Benefits and challenges experienced by participants on long-term methadone maintenance treatment in China: a qualitative study.

BACKGROUND: Methadone maintenance treatment (MMT) has been implemented in China for nearly two decades, with a significant decrease in the number of participants in recent years. However, there is a lack of comprehensive research focusing on the long-term effectiveness in the context of this decline, especially from the perspectives of MMT participants themselves. This study aims to address this gap by examining the benefits and challenges experienced by long-term MMT participants in China, to uncover potential causes of the decrease in participant numbers and to improve the effectiveness of the program. METHODS: We conducted semi-structured interviews with 21 long-term MMT participants (treatment duration ≥ 5 years) recruited through purposive sampling from 6 MMT clinics in the Guangdong Province, China, between December 2021 and August 2022. Thematic analysis was employed to analyze the transcribed interviews. Two analysts independently coded the data, and a third researcher double-coded 20% of transcripts to ensure intercoder reliability. RESULTS: Overall, participants corroborated the notable decline in MMT participants during their long-term MMT, citing death, arrest, and self-perceived abstinence from heroin, as their perceived driving factors. They reported positive changes in their health, family relationships, and social functioning. However, they identified economic hardship as their greatest challenge associated with MMT, further exacerbated by other barriers including the conflict of clinic opening hours and working schedules, discrimination from employers, and COVID-19-related restrictions. Additionally, participants identified issues with dose adjustment and emergency treatment continuation. CONCLUSIONS: This study outlines the overall improvement in the quality of life of long-term MMT participants. However, it highlights the need for official guidelines for dose adjustment and emergency treatment continuation as well as the provision of health education, job referrals, and flexibility of clinic opening times to facilitate the return to society receiving participants. Establishing a follow-up mechanism for those receiving MMT is also recommended to prevent relapses to heroin and other illicit substances.

The evaluation of preventive and control measures on congenital syphilis in Guangdong Province, China: a time series modeling study.

PURPOSE: To evaluate the effectiveness of preventive and control measures for congenital syphilis (CS) implemented since 2012 in Guangdong Province, China, and assess the epidemic trend in the near future. METHODS: The interrupted time series analysis was conducted to compare changes in slope and level of CS notification rate from 2005 to 2020 in Guangdong Province and its three regions with different economic developmental levels. The ARIMA model was established to predict the new CS case number of Guangdong Province in 2021. RESULTS: A total of 12,687 CS cases were reported from 2005 to 2020. The CS notification rate of the province had been increasing until 2012 (128.55 cases per 100,000 live births) and then been decreasing constantly, hitting the lowest point in 2020 (5.76 cases per 100,000 live births). The severe epidemic cluster shifted from the developed region to underdeveloped ones over time. The effectiveness of the measures was proved by the significant change in the slope of the notification rate which was found in both of the provinces (- 18.18, 95% CI - 25.63 to - 10.75) and two less-developed regions (- 10.49, 95% CI - 13.13 to - 7.86 and - 32.89, 95% CI - 41.67 to - 24.10, respectively). In the developed region where the notification rate had already been decreasing in the pre-implementation period, implementing these measures also aided in hastening the rate of descent. The CS case number in 2021 was predicted to be 48, indicating a low-level epidemic. CONCLUSIONS: The preventive and control measures have assisted Guangdong Province to control CS effectively, of which the supportive ones ensured a successful implementation. For resource-limited countries where CS is still endemic, especially guaranteeing the support in financial subsidy, professional training, supervision and so on might trigger the effectiveness of other measures and eventually make significant and sustainable progress.

Association Between Variables and Transitions Among No Opioid Use, Opioid Use, and Subsequent Dropout Among Participants on Methadone Treatment: A Retrospective Study Utilizing a Multistate Model.

