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Approximately, 4% of Stage IV colorectal cancers (CRC) are microsatellite instability-high (MSI-H)/deficient mismatch repair (dMMR) tumors. Patients with metastatic MSI-H/dMMR CRC receiving conventional therapies experience lower response rates and tend to have worse overall survival compared with patients with microsatellite stable (MSS)/proficient mismatch repair (pMMR) CRC. Pembrolizumab received FDA approval in 2020 for first-line treatment of Stage IV MSI-H/dMMR CRC based on significantly longer progression-free survival versus standard of care (SoC, 5-fluorouracil-based therapy with or without bevacizumab or cetuximab). This study evaluated the cost-effectiveness of pembrolizumab vs. SoC as per KEYNOTE-177 and other first-line treatments for MSI-H/dMMR CRC from a US healthcare system perspective. A three-health-state partitioned-survival model was built using progression-free and overall survival data from KEYNOTE-177 and a network meta-analysis. Utilities were derived from KEYNOTE-177 EQ-5D-3L data. Drug acquisition, administration, AE, surgery, monitoring, subsequent treatment, and terminal care costs were included. Sensitivity and scenario analyses were performed, including utilizing a state-transition model structure and adopting a societal perspective. Over a lifetime time horizon, pembrolizumab and SoC were associated with total QALYs of 4.85 and 3.23, and total costs of $381,735 and $370,465, respectively, resulting in an ICER of $6,984 per QALY. QALY gains were mainly driven by extended survival with pembrolizumab. Pembrolizumab incurred higher drug acquisition costs relative to SoC but was cost-saving in terms of drug administration, AE, monitoring, subsequent treatment, and terminal care. Pembrolizumab dominated FOLFOX + panitumumab, FOLFOXIRI, and FOLFOXIRI + bevacizumab, and presented ICERs of $35,220 and $276 against XELOX and XELOX + bevacizumab. Results were robust to sensitivity and scenario analyses. Pembrolizumab is highly cost-effective for the first-line treatment of unresectable or metastatic MSI-H/dMMR CRC in the US at a willingness-to-pay threshold of $100,000/QALY.Key messagesPembrolizumab is a highly cost-effective option for the first-line treatment of patients with unresectable or metastatic MSI-H/dMMR colorectal cancer in the United States at a willingness-to-pay threshold of $100,000. Compared with the current standard of care for these patients, pembrolizumab:Increases survival due to delaying and preventing progression;Increases QALYs due to longer survival, improvement in HRQoL in the progression-free health state, and fewer Grade 3+ adverse events;Reduces costs associated with administering treatment, managing adverse events, monitoring post-progression disease, providing subsequent treatment, and providing terminal care; andReduces indirect health care costs when taking a societal perspective due to productivity gains from delaying and preventing progression and death, less frequent treatment administration and less frequent Grade 3+ adverse events. Pembrolizumab is a highly cost-effective option for the first-line treatment of patients with unresectable or metastatic MSI-H/dMMR colorectal cancer in the United States at a willingness-to-pay threshold of $100,000. Compared with the current standard of care for these patients, pembrolizumab: Increases survival due to delaying and preventing progression; Increases QALYs due to longer survival, improvement in HRQoL in the progression-free health state, and fewer Grade 3+ adverse events; Reduces costs associated with administering treatment, managing adverse events, monitoring post-progression disease, providing subsequent treatment, and providing terminal care; and Reduces indirect health care costs when taking a societal perspective due to productivity gains from delaying and preventing progression and death, less frequent treatment administration and less frequent Grade 3+ adverse events.

To find the prevalence and pattern of congenital heart disease (CHD) at a tertiary care hospital in Uttarakhand, India. A thorough history and clinical examination was done for all the live births and children up to 18 y of age who presented to the institute over a period of 3 y from July 2008 through June 2011. Those suspected of having a CHD, were further evaluated with ECG, chest radiography and the diagnosis was confirmed by color Doppler echocardiography. Of the 36541 children examined, 312 were identified as having congenital heart defects, thus giving a prevalence of 8.54 per 1000 children attending hospital. Only one fifth cases were diagnosed in neonatal period and the diagnosis was delayed beyond infancy in more than half of the cases. Ventricular septal defect (30.45%), atrial septal defect (17.63%), patent ductus arteriosus (9.62%), pulmonary stenosis (6.41%), tetralogy of Fallot (5.45%) and transposition of great arteries (5.13%) were the commonest defects observed. Only 9.29% of children with CHD underwent definitive treatment. The prevalence of CHD at a tertiary referral hospital in Uttarakhand India is 8.54 per 1000 children. VSD and TOF are the most common acyanotic and cyanotic congenital heart defects respectively.