Proton pump inhibitors associated with an increased risk of mortality in elderly: a systematic review and meta-analysis.

PURPOSE: The increased use of proton pump inhibitors (PPIs) in the elderly has raised concerns about potential severe adverse effects. Our systematic review investigated the mortality associated with PPI use in elderly populations. METHODS: We searched MEDLINE, EMBASE, and the Cochrane Library for relevant publications until August 2022. We included randomized controlled trials (RCTs), quasi-RCTs, and observational studies on the association between proton pump inhibitors and mortality in the elderly. To estimate the pooled relative risk (RR) and 95% confidence interval (CI), the inverse-variance random effect model was used. Heterogeneity was assessed using the I2 test. Subgroup analyses were performed by follow-up period, population, and study design. RESULTS: A total of 4 RCTs and 36 cohort studies were included in the meta-analysis. Four RCTs showed that there was no significant association between PPIs and the risk of death. From 23 observational studies (26 cohorts), the use of proton pump inhibitors was not significantly associated with increased mortality in the elderly (RR 1.14; 95% CI, 0.90-1.45). However, when controlling for covariates from 33 observational studies (41 cohorts), proton pump inhibitors in older adults aged 50 years or more were significantly associated with a 15% higher risk of mortality compared to nonusers (RR 1.15; 95% CI, 1.10-1.20). CONCLUSIONS: Our meta-analysis of RCTs found that PPIs did not show a significant association with increased mortality risk in older adults. However, the meta-analysis of cohort studies and long-term follow-up studies showed a higher increased risk of death with PPI use in older adults. The prescription of PPIs in patients aged 50 years or older should be carefully considered.

Factors influencing self-care behaviour in patients with heart failure: Grit as a behavioural support factor.

AIMS: This study aimed to examine the relationship between heart failure knowledge, self-efficacy, social support, grit and self-care behaviour in patients with heart failure and to identify factors associated with patients' self-care behaviour. BACKGROUND: Most patients with heart failure are not as active in implementing self-care behavioural practices as recommended by the guidelines. DESIGN: This descriptive cross-sectional study was designed based on Bandura's Social Cognitive Theory. METHODS: This study included 138 patients who were diagnosed with heart failure in an outpatient department of cardiology at a tertiary hospital in Korea. Data were collected between July and October 2020 using a structured questionnaire and electronic medical records. Data were analysed using the SPSS/WIN 27.0 program. RESULTS: Grit had the strongest association with self-care behaviour among patients with heart failure, followed by social support, self-efficacy and heart failure knowledge. These variables accounted for approximately 52% of the variance in self-care behaviour. CONCLUSIONS: Health-care professionals should assess patients' grit and develop patient-tailored grit enhancement programmes. Based on the social cognitive theory, nursing intervention programmes that can simultaneously manage cognitive (knowledge and self-efficacy), social and environmental (social support) and behavioural support (grit) factors should be developed and applied to nursing practices to promote self-care.

Disparities in Access to Hepatitis C Treatment Among Arizona Medicaid Beneficiaries With Chronic Hepatitis C.

BACKGROUND: High costs of direct-acting antivirals (DAAs) have led to their restricted access for patients with hepatitis C virus (HCV). OBJECTIVE: The aim was to assess how HCV treatment access and predictors of HCV treatment changed in the post-DAA period compared with pre-DAA period. METHODS: A retrospective cohort study using Arizona Medicaid data was conducted for patients with HCV to compare treatment initiation rates between pre-DAA (January 2008-October 2013) and post-DAA (November 2013-December 2018) periods. Multivariable logistic regression was used, controlling for demographic and clinical variables. RESULTS: Twenty-four thousand and ninety and 28,756 patients during the pre-DAA and post-DAA periods were identified. Overall, 12.6% were treated in the post-DAA period compared with 7.8% in the pre-DAA period ( P <0.001). The relative increase in the HCV treatment initiation rate from the pre-DAA to the post-DAA period was significant greater for Black beneficiaries compared with White beneficiaries ( P =0.002). Hispanic beneficiaries were less likely to be treated in the post-DAA period [adjusted odds ratios (aOR): 0.88; CI: 0.79-0.98] compared with White beneficiaries. Those with mental illness (aOR: 0.71; 95% CI: 0.63-0.80) and substance use disorders (aOR: 0.63; 95% CI: 0.58-0.68) were less likely to be treated in the post-DAA period. CONCLUSIONS: Although treatment initiation increased and disparities for Black beneficiaries compared with White beneficiaries attenuated in the post-DAA period, only 13% of Arizona Medicaid patients with HCV received DAA treatment. Disparities in DAA access remained among Hispanic patients and those with mental illness and substance use disorders.

