Ultrasonographic assessment of abnormal fetal growth related to uteroplacental-fetal biometrics and Doppler (U-AID) indices: Protocol for multicenter retrospective cohort study trial.

Fetal growth restriction (FGR) is one of the leading causes of perinatal morbidity and mortality. Many studies have reported an association between FGR and fetal Doppler indices focusing on umbilical artery (UA), middle cerebral artery (MCA), and ductus venosus (DV). The uteroplacental-fetal circulation which affects the fetal growth consists of not only UA, MCA, and DV, but also umbilical vein (UV), placenta and uterus itself. Nevertheless, there is a paucity of large-scale cohort studies that have assessed the association between UV, uterine wall, and placental thickness with perinatal outcomes in FGR, in conjunction with all components of the uteroplacental-fetal circulation. Therefore, this multicenter study will evaluate the association among UV absolute flow, placental thickness, and uterine wall thickness and adverse perinatal outcome in FGR fetuses. This multicenter retrospective cohort study will include singleton pregnant women who undergo at least one routine fetal ultrasound scan during routine antepartum care. Pregnant women with fetuses having structural or chromosomal abnormalities will be excluded. The U-AID indices (UtA, UA, MCA, and UV flow, placental and uterine wall thickness, and estimated fetal body weight) will be measured during each trimester of pregnancy. The study population will be divided into two groups: (1) FGR group (pregnant women with FGR fetuses) and (2) control group (those with normal growth fetus). We will assess the association between U-AID indices and adverse perinatal outcomes in the FGR group and the difference in U-AID indices between the two groups.

Cost Effectiveness of Allogeneic Umbilical Cord Blood-Derived Mesenchymal Stem Cells in Patients with Knee Osteoarthritis.

OBJECTIVES: The aim of this study was to assess the cost effectiveness of allogeneic umbilical cord blood-derived mesenchymal stem cells with sodium hyaluronate (hUCB-MSC) compared with microfracture in patients with knee cartilage defects caused by osteoarthritis (OA) in South Korea. METHODS: A partitioned survival model approach was taken consisting of five mutually exclusive health states: excellent, good, fair, poor, and death over a 20-year time horizon. Utility values were obtained from a randomized clinical trial. Cost data were extracted from a database provided by the Health Insurance Review & Assessment Service, and the utilization of healthcare services was estimated from an expert panel of orthopedic surgeons using a structured questionnaire. The incremental cost-effectiveness ratio (ICER) in terms of quality-adjusted life-years (QALY) was calculated. Deterministic and probabilistic sensitivity analyses were performed. RESULTS: In the base case, the incremental costs of US$14,410 for hUCB-MSC therapy along with its associated QALY gain of 0.857 resulted in an ICER of US$16,812 (₩18,790,773) per QALY (95% confidence interval [CI] US$13,408-US$20,828) when compared with microfracture treatment from a healthcare payer perspective. From a societal perspective, the ICER was US$268 (₩299,255) per QALY (95% CI -US$2915 to US$3784). When using a willingness-to-pay threshold of US$22,367/QALY, the probability of hUCB being cost effectiveness compared with microfracture was 99% from the healthcare payer perspective and 100% from the societal perspective. CONCLUSIONS: The study demonstrated that hUCB-MSC therapy was cost effective compared with microfracture when treating patients with knee OA. These findings should inform health policy decision makers about considerations for cost-effective therapy for treating knee OA to ultimately enhance population health.

Use of budget savings from patent expiration of cancer drugs to improve affordability and accessibility.

