REduced-Carbohydrate intervention for managing Obesity and Reduction of gestational Diabetes (RECORD): A randomized controlled feasibility trial.

AIM: To test the feasibility and acceptability of a reduced-carbohydrate dietary program, intended to reduce the risk of gestational diabetes. MATERIALS AND METHODS: Fifty-one pregnant women at <20 weeks' gestation, with body mass index ≥30 kg/m2 , and a normal baseline oral glucose tolerance test (OGTT), were randomized 2:1 to an intervention or control group and followed-up until delivery. The dietary intervention aimed at providing 130-150 g carbohydrate/day. Feasibility outcomes assessed at 24-28 weeks' gestation, included adoption of the reduced-carbohydrate diet by the intervention group, and retention of all participants, assessed by completion of a second OGTT. Changes in glycemia, weight gain and dietary intake, and the maternal and neonatal outcomes were also assessed. Participants were interviewed about their experience of the intervention and the study. RESULTS: Forty-nine of 51 participants attended the follow-up OGTT, a retention rate of 96% (95% confidence interval [CI] 86.8%-98.9%). In the intervention group, carbohydrate intake at follow-up was 190.4 (95% CI 162.5-215.6) g/day, a reduction of -24.6 (95% CI -51.5-2.4) g/day from baseline. Potentially favourable effects of the intervention on glucose control, weight gain and blood pressure were observed, but the study was not powered to detect significant differences in these. Participants found the intervention acceptable, and were content with the study processes, but some reported barriers to sustained adherence, mainly pertaining to competing priorities. CONCLUSIONS: Retention was high, suggesting the study processes are feasible, but the carbohydrate reduction in the intervention group was small, and did not meet progression criteria, limiting the likelihood of achieving the desired goal to prevent gestational diabetes. TRIAL REGISTRATION NUMBER: ISRCTN16235884.

Pharmacological and electronic cigarette interventions for smoking cessation in adults: component network meta-analyses.

