Predictive model for identifying mild cognitive impairment in patients with type 2 diabetes mellitus: A CHAID decision tree analysis.

BACKGROUND: As the population ages, mild cognitive impairment (MCI) and type 2 diabetes mellitus (T2DM) become common conditions that often coexist. Evidence has shown that MCI could lead to reduced treatment compliance, medication management, and self-care ability in T2DM patients. Therefore, early identification of those with increased risk of MCI is crucial from a preventive perspective. Given the growing utilization of decision trees in prediction of health-related outcomes, this study aimed to identify MCI in T2DM patients using the decision tree approach. METHODS: This hospital-based case-control study was performed in the Endocrinology Department of Xiangya Hospital affiliated to Central South University between March 2021 and December 2022. MCI was defined based on the Petersen criteria. Demographic characteristics, lifestyle factors, and T2DM-related information were collected. The study sample was randomly divided into the training and validation sets in a 7:3 ratio. Univariate and multivariate analyses were performed, and a decision tree model was established using the chi-square automatic interaction detection (CHAID) algorithm to identify key predictor variables associated with MCI. The area under the curve (AUC) value was used to evaluate the performance of the established decision tree model, and the performance of multivariate regression model was also evaluated for comparison. RESULTS: A total of 1001 participants (705 in the training set and 296 in the validation set) were included in this study. The mean age of participants in the training and validation sets was 60.2  ±  10.3 and 60.4  ±  9.5 years, respectively. There were no significant differences in the characteristics between the training and validation sets (p > .05). The CHAID decision tree analysis identified six key predictor variables associated with MCI, including age, educational level, household income, regular physical activity, diabetic nephropathy, and diabetic retinopathy. The established decision tree model had 15 nodes composed of 4 layers, and age is the most significant predictor variable. It performed well (AUC = .75 [95% confidence interval (CI): .71-.78] and .67 [95% CI: .61-.74] in the training and validation sets, respectively), was internally validated, and had comparable predictive value compared to the multivariate logistic regression model (AUC = .76 [95% CI: .72-.80] and .69 [95% CI: .62-.75] in the training and validation sets, respectively). CONCLUSION: The established decision tree model based on age, educational level, household income, regular physical activity, diabetic nephropathy, and diabetic retinopathy performed well with comparable predictive value compared to the multivariate logistic regression model and was internally validated. Due to its superior classification accuracy and simple presentation as well as interpretation of collected data, the decision tree model is more recommended for the prediction of MCI in T2DM patients in clinical practice.

Sleep quality and its associated factors among patients with type 2 diabetes mellitus in Hunan, China: a cross-sectional study.

OBJECTIVES: Type 2 diabetes mellitus (T2DM) is a serious public health issue. Compared with the general population, patients with T2DM have a higher risk of poor sleep quality, which could ultimately result in poor prognosis. Therefore, this study aimed to evaluate sleep quality and its associated factors among patients with T2DM in Hunan, China. DESIGN: This was a cross-sectional study. SETTING: A tertiary hospital in Hunan, China. PARTICIPANTS: Patients with T2DM hospitalised at the Endocrinology Department were consecutively enrolled between March 2021 and December 2022. Sociodemographic characteristics, lifestyle factors and T2DM-related information were collected retrospectively. PRIMARY AND SECONDARY OUTCOME MEASURES: Sleep quality was evaluated using the Pittsburgh Sleep Quality Index, with a cut-off value of >7 suggesting poor sleep quality. Multivariate logistic regression analysis was used to determine factors associated with poor sleep quality. RESULTS: Of the 1039 participants included, 1001 provided complete data. The mean age of the study sample was 60.24±10.09 years, and 40.5% (95% CI 37.5% to 43.5%) of patients had poor sleep quality. Multivariate logistic regression analysis showed that female sex (adjusted OR (aOR) 1.70, 95% CI 1.25 to 2.29), unmarried status (aOR 1.72, 95% CI 1.05 to 2.83), diabetic retinopathy (aOR 1.38, 95% CI 1.04 to 1.83), diabetic foot (aOR 1.80, 95% CI 1.11 to 2.93) and a per capita monthly household income of >5000 RMB (aOR 0.66, 95% CI 0.47 to 0.93) were associated with poor sleep quality. CONCLUSIONS: Nearly two-fifths of patients with T2DM reported poor sleep quality in Hunan, China. Sex, marital status, diabetic retinopathy, diabetic foot and household income were independently associated with sleep quality among patients with T2DM in Hunan, China.

Prevalence of Anxiety and Associated Factors Among Inpatients with Type 2 Diabetes Mellitus in China: A Cross-Sectional Study.

This study aimed to investigate the prevalence of anxiety and its associated factors among inpatients with type 2 diabetes mellitus (T2DM) in China. This study was a cross-sectional study. Inpatients with T2DM admitted to the Endocrinology Department of Xiangya Hospital, Central South University in Hunan Province of China from March 2021 to December 2021 were consecutively included in this study. Participants were interviewed to obtain the data on socio-demographic characteristics, lifestyle characteristics, T2DM-related information, and social support. Anxiety was measured using the Hospital Anxiety and Depression Scale-anxiety subscale by experienced physicians. Multivariable logistic regression analysis was used to estimate the independent contribution of each independent variable to anxiety. A total of 496 inpatients with T2DM were included in this study. The prevalence of anxiety was 21.8% (95% confidence interval [CI]: 18.1%-25.4%). The results of multivariable logistic regression analysis indicated that age of at least 60 (adjusted odd ratio [aOR] = 1.79, 95% CI: 1.04-3.08), and having diabetes specific complications (aOR = 4.78, 95% CI: 1.02-22.44) were risk factors for anxiety, and an educational level of high school or above (aOR = 0.55, 95% CI: 0.31-0.99), regular physical activity (aOR = 0.36, 95% CI: 0.22-0.58), and high social support (aOR = 0.30, 95% CI: 0.17-0.53) were protective factors for anxiety. A predictive model based on these five variables showed good performance (area under the curve = 0.80). Almost one in five inpatients with T2DM suffered from anxiety in China. Age, educational level, regular physical activity, diabetes specific complications, and social support were independently associated with anxiety.