BACKGROUND: The introduction of generics after the loss of patent exclusivity plays a major role in budget savings by significantly decreasing drug prices. The aims of this study were to estimate the budget savings from off-patent cancer drugs in 2020-2024 and to inform decision makers on how these savings could be used to improve the affordability of innovative cancer treatments in South Korea. METHODS: A model was developed to calculate budget savings from off-patent cancer drug use in Korea over 5 years (2020-2024). Cancer drugs with one or more valid patents that expire between 2020 and 2024 in Korea were selected. Key input parameters in the model included market share of generics, market growth, and prices of originators and generics. To reflect market dynamics after patent expiration, the trends of the off-patent market were estimated using historical sales volume data of IQVIA from 2012 to 2018. The study assumed that the prices of off-patent drugs decreased according to the price regulations set by the Korean government and that the off-patent market sales volume did not grow. Sensitivity analyses were performed to investigate the uncertainty in model input parameters. RESULTS: A total of 24 cancer drugs which met selection criteria were identified. In the base case analysis, patent expiration of cancer drugs between 2020 and 2024 could lead to a spending reduction of ₩234,429 million ($203 million), which was 20% of the cancer drug expenditure in the 5-year period. The savings ranged from ₩157,633 million ($136 million) to ₩434,523 million ($376 million) depending on the scenarios in sensitivity analyses. CONCLUSIONS: The findings indicate that patent loss of cancer drugs could lead to a 20% reduction in spending on cancer drugs over the next 5 years in South Korea. The savings could be used to improve the affordability of innovative, advanced cancer drugs for 94,000 cancer patients by reallocating the budget savings from patent expiration.

Budget Impact of Switching to Biosimilar Trastuzumab (CT-P6) for the Treatment of Breast Cancer and Gastric Cancer in 28 European Countries.

BACKGROUND: As the economic burden of treating cancer patients has been soaring in European countries, performing a budget impact analysis is becoming one of the requirements for payers' application dossiers. OBJECTIVE: The objective of this study was to estimate the budgetary impact of introducing the biosimilar trastuzumab (CT-P6) from the payer's perspective and to determine the number of additional patients who could be treated with resulting savings in 28 European countries. METHODS: A budget impact model was developed to analyze the financial impact of switching from originator trastuzumab to biosimilar CT-P6 in the treatment of early and metastatic breast cancer and metastatic gastric cancer with a time horizon of 1-5 years. Budgetary savings and the number of patients potentially affected were measured based on epidemiological and sales volume data. The base-case analysis assumed that the price of CT-P6 is 70% of the originator price, the switching rate of originator to CT-P6 in the first year is 20%, and the annual growth in the switching rate for each subsequent year is 5%. RESULTS: For analyses using the base-case scenario following CT-P6 introduction, the total estimated budgetary savings over a 5-year period (depending on the scenario) ranged from €1.13 billion to €2.27 billion based on epidemiological data, or from €0.91 billion to €1.82 billion based on sales volume data. In the first year only, the projected budgetary savings ranged from €58 million to €136 million, and the number of additional patients who could be treated using the savings ranged from 3503 to 7078 by sensitivity analysis. CONCLUSIONS: The conducted budget impact analysis assessing a switch from originator trastuzumab to biosimilar CT-P6 in 28 European countries indicates that budget savings could be between €0.91 billion and €2.27 billion over the next 5 years. These savings could be used to help improve patient access to local biologics in their respective countries while simultaneously strengthening the overall public health landscape across the European Union.

Improving Patient Access to New Drugs in South Korea: Evaluation of the National Drug Formulary System.

This study reviews and evaluates the national drug formulary system used to improve patient access to new drugs by making reimbursement decisions for new drugs as part of the South Korean national health insurance system. The national health insurance utilizes three methods for improving patient access to costly drugs: risk-sharing agreements, designation of essential drugs, and a waiver of cost-effectiveness analysis. Patients want reimbursement for new drugs to be processed quickly to improve their access to these drugs, whereas payers are careful about listing them given the associated financial burden and the uncertainty in cost-effectiveness. However, pharmaceutical companies are advocating for drug prices above certain thresholds to maintain global pricing strategies, cover the costs of drug development, and fund future investments into research and development. The South Korean government is expected to develop policies that will improve patient access to drugs with unmet needs for broadening health insurance coverage. Simultaneously, the designing of post-listing management methods is warranted for effectively managing the financial resources of the national health insurance system.

The association of socioeconomic and clinical characteristics with health-related quality of life in patients with psoriasis: a cross-sectional study.