BACKGROUND: Tobacco smoking is the leading preventable cause of death and disease worldwide. Stopping smoking can reduce this harm and many people would like to stop. There are a number of medicines licenced to help people quit globally, and e-cigarettes are used for this purpose in many countries. Typically treatments work by reducing cravings to smoke, thus aiding initial abstinence and preventing relapse. More information on comparative effects of these treatments is needed to inform treatment decisions and policies. OBJECTIVES: To investigate the comparative benefits, harms and tolerability of different smoking cessation pharmacotherapies and e-cigarettes, when used to help people stop smoking tobacco. SEARCH METHODS: We identified studies from recent updates of Cochrane Reviews investigating our interventions of interest. We updated the searches for each review using the Cochrane Tobacco Addiction Group (TAG) specialised register to 29 April 2022. SELECTION CRITERIA: We included randomised controlled trials (RCTs), cluster-RCTs and factorial RCTs, which measured smoking cessation at six months or longer, recruited adults who smoked combustible cigarettes at enrolment (excluding pregnant people) and randomised them to approved pharmacotherapies and technologies used for smoking cessation worldwide (varenicline, cytisine, nortriptyline, bupropion, nicotine replacement therapy (NRT) and e-cigarettes) versus no pharmacological intervention, placebo (control) or another approved pharmacotherapy. Studies providing co-interventions (e.g. behavioural support) were eligible if the co-intervention was provided equally to study arms. DATA COLLECTION AND ANALYSIS: We followed standard Cochrane methods for screening, data extraction and risk of bias (RoB) assessment (using the RoB 1 tool). Primary outcome measures were smoking cessation at six months or longer, and the number of people reporting serious adverse events (SAEs). We also measured withdrawals due to treatment. We used Bayesian component network meta-analyses (cNMA) to examine intervention type, delivery mode, dose, duration, timing in relation to quit day and tapering of nicotine dose, using odds ratios (OR) and 95% credibility intervals (CrIs). We calculated an effect estimate for combination NRT using an additive model. We evaluated the influence of population and study characteristics, provision of behavioural support and control arm rates using meta-regression. We evaluated certainty using GRADE. MAIN RESULTS: Of our 332 eligible RCTs, 319 (835 study arms, 157,179 participants) provided sufficient data to be included in our cNMA. Of these, we judged 51 to be at low risk of bias overall, 104 at high risk and 164 at unclear risk, and 118 reported pharmaceutical or e-cigarette/tobacco industry funding. Removing studies at high risk of bias did not change our interpretation of the results. Benefits We found high-certainty evidence that nicotine e-cigarettes (OR 2.37, 95% CrI 1.73 to 3.24; 16 RCTs, 3828 participants), varenicline (OR 2.33, 95% CrI 2.02 to 2.68; 67 RCTs, 16,430 participants) and cytisine (OR 2.21, 95% CrI 1.66 to 2.97; 7 RCTs, 3848 participants) were associated with higher quit rates than control. In absolute terms, this might lead to an additional eight (95% CrI 4 to 13), eight (95% CrI 6 to 10) and seven additional quitters per 100 (95% CrI 4 to 12), respectively. These interventions appeared to be more effective than the other interventions apart from combination NRT (patch and a fast-acting form of NRT), which had a lower point estimate (calculated additive effect) but overlapping 95% CrIs (OR 1.93, 95% CrI 1.61 to 2.34). There was also high-certainty evidence that nicotine patch alone (OR 1.37, 95% CrI 1.20 to 1.56; 105 RCTs, 37,319 participants), fast-acting NRT alone (OR 1.41, 95% CrI 1.29 to 1.55; 120 RCTs, 31,756 participants) and bupropion (OR 1.43, 95% CrI 1.26 to 1.62; 71 RCTs, 14,759 participants) were more effective than control, resulting in two (95% CrI 1 to 3), three (95% CrI 2 to 3) and three (95% CrI 2 to 4) additional quitters per 100 respectively. Nortriptyline is probably associated with higher quit rates than control (OR 1.35, 95% CrI 1.02 to 1.81; 10 RCTs, 1290 participants; moderate-certainty evidence), resulting in two (CrI 0 to 5) additional quitters per 100. Non-nicotine/placebo e-cigarettes (OR 1.16, 95% CrI 0.74 to 1.80; 8 RCTs, 1094 participants; low-certainty evidence), equating to one additional quitter (95% CrI -2 to 5), had point estimates favouring the intervention over control, but CrIs encompassed the potential for no difference and harm. There was low-certainty evidence that tapering the dose of NRT prior to stopping treatment may improve effectiveness; however, 95% CrIs also incorporated the null (OR 1.14, 95% CrI 1.00 to 1.29; 111 RCTs, 33,156 participants). This might lead to an additional one quitter per 100 (95% CrI 0 to 2). Harms There were insufficient data to include nortriptyline and non-nicotine EC in the final SAE model. Overall rates of SAEs for the remaining treatments were low (average 3%). Low-certainty evidence did not show a clear difference in the number of people reporting SAEs for nicotine e-cigarettes, varenicline, cytisine or NRT when compared to no pharmacotherapy/e-cigarettes or placebo. Bupropion may slightly increase rates of SAEs, although the CrI also incorporated no difference (moderate certainty). In absolute terms bupropion may cause one more person in 100 to experience an SAE (95% CrI 0 to 2). AUTHORS' CONCLUSIONS: The most effective interventions were nicotine e-cigarettes, varenicline and cytisine (all high certainty), as well as combination NRT (additive effect, certainty not rated). There was also high-certainty evidence for the effectiveness of nicotine patch, fast-acting NRT and bupropion. Less certain evidence of benefit was present for nortriptyline (moderate certainty), non-nicotine e-cigarettes and tapering of nicotine dose (both low certainty). There was moderate-certainty evidence that bupropion may slightly increase the frequency of SAEs, although there was also the possibility of no increased risk. There was no clear evidence that any other tested interventions increased SAEs. Overall, SAE data were sparse with very low numbers of SAEs, and so further evidence may change our interpretation and certainty. Future studies should report SAEs to strengthen certainty in this outcome. More head-to-head comparisons of the most effective interventions are needed, as are tests of combinations of these. Future work should unify data from behavioural and pharmacological interventions to inform approaches to combined support for smoking cessation.

Direct medical costs of end-stage kidney disease and renal replacement therapy: a cohort study in Guangzhou City, southern China.

