Global Burden, Regional Differences, Trends, and Health Consequences of Medication Nonadherence for Hypertension During 2010 to 2020: A Meta-Analysis Involving 27 Million Patients.

Background Nonadherence to antihypertensive medications is the leading cause of poor blood pressure control and thereby cardiovascular diseases and mortality worldwide. Methods and Results We investigated the global epidemiology, regional differences, and trend of antihypertensive medication nonadherence via a systematic review and meta-analyses of data from 2010 to 2020. Multiple medical databases and clinicaltrials.gov were searched for articles. Observational studies reporting the proportion of patients with anti-hypertensive medication nonadherence were included. The proportion of nonadherence, publication year, year of first recruitment, country, and health outcomes attributable to antihypertensive medication nonadherence were extracted. Two reviewers screened abstracts and full texts, classified countries according to levels of income and locations, and extracted data. The Joanna Briggs Institute prevalence critical appraisal tool was used to rate the included studies. Prevalence meta-analyses were conducted using a fixed-effects model, and trends in prevalence were analyzed using meta-regression. The certainty of evidence concerning the effect of health consequences of nonadherence was rated according to Grading of Recommendations, Assessment, Development and Evaluations. A total of 161 studies were included. Subject to different detection methods, the global prevalence of anti-hypertensive medication nonadherence was 27% to 40%. Nonadherence was more prevalent in low- to middle-income countries than in high-income countries, and in non-Western countries than in Western countries. No significant trend in prevalence was detected between 2010 and 2020. Patients with antihypertensive medication nonadherence had suboptimal blood pressure control, complications from hypertension, all-cause hospitalization, and all-cause mortality. Conclusions While high prevalence of anti-hypertensive medication nonadherence was detected worldwide, higher prevalence was detected in low- to middle-income and non-Western countries. Interventions are urgently required, especially in these regions. Current evidence is limited by high heterogeneity. Registration URL: www.crd.york.ac.uk/prospero/; Unique identifier: CRD42021259860.

Sensitivity and specificity of automated blood pressure devices to detect atrial fibrillation: A systematic review and meta-analysis of diagnostic accuracy.

Background: Atrial fibrillation (AF) is a prevalent and preventable cause of stroke and mortality. Aim: This systematic review and meta-analysis aimed to investigate the sensitivity and specificity of office and out-of-office automated blood pressure (BP) devices to detect AF. Methods: Diagnostic studies, extracted from databases such as Ovid Medline and Embase, on AF detection by BP device(s), electrocardiography, and reported sensitivity and specificity, were included. Screening of abstracts and full texts, data extraction, and quality assessment were conducted independently by two investigators using Covidence software. The sensitivity and specificity of the BP devices were pooled using a random-effects model. Results: Sixteen studies including 10,158 participants were included. Only a few studies were conducted in primary care (n = 3) or with a low risk of bias (n = 5). Office BP devices, which utilised different algorithms to detect AF, had a sensitivity and specificity of 96.2 and 94%, respectively. Specificity was reduced when only one positive result was considered among consecutive BP measurements. Only a few studies (n = 3) investigated out-of-office BP. Only one study (n = 100) suggested the use of ≥79 and ≥26% of positive readings on 24-h ambulatory BP measurements to detect AF and paroxysmal AF, respectively. Conclusions: Office BP devices can be used clinically to screen for AF in high-risk populations. Clinical trials are needed to determine the effect of AF screening using office BP devices in reducing stroke risk and mortality. Further studies are also required to guide out-of-office use of BP devices for detecting paroxysmal AF or AF. Systematic review registration: https://www.crd.york.ac.uk/prospero/display_record.php?ID=CRD42022319541, PROSPERO CRD42022319541.

Controlled-release oral melatonin supplementation for hypertension and nocturnal hypertension: A systematic review and meta-analysis.

Oral melatonin is a potential alternative treatment for hypertension and nocturnal hypertension. However, high-quality and relevant meta-analyses are lacking. This meta-analysis aimed to investigate whether oral melatonin supplementation reduces daytime/asleep blood pressure and cardiovascular risk, improves sleep quality, and is well-tolerated compared with placebo. Relevant articles were searched in multiple databases, including MEDLINE, EMBASE, CINAHL Complete, and the Cochrane Library, from their inception to June 2021. The included studies were randomized controlled trials recruiting patients with hypertension, using oral melatonin as the sole intervention, and investigating its effect on blood pressure. The mean out-of-office (including 24-h, daytime, and asleep) systolic and diastolic blood pressures, sleep quality, and side effects were compared between the melatonin and placebo arms using pairwise random-effect meta-analyses. A risk of bias assessment was performed using the Cochrane risk-of-bias tool. Four studies were included in the analysis and only one study was considered to have a low risk of bias. No study reported on cardiovascular risk or outcomes. Only controlled-release melatonin (not an immediate-release preparation) reduced asleep systolic blood pressure by 3.57 mm Hg (95% confidence interval: -7.88 to .73; I2  = 0%). It also reduced asleep and awake diastolic blood pressure, but these differences were not statistically significant. Melatonin improves sleep efficacy and total sleep time and is safe and well-tolerated. Due to the limited number of high-quality trials, the quality of evidence was low to very low. Therefore, adequately powered randomized controlled trials on melatonin are warranted.