The use of nomogram for detecting mild cognitive impairment in patients with type 2 diabetes mellitus.

BACKGROUND: Type 2 diabetes mellitus (T2DM) is highly prevalent worldwide and may lead to a higher rate of cognitive dysfunction. This study aimed to develop and validate a nomogram-based model to detect mild cognitive impairment (MCI) in T2DM patients. METHODS: Inpatients with T2DM in the endocrinology department of Xiangya Hospital were consecutively enrolled between March and December 2021. Well-qualified investigators conducted face-to-face interviews with participants to retrospectively collect sociodemographic characteristics, lifestyle factors, T2DM-related information, and history of depression and anxiety. Cognitive function was assessed using the Mini-Mental State Examination scale. A nomogram was developed to detect MCI based on the results of the multivariable logistic regression analysis. Calibration, discrimination, and clinical utility of the nomogram were subsequently evaluated by calibration plot, receiver operating characteristic curve, and decision curve analysis, respectively. RESULTS: A total of 496 patients were included in this study. The prevalence of MCI in T2DM patients was 34.1% (95% confidence interval [CI]: 29.9%-38.3%). Age, marital status, household income, diabetes duration, diabetic retinopathy, anxiety, and depression were independently associated with MCI. Nomogram based on these factors had an area under the curve of 0.849 (95% CI: 0.815-0.883), and the threshold probability ranged from 35.0% to 85.0%. CONCLUSIONS: Almost one in three T2DM patients suffered from MCI. The nomogram, based on age, marital status, household income, duration of diabetes, diabetic retinopathy, anxiety, and depression, achieved an optimal diagnosis of MCI. Therefore, it could provide a clinical basis for detecting MCI in T2DM patients.

Prevalence of comorbid depression and associated factors among hospitalized patients with type 2 diabetes mellitus in Hunan, China.

BACKGROUND: Depression and diabetes are major health challenges, with heavy economic social burden, and comorbid depression in diabetes could lead to a wide range of poor health outcomes. Although many descriptive studies have highlighted the prevalence of comorbid depression and its associated factors, the situation in Hunan, China, remains unclear. Therefore, this study aimed to identify the prevalence of comorbid depression and associated factors among hospitalized type 2 diabetes mellitus (T2DM) patients in Hunan, China. METHODS: This cross-sectional study involved 496 patients with T2DM who were referred to the endocrinology inpatient department of Xiangya Hospital affiliated to Central South University, Hunan. Participants' data on socio-demographic status, lifestyle factors, T2DM-related characteristics, and social support were collected. Depression was evaluated using the Hospital Anxiety and Depression Scale-depression subscale. All statistical analyses were conducted using the R software version 4.2.1. RESULTS: The prevalence of comorbid depression among hospitalized T2DM patients in Hunan was 27.22% (95% Confidence Interval [CI]: 23.3-31.1%). Individuals with depression differed significantly from those without depression in age, educational level, per capita monthly household income, current work status, current smoking status, current drinking status, regular physical activity, duration of diabetes, hypertension, chronic kidney disease, stroke, fatty liver, diabetic nephropathy, diabetic retinopathy, insulin use, HbA1c, and social support. A multivariable logistic regression model showed that insulin users (adjusted OR = 1.86, 95% CI: 1.02-3.42) had a higher risk of depression, while those with regular physical activity (adjusted OR = 0.48, 95% CI: 0.30-0.77) or greater social support (adjusted OR = 0.20, 95% CI: 0.11-0.34) had a lower risk of depression. The area under the curve of the receiver operator characteristic based on this model was 0.741 with a sensitivity of 0.785 and specificity of 0.615. CONCLUSIONS: Depression was moderately prevalent among hospitalized T2DM patients in Hunan, China. Insulin treatment strategies, regular physical activity, and social support were significantly independently associated with depression, and the multivariable model based on these three factors demonstrated good predictivity, which could be applied in clinical practice.

Constructing Prediction Models for Freezing of Gait by Nomogram and Machine Learning: A Longitudinal Study.

