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PubMed2006

In pursuit of cumulative knowledge in health communication: the role of meta-analysis.

A major goal in health communication and related disciplines is the building of cumulative knowledge across numerous lines of inquiry. Traditionally, attempts to synthesize research and build knowledge have been achieved through narrative or integrative research reviews. However, the advent of meta-analysis in the late 1970s gave researchers a more sophisticated approach to synthesizing quantitative research literatures. This article (a) provides an overview of the meta-analytic approach, (b) discusses the historical context of meta-analysis, (c) examines the role that meta-analysis has played in the synthesis of health communication research, and (d) suggests future applications of the technique within health communication. It appears that meta-analysis has only recently been applied to the health communication field in a substantive way, and that its potential for moving the field forward has thus only begun to be realized.

Communication↗

PubMed2002

Systematic review of randomised controlled trials of psychological therapy for chronic pain in children and adolescents, with a subset meta-analysis of pain relief.

A systematic review and subset meta-analysis of published randomised controlled trials of psychological therapies for children and adolescents with chronic pain is reported. A search of four computerised abstracting services recovered 123 papers from which 28 potential trials were identified. Eighteen met the criteria for inclusion in the review. The majority of these papers reported brief behavioural and cognitive behavioural interventions for children with headache and many were conducted in community (i.e. school) settings. Meta-analysis was applicable for 12 headache trials and one trial of recurrent abdominal pain using the Pain Index. The odds-ratio for a 50% reduction in pain was 9.62 and the number needed to treat was 2.32, indicating that the psychological treatments examined are effective in reducing the pain of headache. The quality of the 18 trials retrieved is narratively reviewed and suggestions for the development of trials in this field are made.

Abdominal Pain↗

PubMed2005

Motivational interviewing: a systematic review and meta-analysis.

BACKGROUND: Motivational Interviewing is a well-known, scientifically tested method of counselling clients developed by Miller and Rollnick and viewed as a useful intervention strategy in the treatment of lifestyle problems and disease. AIM: To evaluate the effectiveness of motivational interviewing in different areas of disease and to identify factors shaping outcomes. DESIGN OF STUDY: A systematic review and meta-analysis of randomised controlled trials using motivational interviewing as the intervention. METHOD: After selection criteria a systematic literature search in 16 databases produced 72 randomised controlled trials the first of which was published in 1991. A quality assessment was made with a validated scale. A meta-analysis was performed as a generic inverse variance meta-analysis. RESULTS: Meta-analysis showed a significant effect (95% confidence interval) for motivational interviewing for combined effect estimates for body mass index, total blood cholesterol, systolic blood pressure, blood alcohol concentration and standard ethanol content, while combined effect estimates for cigarettes per day and for HbA(1c) were not significant. Motivational interviewing had a significant and clinically relevant effect in approximately three out of four studies, with an equal effect on physiological (72%) and psychological (75%) diseases. Psychologists and physicians obtained an effect in approximately 80% of the studies, while other healthcare providers obtained an effect in 46% of the studies. When using motivational interviewing in brief encounters of 15 minutes, 64% of the studies showed an effect. More than one encounter with the patient ensures the effectiveness of motivational interviewing. CONCLUSION: Motivational interviewing in a scientific setting outperforms traditional advice giving in the treatment of a broad range of behavioural problems and diseases. Large-scale studies are now needed to prove that motivational interviewing can be implemented into daily clinical work in primary and secondary health care.

Data Collection↗

PubMed2000

[Meta-analysis of therapeutic and preventive clinical trials].

The paper surveyes the principles and the models of meta-analysis and gives the basic statistical formulae. For evaluation of data of clinical trials two illustrative examples are presented: 1. evaluation of association and homogeneity in fixed and random models of the common standardized treatment effects measured by continuous variable with known sample sizes, means and standard deviations; 2. evaluation of association and homogeneity in fixed model of: the common InRelative-Risk and Risk-Difference ot treatment effects determined by dichotomous variable categorized in 2 x 2 tables and completed with Stouffer and Fisher methods combining z and p values of percentage differences of the treatment effects. It is demonstrated that the presented two illustrative examples, as models of meta-analysis provide objective statistical methods for data summarization of clinical trials. Evidence based medicine applies also the methods of meta-analysis.

Clinical Trials as Topic↗

PubMed2003

Meta-analysis of data on costs from trials of counselling in primary care: using individual patient data to overcome sample size limitations in economic analyses.

