Risk of contralateral breast cancer among Asian/Pacific Islander women in the United States.

PURPOSE: While breast cancer studies often aggregate Asian/Pacific Islander (API) women, as a single group or exclude them, this population is heterogeneous in terms of genetic background, environmental exposures, and health-related behaviors, potentially resulting in different cancer outcomes. Our purpose was to evaluate risks of contralateral breast cancer (CBC) among subgroups of API women with breast cancer. METHODS: We conducted a retrospective cohort study of women ages 18 + years diagnosed with stage I-III breast cancer between 2000 and 2016 in the Surveillance, Epidemiology and End Results registries. API subgroups included Chinese, Japanese, Filipina, Native Hawaiian, Korean, Vietnamese, Indian/Pakistani, and other API women. Asynchronous CBC was defined as breast cancer diagnosed in the opposite breast 12 + months after first primary unilateral breast cancer. Multivariable-adjusted subdistribution hazard ratios (SHR) and 95% confidence intervals (CI) were estimated and stratified by API subgroups. RESULTS: From a cohort of 44,362 API women with breast cancer, 25% were Filipina, 18% were Chinese, 14% were Japanese, and 8% were Indian/Pakistani. API women as an aggregate group had increased risk of CBC (SHR 1.15, 95% CI 1.08-1.22) compared to NHW women, among whom Chinese (SHR 1.23, 95% CI 1.08-1.40), Filipina (SHR 1.37, 95% CI 1.23-1.52), and Native Hawaiian (SHR 1.69, 95% CI 1.37-2.08) women had greater risks. CONCLUSION: Aggregating or excluding API patients from breast cancer studies ignores their heterogeneous health outcomes. To advance cancer health equity among API women, future research should examine inequities within the API population to design interventions that can adequately address their unique differences.

Reduction in Breast Cancer Death With Adjuvant Chemotherapy Among US Women According to Race, Ethnicity, and the 21-Gene Recurrence Score.

BACKGROUND: We previously showed the 21-gene breast recurrence score (RS) has lower prognostic accuracy for non-Hispanic Black (NHB) compared with non-Hispanic White (NHW) women with estrogen receptor (ER)-positive/HER2-negative breast cancer. The purpose of this study was to determine the clinical validity of the RS for predicting chemotherapy benefit as recommended in the current NCCN Guidelines for Breast Cancer among women from diverse racial/ethnic groups. METHODS: Using the SEER Oncotype database, we estimated propensity score-weighted hazard ratios (HRs) and 95% confidence intervals for breast cancer death with chemotherapy for women with ER-positive/HER2-negative, AJCC stages I-II, axillary node-negative, invasive breast cancer according to race/ethnicity. RESULTS: We included 6,033 (8.2%) Asian/Pacific Islander (API), 5,697 (7.8%) NHB, 6,688 (9.1%) Hispanic, and 54,945 (74.9%) NHW women. Breast cancer death was reduced with chemotherapy for NHB (HR, 0.48, 95% CI, 0.28-0.81), Hispanic (HR, 0.48; 95% CI, 0.25-0.94), and NHW (HR, 0.80; 95% CI, 0.65-0.99) women with an RS of 26 to 100. There was a nonsignificant reduction for API women (HR, 0.59; 95% CI, 0.28-1.24). For women with an RS of 11 to 25, there was no reduction in death for any racial/ethnic group. Among women aged ≤50 years, the reduction in breast cancer death with chemotherapy differed according to race (NHB: HR, 0.37 [95% CI, 0.20-0.67]; NHW: HR, 0.56 [95% CI, 0.44-0.74]; Pinteraction for chemotherapy * race <.0499). An exploratory subgroup analysis found that young NHB women may benefit from chemotherapy at a lower RS cutoff than other women. CONCLUSIONS: The RS was clinically validated as a predictive biomarker for NHB, Hispanic, and NHW women with ER-positive, axillary node-negative breast cancer, but it may underestimate the benefit of chemotherapy for young NHB women. If this finding is confirmed, the RS cutoff for recommending adjuvant chemotherapy for young NHB women with ER-positive, axillary node-negative breast cancer may need to be lower than for other women.

