Cost-effectiveness of universal routine sonographic cervical-length measurement at 19 to 25 weeks' gestation.

BACKGROUND: National second-trimester scanning of cervical length was introduced in Israel in 2010, and in the decade thereafter, a significant systematic reduction in preterm birth and in the delivery of low birthweight babies was found among singletons. OBJECTIVE: In this study, we sought to estimate the cost-effectiveness of a national policy mandating second-trimester cervical length screening by ultrasound, followed by vaginal progesterone treatment for short cervical length in comparison with no screening strategy. STUDY DESIGN: We constructed a decision model comparing 2 strategies, namely (1) universal cervical length screening, and (2) no screening strategy. This study used the national delivery registry of Israel's Ministry of Health. All women diagnosed with a second-trimester cervical length <25 mm were treated with vaginal progesterone and were monitored with a bimonthly ultrasound scan for cervical dynamics and threat of early delivery. Preterm birth prevalence associated with short cervical length, the efficacy of progesterone in preterm birth prevention, and the accuracy of cervical length measurements were derived from previous studies. The cost of progesterone and bimonthly sonographic surveillance, low birthweight delivery, newborn admission to intensive care units, the first-year costs of managing preterm birth and low birthweight, and instances of handicaps and the cost of their follow-up were extracted from the publicly posted registry of Israel's Ministry of Health and Israel Social Securities data. Monte Carlo simulations decision tree mode, Tornado diagrams, and 1- and 2-way sensitivity analyses were implemented and the base case and sensitivity to parameters that were predicted to influence cost-effectiveness were calculated. RESULTS: Without cervical length screening, the discounted quality-adjusted life years were 30.179, and with universal cervical length screening, it increased to 30.198 (difference of 0.018 quality-adjusted life years). The average cost of no screening for cervical length strategy was $1047, and for universal cervical length screening, it was reduced to $998. The calculated incremental cost-effectiveness ratio was -$2676 per quality-adjusted life year (dividing the difference in costs by the difference in quality-adjusted life years). Monte Carlo simulation of cervical length screening of 170,000 singleton newborns (rounded large number close to the number of singleton newborns in Israel) showed that 95.17% of all babies were delivered at gestational week ≥37 in comparison with 94.46% of babies with the no screening strategy. Given 170,000 singleton births, the national savings of screening for short cervical length when compared with no cervical length screening amounted to $8.31M annually, equating to $48.84 for a base case, and the incremental cost-effectiveness ratio for each case of low birthweight or very low birthweight avoided was -$14,718. A cervical length <25 mm was measured for 30,090 women, and of those, 24,650 were false positives. The major parameters that affected the incremental cost-effectiveness ratio were the incidence of preterm birth, the specificity of cervical length measurements, and the efficacy of progesterone treatment. At a preterm birth incidence of <3%, universal screening does not lead to a cost saving. CONCLUSION: National universal cervical length screening should be incorporated into the routine anomaly scan in the second trimester, because it leads to a drop in the incidence of preterm birth and low birthweight babies in singleton pregnancies, thereby saving costs related to the newborn and gaining quality-adjusted life years.

Colorectal cancer screening at age 45 years in Israel: Cost-effectiveness and global implications.