BACKGROUND: This study aimed to determine the socioeconomic and clinical characteristics affecting health-related quality of life (HRQoL) in patients with psoriasis. METHODS: A cross-sectional study was conducted between March and June 2015 using data obtained via an Internet-based survey completed by a psoriasis patient group in Korea. The survey included items regarding demographic, socioeconomic, and clinical characteristics and HRQoL. Patients' HRQoL impairment was classified as severe if their Dermatology Life Quality Index Scores were ≥ 11. Factors influencing HRQoL impairment were identified using multivariate logistic regression analysis. RESULTS: Of the 299 respondents, 161 (53.8%) exhibited severe HRQoL impairment. The Dermatology Life Quality Index scores were significantly associated with gender, annual income, neck psoriasis, psoriasis-related resignation from work, and use of oral and herbal medications. The severity of HRQoL impairment in women was twice that observed in men (odds ratio [OR] = 2.00, 95% confidence interval (CI): 1.05-3.80). Patients with psoriasis on the neck exhibited significantly greater HRQoL impairment than those with psoriasis on other areas of their bodies (OR = 2.30, 95% CI: 1.20-4.43). With respect to the socioeconomic status, patients who earned > 40 million KRW (approximately 34,000 USD; high-income group) showed less HRQoL impairment compared with those who had lower incomes (OR = 0.47, 95% CI: 0.28-0.80). Patients with severe HRQoL impairment used oral (OR = 2.04, 95% CI: 1.20-3.44) and herbal (OR = 1.86, 95% CI: 1.04-3.34) medications more often relative to patients with less severe HRQoL impairment. CONCLUSIONS: HRQoL in patients with psoriasis was significantly associated with their demographic and socioeconomic characteristics and employment status. The presence of psoriasis on exposed areas of the body was significantly associated with patients' HRQoL and employment status. Further research is required to evaluate the impact of psoriasis on patients' productivity.

Prospective observations study protocol to investigate cost-effectiveness of various prenatal test strategies after the introduction of noninvasive prenatal testing.

BACKGROUND: Among the non-invasive screening methods for the identification of fetal aneuploidy, NIPT (non-invasive prenatal testing) shows the highest sensitivity and specificity in high-risk pregnancies. Due to the low false positive rate of NIPT, it is assumed that the implementation of NIPT as a primary screening method may reduce the number of invasive fetal tests and result in a similar or lowered cost in the overall detection of Down syndrome. However, most previous studies are based on theoretical economic analysis. This study aims to determine the cost effectiveness of various prenatal test strategies, including NIPT, in real clinical settings in both low risk and high risk pregnancies. METHODS/DESIGN: In this prospective observational study, women (< 24 weeks) with singleton or twin pregnancies will be enrolled in 12 different healthcare institutions. The participants will be grouped based on the risks of fetal chromosomal abnormalities and will be counseled on the various screening or diagnostic methods, including NIPT, according to the aneuploidy risk. The final decision on screening or diagnostic methods will be made by patients after counseling. Questionnaires regarding factors affecting the decision on prenatal test will be answered by the participants and physicians. The economic analysis on final total costs will be compared according to the various prenatal test strategies. DISCUSSION: The results of present study are expected to have a significant impact on national policies in determining Korean prenatal screening test strategies and to help in developing novel and effective prenatal screening tests in the future.

Assessment of induced CYP3A activity in pregnant women using 4ß-hydroxycholesterol: Cholesterol ratio as an appropriate metabolic marker.

AIMS: This study was aimed at evaluating changes in CYP3A activity following and during pregnancy by analyzing metabolic markers for CYP3A activity, which can help avoid unnecessary drug exposure and invasive sampling. METHODS: Forty-eight pregnant women and 25 non-pregnant women were enrolled in this study. Plasma and urine samples were collected from the pregnant women during each trimester and from the non-pregnant women for evaluation of metabolic markers for CYP3A activity. Metabolic markers for CYP3A activity were measured using GC-MS. RESULTS: An increased 4ß-hydroxycholesterol/cholesterol ratio, consistent with high CYP3A activity, was observed in pregnant women compared with that in non-pregnant women; however, no differences were observed among trimesters. No significant differences were observed in urinary markers. CONCLUSIONS: We observed an increase in the activity of CYP3A following but not during pregnancy when measured using the 4ß-hydroxycholesterol/cholesterol ratio. In addition, based on our results, we suggest that the plasma 4ß-hydroxycholesterol/cholesterol ratio be used to measure CYP3A activity in pregnant women.

Spontaneous Version of Fetal Presentation in Twin Pregnancies During Third Trimester: Longitudinal Assessment.

