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BMJ (Clinical Research Ed.) Aug 2016To systematically review studies quantifying the associations of long term (clinic), mid-term (home), and short term (ambulatory) variability in blood pressure,... (Meta-Analysis)
Meta-Analysis Review
OBJECTIVE
To systematically review studies quantifying the associations of long term (clinic), mid-term (home), and short term (ambulatory) variability in blood pressure, independent of mean blood pressure, with cardiovascular disease events and mortality.
DATA SOURCES
Medline, Embase, Cinahl, and Web of Science, searched to 15 February 2016 for full text articles in English.
ELIGIBILITY CRITERIA FOR STUDY SELECTION
Prospective cohort studies or clinical trials in adults, except those in patients receiving haemodialysis, where the condition may directly impact blood pressure variability. Standardised hazard ratios were extracted and, if there was little risk of confounding, combined using random effects meta-analysis in main analyses. Outcomes included all cause and cardiovascular disease mortality and cardiovascular disease events. Measures of variability included standard deviation, coefficient of variation, variation independent of mean, and average real variability, but not night dipping or day-night variation.
RESULTS
41 papers representing 19 observational cohort studies and 17 clinical trial cohorts, comprising 46 separate analyses were identified. Long term variability in blood pressure was studied in 24 papers, mid-term in four, and short-term in 15 (two studied both long term and short term variability). Results from 23 analyses were excluded from main analyses owing to high risks of confounding. Increased long term variability in systolic blood pressure was associated with risk of all cause mortality (hazard ratio 1.15, 95% confidence interval 1.09 to 1.22), cardiovascular disease mortality (1.18, 1.09 to 1.28), cardiovascular disease events (1.18, 1.07 to 1.30), coronary heart disease (1.10, 1.04 to 1.16), and stroke (1.15, 1.04 to 1.27). Increased mid-term and short term variability in daytime systolic blood pressure were also associated with all cause mortality (1.15, 1.06 to 1.26 and 1.10, 1.04 to 1.16, respectively).
CONCLUSIONS
Long term variability in blood pressure is associated with cardiovascular and mortality outcomes, over and above the effect of mean blood pressure. Associations are similar in magnitude to those of cholesterol measures with cardiovascular disease. Limited data for mid-term and short term variability showed similar associations. Future work should focus on the clinical implications of assessment of variability in blood pressure and avoid the common confounding pitfalls observed to date.
SYSTEMATIC REVIEW REGISTRATION
PROSPERO CRD42014015695.
Topics: Blood Pressure; Blood Pressure Determination; Blood Pressure Monitoring, Ambulatory; Cardiovascular Diseases; Cause of Death; Humans
PubMed: 27511067
DOI: 10.1136/bmj.i4098 -
Evidence Report/technology Assessment Aug 2007To review and synthesize the literature in the following areas: the association of specific circulating 25(OH)D concentrations with bone health outcomes in children,... (Review)
Review
OBJECTIVES
To review and synthesize the literature in the following areas: the association of specific circulating 25(OH)D concentrations with bone health outcomes in children, women of reproductive age, postmenopausal women and elderly men; the effect of dietary intakes (foods fortified with vitamin D and/or vitamin D supplementation) and sun exposure on serum 25(OH)D; the effect of vitamin D on bone mineral density (BMD) and fracture or fall risk; and the identification of potential harms of vitamin D above current reference intakes.
DATA SOURCES
MEDLINE(R) (1966-June Week 3 2006); Embase (2002-2006 Week 25); CINAHL (1982-June Week 4, 2006); AMED (1985 to June 2006); Biological Abstracts (1990-February 2005); and the Cochrane Central Register of Controlled Trials (2nd Quarter 2006).
REVIEW METHODS
Two independent reviewers completed a multi-level process of screening the literature to identify eligible studies (title and abstract, followed by full text review, and categorization of study design per key question). To minimize bias, study design was limited to randomized controlled trials (RCTs) wherever possible. Study criteria for question one were broadened to include observational studies due to a paucity of available RCTs, and question four was restricted to systematic reviews to limit scope. Data were abstracted in duplicate and study quality assessed. Differences in opinion were resolved through consensus or adjudication. If clinically relevant and statistically feasible, meta-analyses of RCTs on vitamin D supplementation and bone health outcomes were conducted, with exploration of heterogeneity. When meta-analysis was not feasible, a qualitative systematic review of eligible studies was conducted.