BACKGROUND: Colorectal cancer (CRC) incidence at ages <50 years is increasing worldwide. Screening initiation was lowered to 45 years in the United States. The cost-effectiveness of initiating CRC screening at 45 years in Israel was assessed with the aim of informing national policy and addressing internationally relevant questions. METHODS: A validated CRC screening model was calibrated to Israeli data and examined annual fecal immunochemical testing (FIT) or colonoscopy every 10 years from 45 to 74 years (FIT45-74 or Colo45-74) versus from 50 to 74 years (FIT50-74 or Colo50-74). The addition of a fourth colonoscopy at 75 years was explored, subanalyses were performed by sex/ethnicity, and resource demands were estimated. RESULTS: FIT50-74 and Colo50-74 reduced CRC incidence by 57% and 70% and mortality by 70% and 77%, respectively, versus no screening, with greater absolute impact in Jews/Other versus Arabs but comparable relative impact. FIT45-74 further reduced CRC incidence and mortality by an absolute 3% and 2%, respectively. With Colo45-74 versus Colo50-74, CRC cases and deaths increased slightly as three colonoscopies per lifetime shifted to 5 years earlier but mean quality-adjusted life-years gained (QALYGs) per person increased. FIT45-74 and Colo45-74 cost 23,800-53,900 new Israeli shekels (NIS)/QALYG and 110,600-162,700 NIS/QALYG, with the lowest and highest values among Jewish/Other men and Arab women, respectively. A fourth lifetime colonoscopy cost 48,700 NIS/QALYG. Lowering FIT initiation to 45 years with modest participation required 19,300 additional colonoscopies in the first 3 years. CONCLUSIONS: Beginning CRC screening at 45 years in Israel is projected to yield modest clinical benefits at acceptable costs per QALYG. Despite different estimates by sex/ethnicity, a uniform national policy is favored. These findings can inform Israeli guidelines and serve as a case study internationally.

Antibiotics or Tonsillectomy for Adult Recurrent Tonsillitis: Analyzing the Lesser of Two Evils.

OBJECTIVE: To determine the best timing for surgical intervention for adults with recurrent tonsillitis (RT). METHODS: A Markov model was constructed using variables and ranges based upon a literature review. A 1-way sensitivity analysis was performed to evaluate the number of yearly bouts at which each algorithm (antibiotics or tonsillectomy) would be favored. A Monte-Carlo probabilistic sensitivity analysis was calculated for gains and cost. Model outcomes were measured with quality-adjusted life-years (QALYs) and incremental cost-effectiveness ratios (ICER) for tonsillectomy versus repeat antibiotic treatment. RESULTS: Patients expected to sustain a single annual tonsillitis event will have a negative QALY of 0.02 if treated with surgery and those with 2 annual events will have a QALY gain from undergoing tonsillectomy of 0.01, 3 events = 0.03, 4 events = 0.05, 5 events = 0.07, 6 events = 0.09, 7 events = 0.1, and 8 events = 0.11. These gains became meaningful only after 2 years of recurrent bouts. The average cost of tonsillectomy was 3,238 USD, and the overall average cost of RT was 7,069 USD (an incremental cost of 3,831 USD). The ICER of tonsillectomy over antibiotic treatment for 1 QALY gain was 44,741 USD. CONCLUSION: Adult patients who sustain more than 3 annual bouts of tonsillitis over a period of at least 2 years will gain QALY after tonsillectomy. These gains increase proportionally to the number of yearly events and perennial episodes. The incremental costs of tonsillectomy fail to meet the NICE guidelines but are within other acceptable reference ranges. LEVEL OF EVIDENCE: NA Laryngoscope, 134:2153-2161, 2024.

A decision-making model for prediction of a stable disease course in chronic hepatitis B patients.

Patients with chronic hepatitis B (CHB) are regularly monitored for HBV DNA and liver enzymes in order to assess disease progression and the need for antiviral therapy. Identifying patients with a stable course of disease can potentially prolong the intervals between visits, withhold unnecessary tests and save money. Accordingly, we aimed to find predictors for a stable disease course in patients with CHB. 579 patients with CHB, who were followed in a tertiary referral center between January 2004-December 2018, were retrospectively analyzed. Patients with low and steady viral load titer (< 2000 IU/ml) and normal ALT levels (< 40 IU/ml) in 6 consecutive clinic encounters were considered to have a stable course of CHB. A stepwise multivariate logistic regression analysis and a decision tree model were used to identify predictors of a stable disease course. Following exclusion of ineligible patients, a total of 220 patients were included in the final analysis. 64/220 patients had a stable disease course. Patients with a stable disease were older (62.99 ± 12.36 Vs. 54.07 ± 13.64, p < 0.001) with a higher percentage of women (53% vs. 38%) and had lower baseline levels of AST, ALT and viral load (VL). In a multivariate analysis, age (OR 0.94, 95% CI 0.91-0.98), baseline ALT (OR 1.06, 95% CI 1.01-1.1) and VL (OR 1.05 95% CI 1.02-1.08), were significantly associated with a stable disease. In a decision tree model, patients 46-67 years old, with baseline VL < 149 IU/mL and ALT < 40 IU/mL had the best probability (91%) for a stable disease course over 4.4 ± 2.2 years. We conclude that integrating patients' age with baseline VL and ALT can predict a stable disease course in patients with CHB off treatment.