Clear cell carcinoma of the urinary bladder: a systematic review.

PURPOSE: We conducted a systematic review of the literature on primary clear cell carcinoma (CCC) of the urinary bladder. METHODS: A literature search using keywords and MeSH terms related to "clear cell carcinoma", "clear cell adenocarcinoma", "mesonephroma" and "urinary bladder" in EMBASE, MEDLINE and Cochrane Central Register of Controlled Trials was performed. A manual search was performed with web-based search engine Google Scholar. Reference lists of the included studies were screened for additional articles. Articles up till 16th July 2020 were retrieved. Observational human studies on primary CCC in urinary bladder with English full-text were included for further analysis. RESULTS: 904 articles were identified and 44 articles were included for further analysis. Data including clinical features, tumour characteristics, treatment and oncological outcomes were reviewed. There were 70 patients (44 females and 26 males) reported in literatures and included in this review. Gross haematuria was the most common presentation (79.7%), followed by irritative urinary symptoms (47.5%). Regarding the histology, tubulocystic pattern is the most common histologic pattern (49.1%), and 52.6% had muscle invasion. Most cases were CK7 (96.6%) and CK20 (88.9%) positive. CA125 (96%) was commonly positive, indicating its potential origin from mullerian duct. Most patients received surgery (95.5%) as primary treatment. However, the oncological outcomes were unsatisfactory with a 2-year survival rate of 60.0%. CONCLUSION: Clear cell carcinoma is an uncommon subtype of bladder cancer which can be diagnosed by histology and immunohistochemical staining result. The majority of patients presented with muscle invasion and had a poor survival despite aggressive treatment.

Comparison Between Automated Office Blood Pressure Measurements and Manual Office Blood Pressure Measurements-Implications in Individual Patients: a Systematic Review and Meta-analysis.

PURPOSE OF REVIEW: Automated office blood pressure (AOBP) measurements may provide more accurate estimation of blood pressure (BP) than manual office blood pressure (MOBP) measurements. This systematic review investigated the diagnostic performance of AOBP and MOBP using ambulatory blood pressure measurement (ABPM) as reference. Several databases including MEDLINE, Embase, Scopus, and China Academic Journals were searched. Data were extracted, double-checked by two investigators, and were analysed using a random effects model. RECENT FINDINGS: A total of 26 observational studies were included. The mean systolic/diastolic BP obtained by AOBP was not significantly different from that obtained by ABPM. The sensitivity and specificity of AOBP to detect elevated BP were approximately 70%. Fewer participants had white-coat hypertension on AOBP measurement than on MOBP measurement (7% versus 14%); however, about 13% had masked hypertension on AOBP measurement. The width of the limit of agreement comparing (i) AOBP and ABPM and (ii) MOBP and ABPM was comparable. AOBP may reduce the rate of the observed white-coat effect but undermine masked hypertension. The current recommendation, however, is limited by the absence of high-quality studies and the high heterogeneity of our results. More high-quality studies using different AOBP machines and in different population are therefore needed.

Effect and Acceptability of Mindfulness-Based Stress Reduction Program on Patients With Elevated Blood Pressure or Hypertension: A Meta-Analysis of Randomized Controlled Trials.

The mindfulness-based stress reduction program (MBSR) may reduce blood pressure (BP) in patients with hypertension or elevated BP. However, some important parameters (such as asleep BP) have not been investigated in previous reviews, and a well-conducted meta-analysis is lacking. This meta-analysis investigates the effect and acceptability of MBSR on patients with elevated BP or hypertension. Relevant articles were searched in multiple databases, including MEDLINE, EMBASE, and APA PsycInfo. Included studies were randomized controlled trials that involved patients with an elevated BP, had a control group, and investigated the effect of MBSR. The mean office and out-of-office (including 24-hour, daytime, and asleep) systolic BP and diastolic BP, psychological outcomes (depression/anxiety/stress), and dropout rate were compared between the MBSR arm and the control arm using a random-effects model. Quality assessment was conducted based on the Cochrane risk-of-bias tool. Twelve studies were included, and only one was considered having low risk of bias. MBSR decreased the office systolic BP and diastolic BP by 6.64 and 2.47 mm Hg at postintervention, respectively; the reduction in diastolic BP was sustained until 3 to 6 months after the recruitment. Our meta-analyses did not find a significant reduction in out-of-office BP after MBSR. MBSR reduced depressive, anxiety, and stress symptoms. The dropout rate from MBSR arm was 15% and was similar to that of control arm. The current evidence is limited by lack of high-quality and adequately powered trials with long-term follow-up. Furthermore, out-of-office BP was only reported by few trials.

