Effect of oral health intervention on cognitive decline in community-dwelling older adults: A randomized controlled trial

PurposeThe incidence of dementia is rapidly increasing worldwide, especially in developed countries. Little is known regarding the effectiveness of dental intervention to prevent dementia or a decline in cognitive functions among community-dwelling older adults, but a few studies have reported a correlation between the lack of regular dental checkups and dementia. For that reason, this study aimed to investigate the effects of oral health intervention on cognitive functions in community-dwelling subjects with a mild cognitive decline via a randomized controlled trial.Patients and methodsFifty-five community-dwelling older adults with a Mini-Mental State Examination score of ≥21 to ≤26 who had not visited a dental clinic in the previous year were randomized to an intervention group (n = 28) or a control group (n = 29). The intervention group received monthly oral health intervention by dental hygienists for 8 months while the control group did not. Data on demographics, cognitive function and oral parameters were collected before and after the intervention.ResultsTwenty-five subjects in the intervention group (mean age 77.0 years) and 25 in the control group (mean age 72.8 years) completed the study. Significant improvements were observed in the Trail Making Test (TMT)-A, TMT-B, bleeding on probing rate, oral diadochokinesis, tongue pressure and chewing ability in the intervention group (P < 0.05). There were also significant interactions between the TMT-A and TMT-B scores, oral diadochokinesis, tongue pressure and chewing ability (P < 0.05).ConclusionOral health intervention by dental hygienists may be effective for improving the oral health and executive function of cognitive function assessed via TMT.     

The effect of oral nutritional supplement therapy on nutritional status and quality of life in patients with esophageal cancer undergoing radiotherapy and chemotherapy: A protocol for randomized controlled trial

Background:The incidence of malnutrition in patients with esophageal cancer is high, which seriously affects the therapeutic effect and quality of life. Oral nutritional supplement is the first choice of nutritional support recommended by current guidelines, which can supplement the lack of energy and protein in patients with esophageal cancer, improve nutritional status and improve the quality of life, but there are few clinical studies. Therefore, the purpose of this randomized controlled trial is to evaluate the effect of oral nutritional supplement therapy on nutritional status and quality of life in patients with esophageal cancer treated undergoing radiotherapy and chemotherapy.Methods:This is a prospective randomized controlled trial to study the effects of oral nutritional supplement therapy on nutritional status and quality of life in patients with esophageal cancer undergoing radiotherapy and chemotherapy. This study is approved by the Clinical Research Society of our hospital. Patients will be randomly divided into ONS group and traditional diet group. The nutritional status, quality of life score and adverse reactions will be observed before and after radiotherapy and chemotherapy. The data will be analyzed by SPSS 16.0.Discussion:This study will evaluate the effect of oral nutritional supplement therapy on nutritional status and quality of life of patients with esophageal cancer undergoing radiotherapy and chemotherapy. The results of this experiment will establish clinical evidence for the application of oral nutritional supplement therapy in patients with esophageal cancer undergoing radiotherapy and chemotherapy.OSF Registration number:DOI 10.17605/OSF.IO/9ZW34.     

A randomized trial of adding insulin glargine vs. avoidance of insulin in people with Type 2 diabetes on either no oral glucose-lowering agents or submaximal doses of metformin and/or sulphonylureas. The Canadian INSIGHT (Implementing New Strategies with Insulin Glargine for Hyperglycaemia Treatment) Study.

AIMS: Insulin is generally withheld until people with Type 2 diabetes are unresponsive to other therapies. However, its potential advantages suggest that it could be added earlier to achieve glycaemic goals; this possibility was tested in a clinical trial. METHODS: Consenting adults aged 18-80 years with Type 2 diabetes for at least 6 months, HbA1c of 7.5-11%, and on 0, 1 or 2 oral agents, were randomized to one of two therapeutic approaches for 24 weeks: evening insulin glargine plus self-titration by 1 unit/day if the fasting plasma glucose (FPG) was > 5.5 mmol/l; or conventional therapy with physician adjustment of oral glucose-lowering agents if capillary FPG levels were > 5.5 mmol/l. The primary outcome was the first achievement of two consecutive HbA1c levels 相似文献   

Effects of oral semaglutide on cardiovascular outcomes in individuals with type 2 diabetes and established atherosclerotic cardiovascular disease and/or chronic kidney disease: Design and baseline characteristics of SOUL,a randomized trial

Aim

To describe the design of the SOUL trial (Semaglutide cardiOvascular oUtcomes triaL) and the baseline clinical data of its participants.