RESULTS
167 studies met our eligibility criteria (112 RCTs, 19 prospective cohorts, 30 case-controls and six before-after studies). The largest body of evidence on vitamin D status and bone health was in older adults with a lack of studies in premenopausal women and infants, children and adolescents. The quality of RCTs was highest in the vitamin D efficacy trials for prevention of falls and/or fractures in older adults. There was fair evidence of an association between low circulating 25(OH)D concentrations and established rickets. However, the specific 25(OH)D concentrations associated with rickets is uncertain, given the lack of studies in populations with dietary calcium intakes similar to North American diets and the different methods used to determine 25(OH)D concentrations. There was inconsistent evidence of an association of circulating 25(OH)D with bone mineral content in infants, and fair evidence that serum 25(OH)D is inversely associated with serum PTH. In adolescents, there was fair evidence for an association between 25(OH)D levels and changes in BMD. There were very few studies in pregnant and lactating women, and insufficient evidence for an association between serum 25(OH)D and changes in BMD during lactation, and fair evidence of an inverse correlation with PTH. In older adults, there was fair evidence that serum 25(OH)D is inversely associated with falls, fair evidence for a positive association with BMD, and inconsistent evidence for an association with fractures. The imprecision of 25(OH)D assays may have contributed to the variable thresholds of 25(OH)D below which the risk of fractures, falls or bone loss was increased. There was good evidence that intakes from vitamin D-fortified foods (11 RCTs) consistently increased serum 25(OH)D in both young and older adults. Eight randomized trials of ultraviolet (UV)-B radiation (artificial and solar exposure) were small and heterogeneous with respect to determination of the exact UV-B dose and 25(OH)D assay but there was a positive effect on serum 25(OH)D concentrations. It was not possible to determine how 25(OH)D levels varied by ethnicity, sunscreen use or latitude. Seventy-four trials examined the effect of vitamin D(3) or D(2) on 25(OH)D concentrations. Most trials used vitamin D(3), and the majority enrolled older adults. In three trials, there was a greater response of serum 25(OH)D concentrations to vitamin D(3) compared to vitamin D(2), which may have been due to more rapid clearance of vitamin D(2) in addition to other mechanisms. Meta-analysis of 16 trials of vitamin D(3) was consistent with a dose-response effect on serum 25(OH)D when comparing daily doses of <400 IU to doses >/= 400 IU. An exploratory analysis of the heterogeneity demonstrated a significant positive association comparable to an increase of 1 - 2 nmol/L in serum 25(OH)D for every 100 additional units of vitamin D although heterogeneity remained after adjusting for dose. Vitamin D(3) in combination with calcium results in small increases in BMD compared to placebo in older adults although quantitative synthesis was limited due to variable treatment durations and BMD sites. The evidence for fracture reduction with vitamin D supplementation was inconsistent across 15 trials. The combined results of trials using vitamin D(3) (700 - 800 IU daily) with calcium (500 - 1,200 mg) was consistent with a benefit on fractures although in a subgroup analysis by setting, benefit was primarily in elderly institutionalized women (fair evidence from two trials). There was inconsistent evidence across 14 RCTs of a benefit on fall risk. However, a subgroup analysis showed a benefit of vitamin D in postmenopausal women, and in trials that used vitamin D(3) plus calcium. In addition, there was a reduction in fall risk with vitamin D when six trials that adequately ascertained falls were combined. Limitations of the fall and fracture trials included poor compliance with vitamin D supplementation, incomplete assessment of vitamin D status and large losses to follow-up. We did not find any systematic reviews that addressed the question on the level of sunlight exposure that is sufficient to maintain serum 25(OH)D concentrations but minimizes risk of melanoma and non-melanoma skin cancer. There is little evidence from existing trials that vitamin D above current reference intakes is harmful. In most trials, reports of hypercalcemia and hypercalciuria were not associated with clinically relevant events. The Women's Health Initiative study did report a small increase in kidney stones in postmenopausal women aged 50 to 79 years whose daily vitamin D(3) intake was 400 IU (the reference intake for 50 to 70 years, and below the reference intake for > 70 years) combined with 1000 mg calcium. The increase in renal stones corresponded to 5.7 events per 10,000 person-years of exposure. The women in this trial had higher calcium intakes than is seen in most post-menopausal women.
