The cost-effectiveness of non-invasive stool-based colorectal cancer screening offerings from age 45 for a commercial and medicare population.

AIM: The United States Preventive Services Taskforce (USPSTF) recently recommended lowering the age for average-risk colorectal cancer (CRC) screening from 50 to 45 years. While initiating screening at age 45 versus 50 provides a greater opportunity for CRC early detection and prevention, the full profile of benefits, risks, and cost-effectiveness of expanding the screen-eligible population requires further evaluation. MATERIALS AND METHODS: The costs and clinical outcomes for screening at age 45 for triennial multi-target stool DNA [mt-sDNA], and other non-invasive stool-based modalities (annual fecal immunochemical test [FIT] and annual fecal-occult blood test [FOBT]), were estimated using the validated CRC-AIM microsimulation model over a lifetime horizon. Test sensitivity and specificity inputs were based on 2021 USPSTF modeling analyses; adherence rates were based on published real-world data and the costs of the screening test, follow-up colonoscopies, complications, and CRC care were included. Outcomes are reported from the perspective of a United States payer as clinical, life-years gained (LYG), and incremental cost-effectiveness ratio (ICER); stool-based and follow-up colonoscopy adherence ranges were explored in one-way, probabilistic and threshold analyses. RESULTS: When compared to initiation of CRC screening at age 45 versus 50, all modalities reduced both the incidence of and mortality from CRC and increased LYG. Initiating CRC screening at age 45 was cost-effective with an ICER of $59,816 and $35,857 per quality-adjusted life year (QALY) for mt-sDNA versus FIT and FOBT, respectively. In the threshold analyses, at equivalent rates to stool-based screening, mt-sDNA was always cost-effective at a willingness-to-pay threshold of $100,000 per QALY versus FIT and FOBT. CONCLUSIONS: Initiating average-risk CRC screening at age 45 instead of age 50 increases the estimated clinical benefit by reducing disease burden while remaining cost-effective. Among stool-based screening modalities, mt-sDNA provides the most clinical benefit in a Commercial and Medicare population.

Screening for colorectal cancer at an earlier age can provide additional benefits in terms of reducing disease complications and death. This study looked at the occurrence of disease complications and costs related to different types of colorectal cancer screening in 45 vs. 50 year old people. A model that has previously been used to project lifetime costs and disease complications in people receiving colorectal cancer screening was used in this study. We found that beginning screening at age 45 as compared to at age 50 reduced disease complications and death. In people who started screening at age 45, one particular screening type (multitarget stool DNA) was found to provide better economic value to a greater degree relative to other strategies. These findings were consistent even when many inputs into the model were changed over reasonable ranges. Therefore, our study helps show that starting screening in people at age 45 with average risk for developing colorectal cancer is beneficial by reducing disease complications and deaths, and that multitarget stool DNA is the strategy that provides the most benefits while being economically justifiable.

Physicians differ in their perceptions of sensitive medical records: Survey and interview study.

Physician categorizations of electronic health record (EHR) data (e.g., depression) into sensitive data categories (e.g., Mental Health) and their perspectives on the adequacy of the categories to classify medical record data were assessed. One thousand data items from patient EHR were classified by 20 physicians (10 psychiatrists paired with ten non-psychiatrist physicians) into data categories via a survey. Cluster-adjusted chi square tests and mixed models were used for analysis. 10 items were selected per each physician pair (100 items in total) for discussion during 20 follow-up interviews. Interviews were thematically analyzed. Survey item categorization yielded 500 (50.0%) agreements, 175 (17.5%) disagreements, 325 (32.5%) partial agreements. Categorization disagreements were associated with physician specialty and implied patient history. Non-psychiatrists selected significantly (p = .016) more data categories than psychiatrists when classifying data items. The endorsement of Mental Health and Substance Use categories were significantly (p = .001) related for both provider types. During thematic analysis, Encounter Diagnosis (100%), Problems (95%), Health Concerns (90%), and Medications (85%) were discussed the most when deciding the sensitivity of medical information. Most (90.0%) interview participants suggested adding additional data categories. Study findings may guide the evolution of digital patient-controlled granular data sharing technology and processes.

