The prevalence of contraceptive use among postpartum women and its associated factors during the early phase of COVID-19 outbreak: a time series study.

BACKGROUND: Unintended pregnancies can adversely affect maternal health, preventable through timely postpartum contraception. During the COVID-19 pandemic, family planning services were constrained by policies that curtailed outpatient visits. We investigated the prevalence of postpartum contraceptive initiation at King Chulalongkorn Memorial Hospital (KCMH) during January to June 2020, comparing with the same period in 2019, and identified factors associated with such initiation. METHODS: We reviewed the medical records of 4506 postpartum women who delivered at KCMH during the study period. Logistic regression was conducted to test the association between early COVID-19 phase deliveries and post-partum long acting reversible contraception (LARC) initiation including copper intrauterine devices, levonorgestrel intrauterine systems, contraceptive implants, and progestogen-only injectable contraceptives. RESULTS: A total of 3765 women (83.6%), of whom 1821 delivered during the pandemic and 1944 during the historical cohort period, were included in this study. The proportion of women who initiated non-permanent modern contraceptives at six weeks postpartum was comparable between the COVID-19 (73.4%) and historical cohort (75.3%) (p = 0.27) periods. The proportion of women who initiated LARC at six weeks postpartumwas comparable between the historical cohort period (22.5%) and the COVID-19 (19.7%) (p = 0.05) period. Accessing a six-week postpartum check-up was independently associated with LARC initiation, of which the adjusted odds ratio (OR) (95% confidence interval) was 3.01 (2.26 to 4.02). CONCLUSIONS: Our findings demonstrated that accessing postpartum care significantly associate with the use of LARC. The data suggest the strong influence of postpartum check-ups in facilitating the adoption of effective contraception, emphasizing the need for accessible postpartum care to sustain maternal health during health crises.

A randomized single-blind non-inferiority trial of delayed start with drospirenone-only and ethinyl estradiol-gestodene pills for ovulation inhibition.

We compared the efficacy of 4 mg drospirenone (DRSP) progestin-only pills (POPs) versus combined oral contraceptive pills (COCs) containing 0.02 mg of ethinyl estradiol (EE) and 0.075 mg of gestodene (GS) in ovulation inhibition and inducing unfavorable cervical mucus changes using a delayed-starting approach. This randomized controlled trial involved 36 participants aged 18-45 years. The major outcomes included ovulation inhibition assessed using the Hoogland and Skouby score, and cervical mucus permeability, assessed using the modified World Health Organization score. The results demonstrated ovulation inhibition rates of 77.8% for the EE/GS group and 88.9% for the DRSP group. The risk ratio and absolute risk reduction were 0.50 (95% confidence interval [CI]: 0.10, 2.40) and - 0.11 (95% CI: - 0.35, 0.13), respectively, satisfying the 20% non-inferiority margin threshold. The median time to achieve unfavorable cervical mucus changes was comparable between the DRSP (3 days, interquartile range [IQR]: 6 days) and EE/GS (3.5 days, IQR: 4 days) groups. However, the DRSP group had a higher incidence of unscheduled vaginal bleeding (55.56% vs. 11.11%; p = 0.005). DRSP-only pills, initiated on days 7-9 of the menstrual cycle, were non-inferior to EE/GS pills in ovulation inhibition. However, they exhibited delayed unfavorable cervical mucus changes compared to the standard two-day backup recommendation.Clinical trial registration: Thai Clinical Trials Registry (TCTR20220819001) https://www.thaiclinicaltrials.org/show/TCTR20220819001 .

Efficacy and mechanisms of cannabis oil for alleviating side effects of breast cancer chemotherapy (CBC2): protocol for randomized controlled trial.