Short-term reproducibility of ambulatory blood pressure measurements: a systematic review and meta-analysis of 35 observational studies.

OBJECTIVE: A systematic review on the reproducibility of ambulatory blood pressure measurements (ABPM) has not yet been conducted. This meta-analysis compared 24-h/daytime/night-time SBP and DBP mean values and SBP/DBP nocturnal dipping status from ABPMs in participants with or without hypertension. METHODS: Ovid MEDLINE, EMBASE, and CINAHL Complete databases were searched for articles published before 3 May 2019. Eligible studies reporting a 24-h ABPM repeated at least once within 1 month were included. The mean daytime/night-time/24-h BP values, percentage of nocturnal dipping, and proportion of nondippers were compared between the first and second day of measurements, and the proportion of participants with inconsistent dipping status were estimated using a random effect model. RESULTS: Population-based analysis found a 0-1.1 mmHg difference between the first and second ABPM for 24-h/daytime/night-time SBP and DBP and 0-0.5% for percentage of SBP/DBP nocturnal dipping. The proportion of non-dippers was not different between the first and second ABPM. Intra-individual analysis found that the 95% limit of agreements (LOA) for SBP/DBP were wide and the 95% LOA for daytime SBP, common reference to diagnose hypertension, ranged -16.7 to 18.4 mmHg. Similarly, 32% of participants had inconsistent nocturnal dipping status. CONCLUSION: ABPM had excellent reproducibility at the population level, favouring its application for research purposes; but reproducibility of intra-individual BP values and dipping status from a 24-h ABPM was limited. The available evidence was limited by the lack of high-quality studies and lack of studies in non-Western populations.

An International Collaborative Consensus Statement on En Bloc Resection of Bladder Tumour Incorporating Two Systematic Reviews, a Two-round Delphi Survey, and a Consensus Meeting.

BACKGROUND: There has been increasing interest in en bloc resection of bladder tumour (ERBT) as an oncologically noninferior alternative to transurethral resection of bladder tumour (TURBT) with fewer complications and better histology specimens. However, there is a lack of robust randomised controlled trial (RCT) data for making recommendations. OBJECTIVE: We aimed to develop a consensus statement to standardise various aspects of ERBT for clinical practice and to guide future research. DESIGN, SETTING, AND PARTICIPANTS: We developed the consensus statement on ERBT using a modified Delphi method. First, two systematic reviews were performed to investigate the clinical effectiveness of ERBT versus TURBT (effectiveness review) and to identify areas of uncertainty in ERBT (uncertainties review). Next, 200 health care professionals (urologists, oncologists, and pathologists) with experience in ERBT were invited to complete a two-round Delphi survey. Finally, a 16-member consensus panel meeting was held to review, discuss, and re-vote on the statements as appropriate. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: Meta-analyses were performed for RCT data in the effectiveness review. Consensus statements were developed from the uncertainties review. Consensus was defined as follows: (1) ≥70% scoring a statement 7-9 and ≤15% scoring the statement 1-3 (consensus agree), or (2) ≥70% scoring a statement 1-3 and ≤15% scoring the statement 7-9 (consensus disagree). RESULTS AND LIMITATIONS: A total of 10 RCTs were identified upon systematic review. ERBT had a shorter irrigation time (mean difference -7.24 h, 95% confidence interval [CI] -9.29 to -5.20, I2 = 85%, p < 0.001) and a lower rate of bladder perforation (risk ratio 0.30, 95% CI 0.11-0.83, I2 = 1%, p = 0.02) than TURBT, both with moderate certainty of evidence. There were no significant differences in recurrences at 0-12, 13-24, or 25-36 mo (all very low certainty of evidence). A total of 103 statements were developed, of which 99 reached a consensus. A summary of statements is as follows: ERBT should always be considered for treating non-muscle-invasive bladder cancer; ERBT should be considered feasible even for bladder tumours larger than 3 cm; number and location of bladder tumours are not major limitations in performing ERBT; the planned circumferential margin should be at least 5 mm from any visible bladder tumour; after ERBT, additional biopsy of the tumour edge or tumour base should not be performed routinely; for the ERBT specimen, T1 substage, and circumferential and deep resection margins must be assessed; it is safe to give a single dose of immediate intravesical chemotherapy, perform second-look transurethral resection, and give intravesical bacillus Calmette-Guérin (BCG) therapy after ERBT; and in studies of ERBT, both per-patient and -tumour analysis should be performed for different outcomes as appropriate. Important outcomes for future ERBT studies were also identified. A limitation is that as consensus statements are brief, concise and binary in nature, areas of uncertainty that are complex in nature may not be addressed adequately. CONCLUSIONS: We have provided the most comprehensive review of the evidence base to date using a meta-analysis where appropriate and applying the Grading of Recommendations Assessment, Development and Evaluation (GRADE) methodology, and mobilised the international urology community to develop a consensus statement on ERBT using transparent and robust methods. The consensus statement will provide interim guidance for health care professionals who practice ERBT and inform researchers regarding ERBT-related studies in the future. PATIENT SUMMARY: En bloc resection of bladder tumour (ERBT) is a surgical technique aiming to resect a bladder tumour in one piece. We included an international panel of experts to agree on the best practice of ERBT, and this will provide guidance to clinicians and researchers in the future.

