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Abstract Background Due to increasing life expectancy, almost half of people with type 2 diabetes are aged 65 years or over worldwide. When metformin alone does not control blood sugar, the choice of which second-line therapy to prescribe next is not clear from currently available evidence. The existence of frailty and comorbidities in older adults further increases the complexity of medical decision-making. As only a relatively small proportion of trials report results separately for older adults, the relative efficacy and safety of second-line therapies in older adults with type 2 diabetes mellitus are unknown and require further investigation. This individual participant data (IPD) network meta-analysis evaluates the relative efficacy and safety of second-line therapies on their own or in combination in older adults with type 2 diabetes mellitus. Methods All relevant published and unpublished trials will be identified. Studies published prior to 2015 will be identified from two previous comprehensive aggregate data network meta-analyses. Searches will be conducted in CENTRAL, MEDLINE, and EMBASE from 1st January 2015 onwards, and in clinicaltrials.gov from inception. Randomised controlled trials with at least 100 estimated older adults (≥ 65 years) receiving at least 24 weeks of intervention that assess the effects of glucose-lowering drugs on mortality, glycemia, vascular and other comorbidities outcomes, and quality of life will be eligible. The screening and data extraction process will be conducted independently by two researchers. The quality of studies will be assessed using the Cochrane risk of bias tool 2. Anonymised IPD of all eligible trials will be requested via clinical trial portals or by contacting the principal investigators or sponsors. Received data will be reanalysed where necessary to standardise outcome metrics. Network meta-analyses will be performed to determine the relative effectiveness of therapies. Discussion With the increasing number of older adults with type 2 diabetes worldwide, an IPD network meta-analysis using data from all eligible trials will provide new insights into the optimal choices of second-line antidiabetic drugs to improve patient management and reduce unnecessary adverse events and the subsequent risk of comorbidities in older adults. Systematic review registration PROSPERO CRD42021272686.

Abstract Background Measuring treatment burden is important for the effective management of Type 2 Diabetes Mellitus (T2DM) care. The purpose of this systematic review was to identify the most robust approach for measuring treatment burden in people with T2DM based on existing evidence. Methods Articles from seven databases were retrieved. Qualitative, quantitative, and mixed-methods studies examining treatment burden in adults with T2DM and/or reporting relevant experiences were included. A convergent segregated approach with a mixed-methods design of systematic review was employed, creating a measurement framework in a narrative review for consistent critical appraisal. The quality of included studies was assessed using the Joanna Briggs Institute tool. The measurement properties of the instruments were evaluated using the Consensus based Standards for selection of Health Measurement Instruments (COSMIN) checklist. Results A total of 21,584 records were screened, and 26 articles were included, comprising 11 quantitative, 11 qualitative, and 4 mixed-methods studies. A thematic analysis of qualitative data extracted from the included articles summarised a measurement framework encompassing seven core and six associated measurements. The core measurements, including financial, medication, administrative, lifestyle, healthcare, time/travel, and medical information burdens, directly reflect the constructs pertinent to the treatment burden of T2DM. In contrast, the associated measurement themes do not directly reflect the burdens or are less substantiated by current evidence. The results of the COSMIN checklist evaluation demonstrated that the Patient Experience with Treatment and Self-management (PETS), Treatment Burden Questionnaire (TBQ), and Multimorbidity Treatment Burden Questionnaire (MTBQ) have robust instrument development processes. These three instruments, with the highest total counts combining the number of themes covered and "positive" ratings in COSMIN evaluation, were in the top tertile stratification, demonstrating superior applicability for measuring T2DM treatment burden. Conclusions This systematic review provides evidence for the currently superior option of measuring treatment burden in people with T2DM. It also revealed that most current research was conducted in well-resourced institutions, potentially overlooking variability in under-resourced settings.