Impact of Direct-acting Antivirals on Hepatocellular Carcinoma and Mortality Among Medicaid Beneficiaries With Hepatitis C.

OBJECTIVE: The effects of all-oral direct-acting antivirals (DAAs) on hepatocellular carcinoma (HCC) and liver-related and all-cause mortality were assessed among Medicaid beneficiaries with hepatitis C virus (HCV). SUBJECTS: This cohort study used 2013-2019 Arizona Medicaid data from beneficiaries with HCV aged 18-64 years. METHODS: Risks of HCC and liver-related and all-cause mortality were compared between patients with or without DAA treatment, stratified by liver disease severity, using inverse probability of treatment weighted multivariable Cox proportional hazards regression models. RESULTS: Of 29,289 patients, 13.3% received DAAs. Among patients with compensated cirrhosis (CC), DAA treatment was associated with a lower risk of HCC [adjusted hazard ratio (aHR), 0.57; 95% CI, 0.37-0.88] compared with untreated patients although this association was not statistically significant for patients without cirrhosis or with decompensated cirrhosis (DCC). Compared with untreated patients, DAA treatment was associated with decreased risk of liver-related mortality for patients without cirrhosis (aHR: 0.02; 95% CI: 0.004-0.11), with CC (aHR: 0.09; 95% CI: 0.06-0.13), or with DCC (aHR: 0.20; 95% CI: 0.14-0.27). Similarly, compared with untreated patients, DAA treatment was associated with lower all-cause mortality for patients without cirrhosis (aHR: 0.10; 95% CI: 0.08-0.14), with CC (aHR: 0.07; 95% CI: 0.05-0.10), or with DCC (aHR: 0.15; 95% CI: 0.11-0.20). CONCLUSIONS: Among Arizona Medicaid beneficiaries with HCV, DAA treatment was associated with decreased risk of HCC for patients with CC but not for patients without cirrhosis or with DCC. However, DAA treatment was associated with decreased risk of liver-related and all-cause mortality.

An economic evaluation of pharmacopuncture versus usual care for chronic neck pain: a pragmatic randomized controlled trial.

BACKGROUND: This study aimed to evaluate the cost utility of pharmacopuncture in comparison with usual care for patients with chronic neck pain. METHODS: A 12-week, multicenter, pragmatic randomized controlled trial was conducted, and 101 patients suffering from chronic neck pain for more than six months were randomly placed into the pharmacopuncture and usual care groups to receive four weeks of treatment and 12 weeks of follow-up observations. The quality-adjusted life year (QALY) was calculated using EQ-5D and SF-6D. Concerning costs in 2019, a primary analysis was performed on societal perspective cost, and an additional analysis was performed on healthcare perspective cost. RESULTS: Compared to usual care, pharmacopuncture was superior as it showed a slightly higher QALY and a lower incremental cost of $1,157 from a societal perspective. The probability that pharmacopuncture would be more cost-effective at a willingness-to-pay (WTP) of $26,374 was 100%. Pharmacopuncture was also superior from a healthcare perspective, with a lower incremental cost of $26. The probability that pharmacopuncture would be more cost-effective at a WTP of $26,374 was 83.7%. CONCLUSIONS: Overall, pharmacopuncture for chronic neck pain was found to be more cost-effective compared to usual care, implying that clinicians and policy makers should consider new treatment options for neck pain. TRIAL REGISTRATION: Number NCT04035018 (29/07/2019) Clinicaltrials.gov; Number KCT0004243 (26/08/2019) Clinical Research Information Service.