Evaluating the use of methods to mitigate bias from non-transient medications in the case-crossover design: A systematic review.

PURPOSE: The case-crossover design is a self-controlled study design used to compare exposure immediately preceding an event occurrence with exposure in earlier control periods. The design is most suitable for transient exposures in order to avoid biases that can be problematic when using the case-crossover design for non-transient (i.e., chronic) exposures. Our goal was to conduct a systematic review of case-crossover studies and its variants (case-time-control and case-case-time-control) in order to compare design and analysis choices by medication type. METHODS: We conducted a systematic search to identify recent case-crossover, case-time-control, and case-case-time-control studies focused on medication exposures. Articles indexed in MEDLINE and EMBASE using these study designs that were published between January 2015 and December 2021 in the English language were identified. Reviews, methodological studies, commentaries, articles without medications as the exposure of interest, and articles with no available full text were excluded. Study characteristics including study design, outcome, risk window, control window, reporting of discordant pairs, and inclusion of sensitivity analyses were summarized overall and by medication type. We further evaluated the implementation of recommended methods to account for biases introduced by non-transient exposures among articles that used the case-crossover design on a non-transient exposure. RESULTS: Of the 2036 articles initially identified, 114 articles were included. The case-crossover was the most common study design (88%), followed by the case-time-control (17%), and case-case-time-control (3%). Fifty-three percent of the articles included only transient medications, 35% included only non-transient medications, and 12% included both. Across years, the proportion of case-crossover articles evaluating a non-transient medication ranged from 30% in 2018 to 69% in 2017. We found that 41% of the articles that evaluated a non-transient medication did not apply any of the recommended methods to account for biases and more than half of which were conducted by authors with no previous publication history of case-crossover studies. CONCLUSION: Using the case-crossover design to evaluate a non-transient medication remains common in pharmacoepidemiology. Researchers should apply appropriate design and analysis choices when opting to use a case-crossover design with non-transient medication exposures.

Impact of socioeconomic status and rurality on cancer-specific survival among women with de novo metastatic breast cancer by race/ethnicity.

PURPOSE: There are approximately 150,000 women living with metastatic breast cancer (mBC) in the United States. Disparities in de novo mBC incidence and mortality exist across race/ethnicity, socioeconomic status (SES), and rurality. However, how SES and rurality independently impact mBC outcomes across different racial/ethnic groups is not fully understood. The purpose of this study was to determine the impact of SES and rurality on cancer-specific mortality among women with mBC by race/ethnicity. METHODS: We conducted a large, population-based retrospective cohort study in women aged 18 + years diagnosed with de novo mBC using the Surveillance, Epidemiology and End Results Census Tract-level SES and Rurality Database (2000-2015). Associations between SES/rurality and cancer-specific mortality were determined using Fine and Gray regression models. Subdistribution hazard ratios (SHR) and 95% confidence intervals (CI) by race/ethnicity and hormone receptor (HR) status were calculated. RESULTS: A cohort of 33,976 women were included with the majority being White (67%), 17% Black, 0.4% American Indian/Alaskan Native, 6% Asian/Pacific Islander, and 10% Latina/Hispanic. We observed the greatest increased risk of BC mortality among Black women with HR-negative mBC residing in neighborhoods with lower SES (lowest versus highest quintile: SHR 1.38, 95% CI 1.00-1.90) and in rural areas compared to urban areas (SHR 1.27, 95% CI 1.01-1.59). CONCLUSION: Overall, BC-specific survival among women with de novo mBC differs by race/ethnicity, with the greatest adverse impacts of SES and rurality affecting Black women with HR-negative disease.

[Health Awareness and Culturally Appropriate Epidemic Prevention Strategy for COVID-19 in Taiwan's Indigenous Townships].