OBJECTIVE: To assess the feasibility of overcoming sample size limitations in economic analyses of clinical trials through meta-analysis of data on individual patients from multiple trials. DESIGN: Meta-analysis of individual patient data from trials of counselling in primary care compared with usual care by a general practitioner. SETTING: Primary care. PATIENTS: People with mental health problems. MAIN OUTCOME MEASURES: Direct treatment costs, depressive symptoms, and cost effectiveness. RESULTS: Meta-analysis of individual patient data proved feasible. The results showed that the previous analyses of individual trials were underpowered to provide useful conclusions about the cost comparisons. The results are sensitive to assumptions made about the costs of sessions with a counsellor and the management of patients by a general practitioner. CONCLUSIONS: Meta-analysis of individual patient data may assist in overcoming sample size limitations in economic analyses. Although feasible, such analysis has shortcomings that may limit the validity of the results. The relative costs and benefits of this method, as opposed to further collection of primary data, are as yet unclear.

Clinical Trials as Topic↗

PubMed1997

Prognostic factors influencing relapse of oesophagitis during maintenance therapy with antisecretory drugs: a meta-analysis of long-term omeprazole trials.

BACKGROUND: This meta-analysis investigated factors that may affect the risk of relapse of oesophagitis, and evaluated the predictive value of symptoms for the presence of relapse during long-term treatment. METHODS: Individual data from 1154 patients included in five independently conducted, randomized, long-term clinical trials of the efficacy of different dosage regimens of omeprazole, standard ranitidine treatment and placebo for the prevention of relapse of oesophagitis were pooled for this meta-analysis. The therapeutic regimens studied were omeprazole 20 mg o.m. (OME20) in 366 patients, omeprazole 10 mg o.m. (OME10) in 225 patients, omeprazole 20 mg weekends (OMEW) in 235 patients, ranitidine 150 mg b.d. (RAN) in 179 patients, or placebo (PLA) in 149 patients. RESULTS: OME20 maintained 82.4% (95% CI: 78.2-86.6%) of patients in endoscopic remission over the 6-month period compared to 71.9% (95% CI: 65.5-78.3%) for OME10, 52.3% (95% CI: 44.4-60.1%) for RAN, 42.7% (95% CI: 35.8-49.5%) for OMEW, and 10.6% (95% CI: 5.0-16.3%) for PLA. A Cox's regression analysis of time to recurrence of oesophagitis showed that four factors were associated with a higher relapse rate during placebo and active maintenance therapy: (a) pre-treatment severity of oesophagitis (P < 0.0001), (b) young age (P = 0.01), (c) non-smoking (P = 0.02) and (d) moderate/severe regurgitation before entry into the trials (P = 0.03). Asymptomatic relapse of oesophagitis was uncommon, being found in only 8.6% of the patients. CONCLUSIONS: Maintenance treatment with omeprazole 10 and 20 mg daily is superior to all other regimens tested, and is only marginally influenced by the pretreatment severity of oesophagitis. Age contributes to the factors that influence the outcome during long-term treatment with omeprazole. Symptom relief is highly predictive for the maintenance of healing.

Adolescent↗

PubMedDate not supplied

Efficacy of a herbal preparation in patients with functional dyspepsia: a meta-analysis of double-blind, randomized, clinical trials.

A meta-analysis was performed of double-blind, randomized clinical studies that evaluated the efficacy of the herbal preparation Iberogast in patients with functional dyspepsia. All studies had the same duration and used the same dosage of active treatment and the same primary outcome measure, a dyspepsia-specific gastrointestinal symptom score. Of the 592 trial participants, 196 were treated with Iberogast and 192 with placebo or cisapride (positive control). The individual studies all showed a substantial improvement of symptoms with Iberogast but varying results regarding its statistically significant superiority to placebo. The meta-analysis of all studies, however, demonstrated a clear, highly significant overall therapeutic effect of Iberogast in the treatment of functional dyspepsia. Tolerability of the preparation was excellent.

Adult↗

PubMed2002

Aggregate data meta-analysis with time-to-event outcomes.

In a meta-analysis of randomized controlled trials with time-to-event outcomes, an aggregate data approach may be required for some or all included studies. Variation in the reporting of survival analyses in journals suggests that no single method for extracting the log(hazard ratio) estimate will suffice. Methods are described which improve upon a previously proposed method for estimating the log(HR) from survival curves. These methods extend to life-tables. In the situation where the treatment effect varies over time and the trials in the meta-analysis have different lengths of follow-up, heterogeneity may be evident. In order to assess whether the hazard ratio changes with time, several tests are proposed and compared. A cohort study comparing life expectancy of males and females with cerebral palsy and a systematic review of five trials comparing two anti-epileptic drugs, carbamazepine and sodium valproate, are used for illustration.