Objectives: Although risk factors for freezing of gait (FOG) have been reported, there are still few prediction models based on cohorts that predict FOG. This 1-year longitudinal study was aimed to identify the clinical measurements closely linked with FOG in Chinese patients with Parkinson's disease (PD) and construct prediction models based on those clinical measurements using Cox regression and machine learning. Methods: The study enrolled 967 PD patients without FOG in the Hoehn and Yahr (H&Y) stage 1-3 at baseline. The development of FOG during follow-up was the end-point. Neurologists trained in movement disorders collected information from the patients on a PD medication regimen and their clinical characteristics. The cohort was assessed on the same clinical scales, and the baseline characteristics were recorded and compared. After the patients were divided into the training set and test set by the stratified random sampling method, prediction models were constructed using Cox regression and random forests (RF). Results: At the end of the study, 26.4% (255/967) of the patients suffered from FOG. Patients with FOG had significantly longer disease duration, greater age at baseline and H&Y stage, lower proportion in Tremor Dominant (TD) subtype, a higher proportion in wearing-off, levodopa equivalent daily dosage (LEDD), usage of L-Dopa and catechol-O-methyltransferase (COMT) inhibitors, a higher score in scales of Unified Parkinson's Disease Rate Scale (UPDRS), 39-item Parkinson's Disease Questionnaire (PDQ-39), Non-Motor Symptoms Scale (NMSS), Hamilton Depression Rating Scale (HDRS)-17, Parkinson's Fatigue Scale (PFS), rapid eye movement sleep behavior disorder questionnaire-Hong Kong (RBDQ-HK), Epworth Sleepiness Scale (ESS), and a lower score in scales of Parkinson's Disease Sleep Scale (PDSS) (P < 0.05). The risk factors associated with FOG included PD onset not being under the age of 50 years, a lower degree of tremor symptom, impaired activities of daily living (ADL), UPDRS item 30 posture instability, unexplained weight loss, and a higher degree of fatigue. The concordance index (C-index) was 0.68 for the training set (for internal validation) and 0.71 for the test set (for external validation) of the nomogram prediction model, which showed a good predictive ability for patients in different survival times. The RF model also performed well, the C-index was 0.74 for the test set, and the AUC was 0.74. Conclusions: The study found some new risk factors associated with the FOG including a lower degree of tremor symptom, unexplained weight loss, and a higher degree of fatigue through a longitudinal study, and constructed relatively acceptable prediction models.

Extent, reasons and consequences of off-labeled and unlicensed drug prescription in hospitalized children: a narrative review.

BACKGROUND: Off-label and unlicensed prescriptions pose a severe safety concern among the pediatric population. We aimed to summarize the up-to-date evidence on the extent, reasons, and consequences of off-label and unlicensed drugs in hospitalized pediatric patients. METHODS: We systematically searched PubMed, EMBASE, SCOPUS, Web of Science and Google Scholar between 1990 and 2020 in which the last search was conducted on 12 February 2021. We included studies with the following inclusion criteria: (1) observational studies in design; (2) target population was hospitalized pediatric patients whether admitted in the intensive care unit or in the general ward; (3) study reporting the prevalence of off-label, unlicensed prescriptions or both; and (4) published in English. RESULTS: A total of 47 studies were eligible for inclusion. The proportion of off-label and unlicensed prescriptions ranged from 7.4% to 99.5% and 0.1% to 74.4%, respectively. The most frequent category of off-label prescriptions was prescription outside the age range, with the most commonly reported reason for off-label prescriptions being the lack of information specifically for pediatrics on the drug information leaflets. The consequences of off-label and unlicensed prescriptions ranged from minor and bearable skin reactions to debilitating renal failure, risking deaths. CONCLUSIONS: Off-label and unlicensed prescriptions are extensive and require progressively meditative interventions. However, the pediatric population is currently a "therapeutic orphan". Unless adequate pediatric clinical trials and licensed drugs become available, off-label and unlicensed drug prescription should not entirely be banned but rather promoted in an organized manner.

Lifetime prevalence of suicidal attempt among homeless individuals in North America: a meta-analysis.

BACKGROUND: Homelessness is a compelling public health problem, and homeless individuals are at increased risk for attempting suicide. However, the reported lifetime prevalence of suicidal attempt among homeless individuals in North America varied considerably. Therefore, this meta-analysis aimed to estimate the pooled lifetime prevalence of suicidal attempt among homeless individuals in North America and explore factors that may moderate this estimation. METHODS: The protocol was registered in PROSPERO database (CRD42018102593). A systematic literature search was conducted in the electronic databases of PubMed, Embase, Web of Science, PsycINFO, and Google Scholar. Observational studies exploring the lifetime prevalence of suicidal attempt among homeless individuals in North America were included. Heterogeneity across studies was evaluated using the Cochran Q test and quantified using the I2 statistic. Subgroup analyses were performed to identify possible sources of heterogeneity. RESULTS: Twenty-two eligible studies with a total of 9,727 homeless individuals were included, of which 2,986 reported having attempted suicide in their lifetime. A high degree of heterogeneity (I2=96.4%, P<0.001) was observed, and the pooled lifetime prevalence was 31.83% (95% confidence interval: 26.87%-36.99%). Subgroup analyses showed that the heterogeneity was quite low when estimating the pooled lifetime prevalence of suicidal attempt among heterosexual (I2=0.0, P=0.401) and non-heterosexual homeless individuals (I2=0.0, P=0.405). LIMITATIONS: All eligible studies were exclusively conducted in the US and Canada. CONCLUSIONS: Nearly three tenths of homeless individuals in North America have attempted suicide in their lifetime, and the differences in sexual orientation might have contributed to the heterogeneity.

Impact of mTOR gene polymorphisms and gene-tea interaction on susceptibility to tuberculosis.