The COVID-19 pandemic has imposed an extremely heavy burden on the medical system in Taiwan. Thus, improving the effectiveness of epidemic prevention efforts and reducing the related burdens on medical staff are critical. Between the initial outbreak of COVID-19 in Taiwan in early 2022 until May of that same year, two townships with high percentages of indigenous (Malayo-Polynesian) residents reported the highest rates of infection nationwide. As the indigenous culture in these and other similar townships differs significantly from Taiwan's mainstream culture, determining how to improve health awareness and provide culturally appropriate treatments during this pandemic in indigenous communities is vital. In the context of Taiwan's indigenous population, this paper addresses the importance of improving health awareness, proposes how to foster a more-friendly health awareness environment, and suggests a strategy for providing effective healthcare under current pandemic conditions. Prevention measures include improving the ability of indigenous citizens to assess the correctness of information provided, improving compliance with epidemic prevention measures, improving knowledge regarding vaccines and rapid screening reagents, and improving the notification process for diagnoses. A culturally appropriate township-based promotion strategy for epidemic prevention should be proposed to increase the effectiveness of epidemic prevention and health promotion to improve health conditions in indigenous communities.

[Health of Indigenous People and Cultural Sovereignty: Developing the Competence of Culture Safety Instructors Under the Long-Term Care 2.0 Program].

Taiwan`s various ethnic groups, including 16 indigenous groups, represent disparate distinct cultures and backgrounds. In long-term care, culturally safe services that reflect cultural expectations and practices must be provided to older-adult recipients of care. As frontline healthcare workers face practical challenges in providing these services appropriately, "cultural safety instructors" may be used to help facilitate indigenous cultural care. Therefore, it is vital to develop the role function and cultural competence of these instructors. In this article, related instructor qualifications, course contents, and expected results of an indigenous cultural safety instruction program are presented based on the theory of cultural competence and cultural safety. In addition, relevant perspectives on cultural safety instructors and their cross-cultural competence specific to indigenous peoples, including Dimitrov and Haque (2016) and Leininiger (1996), are integrated. It is hoped that this study promotes reflection and provides a reference on practice and policies related to long-term care for indigenous people.

Statin Dosing Instructions, Medication Adherence, and Low-Density Lipoprotein Cholesterol: a Cohort Study of Incident Statin Users.

BACKGROUND: Robust evidence is lacking on optimal timing of statin administration and its impact on patient outcomes. OBJECTIVE: This study aims to evaluate among incident statin users the relationship between those prescribed evening vs. daily dosing instructions, medication adherence, and changes in low-density lipoprotein cholesterol (LDL-c). DESIGN: This is an observational cohort study at Sutter Health, a community-based healthcare system, 2010-2016. PARTICIPANTS: Patients were ≥ 35 years of age as of the first statin prescription (baseline), with 12 to 36 months of electronic health record activity before and after baseline. Incident use was defined as no statin prescription in 12 months prior to baseline. MAIN MEASURES: Differences in medication adherence (proportion of days covered ≥ 0.80) over 12 months from baseline and mean change in LDL-c between 12 and 24 months from baseline were measured using regression modeling, adjusting for baseline demographics and clinical, prescriber, and statin characteristics. KEY RESULTS: Among 31,252 patients with valid statin prescriptions between 2010 and 2016, 5099 eligible incident statin users (mean age, 63 years) were identified, of whom 53% were prescribed evening and 47% daily dosing instructions. No difference in likelihood of statin adherence over 12 months was observed for evening vs. daily dosing (adjusted odds ratio [OR] 0.90; 95% CI 0.75, 1.08). No differences were observed in mean change in LDL-c (adjusted mean difference 1.42 mg/dL; 95% CI - 1.02, 3.89) or likelihood of attaining LDL-c < 70 mg/dL (adjusted OR 0.83; 95% CI 0.67, 1.04) for evening vs. daily dosing over a mean of 19 months follow-up. CONCLUSIONS: Among incident statin users from a real-world clinical setting, those with daily and evening dosing instructions had similar adherence rates and mean changes in LDL-c. Given potential clinical equipoise for evening and daily dosing, clinicians should consider patient-tailored statin dosing instructions to reduce potentially unnecessary regimen complexity.