BACKGROUND: Although previous studies have reported the variables that influence opioid use or dropout among participants receiving methadone treatment, limited attention has been given to the variables related to transitions among no opioid use, opioid use, and dropout. METHODS: This retrospective study utilized data collected from June 2010 to June 2022 at 11 methadone treatment clinics in Guangdong Province, China. Two transient states (no opioid use and opioid use) and 1 absorbing state (dropout) were defined based on monthly urine morphine test results and daily methadone intake records. We used a multistate model to explore the variables associated with transitions among no opioid use, opioid use, and dropout among participants. RESULTS: Among 3136 participants, with an average treatment duration of 497 days, 1646 (52.49%) underwent at least 1 period of opioid use, resulting in 3283 transitions from no opioid use to opioid use. The transitions between no opioid use and opioid use were significantly associated with variables such as age, gender, employment status, marital status, living situation, travel time to the clinic, human immunodeficiency virus and hepatitis C virus infection statuses, average methadone dosage, and attendance rates. The variables influencing participants' dropout varied depending on their opioid use behaviors. Additionally, the probability of a specified opioid use state remaining unchanged or transitioning to a different state at a defined time point would change over time. CONCLUSIONS: The opioid use behaviors of participants are dynamic. Methadone providers should offer targeted interventions based on participants' opioid use behaviors to effectively decrease rates of opioid use and improve retention.

Maternal Hypertension and Fecundability: A Population-Based Cohort Study.

BACKGROUND: The association of hypertension and blood pressure control with fecundability among women is not yet elucidated. The purpose of this study was to evaluate the hypothesis that maternal preconception hypertension would be associated with reduced fecundability and that blood pressure control could reduce excess risk. METHODS: Using the National Free Preconception Checkup Projects in Guangdong Province, China, 1422 couples whose female partners had been diagnosed with hypertension and 997 703 reference couples whose female partners were without hypertension were included in this prospective cohort study. Fecundability was measured by time to pregnancy (TTP) and infertility (TTP >12 months). RESULTS: Compared with women without hypertension, those with controlled hypertension (time ratio, 1.47 [95% CI, 1.24-1.73]) or uncontrolled hypertension (time ratio, 1.59 [95% CI, 1.34-1.90]) were associated with prolonged TTP and increased risk of infertility (relative risk, 1.19 [95% CI, 1.09-1.31]; relative risk, 1.24 [95% CI, 1.14-1.34]). However, using instrumental variable analyses, there was no significant association between blood pressure control and TTP (time ratio, 0.68 [95% CI, 0.34-1.36]; P=0.270) or infertility (relative risk, 0.97 [95% CI, 0.70-1.34]; P=0.849) among women with hypertension. These results were consistent in the propensity score matching and inverse probability of treatment weighting analyses. CONCLUSIONS: Maternal hypertension, with or without controlled blood pressure, was independently associated with prolonged TTP and an increased risk of infertility. These findings may provide insights for the implementation of preconception hypertension screening and the design of future trials.

Association of maternal preconception blood pressure with preterm birth: a population-based cohort study.

The association between maternal preconception blood pressure (BP) and preterm birth (PTB) is still unclear. The purpose of this study was to investigate the association between maternal preconception BP and PTB. This population-based cohort study included 715 984 Chinese women aged 20-49 years who participated in the National Free Preconception Health Examination Project and successfully had a singleton livebirth during 2014-2019 in Guangdong Province, China. Maternal preconception BP were measured by trained health workers. Multivariate logistic regression models and restricted cubic spline regressions were used to examine the association and dose-response relationship between maternal preconception BP and PTB, respectively. Maternal preconception hypertension was associated with the increased risk of PTB (adjusted odds ratios (aOR): 1.24; 95% CI: 1.14-1.34). Compared to women with normal preconception BP, the aORs for PTB were 1.09 (95% CI: 1.06-1.12), 1.24 (95% CI: 1.13-1.36), and 1.43 (95% CI: 1.15-1.79) for women with preconception elevated BP (120-139/ 80-89 mmHg, stage-1 hypertension (140-159/ 90-99 mmHg, and stage-2 hypertension (160-179/100-109 mmHg), respectively. According to the 2017 American College of Cardiology/American Heart Association criteria, maternal preconception elevated BP and hypertension were also significantly associated with an increased risk of PTB. Preconception systolic and diastolic BP showed a U-shaped (χ2 = 40.54; nonlinear P < 0.001) and linear (χ2 = 6.62; nonlinear P = 0.085) dose-response relationship with PTB, respectively. The association was modified by maternal age and preconception body mass index. These findings identify maternal preconception elevated BP and hypertension as a modifiable risk factor for PTB, providing evidence for future research studies, public health and clinical interventions.

