Zhitong Zhang

Effect of a training and educational intervention for physicians and caregivers on antibiotic prescribing for upper respiratory tract infections in children at primary care facilities in rural China: a cluster-randomised controlled trial

BACKGROUND Inappropriate antibiotic prescribing contributes to the generation of drug resistance worldwide, and is particularly common in China. We assessed the effectiveness of an antimicrobial stewardship programme aiming to reduce inappropriate antibiotic prescribing in paediatric outpatients by targeting providers and caregivers in primary care hospitals in rural China. METHODS We did a pragmatic, cluster-randomised controlled trial with a 6-month intervention period. Clusters were primary care township hospitals in two counties of Guangxi province in China, which were randomly allocated to the intervention group or the control group (in a 1:1 ratio in Rong county and in a 5:6 ratio in Liujiang county). Randomisation was stratified by county. Eligible participants were children aged 2-14 years who attended a township hospital as an outpatient and were given a prescription following a primary diagnosis of an upper respiratory tract infection. The intervention included clinician guidelines and training on appropriate prescribing, monthly prescribing peer-review meetings, and brief caregiver education. In hospitals allocated to the control group, usual care was provided, with antibiotics prescribed at the individual clinicians discretion. Patients were masked to their allocated treatment group but doctors were not. The primary outcome was the antibiotic prescription rate in children attending the hospitals, defined as the cluster-level proportion of prescriptions for upper respiratory tract infections in 2-14-year-old outpatients, issued during the final 3 months of the 6-month intervention period (endline), that included one or more antibiotics. The outcome was based on prescription records and analysed by modified intention-to-treat. This study is registered with the ISRCTN registry, number ISRCTN14340536. FINDINGS We recruited all 25 eligible township hospitals in the two counties (14 hospitals in Rong county and 11 in Liujiang county), and randomly allocated 12 to the intervention group and 13 to the control group. We implemented the intervention in three internal pilot clusters between July 1, 2015, and Dec 31, 2015, and in the remaining nine intervention clusters between Oct 1, 2016 and March 31, 2016. Between baseline (the 3 months before implementation of the intervention) and endline (the final 3 months of the 6-month intervention period) the antibiotic prescription rate at the individual level decreased from 82% (1936/2349) to 40% (943/2351) in the intervention group, and from 75% (1922/2548) to 70% (1782/2552) in the control group. After adjusting for the baseline antibiotic prescription rate, stratum (county), and potentially confounding patient and prescribing doctor covariates, this endline difference between the groups represented an intervention effect (absolute risk reduction in antibiotic prescribing) of -29% (95% CI -42 to -16; p=0·0002). INTERPRETATION In Chinas primary care setting, pragmatic interventions on antimicrobial stewardship targeting providers and caregivers substantially reduced prescribing of antibiotics for childhood upper respiratory tract infections. FUNDING Department of International Development (UKAID) through Communicable Diseases Health Service Delivery.

Evaluation of a systematic cardiovascular disease risk reduction strategy in primary healthcare: an exploratory study from Zhejiang, China

BACKGROUND In China, cardiovascular disease (CVD) risk reduction strategies are not systematically implemented in primary healthcare (PHC). We conducted an exploratory study to evaluate the preliminary effectiveness of our systematic CVD risk reduction package in one township hospital of Zhejiang. METHODS Using the Asian Equation, we selected subjects aged 40-74 years with a calculated 10-year CVD risk of 20% or higher from the existing resident health records and research checkup. The subjects were provided, as appropriate, with the low-dose combination of CVD-preventive drugs (antihypertensive drugs, aspirin, statin), lifestyle modification and adherence strategies monthly. The intervention was piloted for three months in 2012, preceding the conduct of a cluster-based randomized controlled trial (RCT). RESULTS A total of 153 (40%) subjects were recruited, with an average total 10-year risk of CVD of 28.5 ± 7.9%. After intervention, the appointment rate was up to 90%. An upward trend was observed for the use of CVD-preventive drugs. The smoking rates significantly reduced from 38 to 35%, with almost no change for salt reduction. The systolic blood pressure (BP) and diastolic BP decreased slightly. CONCLUSION A holistic CVD risk reduction approach shows preliminary effects in a rural PHC setting of Zhejiang, China. However, further understanding is needed regarding its long-term effectiveness and feasibility in PHC practices. Our cluster-based RCT will provide the highest level of evidence for the policy development of preventing CVD in a rural PHC of China.