BACKGROUND: In a pilot study using both cannabidiol (CBD) and tetrahydrocannabinol (THC) as single agents in advanced cancer patients undergoing palliative care in Thailand, the doses were generally well tolerated, and the outcome measure of total symptom distress scores showed overall symptom benefit. The current study aims to determine the intensity of the symptoms experienced by breast cancer patients, to explore the microbiome profile, cytokines, and bacterial metabolites before and after the treatment with cannabis oil or no cannabis oil, and to study the pharmacokinetics parameters and pharmacogenetics profile of the doses. METHODS: A randomized, double-blinded, placebo-controlled trial will be conducted on the breast cancer cases who were diagnosed with breast cancer and currently receiving chemotherapy at King Chulalongkorn Memorial Hospital (KCMH), Bangkok, Thailand. Block randomization will be used to allocate the patients into three groups: Ganja Oil (THC 2 mg/ml; THC 0.08 mg/drop, and CBD 0.02 mg/drop), Metta Osot (THC 81 mg/ml; THC 3 mg/drop), and placebo oil. The Edmonton Symptom Assessment System (ESAS), Food Frequency Questionnaires (FFQ), microbiome profile, cytokines, and bacterial metabolites will be assessed before and after the interventions, along with pharmacokinetic and pharmacogenetic profile of the treatment during the intervention. TRIAL REGISTRATION: TCTR20220809001.

Should a Narrow Corridor Be a Contraindication for Performing Oblique Lateral Interbody Fusion Procedure or Not?

STUDY DESIGN: Retrospective study. OBJECTIVES: We investigated the effect of corridor width on the postoperative outcomes of patients who underwent the OLIF procedure. METHODS: Patients who underwent OLIF surgery, which included L4-5, between 2015 and 2021 were retrospectively studied. The patients were divided into three groups by the width of the corridor: not more than 10 mm, between 10 and 20 mm, and 20 mm or more. We compared clinical and radiographic outcomes and complications between these groups. RESULTS: A total of 81 patients were included. There were no significant differences in VAS leg and back pain scores, ODI scores, or complications between each group. The radiographic findings, including cage position, anterior and posterior disc height, segmental Cobb angle, and foraminal height, also showed no significant differences between each group. The only radiographic finding that showed a significant difference between each group was the angle of the cage. We found significantly less degree of angle in the wider than 20 mm group when compared to the other two groups. (P-value = .01). There was no recorded incidence of major vascular complications. CONCLUSIONS: The width of oblique corridor does not affect clinical outcomes, complications, or radiographic findings, including position of the cage, anterior and posterior disc height, segmental angle, and foraminal height after OLIF procedure, including L4-5 level. Thus, the OLIF procedure can be performed safely even in patients with limited oblique corridors, especially at L4-5.

Reproductive care in Thai women with diabetes mellitus: a descriptive cross-sectional study.

BACKGROUND: Pre-existing diabetes mellitus (DM) is a challenging pregnancy complication as poor glycemic control is associated with adverse maternal and fetal outcomes. In this study, we aimed to investigate DM-related knowledge, attitudes, preconception care practices, and contraceptive prevalence in women with DM. METHODS: This descriptive cross-sectional survey was conducted among reproductive-aged Thai women receiving DM treatment at King Chulalongkorn Memorial Hospital between August 1, 2021, and June 30, 2022. Patients with DM who were not pregnant or trying to conceive and could be contacted via the phone were included and a validated self-administered questionnaire was distributed electronically. RESULTS: A total of 238 participants were included in the final analysis, yielding 69.4% response rates. The mean (standard deviation) score for knowledge of pregnancy planning and pregnancy-related risks was 6.8 (3.5) out of 15. Only about half of the participants had discussed pregnancy planning with their physicians. Multivariable analysis showed that younger age at DM diagnosis, non-Buddhism, married, higher education, and medical personnel were significantly associated with higher knowledge scores. Women aged > 45 years and those with higher practice scores had significantly higher adjusted odds of using highly effective contraception; the most common methods included male condoms and combined oral contraceptive pills. There was an unmet need for contraception in 9.5% of women with DM. CONCLUSIONS: Although highly effective contraception is safe for patients with DM, only about half of our participants used tier one or two contraceptives or had received consultation regarding preconception planning. There was a notable gap in care coordination among specialists; integrating reproductive healthcare into DM therapy would improve access to preconception care.

We aimed to study the knowledge, attitudes, preconception care practices, and contraceptive usage among women with diabetes mellitus (DM) who were of reproductive age. A survey was conducted among Thai women receiving DM treatment at a university hospital. The results showed that participants had limited knowledge about pregnancy planning and diabetic-related risks. Only half of them had discussed pregnancy planning with their doctors. Factors such as younger age at DM diagnosis, being non-Buddhism, being married, having higher education, and being medical personnel were associated with higher knowledge scores. Older women and those with better practice scores were more likely to use highly effective contraception. However, there was still a need for contraception in some women with DM. We concluded that there was a lack of integration between specialists in reproductive healthcare and DM therapy, and improving this coordination would enhance access to preconception care for women with DM.