Estimating recurrences prevented and costs avoided with atezolizumab in early non-small cell lung cancer in the United States.

BACKGROUND: Recurrence of early-stage non-small cell lung cancer (eNSCLC) is associated with significant mortality and costs. Atezolizumab (ATZ) was recently approved as adjuvant treatment following resection and platinum-based chemotherapy for adults with stage II-IIIA NSCLC with PD-L1 expression ≥1% after demonstrating significant improvement in disease-free survival (DFS) relative to best supportive care (BSC) in the IMpower010 trial (NCT02486718). This study evaluated the population-level impact of ATZ as adjuvant treatment for eNSCLC in the United States by estimating the number and costs of recurrences avoided. METHODS: A Monte Carlo simulation model estimated the cumulative number of recurrences and deaths prevented, along with direct, indirect, and terminal care costs, by treating eNSCLC patients with ATZ compared to BSC. The model included eligible patients treated in any given year and followed over a 5-year period. Recurrence and mortality rates and costs were based on the IMpower010 data and supplemented by estimates from published literature. RESULTS: An estimated 4400 eNSCLC patients in the United States were eligible for adjuvant ATZ in any given year, of whom 2387 would experience recurrence within 5 years with BSC. Following the introduction of ATZ, 1030 (95% confidence interval [CI]: 1023, 1036) recurrences and 369 (95% CI: 362, 376) deaths would be avoided with estimated reductions in cumulative recurrence-related direct, indirect, and terminal care costs of $785 million, $15 million, and $32 million, respectively, over a 5-year time horizon. CONCLUSIONS: Adjuvant ATZ is estimated to prevent a significant number of recurrences and reduce the economic burden of eNSCLC.

Mother to Newborn Transmission of SARS-CoV-2 Infection: Evolution of Evidence in 1.5 Years of COVID-19 Pandemic.

Coronavirus disease 2019 (COVID-19) pandemic caused significant mortality and morbidity in people of all age groups worldwide. Given the uncertainty regarding the mode of transmission and potential effects of COVID-19 on pregnant mothers and their newborns, guidelines for taking care of maternal-newborn dyads have evolved tremendously since the pandemic began. There has been an enormous influx of published materials regarding the outcomes of mothers and newborns. Still, multiple knowledge gaps regarding comprehensive information about risk to the mothers and newborns exist, which need to be addressed. Current evidence suggests that mothers with symptomatic COVID-19 infection are at increased risk of severe illness during pregnancy, with a higher need for respiratory support and premature deliveries. Neonates born to mothers with COVID-19 are at increased risk of needing intensive care; however, most newborns do well after birth. As new mutant variants arise, we need to be cautious while proactively understanding any new evolving patterns. All leading health authorities strongly recommend COVID-19 vaccination before or during pregnancy to reduce the risk of maternal morbidities and benefit from passing antibodies to newborns prenatally and via breastmilk. Additionally, there are racial, ethnic, and socioeconomic disparities in outcomes and vaccination coverage for pregnant women. This article summarizes the rapidly evolving evidence for the last 1.5 years and aims to help health care professionals care for mothers with COVID-19 and their newborns. KEY POINTS: · COVID-19 in pregnancy can cause perinatal morbidities.. · Breastfeeding and breast milk are safe for newborns.. · COVID-19 vaccination reduces the risk for morbidities..

Cutting the umbilical cord: Cancer stem cell-targeted therapeutics.