Cost-Utility Analysis of Open Radical Hysterectomy Compared to Minimally Invasive Radical Hysterectomy for Early-Stage Cervical Cancer.

We aimed to investigate the cost-effectiveness of open surgery, compared to minimally invasive radical hysterectomy for early-stage cervical cancer, using updated survival data. Costs and utilities of each surgical approach were compared using a Markovian decision analysis model. Survival data stratified by surgical approach and surgery costs were received from recently published data. Average costs were discounted at 3%. The value of health benefits for each strategy was calculated using quality-adjusted life years (QALYs). Incremental cost-effectiveness ratio, calculated using the formula (average cost minimal invasive surgery-average cost open surgery)/(average QALY minimal invasive surgery-average QALY open surgery), was used for cost-effectiveness analysis. One-way sensitivity analysis was conducted for all variables. Open radical hysterectomy was found to be cost-saving compared to minimally invasive surgery with an incremental cost-effectiveness ratio of USD -66 and USD -373 for laparoscopic and robotic surgery, respectively. The most influential parameters in the model were surgery costs, followed by the disutility involved with open surgery. Until further data are generated regarding the survival of patients with early-stage cervical cancer treated by minimally invasive surgery, at current pricing, open radical hysterectomy is cost-saving compared to minimally invasive radical hysterectomy, both laparoscopic and robotic.

Is There a Role for Molecular Testing for Low-Risk Differentiated Thyroid Cancer? A Cost-Effectiveness Analysis.

Molecular testing for thyroid nodules has been rapidly developed in recent years, aiming to predict the presence of malignancy and aggressive features. While commonly utilized to predict malignancy, its role in guiding the management approach is still developing. The high cost of genetic tests and long-term sequences of thyroid cancer is limiting to real-life studies. Objective: To evaluate the cost effectiveness of molecular testing for low-risk differentiated thyroid cancer (lrDTC). Methods: We developed a Markovian decision tree model of a simulated lrDTC cohort, comparing two management strategies: (I) Conducting genetic tests (GT)-patients are stratified into three risk groups for distant metastasis by the identified molecular markers: low-, intermediate- and high-risk molecular profile; followed by management accordingly: patients with low-risk will undergo hemithyroidectomy (HT), patients with intermediate-risk will undergo total thyroidectomy (TT), and high-risk patients will undergo TT with central neck dissection; (II) Without genetic tests (wGT)-all patients will undergo HT according to the ATA recommendations for lrDTC. Outcomes were measured as quality-adjusted life years (QALYs) and costs of each strategy. Results: GT was found as cost effective, leading to a gain of 1.7 QALYs with an additional cost of $327 per patient compared to wGT strategy. This yielded an incremental cost-effectiveness ratio of $190 per QALY. Sensitivity analysis demonstrated robust results across the variables' ranges. The most impactful variable was the benefit from performing TT rather than HT for intermediate to high-risk patients. Conclusions: Our model found that molecular testing for lrDTC is cost-effective, allowing tailored management according to the patient's personal risk level reflected in the genetic profile, hence improving outcomes.

Revisiting Age Criterion for Surgery in Asymptomatic Primary Hyperparathyroidism.