[Applying Intelligent Technology in Gender Competence Training for Nurses].

Despite an increased focus on the healthcare rights of people of different genders and the establishment of gender policies related to healthcare in Taiwan, the promotion of gender rights in nursing education and clinical care remains unsatisfactory. Given the increasingly diversified nature of healthcare systems and nursing knowledge bases, many experienced nurses have expressed the need for self-growth through continuing education and in-service training. The professional knowledge required of nurses increases continuously, and gender issues have received little attention in conventional nursing education. Consequently, gender education has been overlooked because of insufficient teaching time and a lack of qualified teachers. In promoting online courses for nurses, the government should focus on the different nursing care needs of different genders and sexual orientations as well as design online courses based on intelligent technology that satisfy the desire of nurses to improve their gender competence. This study adopts an intelligent technology perspective in order to highlight the importance of gender competence for nurses and to propose incorporating augmented reality into case scenarios that facilitate the creation of online healthcare courses and teaching materials that enhance gender competence. This approach may effectively resolve the problem of teachers having insufficient time to provide gender education effectively. Nurses must possess diverse gender perspectives and reinforce their gender competence and cross-disciplinary integration capabilities in order to provide appropriate care for patients of different gender identities and sexual orientations.

[Reflection on the Health and Gender Mainstreaming of Indigenous Women in Taiwan].

Gender and race issues have caused rapid cultural and societal changes to affect the healthcare of indigenous women, which involves complicated, cultural meanings. The present paper begins by outlining the gender perspective and then elaborates on the present gender mainstreaming and status of indigenous women's healthcare in Taiwan. Furthermore, this paper identifies the current difficulties experienced by Taiwanese indigenous women, including those related to the lack of adequate healthcare data and gender analyses on indigenous women and the lack of regular research on healthcare strategies for indigenous women. Therefore, the present paper proposes to establish health policy references that are gender and race sensitive. The health policy not only addresses racial and gender concerns regarding healthcare information but also focuses on the analysis of indigenous healthcare information. Indigenous women's health concerns are discussed here within the framework of healthcare policy through the perspective of gender mainstreaming. Additionally, we will analyze and evaluate the effects of gender in order to establish inspection and management processes that integrate the concept of gender into policy development and implementation, thus promoting relevant health policies. During the processes of planning, implementing, and evaluating healthcare policies, women should unite to contribute toward indigenous women's health policies and gender mainstreaming.

Association of Social Determinants and Tumor Biology With Racial Disparity in Survival From Early-Stage, Hormone-Dependent Breast Cancer.

Importance: Black women with hormone receptor-positive breast cancer experience the greatest racial disparity in survival of all breast cancer subtypes. The relative contributions of social determinants of health and tumor biology to this disparity are uncertain. Objective: To determine the proportion of the Black-White disparity in breast cancer survival from estrogen receptor (ER)-positive, axillary node-negative breast cancer that is associated with adverse social determinants and high-risk tumor biology. Design, Setting, and Participants: A retrospective mediation analysis of factors associated with the racial disparity in breast cancer death for cases diagnosed between 2004 and 2015 with follow-up through 2016 was carried out using the Surveillance, Epidemiology, and End Results (SEER) Oncotype registry. The study included women in the SEER-18 registry who were aged 18 years or older at diagnosis of a first primary invasive breast cancer tumor that was axillary node-negative and ER-positive, who were Black (Black), non-Hispanic White (White), and for whom the 21-gene breast recurrence score was available. Data analysis took place between March 4, 2021, and November 15, 2022. Exposures: Census tract socioeconomic disadvantage, insurance status, tumor characteristics including the recurrence score, and treatment variables. Main Outcomes and Measures: Death due to breast cancer. Results: The analysis with 60 137 women (mean [IQR] age 58.1 [50-66] years) included 5648 (9.4%) Black women and 54 489 (90.6%) White women. With a median (IQR) follow-up time of 56 (32-86) months, the age-adjusted hazard ratio (HR) for breast cancer death among Black compared with White women was 1.82 (95% CI, 1.51-2.20). Neighborhood disadvantage and insurance status together mediated 19% of the disparity (mediated HR, 1.62; 95% CI, 1.31-2.00; P < .001) and tumor biological characteristics mediated 20% (mediated HR, 1.56; 95% CI, 1.28-1.90; P < .001). A fully adjusted model that included all covariates accounted for 44% of the racial disparity (mediated HR, 1.38; 95% CI, 1.11-1.71; P < .001). Neighborhood disadvantage mediated 8% of the racial difference in the probability of a high-risk recurrence score (P = .02). Conclusions and Relevance: In this study, racial differences in social determinants of health and indicators of aggressive tumor biology including a genomic biomarker were equally associated with the survival disparity in early-stage, ER-positive breast cancer among US women. Future research should examine more comprehensive measures of socioecological disadvantage, molecular mechanisms underlying aggressive tumor biology among Black women, and the role of ancestry-related genetic variants.