BACKGROUND: mTOR gene is a key component of the PI3K/Akt/mTOR signaling pathway, and its dysregulation is associated with various diseases. Several studies have demonstrated that tea drinking is a protective factor against tuberculosis (TB). This study was designed to explore five single nucleotide polymorphisms (SNPs) of mTOR in the Han population of China to determine how their interactions with tea drinking affect susceptibility to TB. AIM: To investigate if the polymorphisms of mTOR gene and the gene-tea interaction are associated with susceptibility to TB. METHODS: In this case-control study, 503 patients with TB and 494 healthy controls were enrolled by a stratified sampling method. The cases were newly registered TB patients from the county-level centers for disease control and prevention, and the healthy controls were permanent residents from Xin'ansi Community, Changsha city. Demographic data and environmental exposure information including tea drinking were obtained from the study participants. We genotyped five potentially functional SNP sites (rs2295080, rs2024627, rs1057079, rs12137958, and rs7525957) of mTOR gene and assessed their associations with the risk of TB using logistic regression analysis, and marginal structural linear odds models were used to estimate the gene-environment interactions. RESULTS: The frequencies of four SNPs (rs2295080, rs2024627, rs1057079, and rs7525957) were found to be associated with susceptibility to TB (P < 0.05). Genotypes GT (OR 1.334), GG (OR 2.224), and GT + GG (OR 1.403) at rs2295080; genotypes CT (OR 1.562) and CT + TT (OR 1.578) at rs2024627, genotypes CT (OR 1.597), CC (OR 2.858), and CT + CC (OR 1.682) at rs1057079; and genotypes CT (OR 1.559) and CT + CC (OR 1.568) at rs7525957 of mTOR gene were significantly more prevalent in TB patients than in healthy controls. The relative excess risk of interaction between the four SNPs (rs2295080, rs2024627, rs1057079, and rs7525957) of mTOR genes and tea drinking were found to be -1.5187 (95%CI: -1.9826, -1.0547, P < 0.05), -1.8270 (95%CI: -2.3587, -1.2952, P < 0.05), -2.3246 (95%CI: -2.9417, -1.7076, P < 0.05) and -0.4235 (95%CI: -0.7756, -0.0714, P < 0.05), respectively, which suggest negative interactions. CONCLUSION: The polymorphisms of mTOR (rs2295080, rs2024627, rs1057079, and rs7525957) are associated with susceptibility to TB, and there is a negative interaction between each of the four SNPs and tea drinking.

Effects of vibration therapy on muscle mass, muscle strength and physical function in older adults with sarcopenia: a systematic review and meta-analysis.

BACKGROUND: Sarcopenia, a progressive loss of muscle mass and function with advancing age, is a prevalent condition among older adults. As most older people are too frail to do intensive exercise and vibration therapy has low risk and ease of participation, it may be more readily accepted by elderly individuals. However, it remains unclear whether vibration therapy would be effective among older adults with sarcopenia. This systematic review and meta-analysis examined the effect of vibration therapy including local vibration therapy and whole-body vibration therapy, for enhancing muscle mass, muscle strength and physical function in older people with sarcopenia. METHODS: A systematic literature search was conducted in March 2019 in the following 5 electronic databases: PubMed, CINAHL, Embase, PEDro, and the Cochrane Central Register of Controlled Trials, with no restriction of language or the year of publication. Randomized controlled trials and quasi-experimental studies examining effects of vibration therapy on muscle mass, muscle strength or physical function in older adults with sarcopenia were included in this systematic review. Two reviewers independently assessed the methodological quality of the selected studies. RESULTS: Of the 1972 identified studies, seven publications from six studies involving 223 participants were included in this systematic review. Five of them conducted whole-body vibration therapy, while two conducted local vibration therapy. A meta-analysis of randomized controlled studies indicated that muscle strength significantly increased after whole-body vibration therapy (SMD 0.69, 95% CI 0.28 to 1.11, I2 = 0%, P = 0.001) and local vibration therapy (SMD 3.78, 95% CI 2.29 to 5.28, P < 0.001). Physical performance measured by the sit-to-stand test and the timed-up-and-go test were significantly improved after the intervention (SMD -0.79, 95% CI - 1.21 to - 0.37, I2 = 0%, P < 0.001) and SMD -0.83, 95% CI - 1.56 to - 0.11, I2 = 64%, P = 0.02, respectively). CONCLUSION: Vibration therapy could be a prospective strategy for improving muscle strength and physical performance in older adults with sarcopenia. However, due to the limited number of the included studies, caution is needed when interpreting these results. More well-designed, large sample size studies should be conducted to further explore and validate the benefits of vibration therapy for this population.

Nursing home staff experiences of implementing mentorship programmes: A systematic review and qualitative meta-synthesis.

AIM: To determine nursing home staff experiences in mentorship programmes, and staff perceptions of the enablers and barriers to implement mentorship programmes. BACKGROUND: Mentorship programmes are perceived as playing an important role in improving the quality of care in nursing homes. However, little is known about research evidence across the global about staff's experiences in the programmes. METHODS: A search for studies published from the earliest available date to April 2019 was undertaken. Two reviewers performed data extraction and an appraisal of eight studies using tools from the Joanna Briggs Institute. A pragmatic meta-aggregative approach was applied to synthesise the findings. The qualitative research that was included was analysed to identify 63 findings that were organised into 12 categories and combined into three syntheses. RESULTS: The implementation of effective mentorship programmes is influenced by three factors: mentor capability, opportunity in the mentorship programmes, and motivation in the mentorship programmes. CONCLUSIONS: There are a number of studies of nursing home staff experiences of mentorship programmes. However, systematic reviews that synthesise findings in this field are lacking. It is crucial to tailor the programme design to suit each unique nursing home care setting. We identified barriers and enablers, and learned that no barriers are insurmountable. IMPLICATIONS FOR NURSING MANAGEMENT: Findings will inform nurse managers of an ideal environment for the implementation of a successful mentorship programme. Nursing homes need to establish and sustain mentorship programmes to help improve workforce capacity in delivering high-quality care for residents.