OBJECTIVE: To revisit the current age criterion (50 years) for surgical candidacy in patients diagnosed with asymptomatic primary hyperparathyroidism (PHPT). STUDY DESIGN: A predictive model relying on past publications using the electronic databases "PubMed," "Embase," "Medline," and "Google Scholar." SETTING: Hypothetical large cohort. METHODS: A Markov model was constructed, based on relevant literature, to compare 2 potential treatment algorithms for asymptomatic PHPT patients, parathyroidectomy (PTX), and observation. The various potential health states were characterized for the 2 treatment options and included potential surgical complications, end-organ deterioration, and death. A 1-way sensitivity analysis was performed to calculate the quality-adjusted life year (QALY) gains of both strategies. A Monte-Carlo simulation for 30,000 subjects was performed and cycled per annum. RESULTS: On the basis of the model's assumptions, the QALY value for the PTX strategy was 19.17 versus 17.82 for the observation strategy. The incremental QALY gains for various ages according to the sensitivity analyses for PTX in comparison to observation were: 2.84 QALY for 40-year-old patients, 2.2 QALY for 50-year-old patients, 1.81 QALY for 55-year-old patients, 1.35 QALY for 60-year-old patients, and 0.86 QALY for 65-year-old patients. The incremental QALY is below 0.5 after the age of 75 years. CONCLUSION: This study found PTX to be advantageous for asymptomatic PHPT patients older than the current age criterion of 50 years. The calculated QALY gains support a surgical approach for medically fit patients in their 50s. The current guidelines for the surgical treatment of young asymptomatic PHPT patients should be revisited by the next steering committee.

Development and validation of a prediction model for histologic progression in patients with nondysplastic Barrett's esophagus.

OBJECTIVES: Patients with Barrett's esophagus (BE) are at risk of progression to esophageal adenocarcinoma (EAC). We developed a model to predict histologic progression in patients with nondysplastic BE (NDBE). METHODS: A longitudinal study in three referral centers was performed between January 2010 and December 2019. As progression to low-grade dysplasia (LGD) can be considered an indication for ablative therapy, the study end-point was histopathologic progression to LGD, high-grade dysplasia, or EAC at 3 years after diagnosis. We used logistic regression to create the model. Seventy percent of the cohort were used to stem the model and the remaining 30% for internal validation. RESULTS: A total of 542 patients were included, 69.4% of whom were male, mean age 62.2 years. Long-segment BE at index endoscopy was diagnosed in 20.8% of the patients. After a mean follow-up of 6.7 years, 133 patients (24.5%) had histologic progression. Our model identified a neutrophil-to-lymphocyte ratio (odds ratio [OR] 2.08, 95% confidence interval [CI] 1.77-2.32, P < 0.001), BE length (OR 1.22, 95% CI 1.09-1.36, P < 0.001), age (OR 1.03, 95% CI 1.02-1.05, P = 0.02), smoking (OR 1.66, 95% CI 1.09-2.75, P = 0.04), and renal failure (OR 1.51, 95% CI 0.93-2.43, P = 0.07) as predictors of histologic progression at 3 years. The areas under the receiver operating characteristic curves of this model were 0.88 and 0.76 in the training and validation cohorts, respectively. CONCLUSION: This novel, internally validated model may predict histologic progression, even in patients with NDBE who generally have low rates of progression over time, and may contribute to enhanced patient selection for more intense surveillance programs.

Informing Risk Management for Patients With Cow's Milk Allergy Based on Threshold Dose Distributions Using Low-Dose Food Challenges.

BACKGROUND: The safe consumption of foods depends on their allergen content in relation to patients' lowest observed adverse effect level (LOAEL) and no observed adverse effect level (NOAEL), as well as other factors. In the case of milk, data on LOAEL and NOAEL are limited and conflicting. OBJECTIVE: To determine the threshold dose distribution and the lowest individual eliciting dose (ED) for milk in a large group of milk-allergic patients METHODS: Individuals with confirmed cow's milk allergy who underwent a diagnostic or pre-oral immunotherapy open milk oral food challenge at the Institute of Allergy, Immunology, and Pediatric Pulmonology at Shamir Medical Center between 2010 and 2015 were included. A subgroup of patients with severe milk allergy underwent a modified challenge with a 90- to 120-minute interval after a starting dose of 0.3 mg cow's milk protein. RESULTS: A total of 866 participants (193 with diagnostic challenges and 673 with pre-oral immunotherapy challenges) were included in the study. The discrete ED01 and ED05, or values derived in which 1% or 5% of the respective allergic population would be predicted to experience an allergic reaction, were 1.1 to 1.9 and 4.7 to 5.6 mg milk protein, respectively, and values for cumulative doses for ED01 and ED05 were 0.9 to 1.8 and 5.2 to 6.2 mg milk protein, respectively. No patients, including the most severely milk-allergic individuals who underwent the modified challenge, reacted to the first 0.3 mg protein dose. CONCLUSION: This report provides valuable information about milk NOAELs, LOAELs, and EDs that might assist regulators in decisions about food labeling in general, and milk in particular.