Little is known about longitudinal changes of the first twin presentation in twin gestations. This is a retrospective cohort study including 411 women who were admitted consecutively and delivered live-born twins at 36 weeks of gestation or more. Longitudinal assessment of the first twin presentation was conducted during gestation and at birth in all cases. Gestational age at antenatal assessment was divided into two intervals: early-third trimester (28-31 weeks) and mid-third trimester (32-35 weeks). Fetal presentation was categorized as vertex or non-vertex. We analyzed change of fetal presentation between antepartum intervals and birth. First twin presentation at early-third trimester had the same presentation at birth in 87.6% (360/411) of the study population. In this 'no change' group, vertex presentation was seen in 95.6% (283/296) and non-vertex was seen in 67.0% (77/115) of cases. In total, 96.1% (395/411) of the study population maintained their presentation between mid-third trimester and birth. Vertex presentation was seen in 98.4% (310/315) and non-vertex was seen in 88.5% (85/96) of cases. When comparing vertex with non-vertex, vertex presentation during third trimester was a more reliable predictor of presentation at birth (p < .001). The only factor that contributed significantly to spontaneous version of the first twin during mid-third trimester and birth was a lower birth weight of the first twin compared with the second twin. In conclusion, first twin presentation with vertex during third trimester is not likely to change into non-vertex at birth. We concluded that vertex presentation in twin gestations at early- and mid-third trimester is very predictable. In contrast, a non-vertex first twin presentation is relatively unstable.

Impact of warfarin discharge education program on hospital readmission and treatment costs.

Background Although warfarin is highly effective, management of patients prescribed warfarin is complex due to its narrow therapeutic window. Objective To evaluate the impact of a formal warfarin discharge education program (WDEP) on hospital readmission and treatment costs in patients who received warfarin therapy. Setting Robert Wood Johnson University Hospital Somerset in Somerville, New Jersey, USA. Method In this interventional cohort study, patients were assigned to either the WDEP group or the usual care group. The effects of the WDEP on readmission within 90 days after discharge were analyzed using Cox proportional hazards models. Factors influencing treatment cost were identified using generalized linear model with log-link function and gamma distribution. Main outcome measure Hospital readmission within 90 days and treatment costs associated with hospital readmission. Results Among 692 eligible patients, 203 in each group were matched using propensity scores and there were no statistically significant differences in the patient baseline characteristics between two groups. The risk of all-cause readmission within 90 days was significantly lower in the WDEP group compared to the usual care group (relative risk = 0.46, 95% CI 0.28-0.76). The treatment costs associated with hospital readmission in the WDEP group were 19% lower than those in the usual care group after adjusting for the study variables. Conclusion A formal, individualized WDEP provided by pharmacists resulted in significant reduction of readmission and treatment costs. The economic burden of treatment costs associated with warfarin can be controlled if well-organized warfarin education is provided to patients who received warfarin therapy.

Treatment Costs and Factors Associated with Glycemic Control among Patients with Diabetes in the United Arab Emirates.

BACKGROUND: We aimed to estimate the proportion of patients with diabetes who achieved target glycemic control, to estimate diabetes-related costs attributable to poor control, and to identify factors associated with them in the United Arab Emirates. METHODS: This retrospective cohort study used administrative claims data handled by Abu Dhabi Health Authority (January 2010 to June 2012) to determine glycemic control and diabetes-related treatment costs. A total of 4,058 patients were matched using propensity scores to eliminate selection bias between patients with glycosylated hemoglobin (HbA1c) <7% and HbA1c ≥7%. Diabetes-related costs attributable to poor control were estimated using a recycled prediction method. Factors associated with glycemic control were investigated using logistic regression and factors associated with these costs were identified using a generalized linear model. RESULTS: During the 1-year follow-up period, 46.6% of the patients achieved HbA1c <7%. Older age, female sex, better insurance coverage, non-use of insulin in the index diagnosis month, and non-use of antidiabetic medications during the follow-up period were significantly associated with improved glycemic control. The mean diabetes-related annual costs were $2,282 and $2,667 for patients with and without glycemic control, respectively, and the cost attributable to poor glycemic control was $172 (95% confidence interval [CI], $164-180). The diabetes-related costs were lower with mean HbA1c levels <7% (cost ratio, 0.94; 95% CI, 0.88-0.99). The costs were significantly higher in patients aged ≥65 years than those aged ≤44 years (cost ratio, 1.45; 95% CI, 1.25-1.70). CONCLUSION: More than 50% of patients with diabetes had poorly controlled HbA1c. Poor glycemic control may increase diabetes-related costs.