Cancer Stem Cells (CSCs) are a notoriously quiescent subpopulation of cells within heterogeneous tumors exhibiting self-renewal, differentiation and drug-resistant capabilities leading to tumor relapse. Heterogeneous cell populations in tumor microenvironment develop an elaborate network of signalling and factors supporting the CSC population within a niche. Identification of specific biomarkers for CSCs facilitates their isolation. CSCs demonstrate abilities that bypass immune surveillance, exhibit resistance to therapy, and induce cancer recurrence while promoting altered metabolism of the bulk tumor, thereby encouraging metastasis. The fight against cancer is prone to relapse without discussing the issue of CSCs, making it imperative for encapsulation of current studies. In this review, we provide extensive knowledge of recent therapeutics developed that target CSCs via multiple signalling cascades, altered metabolism and the tumor microenvironment. Thorough understanding of the functioning of CSCs, their interaction with different cells in the tumor microenvironment as well as current gaps in knowledge are addressed. We present possible strategies to disrupt the cellular and molecular interplay within the tumor microenvironment and make it less conducive for CSCs, which may aid in their eradication with subsequently better treatment outcomes. In conclusion, we discuss a brief yet functional idea of emerging concepts in CSC biology to develop efficient therapeutics acting on cancer recurrence and metastasis.

A Case of Idiopathic Thrombocytopenic Purpura After Booster Dose of BNT162b2 (Pfizer-Biontech) COVID-19 Vaccine.

Vaccination is now considered the best measure in minimizing the morbidity and mortality from the Covid-19 pandemic. Almost all the vaccines are considered safe except for minor and occasional side effects. Some of the commonly reported complications from the COVID-19 vaccines are vaccine-induced thrombotic thrombocytopenia (VITT)/thrombosis with thrombocytopenia syndrome/vaccine-induced pro-thrombotic immune thrombocytopenia syndrome. In this case report, we present a case of a 75-year-old female who had an uncomplicated first and second vaccine dose but developed VITT after the booster dose of the vaccine. The patient was treated with dexamethasone and platelet transfusions. So far no such cases have been reported after the third (booster) dose of the Pfizer-Biontech vaccine. With this case report, we present the case of the patient and discuss the literature related to vaccine-induced thrombocytopenia.

Pancreatic Neuroendocrine Tumors (panNETs): Analysis of Overall Survival of Nonsurgical Management Versus Surgical Resection.

BACKGROUND: Outcomes of patients with pancreatic neuroendocrine tumors (panNETs) undergoing surgical or nonsurgical management and outcomes of enucleation versus standard resection were compared. METHODS: MEDLINE, EMBASE, PubMed, Scopus, and Cochrane were queried (2000 to present). All studies comparing patients undergoing surgical versus nonsurgical treatments, or enucleation versus standard resection, were included. Pooled risk ratios and 95% CI for survival were calculated. RESULTS: Eleven studies met criteria with 1491 resected and 1607 nonsurgically managed patients. Meta-analysis showed improved overall survival with resection at 1 year (risk ratio (RR) = 1.281, CI 1.064-1.542, p = 0.009), 3 years (RR = 1.837, CI 1.594-2.117, p < 0.001), and 5 years (RR = 2.103, CI 1.50-2.945, p < 0.001). OS of patients with resected nonfunctioning panNETs was improved at 3 years (RR = 1.847, CI 1.477-2.309, p < 0.001) and 5 years (RR = 1.767, CI 1.068-2.924, p = 0.027). OS was improved when panNETs ≤2 cm were resected at 3 years (RR = 1.695, CI 1.269-2.264, p < 0.001) and 5 years (RR = 2.210, CI 1.749-2.791, p < 0.001). Fifteen articles met criteria for enucleation versus standard resection (n = 1035; 620 were nonfunctioning). Enucleation had shorter operative time (weighted mean difference (WMD) = -95.6 min, 95% CI -131.4 to -59.8, p < 0.01), less operative blood loss (WMD = -172.6 ml, 95% CI -340 to -5.1, p = 0.04), but increased postoperative pancreatic fistula (POPF) (RR = 2.08, 95% CI 1.39-3.12, p < 0.01). CONCLUSION: Surgical resection of panNETs, including small and nonfunctioning, appears to be associated with improved OS. Enucleation is associated with shorter operative time, less blood loss, but greater incidence of POPF. Prospective, randomized clinical trials are needed to confirm these results.