CONCLUSIONS
The results highlight the need for additional high quality studies in infants, children, premenopausal women, and diverse racial or ethnic groups. There was fair evidence from studies of an association between circulating 25(OH)D concentrations with some bone health outcomes (established rickets, PTH, falls, BMD). However, the evidence for an association was inconsistent for other outcomes (e.g., BMC in infants and fractures in adults). It was difficult to define specific thresholds of circulating 25(OH)D for optimal bone health due to the imprecision of different 25(OH)D assays. Standard reference preparations are needed so that serum 25(OH)D can be accurately and reliably measured, and validated. In most trials, the effects of vitamin D and calcium could not be separated. Vitamin D(3) (>700 IU/day) with calcium supplementation compared to placebo has a small beneficial effect on BMD, and reduces the risk of fractures and falls although benefit may be confined to specific subgroups. Vitamin D intake above current dietary reference intakes was not reported to be associated with an increased risk of adverse events. However, most trials of higher doses of vitamin D were not adequately designed to assess long-term harms.
Topics: Adolescent; Aged; Bone Density; Bone Density Conservation Agents; Bone and Bones; Child; Child, Preschool; Dietary Supplements; Female; Fractures, Bone; Humans; Infant; Lactation; Male; Osteoporosis, Postmenopausal; Pregnancy; Rickets; Sunlight; Ultraviolet Rays; Vitamin D; Vitamin D Deficiency
PubMed: 18088161
DOI: No ID Found -
Journal of the National Cancer Institute Mar 2019Barriers to cancer clinical trial participation have been the subject of frequent study, but the rate of trial participation has not changed substantially over time.... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Barriers to cancer clinical trial participation have been the subject of frequent study, but the rate of trial participation has not changed substantially over time. Studies often emphasize patient-related barriers, but other types of barriers may have greater impact on trial participation. Our goal was to examine the magnitude of different domains of trial barriers by synthesizing prior research.
METHODS
We conducted a systematic review and meta-analysis of studies that examined the trial decision-making pathway using a uniform framework to characterize and quantify structural (trial availability), clinical (eligibility), and patient/physician barrier domains. The systematic review utilized the PubMed, Google Scholar, Web of Science, and Ovid Medline search engines. We used random effects to estimate rates of different domains across studies, adjusting for academic vs community care settings.
RESULTS
We identified 13 studies (nine in academic and four in community settings) with 8883 patients. A trial was unavailable for patients at their institution 55.6% of the time (95% confidence interval [CI] = 43.7% to 67.3%). Further, 21.5% (95% CI = 10.9% to 34.6%) of patients were ineligible for an available trial, 14.8% (95% CI = 9.0% to 21.7%) did not enroll, and 8.1% (95% CI = 6.3% to 10.0%) enrolled. Rates of trial enrollment in academic (15.9% [95% CI = 13.8% to 18.2%]) vs community (7.0% [95% CI = 5.1% to 9.1%]) settings differed, but not rates of trial unavailability, ineligibility, or non-enrollment.
CONCLUSIONS
These findings emphasize the enormous need to address structural and clinical barriers to trial participation, which combined make trial participation unachievable for more than three of four cancer patients.
Topics: Clinical Trials as Topic; Decision Making; Eligibility Determination; Humans; Neoplasms; Patient Acceptance of Health Care; Patient Participation; Patient Selection; Physician-Patient Relations; Physicians
PubMed: 30856272
DOI: 10.1093/jnci/djy221 -
BMJ (Clinical Research Ed.) Feb 2020To examine the dose-response relation between reduction in dietary sodium and blood pressure change and to explore the impact of intervention duration. (Meta-Analysis)
Meta-Analysis
OBJECTIVE
To examine the dose-response relation between reduction in dietary sodium and blood pressure change and to explore the impact of intervention duration.