Incremental Treatment Costs Attributable to Overweight and Obesity in Patients with Diabetes: Quantile Regression Approach.

OBJECTIVE: This study aimed to estimate treatment costs attributable to overweight and obesity in patients with diabetes who were less than 65 years of age in the United States. METHODS: This study used data from the Medical Expenditure Panel Survey from 2001 to 2013. Patients with diabetes were identified by using the International Classification of Diseases, Ninth Revision, Clinical Modification code (250), clinical classification codes (049 and 050), or self-reported physician diagnoses. Total treatment costs attributable to overweight and obesity were calculated as the differences in the adjusted costs compared with individuals with diabetes and normal weight. Adjusted costs were estimated by using generalized linear models or unconditional quantile regression models. RESULTS: The mean annual treatment costs attributable to obesity were $1,852 higher than those attributable to normal weight, while costs attributable to overweight were $133 higher. The unconditional quantile regression results indicated that the impact of obesity on total treatment costs gradually became more significant as treatment costs approached the upper quantile. CONCLUSIONS: Among patients with diabetes who were less than 65 years of age, patients with diabetes and obesity have significantly higher treatment costs than patients with diabetes and normal weight. The economic burden of diabetes to society will continue to increase unless more proactive preventive measures are taken to effectively treat patients with overweight or obesity.

Comparative effectiveness of lipid-lowering treatments to reduce cardiovascular disease.

INTRODUCTION: The proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitor is a new treatment option for patients with hypercholesterolemia. The objective of this study was to systematically review the cost-effectiveness of lipid-lowering agents. AREAS COVERED: Based on Pubmed, Embase, and Cochrane Database of Systematic Reviews, we identified 29 relevant articles. Studies found statins were cost-effective compared with placebo or no treatment in general. Atorvastatin was reported to be cost-effective against simvastatin. In most cases, rosuvastatin was more cost-effective than atorvastatin or simvastatin. Additionally, ezetimibe was considered to be cost-effective compared with no treatment for statin intolerant patients. For patients not meeting treatment goals with their statins, switching to ezetimibe plus simvastatin was consistently reported cost-effective. The cost-effectiveness of ezetimibe plus a hybrid of a statin varied by the source of clinical data and cost of ezetimibe. Finally, the cost-effectiveness of PCSK9 inhibitor plus a statin against statin monotherapy was uncertain. The PCSK9 inhibitor plus a stain was cost-ineffective compared with ezetimibe plus a statin. EXPERT COMMENTARY: Drug costs and treatment efficacy were the key drivers of the cost-effectiveness results in prior analyses. Future evaluations are warranted to reflect the decreasing drug prices and the long-term treatment effects of PCSK9 inhibitors.

Costs Attributable to Overweight and Obesity in Working Asthma Patients in the United States.

PURPOSE: To estimate annual health care and productivity loss costs attributable to overweight or obesity in working asthmatic patients. MATERIALS AND METHODS: This study was conducted using the 2003-2013 Medical Expenditure Panel Survey (MEPS) in the United States. Patients aged 18 to 64 years with asthma were identified via self-reported diagnosis, a Clinical Classification Code of 128, or a ICD-9-CM code of 493.xx. All-cause health care costs were estimated using a generalized linear model with a log function and a gamma distribution. Productivity loss costs were estimated in relation to hourly wages and missed work days, and a two-part model was used to adjust for patients with zero costs. To estimate the costs attributable to overweight or obesity in asthma patients, costs were estimated by the recycled prediction method. RESULTS: Among 11670 working patients with a diagnosis of asthma, 4428 (35.2%) were obese and 3761 (33.0%) were overweight. The health care costs attributable to obesity and overweight in working asthma patients were estimated to be $878 [95% confidence interval (CI): $861-$895] and $257 (95% CI: $251-$262) per person per year, respectively, from 2003 to 2013. The productivity loss costs attributable to obesity and overweight among working asthma patients were $256 (95% CI: $253-$260) and $26 (95% CI: $26-$27) per person per year, respectively. CONCLUSION: Health care and productivity loss costs attributable to overweight and obesity in asthma patients are substantial. This study's results highlight the importance of effective public health and educational initiatives targeted at reducing overweight and obesity among patients with asthma, which may help lower the economic burden of asthma.