The Impact of Direct-Acting Antiviral Therapy on End-Stage Liver Disease Among Individuals with Chronic Hepatitis C and Substance Use Disorders.

BACKGROUND AND AIMS: Our aim was to evaluate the impact of direct-acting antivirals (DAAs) on decompensated cirrhosis (DCC) and HCC in patients with chronic HCV and substance use disorder (SUD) compared with those without an SUD. APPROACH AND RESULTS: This retrospective cohort study used the MarketScan database (2013-2018) to identify 29,228 patients with chronic HCV, where 22% (n = 6,385) had ≥1 SUD diagnosis. The inverse probability of treatment weighted multivariable Cox proportional hazard models were used to compare the risk of developing DCC and HCC. Among the those who were noncirrhotic, treatment reduced the DCC risk among SUD (adjusted hazard ratio [aHR] 0.13; 95% CI, 0.06-0.30) and non-SUD (aHR 0.11; 95% CI, 0.07-0.18), whereas the risk for HCC was not reduced for the SUD group (aHR 0.91; 95% CI, 0.33-2.48). For those with cirrhosis, compared with patients who were untreated, treatment reduced the HCC risk among SUD (aHR, 0.33; 95% CI, 0.13-0.88) and non-SUD (aHR, 0.40; 95% CI, 0.25-0.65), whereas the risk for DCC was not reduced for the SUD group (aHR, 0.64; 95% CI, 0.37-1.13). Among patients with cirrhosis who were untreated, the SUD group had a higher risk of DCC (aHR, 1.52; 95% CI, 1.03-2.24) and HCC (aHR, 1.69; 95% CI, 1.05-2.72) compared with non-SUD group. CONCLUSIONS: Among the HCV SUD group, DAA treatment reduced the risk of DCC but not HCC for those who were noncirrhotic, whereas DAA treatment reduced the risk of HCC but not DCC for those with cirrhosis. Among the nontreated, patients with an SUD had a significantly higher risk of DCC and HCC compared with those without an SUD. Thus, DAA treatment should be considered for all patients with HCV and an SUD while also addressing the SUD.

A National Catalog of Mapped Short-Form Six-Dimension Utility Scores for Chronic Conditions in the United States From 2010 to 2015.

OBJECTIVES: This study examined health preference utility weights and utility decrements associated with different types of chronic conditions in the United States. METHODS: We used the 2010-2015 Medical Expenditure Panel Survey data for persons aged ≥ 18 years with 12-Item Short-Form Survey Physical and Mental Component Summary scores. 12-Item Short-Form Survey scores were converted to Short-Form Six-Dimension (SF-6D) preference scores to measure utilities of different chronic diseases. We used the Clinical Classification Code to identify 30 chronic diseases from 12 categories, such as cardiovascular diseases, cerebrovascular diseases, hypertension, hyperlipidemia, obesity, cancers, musculoskeletal diseases, endocrine or metabolic diseases, oral diseases, respiratory diseases, and mental disorders. A generalized linear model was used to quantify the utility decrements for 30 chronic diseases, controlling for demographic characteristics. RESULTS: We identified 132 737 adults (mean age 47.2 years, 52.2% female, 80% white); 73% had at least one identified chronic disease, and the mean SF-6D was 0.786. Among 30 chronic diseases, the unadjusted mean SF-6D scores of patients with cognitive disorder (0.607) were the lowest, followed by congestive heart failure (0.629), rheumatoid arthritis (0.654), and lung cancer (0.662). After controlling for demographic variables (ie, age, sex) and comorbidities, cognitive disorders (-0.116), mood disorders (-0.099), rheumatoid arthritis (-0.090), liver cancer (-0.078), and stroke (-0.063) showed the highest decrements in the SF-6D scores (P < .05). CONCLUSIONS: This study provides a nationally representative catalog of utility weights for major chronic diseases in the US general population. The utility decrements will enable researchers to calculate the health utilities of patients with multiple comorbid diseases.

