphonates for those with osteoporosis or osteopenia was dominated. Our results were sensitive to age at the initiation of AI therapy, type of bisphosphonates, post-treatment residual effect of bisphosphonates, and a potential adjuvant benefit of intravenous bisphosphonates. CONCLUSION: In postmenopausal women receiving adjuvant AIs for HR-positive EBC, a policy of baseline and annual BMD screening followed by selective treatment with oral bisphosphonates for those diagnosed with osteoporosis is a cost-effective use of societal resources.

Cost-effectiveness of fracture prevention in men who receive androgen deprivation therapy for localized prostate cancer.

BACKGROUND: Androgen deprivation therapy (ADT) increases the risk for fractures in patients with prostate cancer. OBJECTIVE: To assess the cost-effectiveness of measuring bone mineral density (BMD) before initiating ADT followed by alendronate therapy in men with localized prostate cancer. DESIGN: Markov state-transition model simulating the progression of prostate cancer and the incidence of hip fracture. DATA SOURCES: Published literature. TARGET POPULATION: A hypothetical cohort of men aged 70 years with locally advanced or high-risk localized prostate cancer starting a 2-year course of ADT after radiation therapy. TIME HORIZON: Lifetime. PERSPECTIVE: Societal. INTERVENTION: No BMD test or alendronate therapy, a BMD test followed by selective alendronate therapy for patients with osteoporosis, or universal alendronate therapy without a BMD test. OUTCOME MEASURES: Incremental cost-effectiveness ratio (ICER), measured by cost per quality-adjusted life-year (QALY) gained. RESULTS OF BASE-CASE ANALYSIS: The ICERs for the strategy of a BMD test and selective alendronate therapy for patients with osteoporosis and universal alendronate therapy without a BMD test were $66,800 per QALY gained and $178,700 per QALY gained, respectively. RESULTS OF SENSITIVITY ANALYSES: The ICER for universal alendronate therapy without a BMD test decreased to $100,000 per QALY gained, assuming older age, a history of fractures, lower mean BMD before ADT, or a lower cost of alendronate. LIMITATIONS: No evidence shows that alendronate reduces actual fracture rates in patients with prostate cancer who receive ADT. The model predicted fracture rates by using data on the surrogate BMD end point. CONCLUSION: In patients starting adjuvant ADT for locally advanced or high-risk localized prostate cancer, a BMD test followed by selective alendronate for those with osteoporosis is a cost-effective use of resources. Routine use of alendronate without a BMD test is justifiable in patients at higher risk for hip fractures.

Syndactyly lethal: new mutation with multiple malformations occurring in Sprague Dawley rats.

We previously found newborns exhibiting syndactyly of both fore- and hindlimbs in a litter from a pair of Sprague Dawley rats. Continuous breeding of the parental animals yielded pups with the same anomaly in following litters, suggesting that the syndactyly was genetic in origin. In the present study, as all the syndactylous pups died on postnatal day 0, we conducted genetic analyses using 30 phenotypically normal female progeny and the sire. The females were subjected to caesarean section on day 20 of gestation and the fetuses were examined for the phenotypes. The results of the mating experiments suggest that the mutant phenotype is caused by a single autosomal recessive gene at a homozygous condition. As homozygous mutants are lethal at the neonatal stage, the mutant gene was named syndactyly lethal, gene symbol syl. The mutant rats have multiple abnormalities, such as syndactyly, micrognathia, fused/absent/small lung lobes, absent kidney and ureter, small spleen, small uterus, fused phalanges, sternoschisis, absent/detached rib, and splitting/fused/absent/small thoracic vertebra, some of which must be the cause of death on postnatal day 0. This mutant is considered to be useful for investigating the mechanisms and/or pathogenesis of syndactyly, as well as the accompanying malformations.