DESIGN
Systematic review and meta-analysis following PRISMA guidelines.
DATA SOURCES
Ovid MEDLINE(R), EMBASE, and Cochrane Central Register of Controlled Trials (Wiley) and reference lists of relevant articles up to 21 January 2019.
INCLUSION CRITERIA
Randomised trials comparing different levels of sodium intake undertaken among adult populations with estimates of intake made using 24 hour urinary sodium excretion.
DATA EXTRACTION AND ANALYSIS
Two of three reviewers screened the records independently for eligibility. One reviewer extracted all data and the other two reviewed the data for accuracy. Reviewers performed random effects meta-analyses, subgroup analyses, and meta-regression.
RESULTS
133 studies with 12 197 participants were included. The mean reductions (reduced sodium usual sodium) of 24 hour urinary sodium, systolic blood pressure (SBP), and diastolic blood pressure (DBP) were 130 mmol (95% confidence interval 115 to 145, P<0.001), 4.26 mm Hg (3.62 to 4.89, P<0.001), and 2.07 mm Hg (1.67 to 2.48, P<0.001), respectively. Each 50 mmol reduction in 24 hour sodium excretion was associated with a 1.10 mm Hg (0.66 to 1.54; P<0.001) reduction in SBP and a 0.33 mm Hg (0.04 to 0.63; P=0.03) reduction in DBP. Reductions in blood pressure were observed in diverse population subsets examined, including hypertensive and non-hypertensive individuals. For the same reduction in 24 hour urinary sodium there was greater SBP reduction in older people, non-white populations, and those with higher baseline SBP levels. In trials of less than 15 days' duration, each 50 mmol reduction in 24 hour urinary sodium excretion was associated with a 1.05 mm Hg (0.40 to 1.70; P=0.002) SBP fall, less than half the effect observed in studies of longer duration (2.13 mm Hg; 0.85 to 3.40; P=0.002). Otherwise, there was no association between trial duration and SBP reduction.
CONCLUSIONS
The magnitude of blood pressure lowering achieved with sodium reduction showed a dose-response relation and was greater for older populations, non-white populations, and those with higher blood pressure. Short term studies underestimate the effect of sodium reduction on blood pressure.
SYSTEMATIC REVIEW REGISTRATION
PROSPERO CRD42019140812.
Topics: Blood Pressure; Blood Pressure Determination; Diet, Sodium-Restricted; Dose-Response Relationship, Drug; Humans; Hypertension; Randomized Controlled Trials as Topic; Sodium Chloride, Dietary
PubMed: 32094151
DOI: 10.1136/bmj.m315 -
British Journal of Sports Medicine Nov 2016This systematic review and meta-analysis sought to identify return to play (RTP) rates following Achilles tendon rupture and evaluate what measures are used to determine...
AIM
This systematic review and meta-analysis sought to identify return to play (RTP) rates following Achilles tendon rupture and evaluate what measures are used to determine RTP.
DESIGN
A systematic review and meta-analysis were performed. Studies were assessed for risk of bias and grouped based on repeatability of their measure of RTP determination.
DATA SOURCES
PubMed, CINAHL, Web of Science and Scopus databases were searched to identify potentially relevant articles.
ELIGIBILITY CRITERIA FOR SELECTING STUDIES
Studies reporting RTP/sport/sport activity in acute, closed Achilles tendon rupture were included.
RESULTS
108 studies encompassing 6506 patients were included for review. 85 studies included a measure for determining RTP. The rate of RTP in all studies was 80% (95% CI 75% to 85%). Studies with measures describing determination of RTP reported lower rates than studies without metrics described, with rates being significantly different between groups (p<0.001).
CONCLUSIONS
80 per cent of patients returned to play following Achilles tendon rupture; however, the RTP rates are dependent on the quality of the method used to measure RTP. To further understand RTP after Achilles tendon rupture, a standardised, reliable and valid method is required.
PubMed: 27259751
DOI: 10.1136/bjsports-2016-096106 -
BMJ (Clinical Research Ed.) Dec 2021To evaluate pathological complete response as a surrogate endpoint for disease-free survival and overall survival in regulatory neoadjuvant trials of early stage breast... (Meta-Analysis)
Meta-Analysis
Evaluation of pathological complete response as surrogate endpoint in neoadjuvant randomised clinical trials of early stage breast cancer: systematic review and meta-analysis.