Acid-suppressive agents and survival outcomes in patients with cancer: a systematic review and meta-analysis.

BACKGROUND: Patients with cancer often receive acid-suppressive agents (ASAs) to treat common gastroesophageal reflux and peptic ulcer diseases. Our systematic review addresses the association between ASAs and survival outcomes in these patients. METHODS: We searched MEDLINE, EMBASE, and Cochrane until December 2019, including randomized controlled trials (RCTs), quasi-RCTs, and observational studies concerning ASAs that reported progression-free survival (PFS) and/or overall survival (OS). We estimated hazard ratios (HRs) with 95% confidence intervals (CIs) using the random-effects model, and assessed heterogeneity with I2 statistic. RESULTS: We included 45,626 patients from 7 RCTs and 18 observational studies, including esophageal/gastric, colorectal, pancreatic, lung, breast, prostate, kidney, and other cancers. Five studies showed that ASAs in lung cancer patients received tyrosine kinase inhibitors (TKIs) had significantly worse PFS (HR 1.64, 95% CI 1.14 - 2.37, I2 = 57%) and OS (HR 1.13, 95% CI 1.05 - 1.21, I2 = 0%) than nonusers. Each of five studies found no significant association between ASAs and OS in esophageal/gastric (HR 0.91, 95% CI 0.77 - 1.09, I2 = 32%) or colorectal cancer patients (HR 1.33, 95% CI 0.96- 1.85, I2 = 0%). ASAs were not significantly associated with an OS in patients with kidney cancer (HR 1.04, 95% CI 0.96 - 1.13, I2 = 28%). CONCLUSIONS: Meta-analysis showed that ASAs significantly associated with an increased mortality risk in lung cancer patients treated TKIs, but not in patients with esophageal/gastric, colorectal, or kidney cancer. Until further studies confirm these results, caution should be used when administering ASAs and TKIs to patients with lung cancer.

The association between acid-suppressive agent use and the risk of cancer: a systematic review and meta-analysis.

BACKGROUND: Acid-suppressive agents (ASAs) may be associated with cancer; previous studies reported that the risk of cancer with acid suppressants has differed depending on the site of cancer. Here, we conducted a systematic review and meta-analysis of the association between ASA use and the type of cancer risk. METHODS: MEDLINE, EMBASE, and Cochrane library databases were searched for publications up to the end of September 2019 for MeSH terms and text words related to cancer and ASAs. Studies on the association between ASAs and cancer risk, which included a control group and reported the relative risk of cancer, were included. The inverse-variance random effect model was used to estimate the pooled relative risk (RR) and 95% confidence interval (CI), and subgroup analysis for type of acid suppressants, drug uptake duration, and cumulative doses was performed. Heterogeneity was assessed using the I2 test and Q statistic. RESULTS: Thirty-nine cohort and case-control studies were included. ASA use was found to be significantly associated with a 46% higher risk of gastric cancer (RR, 1.46; 95% CI, 1.18-1.80) and a 53% higher risk of liver cancer (RR, 1.53; 95% CI, 1.31-1.78) compared with nonuse; however, there was no significant association for esophageal, colorectal, pancreatic, lung, breast, prostate, and kidney cancer; melanoma; and lymphoma. CONCLUSIONS: ASAs were significantly associated with an increased risk of gastric and liver cancer; therefore, special attention of ASA use considering the potential risk of gastric and liver cancer is needed.