Preconception Blood Pressure and Adverse Pregnancy Outcomes: A Population-Based Cohort Study.

BACKGROUND: Adverse pregnancy outcomes (APOs) share clinical features and risk factors with cardiovascular disease and there is an increasing prevalence of hypertension among reproductive women. However, the associations between maternal preconception blood pressure (BP) and APOs remain controversial and inconclusive. METHODS: This population-based cohort study used data of 567 127 mother-neonate-father triads from the National Free Preconception Checkup Project in Guangdong Province, China. Maternal BP levels within 1 year before pregnancy were classified using the American College of Obstetricians and Gynecologists definition of hypertension. The primary outcome was a composite of APOs, including preterm birth, small for gestational age, and perinatal infant death. Log-binomial and marginal structural binomial regressions were employed to estimate adjusted risk ratios and absolute risk differences, respectively. RESULTS: Compared with women with normal BP, women with elevated BP (adjusted risk ratio, 1.07 [95% CI, 1.05-1.09]; absolute risk difference, 1.03% [95% CI, 0.72%-1.29%]), hypertension (adjusted risk ratio, 1.25 [95% CI, 1.18-1.32]; and absolute risk difference, 3.42% [95% CI, 1.97%-5.42%]) had a higher risk of a composite of APOs. Compared with women with normal BP, women with elevated BP and hypertension had higher risks of multiple APOs, preterm birth, small for gestational age, and perinatal infant death. However, these associations attenuated with increasing duration of pregnancy preparation and were not statistically significant beyond 90 days of pregnancy preparation. CONCLUSIONS: Women with elevated BP or hypertension before pregnancy were associated with an increased risk of APOs. Preconception hypertension screening and control among women should not be ignored by policymakers, clinicians, and the general population.

Exploring factors jointly associated with recurrent relapse and dropout of methadone maintenance treatment clients in Guangdong, China: A retrospective cohort study.

BACKGROUND: Clients receiving methadone maintenance treatment (MMT) may experience multiple relapses, which may lead to dropout. However, previous studies mostly only explored the influencing factors of relapse or dropout separately. In this study, we investigated the influencing factors jointly associated with both recurrent relapse and dropout. METHODS: This study was conducted in 16 MMT clinics in Guangdong, China. Data on the clients' demographic characteristics; drug-related behavior; HIV, HCV, and urine morphine test results; and daily methadone doses were collected. The outcomes were time to recurrent relapse and time to dropout. A joint frailty model was used to explore factors jointly associated with recurrent relapse and dropout. The hazard ratios (HRs) of the covariates in the multivariable model were adjusted, with HR > 1 indicating a faster time to recurrent relapse and dropout. RESULTS: Among 1539 clients, 39.5% had ≥ 2 relapse events, and 90.8% of the clients dropped out. A high attendance rate was protective for recurrent relapse (HR50-80%=0.63, 95% CI: 0.51, 0.79; HR>80%=0.35, 95% CI: 0.28, 0.44) and dropout (HR50-80%=0.56, 95% CI: 0.47, 0.68; HR>80%=0.27, 95% CI: 0.23, 0.33). Being married (HR=0.80, 95% CI: 0.67, 0.96), having a fair relationship with family (HR=0.79, 95% CI: 0.67, 0.93) and drug injection (HR=0.80, 95% CI: 0.67, 0.96) were also protective for recurrent relapse. Female (HR=0.64, 95% CI: 0.50, 0.82) and a high methadone dose (≥60 ml/day; HR=0.79, 95% CI: 0.65, 0.96) were protective for dropout, and a longer traveling time to the clinic (>60 min; HR=1.59, 95% CI: 1.20, 2.10) was associated with an increased risk of dropout. CONCLUSIONS: It is common for clients to experience recurrent relapse and dropout. The findings suggest that MMT clinics should provide holistic interventions and appropriate methadone doses for clients to improve treatment compliance.