Overview of systematic reviews with meta-analyses on acupuncture in post-stroke cognitive impairment and depression management.

Background: Acupuncture has been using as an alternative non-pharmacological therapy in the management of post stroke depression and cognitive impairment but its effectiveness and safety remain controversial. We conducted an overview of systematic reviews with meta-analyses to evaluate the evidence on the effect of acupuncture in the treatment of stroke with conventional medicine intervention. Methods: Systematic reviews summarized the treatment effects of acupuncture for post stroke cognitive impairment and post stroke depression were considered eligible. Methodological quality of included systematic reviews was assessed using A MeaSurement Tool to Assess systematic Reviews 2 (AMSTAR 2). Results: Four systematic reviews on post stroke cognitive impairment and ten systematic reviews on post stroke depression with good methodological quality were included. Meta-analyses revealed that acupuncture plus cognitive rehabilitation; and acupuncture or moxibustion plus cognitive rehabilitation, versus cognitive rehabilitation demonstrated statistically significant increase in Mini-Mental State Examination scores in compared to cognitive rehabilitation after 4 weeks treatment [Pooled weighted mean difference (WMD) = 3.14, 95% confidence interval (CI) = 2.06 to 4.21, I2 = 36%]; and (Pooled WMD = 3.22, 95% CI = 2.09 to 4.34, I2 = 0%). Furthermore, acupuncture versus antidepressant demonstrated statistically significant improve depression measured by increasing in 17-item Hamilton Depression Rating Scale in comparing to cognitive rehabilitation after 2 weeks treatment (Pooled WMD= -2.34, 95% CI= -3.46 to -1.22, I2 = 5%). Acupuncture usage was not associated with increased risk of adverse events. Conclusions: Acupuncture is safe and improves cognitive function and depressive disorder without obvious serious adverse events for post stroke patients.

Safety of Acupuncture: Overview of Systematic Reviews.

Acupuncture is increasingly used worldwide. It is becoming more accepted by both patients and healthcare providers. However, the current understanding of its adverse events (AEs) is fragmented. We conducted this overview to collect all systematic reviews (SRs) on the AEs of acupuncture and related therapies. MEDLINE and EMBASE were searched from inception to December 2015. Methodological quality of included reviews was assessed with a validated instrument. Evidence was narratively reported. Seventeen SRs covering various types of acupuncture were included. Methodological quality of the reviews was overall mediocre. Four major categories of AEs were identified, which are organ or tissue injuries (13 reviews, median: 36 cases, median deaths: 4), infections (11 reviews, median: 17 cases, median deaths: 0.5), local AEs or reactions (12 reviews, median: 8.5 cases, no deaths were reported), and other complications such as dizziness or syncope (11 reviews, median: 21 cases, no deaths were reported). Minor and serious AEs can occur during the use of acupuncture and related modalities, contrary to the common impression that acupuncture is harmless. Serious AEs are rare, but need significant attention as mortality can be associated with them. Referrals should consider acupuncturists' training credibility, and patient safety should be a core part of acupuncture education.

Characteristics and Methodological Quality of Meta-Analyses on Hypertension Treatments-A Cross-Sectional Study.

Methodological quality of meta-analyses on hypertension treatments can affect treatment decision-making. The authors conducted a cross-sectional study to investigate the methodological quality of meta-analyses on hypertension treatments. One hundred and fifty-eight meta-analyses were identified. Overall, methodological quality was unsatisfactory in the following aspects: comprehensive reporting of financial support (1.9%), provision of included and excluded lists of studies (22.8%), inclusion of grey literature (27.2%), and inclusion of protocols (32.9%). The 126 non-Cochrane meta-analyses had poor performance on almost all the methodological items. Non-Cochrane meta-analyses focused on nonpharmacologic treatments were more likely to consider scientific quality of included studies when making conclusions. The 32 Cochrane meta-analyses generally had good methodological quality except for comprehensive reporting of the sources of support. These results highlight the need for cautious interpretation of these meta-analyses, especially among physicians and policy makers when guidelines are formulated. Future meta-analyses should pay attention to improving these methodological aspects.

Yoga for asthma.