Curcumin and proton pump inhibitors for functional dyspepsia: a randomised, double blind controlled trial.

OBJECTIVE: To compare the efficacy of curcumin versus omeprazole in improving patient reported outcomes in people with dyspepsia. DESIGN: Randomised, double blind controlled trial, with central randomisation. SETTING: Thai traditional medicine hospital, district hospital, and university hospitals in Thailand. PARTICIPANTS: Participants with a diagnosis of functional dyspepsia. INTERVENTIONS: The interventions were curcumin alone (C), omeprazole alone (O), or curcumin plus omeprazole (C+O). Patients in the combination group received two capsules of 250 mg curcumin, four times daily, and one capsule of 20 mg omeprazole once daily for 28 days. MAIN OUTCOME MEASURES: Functional dyspepsia symptoms on days 28 and 56 were assessed using the Severity of Dyspepsia Assessment (SODA) score. Secondary outcomes were the occurrence of adverse events and serious adverse events. RESULTS: 206 patients were enrolled in the study and randomly assigned to one of the three groups; 151 patients completed the study. Demographic data (age 49.7±11.9 years; women 73.4%), clinical characteristics and baseline dyspepsia scores were comparable between the three groups. Significant improvements were observed in SODA scores on day 28 in the pain (-4.83, -5.46 and -6.22), non-pain (-2.22, -2.32 and -2.31) and satisfaction (0.39, 0.79 and 0.60) categories for the C+O, C, and O groups, respectively. These improvements were enhanced on day 56 in the pain (-7.19, -8.07 and -8.85), non-pain (-4.09, -4.12 and -3.71) and satisfaction (0.78, 1.07, and 0.81) categories in the C+O, C, and O groups, respectively. No significant differences were observed among the three groups and no serious adverse events occurred. CONCLUSION: Curcumin and omeprazole had comparable efficacy for functional dyspepsia with no obvious synergistic effect. TRIAL REGISTRATION NUMBER: TCTR20221208003.

Knowledge, Moral Attitude, and Practice of Nursing Students Toward Abortion.

In 2021, Thailand decriminalized abortions to allow for legal abortions on request up to 12 weeks' gestation and conditionally up to 20 weeks' gestation, or in the case of sexual assault, maternal mental or physical harm, or fetal abnormality. We intend to say that healthcare practitioners' positive attitudes toward abortion will destigmatize abortion for both themselves and their patients. We explored the knowledge, attitudes, and intended practices of nursing students toward safe abortion practices in light of the recent law reform. This was a cross-sectional study using a self-administered questionnaire. The questionnaire consisted of 4 parts: a demographic information questionnaire; and measures to assess their knowledge, moral attitudes, and intended practice regarding safe abortion care. Questionnaires were sent to 206 nursing students who had completed the Midwifery and Maternal-Newborn Nursing rotation in Bangkok, Thailand. The survey response rate was 90.8%. Mean (standard deviation) knowledge score was 6.72 (1.86) out of 10. Buddhist students were more likely to have a positive attitude toward abortions. Most students intended to practice safe abortions in pregnancies that affect maternal physical or mental health, or in pregnancies that resulted from unlawful sexual contact. Students were more ambivalent toward abortion practices for socioeconomic reasons. Better knowledge of abortion legislation was associated with a more positive attitude toward abortions and safe abortion practice intention. Approximately 1 year after the abortion law reform in Thailand, nursing students had incomplete knowledge of the amendment. Most students were inclined to provide abortion care services for certain conditions.

Does socioeconomic factors and healthcare coverage affect postpartum sterilization uptake in an urban, tertiary hospital?