Incidence and treatment costs attributable to medication errors in hospitalized patients.

BACKGROUND: A significant financial burden arises from medication errors that cause direct injury and those without patient harm that represent waste and inefficiency. OBJECTIVE: To estimate the incidence, types, and causes of medication errors as well as their attributable costs in a hospital setting. METHODS: For a retrospective case-control study, data were collected for 57,554 patients admitted to two New Jersey (U.S. State) hospitals during 2005-2006 as well as hospital-specific voluntary error reports from these two hospitals for the same period. Medication errors were classified into categories of stage, error type, and proximal cause, and the incidence was estimated. The costs attributable to medication errors were calculated using both the recycled prediction method, and the Blinder-Oaxaca decomposition method after propensity score matching. RESULTS: Medication errors occurred at a rate of 0.8 per 100 admissions, or 1.6 per 1000 patient days. Most errors occurred at the administration stage of the medication use process. The most frequent types of errors were wrong time, wrong medication, wrong dose, and omission errors. Treatment costs attributable to medication errors were in the range of $8,439 using the Blinder-Oaxaca decomposition method and $8,898 using the recycled prediction method. CONCLUSIONS: Medication errors are associated with significant additional costs, even without patient harm. Considering the substantial costs associated with adverse drug events, the elimination of medication errors should be further emphasized and promoted, and guidelines should be developed to facilitate this goal.

A transcervical amniotic fluid collector: a new medical device for the assessment of amniotic fluid in patients with ruptured membranes.

AIM: To describe a new device for the transcervical collection of amniotic fluid (AF) in patients with ruptured membranes, and to compare the concentration of proteins in fluid retrieved by transabdominal amniocentesis and the transcervical AF collector. STUDY DESIGN: Paired AF samples were collected in patients with preterm prelabor rupture of membranes (PROM) (n=11) by transabdominal amniocentesis and with the transcervical AF collector (Yoon's AF Collector™). Three proteins known to have high concentrations in AF [α-fetoprotein (AFP), ß-human chorionic gonadotrophin (ß-hCG), and prolactin] were measured. RESULTS: (1) There was a significant correlation between the concentrations of analytes in AF obtained by transabdominal amniocentesis and by the transcervical AF collector (r=0.94, P<0.001 for AFP; r=0.96, P<0.001 for ß-hCG; r=0.72, P<0.05 for prolactin); (2) Bland-Altman plots showed no evidence of heteroscedasticity between transabdominal or transcervical AF concentrations of these markers. CONCLUSIONS: There was a strong correlation between the concentrations of proteins in AF collected by amniocentesis or with the transcervical device.

Comparison of hospital charge prediction models for colorectal cancer patients: neural network vs. decision tree models.

Analysis and prediction of the care charges related to colorectal cancer in Korea are important for the allocation of medical resources and the establishment of medical policies because the incidence and the hospital charges for colorectal cancer are rapidly increasing. But the previous studies based on statistical analysis to predict the hospital charges for patients did not show satisfactory results. Recently, data mining emerges as a new technique to extract knowledge from the huge and diverse medical data. Thus, we built models using data mining techniques to predict hospital charge for the patients. A total of 1,022 admission records with 154 variables of 492 patients were used to build prediction models who had been treated from 1999 to 2002 in the Kyung Hee University Hospital. We built an artificial neural network (ANN) model and a classification and regression tree (CART) model, and compared their prediction accuracy. Linear correlation coefficients were high in both models and the mean absolute errors were similar. But ANN models showed a better linear correlation than CART model (0.813 vs. 0.713 for the hospital charge paid by insurance and 0.746 vs. 0.720 for the hospital charge paid by patients). We suggest that ANN model has a better performance to predict charges of colorectal cancer patients.