Antibiotic Prescribing for Upper Respiratory Infections Among Children in Rural China: a Cross-Sectional Study of Outpatient Prescriptions

ABSTRACT Background: Overuse of antibiotics contributes to the development of antimicrobial resistance. Objective: This study aims to assess the condition of antibiotic use at health facilities at county, township and village levels in rural Guangxi, China. Methods: We conducted a cross-sectional study of outpatient antibiotic prescriptions in 2014 for children aged 2–14 years with upper respiratory infections (URI). Twenty health facilities were randomly selected, including four county hospitals, eight township hospitals and eight village clinics. Prescriptions were extracted from the electronic records in the county hospitals and paper copies in the township hospitals and village clinics. Results: The antibiotic prescription rate was higher in township hospitals (593/877, 68%) compared to county hospitals (2736/8166, 34%) and village clinics (96/297, 32%) (p < 0.001). Among prescriptions containing antibiotics, county hospitals were found to have the highest use rate of broad-spectrum antibiotics (82 vs 57% [township], vs 54% [village], p < 0.001), injectable antibiotics (65 vs 43% [township], vs 33% [village], p < 0.001) and multiple antibiotics (47 vs 15% [township], vs 0% [village], p < 0.001). Logistic regression showed that the likelihood of prescribing an antibiotic was significantly associated with patients being 6–14 years old compared with being 2–5 years old (adjusted odds ratio [aOR] = 1.3, 95% CI 1.2–1.5), and receiving care at township hospitals compared with county hospitals (aOR = 5.0, 95% CI 4.1–6.0). Prescriptions with insurance copayment appeared to lower the risk of prescribing antibiotics compared with those without (aOR = 0.8, 95% CI 0.7–0.9). Conclusions: Inappropriate use of antibiotics was high for outpatient childhood URI in the four counties of Guangxi, China, with the highest rate found in township hospitals. A significant high proportion of prescriptions containing antibiotics were broad-spectrum, by intravenous infusion or with multiple antibiotics, especially at county hospitals. Urgent attention is needed to address this challenge.

Impact of China's essential medicines scheme and zero‐mark‐up policy on antibiotic prescriptions in county hospitals: a mixed methods study

To evaluate the impact of the national essential medicines scheme and zero‐mark‐up policy on antibiotic prescribing behaviour.

Diagnostic and treatment delays of multidrug‐resistant tuberculosis before initiating treatment: a cross‐sectional study

Shandong Province has implemented the standardised treatment of multidrug‐resistant tuberculosis (MDR‐TB) supported by the Global Fund. The study aimed to understand the managements and delays of patients with MDR‐TB before initiating their treatments.

Use of Medications and Lifestyles of Hypertensive Patients with High Risk of Cardiovascular Disease in Rural China

Background Hypertension, with a global prevalence of 40%, is a risk factor for cardiovascular diseases (CVD). We conducted an exploratory study in Zhejiang China to understand the prevention of CVD among hypertensive patients with a 10 year CVD risk of 20% or higher. We assessed current practices in a rural ‘township hospital’ (a primary care facility), and compared them with international evidence-based practice. Methods A questionnaire survey was conducted to examine the use of modern drugs (antihypertensive drugs, statins and aspirin) and traditional drugs, compliance to medications and lifestyle among 274 hypertensive patients aged 40-74, with a CVD risk of 20% or higher (using the Asian Equation). Results The majority (72%) were diagnosed with hypertension at township hospitals. Only 15% of study participants used two anti-hypertensive drugs, 0.7% took statin and 2.9% aspirin. Only 2.9% combined two types of modern drugs, while 0.4% combined three types (antihypertensives, statins and aspirin). Herbal compounds, sometimes with internationally rarely recommended drugs such as Reserpine were taken by 44%. Analysis of drug adherence showed that 9.8% had discontinued their drug therapy by themselves. 16% had missed doses and these were on less anti-hypertensive drugs than those who did not (t=-5.217, P=0.003). Of all participants, 28% currently smoked, 39% drank regularly and only 21% exercised frequently. The average salt intake per day was 7.1 (±3.8) g, while the national recommended level is 6g. Conclusion The study revealed outdated and inadequate treatment and health education for hypertensive patients, especially for those who have high risk scores for CVD. There is a need to review the community-based guidelines for hypertension management. Health providers and patients should make a transition from solely treating hypertension, towards prevention of CVD. Health system issues need addressing including improving rural health insurance cover and primary care doctors’ capacity to manage chronic disease patients.

Implementation of a comprehensive intervention for patients at high risk of cardiovascular disease in rural China: A pragmatic cluster randomized controlled trial.

Objective This study aims to assess whether a standard intervention package of cardiovascular disease (CVD) care was being delivered effectively, and if it was associated with improved lifestyle and biomedical indicators. Methods In rural China, we implemented a pragmatic cluster randomized controlled trial for 12 months, randomized at the township hospital level, and compared with usual care. Intervention case management guideline, training and performance monitoring meeting and patient support activities were designed to fit within the job description of family doctors in the township hospitals and comprised: 1) prescription of a standardised package of medicines targeted at those with hypertension or diabetes; 2) advice about specific lifestyle interventions; and 3) advice about medication adherence. Participants were 50–74 years old, had hypertension and CVD risk scores >20% or diabetes, but were excluded if a history of severe CVD events. We also randomly selected 100 participants from six selected clusters per arm as a panel to collect intermediate biomedical indicators over time. Results A total of 28,130 participants, in 33 intervention and 34 control township hospitals, were recruited. Compared with the control arm, participants in the intervention arm had substantially improved prescribing rates of anti-hypertensives, statins and aspirin (P<0.001), and had higher medication taking rates of aspirin and statins (P<0.001). Mean systolic and diastolic blood pressures were similar across both arms (0.15 mmHg, P = 0.79, and 0.52 mmHg, P = 0.05, respectively). In the panel, (950) rates of smoking (OR = 0.23, P = 0.02) and salt intake (OR = 2.85, P = 0.03) were significantly reduced in the intervention versus control arms, but there were no statistically significant improvement over the 12 month follow-up period in biomedical indicators (P>0.05). Conclusion Implementation of the package by family doctors was feasible and improved prescribing and some lifestyle changes. Additional measures such as reducing medication costs and patient education are required. Trial registration Current Controlled Trials ISRCTN58988083