The Effects of Surgical Approaches and Enhanced Recovery Protocols on the Cost Effectiveness of Radical Cystectomy.

Enhanced recovery protocols and robotic approaches to radical cystectomy are known to reduce perioperative complications; however, the most cost-effective strategy is unknown. We aim to assess the cost effectiveness of radical cystectomy with different surgical techniques and perioperative treatment protocols. We performed a meta-analysis of studies comparing open radical cystectomy (ORC), robotic assisted radical cystectomy (RARC) using extracorporeal (ECUD) or intracorporeal urinary diversion (ICUD) and enhanced recovery after surgery (ERAS) protocols. Operative time, transfusion, complication, Ileus, length of stay and re-admission rates were extracted. US costs for surgery, treatment, hospitalization and complications were obtained from the literature. Israeli costs were obtained from hospital administrative data. Two cost effectiveness models (US and Israel) were developed. The two most cost-effective strategies in both models were ORC with ERAS and RARC with ICUD and ERAS. RARC with ERAS produced the two most effective strategies with ICUD being dominant over ECUD. All strategies implementing the ERAS protocol were more effective than their parallel non-ERAS strategies. RARC with ICUD and ERAS is cost effective compared to ORC. ERAS protocol improves treatment effectiveness and lowers overall costs. ICUD was shown to be more effective and less costly in comparison to ECUD.

Is molecular testing in patients with low risk papillary thyroid carcinoma justified? A Markovian model.

BACKGROUND: Current guidelines consider all cases of papillary thyroid carcinoma (PTC) smaller than 4 cm and without extrathyroidal extension (ETE) and/or lymph node metastases as belonging to the same prognostic group, and therefore the recommendation is for uniform treatment. Xing draws our attention to a small subgroup with Duet Mutations (BRAF E600 and TERT 3636 genes) that are aggressive biologically and should be treated differently. Thus the aim of the present study is to test the validity of this recommendation. METHODS: A Markovian Model is used to evaluate the above hypothesis. RESULTS: A Monte Carlo sensitivity test shows a 5.6 year survival advantage for patients with low-grade PTC, who have the Duet Mutations, and were treated by total thyroidectomy rather than hemithyroidectomy. CONCLUSIONS: We conclude that there is a place for routine molecular tests in low-risk patients with PTC.

Exploring Popular Social Media Networks for Patients With Inflammatory Bowel Diseases: Insights for Better Care.

GOAL: The aim was to assess topics of interest and concerns among patients with inflammatory bowel diseases (IBD) who are active online. BACKGROUND: Social media (SM) networks are a major communication tool for patients with IBD and health care professionals. PATIENTS AND METHODS: We performed an anonymized investigation of SM networks for IBD patients; I-a thematic analysis of patients' posts, II-an online survey advertised through Facebook and other popular SM networks throughout November 2019. RESULTS: Analyzing 2133 posts (2014 to 2019) revealed 18 topics of interest. The online survey was completed by 534 respondents [63%-Crohn's disease, 56%-female, median age-38 years (interquartile range: 28.7 to 51.0)]. Most respondents (70%) were followed in referral centers, and 45% were receiving biological therapy. Respondents reported high satisfaction with IBD care and health care provider professionalism. The top 5 topics of interest were diet, lifestyle, complementary and alternative medicine, diagnostic test interpretation, and specialist referrals and reviews. Cluster analysis demonstrated that gender, income, and education level were associated with specific interest and concerns. CONCLUSION: Patients' activity on SM is independent of their satisfaction with formal IBD care and rather reflects an ongoing need for information and support. These needs may be addressed both in clinical settings and through online tools.