Anticonvulsants↗

PubMed2003

A likelihood ratio approach to meta-analysis of diagnostic studies.

OBJECTIVE: To develop a clinically and methodologically sound approach to diagnostic meta-analysis. METHODS: Two-step model was used involving four fictitious sets of 10 studies each with varying sensitivity and specificity; this was followed by the application of the method to data from a published systematic review of emergency ultrasound. Multidimensional test characteristics (relating to the detection or exclusion of the condition of interest) were described by likelihood ratio scatterplots and pooled likelihood ratios. Likelihood ratios summarise the ability of a test to revise the prior probability of disease. They can be summarised by established fixed-effects and random-effects methods. RESULTS: Likelihood ratios precisely describe both directions of test performance. By plotting positive against negative likelihood ratios, together with their 95% confidence intervals, a multidimensional forest plot is obtained that can be interpreted in analogy to therapeutic meta-analyses. There are accepted threshold values of positive and negative likelihood ratios (i.e. 10.0 and 0.1) to recommend a test for clinical use. In the matrix space, distinct test characteristics can even be assessed by eyeballing. With regard to data from the real meta-analysis, the suggested high discriminatory power of ultrasound was only partially qualified by likelihood ratios. The positive value confirms the reliability of a positive scan, whereas the negative value questions a normal sonogram. CONCLUSIONS: A full characterisation of test performance requires multidimensional effect measures. Likelihood ratios are recommended descriptors of the two dimensions of diagnostic research evidence and provide a convenient means to visualise and to communicate results as weighted summary estimates of a diagnostic meta-analysis.

Diagnosis↗

PubMed2005

Prostate-specific antigen, digital rectal examination and transrectal ultrasonography: a meta-analysis for this diagnostic triad of prostate cancer in symptomatic korean men.

We conducted a meta-analysis using results from the Korean literature to determine whether prostate-specific antigen (PSA) or digital rectal examination (DRE) or transrectal ultrasonography (TRUS) provides a better diagnostic outcome for possible prostate cancer patients. An extensive literature search of MedRIC database et al. (1980 to 2003) was performed using the medical subject headings "PSA", "DRE", "TRUS" and "prostate cancer". Of the 108 articles that we retrieved, 13 studies (2,029 subjects) were selected for this meta-analysis. The criteria for quality evaluation were as follows: the study subjects must have been compared clinically for suspected prostate cancer, and the articles must have included individual data about sensitivity and specificity for this diagnostic triad based on the biopsy results as a reference standard. For the quantitative meta-analysis process the Hasselblad method was utilized. The pooled sensitivity and specificity for a PSA level greater than 4ng/mL were 91.3 % and 35.9 %, respectively; and those for a PSA level greater than 10ng/mL were 77.3 % and 67.5 %, respectively; and those for DRE were 68.4 % and 71.5 %, respectively; and those for TRUS were 73.6 % and 61.3 %, respectively. According to the results in a fixed effect model for PSA criteria, the estimates of d for PSA4 and PSA10 were 0.8517 [95 % confidence interval (CI): 0.6694, 1.0340] and 1.0996 (95 % CI: 0.9459, 1.2534), respectively. Also, according to the results using a random effect model for both DRE and TRUS criteria, the estimates of d for DRE and TRUS were 0.8398 (95 % CI: 0.7169, 0.9627) and 0.8002 (95 % CI: 0.6714, 0.9289), respectively. The detection rate for combination testing of PSA, DRE and TRUS for the diagnosis of prostate cancer jumped further to 68.3 % or to 76.8 %. In conclusion, this study suggests that this diagnostic triad for prostate cancer was noneffective when they were used separately. Therefore, we recommend that the urologists should use PSA together with DRE and TRUS for the primary diagnosis of prostate cancer in men with lower urological symptoms.

Humans↗

PubMed2025

A comprehensive integration of data on the association of ITPKC polymorphisms with susceptibility to Kawasaki disease: a meta-analysis.