Distal pancreatectomy for benign and low grade malignant tumors: Short-term postoperative outcomes of spleen preservation-A systematic review and update meta-analysis.

BACKGROUND: The value of spleen preservation with distal pancreatectomy (DP) for benign and low grade malignant tumors remains unclear. The aim of this study was to evaluate the short-term postoperative clinical outcomes in patients undergoing DP with splenectomy (DPS) or spleen preservation (SPDP). METHODS: Online database search was performed (2000 to present); key bibliographies were reviewed. Studies comparing patients undergoing DP with either DPS or SPDP, and assessing postoperative complications were included. RESULTS: Meta-analysis of included data showed SPDP patients had significantly less operative blood loss, shorter duration of hospitalization, lower incidence of fluid collection and abscess, lower incidence of postoperative splenic and portal vein thrombosis, and lower incidence of new onset postoperative diabetes. For the whole group, there was no difference in incidence of postoperative pancreatic fistula (POPF) (RR = 0.95; 95%CI 0.65-1.40, P = 0.80), however, subgroup analysis of studies using ISGPF criteria showed that DPS patients had increased rates of Grade B/C POPF (RR = 1.35; 95%CI 1.08-1.70, P = 0.01). CONCLUSIONS: SPDP for benign and low grade malignant tumors is associated with shorter hospital stay and decreased morbidity compared to DPS. J. Surg. Oncol. 2017;115:137-143. © 2017 Wiley Periodicals, Inc.

Unresectable Hepatocellular Carcinoma: Radioembolization Versus Chemoembolization: A Systematic Review and Meta-analysis.

BACKGROUND: Transarterial radioembolization (TARE) has emerged as a newer regional therapy to transarterial chemoembolization (TACE) for treatment of unresectable hepatocellular carcinoma (HCC). The aim of this study is to compare clinical outcomes of both the techniques. METHODS: Online search for studies comparing TARE to TACE from 2005 to present was performed. Primary outcome was overall survival rate for up to 4 years. Secondary outcomes included post-treatment complications and treatment response. Quality of included studies was evaluated by STrengthening the Reporting of OBservational studies in Epidemiology criteria. Relative risk (RR) and 95 % confidence intervals (CI) were calculated from pooled data. RESULTS: The search strategy yielded 172 studies, five met selection criteria and included 553 patients with unresectable HCC, 284 underwent TACE and 269 underwent TARE. Median ages were 63 and 64 years for TACE and TARE, respectively. Meta-analysis showed no statistically significant difference in survival for up to 4 years between the two groups (HR = 1.06; 95 % CI 0.81-1.46, p = 0.567). TACE required at least one day of hospital stay compared to TARE which was mostly an outpatient procedure. TACE had more post-treatment pain than TARE (RR = 0.51, 95 % CI 0.36-0.72, p < 0.01), but less subjective fatigue (RR = 1.68, 95 % CI 1.08-2.62, p < 0.01). There was no difference between the two groups in the incidence of post-treatment nausea, vomiting, fever, or other complications. In addition, there was no difference in partial or complete response rates between the two groups. CONCLUSION: TARE appears to be a safe alternative treatment to TACE with comparable complication profile and survival rates. Larger prospective randomized trials, focusing on patient-reported outcomes and cost-benefit analysis are required to consolidate these results.

Gender based differences in management and outcomes of cholecystitis.