Effectiveness of Coronary Sinus Reducer for Treatment of Refractory Angina: A Meta-analysis.

BACKGROUND: Refractory angina is a debilitating condition that affects the quality of life of patients worldwide, who after exhausting standard available therapies are regarded as "no option" patients. Recently, CS (coronary sinus) reducer (Neovasc Reducer) implantation became available and is gaining popularity in the treatment of refractory angina. The effectiveness of this therapy was demonstrated in 1 randomised sham-control trial and numerous uncontrolled prospective studies entailing several hundred patients altogether. We performed a meta-analysis to incorporate the data and elucidate its efficacy and safety. METHODS: A meta-analysis of prospective studies assessing the effects of CS narrowing published in English to June 2021 was performed. The primary outcome was the proportion of patients improving ≥ 1 class in the Canadian Cardiovascular Society (CCS) angina score. Other end points included proportion of patients improving ≥ 2 CCS classes, procedural success, periprocedural complications, changes in Seattle Angina Questionnaire (SAQ) scores, and 6-minute walk test (6MWT). RESULTS: Data from 9 studies including 846 patients were included. An improvement of ≥ 1 CCS class occurred in 76% (95% confidence interval [CI] 73%-80%) of patients. Improvement of ≥ 2 CCS classes was observed in 40% of patients (95% CI 35%-46%). Procedure success was 98%, with no major and 3% nonmajor periprocedural complications. Post procedural SAQ scores and 6MWT distance were significantly improved. CONCLUSIONS: In patients suffering from angina refractory to medical and interventional therapies, Reducer implantation improves symptoms and quality of life with a low complication rate. These results are consistent in 1 randomised trial and multiple prospective uncontrolled studies.

Preimplantation genetic testing for BRCA gene mutation carriers: a cost effectiveness analysis.

BACKGROUND: Gynecologic oncologists should be aware of the option of conception through IVF/PGT-M for families with high BRCA related morbidity or mortality. Our objective was to investigate the cost-effectiveness of preimplantation genetic testing for selection and transfer of BRCA negative embryo in BRCA mutation carriers compared to natural conception. METHODS: Cost-effectiveness of two strategies, conception through IVF/PGT-M and BRCA negative embryo transfer versus natural conception with a 50% chance of BRCA positive newborn for BRCA mutation carriers was compared using a Markovian process decision analysis model. Costs of the two strategies were compared using quality adjusted life years (QALYs'). All costs were discounted at 3%. Incremental cost effectiveness ratio (ICER) compared to willingness to pay threshold was used for cost-effectiveness analysis. RESULTS: IVF/ PGT-M is cost-effective with an ICER of 150,219 new Israeli Shekels, per QALY gained (equivalent to 44,480 USD), at a 3% discount rate. CONCLUSIONS: IVF/ PGT-M and BRCA negative embryo transfer compared to natural conception among BRCA positive parents is cost effective and may be offered for selected couples with high BRCA mutation related morbidity or mortality. Our results could impact decisions regarding conception among BRCA positive couples and health care providers.

Real-World Management of Patients with Primary Biliary Cholangitis-A Retrospective Study from a Tertiary Medical Center in Israel.