Urban and Rural Differences of Acute Cardiovascular Disease Events: A Study from the Population-Based Real-Time Surveillance System in Zhejiang, China in 2012

Zhejiang province, China, has implemented a population based, real-time surveillance system that tracks acute cardiovascular diseases (CVDs) events since 2001. This study aimed to describe the system and report CVD incidence, mortality and case-fatality between urban and rural areas in Zhejiang in 2012. The surveillance system employs a stratified random sampling method covering all permanent residents of 30 counties/districts in Zhejiang. Acute CVD events such as coronary heart disease (CHD) and stroke were defined, registered and reviewed based on the adapted MONICA (Monitoring Trends and Determinants in Cardiovascular Disease) definitions. Data were collected from health facilities, vital registries, supplementary surveys, and additional investigations, and were checked for data quality before input in the system. We calculated the rates and compared them by gender, age and region. In 2012, the incidence, mortality and case-fatality of total acute CVD events were 367.0 (CHD 59.1, stroke 307.9), 127.1 (CHD 43.3, stroke 83.8) per 100,000 and 34.6% (CHD 73.2%, stroke 27.2%), respectively. Compared with rural areas, urban areas reported higher incidence and mortality but lower case-fatality rates for CHD (P<0.001), while lower incidence but higher mortality and case-fatality rates for stroke (P<0.001). We found significant differences on CHD and stroke epidemics between urban and rural areas in Zhejiang. Special attentions need to be given to stroke control, especially in rural areas.

Cost-effectiveness analysis of a multi-dimensional intervention to reduce inappropriate antibiotic prescribing for children with upper respiratory tract infections in China

We developed a multifaceted intervention to reduce antibiotic prescription rate for children with upper respiratory tract infections (URTIs) among primary care doctors in township hospitals in China. The intervention achieved a 29% (95% CI 16–42) absolute risk reduction in antibiotic prescribing. This study was to assess the cost‐effectiveness of our intervention at reducing antibiotic prescribing in rural primary care facilities as measured by the interventions effect on the antibiotic prescription rates for childhood URTIs.

Treatment interruption and directly observed treatment for patients with multidrug-resistant tuberculosis in China: a cross-sectional survey

Abstract Background China has nearly a fifth of all cases of multidrug-resistant tuberculosis and follows WHOs standardised 24 month regimens. The aim of this study was to assess treatment interruption in patients with multidrug-resistant tuberculosis and its association with the provision of directly observed treatment. Methods We reviewed clinical charts and administered a questionnaire survey to all patients with confirmed multidrug-resistant tuberculosis who had been treated for at least 6 months between Jan 1, 2009, and April 30, 2012, in Shandong province, China. This questionnaire was developed by a panel of experts but has yet to be validated. The primary outcome was treatment interruption and logistic regression was used to explore its associated factors. Treatment interruption was defined as missing a dose for at least 1 day for less than 8 consecutive weeks. Severe interruption was defined as missing doses for 2–8 consecutive weeks. Ethics approval was obtained from the Ethics Committees of the University of Leeds, Leeds, UK, and Shandong Provincial Chest Hospital, Jinan, China. Patient consent forms were collected at the beginning of the survey. Findings Of 110 patients, 75 (68%) interrupted treatment. 19 (17%) patients reported severe interruption, with a median duration of 30 days (IQR 15–50). Of the 110 patients, 26 (24%) received injections from family members, and 55 (50%) patients received directly observed treatment (7 [13%] from village doctors and 48 [87%] from family members). Patients who underwent directly observed treatment with a family member had less severe interruptions (odds ratio 0·25, 95% CI 0·05–0·98) than patients who were given directly observed treatment by a village doctor or who did not undergo treatment. Interpretation We found that directly observed treatment by family members was linked to fewer severe treatment interruptions, which indicates that family members should be properly trained to provide directly observed treatment to patients with multidrug-resistant tuberculosis and that more structured involvement of family members should be prospectively studied as a potentially effective service delivery approach for this disease. Funding The Communicable Disease and Health Service Delivery (Comdis-HSD) Research Consortium is funded by the Department of International Development of the UK Government (grant number HRPC09).