BACKGROUND: During the reproductive years, women have a 4-fold higher prevalence of gallstones than men, making gallbladder disease a critically important topic in women's health. Among age-matched women and men hospitalized for cholecystitis, gender based differences in demographics, management, and economic and clinical outcomes were identified. METHODS: A cross-sectional study was conducted using the Nationwide Inpatient Sample. Outcomes were mortality, complications, length of stay, and cost. RESULTS: Women accounted for 65% of admissions for cholecystitis, with women more likely to have shorter time to surgery (1.6 vs. 1.9 days) and laparoscopy (86 vs. 76%) (P < .05). After cholecystectomy, women had lower mortality (.6% vs. 1.1%), fewer complications (16.9 vs. 24.1), shorter lengths of stay (4.2 vs. 5.4 days), and lower costs ($10,556 vs. $13,201) (P < .05). On multivariate analysis of age-matched patients, women had lower odds of mortality (odds ratio [OR], .75), complications (OR, .86), length of stay (OR, .95), and cost (OR, .93). Longer time to surgery and open cholecystectomy were independent predictors of worse outcomes. CONCLUSIONS: In cholecystitis and cholecystectomy, women have better clinical and economic outcomes then age-matched men.

Prediction of recurrent coarctation by early postoperative blood pressure gradient.

OBJECTIVE: Blood pressure gradients that are noted early after repair of coarctation in neonates and infants are often attributed to proximal arch hypoplasia. Rapid growth of the hypoplastic proximal arch is usually observed, although in some individuals an early gradient predicts the subsequent need for reintervention. To define the predictive reliability of blood pressure gradients between arms and legs and to identify predictors of arch growth, we undertook a retrospective study. METHODS: Between January 2000 and June 2008, 77 infants underwent surgical repair of coarctation. Data collected included preoperative dimensions of aortic segments. Blood pressure gradients between arms and legs determined by cuff were compared intraoperatively and postoperatively, as well as 2-dimensional echocardiographic dimensions of the aorta between those who did not require reintervention for recoarctation (group A) and those who did (group B). Receiver operating characteristic curve analysis was applied to evaluate discrimination of the systolic gradient in differentiating the 2 groups of patients. RESULTS: At surgery, patients' median age was 10 days and weight was 3.3 kg. There was 1 early death. Median follow-up was 40 months (interquartile range, 24-63 months). Recoarctation developed in 11 patients (14.3%), defined as a resting blood pressure gradient of greater than 20 mm Hg with a corresponding decrease in the diameter of the aorta by 50%. Freedom from recoarctation was 87% at 1 year and 85% at 5 years. Multivariable logistic regression analysis identified the size of the ascending aorta as a risk factor for recoarctation. Blood pressure gradient at the end of surgery was not predictive of recoarctation. The ascending aorta and transverse arch showed rapid growth in group A, and this was associated with a decrease in blood pressure gradient over time. In comparison, the growth of the ascending aorta and arch in group B was significantly less than in group A and associated with worsening of gradients. Receiver operating characteristic curve analysis revealed that gradients at the time of hospital discharge (>13 mm Hg) had excellent discriminative accuracy in identifying patients in whom subsequent recoarctation developed. CONCLUSIONS: Small size of the ascending aorta is a risk factor for recoarctation. Limb gradient in the operating room at completion of surgery is not a reliable tool to assess repair of coarctation, although the gradient at the time of hospital discharge can be used to accurately predict recoarctation. Rapid growth of both the ascending and the transverse aorta is frequently observed and associated with improvement in gradients over time.

Use of tree-based models to identify subgroups and increase power to detect linkage to cardiovascular disease traits.

BACKGROUND: Our goal was to identify subgroups of sib pairs from the Framingham Heart Study data set that provided higher evidence of linkage to particular candidate regions for cardiovascular disease traits. The focus of this method is not to claim identification of significant linkage to a particular locus but to show that tree models can be used to identify subgroups for use in selected sib-pair sampling schemes. RESULTS: We report results using a novel recursive partitioning procedure to identify subgroups of sib pairs with increased evidence of linkage to systolic blood pressure and other cardiovascular disease-related quantitative traits, using the Framingham Heart Study data set provided by the Genetic Analysis Workshop 13. This procedure uses a splitting rule based on Haseman-Elston regression that recursively partitions sib-pair data into homogeneous subgroups. CONCLUSIONS: Using this procedure, we identified a subgroup definition for use as a selected sib-pair sampling scheme. Using the characteristics that define the subgroup with higher evidence for linkage, we have identified an area of focus for further study.