OBJECTIVE
To evaluate pathological complete response as a surrogate endpoint for disease-free survival and overall survival in regulatory neoadjuvant trials of early stage breast cancer.
DESIGN
Systematic review and meta-analysis.
DATA SOURCES
Medline, Embase, and Scopus to 1 December 2020.
ELIGIBILITY CRITERIA FOR STUDY SELECTION
Randomised clinical trials that tested neoadjuvant chemotherapy given alone or combined with other treatments, including anti-human epidermal growth factor 2 (anti-HER2) drugs, targeted treatments, antivascular agents, bisphosphonates, and immune checkpoint inhibitors.
DATA EXTRACTION AND SYNTHESIS
Trial level associations between the surrogate endpoint pathological complete response and disease-free survival and overall survival.
METHODS
A weighted regression analysis was performed on log transformed treatment effect estimates (hazard ratio for disease-free survival and overall survival and relative risk for pathological complete response), and the coefficient of determination (R) was used to quantify the association. The secondary objective was to explore heterogeneity of results in preplanned subgroups analysis, stratifying trials according treatment type in the experimental arm, definition used for pathological complete response (breast and lymph nodes breast only), and biological features of the disease (HER2 positive or triple negative breast cancer). The surrogate threshold effect was also evaluated, indicating the minimum value of the relative risk for pathological complete response necessary to confidently predict a non-null effect on hazard ratio for disease-free survival or overall survival.
RESULTS
54 randomised clinical trials comprising a total of 32 611 patients were included in the analysis. A weak association was observed between the log(relative risk) for pathological complete response and log(hazard ratio) for both disease-free survival (R=0.14, 95% confidence interval 0.00 to 0.29) and overall survival (R =0.08, 0.00 to 0.22). Similar results were found across all subgroups evaluated, independently of the definition used for pathological complete response, treatment type in the experimental arm, and biological features of the disease. The surrogate threshold effect was 5.19 for disease-free survival but was not estimable for overall survival. Consistent results were confirmed in three sensitivity analyses: excluding small trials (<200 patients enrolled), excluding trials with short median follow-up (<24 months), and replacing the relative risk for pathological complete response with the absolute difference of pathological complete response rates between treatment arms.
CONCLUSION
A lack of surrogacy of pathological complete response was identified at trial level for both disease-free survival and overall survival. The findings suggest that pathological complete response should not be used as primary endpoint in regulatory neoadjuvant trials of early stage breast cancer.
Topics: Biomarkers; Breast Neoplasms; Chemotherapy, Adjuvant; Disease-Free Survival; Female; Humans; Neoadjuvant Therapy; Randomized Controlled Trials as Topic
PubMed: 34933868
DOI: 10.1136/bmj-2021-066381 -
International Journal of Environmental... Oct 2022While there have been ongoing calls to reform child welfare so that it better meets children's and families' needs, to date there have been no comprehensive summaries of... (Review)
Review
While there have been ongoing calls to reform child welfare so that it better meets children's and families' needs, to date there have been no comprehensive summaries of child welfare reform strategies. For this systematic scoping review, we summarized authors' recommendations for improving child welfare. We conducted a systematic search (2010 to 2021) and included published reviews that addressed authors' recommendations for improving child welfare for children, youth, and families coming into contact with child welfare in high-income countries. A total of 4758 records was identified by the systematic search, 685 full-text articles were screened for eligibility, and 433 reviews were found to be eligible for this scoping review. Reviews were theoretically divided, with some review authors recommending reform efforts at the macro level (e.g., addressing poverty) and others recommending reform efforts at the practice level (e.g., implementing evidence-based parenting programs). Reform efforts across socioecological levels were summarized in this scoping review. An important next step is to formulate what policy solutions are likely to lead to the greatest improvement in safety and well-being for children and families involved in child welfare.