BACKGROUND: Primary biliary cholangitis (PBC) is a rare autoimmune liver disease with variation in prevalence, phenotype and prognosis across different geographical regions. Little is known about PBC in Israel. Our aim was to characterize the demography, clinical presentation, treatment patterns and prognosis in a cohort of PBC patients followed in a referral center in central Israel. METHODS: Clinical, demographic and laboratory data were collected from the medical records of PBC patients followed at Tel Aviv Medical Center in the years 2003-2020. RESULTS: We have identified 189 patients with a confirmed diagnosis of PBC; 92.6% were female and the mean age at diagnosis was 54.7 years. Thirty-nine percent were diagnosed with another autoimmune disease and 5.9% were diagnosed with a PBC-AIH (autoimmune hepatitis) variant syndrome. Ninety-six percent were treated with ursodeoxycholic acid (UDCA) at a mean dose of 13.3 mg/kg. A total of 28.1% were found with inadequate response to UDCA according to the Toronto criteria, and 53% of the UDCA non-responders were treated with bezafibrate. Younger age at diagnosis, higher baseline levels of alkaline phosphatase (ALP) and gamma-glutamyltransferase (GGT), AIH-PBC variant and positive anti-smooth muscle antibodies (ASMA) were associated with an inadequate UDCA response. In a multivariable analysis, higher ALP at diagnosis (OR = 1.92 CI 1.11-3.20 per 50-unit change, p = 0.018) and ASMA (OR = 27.6 CI 2.58-295, p = 0.006) independently predicted inadequate UDCA response. Higher alanine transaminase (ALT), ALP and GGT, lower albumin, younger age at diagnosis and pruritus conferred an increased risk for disease progression. CONCLUSIONS: Disease characteristics, treatment patterns, response to therapy and prognosis of a PBC patient cohort in a tertiary center in central Israel were revealed. The results highlight the importance of risk stratification in PBC, specifically in younger patients, those presenting with a high level of liver enzymes and in ASMA-positive patients with an assumed diagnosis of the AIH-PBC variant.

Improvement in the Prediction of Coronary Heart Disease Risk by Using Artificial Neural Networks.

BACKGROUND AND OBJECTIVES: Cardiovascular diseases, such as coronary heart disease (CHD), are the main cause of mortality and morbidity worldwide. Although CHD cannot be entirely predicted by classic risk factors, it is preventable. Therefore, predicting CHD risk is crucial to clinical cardiology research, and the development of innovative methods for predicting CHD risk is of great practical interest. The Framingham risk score (FRS) is one of the most frequently implemented risk models. However, recent advances in the field of analytics may enhance the prediction of CHD risk beyond the FRS. Here, we propose a model based on an artificial neural network (ANN) for predicting CHD risk with respect to the Framingham Heart Study (FHS) dataset. The performance of this model was compared to that of the FRS. METHODS: A sample of 3066 subjects from the FHS offspring cohort was subjected to an ANN. A multilayer perceptron ANN architecture was used and the lift, gains, receiver operating characteristic (ROC), and precision-recall predicted by the ANN were compared with those of the FRS. RESULTS: The lift and gain curves of the ANN model outperformed those of the FRS model in terms of top percentiles. The ROC curve showed that, for higher risk scores, the ANN model had higher sensitivity and higher specificity than those of the FRS model, although its area under the curve (AUC) was lower. For the precision-recall measures, the ANN generated significantly better results than the FRS with a higher AUC. CONCLUSIONS: The findings suggest that the ANN model is a promising approach for predicting CHD risk and a good screening procedure to identify high-risk subjects.

Cost-effectiveness analysis of screening for first-degree relatives of patients with bicuspid aortic valve.

AIMS: Bicuspid aortic valve (BAV) is the commonest congenital heart valve malformation, and is associated with life-threatening complications. Given the high heritability index of BAV, many experts recommend echocardiography screening for first-degree relatives (FDRs) of an index case. Here, we aim to evaluate the cost-effectiveness of such cascade screening for BAV. METHODS AND RESULTS: Using a decision-analytic model, we performed a cost-effectiveness analysis of echocardiographic screening for FDRs of a BAV index case. Data on BAV probabilities and complications among FDRs were derived from our institution's BAV familial cohort and from the literature on population-based BAV cohorts with long-term follow-up. Health gain was measured as quality-adjusted life years (QALYs). Cost inputs were based on list prices and literature data. One-way and probabilistic sensitivity analyses were performed to account for uncertainty in the model's variables. Screening of FDRs was found to be the dominant strategy, being more effective and less costly than no screening, with savings of €644 and gains of 0.3 QALY. Results were sensitive throughout the range of the main model's variables, including the full range of reported BAV rates among FDRs across the literature. A gradual decrease of the incremental effect was found with the increase in screening age. CONCLUSION: This economic evaluation model found that echocardiographic screening of FDRs of a BAV index case is not only clinically important but also cost-effective and cost-saving. Sensitivity analysis supported the model's robustness, suggesting its generalization.

Early post-liver transplantation infections and their effect on long-term survival.