BACKGROUND: Postpartum sterilization in Thailand has relatively few barriers compared to other countries. The procedure is covered by some healthcare plans, and paid out-of-pocket for others. We aim to determine if healthcare coverage and other socioeconomic factors affect the rate of postpartum sterilization in an urban, tertiary hospital. METHODS: We conducted a secondary analysis of data from a retrospective cohort of 4482 postpartum women who delivered at our hospital. Multivariable logistic regression was conducted to determine if sterilization reimbursement affects immediate postpartum sterilization rate. RESULTS: Overall immediate postpartum sterilization rate was 17.8%. Route of delivery and parity were similar in those who were reimbursed and those who were not. Women aged over 25 were more likely to have a healthcare plan that does not cover postpartum sterilization. Women whose healthcare plan reimbursed the procedure trended towards postpartum sterilization when compared to women who were not (aOR 1.05, 95% CI 0.86-1.28, p-value = 0.632). Women who delivered via cesarean section were more likely to undergo sterilization at the time of delivery (aOR = 5.87; 95% CI 4.77-7.24, p-value = < 0.001). Women aged 40-44 years were 2.70 times as likely to choose sterilization than those aged 20-24 years (aOR = 2.70; 95% CI 1.61-4.53, p-value < 0.001). CONCLUSIONS: Healthcare coverage of the procedure was not associated with increased postpartum sterilization in our setting.

Postpartum sterilization is an effective and popular method of contraception. In our hospital, postpartum sterilization is easily accessible compared to other countries where there are barriers such as mandatory waiting time, limited operating rooms and anesthesiologists. We examine factors that affect sterilization rates and found that older women and women with more children were more likely to choose postpartum sterilization. We also found that women who delivered by cesarean section were more likely to choose sterilization. Interestingly, whether the woman's healthcare plan covers postpartum sterilization does not affect the likelihood of sterilization.

Breakthrough infections, hospital admissions, and mortality after major COVID-19 vaccination profiles: A prospective cohort study.

Background: Several COVID-19 vaccination rollout strategies are implemented. Real-world data from the large-scale, government-mandated Central Vaccination Center (CVC), Thailand, could be used for comparing the breakthrough infection, across all available COVID-19 vaccination profiles. Methods: This prospective cohort study combined the vaccine profiles from the CVC registry with three nationally validated outcome datasets to assess the breakthrough COVID-19 infection, hospitalization, and death among Thais individuals who received at least one dose of the COVID-19 vaccine. The outcomes were analyzed by comparing vaccine profiles to investigate the shot effect and homologous effect. Findings: Of 2,407,315 Thais who had at least one dose of COVID-19 vaccine, 63,469 (2.75%) had breakthrough infection, 42,001 (1.79%) had been hospitalized, and 431 (0.02%) died. Per one vaccination shot added, there was an 18% risk reduction of breakthrough infection (adjusted hazard ratio [HR] 0.82, 95% confidence interval [CI] 0.80-0.82), a 25% risk reduction of hospitalization (HR 0.75, 95% CI 0.73-0.76), and a 96% risk reduction of mortality (HR 0.04, 95% CI 0.03-0.06). The heterologous two-shot vaccine profiles had a higher protective effect against infection, hospitalization, and mortality compared to the homologous counterparts. Interpretation: COVID-19 breakthrough infection, hospitalization, and death differ across vaccination profiles that had a different number of shots and types of vaccines. Funding: This study did not involve any funding.

Alu hypomethylation in naturally and surgically postmenopausal women; a cross-sectional study.

Menopause, which may accelerate the hallmarks of the natural aging process, represents a point in time characterized by the permanent cessation of menstruation following the loss of ovarian estrogen production. Unlike natural menopause, which is characterized by a gradual decrease in estrogen production, when both ovaries are removed before the natural age of menopause, the onset of estrogen deprivation is abrupt. Further, a decrease in genome methylation frequently occurs in aging cells, and the major interspersed repetitive DNA elements in humans are Alu elements. In blood cells, Alu demethylation starts at an age of approximately 40 years, and increases with age. Here, we explored the Alu methylation levels corresponding to age-matched pre-menopausal, naturally postmenopausal, and surgically postmenopausal women aged 45-55 years (n = 60 in each group). Our results indicated that the body mass index (BMI), time-since-menopause, and Alu methylation levels corresponding to the three groups were significantly different. However, no correlations between Alu methylation level and BMI, time-since-menopause, or age were observed. Additionally, the Alu methylation level corresponding to the natural post-menopause group was significantly lower those corresponding to the pre-menopausal (p = 0.001) and surgical post-menopausal (p = 0.037) groups. In conclusion, Alu hypomethylation occurs in naturally postmenopausal women, implying that when women reach the age of natural menopause, the cell aging process may progress significantly with genome hypomethylation. These findings, notwithstanding, further studies are necessary to clarify whether bilateral oophorectomy before the age of menopause affects the cell aging process to a greater extent than natural menopause, and whether estrogen therapy or other interventions can delay cell aging in this regard.