The Obesity-Related Dietary Pattern Is Associated with Higher Risk of Sleep Disorders: A Cross-Sectional Study from NHANES.

Evidence on the association between dietary patterns and sleep disorders is limited and controversial. In addition, studies evaluating the effect of dietary patterns on sleep disorders have seldom considered the critical role of obesity. We aimed to explore obesity-related dietary patterns and evaluate their impact on sleep disorders using data from the National Health and Nutrition Examination Survey 2005-2014. In total, 19,892 participants aged over 20 years with two-day dietary recalls were enrolled. Obesity-related dietary patterns explaining most variance in waist circumference and BMI simultaneously were extracted from twenty-six food groups by the using partial least squares method. Sleep disorder and sleep duration, which were defined by self-reported questions, were the primary and the secondary outcome, respectively. Generalized linear models were performed to estimate the association of sleep disorders and sleep duration with dietary patterns. Two types of dietary patterns were identified. The "high fats, refined grains, and meat" pattern was characterized by high intakes of solid fats, cured meat, potatoes, refined grains, meat, cheese, and added sugars. The "low whole grains, vegetables, and fruits" pattern was characterized by low intakes of oils, whole grains, nuts and seeds, milk, fruits, and several vegetables. Participants with the highest adherence to the "high fats, refined grains, and meat" pattern had a higher risk for sleep disorders (OR (95%CI): 1.43 (1.12, 1.84)) and shorter sleep duration (ß (95%CI): -0.17 (-0.26, -0.08)) compared to those with the lowest adherence. The corresponding associations for the "low whole grains, vegetables, and fruits" pattern were only significant for sleep duration (ß (95%CI): -0.26 (-0.37, -0.15)). Our results found that the dietary pattern characterized by high solid fats, cured meat, potatoes, refined grains, meat, cheese, and added sugars, was associated with a higher risk for sleep disorders and shorter sleep duration.

Couple-level determinants of syphilis infection among heterosexual married couples of reproductive age in Guangdong Province, China: A population-based cross-sectional study.

Background: Syphilis remains a major public health problem worldwide, and its prevention requires knowledge of factors that go beyond the individual-level. However, most syphilis-related studies have focused on individual-level and regional-level factors, neglecting couple-level factors. Thus, this study aimed to explore couple-level determinants of syphilis infection among heterosexual married couples. Methods: This population-based cross-sectional study used data from heterosexual married couples who participated in the National Free Preconception Health Examination Project in Guangdong Province, China during 2014-2019. The syphilis infection was tested by the rapid plasma reagin test. Couple-level data were obtained by combining information provided by the man and woman living in the same household. Multivariate logistic models were employed to explore the couple-level determinants of syphilis infection by gender after adjusting for potential confounders. Results: A total of 1,755,156 couples were recruited in this analysis. The seroprevalence was 0.25% (95%CI: 0.24-0.25%) and 0.26% (95%CI: 0.25-0.27%) among men and women, respectively. The median age was 28.0 (interquartile range, IQR: 25.0-31.0) years, and the median duration of marriage was 0.2 (IQR: 0.0-2.5) years. After adjusting for individual and regional-level variables, duration of marriage was a protective factor for syphilis infection in men (adjusted odds ratios, AOR: 0.97; 95% CI: 0.96-0.98) and women (AOR: 0.95, 95% CI: 0.94-0.96). The age gap and the difference in education level between the husband and wife were associated with syphilis infection, but these associations were somewhat different between men and women. Condom use was negatively associated with syphilis infection in men (AOR: 0.77; 95% CI: 0.70-0.84) and women (AOR: 0.77, 95% CI: 0.71-0.84). Our results also showed that couple mobility and the number of children were not statistically significant determinants of syphilis infection among heterosexual married couples. Conclusion: This study contributes to a more comprehensive understanding of syphilis outcomes in individuals in the context of marriage in China. Several couple-level factors are indeed associated with syphilis infection, but these associations differ between men and women. Couple-based strategies that engage both women and men and efforts to promote condom use among heterosexual married couples need to be developed and further evaluated for syphilis prevention.