Lifestyle change program engagement in real-world clinical practice: a mixed-methods analysis.

Participant engagement in structured lifestyle change programs (LCPs) is essential for adopting behaviors that promote weight loss; however, the challenges to, and facilitators that promote, engagement with such programs are not well understood. We conducted a mixed-methods study among real-world LCP participants to assess factors associated with program engagement and to examine the reasons for withdrawal. Using electronic health records (EHR), we identified LCP eligible participants between 2010 and 2017. Multivariable logistic regression was used to assess associations between program engagement and baseline characteristics. Semi-structured interviews with LCP participants were conducted and thematically analyzed to examine reasons for withdrawal. A total of 1,813 LCP participants were included. The median number of sessions attended was 10 of 21-25 sessions. Highest LCP engagement was associated with factors potentially related to self-efficacy/motivation, such as older age, higher baseline weight, prior healthcare utilization and an absence of a history of smoking or depression. Engagement was also negatively associated with being Non-Hispanic Black versus White. The qualitative analysis of the interviews revealed four general themes pertaining to participants' withdrawal: competing priorities, perceived program effectiveness, characteristics of the program, and facilitator-related factors. Taken together, results from this mixed-methods study suggest that motivation and self-efficacy are important for program engagement; future LCP enhancements should incorporate flexible formats that may help participants manage competing priorities and maximize personal and cultural relevance for all racial/ethnic groups, especially those who have not benefitted fully. Furthermore, participants should be encouraged to set realistic goals to manage expectations.

Engaging in a structured lifestyle change program (LCP) is essential to learn healthy behaviors, however, it is not well understood. This study examined factors associated with program engagement and reasons for program withdrawal at a large healthcare system. Highest LCP engagement was found to be associated to factors potentially related to self-efficacy/motivation including older age, higher initial weight, and prior healthcare utilization. Non-Hispanic Black, history of smoking, and prior diagnosis of depression were found to be negatively associated with LCP engagement. Program withdrawal was related to four themes: competing priorities, perceived program effectiveness, characteristics of the program, and facilitator-related factors. These findings suggest that motivation and self-efficacy are important for behavior change program engagement.

Relationship Between Motor Skills and Language Abilities in Children With Autism Spectrum Disorder.

OBJECTIVES: Few studies have examined the relationship between language abilities and specific motor skills in toddlers with autism spectrum disorder (ASD). The aim of this study was to compare the relationship of receptive language (RL) and expressive language (EL) abilities with motor functioning in toddlers with ASD aged 24 to 36 months and their peers with typical development (TD). Furthermore, the study compared multidimensional motor functioning in toddlers with ASD with delayed RL and EL development and toddlers with ASD and typical RL and EL development. The predictive powers of the motor skills were examined for the group with delayed RL and EL development. METHODS: The language abilities of 38 toddlers with ASD and 38 age-matched toddlers with TD were evaluated using the Receptive and Expressive Language Subscales of the Mullen Scale of Early Learning, and their motor skills were assessed using the Peabody Developmental Motor Scales, Second Edition. RESULTS: Significant correlations between language ability and motor functioning were observed in the ASD and TD groups. The ASD group with delayed RL and EL development had lower scores for multidimensional motor functioning than the ASD group with typical RL and EL development and the TD group. Moreover, the risks of delayed EL and RL development could be predicted by the lower motor scores in toddlers with ASD. CONCLUSIONS: The positive correlation between language abilities and motor functioning in toddlers with ASD indicated potential connections between the early onsets of motor and speech-language impairments in these toddlers. IMPACT: The results may have implications for the development of motor-based interventions targeting language development in young children with ASD.

