Corrigendum: Chinese herbal medicine is associated with higher body weight reduction than liraglutide among the obese population: a real-world comparative cohort study.

[This corrects the article DOI: 10.3389/fphar.2022.978814.].

Chinese herbal medicine is associated with higher body weight reduction than liraglutide among the obese population: A real-world comparative cohort study.

Introduction: In Taiwan, many people receive Chinese herbal medicine (CHM) as an alternative choice to help control body weight. However, the clinical effectiveness of CHM on weight control has not been well studied, while potential risks and adverse effects are still unknown. The aim of our study is to find out a safe and efficient treatment model of CHM for weight control compared to liraglutide in a real-world setting. Methods: we retrospectively analyzed obese subjects [body mass index (BMI)≧25 kg/m2] from Chang Gung Research Database (2013-2018). We evaluated the effect on body weight and BMI changes in obese groups receiving CHM or western medicine (WM, represented liraglutide) within 180 days. The proportion of subjects who achieved 5 and 10% weight reduction was calculated as well. Furthermore, the potential adverse events were analyzed during the study period. Overlap weighting was used to balance the baseline differences between CHM and WM groups. Results: The full cohort comprised 1,360 participants: 701 in the CHM group and 659 in the WM group. At baseline, the CHM group was younger (42.75 ± 12.12 years old in CHM vs. 52.31 ± 11.7 years old in WM, p-value <0.001) and has more female subjects (77.6% in CHM vs. 53.0% in WM, p-value <0.001). On the other hand, CHM users had lower body weight (79.83 ± 15.66 kg vs. 84.68 ± 17.14 kg, p-value <0.001) and BMI (30.58 ± 5.20 vs. 32.84 ± 6.95, p-value <0.001). At day 180, CHM users lost more body weight (-4.5 ± 4.07 kg vs. -2.15 ± 4.05 kg, p-value <0.001) and higher reduction in BMI (-1.77 ± 1.73 vs. -0.9 ± 2.14, p-value <0.001). A total of 53.21% (n = 373) CHM users lost at least 5% of body weight (22.46% for WM users, p-value <0.001), and 18.97% (n = 132) lost at least 10% of body weight (4.55% for WM users, p-value <0.001). The benefit remained consistent with and without overlap weighting. For adverse events, 18 cases of hypertension occurred in 659 subjects in the WM group (2.7%) in comparison to 1 of 701 subjects in the CHM group (0.1%). Conclusion: CHM led to clinically meaningful weight loss without serious adverse events in a real-world setting. Further clinical trials are warranted to validate this result.

Efficacy of adavosertib therapy against anaplastic thyroid cancer.

Wee1 is a kinase that regulates the G2/M progression by the inhibition of CDK1, which is critical for ensuring DNA damage repair before initiation of mitotic entry. Targeting Wee1 may be a potential strategy in the treatment of anaplastic thyroid cancer, a rare but lethal disease. The therapeutic effects of adavosertib, a Wee1 inhibitor for anaplastic thyroid cancer was evaluated in this study. Adavosertib inhibited cell growth in three anaplastic thyroid cancer cell lines in a dose-dependent manner. Cell cycle analysis revealed cells were accumulated in the G2/M phase. Adavosertib induced caspase-3 activity and led to apoptosis. Adavosertib monotherapy showed significant retardation of the growth of two anaplastic thyroid cancer tumor models. The combination of adavosertib with dabrafenib and trametinib revealed strong synergism in vitro and demonstrated robust suppression of tumor growth in vivo in anaplastic thyroid cancer xenograft models with BRAFV600E mutation. The combination of adavosertib with either sorafenib or lenvatinib also demonstrated synergism in vitro and had strong inhibition of tumor growth in vivo in an anaplastic thyroid cancer xenograft model. No appreciable toxicity appeared in mice treated with either a single agent or combination treatment. Our findings suggest adavosertib holds the promise for the treatment of patients with anaplastic thyroid cancer.

Synergy between the pay-for-performance scheme and better physician-patient relationship might reduce the risk of retinopathy in patients with type 2 diabetes.