Topics: Child; Adolescent; Humans; Child Welfare; Eligibility Determination; Poverty; Income; Longitudinal Studies
PubMed: 36360960
DOI: 10.3390/ijerph192114071 -
Journal of Medical Internet Research Nov 2022Smartphone apps have the potential to address some of the current issues facing service provision for young people's mental health by improving the scalability of... (Review)
Review
BACKGROUND
Smartphone apps have the potential to address some of the current issues facing service provision for young people's mental health by improving the scalability of evidence-based mental health interventions. However, very few apps have been successfully implemented, and consensus on implementation measurement is lacking.
OBJECTIVE
This review aims to determine the proportion of evidence-based mental health and well-being apps that have been successfully adopted and sustained in real-world settings. A secondary aim is to establish if key implementation determinants such as coproduction, acceptability, feasibility, appropriateness, and engagement contribute toward successful implementation and longevity.
METHODS
Following the PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) guidelines, an electronic search of 5 databases in 2021 yielded 18,660 results. After full-text screening, 34 articles met the full eligibility criteria, providing data on 29 smartphone apps studied with individuals aged 15 to 25 years.
RESULTS
Of 34 studies, only 10 (29%) studies were identified that were evaluating the effectiveness of 8 existing, commercially available mental health apps, and the remaining 24 (71%) studies reported the development and evaluation of 21 newly developed apps, of which 43% (9/21) were available, commercially or otherwise (eg, in mental health services), at the time of enquiry. Most studies addressed some implementation components including adoption, acceptability, appropriateness, feasibility, and engagement. Factors including high cost, funding constraints, and lengthy research processes impeded implementation.
CONCLUSIONS
Without addressing common implementation drivers, there is considerable redundancy in the translation of mobile mental health research findings into practice. Studies should embed implementation strategies from the outset of the planned research, build collaborations with partners already working in the field (academic and commercial) to capitalize on existing interventions and platforms, and modify and evaluate them for local contexts or target problems and populations.
TRIAL REGISTRATION
PROSPERO CRD42021224365; https://tinyurl.com/4umpn85f.
Topics: Humans; Adolescent; Mental Health; Mobile Applications; Telemedicine; Text Messaging; Mental Health Services
PubMed: 36350704
DOI: 10.2196/40347 -
The Cochrane Database of Systematic... Mar 2015This represents the first update of this review, which was published in 2012. Atorvastatin is one of the most widely prescribed drugs and the most widely prescribed... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
This represents the first update of this review, which was published in 2012. Atorvastatin is one of the most widely prescribed drugs and the most widely prescribed statin in the world. It is therefore important to know the dose-related magnitude of effect of atorvastatin on blood lipids.
OBJECTIVES
Primary objective To quantify the effects of various doses of atorvastatin on serum total cholesterol, low-density lipoprotein (LDL)-cholesterol, high-density lipoprotein (HDL)-cholesterol and triglycerides in individuals with and without evidence of cardiovascular disease. The primary focus of this review was determination of the mean per cent change from baseline of LDL-cholesterol. Secondary objectives • To quantify the variability of effects of various doses of atorvastatin.• To quantify withdrawals due to adverse effects (WDAEs) in placebo-controlled randomised controlled trials (RCTs).
SEARCH METHODS
We searched the Cochrane Central Register of Controlled Trials (CENTRAL) (Issue 11, 2013), MEDLINE (1966 to December Week 2 2013), EMBASE (1980 to December Week 2 2013), Web of Science (1899 to December Week 2 2013) and BIOSIS Previews (1969 to December Week 2 2013). We applied no language restrictions.
SELECTION CRITERIA
Randomised controlled and uncontrolled before-and-after trials evaluating the dose response of different fixed doses of atorvastatin on blood lipids over a duration of three to 12 weeks.
DATA COLLECTION AND ANALYSIS
Two review authors independently assessed eligibility criteria for studies to be included and extracted data. We collected information on withdrawals due to adverse effects from placebo-controlled trials.