BACKGROUND: Asthma is a common chronic inflammatory disorder affecting about 300 million people worldwide. As a holistic therapy, yoga has the potential to relieve both the physical and psychological suffering of people with asthma, and its popularity has expanded globally. A number of clinical trials have been carried out to evaluate the effects of yoga practice, with inconsistent results. OBJECTIVES: To assess the effects of yoga in people with asthma. SEARCH METHODS: We systematically searched the Cochrane Airways Group Register of Trials, which is derived from systematic searches of bibliographic databases including the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, EMBASE, CINAHL, AMED, and PsycINFO, and handsearching of respiratory journals and meeting abstracts. We also searched PEDro. We searched ClinicalTrials.gov and the WHO ICTRP search portal. We searched all databases from their inception to 22 July 2015, and used no restriction on language of publication. We checked the reference lists of eligible studies and relevant review articles for additional studies. We attempted to contact investigators of eligible studies and experts in the field to learn of other published and unpublished studies. SELECTION CRITERIA: We included randomized controlled trials (RCTs) that compared yoga with usual care (or no intervention) or sham intervention in people with asthma and reported at least one of the following outcomes: quality of life, asthma symptom score, asthma control, lung function measures, asthma medication usage, and adverse events. DATA COLLECTION AND ANALYSIS: We extracted bibliographic information, characteristics of participants, characteristics of interventions and controls, characteristics of methodology, and results for the outcomes of our interest from eligible studies. For continuous outcomes, we used mean difference (MD) with 95% confidence interval (CI) to denote the treatment effects, if the outcomes were measured by the same scale across studies. Alternatively, if the outcomes were measured by different scales across studies, we used standardized mean difference (SMD) with 95% CI. For dichotomous outcomes, we used risk ratio (RR) with 95% CI to measure the treatment effects. We performed meta-analysis with Review Manager 5.3. We used the fixed-effect model to pool the data, unless there was substantial heterogeneity among studies, in which case we used the random-effects model instead. For outcomes inappropriate or impossible to pool quantitatively, we conducted a descriptive analysis and summarized the findings narratively. MAIN RESULTS: We included 15 RCTs with a total of 1048 participants. Most of the trials were conducted in India, followed by Europe and the United States. The majority of participants were adults of both sexes with mild to moderate asthma for six months to more than 23 years. Five studies included yoga breathing alone, while the other studies assessed yoga interventions that included breathing, posture, and meditation. Interventions lasted from two weeks to 54 months, for no more than six months in the majority of studies. The risk of bias was low across all domains in one study and unclear or high in at least one domain for the remainder.There was some evidence that yoga may improve quality of life (MD in Asthma Quality of Life Questionnaire (AQLQ) score per item 0.57 units on a 7-point scale, 95% CI 0.37 to 0.77; 5 studies; 375 participants), improve symptoms (SMD 0.37, 95% CI 0.09 to 0.65; 3 studies; 243 participants), and reduce medication usage (RR 5.35, 95% CI 1.29 to 22.11; 2 studies) in people with asthma. The MD for AQLQ score exceeded the minimal clinically important difference (MCID) of 0.5, but whether the mean changes exceeded the MCID for asthma symptoms is uncertain due to the lack of an established MCID in the severity scores used in the included studies. The effects of yoga on change from baseline forced expiratory volume in one second (MD 0.04 liters, 95% CI -0.10 to 0.19; 7 studies; 340 participants; I2 = 68%) were not statistically significant. Two studies indicated improved asthma control, but due to very significant heterogeneity (I2 = 98%) we did not pool data. No serious adverse events associated with yoga were reported, but the data on this outcome was limited. AUTHORS CONCLUSIONS: We found moderate-quality evidence that yoga probably leads to small improvements in quality of life and symptoms in people with asthma. There is more uncertainty about potential adverse effects of yoga and its impact on lung function and medication usage. RCTs with a large sample size and high methodological and reporting quality are needed to confirm the effects of yoga for asthma.

Epidemiological characteristics and methodological quality of meta-analyses on diabetes mellitus treatment: a systematic review.

OBJECTIVE: Well-conducted meta-analyses (MAs) are considered as one of the best sources of clinical evidence for treatment decision. MA with methodological flaws may introduce bias and mislead evidence users. The aim of this study is to investigate the characteristics and methodological quality of MAs on diabetes mellitus (DM) treatments. DESIGN: Systematic review. METHODS: Cochrane Database of Systematic Review and Database of Abstract of Reviews of Effects were searched for relevant MAs. Assessing methodological quality of systematic reviews (AMSTAR) tool was used to evaluate the methodological quality of included MAs. Logistic regression analysis was used to identify association between characteristics of MA and AMSTAR results. RESULTS: A total of 252 MAs including 4999 primary studies and 13,577,025 patients were included. Over half of the MAs (65.1%) only included type 2 DM patients and 160 MAs (63.5%) focused on pharmacological treatments. About 89.7% MAs performed comprehensive literature search and 89.3% provided characteristics of included studies. Included MAs generally had poor performance on the remaining AMSTAR items, especially in assessing publication bias (39.3%), providing lists of studies (19.0%) and declaring source of support comprehensively (7.5%). Only 62.7% MAs mentioned about harm of interventions. MAs with corresponding author from Asia performed less well in providing MA protocol than those from Europe. CONCLUSIONS: Methodological quality of MA on DM treatments was unsatisfactory. There is considerable room for improvement, especially in assessing publication bias, providing lists of studies and declaring source of support comprehensively. Also, there is an urgent need for MA authors to report treatment harm comprehensively.

Yoga for asthma.