Abstract Background Understanding treatment burden is a critical element to the effective management of Type 2 Diabetes Mellitus (T2DM). The current study aims to address the knowledge gap surrounding treatment burden of T2DM from the patient’s perspective in China’s primary care settings. Methods A narrative review informed the creation of an a priori coding structure to identify aspects of T2DM treatment burden. Focus groups were conducted, employing a maximum variation sampling strategy to select participants from diverse sociodemographic backgrounds across urban, suburban, rural, and remote areas in China. Participants included adults with T2DM care in primary care settings for over a year and a Treatment Burden Questionnaire score of 25 or higher. Deductive thematic analysis, guided by the coding structure, facilitated a comprehensive exploration and further development of the conceptual framework of T2DM treatment burden. Results Four focus groups, each comprising five participants from diverse areas, were conducted. Utilising the Cumulative Complexity Model and Normalisation Process Theory as theoretical underpinnings, the thematic analysis refined the conceptual framework based on the coding structure from the narrative review. Five key themes were refined, encompassing medical information, medication, administration, healthcare system, and lifestyle. Additionally, the financial and time/travel themes merged into a new theme termed "personal resources", illustrating their overlapping within the framework. Participants in these focus groups highlighted challenges in managing medical information, an aspect often underrepresented in prior treatment burden research. The thematic analysis culminated in a finalised conceptual framework, offering a comprehensive understanding of the treatment burden experiences of people with T2DM in China’s primary care settings. This framework includes six key constructs, delineating T2DM treatment burden and associated factors, such as antecedents and consequences. Conclusions This study provides insights into the treatment burden of T2DM. A conceptual framework was finalised to deepen the understanding of the multifaceted constructs and the nature of treatment burden in people with T2DM. Furthermore, it emphasises the need to tailor T2DM treatment to individual capacities, considering their personal resource allocation and treatment utilisation.

Abstract Background Vaccination is important in influenza prevention but the immune response wanes with age. The circadian nature of the immune system suggests that adjusting the time of vaccination may provide an opportunity to improve immunogenicity. Our previous cluster trial in Birmingham suggested differences between morning and afternoon vaccination for some strains in the influenza vaccine in older adults. Whether this effect is also seen in a younger age group with less likelihood of compromised immunity is unknown. We therefore conducted an individual-based randomized controlled trial in Guangzhou to test the hypothesis that influenza vaccination in the morning induces a stronger immune response in older adults than afternoon vaccination. We included adults in middle age to determine if the effect was also seen in younger age groups. Results Of the 418 participants randomised, 389 (93.1%, 191 middle-aged adults aged 50–60 years and 198 older adults aged 65–75 years) were followed up. Overall, there was no significant difference between the antibody titers (geometric mean /95% CI) after morning vs afternoon vaccination (A/H1N1: 39.9 (32.4, 49.1) vs. 33.0 (26.7, 40.7), p = 0.178; A/H3N2: 92.2 (82.8, 102.7) vs. 82.0 (73.8, 91.2), p = 0.091; B: 15.8 (13.9, 17.9) vs. 14.4 (12.8, 16.3), p = 0.092), respectively. However, in pre-specified subgroup analyses, post-vaccination titers for morning versus afternoon vaccination in the 65–75 years subgroup were (A/H1N1): 49.5 (36.7, 66.6) vs. 32.9 (24.7, 43.9), p = 0.050; (A/H3N2): 93.5 (80.6, 108.5) vs. 73.1 (62.9, 84.9), p = 0.021; (B): 16.6 (13.8, 20.1) vs. 14.4 (12.3, 17.0), p = 0.095, respectively. Among females, antibody titers for morning versus afternoon vaccination were (A/H1N1): 46.9 (35.6, 61.8) vs. 31.1 (23.8, 40.7), p = 0.030; (A/H3N2): 96.0 (83.5, 110.3) vs. 84.7 (74.4, 96.5), p = 0.176; (B): 14.8 (12.7, 17.3) vs. 13.0 (11.3, 14.9), p = 0.061, respectively. In the 50–60 years old subgroup and males, there were no significant differences between morning and afternoon vaccination. Conclusions Morning vaccination may enhance the immunogenicity to influenza vaccine in adults aged over 65 and women. An intervention to modify vaccination programs to vaccinate older individuals in the morning is simple, cost free and feasible in most health systems.