MAIN RESULTS
In this update, we found an additional 42 trials and added them to the original 254 studies. The update consists of 296 trials that evaluated dose-related efficacy of atorvastatin in 38,817 participants. Included are 242 before-and-after trials and 54 placebo-controlled RCTs. Log dose-response data from both trial designs revealed linear dose-related effects on blood total cholesterol, LDL-cholesterol, HDL-cholesterol and triglycerides. The Summary of findings table 1 documents the effect of atorvastatin on LDL-cholesterol over the dose range of 10 to 80 mg/d, which is the range for which this systematic review acquired the greatest quantity of data. Over this range, blood LDL-cholesterol is decreased by 37.1% to 51.7% (Summary of findings table 1). The slope of dose-related effects on cholesterol and LDL-cholesterol was similar for atorvastatin and rosuvastatin, but rosuvastatin is about three-fold more potent. Subgroup analyses suggested that the atorvastatin effect was greater in females than in males and was greater in non-familial than in familial hypercholesterolaemia. Risk of bias for the outcome of withdrawals due to adverse effects (WDAEs) was high, but the mostly unclear risk of bias was judged unlikely to affect lipid measurements. Withdrawals due to adverse effects were not statistically significantly different between atorvastatin and placebo groups in these short-term trials (risk ratio 0.98, 95% confidence interval 0.68 to 1.40).
AUTHORS' CONCLUSIONS
This update resulted in no change to the main conclusions of the review but significantly increases the strength of the evidence. Studies show that atorvastatin decreases blood total cholesterol and LDL-cholesterol in a linear dose-related manner over the commonly prescribed dose range. New findings include that atorvastatin is more than three-fold less potent than rosuvastatin, and that the cholesterol-lowering effects of atorvastatin are greater in females than in males and greater in non-familial than in familial hypercholesterolaemia. This review update does not provide a good estimate of the incidence of harms associated with atorvastatin because included trials were of short duration and adverse effects were not reported in 37% of placebo-controlled trials.
Topics: Atorvastatin; Cholesterol; Cholesterol, HDL; Cholesterol, LDL; Controlled Before-After Studies; Dose-Response Relationship, Drug; Female; Heptanoic Acids; Humans; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Hyperlipidemias; Lipids; Male; Pyrroles; Randomized Controlled Trials as Topic; Sex Factors; Triglycerides
PubMed: 25760954
DOI: 10.1002/14651858.CD008226.pub3 -
CNS Neuroscience & Therapeutics Oct 2022To systematically review studies using remote ischemia postconditioning (RIPostC) for ischemic stroke in experimental models and obtain factors that significantly... (Meta-Analysis)
Meta-Analysis Review
OBJECTIVES
To systematically review studies using remote ischemia postconditioning (RIPostC) for ischemic stroke in experimental models and obtain factors that significantly influence treatment outcomes.
MATERIALS AND METHODS
Peer-reviewed studies were identified and selected based on the eligibility criteria, followed by extraction of data on potentially influential factors related to model preparation, postconditioning, and measure time based on outcome measures including infarct size, neurological scales, and cell tests with autophagy, apoptosis, normal-neuron, and damaged-neuron counting. Then, all data were preprocessed, grouped, and meta-analyzed with the indicator of the standardized mean difference.
RESULTS
Fifty-seven studies with 224 experiments (91 for infarct size, 92 for neurological scales, and 41 for cell-level tests) were included. There was little statistical difference between different model preparations, treated body parts, number of treatments, and sides. And treatment effect was generally a positive correlation with the duration of conditioning time to stroke onset with exceptions at some time points. Based on infarct size, the number of cycles per treatment, duration of occlusion, and release per cycle showed significant differences. Combined with the effect sizes by other measures, the occlusion/release duration of 8-10 min per cycle is better than 5 min, and three cycles per treatment were most frequently used with good effects. Effect also varied when measuring at different times, showing statistical differences in infarct size and most neurological scales. RIPostC is confirmed as an effective therapeutic intervention for ischemic stroke, while the RIPostC-mediated autophagy level being activated or inhibited remained conflicting.
CONCLUSIONS
Conditioning time, number of cycles per treatment, duration of occlusion, and release per cycle were found to influence the treatment effects of RIPostC significantly. More studies on the relevant influential factors and autophagy mechanisms are warranted.
Topics: Autophagy; Humans; Infarction; Ischemic Postconditioning; Ischemic Stroke; Stroke
PubMed: 35896511
DOI: 10.1111/cns.13925