Materials and methods

In SOUL, the effects of oral semaglutide, the first oral glucagon-like peptide-1 receptor agonist, on the risk of cardiovascular (CV) events in individuals with type 2 diabetes and established atherosclerotic CV disease (ASCVD) and/or chronic kidney disease (CKD) will be assessed. SOUL is a randomized, double-blind, parallel-group, placebo-controlled CV outcomes trial comparing oral semaglutide (14 mg once daily) with placebo, both in addition to standard of care, in individuals aged ≥50 years with type 2 diabetes and evidence of ASCVD (coronary artery disease [CAD], cerebrovascular disease, symptomatic peripheral arterial disease [PAD]) and/or CKD (estimated glomerular filtration rate <60 mL/min/1.73 m²). The primary outcome is time from randomization to first occurrence of a major adverse CV event (MACE; a composite of CV death, nonfatal myocardial infarction or nonfatal stroke). This event-driven trial will continue until 1225 first adjudication-confirmed MACEs have occurred. Enrolment has been completed.

Results

Overall, 9650 participants were enrolled between June 17, 2019 and March 24, 2021 (men 71.1%, White ethnicity 68.9%, mean age 66.1 years, diabetes duration 15.4 years, body mass index 31.1 kg/m², glycated haemoglobin 63.5 mmol/mol [8.0%]). The most frequently used antihyperglycaemic medications at baseline were metformin (75.7%), insulin and insulin analogues (50.5%), sulphonylureas (29.1%), sodium-glucose cotransporter-2 inhibitors (26.7%) and dipeptidyl peptidase-4 inhibitors (23.0%). At randomization, 70.7% of participants had CAD, 42.3% had CKD, 21.1% had cerebrovascular disease and 15.7% had symptomatic PAD (categories not mutually exclusive). Prevalent heart failure was reported in 23.0% of participants.

Conclusion

SOUL will provide evidence regarding the CV effects of oral semaglutide in individuals with type 2 diabetes and established ASCVD and/or CKD.     

Comparison of repaglinide vs. gliclazide in combination with bedtime NPH insulin in patients with Type 2 diabetes inadequately controlled with oral hypoglycaemic agents.

AIMS: This open-label randomized controlled clinical trial compared the effect on glycaemic control and weight gain of repaglinide vs. gliclazide combined with bedtime NPH insulin in patients with Type 2 diabetes inadequately controlled with oral hypoglycaemic therapy [HbA1c>7.0% (DCCT aligned assay, normal range 4.6-6.2%)]. METHODS: Eighty subjects with Type 2 diabetes were randomized to 13 weeks' open-label treatment with repaglinide 4 mg t.i.d. or gliclazide 160 mg b.i.d. in combination with bedtime NPH insulin (initial dose 0.5 units/kg). The fasting blood glucose (FBG) target was < or =6.0 mmol/l. RESULTS: Baseline characteristics were similar for age, sex, weight, BMI, FBG and HbA1c. Glycaemic control improved similarly in both groups-insulin/gliclazide by (mean) 1.0%, from 9.2 to 8.2% (P=0.001) and by 0.9%, from 9.4 to 8.5% in the insulin/repaglinide group (P=0.005) (P=0.83 between groups). Weight gain averaged (mean +/- sem) 4.1 +/- 0.5 and 3.4 +/- 0.4 kg in the insulin/gliclazide and insulin/repaglinide groups, respectively (P<0.0001 for both groups from baseline) (P=0.29 between groups). The mean number of hypoglycaemic episodes experienced per patient was 2.95 +/- 0.82 (insulin/gliclazide) and 2.3 +/- 0.52 (insulin/repaglinide) (P=0.81 between groups). Both treatments were associated with significant improvements in Diabetes Treatment Satisfaction [Diabetes Treatment Satisfaction Questionnaire-potential range 0 (min) to 36 (max)]; in the insulin/gliclazide group, by 4.9 +/- 1.1 points to 33.3 +/- 0.6 (P<0.0001) and by 3.0 +/- 0.9 points to 34.6 +/- 0.4 (P=0.0006) in the insulin/repaglinide group (P=0.29 between groups). CONCLUSIONS: Over 13 weeks, both repaglinide and gliclazide, when combined with bedtime NPH insulin produce similar significant improvements in glycaemic control (-1%) and similar weight gain.     

Effects of antihypertensive treatment in Asian populations: A meta-analysis of prospective randomized controlled studies (CARdiovascular protectioN group in Asia: CARNA)