Proton pump inhibitors and risk of liver cancer and mortality in patients with chronic liver disease: a systematic review and meta-analysis.

BACKGROUND: Epidemiological studies investigating the use of proton pump inhibitors (PPI) on the risk of liver cancer and/or mortality among persons with chronic liver disease (CLD) have reported conflicting results. We conducted a systematic review and meta-analysis to determine the impact of PPI use on liver cancer and/or death among patients with CLD. METHODS: The core databases including MEDLINE, EMBASE, and Cochrane library were searched through January 2020. We included studies, evaluating the association between PPIs and liver cancer or mortality among patients with CLD including randomized controlled, nonrandomized controlled, and observational studies. We used inverse-variance random-effects models to estimate the pooled relative risk (RR) and 95% confidence interval (CI) for liver cancer or mortality. RESULTS: Eleven studies including 173,894 patients were selected. In three studies, individuals with CLD who used PPIs had a 67% greater risk of developing hepatocellular carcinoma (HCC) compared to nonusers (RR, 1.67; 95% CI, 1.12-2.50; I2 = 92%). Combining data from the eight studies relating PPI to overall mortality, we observed a 57% increased risk of mortality in PPI users with CLD compared to CLD nonusers (RR: 1.57; 95% CI, 1.24-1.99; I2 = 69%). CONCLUSION: PPI use was associated with an increased risk of HCC and mortality in patients with CLD suggesting that PPI prescriptions in patients with CLD should be considered carefully.

Alterations in intracellular Ca2+ levels in human endometrial stromal cells after decidualization.

Calcium (Ca2+) is an important element for many physiological functions of the uterus, including embryo implantation. Here, we investigated the possible involvement of altered intracellular Ca2+ levels in decidualization in human endometrial stromal cells (hEMSCs). hEMSCs showed high levels of mesenchymal stem cell marker expression (CD73, CD90, and CD105) and did not express markers of hematopoietic progenitor cells (CD31, CD34, CD45, and HLA-DR). Decidualization is a process of ovarian steroid-induced endometrial stromal cell proliferation and differentiation. Several types of ion channels, which are regulated by the ovarian hormones progesterone and estradiol, as well as growth factors, are important for endometrial receptivity and embryo implantation. The combined application of progesterone (1 µM medroxyprogesterone acetate) and cyclic AMP (0.5 mM) for 6 days not only elevated inositol 1,4,5-triphosphate receptor (IP3R)-mediated Ca2+ release and IP3R expression, it also promoted ORAI and STIM expression as well as cyclopiazonic acid-induced Ca2+ release. Finally, intracellular Ca2+ levels and ion channel gene expression influenced hEMSC proliferation. These results suggest that cytosolic Ca2+ dynamics, mediated by specific ion channels, serve as an important step in the decidualization of hEMSCs.

The association between proton pump inhibitor use and the risk of tuberculosis: A case-control study.

PURPOSE: Few studies have reported an association between proton pump inhibitor (PPI) use and tuberculosis. Tuberculosis incidence is relatively high in Asian people, and an increase in PPI prescriptions has been reported in South Korea. Thus, we investigated the association between PPI use and tuberculosis development. METHODS: We conducted a case-control study on 25 672 newly diagnosed tuberculosis patients using the National Health Insurance Service-National Sample Cohort (NHIS-NSC) database (2002-2013). We selected a control group without tuberculosis using 1:1 exact matching based on age, sex, index year, insurance type, and income level. We investigated PPI exposure 2 years prior to the index date and classified the subjects into nonuser, continuous user, recent user, and former user groups. Odds ratios (ORs) and 95% confidence intervals (CIs) for tuberculosis development were calculated using conditional logistic regression. RESULTS: A total of 51 344 cases and controls were analyzed. Recent PPI use (adjusted odds ratio [aOR], 1.28; 95% CI, 1.18-1.39) and continuous PPI use (aOR, 1.13; 95% CI 1.10-1.28) were significantly associated with tuberculosis development, compared with nonuse of PPIs. An increased tuberculosis incidence was not observed in the former use group compared with the nonuse group (aOR 1.05, 95% CI 0.95-1.17). CONCLUSIONS: In this case-control study, we found that recent PPI use and continuous PPI use were associated with increased tuberculosis development. Although further investigation is needed, the tuberculosis risk accompanying PPI treatment should be considered.