Clinical ascertainment of health outcomes in Asian survivors of childhood cancer: a systematic review.

PURPOSE: Survivorship in children with cancer comes at a cost of developing chronic treatment-related complications. Yet, it is still an under-researched area in Asia, which shares the largest proportion of the global childhood cancer burden given its vast population. This systematic review summarizes existing literature on clinically ascertained health outcomes in Asian survivors of childhood cancer. METHODS: A search was conducted on Ovid Medline and EMBASE for studies that focused on survivors of childhood cancer from countries in East and Southeast Asia; adopted post-treatment clinical ascertainment of organ-specific toxicities or/and secondary malignancy. Studies were excluded if health outcomes were assessed during the acute treatment. RESULTS: Fifty-nine studies, enrolling a total of 13,442 subjects, were conducted on survivors of leukemia (34%), CNS tumor (14%), and cohorts of survivors with heterogeneous cancer diagnoses (52%). The studies used different medical evaluation methods to assess cardiovascular (15%), metabolic and infertility (32%), and neurological/neurocognitive (20%) outcomes in survivors. The collective findings suggest potential differences in the prevalence of certain late effects (e.g., secondary malignancy and obesity) among Asian and non-Asian populations, which may reflect differences in treatment regimens, practice, genetic variations, or/and socioeconomic disparity. CONCLUSIONS: We recommend developing collaborative initiatives to build a regional repository of systematically assessed health outcomes and biospecimens to investigate treatment, social-environmental and genetic predictors, and interventions for late effects in this population. IMPLICATIONS FOR CANCER SURVIVORS: The existing types of chronic health problems identified in this review suggest the need for active screening, better access to survivorship care, and promotion of protective health behavior in Asia.

Association between investigator-measured body-mass index and colorectal adenoma: a systematic review and meta-analysis of 168,201 subjects.

The objective of this meta-analysis is to evaluate the odds of colorectal adenoma (CRA) in colorectal cancer screening participants with different body mass index (BMI) levels, and examine if this association was different according to gender and ethnicity. The EMBASE and MEDLINE were searched to enroll high quality observational studies that examined the association between investigator-measured BMI and colonoscopy-diagnosed CRA. Data were independently extracted by two reviewers. A random-effects meta-analysis was conducted to estimate the summary odds ratio (SOR) for the association between BMI and CRA. The Cochran's Q statistic and I2 analyses were used to assess the heterogeneity. A total of 17 studies (168,201 subjects) were included. When compared with subjects having BMI < 25, individuals with BMI 25-30 had significantly higher risk of CRA (SOR 1.44, 95% CI 1.30-1.61; I2 = 43.0%). Subjects with BMI ≥ 30 had similarly higher risk of CRA (SOR 1.42, 95% CI 1.24-1.63; I2 = 18.5%). The heterogeneity was mild to moderate among studies. The associations were significantly higher than estimates by previous meta-analyses. There was no publication bias detected (Egger's regression test, p = 0.584). Subgroup analysis showed that the magnitude of association was significantly higher in female than male subjects (SOR 1.43, 95% CI 1.30-1.58 vs. SOR 1.16, 95% CI 1.07-1.24; different among different ethnic groups (SOR 1.72, 1.44 and 0.88 in White, Asians and Africans, respectively) being insignificant in Africans; and no difference exists among different study designs. In summary, the risk conferred by BMI for CRA was significantly higher than that reported previously. These findings bear implications in CRA risk estimation.