ChAdOx1 nCoV-19 Immunogenicity and Immunological Response Following COVID-19 Infection in Patients Receiving Maintenance Hemodialysis.

Patients with end-stage renal disease (ESRD) receiving hemodialysis (HD) were found to have a decreased immune response following mRNA COVID-19 immunization. ChAdOx1 nCoV-19 was a promising COVID-19 vaccine that performed well in the general population, but the evidence on immunogenicity in ESRD with HD patients was limited. Moreover, the immunological response to COVID-19 infection was inconclusive in patients with ESRD and HD. The aim of this study was to investigate the immunogenicity of ChAdOx1 nCoV-19 vaccination and the immunological response after COVID-19 infection in ESRD patients with HD. The blood samples were obtained at baseline, 1-month, and 3-month follow-up after each shot or recovery. All participants were measured for anti-spike IgG by the ELISA method, using Euroimmun. This study found a significant increase in anti-spike IgG after 1 month of two-shot ChAdOx1 nCoV-19 vaccination, followed by a significant decrease after 3 months. On the other hand, the anti-spike IgG was maintained in the post-recovery group. There was no significant difference in the change of anti-spike IgG between the one-shot ChAdOx1 nCoV-19-vaccinated and post-recovery groups for both 1-month and 3-month follow-ups. The seroconversion rate for the vaccinated group was 60.32% at 1 month after one-shot vaccination and slightly dropped to 58.73% at the 3-month follow-up, then was 92.06% at 1 month after two-shot vaccination and reduced to 82.26% at the 3-month follow-up. For the recovered group, the seroconversion rate was 95.65% at 1 month post-recovery and 92.50% at 3-month follow-up. This study demonstrated the immunogenicity of two-dose ChAdOx1 nCoV-19 in ESRD patients with HD for humoral immunity. After COVID-19 infection, the humoral immune response was strong and could be maintained for at least three months.

Immunogenicity of ChAdOx1 nCoV-19 Booster Vaccination Following Two CoronaVac Shots in Healthcare Workers.

During the early phase of the COVID-19 pandemic, several countries, including Thailand, provided two shots of CoronaVac to healthcare workers. Whereas ChAdOx1 nCoV-19 is the promising vaccine as the booster dose, the data on immunogenicity when administered after CoronaVac have been limited. The purpose of this study was to evaluate the immunogenicity of ChAdOx1 nCoV-19 as the third dose vaccine in healthcare workers who previously received two shots of CoronaVac. The blood samples were obtained before the third vaccination dose, and one month and three months after vaccination. All participants were measured for humoral immunity including anti-spike IgG and neutralizing antibody by ELISA. Twenty participants were stratified by random samples based on baseline IgG status for a cellular immunity function test at three-month post-vaccination, which included T cell and B cell functions by ELISpot. This study showed significant improvement for both humoral and cellular immunity one month after vaccination. Subgroup analysis indicated a significantly higher neutralizing antibody improvement for the population with a negative anti-spike IgG at baseline. Our study suggests that, while immunity level declines at three months post-vaccination, the level was sufficiently high to protect against SARS-CoV-2.

Acceptance and use of complementary and alternative medicine among medical specialists: a 15-year systematic review and data synthesis.