BACKGROUND: Renal replacement therapy was a lifesaving yet high-cost treatment for people with end-stage kidney disease (ESKD). This study aimed to estimate the direct medical costs per capita of ESKD by different treatment strategies: haemodialysis (HD); peritoneal dialysis (PD); kidney transplantation (KT) (in the first year); KT (in the second year), and by two urban health insurance schemes. METHODS: This was a retrospective observational cohort study. Data were obtained from outpatient and inpatient claims database of two urban health insurance from Guangzhou City, Southern China. Adult patients with HD (n = 3765; mean age 58 years), PD (n = 1237; 51 years), KT (first year) (n = 117; 37 years) and KT (second year) (n = 41; 39 years) were identified between 2010 and 2012. The primary outcome was the annual per patient medical costs in 2013 Chinese Yuan (CNY) incurred in the outpatient and inpatient sectors. Secondary outcomes were annual outpatient visits and inpatient admissions, length of stay per admission. Generalized linear regression and bootstrapping statistical methods were used for analysis. RESULTS: The estimated average annual medical costs for patients on HD were CNY 94,760.5 (US$15,066.0), 95% Confidence Interval (CI): CNY85,166.6-106,972.2, which was higher than those for patients on PD [CNY80,762.9 (US$12,840.5), 95% CI: CNY 76,249.8-85,498.9]. The estimated annual cost ratio of HD versus PD was 1.17 (95% CI: 1.12-1.25). Among the transplanted patients, the estimated average annual medical costs in the first year were CNY132,253.0 (US$21,026.9), 95%CI: CNY114,009.9-153,858.6, and in the second year were CNY93,155.3 (US$14,810.8), 95%CI: CNY61,120.6-101,989.1. The mean annual medical costs for dialysis patients under Urban Employee-based Basic Medical Insurance scheme were significantly higher than those for patients under Urban Resident-based Basic Medical Insurance scheme (P < 0.001). CONCLUSIONS: The direct medical costs of ESKD patients were high and different by types of renal replacement therapy and insurance. The findings can be used to conduct cost-effectiveness research on different types of RRT for ESKD patients that provides economic evidence for health policy design in China.

Targeted delivery of siRNA against hepatitis B virus by preS1 peptide molecular ligand.

AIM: For chronic hepatitis B virus (HBV) infection, the effects of current therapies are limited. RNA interference of virus-specific genes has emerged as a potential antiviral mechanism. However, a suitable delivery vector is still to be developed. We studied a novel vector transferring siRNA targeting hepatic cells in vivo and in vitro in order to find a new way to cure HBV-related live diseases. METHODS: The preS1-9Arg ligand was used to deliver siRNA to HepG2 and to HepG2 2.2.15 cells. To validate the antiviral efficacy in vivo, a HBV viremic animal model was established by s.c. inoculation of HepG2 2.2.15 tumor cells in nude mice. The minimal retardation effect on the migration of siRNA was detected by gel electrophoresis to confirm the combination and the optimal ratio. Hepatitis B surface antigen (HBsAg) levels were detected by semiquantitatively enzyme-linked immunosorbent assay RNA levels were quantified with quantitative real-time polymerase chain reaction and protein levels were determined with immunoblots and immunohistochemistry. RESULTS: PreS1-9Arg peptide strongly combined and transferred siRNA into HepG2 cells. PreS1-9Arg-siRNA molecular conjugate effectively reduced the production of HBsAg and HBV DNA without liver toxicity in vitro and in vivo. CONCLUSION: The results indicated that preS1-9Arg may be a potential novel vector to deliver siRNA targeting liver cells.

Effectiveness of behavioural interventions with motivational interviewing on physical activity outcomes in adults: systematic review and meta-analysis.