Effectiveness of a Group-Based Lifestyle Change Program Versus Usual Care: An Electronic Health Record, Propensity Score-Matched Cohort Study.

INTRODUCTION: Translational lifestyle change programs for community and clinical settings have been available for a decade, yet there are limited data on their comparative effectiveness. This study examines the effectiveness of a Centers for Disease Control and Prevention-aligned lifestyle change program relative to usual care in clinical practice. METHODS: This was an electronic health record-based retrospective cohort study conducted in a community-based healthcare system. Investigators identified adult program participants and usual-care patients in the electronic health record between 2010 and 2018 and defined their index date (baseline) as the first lifestyle change program encounter or a random encounter date, respectively. Participants were matched 1:2 to usual-care patients on baseline demographics and clinical characteristics using propensity-score methods. Changes in body weight and blood pressure were examined from baseline through 24 months. RESULTS: The authors identified 2,833 program participants and 438,432 usual-care patients meeting study eligibility criteria. A total of 2,833 program participants were matched to 4,776 usual-care patients; the average age was 54 years, and 80% of the participants were female. Program participation was associated with a 1.9- and 1.6-fold higher prevalence of clinically meaningful (≥5%) weight loss at 12- and 24-month follow-up than usual care and a higher prevalence of blood pressure control at 12 months but not at 24 months. Patients without type 2 diabetes at baseline had more pronounced outcomes than those with type 2 diabetes. CONCLUSIONS: This study demonstrates the effectiveness of an evidence-based, Centers for Disease Control and Prevention-aligned lifestyle change program in reducing cardiometabolic risk factors compared with usual care in clinical practice, with long-term reductions in weight and transient reductions in blood pressure.

Statin utilization and low-density lipoprotein cholesterol in statin-treated patients with atherosclerotic cardiovascular disease: Trends from a community-based health care delivery system, 2002-2016.

BACKGROUND: A better understanding of patterns in statin utilization and low-density lipoprotein cholesterol (LDL-C) among patients with atherosclerotic cardiovascular disease (ASCVD) in a clinical practice setting is needed. OBJECTIVES: The objective of this study was to examine statin utilization and LDL-C among new statin users with ASCVD. METHODS: This retrospective study used an electronic health record database from a community-based health care system. We identified ASCVD patients ≥21 years of age with a new statin prescription during the study period (2002-2016). Outcomes included high-intensity statin therapy (HIST) prescribing at treatment initiation, medication adherence (defined as proportion of days covered ≥0.80), statin therapy titrations rates, and changes in LDL-C during follow-up. RESULTS: Among 6199 eligible patients, mean follow-up was 16.8 months. At treatment initiation, 16.6% of patients received HIST. Approximately 53% of patients were adherent to statin regimens. Mean percent reduction in LDL-c was 25% during follow-up; 18% of patients, overall, and 30% of those initiating on HIST attained LDL-C reductions >50%. Rates of statin intensity-level increases were 8.4 per 100 person-years. HIST prescribing increased over time, beginning after generic atorvastatin availability and preceded treatment guidelines by two years. Initiation on HIST, higher adherence, and treatment intensification during follow-up were independent predictors of attaining LDL-C goals of <70 mg/dL or <100 mg/dL. CONCLUSIONS: In a community-based health care system, modest LDL-C lowering for secondary ASCVD prevention is likely driven by suboptimal adherence and low HIST prescribing and treatment intensification rates. Clinician and patient education are needed to reduce clinical inertia and improve medication adherence to better manage ASCVD.