Quality of life of middle-aged adults in single households in South Korea.

PURPOSE: The number of single households has increased worldwide with middle-aged people in such households indicating the highest increase. However, there is a lack of studies on the topic. This study estimated the quality of life (QOL) by household type for middle-aged Korean adults. METHODS: We used the Korea National Health and Nutrition Examination Survey data from 2007 to 2015. QOL was analyzed using EQ-5D 3-level, and demographic and health-related variables were included as confounders. The households were divided into single household, married couple without child, other one-generation, married couple with child, single parent with child, other two-generation, and three-generation. Logistic regression using level, strata, and sample weight of data was performed based on average QOL. RESULTS: This study included 18,147 responders aged 45-64 years, with single households constituting 5.7%. Single households having average or less QOL were 48.4%, with men and women constituting 40.1 and 53.3%, respectively. After adjusting socioeconomic factors and health-related factors, the odds ratio (OR) of single households was 1.375 (95% CI 1.122-1.684) compared to the three-generation group. According to the sex, the OR of single households with men was higher (OR 1.552, 95% CI 1.121-2.149). However, no significance was found in women. CONCLUSIONS: The study results revealed that middle-aged people in single households had low QOL than those in multi-person households. The trend was significantly observable in men than in women. Because middle-aged adults might transform into elderly with low QOL, program development and social support for middle-aged adults in single households should be provided.

Structural basis for the bifunctionality of fructose-1,6-bisphosphate aldolase/phosphatase.

Enzymes catalyse specific reactions and are essential for maintaining life. Although some are referred to as being bifunctional, they consist of either two distinct catalytic domains or a single domain that displays promiscuous substrate specificity. Thus, one enzyme active site is generally responsible for one biochemical reaction. In contrast to this conventional concept, archaeal fructose-1,6-bisphosphate (FBP) aldolase/phosphatase (FBPA/P) consists of a single catalytic domain, but catalyses two chemically distinct reactions of gluconeogenesis: (1) the reversible aldol condensation of dihydroxyacetone phosphate (DHAP) and glyceraldehyde-3-phosphate (GA3P) to FBP; (2) the dephosphorylation of FBP to fructose-6-phosphate (F6P). Thus, FBPA/P is fundamentally different from ordinary enzymes whose active sites are responsible for a specific reaction. However, the molecular mechanism by which FBPA/P achieves its unusual bifunctionality remains unknown. Here we report the crystal structure of FBPA/P at 1.5-Å resolution in the aldolase form, where a critical lysine residue forms a Schiff base with DHAP. A structural comparison of the aldolase form with a previously determined phosphatase form revealed a dramatic conformational change in the active site, demonstrating that FBPA/P metamorphoses its active-site architecture to exhibit dual activities. Thus, our findings expand the conventional concept that one enzyme catalyses one biochemical reaction.

Comparative effectiveness of ramosetron for preventing chemotherapy-induced nausea and vomiting: a systematic review and meta-analysis.