The risk assessment of relapse among newly enrolled participants in methadone maintenance treatment: A group-LASSO based Bayesian network study.

Background: Relapse is a great barrier to improving the effectiveness of methadone maintenance treatment (MMT). Participants with different treatment durations could vary in their compliance with MMT, which may lead to different levels of relapse risk. This study aims to identify the risk factors for relapse and assess the relapse risk of MMT participants of different treatment durations. Method: This retrospective study used data collected from seven MMT clinics in Guangdong Province, China, from January 2010 to April 2017. Newly enrolled participants who received 6 (n = 903) and 12 (n = 710) months of consecutive treatment with complete data were included. We selected significant risk factors for relapse through the group lasso regression and then incorporated them into Bayesian networks to reveal relationships between factors and predict the relapse risk. Results: The results showed that participants who received 6-month treatment had a lower relapse rate (32.0%) than those of 12-month treatment (39.0%, P < 0.05). Factors including personal living status and daily methadone dose were only influential to those who received the 6-month treatment. However, age, age at the initial drug use, HIV infection status, sexual behaviors, and continuous treatment days were common factors of both durations. The highest relapse risk for those after the 6-month treatment was inferred as 66.7% while that of the 12-month treatment was 83.3%. Farmers and those who have high accessibility to MMT services may require additional attention. Conclusion: It is necessary to implement targeted interventions and education based on the treatment durations of participants to decrease the relapse rate. Meanwhile, those about HIV/sexually transmitted infection prevention and anti-narcotics should be held in the whole process.

Preconception syphilis seroprevalence and association with duration of marriage and age among married individuals in Guangdong Province, China: A population-based cross-sectional study.

BACKGROUND: Duration of marriage (DoM) and age are important characteristics of married individuals, who are the critical population for eliminating mother-to-child transmission (MTCT) of syphilis. A deep understanding of the preconception syphilis seroprevalence (PSS) and its distribution among this population may be able to help to eliminate MTCT. However, few population-based epidemiological studies have been focused on this group, and the association of DoM and age with PSS remains unclear. METHODOLOGY/PRINCIPAL FINDINGS: This study used data from 4,826,214 married individuals aged 21-49 years who participated in the National Free Preconception Health Examination Project in Guangdong Province, China, between 2014 and 2019. Syphilis was screened using the rapid plasma reagin (RPR) test. The seroprevalence time series, seroprevalence map, and hot spot analysis (HSA) were employed to visualize the spatiotemporal distribution. The restricted cubic spline (RCS) based on multivariate logistic regression was used to model the association of DoM and age with PSS. The interactions on the additive scale of DoM and age were also assessed. The PSS was 266.61 per 100,000 persons (95% CI: 262.03-271.24) and the burden was higher in economically underdeveloped area within the province. A strong J-shaped non-linearity association was observed between age and PSS. Specifically, the risk of seropositivity was relatively flat until 27 years of age among men and increased rapidly afterwards, with an adjusted odds ratio (aOR) of 1.13 (95% CI: 1.12-1.13) per unit. Among women, the risk of seropositivity was relatively flat until 25 years of age and increased rapidly afterwards with an aOR of 1.08 (95% CI: 1.08-1.09) per unit. DoM was negatively associated with PSS among married individuals. Moreover, the combined effects of age and DoM appeared to be synergistic. CONCLUSIONS/SIGNIFICANCE: Our findings suggest that attention should be paid to preventing syphilis in underdeveloped areas and that syphilis screening in newly married individuals who are in their late 20s or older should be recommended. Additionally, early syphilis prevention strategies should be implemented among young people as early as possible.

Exploration of dose tapering strategies for methadone maintenance treatment based on relapse risks: A subpopulation treatment effect pattern plot (STEPP) analysis.