To examine the effects of antihypertensive treatment on cardiovascular disease (CVD) in Asian populations, we systematically evaluated prospective randomized studies carried out in Asia (1991–2013). We identified 18 trials with 23,215 and 21,986 hypertensive patients in the intervention (ie, strict blood pressure [BP] lowering or add-on treatment) and reference groups, respectively (mean age, 65 years; follow-up duration, 3.2 years). Analysis was performed through 1) first subgroup: eight trials that compared active antihypertensive treatment with placebo or intensive with less intensive BP control and 2) second subgroup: 10 trials that compared different antihypertensive treatments. In the first subgroup analysis, BP was reduced from 160.3/87.3 mm Hg to 140.2/78.4 mm Hg in the intervention group with a −6.7/−2.2 mm Hg (P < .001) greater BP reduction than the reference group. Compared with the reference group, the intervention group had a lower risk of composite CVD events (odd ratio [OR], 0.73; 95% confidence interval [CI], 0.66–0.81), myocardial infarction (OR, 0.79; 95% CI, 0.63–1.0), stroke (OR, 0.71; 95% CI, 0.63–0.80), and CVD mortality (OR, 0.81; 95% CI, 0.68–0.97; all P ≤ .05). In the second subgroup analysis, no difference was found for any outcome between renin-angiotensin blockers and calcium-channel blockers or diuretics. The meta-regression line among the 18 trials indicated that a 10 mm Hg reduction in systolic BP was associated with a reduced risk for composite CVD events (−39.5%) and stroke (−30.0%). Our meta-analysis shows a benefit when a BP target of less than 140/80 mm Hg is achieved in Asian hypertensives. BP reduction itself, regardless of BP lowering agents, is important for achieving CVD risk reduction.     

Efficacy and safety of dalcetrapib in type 2 diabetes mellitus and/or metabolic syndrome patients, at high cardiovascular disease risk

Aims: Mixed dyslipidaemia, characterized by low levels of high‐density lipoprotein cholesterol (HDL‐C) and high levels of triglycerides, is common in patients with type 2 diabetes mellitus (T2DM) and/or metabolic syndrome. Dalcetrapib effectively increases HDL‐C levels by modulating cholesteryl ester transfer protein (CETP) activity. The aim of this analysis was to investigate the lipid modifying efficacy and safety of dalcetrapib in patients with T2DM and/or metabolic syndrome. Methods: Post hoc analysis of dalcetrapib therapy in five placebo‐controlled, Phase II trials (4–48 weeks of duration) involving T2DM and/or metabolic syndrome, in dyslipidaemic patients with coronary heart disease (CHD) or CHD risk equivalent. Results: Both in patients with and without T2DM and/or metabolic syndrome, dalcetrapib decreased CETP activity by 26–58% and increased HDL‐C levels by 23–34%, depending on dose and duration of treatment. Dalcetrapib did not significantly affect low‐density lipoprotein cholesterol (LDL‐C) or apolipoprotein B levels. Treatment with dalcetrapib was generally well tolerated with a similar number of adverse events reported between patient groups and between those receiving dalcetrapib compared with placebo. Conclusions: Dalcetrapib similarly decreased CETP activity and increased HDL‐C levels in patients with and without T2DM or metabolic syndrome; the ongoing Phase III dal‐OUTCOMES study will help to determine if dalcetrapib's improvement in lipid levels also reduces cardiovascular morbidity and mortality.     

Genetic basis of dyslipidemia in disease precipitation of coronary artery disease (CAD) associated type 2 diabetes mellitus (T2DM)

Type 2 diabetes mellitus (T2DM) and its complications are linked to environmental, clinical, and genetic factors. This review analyses the disorders of lipids and their genetics with respect to coronary artery disease (CAD) associated with T2DM. Cell organelles, hepatitis C‐virus infection, reactive oxygen species produced in mitochondria, and defective insulin signaling due to the arrest of G1 phase to S phase transition of β‐cells have significant roles in the precipitation of the diseases. Adiponectin is anti‐inflammatory and anti‐atherosclerotic and improves insulin resistance. Low‐density lipoprotein (LDL) is atherosclerotic, and LDL‐cholesterol in T2DM is associated with high‐cardiovascular risk. Further, LDL cholesterol reduction significantly reduces cardiovascular morbidity and mortality. High‐density lipoprotein (HDL) is also anti‐atherosclerotic due to HDL associated paraoxonase‐1 serum enzyme, which prevents LDL oxidative modifications and the development of CAD. Moreover, elevated apolipoprotein B and apolipoprotein A‐I (ApoB/ApoA‐I) ratio in plasma is also a risk factor for CAD. LDL receptor, adiponectin, and endocannabinoid receptor‐1 genes are independently associated with CAD and T2DM. Polymorphism of Apo E2 (epsilon2) is a positive factor to increase the T2DM risk and Apo E4 (epsilon4) is a negative factor to reduce the disease risk. Taq 1B polymorphism of cholesterol ester transfer protein (CETP) gene contributes to the development of atherosclerosis, whereas haplotypes of APOA5, APOC3, APOC4, and APOC5 genes are in the same cluster and are independently associated with high plasma triglyceride level, CAD and T2DM. In conclusion, because various genes, LDLR, CETP, APOA5, Apo E, Apo B, and Apo A‐I, are associated with the precipitation of CAD associated with T2DM, a personalized diet–gene intervention therapy may be advocated to reduce the disease precipitation. Copyright © 2014 John Wiley & Sons, Ltd.     