BACKGROUND: Complementary and Alternative Medicine (CAM) has gained popularity among the general population, but its acceptance and use among medical specialists have been inconclusive. This systematic review aimed to identify relevant studies and synthesize survey data on the acceptance and use of CAM among medical specialists. METHODS: We conducted a systematic literature search in PubMed and Scopus databases for the acceptance and use of CAM among medical specialists. Each article was assessed by two screeners. Only survey studies relevant to the acceptance and use of CAM among medical specialists were reviewed. The pooled prevalence estimates were calculated using random-effects meta-analyses. This review followed both PRISMA and SWiM guidelines. RESULTS: Of 5628 articles published between 2002 and 2017, 25 fulfilled the selection criteria. Ten medical specialties were included: Internal Medicine (11 studies), Pediatrics (6 studies), Obstetrics and Gynecology (6 studies), Anesthesiology (4 studies), Surgery (3 studies), Family Medicine (3 studies), Physical Medicine and Rehabilitation (3 studies), Psychiatry and Neurology (2 studies), Otolaryngology (1 study), and Neurological Surgery (1 study). The overall acceptance of CAM was 52% (95%CI, 42-62%). Family Medicine reported the highest acceptance, followed by Psychiatry and Neurology, Neurological Surgery, Obstetrics and Gynecology, Pediatrics, Anesthesiology, Physical Medicine and Rehabilitation, Internal Medicine, and Surgery. The overall use of CAM was 45% (95% CI, 37-54%). The highest use of CAM was by the Obstetrics and Gynecology, followed by Family Medicine, Psychiatry and Neurology, Pediatrics, Otolaryngology, Anesthesiology, Internal Medicine, Physical Medicine and Rehabilitation, and Surgery. Based on the studies, meta-regression showed no statistically significant difference across geographic regions, economic levels of the country, or sampling methods. CONCLUSION: Acceptance and use of CAM varied across medical specialists. CAM was accepted and used the most by Family Medicine but the least by Surgery. Findings from this systematic review could be useful for strategic harmonization of CAM and conventional medicine practice. SYSTEMATIC REVIEW REGISTRATION: PROSPERO CRD42019125628.

Self-Medication With Over-the-counter Medicines Among the Working Age Population in Metropolitan Areas of Thailand.

Background and Objectives: Self-medication with over-the-counter (OTC) medicines is becoming an increasingly popular practice around the world. The global prevalence rate of self-medication ranges from 11.2% to 93.7%, depending on the target population and country. However, there is a lack of data on the prevalence and practices of self-medication among the working-age population, particularly in Thailand metropolitan areas. The current study describes the prevalence of self-medication practices, adverse drug reactions and severity, reasons for self-medication, and basic medication knowledge among people of working age in metropolitan areas in Thailand. Methods: We conducted an online cross-sectional study between December 2020 and January 2021. Descriptive statistics were used to analyze self-medication data. A chi-square test was used to assess the association between self-medication and sociodemographic characteristics. Results: This study found high prevalence of self-medication among the working-age population in metropolitan areas of Thailand (88.2%). The most commonly used drug groups were NSAIDs (34.8%) and antibiotics (30.2%). Minor illness and easy access to pharmacies were the most common reasons for self-medication. Almost half of the participants' illnesses (42.6%) for which they self-medicated were not always completely cured, necessitating treatment at a hospital or clinic. Although only a small number of participants (ranged from 0.6 to 6.6%) experienced adverse drug reactions as a result of self-medication, some had severe symptoms that disrupted their daily lives or required hospitalization. In terms of basic medication knowledge, we discovered that study participants misunderstood some antibiotic drug concepts. Conclusions: According to the study findings, it is recommended that more information about the risks of self-medication, drug adverse reactions, antibiotic stewardship, more supervision of the prohibition of over-the-counter drugs and selling practices, and adequate facilities for peoples access to medical services be provided at the policy level.

Glutathione and its antiaging and antimelanogenic effects.

BACKGROUND: Previous studies showed that supplementation of reduced form of glutathione (GSH, 500 mg/d) has a skin-lightening efficacy in humans. This study was designed to evaluate the influences of both GSH and oxidized form (GSSG), at doses lower than 500 mg/d, on improving skin properties. PATIENTS AND METHODS: A randomized, double-blind, placebo-controlled, parallel, three-arm study was conducted. Healthy female subjects were equally randomized into three groups and took GSH (250 mg/d), GSSG (250 mg/d), or placebo orally for 12 weeks. At each visit at baseline and for 12 weeks, skin features including melanin index, wrinkles, and other relevant biophysical properties were measured. Blood samples were collected for safety monitoring. RESULTS: In generalized estimating equation analyses, melanin index and ultraviolet spots of all sites including face and arm when given GSH and GSSG tended to be lower than placebo. At some sites evaluated, subjects who received GSH showed a significant reduction in wrinkles compared with those taking placebo. A tendency toward increased skin elasticity was observed in GSH and GSSG compared with placebo. There were no serious adverse effects throughout the study. CONCLUSION: We showed that oral glutathione, 250 mg/d, in both reduced and oxidized forms effectively influences skin properties. Overall, glutathione in both forms are well tolerated.