PURPOSE: This study aimed to evaluate the effectiveness and safety of ramosetron for chemotherapy-induced nausea and vomiting (CINV) through a systematic review of randomized controlled trials (RCTs). METHODS: An electronic search of CENTRAL, Ovid MEDLINE, Ovid EMBASE, KoreaMed, KISS, KMbase, and DBpia was performed. Published RCTs comparing ramosetron treatment and other 5-HT3RAs to prevent CINV were included, and studies reporting at least one clinical outcome about efficacy were included. Assessment of risk of bias and data extraction of the included studies was conducted by two independent reviewers. RESULTS: Sixteen RCTs were included, with nine studies reporting nausea and 13 reporting vomiting. In the acute phase, ramosetron significantly reduced nausea compared to other 5-HT3RAs (RR 1.11; 95 % CI 1.10 to 1.22, P = 0.03), as well as acute vomiting (RR 1.04, 95 % CI 1.01 to 1.08, P = 0.02). In the delayed phase, there was no difference in the complete response of nausea between ramosetron and other 5-HT3RAs, whereas ramosetron significantly decreased emesis compared to other 5-HT3RAs. Also, there were no significant differences between ramosetron versus other 5-HT3RAs for common adverse reactions such as headache, diarrhea, dizziness, and constipation. CONCLUSIONS: This study's findings suggest that ramosetron for CINV is as effective and tolerable as other 5-HT3RAs, based on the currently available evidence from RCTs. However, owing to methodological flaws in the current RCTs, well-designed randomized controlled trials are needed to confirm the effect of ramosetron on acute or delayed CINV in cancer patients.

Mapping health assessment questionnaire disability index (HAQ-DI) score, pain visual analog scale (VAS), and disease activity score in 28 joints (DAS28) onto the EuroQol-5D (EQ-5D) utility score with the KORean Observational study Network for Arthritis (KORONA) registry data.

The aim of this study was to estimate the mapping model for EuroQol-5D (EQ-5D) utility values using the health assessment questionnaire disability index (HAQ-DI), pain visual analog scale (VAS), and disease activity score in 28 joints (DAS28) in a large, nationwide cohort of rheumatoid arthritis (RA) patients in Korea. The KORean Observational study Network for Arthritis (KORONA) registry data on 3557 patients with RA were used. Data were randomly divided into a modeling set (80 % of the data) and a validation set (20 % of the data). The ordinary least squares (OLS), Tobit, and two-part model methods were employed to construct a model to map to the EQ-5D index. Using a combination of HAQ-DI, pain VAS, and DAS28, four model versions were examined. To evaluate the predictive accuracy of the models, the root-mean-square error (RMSE) and mean absolute error (MAE) were calculated using the validation dataset. A model that included HAQ-DI, pain VAS, and DAS28 produced the highest adjusted R (2) as well as the lowest Akaike information criterion, RMSE, and MAE, regardless of the statistical methods used in modeling set. The mapping equation of the OLS method is given as EQ-5D = 0.95-0.21 × HAQ-DI-0.24 × pain VAS/100-0.01 × DAS28 (adjusted R (2) = 57.6 %, RMSE = 0.1654 and MAE = 0.1222). Also in the validation set, the RMSE and MAE were shown to be the smallest. The model with HAQ-DI, pain VAS, and DAS28 showed the best performance, and this mapping model enabled the estimation of an EQ-5D value for RA patients in whom utility values have not been measured.

Lifetime effectiveness of mifamurtide addition to chemotherapy in nonmetastatic and metastatic osteosarcoma: a Markov process model analysis.