Longitudinal Weight Outcomes From a Behavioral Lifestyle Intervention in Clinical Practice.

PURPOSE: The purpose of this electronic health record (EHR)-based retrospective cohort study was to characterize a population of patients participating in a 12-month, lifestyle change program in a community-based health system and to examine longitudinal weight outcomes. METHODS: Program participants were identified in the EHRs of a health care delivery system across 18 sites between 2010 and 2017. Outcomes were mean weight change and proportion of patients with ≥5% weight loss through 24 months from program initiation. RESULTS: Among 4463 program participants, 3156 met study eligibility criteria, with a mean ± SD age of 53.5 ± 13.1 years; 77.7% were women. Mean baseline weight ± SD was 101.3 ± 23.8 kg. Three main cardiometabolic risk groups were identified: prediabetes/high risk for diabetes (47.3%), overweight/obese in the absence of elevated diabetes risk (27.2%), and existing diabetes (23.9%). Maximal mean weight loss was 3.9% at 6 months from baseline. At 12 and 24 months from baseline, mean weight loss was 3.2% and 2.3%, respectively, with 31% and 29% of participants attaining ≥5% weight loss. Long-term weight outcomes were similar across risk groups. CONCLUSIONS: A lifestyle change program in a clinical practice setting is associated with modest weight loss, sustained through 24 months, among participants with a range of cardiometabolic risk factors. More than one-quarter of participants achieve ≥5% weight loss, regardless of cardiometabolic risk.

Multidimensional Developments and Free-Play Movement Tracking in 30- to 36-Month-Old Toddlers With Autism Spectrum Disorder Who Were Full Term.

BACKGROUND: Few studies have investigated multidimensional developments and free-play movement performance in toddlers with an early diagnosis of autism spectrum disorder (ASD). OBJECTIVE: This study compared cognitive, motor, and behavioral developments and free-play movement performance in toddlers with ASD who were full term (FT-ASD), toddlers who were full term and are typically developing (FT-TD), and toddlers who were born preterm and had a very low birth weight (VLBW-PT). DESIGN: This was a prospective cross-sectional study. METHODS: Forty-five 30- to 36-month-old age-matched toddlers were recruited and divided into FT-ASD, FT-TD, and VLBW-PT groups. Their developments were examined using the Mullen Scales of Early Learning; the Peabody Developmental Motor Scales, Second Edition; the Child Behavior Checklist for Ages 1.5 to 5; and the Repetitive Behavior Scale-Revised. In addition, the toddlers' free-play movements were tracked in laboratory settings using an automatic movement tracking system. RESULTS: Toddlers with FT-ASD exhibited lower cognitive and motor scores and a higher degree of behavioral problems compared with toddlers with FT-TD or VLBW-PT. Furthermore, the movement tracking data in a free-play setting revealed that toddlers with FT-ASD displayed a higher degree of turning velocity, a higher moving time, and a higher frequency of moving toward the peripheral region compared with toddlers with FT-TD or VLBW-PT. Moreover, several motor developmental and movement-tracking indicators were found to correlate with behavioral problems and cognitive scores in toddlers with FT-ASD. LIMITATIONS: The study results may have been affected by the small sample size, the cross-sectional design, and tracking only the whole body without subtle movements or segmental motions. CONCLUSIONS: The findings suggest varied aspects of co-occurring developmental conditions and movement-based problems in toddlers with FT-ASD. Using standardized and sensitive measures for the early assessment of perceptuo-motor impairments is necessary for timely early intervention for such toddlers.

A Long Neglected Damper in the El Niño--Typhoon Relationship: a 'Gaia-Like' Process.