BACKGROUND: Half of methadone maintenance treatment (MMT) participants experience a tapering phase, however, the guidelines vary from country to country and lack individualized strategies based on relapse risk. A detailed and individualized tapering strategy is needed in China. This study aims to explore dose tapering strategies for Chinese individuals with different relapse risks. METHODS: A retrospective study was conducted from 2006 to 2017 at nine MMT clinics in Guangdong, China, involving 549 participants. The end point was the first relapse within 12 months of the start of tapering. Relapse risks before tapering for each participant were determined from a Cox model. RESULTS: Out of 549 participants, 173 (31.5 %) relapsed within 12 months after tapering. Findings indicated that a taper dose of less than 5 mg/week is better than other taper doses. Subpopulation treatment effect pattern plot (STEPP) methodology revealed different tapering strategies benefit participants according to relapse risk before tapering. Overall, findings indicated that a less than 5 mg/week reduction in MMT dose is better than reductions of other amounts. For participants with a low relapse risk before tapering, a reduction of less than 2.5 mg/week in MMT dose is better than a 2.5-5 mg/week reduction. CONCLUSIONS: A taper dose of less than 5 mg/week appears to be the best dose tapering strategy for Chinese participants. Furthermore, for participants with a low relapse risk, a more gradual taper dose (less than 2.5 mg/week) works better than 2.5-5 mg/week. This benefit was not seen in participants with a high relapse risk before tapering.

Development and validation of equations for conversion from DAS28ESR and DAS28CRP to the SDAI in patients with rheumatoid arthritis.

INTRODUCTION: Disease Activity Score-28 (DAS28) with erythrocyte sedimentation rate (DAS28ESR), DAS28 with C-reactive protein (DAS28CRP), and simplified disease activity index (SDAI) are widely used to assess disease activity as low, moderate, or high or in remission in patients with rheumatoid arthritis (RA). However, these indicators can generate inconsistent results, influencing treatment decisions and limiting comparisons across studies. We aimed to establish equations for conversion from DAS28ESR and DAS28CRP to SDAI. METHODS: We conducted a retrospective study, including 933 outpatients who were simultaneously assessed using DAS28ESR, DAS28CRP, and SDAI. The patients were divided into a training set (70%) and a validation set (30%). We developed equations to convert DAS28ESR and DAS28CRP values into SDAI values by bisquare-weighted robust regression to obtain SDAI-DAS28ESR and SDAI-DAS28CRP. In addition to using kappa values to assess consistency, differences in disease activity classification between SDAI-DAS28ESR and SDAI-DAS28CRP were examined by the Stuart-Maxwell test and the Bowker test. RESULTS: Two quadratic equations were developed as follows: SDAI-DAS28ESR = 1.168 × (DAS28ESR)^2 - 2.432 × (DAS28ESR) + 2.649 and SDAI-DAS28CRP = 1.2 × (DAS28CRP)^2 - 0.3522 × (DAS28CRP) - 0.6014. After applying the equations, the Stuart-Maxwell test and the Bowker test were no longer significant between SDAI-DAS28ESR and SDAI or between SDAI-DAS28CRP and SDAI. The kappa values increased from 0.57 to 0.73 between SDAI-DAS28ESR and SDAI and 0.76 to 0.86 between SDAI-DAS28CRP and SDAI. CONCLUSION: SDAI-DAS28ESR and SDAI-DAS28CRP are interchangeable with the SDAI on the group level, which will facilitate comparisons among studies. In addition, the equations improved consistency between indicators. Key Points • There is disagreement in assessing disease activity in patients with rheumatoid arthritis between Disease Activity Score-28 (DAS28) with erythrocyte sedimentation rate (DAS28ESR), DAS28 with C-reactive protein (DAS28CRP), and simplified disease activity index (SDAI). • We developed and validated two quadratic equations to convert DAS28ESR and DAS28CRP into SDAI. We found there was no longer significant difference in disease activity between indicators after applying the equations. • This work may allow comparisons across studies which use different indicators.