BACKGROUND: Asthma is a common chronic inflammatory disorder affecting about 300 million people worldwide. As a holistic therapy, yoga has the potential to relieve both the physical and psychological suffering of people with asthma, and its popularity has expanded globally. A number of clinical trials have been carried out to evaluate the effects of yoga practice, with inconsistent results. OBJECTIVES: To assess the effects of yoga in people with asthma. SEARCH METHODS: We systematically searched the Cochrane Airways Group Register of Trials, which is derived from systematic searches of bibliographic databases including the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, EMBASE, CINAHL, AMED, and PsycINFO, and handsearching of respiratory journals and meeting abstracts. We also searched PEDro. We searched ClinicalTrials.gov and the WHO ICTRP search portal. We searched all databases from their inception to 22 July 2015, and used no restriction on language of publication. We checked the reference lists of eligible studies and relevant review articles for additional studies. We attempted to contact investigators of eligible studies and experts in the field to learn of other published and unpublished studies. SELECTION CRITERIA: We included randomised controlled trials (RCTs) that compared yoga with usual care (or no intervention) or sham intervention in people with asthma and reported at least one of the following outcomes: quality of life, asthma symptom score, asthma control, lung function measures, asthma medication usage, and adverse events. DATA COLLECTION AND ANALYSIS: We extracted bibliographic information, characteristics of participants, characteristics of interventions and controls, characteristics of methodology, and results for the outcomes of our interest from eligible studies. For continuous outcomes, we used mean difference (MD) with 95% confidence interval (CI) to denote the treatment effects, if the outcomes were measured by the same scale across studies. Alternatively, if the outcomes were measured by different scales across studies, we used standardised mean difference (SMD) with 95% CI. For dichotomous outcomes, we used risk ratio (RR) with 95% CI to measure the treatment effects. We performed meta-analysis with Review Manager 5.3. We used the fixed-effect model to pool the data, unless there was substantial heterogeneity among studies, in which case we used the random-effects model instead. For outcomes inappropriate or impossible to pool quantitatively, we conducted a descriptive analysis and summarised the findings narratively. MAIN RESULTS: We included 15 RCTs with a total of 1048 participants. Most of the trials were conducted in India, followed by Europe and the United States. The majority of participants were adults of both sexes with mild to moderate asthma for six months to more than 23 years. Five studies included yoga breathing alone, while the other studies assessed yoga interventions that included breathing, posture, and meditation. Interventions lasted from two weeks to 54 months, for no more than six months in the majority of studies. The risk of bias was low across all domains in one study and unclear or high in at least one domain for the remainder.There was some evidence that yoga may improve quality of life (MD in Asthma Quality of Life Questionnaire (AQLQ) score per item 0.57 units on a 7-point scale, 95% CI 0.37 to 0.77; 5 studies; 375 participants), improve symptoms (SMD 0.37, 95% CI 0.09 to 0.65; 3 studies; 243 participants), and reduce medication usage (RR 5.35, 95% CI 1.29 to 22.11; 2 studies) in people with asthma. The MD for AQLQ score exceeded the minimal clinically important difference (MCID) of 0.5, but whether the mean changes exceeded the MCID for asthma symptoms is uncertain due to the lack of an established MCID in the severity scores used in the included studies. The effects of yoga on change from baseline forced expiratory volume in one second (MD 0.04 litres, 95% CI -0.10 to 0.19; 7 studies; 340 participants; I(2) = 68%) were not statistically significant. Two studies indicated improved asthma control, but due to very significant heterogeneity (I(2) = 98%) we did not pool data. No serious adverse events associated with yoga were reported, but the data on this outcome was limited. AUTHORS' CONCLUSIONS: We found moderate-quality evidence that yoga probably leads to small improvements in quality of life and symptoms in people with asthma. There is more uncertainty about potential adverse effects of yoga and its impact on lung function and medication usage. RCTs with a large sample size and high methodological and reporting quality are needed to confirm the effects of yoga for asthma.

Interleukin-2 as maintenance therapy for children and adults with acute myeloid leukaemia in first complete remission.

BACKGROUND: Acute myeloid leukaemia (AML) is a malignant cancer of hematopoietic stem cells. The treatment of AML consists of two treatment phases: the remission induction phase to achieve a rapid, complete remission (CR) and the consolidation phase to achieve a durable molecular remission. People in CR are at risk of AML relapse, and people with relapsed AML have poor survival prospects. Thus, there is a continuous need for treatments to further improve prognosis. Interleukin-2 (IL-2), an immune-stimulatory cytokine, is an alternative to standard treatment for people with AML to maintain the efficacy after consolidation therapy. Maintenance therapy is not an integral part of the standard treatment for AML. Studies have been conducted to evaluate the efficacy of IL-2 as maintenance therapy for people with AML in first CR, but the effect of IL-2 is not yet fully established. OBJECTIVES: To evaluate the efficacy and safety of IL-2 as maintenance therapy for children and adults with AML who have achieved first CR and have not relapsed. SEARCH METHODS: We systematically searched the Cochrane Central Register of Controlled Trials (CENTRAL) (Cochrane Library 2015, Issue 8), MEDLINE (1950 to August 2015), EMBASE (1950 to August 2015), LILACS (1982 to August 2015), CBM (1978 to August 2015), relevant conference proceedings (2000 to 2015), and metaRegister of Controlled Trials (since inception to August 2015) of ongoing and unpublished trials. In addition, we screened the reference lists of relevant trials and reviews. SELECTION CRITERIA: Eligible studies were randomised controlled trials (RCTs) comparing IL-2 with no treatment in people with AML who had achieved first CR and had not relapsed. We did not identify studies comparing IL-2 versus best supportive care or maintenance chemotherapy or studies comparing IL-2 plus maintenance chemotherapy versus maintenance chemotherapy alone. DATA COLLECTION AND ANALYSIS: Two review authors independently screened studies, extracted data with a predefined extraction form, and assessed risk of bias of included studies. We extracted data on the following outcomes: disease-free survival, overall survival, event-free survival, treatment-related mortality, adverse events, and quality of life. We measured the treatment effect on time-to-event outcomes and dichotomous outcomes with hazard ratio (HR) and risk ratio, respectively. We used inverse-variance method to combine HRs with fixed-effect model unless there was significant between-study heterogeneity. MAIN RESULTS: We included nine RCTs with a total of 1665 participants, comparing IL-2 with no treatment. Six studies included adult participants, and three studies included both adults and children. However, the latter three studies did not report data for children, thus we were unable to conduct subgroup analysis of children. One Chinese study did not report any outcomes of interest for this review. We included six trials involving 1426 participants in the meta-analysis on disease-free survival, and included five trials involving 1355 participants in the meta-analysis on overall survival. There is no evidence for difference between IL-2 group and no-treatment group regarding disease-free survival (HR 0.95; 95% CI 0.86 to 1.06, P = 0.37; quality of evidence: low) or overall survival (HR 1.05; 95% CI 0.95 to 1.16, P = 0.35; quality of evidence: moderate). Based on one trial of 161 participants, IL-2 exerted no effect on event-free survival (HR 1.02; 95% CI 0.79 to 1.32, P = 0.88; quality of evidence: low). Adverse events (including thrombocytopenia, neutropenia, malaise/fatigue, and infection/fever) were more frequent in participants receiving IL-2, according to one trial of 308 participants. No mortality due to adverse events was reported. None of the included studies reported treatment-related mortality or quality of life. AUTHORS' CONCLUSIONS: There is no evidence for a difference between IL-2 maintenance therapy and no treatment with respect to disease-free survival or overall survival of people with AML in first CR; however, the quality of the evidence is moderate or low, and further research is likely or very likely to have an important impact on the estimate or our confidence in the estimate. Adverse events seem to be more frequent in participants treated with IL-2, but the quality of the evidence is very low and our confidence in the estimates is very uncertain. Thus, further prospective randomised trials are needed before definitive conclusions can be drawn on these issues.