Proposed in the early 1970's, the Gaia hypothesis suggests that our planet earth has a self-regulating ability to maintain a stable condition for life. Tropical cyclone (TC) is one of the earth's most hazardous disasters; it is intriguing to explore whether 'Gaia-like' processes may exist in nature to regulate TC activities. El Niño can shift the forming position of the Western Pacific typhoons away from land. This shift enables typhoons to travel longer distances over ocean and is known to be a positive process to promote TCs to achieve higher intensity. What is neglected, however, is that there co-exists a negative process. Here we show that during El Niño, typhoons intensify over region undergoing strong ocean subsurface shoaling where upper ocean heat content can drop by 20-50%. This 'worsen' ocean pre-condition can effectively reduce ocean's energy supply for typhoon intensification during typhoon-ocean interaction. We find this an elegant, 'Gaia-like' process demonstrating nature's self-regulating ability. Though during El Niño, typhoons can take advantage of the longer travelling distance over ocean to achieve higher intensity, nature is also providing a damper to partially cancel this positive impact. Without the damper, the situation could be even worse.

Association of polymorphisms in EPHX1, UGT2B7, ABCB1, ABCC2, SCN1A and SCN2A genes with carbamazepine therapy optimization.

AIM: Carbamazepine (CBZ) is one of the most widely used antiepileptic drugs. The aim of the present study is to investigate the impacts of polymorphisms in genes related to pharmacokinetic and pharmacodynamic pathways of CBZ on the large interindividual variability in dosages and concentrations. METHODS & RESULTS: Genetic polymorphisms in the candidate genes were detected in 234 epileptic patients under maintenance CBZ monotherapy by real-time PCR and PCR-RFLP. Results of statistical analysis demonstrated that carriers of the variant SCN1A IVS5-91G>A and EPHX1 c.337T>C allele tended to require higher CBZ dosages and lower ln(concentration-dose ratios) than noncarriers (p < 0.0001) and the homozygous carriers also seemed to require higher CBZ dosages and lower ln(concentration-dose ratios) (p < 0.0001). In addition, the multiple regression model of concentration-dose ratio of CBZ also revealed that genetic variants in SCN1A, EPHX1 and UGT2B7 genes interactively affect the concentration-dose ratio of CBZ (adjusted r(2) = 55%). CONCLUSION: The present study identified genetic factors associated with CBZ therapy optimization and provided useful information for individualized CBZ therapy in epileptic patients. Further studies in larger populations are needed to confirm our results.

Effects of polymorphisms in six candidate genes on phenytoin maintenance therapy in Han Chinese patients.

AIM: The present study aimed to investigate the associations between variants in pharmacokinetic- and pharmacodynamic-related genes with the dosages, concentrations and concentration-dose ratios (CDRs) of phenytoin (PHT). METHODS & RESULTS: Eleven genetic polymorphisms in the six candidate genes were detected in 269 epileptic patients under maintenance PHT monotherapy by real-time PCR and PCR-RFLP. Results of a bivariate analysis demonstrated that among tested polymorphisms, carriers of the variant CYP2C9*3 tended to require significantly lower maintenance PHT dosages than wild-type carriers (p < 0.0001); on the other hand, carriers of the variants CYP2C9*3 or CYP2C19*3 revealed significantly higher CDRs than wild-type carriers (p < 0.004). In a further multivariate analysis, variants in SCN1A, CYP2C9, CYP2C19 and ABCB1 genes were significantly associated with CDRs of PHT under adjustment of age, gender and epilepsy classifications (adjusted r(2) = 20.07%). CONCLUSION: The results of present study indicated that polygenic analysis may provide useful information in PHT therapy optimization.

Applying preoperative multidetector computed tomography to bilateral coronary artery fistulas.

Coronary artery fistula arising from both the right coronary artery and the circumflex coronary artery is rare. A 28-year-old woman with non-insulin-dependent diabetes mellitus and end-stage renal disease who was on regular hemodialysis complained of recent progressive exertional dyspnea. Congestive heart failure was diagnosed during work-up for simultaneous kidney and pancreas transplantation. Bilateral coronary fistulas draining into the coronary sinus were found by coronary angiography and further characterized by multidetector computed tomography followed by 3D reconstruction preoperatively. The operation was performed smoothly without heart arrest.