Abstract Background In China diabetes care is gradually shifting from secondary to primary care with great infrastructure investment and GP training. However, most GPs in China lack communication skills training, which is a huge obstacle in communication with their patients in primary care. In this study we seek to identify training priorities that is evidence-based, appropriate for the context of primary care in China, and that meet the real needs of both GPs and people with diabetes. Methods A mixed method approach was used. A conceptual framework was designed based on the MRC framework, action research and adult learning theories. Through a systematic review of the literature and qualitative research with GPs and patients with diabetes, a list of communication skills training components was developed by the research team. A modified nominal group technique (NGT) with GPs was used to evaluate these contents. Purposive sampling was used to recruit a variation of participants (age, work area, practice years and education background) from general practices in Guangzhou city, China. Eight structured nominal groups were facilitated to elicit the views of group members, and participants rated the 9-point Likert scale of importance and feasibility of the training items independently, before and after focus groups. The ranking of each item was calculated, based on the mean Likert score ratings from all participants. Video recordings of four NGT group discussions were thematically analysed using the Framework Method to explore reasons for any differences in rating items. Results 29 males and 29 female GPs from 28 general practices participated in NGT group discussions, with a mean age of 38.5 years and mean 12.3 years of practice experience. Based on the mean scores of importance and feasibility rating scores, the top 3 ranked priorities for communication training were ‘health education’ (importance 8.39, feasibility 7.67), ‘discussing and explaining blood glucose monitoring’ (8.31, 7.46), and ‘diabetes complications and cardiovascular disease risk communication’ (8.36, 7.12). Five main themes were identified from focus group discussions through qualitative analysis: ‘impact on diabetes patients’, ‘GP attitudes towards communication skills’, ‘patient-related factors influencing the application of communication skills by GPs, ‘local contextual factors’, and ‘training implementation’. Conclusions Priorities for communication skills training for Chinese GPs in diabetes care were identified. These are set in the context of GPs’ current experience of communication with patients in China who have diabetes, which is often unsatisfactory. This study describes the baseline from which better primary care for diabetes in China needs to be developed. Based on suggestions from GPs themselves, it identifies an agenda for improvement in communication as a key component of diabetes care in China.

The popularity of teleconsultation during the COVID-19 pandemic enabled increased accessibility for individuals with type 2 diabetes mellitus (T2DM). However, previous studies did not distinguish between synchronous and asynchronous teleconsultation. We evaluated the effectiveness of synchronous teleconsultation for patients with T2DM. We searched Medline, Embase, Cochrane Central Register of Controlled Trials, Cochrane Library and Cochrane Database of Systematic Reviews, ClinicalTrials.gov, and the WHO International Clinical Trials Registry Platform databases from inception to July 2021. All included studies were randomized controlled trials of synchronous teleconsultation for adults with T2DM compared with usual care. Reviewers independently extracted data and used the Cochrane tool to evaluate risk of bias. Meta-analyses were conducted using random-effects models. A pooled mean difference for both HbA1c (%) and body mass index (BMI) (kg/m2), systolic blood pressure (SBP) (mm Hg), diastolic blood pressure (DBP) (mm Hg), and low density lipoprotein cholesterol (LDL-cholesterol) (mg/dL) were calculated. Patient-reported outcomes, such as depression, medication adherence, and quality of life, were also assessed. A total of 9807 abstracts were identified and 27 trials were included. Synchronous teleconsultation significantly resulted in greater decrease in HbA1c compared with usual care group (n=8746, 0.35, 95% CI 0.20 to 0.49, I2=73%, p