BACKGROUND: Infections post-liver transplantation are major drivers for morbidity and mortality. However, the impact of infections within 180 days post-liver transplantation on long-term survival is not clear. METHODS: We present a retrospective cohort of 317 liver transplant patients for whom all infectious episodes were prospectively collected during a mean follow-up of 4.4 years. RESULTS: A total of 143/317 (45%) of patients suffered from any infectious episode during the first 6 months following liver transplantation. Patients with surgical site infections have a reduced survival compared to those with no infection (HR 0.33, 95% CI 0.172-0.636, P = .001), whereas infections from other sources, including pneumonia, UTI, and line-related infections, were not associated with increased mortality. Furthermore, even though the presence of any infection within 30 days or 6 months post-transplantation did not affect survival, more than a single infectious episode per patient was significantly associated with increased mortality (HR 1.70, CI 1.12-2.60, P = .013). In a multivariate analysis, the number of infectious episodes remained statistically significant (HR 1.58, 95% CI 1.03-2.43, P = .035) upon adjustment for other major variables associated with comorbidities and infection risk. CONCLUSIONS: Surgical site infections and the number of infectious episodes within 180 days post-liver transplantation are major determinants of long-term survival among these patients.

Modeling Social Distancing Strategies to Prevent SARS-CoV-2 Spread in Israel: A Cost-Effectiveness Analysis.

OBJECTIVES: While highly effective in preventing SARS-CoV-2 spread, national lockdowns come with an enormous economic price. Few countries have adopted an alternative "testing, tracing, and isolation" approach to selectively isolate people at high exposure risk, thereby minimizing the economic impact. To assist policy makers, we performed a cost-effectiveness analysis of these 2 strategies. METHODS: A modified Susceptible, Exposed, Infectious, Recovered, and Deceased (SEIRD) model was employed to assess the situation in Israel, a small country with ∼9 million people. The incremental cost-effectiveness ratio (ICER) of these strategies as well as the expected number of infected individuals and deaths were calculated. RESULTS: A nationwide lockdown is expected to save, on average, 274 (median 124, interquartile range: 71-221) lives compared to the "testing, tracing, and isolation" approach. However, the ICER will be, on average, $45 104 156 (median $49.6 million, interquartile range: 22.7-220.1) to prevent 1 case of death. CONCLUSION: A national lockdown has a moderate advantage in saving lives with tremendous costs and possible overwhelming economic effects. These findings should assist decision makers dealing with additional waves of this pandemic.

Hepatitis C related cognitive impairment: Impact of viral and host factors and response to therapy.

Chronic hepatitis C virus (HCV) infection is associated with cognitive impairment via several suggested mechanisms including direct neurotoxicity and minimal hepatic encephalopathy. The prevalence of HCV-related cognitive impairment and whether it is reversed by anti-viral therapy is unknown. We aimed to assess predictors and reversibility of cognitive impairment of HCV-infected patients after successful treatment. Consecutive HCV patients treated during the EMERALD study (AbbVie 3D regimen for protease inhibitors failure) underwent neuropsychological (number connection test A [NCTA] and digital symbol test [DST]) and neurophysiological (critical flicker frequency [CFF]) tests at baseline and at 12 weeks post-treatment. Patient self-reported outcomes (PROs) were prospectively collected. Patients with a history of hepatic encephalopathy were excluded. Thirty-two patients underwent the cognitive tests at baseline. Seven of them had abnormal CFF test findings. Twenty-five (25/32, 78%) patients had repeated evaluations 3 months post-treatment. High viral loads were significantly associated with abnormal CFF across fibrosis levels (area under the ROC curve 0.817). CFF results significantly improved following viral eradication, from 40.9 (interquartile range 38.6-42.9) at baseline to 41.5 (39.8-44), p = .042, at follow-up. Both NCTA and DST results improved, but not significantly. There was improvement in the PROs of general health perception and vitality. The NCTA and DST results were more significantly associated with PROs than CFF. This prospective interventional study showed greater cognitive impairment in HCV patients with high viral load and demonstrated partial reversibility of HCV neurotoxicity and subsequent improvement in PROs following treatment.