The efficacy and safety of Yijinjing exercise in the adjuvant treatment of ankylosing spondylitis: A protocol of randomized controlled trial

Background:Ankylosing spondylitis (AS) is a chronic systemic autoimmune disease with high disability rate. Conventional treatment regimens have long medication cycles and are associated with adverse reactions. Therapeutic exercise is also considered to be an effective treatment for AS. Evidence suggests that Yijinjing as a low-energy exercise has advantages in adjuncting AS, but there is a lack of standard clinical studies to evaluate its efficacy and safety.Methods:This is a prospective randomized controlled trial to investigate the efficacy and safety of Yijinjing in the adjuvant treatment of AS. Approved by the Clinical Research Ethics Association of our hospital, patients were randomly divided into treatment or control groups in a ratio of 1:1. The treatment group received 4-month Yijinjing training on the basis of conventional treatment, while the control group received conventional treatment and maintained their current lifestyle. The outcome indicators included: activity index, functional ability, Bath Ankylosing Spondylitis Metrology Index, adverse reaction, etc. Finally, SPASS 22.0 software was used for statistical analysis of the data.Discussion:This study evaluated the clinical efficacy of Yijinjing exercise in the adjuvant treatment of AS, and the results of our study will provide a reference for the clinical use of Yijinjing exercise as an effective complementary alternative for the treatment of AS.     

Rationale and protocol of the Study Of diabetic Nephropathy with AtRasentan (SONAR) trial: A clinical trial design novel to diabetic nephropathy

Aims

Individuals with diabetes and chronic kidney disease (CKD) are at high risk for renal events. Recent trials of novel treatments have been negative, possibly because of variability in response to treatment of the target risk factor. Atrasentan is a selective endothelin A receptor antagonist that reduces urinary albumin‐to‐creatinine ratio (UACR), with a large variability between patients. We are assessing its effect on renal outcomes in the Study Of diabetic Nephropathy with AtRasentan (SONAR; NCT01858532) with an enrichment design (>30% lowering of albuminuria) to select patients most likely to benefit.

Materials and Methods

SONAR is a randomized, double‐blind, placebo‐controlled trial with approximately 3500 participants who have stage 2–4 CKD and macroalbuminuria and are receiving a maximum tolerated dose of a renin‐angiotensin system inhibitor.

Results

After 6 weeks of exposure to atrasentan 0.75 mg once daily (enrichment period), participants with ≥30% UACR decrease and no tolerability issues (responders) were randomly assigned to placebo or atrasentan 0.75 mg/day. The responder group will be used for primary efficacy and safety analyses. Approximately 1000 participants with <30% UACR reduction (non‐responders) were also randomized to placebo or atrasentan. The primary endpoint is a composite of a sustained doubling of serum creatinine or end‐stage renal disease. The original power calculation indicated that a total of 425 primary renal events in the responder group provides 90% power to detect a 27% reduction in relative risk (alpha level of .05).

Conclusion

SONAR aims to determine whether atrasentan added to guideline‐recommended therapies safely reduces the risk of CKD progression and delays the onset of end‐stage renal disease in patients with type 2 diabetes and nephropathy. SONAR also aims to establish whether the enrichment of patients based on their initial “surrogate” response to atrasentan will deliver a trial design in accord with personalized treatment of diabetic kidney disease.     

Effect of switching from pioglitazone to the sodium glucose co-transporter-2 inhibitor dapagliflozin on body weight and metabolism-related factors in patients with type 2 diabetes mellitus: An open-label,prospective, randomized,parallel-group comparison trial

The effects of dapagliflozin (DAP) and pioglitazone (PIO) on body weight and glycaemic control were compared in patients with type 2 diabetes mellitus. Seventy-one patients on PIO were either switched to DAP (n = 36) at 5 mg per day or continued on PIO (n = 35). Primary endpoints were superiority of body weight loss and non-inferiority of HbA1c level after 24 weeks with DAP. Body weight decrease was greater with DAP than with PIO (75.3 ± 14.9 to 71.3 ± 15.1 kg vs. 74.7 ± 13.8 to 75.2 ± 13.9 kg; P < 0.01). Change in the HbA1c level was comparable (P = 0.64). The level of N-terminal prohormone of brain natriuretic peptide (NT-proBNP) and urinary albumin : creatinine ratio (ACR) decreased only with DAP (NT-proBNP, P < 0.01; ACR, P = 0.02), and the change in NT-proBNP correlated negatively with baseline NT-proBNP level (ρ = −0.68, P < 0.01) and log-converted ACR (ρ = −0.35, P < 0.05). DAP promotes body weight loss in type 2 diabetes mellitus and may decrease fluid retention, thus reducing the occurrence of cardiovascular events.