Abstract Background Diabetes and hypertension care require effective communication between healthcare professionals and patients. Training programs may improve the communication skills of healthcare professionals but no systematic review has examined their effectiveness at improving clinical outcomes and patient experience in the context of diabetes and hypertension care. Methods We conducted a systematic review of randomized controlled trials to summarize the effectiveness of any type of communication skills training for healthcare professionals to improve diabetes and/or hypertension care compared to no training or usual care. We searched Medline, Embase, CINAHL, PsycINFO, Cochrane Central Register of Controlled Trials (CENTRAL), Cochrane Database of Systematic Reviews (CDSR), ClinicalTrials.gov and the World Health Organization International Clinical Trials Registry Platform from inception to August 2020 without language restrictions. Data on the country, type of healthcare setting, type of healthcare professionals, population, intervention, comparison, primary outcomes of glycated hemoglobin (HbA1c) and blood pressure, and secondary outcomes of quality of life, patient experience and understanding, medication adherence and patient-doctor relationship were extracted for each included study. Risk of bias of included studies was assessed by Cochrane risk of bias tool. Results 7011 abstracts were identified, and 19 studies met the inclusion criteria. These included a total of 21,762 patients and 785 health professionals. 13 trials investigated the effect of communication skills training in diabetes management and 6 trials in hypertension. 10 trials were at a low risk and 9 trials were at a high risk of bias. Training included motivational interviewing, patient centred care communication, cardiovascular disease risk communication, shared decision making, cultural competency training and psychological skill training. The trials found no significant effects on HbA1c (n = 4501, pooled mean difference -0.02 mmol/mol, 95% CI -0.10 to 0.05), systolic blood pressure (n = 2505, pooled mean difference -2.61 mmHg, 95% CI -9.19 to 3.97), or diastolic blood pressure (n = 2440, pooled mean difference -0.06 mmHg, 95% CI -3.65 to 2.45). There was uncertainty in whether training was effective at improving secondary outcomes. Conclusion The communication skills training interventions for healthcare professionals identified in this systematic review did not improve HbA1c, BP or other relevant outcomes in patients with diabetes and hypertension. Further research is needed to methodically co-produce and evaluate communication skills training for chronic disease management with healthcare professionals and patients.

Abstract Background China has more ascertained cases of diabetes than any other country. Much of the care of people with type 2 diabetes (T2DM) in China is managed by GPs and this will increase with the implementation of health care reforms aimed at strengthening China’s primary health care system. Diabetes care requires effective communication between physicians and patients, yet little is known about this area in China. We aimed to explore the experiences of Chinese GPs in communicating with diabetes patients and how this may relate to communication skills training. Methods Focus groups with Chinese GPs were undertaken. Purposive sampling was used to recruit 15 GPs from Guangzhou city in China. All data were audio-recorded and transcribed. A thematic analysis using the Framework Method was applied to code the data and identify themes. Results Seven males and 8 females from 12 general practices attended 4 focus groups with a mean age of 37.6 years and 7.5 years’ work experience. Four major themes were identified: diversity in diabetic patients, communication with patients, patient-doctor relationship, and communication skills training. GPs reported facing a wide variety of diabetes patients in their daily practice. They believed insufficient knowledge and misunderstanding of diabetes was common among patients. They highlighted several challenges in communicating with diabetes patients, such as insufficient consultation time, poor communication regarding blood glucose monitoring and misunderstanding the risk of complications. They used terms such as “blind spot” or “not on the same channel” to describe gaps in their patients’ understanding of diabetes and its management, and cited this as a cause of ineffective patient-doctor communication. Mutual understanding of diabetes was perceived to be an important factor towards building positive patient-doctor relationships. Although GPs believed communication skills training was necessary, they reported rarely received this. Conclusions Chinese GPs reported facing challenges in communicating with diabetes patients. Some of these were perceived as being due to the patients themselves, others were attributed to system constraints, and some were seen as related to a lack of clinician training. The study identified key issues for the development of primary care-based management of diabetes in China, and for developing appropriate communication skills training programs for the primary care workforce.

Background and Objectives: To achieve the goal of 300,000 general practitioners by 2020-an increase of 215,200 in a decade-China is utilizing multiple training pathways. To comprehensively illustrate general practitioner training strategies in China, this article introduces and describes these pathways.Methods: We used descriptive policy analysis. This involved taking an inventory of existing literature and source documents and developing a model to illustrate pathways for training general practice physicians.Results: The rural doctor pathway represents rural clinicians who had only basic training and practiced multiple years prior to training reforms. The 3+2 pathway to assistant general practitioners requires 3 years of junior college and 2 years of clinical training. The transfer pathway for current physicians requires 1-2 years of training. The 5+3 pathway comprises 5 years of bachelor of science degree training in clinical medicine and 3 years of standardized residency training. Despite the development of advanced degree programs, their use remains limited.Conclusions: These pathways illustrate significant heterogeneity in training of general practitioners. Training ranges from a 2-year technical degree to a doctorate with research. Emphasis on the 5+3 track shows promise for China's goals of improved quality and new goal of 500,000 additional general practitioners by 2030. [ABSTRACT FROM AUTHOR]