AIMS/INTRODUCTION: This study investigated whether participation by patients with type 2 diabetes in Taiwan's pay-for-performance (P4P) program and maintaining good continuity of care (COC) with their healthcare provider reduced the likelihood of future complications, such as retinopathy. MATERIALS AND METHODS: The analysis used longitudinal panel data for newly diagnosed type 2 diabetes from the National Health Insurance claims database in Taiwan. COC was measured annually from 2003 to 2013, and was used to allocate the patients to low, medium and high groups. Cox regression analysis was used with time-dependent (time-varying) covariates in a reduced model (with only P4P or COC), and the full model was adjusted with other covariates. RESULTS: Despite the same significant effects of treatment at primary care, the Diabetes Complications Severity Index scores were significantly associated with the development of retinopathy. After adjusting for these, the hazard ratios for developing retinopathy among P4P participants in the low, medium and high COC groups were 0.594 (95% confidence interval [CI] 0.398-0.898, P = 0.012), 0.676 (95% CI 0.520-0.867, P = 0.0026) and 0.802 (95% CI 0.603-1.030, P = 0.1062), respectively. Thus, patients with low or median COC who participated in the P4P program had a significantly lower risk of retinopathy than those who did not. CONCLUSIONS: Diabetes care requires a long-term relationship between patients and their care providers. Besides encouraging patients to participate in P4P programs, health authorities should provide more incentives for providers or patients to regularly survey patients' lipid profiles and glucose levels, and reward the better interpersonal relationship to prevent retinopathy.

Targeting PLKs as a therapeutic approach to well-differentiated thyroid cancer.

Polo-like kinases (PLKs) are pivotal regulators of cell proliferation and cell survival; therefore, PLKs may be potential targets in the treatment of malignancy. The therapeutic effects of volasertib, a PLKs inhibitor for papillary and follicular thyroid cancer (known as well-differentiated thyroid cancer (WDTC)), were evaluated in this study. Volasertib inhibited cell proliferation in two papillary and two follicular thyroid cancer cell lines in a dose-dependent manner. Volasertib treatment reduced cells in the S phase and increased cells in the G2/M phase. Volasertib activated caspase-3 activity and induced apoptosis. Drug combinations of volasertib and sorafenib showed mostly synergism in four well-differentiated thyroid carcinoma cell lines in vitro. Volasertib treatment in vivo retarded the growth of a papillary thyroid tumor model. Furthermore, the combination of volasertib with sorafenib was more effective than a single treatment of either in a follicular thyroid cancer xenograft model. Promising safety profiles appeared in animals treated with either volasertib alone or volasertib and sorafenib combination therapy. These findings support volasertib as a potential drug for the treatment of patients with WDTC.

Primary and repeated surgeries for ectopic pregnancies and distribution by patient age, surgeon age, and hospital levels: an 11-year nationwide population-based descriptive study in Taiwan.

STUDY OBJECTIVE: To describe the changing trend, repeat operation rate, and distribution of laparoscopy, as compared with laparotomy, in treating ectopic pregnancy, according to patient age, preoperative conditions, surgeon age, and hospital accreditation level, in Taiwan over 11-years. DESIGN: Retrospective cohort study (Canadian Task Force classification II-2). SETTING: Population-based nationwide insurance database. PATIENTS: Women who underwent either laparotomy or laparoscopy because of ectopic pregnancy. INTERVENTIONS: Women who had National Health Insurance (NHI) underwent various surgical procedures to treat ectopic pregnancy. Data for this study were obtained from the Inpatient Expenditures by Admissions files of the NHI Research Database, released by the NHI program in Taiwan between 1997 and 2007. MEASUREMENTS AND MAIN RESULTS: A total of 43 170 women with 44 928 operations were identified. Only the primary surgeries, via either laparotomy or laparoscopy, performed because of ectopic pregnancy were included for analysis. The annual number of procedures to treat ectopic pregnancies decreased in the later years of the 11-year study. Laparotomy decreased significantly, from 81.2% in 1997 to 26.2% in 2007, whereas laparoscopic procedures increased significantly, from 18.8% in 1997 to 73.8% in 2007, as evidenced at log-linear regression analysis (p < .001). The rate of repeat operations because of persistent ectopic pregnancy was higher in the laparoscopy group than in the laparotomy group (0.38% vs 0.14 %; p < .001). Patients were more likely to undergo the same type of operation for the repeated surgery (i.e., laparotomy to laparotomy in 73.1% or laparoscopy to laparoscopy in 80.2%; p = 0.43). Use of laparoscopy (58.1%) and laparotomy (41.9%) differed according to patient age, preoperative comorbidities, surgeon age, and hospital accreditation level and ownership type. With older patients, those with preoperative anemia or shock, and elder surgeons, there was a greater chance that laparotomy would be performed. The probability of undergoing laparotomy was greater in patients in regional hospitals, local hospitals, and office-based clinics compared with those in medical centers. CONCLUSIONS: There has been considerable change in the type of surgical approach used to treat ectopic pregnancy in Taiwan over the past 11 years. Laparoscopy is preferred to laparotomy, and has become the standard surgical approach to treating ectopic pregnancies in Taiwan. However, laparoscopy is associated with a higher rate of repeat operations. The laparoscopic approach signifies a profound change in treating ectopic pregnancies among patients, surgeons, and hospital types.