OBJECTIVE: To evaluate the effectiveness of behavioural interventions that include motivational interviewing on physical activity outcomes in adults. DESIGN: Systematic review and meta-analysis. STUDY SELECTION: A search of seven databases for randomised controlled trials published from inception to 1 March 2023 comparing a behavioural intervention including motivational interviewing with a comparator without motivational interviewing on physical activity outcomes in adults. Outcomes of interest were differences in change in quantitative measures of total physical activity, moderate to vigorous physical activity (MVPA), and sedentary time. DATA EXTRACTION AND SYNTHESIS: Two reviewers extracted data and assessed risk of bias. Population characteristics, intervention components, comparison groups, and outcomes of studies were summarised. For overall main effects, random effects meta-analyses were used to report standardised mean differences (SMDs) and 95% confidence intervals (CIs). Differential effects based on duration of follow-up, comparator type, intervention duration, and disease or health condition of participants were also examined. RESULTS: 129 papers reporting 97 randomised controlled trials totalling 27 811 participants and 105 comparisons were included. Interventions including motivational interviewing were superior to comparators for increases in total physical activity (SMD 0.45, 95% CI 0.33 to 0.65, equivalent to 1323 extra steps/day; low certainty evidence) and MVPA (0.45, 0.19 to 0.71, equivalent to 95 extra min/week; very low certainty evidence) and for reductions in sedentary time (-0.58, -1.03 to -0.14, equivalent to -51 min/day; very low certainty evidence). Evidence for a difference in any outcome compared with comparators of similar intensity was lacking. The magnitude of effect diminished over time, and evidence of an effect of motivational interviewing beyond one year was lacking. Most interventions involved patients with a specific health condition, and evidence of an effect of motivational interviewing to increase MVPA or decrease sedentary time was lacking in general population samples. CONCLUSIONS: Certainty of the evidence using motivational interviewing as part of complex behavioural interventions for promoting total physical activity in adults was low, and for MVPA and sedentary time was very low. The totality of evidence suggests that although interventions with motivational interviewing increase physical activity and decrease sedentary behaviour, no difference was found in studies where the effect of motivational interviewing could be isolated. Effectiveness waned over time, with no evidence of a benefit of motivational interviewing to increase physical activity beyond one year. SYSTEMATIC REVIEW REGISTRATION: PROSPERO CRD42020219881.

The Association between Blood Test Trends and Undiagnosed Cancer: A Systematic Review and Critical Appraisal.

Clinical guidelines include monitoring blood test abnormalities to identify patients at increased risk of undiagnosed cancer. Noting blood test changes over time may improve cancer risk stratification by considering a patient's individual baseline and important changes within the normal range. We aimed to review the published literature to understand the association between blood test trends and undiagnosed cancer. MEDLINE and EMBASE were searched until 15 May 2023 for studies assessing the association between blood test trends and undiagnosed cancer. We used descriptive summaries and narratively synthesised studies. We included 29 articles. Common blood tests were haemoglobin (24%, n = 7), C-reactive protein (17%, n = 5), and fasting blood glucose (17%, n = 5), and common cancers were pancreatic (29%, n = 8) and colorectal (17%, n = 5). Of the 30 blood tests studied, an increasing trend in eight (27%) was associated with eight cancer types, and a decreasing trend in 17 (57%) with 10 cancer types. No association was reported between trends in 11 (37%) tests and breast, bile duct, glioma, haematological combined, liver, prostate, or thyroid cancers. Our review highlights trends in blood tests that could facilitate the identification of individuals at increased risk of undiagnosed cancer. For most possible combinations of tests and cancers, there was limited or no evidence.

Electronic cigarettes and subsequent use of cigarettes in young people: An evidence and gap map.