LBD(lateral organ boundaries)transcription factors play an important role in the regulation of plant growth, development and secondary metabolism. In order to explore the function of LBD genes in cannabis, the Cannabis sativa genome and transcriptome were used to identify the C. sativa LBD gene family, and analyzed their expression patterns. Our results showed that the cannabis LBD contains 32 members, which were divided into two major categories, seven sub-families. Class Ⅰ was divided into 5 sub-families, named Class Ⅰ_a to Class Ⅰ_e, while Class Ⅱ was divided into 2 sub-families, including Class Ⅱ_a and Class Ⅱ_b. Analysis showed that the number of amino acids encoded LBDs was between 172 and 356, and the isoelectric point was between 4.92 and 9.43. The mole-cular weight of LBD was between 18 862.92 Da and 40 081.33 Da, and most members are located in the nucleus. Chromosome positioning of LBD showed that 32 members were unevenly distributed on 10 chromosomes of C. sativa LBD transcription factor domain, gene structure and motifs are relatively conservative, and the characteristics of different class members are similar. The upstream promoter region of the gene contains a variety of cis-acting elements related to plant hormones and environmental factors, C. sativa LBD genes have different expression patterns in the stems, leaves, and flowers of ZYS varieties(low tetrahydrocannabinol, high cannabidiol). The members of the LBD gene family are mainly expressed in the flowers and stems of ZYS varieties, while members expressed in the leaves very few; Class Ⅱ members CsLBD21 and CsLBD23 are expressed in flowers and stems, and CsLBD8 and CsLBD18 are expressed in flowers, stems and leaves. These genes may participate in the growth and development of cannabis and affect the biosynthesis of cannabinoids. This study laid the foundation for the subsequently functional research of the cannabis LBD gene family.

Natural indigo, as one of the oldest dyes, is also a pivotal dye utilized in cotton fabrics today. A diversity of plants rich in indigo compounds belong to traditional Chinese herbal medicines. Indigo compounds have a variety of biological and pharmacological activities, including anticonvulsant, antibacterial, antifungal, antiviral and anticancer activities. A substantial progress in indigo biosynthesis has been made lately. This paper summarizes the value of indigo from the aspects of cultural history, biosynthetic pathways and the medicinal activities of its related derivatives involved in the pathways. In addition, the latest research advancements in indigo biosynthetic pathways is demonstrated in this paper, which would lay the theoretical foundation for the exploration and utilization of natural indigo.

Matrix-assisted laser desorption/ionization mass spectrometry imaging(MALDI-MSI) is a novel technique for in-situ distribution of various substances in tissue without labeling. This technique is increasingly applied to the study of medicinal plants owing to its high spatial resolution and its potential of in-situ analysis in small molecules. In this study, the structural information and their fragmentation patterns of the midazole alkaloids(1,3-dibenzyl-4,5-dimethylimidazolium chloride and 1,3-dibenzyl-2,4,5-trimethylimi-dazolium chloride) and benzylglucosinolate in the medicinal plant Maca(Lepdium meyeni) root were analyzed by ultra-high-performance liquid phase combined with LTQ-Orbitrap mass spectrometry(UHPLC-HR-MS). The localization of these active ingredients in the cross-sections of Maca root was performed by MALDI-MSI. These results demonstrated that the two types of imidazole alkaloids had a similar distributed pattern. They were located more in the cortex and the periderm than those in the medulla of a lateral root, while the localization of benzylglucosinolate was concentrated in the center of the root rather than in the cortex and the periderm. The precise spatial distribution of various secondary metabolites in tissue provides an important scientific basis for the accumulation of medicinal plant active ingredients in tissues. In addition, this imaging method is a promising technique for the rapid evaluation and identification of the active ingredients of traditional Chinese medicine in plant tissues, as well as assisting the research on the processing of medicinal plants.