Blood as a Substitute for Tumor Tissue in Detecting EGFR Mutations for Guiding EGFR TKIs Treatment of Nonsmall Cell Lung Cancer: A Systematic Review and Meta-Analysis.

Tumor tissues are often absent or insufficient for testing epidermal growth factor receptor (EGFR) mutations to guide EGFR tyrosine kinase inhibitors (TKIs) treatment of patients with nonsmall cell lung cancer (NSCLC). We conducted this systematic review and meta-analysis to assess whether blood can be used as a substitute for tumor tissue in detecting EGFR mutations. MEDLINE, EMBASE, and the Cochrane Library were searched for studies that provided data to estimate the accuracy of blood testing against tissue testing in NSCLC patients and/or those directly compared the efficacy of EGFR TKIs in EGFR mutant and wild-type patients according to sources of specimens. Sensitivity, specificity, and concordance rate were used as measures of the accuracy. Risk ratio (RR) for objective response and hazard ratio (HR) for progression-free survival (PFS) and overall survival (OS) were used as measures for treatment efficacy. We combined the effects by using the fixed-effects model unless there was evidence of heterogeneity, in which case a random-effects mode was used. This systematic review included 25 studies with 2605 patients. The pooled overall sensitivity, specificity, and concordance rate were 0.61, 0.90, and 0.79, respectively. Serum showed lower sensitivity (0.56 vs 0.65) but higher specificity (0.95 vs 0.85) and higher concordance (0.86 vs 0.74) than plasma. EGFR mutations (exon 19 or 21) in blood were significantly associated with objective response (RR: 4.08; 95% confidence interval [CI] 2.48-6.70), PFS (HR: 0.72; 95% CI 0.64-0.80), and OS (HR: 0.71; 95% CI 0.50-0.99). Importantly, the association of the mutations with the 3 clinical outcomes for serum was similar to that for tumor tissue and higher than that for plasma. Blood, in particular serum, is a good substitute when tumor tissue is absent or insufficient for testing EGFR mutations to guide EGFR TKIs treatment in patients with NSCLC. EGFR mutation positivity in blood could be used to recommend EGFR TKIs treatment, but the absence of blood positivity should not necessarily be construed with confirmed negativity.

Concordant analysis of KRAS, BRAF, PIK3CA mutations, and PTEN expression between primary colorectal cancer and matched metastases.

Current data on the concordance of KRAS, BRAF, PIK3CA mutation status or PTEN expression status between primary tumors and metastases in colorectal cancer (CRC) are conflicting. We conducted a systematic review and meta-analysis to examine concordance and discordance of the status of these four biomarkers between primary tumors and corresponding metastases in CRC patients. The biomarker status in primary tumors was used as the reference standard. Concordance data for KRAS, BRAF, PIK3CA and PTEN were provided by 43, 16, 9 and 7 studies, respectively. The pooled concordance rate was 92.0% (95% CI: 89.7%-93.9%) for KRAS, 96.8% (95% CI: 94.8%-98.0%) for BRAF, 93.9% (95% CI: 89.7%-96.5%) for PIK3CA and 71.7% (95% CI: 57.6%-82.5%) for PTEN. The pooled false positive and false negative rates for KRAS were 9.0% (95% CI: 6.5%-12.4%) and 11.3% (95% CI: 8.0%-15.8%), respectively. KRAS, BRAF and PIK3CA mutations are highly concordant between primary tumors and corresponding metastases in CRC, but PTEN loss is not. Nine percent of patients with wild-type KRAS in primary tumors who received anti-EGFR treatment had mutant KRAS in metastases, while 11.3% patients with mutant KRAS primary tumors had wild-type KRAS in the metastases. These 11.3% patients currently do not receive potentially beneficial anti-EGFR treatment.