BACKGROUND AND AIMS: The use of e-cigarettes may influence later smoking uptake in young people. Evidence and gap maps (EGMs) are interactive on-line tools that display the evidence and gaps in a specific area of policy or research. The aim of this study was to map clusters and gaps in evidence exploring the relationship between e-cigarette use or availability and subsequent combustible tobacco use in people aged < 30 years. METHODS: We conducted an EGM of primary studies and systematic reviews. A framework and an interactive EGM was developed in consultation with an expert advisory group. A systematic search of five databases retrieved 9057 records, from which 134 studies were included. Systematic reviews were appraised using AMSTAR-2, and all included studies were coded into the EGM framework resulting in the interactive web-based EGM. A descriptive analysis of key characteristics of the identified evidence clusters and gaps resulted in this report. RESULTS: Studies were completed between 2015 and 2023, with the first systematic reviews being published in 2017. Most studies were conducted in western high-income countries, predominantly the United States. Cohort studies were the most frequently used study design. The evidence is clustered on e-cigarette use as an exposure, with an absolute gap identified for evidence looking into the availability of e-cigarettes and subsequent cessation of cigarette smoking. We also found little evidence analysing equity factors, and little exploring characteristics of e-cigarette devices. CONCLUSIONS: This evidence and gap map (EGM) offers a tool to explore the available evidence regarding the e-cigarette use/availability and later cigarette smoking in people under the age of 30 years at the time of the search. The majority of the 134 reports is from high-income countries, with an uneven geographic distribution. Most of the systematic reviews are of lower quality, suggesting the need for higher-quality reviews. The evidence is clustered around e-cigarette use as an exposure and subsequent frequency/intensity of current combustible tobacco use. Gaps in evidence focusing on e-cigarette availability, as well as on the influence of equity factors may warrant further research. This EGM can support funders and researchers in identifying future research priorities, while guiding practitioners and policymakers to the current evidence base.

Changes in body weight and cardiovascular risk factors in a Chinese population with type 2 diabetes mellitus: a longitudinal study.

Introduction: The primary care management of blood glucose, blood pressure, lipid profiles, and body weight is important among patients with type 2 diabetes mellitus (T2DM) to prevent disease progression. Information on how weight changes would improve or deteriorate cardiovascular (CV) risk factors is warranted for making primary care recommendations. We aimed to investigate the changes in body weight and CV risk factors and to analyse their association in a Chinese population with T2DM. Methods: We retrieved longitudinal data between 2020 and 2021 from 1,758 adult primary care patients enrolled in a diabetic retinopathy (DR) screening programme. Linear associations of changes in body weight with CV risk factors were explored. Multivariable logistic regression analysis was performed to examine associations between different weight change categories and the worsening of CV risk factors. Results: The mean age of all the participants was 63.71 years, and over half of participants were females. During a one-year follow-up period, 24.7% of patients had a weight loss of ≥3%, while 22.2% of patients had a weight gain of ≥3%. Patients who had a weight loss of ≥3% were more likely to prevent the worsening of haemoglobin A1c (HbA1c) and triglycerides, while those who had a weight gain of ≥3% tended to have worsened HbA1c, lipid profiles, and blood pressure. Conclusion: Results from this real-world investigation suggested the concurrent need for weight loss intervention among patients who are overweight or obese and weight gain prevention among patients whose body weight falls within the normal range in the context of community-based diabetes management.

Longitudinal changes in blood pressure and fasting plasma glucose among 5,398 primary care patients with concomitant hypertension and diabetes: An observational study and implications for community-based cardiovascular prevention.

Aims: To assess longitudinal changes in blood pressure (BP) and fasting plasma glucose (FPG) in primary care patients with concomitant hypertension and type 2 diabetes mellitus (T2DM), and to explore factors associated with patients' inability to improve BP and FPG at follow-up. Methods: We constructed a closed cohort in the context of the national basic public health (BPH) service provision in an urbanised township in southern China. Primary care patients who had concomitant hypertension and T2DM were retrospectively followed up from 2016 to 2019. Data were retrieved electronically from the computerised BPH platform. Patient-level risk factors were explored using multivariable logistic regression analysis. Results: We included 5,398 patients (mean age 66 years; range 28.9 to 96.1 years). At baseline, almost half [48.3% (2,608/5,398)] of patients had uncontrolled BP or FPG. During follow-up, more than one-fourth [27.2% (1,467/5,398)] of patients had no improvement in both BP and FPG. Among all patients, we observed significant increases in systolic BP [2.31 mmHg, 95% confidence interval (CI): 2.04 to 2.59, p < 0.001], diastolic BP (0.73 mmHg, 0.54 to 0.92, p < 0.001), and FPG (0.12 mmol/l, 0.09 to 0.15, p < 0.001) at follow-up compared to baseline. In addition to changes in body mass index [adjusted odds ratio (aOR)=1.045, 1.003 to 1.089, p = 0.037], poor adherence to lifestyle advice (aOR = 1.548, 1.356 to 1.766, p < 0.001), and unwillingness to actively enrol in health-care plans managed by the family doctor team (aOR = 1.379, 1.128 to 1.685, p = 0.001) were factors associated with no improvement in BP and FPG at follow-up. Conclusion: A suboptimal control of BP and FPG remains an ongoing challenge to primary care patients with concomitant hypertension and T2DM in real-world community settings. Tailored actions aiming to improve patients' adherence to healthy lifestyles, expand the delivery of team-based care, and encourage weight control should be incorporated into routine healthcare planning for community-based cardiovascular prevention.