The impact of universal National Health Insurance on population health: the experience of Taiwan.

BACKGROUND: Taiwan established a system of universal National Health Insurance (NHI) in March, 1995. Today, the NHI covers more than 98% of Taiwan's population and enrollees enjoy almost free access to healthcare with small co-payment by most clinics and hospitals. Yet while this expansion of coverage will almost inevitably have improved access to health care, however, it cannot be assumed that it will necessarily have improved the health of the population. The aim of this study was to determine whether the introduction of National Health Insurance (NHI) in Taiwan in 1995 was associated with a change in deaths from causes amenable to health care. METHODS: Identification of discontinuities in trends in mortality considered amenable to health care and all other conditions (non-amenable mortality) using joinpoint regression analysis from 1981 to 2005. RESULTS: Deaths from amenable causes declined between 1981 and 1993 but slowed between 1993 and 1996. Once NHI was implemented, the decline accelerated significantly, falling at 5.83% per year between 1996 and 1999. In contrast, there was little change in non-amenable causes (0.64% per year between 1981 and 1999). The effect of NHI was highest among the young and old, and lowest among those of working age, consistent with changes in the pattern of coverage. NHI was associated with substantial reductions in deaths from circulatory disorders and, for men, infections, whilst an earlier upward trend in female cancer deaths was reversed. CONCLUSIONS: NHI was associated in a reduction in deaths considered amenable to health care; particularly among those age groups least likely to have been insured previously.

Adverse pharmaceutical payment incentives and providers' behaviour: the emergence of GP-owned gateway pharmacies in Taiwan.

OBJECTIVES: We investigated whether a 2002 pharmaceutical payment reform policy, which provided adverse incentives, fostered an increase in market share of 'gateway pharmacies' (G-pharmacies--pharmacies owned, operated and located by the same clinics that prescribe medicines); what the financial impact of G-pharmacies to the clinics is; and what factors determine whether a clinic decides to open a G-pharmacy. METHODS: Using the database of the National Health Research Institutes, we collected secondary data on all of Taiwan's National Health Insurance prescription claims from pharmacies and clinics between 1997 and 2003. A G-pharmacy was defined as a pharmacy in which more than 70% of the prescriptions it filled came from the same clinic, which prescribed at least 900 prescriptions monthly, more than 70% of which were released to the pharmacy. Trend plot and frequency were used to analyse the distribution of G-pharmacy data. Logistic regression was used to explore what factors determined whether a clinic decided to open a G-pharmacy. RESULTS: After the 2002 reform, the percentage of total prescriptions filled by G-pharmacies reached 78.71%, the increase in percentage (15.23%) was the highest ever and significant (P < 0.01). The reform's adverse payment incentives resulted in a loss of NT$1.86 billion New Taiwan dollars to all clinics and resulted in a reduction in Taiwan's 2003 fee schedules under the global budget payment system. The decision to establish a G-pharmacy was associated with a clinic's being located in less urbanized areas, being a group practice, having higher patient volumes, being a general practitioner, and being privately owned. CONCLUSION: The 2002 reform's adverse incentive fostered a significant increase in the market share of G-pharmacies, and reduced the earnings of clinics which did not own them. It is necessary to break the link between profits from pharmaceutical sales and physician prescribing behaviour to prevent the conflict of interest in how medicines are prescribed.