The mortality and progression rates in osteosarcoma differ depending on the presence of metastasis. A decision model would be useful for estimating long-term effectiveness of treatment with limited clinical trial data. The aim of this study was to explore the lifetime effectiveness of the addition of mifamurtide to chemotherapy for patients with metastatic and nonmetastatic osteosarcoma. The target population was osteosarcoma patients with or without metastasis. A Markov process model was used, whose time horizon was lifetime with a starting age of 13 years. There were five health states: disease-free (DF), recurrence, post-recurrence disease-free, post-recurrence disease-progression, and death. Transition probabilities of the starting state, DF, were calculated from the INT-0133 clinical trials for chemotherapy with and without mifamurtide. Quality-adjusted life-years (QALY) increased upon addition of mifamurtide to chemotherapy by 10.5 % (10.13 and 9.17 QALY with and without mifamurtide, respectively) and 45.2 % (7.23 and 4.98 QALY with and without mifamurtide, respectively) relative to the lifetime effectiveness of chemotherapy in nonmetastatic and metastatic osteosarcoma, respectively. Life-years gained (LYG) increased by 10.1 % (13.10 LYG with mifamurtide and 11.90 LYG without mifamurtide) in nonmetastatic patients and 42.2 % (9.43 LYG with mifamurtide and 6.63 LYG without mifamurtide) in metastatic osteosarcoma patients. The Markov model analysis showed that chemotherapy with mifamurtide improved the lifetime effectiveness compared to chemotherapy alone in both nonmetastatic and metastatic osteosarcoma. Relative effectiveness of the therapy was higher in metastatic than nonmetastatic osteosarcoma over lifetime. However, absolute lifetime effectiveness was higher in nonmetastatic than metastatic osteosarcoma.

The addition of mifamurtide to chemotherapy improves lifetime effectiveness in children with osteosarcoma: a Markov model analysis.

In the absence of long-term clinical trials that compare mifamurtide plus chemotherapy versus chemotherapy only for treatment of osteosarcoma, decision analysis is a useful tool that helps to determine the optimal treatment strategy. We analyzed the differences between mifamurtide plus chemotherapy versus chemotherapy only by using modeling to determine the treatment approach that results in longer life expectancy among children with osteosarcoma. We used the Markov model to compare the expected lifetime quality-adjusted life years (QALYs) between mifamurtide plus chemotherapy versus chemotherapy only. Our target cohort consisted of children with osteosarcoma. The starting age of the cohort was 12 years and cycle length was 3 months. The transition probabilities for each disease state and death were calculated using overall survival or progression free survival data from randomized controlled trials. Utility weights from scenario-based survey for 303 Korean general populations were applied to the model. Based on the base case analysis, the incremental benefit analysis indicated that mifamurtide plus chemotherapy resulted in an incremental QALY increase of 1.57 (a relative increase of 16.3 % in QALY expectancy) compared to chemotherapy only. Also, the incremental life years gained (LYG) from mifamurtide plus chemotherapy was 1.96 on comparison with chemotherapy only; this is a relative increase of 15.7 % in LYG expectancy. The decision analysis model indicated that mifamurtide plus chemotherapy was associated with a substantially longer survival than chemotherapy only among children with osteosarcoma during their lifetime.

Functionalized mesoporous silicas with crown ether moieties for selective adsorption of lithium ions in artificial sea water.

Lithium ion has been increasingly recognized in a wide range of industrial applications. In this work, we studied on the adsorption of Li+ in the artificial seawater with high selectivity using methyl-crown ether (AC-SBA-15) and aza-crown ether (HMC-SBA-15) moieties-functionalized mesoporous silica materials. First, methyl-crown ether and aza-crown ether moieties-functionalized mesoporous silica materials were synthesized via two-step post-synthesis process using a grafting method. The functionalized materials were employed to the metal ion adsorption from aqueous solution (artificial seawater) containing Li+, Co2+, Cr3+ and Hg2+. The prepared hybrid material showed high selectivity for Li+ ion in the artificial seawater at pH 8.0. The absorbed amount of Li+ was 73 times higher than Cr3+ for aza-crown ether containing AC-SBA-15 as an absorbent. The absorbed amount of Co2+ (4.5 x 10(-5) mol/g), Cr3+ (1.5 x 10(-5) mol/g) and Hg2+ (2.25 x 10(-4) mol/g) were remarkably lower than the case of Li+. On the other hand, the absorbed amount of various metal ions of HMC-SBA-15 with amine groups in alky chains and crown ether moieties were 1.1 x 10(-3) mol/g for Li+, 5.0 x 10(-5) mol/g for Co2+, 2.9 x 10(-4) mol/g for Cr3+, 2.8 x 10(-4) mol/g for Hg2+ mol/g, respectively.