Time Window for Acute Stroke Management: A Cross-Sectional Study Among Community Healthcare Practitioners in Primary Care.

Introduction: Time-to-treatment window is critical for managing acute ischaemic stroke. The community healthcare practitioners (CHPs) who deliver frontline care in the health system play an important role in stroke prevention and treatment. Methods: A multi-stage sampling design was adopted in Guangdong province, China. A total of 997 CHPs who participated in the survey were divided into two groups (the awareness group vs the unawareness group) according to their knowledge on the time window for stroke management. Logistic regression analysis was performed to explore factors associated with the awareness of "time window". Results: Overall, less than half (49.1%) of CHPs were aware of the time window for stroke management. The proportion of CHPs who were able to recognise stroke symptoms were higher in the awareness group (42.7%) than that in the unawareness group (38.8%). Most CHPs (82.9%) in the awareness group had the knowledge about the effectiveness of intravenous thrombolysis in treating acute cerebral infarction, whereas this was perceived by only less than half (43.6%) of CHPs in the unawareness group. Factors associated with the knowledge of time window for stroke management included participation in cerebrovascular disease management training (adjusted odds ratio [aOR]=4.203, 95% CI: 1.707-10.348, p=0.002), awareness of the time frame for CT initiation (aOR=5.214, 95% CI: 1.803-15.078, p=0.002) and for urokinase thrombolysis administration (aOR=11.927, 95% CI: 4.393-32.382, p<0.001), accurate perceptions about the target for blood pressure lowering (aOR=4.181, 95% CI: 1.713-10.207, p=0.002) and blood glucose control (aOR=2.446, 95% CI: 1.019-5.869, p=0.045), and the familiarity with prehospital stroke management principles (aOR=3.593, 95% CI: 1.383-9.332, p=0.009). Conclusion: The CHPs need to enhance their ability to address the acute ischaemic stroke onset promptly to provide effective treatment within the beneficial "time window". This may help improve the stroke chain of survival with better multidisciplinary decision support systems that enable optimal stroke care delivery.

Frequency of Follow-Up Attendance and Blood Glucose Monitoring in Type 2 Diabetic Patients at Moderate to High Cardiovascular Risk: A Cross-Sectional Study in Primary Care.

Regular follow-up attendance in primary care and routine blood glucose monitoring are essential in diabetes management, particularly for patients at higher cardiovascular (CV) risk. We sought to examine the regularity of follow-up attendance and blood glucose monitoring in a primary care sample of type 2 diabetic patients at moderate-to-high CV risk, and to explore factors associated with poor engagement. Cross-sectional data were collected from 2130 patients enrolled in a diabetic retinopathy screening programme in Guangdong province, China. Approximately one-third of patients (35.9%) attended clinical follow-up <4 times in the past year. Over half of patients (56.9%) failed to have blood glucose monitored at least once per month. Multivariable logistic regression analysis showed that rural residents (adjusted odds ratio [aOR] = 0.420, 95% confidence interval [CI] = 0.338-0.522, p < 0.001, for follow-up attendance; aOR = 0.580, 95%CI: 0.472-0.712, p < 0.001, for blood glucose monitoring) and subjects with poor awareness of adverse consequences of diabetes complications (aOR = 0.648, 95%CI = 0.527-0.796, p < 0.001, for follow-up attendance; aOR = 0.770, 95%CI = 0.633-0.937, p = 0.009, for blood glucose monitoring) were both less likely to achieve active engagement. Our results revealed an urban-rural divide in patients' engagement in follow-up attendance and blood glucose monitoring, which suggested the need for different educational approaches tailored to the local context to enhance diabetes care.