BACKGROUND: This study aims to conduct a comprehensive meta-analysis of existing research to define clear associations between variations in the ITPKC gene and the risk of developing Kawasaki disease (KD). METHODS: A comprehensive search was conducted across multiple databases, including but not limited to PubMed, Scopus, EMBASE, and CNKI, up to June 1, 2024, to gather relevant information. This search utilized keywords and MeSH terms related to hyperbilirubinemia and genetic factors. The inclusion criteria encompassed original case-control, longitudinal, or cohort studies. Correlations were analyzed as odds ratios (ORs) with 95% confidence intervals (CIs) using Comprehensive Meta-Analysis software. RESULTS: Eighteen case-control studies with 5,434 KD cases and 9,419 controls were analyzed. Of these, ten studies assessed 3,129 KD cases and 6,172 controls for the rs28493229 variant, four examined 1,039 cases and 1,688 controls for the rs2290692 variant, two focused on 595 cases and 820 controls for the rs7251246 variant, and two investigated 671 cases and 739 controls for the rs10420685 variant. Results showed a significant association between the rs28493229 polymorphism and increased KD risk across all five genetic models. Subgroup analysis indicated this polymorphism correlates with KD susceptibility in Asians but not in the Chinese population. In contrast, no associations were found between the rs2290692, rs7251246, and rs10420685 polymorphisms and KD risk. CONCLUSIONS: Our pooled data indicate a significant association between the ITPKC rs28493229 polymorphism's minor allele and an increased risk of developing KD, suggesting this variant may enhance susceptibility. Conversely, SNPs rs2290692, rs7251246, and rs10420685 do not demonstrate a statistically significant relationship with KD.

Humans↗

PubMed2003

Does adjuvant interferon-alpha for high-risk melanoma provide a worthwhile benefit? A meta-analysis of the randomised trials.

BACKGROUND: Several randomised trials have compared interferon-alpha with control as adjuvant therapy for high-risk malignant melanoma. The results of the individual trials have been either inconclusive or even apparently conflicting. To assess all the available evidence we performed a meta-analysis of these trials. METHODS: Standard methods for quantitative meta-analysis based on published data were used. Endpoints evaluated were recurrence-free survival and overall survival. A subgroup analysis by dose of interferon-alpha was performed. FINDINGS: Twelve trials, comprising 14 comparisons of interferon-alpha with control, with results available were identified. Recurrence-free survival was improved with interferon-alpha: hazard ratio 0.83, 95% confidence interval 0.77 to 0.90, p=0.000003. The benefit on overall survival was less clear (0.93, 0.85 to 1.02, p=0.1) and the confidence interval is compatible both with no benefit and with a moderate, but clinically worthwhile, benefit. There was some evidence of a dose response relationship with a significant trend for the benefit of interferon-alpha to increase with increasing dose for recurrence-free survival (test for trend: p=0.02) but not for overall survival (trend: p=0.8). INTERPRETATION: This meta-analysis provides the most reliable synthesis of the data currently available. Adjuvant interferon-alpha produces clear reductions in recurrence of high-risk melanoma, with some evidence of an effect of dose of interferon-alpha, but it is unclear whether this translates into a worthwhile survival benefit or not. Additional and more mature data are needed to resolve these issues and an individual patient data meta-analysis should be performed.

Antineoplastic Agents↗

PubMed1999

Bias in meta-analysis and funnel plot asymmetry.

International experiences reveal the important role played by scientific research and systematic study a problems, in effectively tackling change in the health sector. Meta-analysis was introduced to address the problem of synthesizing the large quantity of information on a particular subject. It is viewed, only as a step in the process of developing better tools to quantify information across studies. The selection of trials for inclusion in a meta-analysis may be biased if selection is restricted to published trials, to trials published in English language journals, to trials published in prestigious journals or to trials cited by other authors. Funnel plot is graphical display of sample size plotted against effect size for the studies included in a meta-analysis, which can be used to investigate bias. When all the studies have been located, the distribution of points should resemble a funnel. If there are gaps in the funnel shape it indicates that some studies may have not been published or located. In evaluating bias, we use meta-analysis studies about radiotherapy alone versus combined radiotherapy and chemotherapy in stages IIIa and IIIb non-small cell lung cancer. A simple analysis of funnel plots provides useful test for the likely presence of bias in meta-analyses, but as the capacity to detect bias will be limited when meta-analyses are based on a limited number of small trials the results from such analyses should be treated with considerable caution.

Clinical Trials as Topic↗

PubMed2007

The predictive validity of the MCAT for medical school performance and medical board licensing examinations: a meta-analysis of the published research.

PURPOSE: To conduct a meta-analysis of published studies to determine the predictive validity of the MCAT on medical school performance and medical board licensing examinations. METHOD: The authors included all peer-reviewed published studies reporting empirical data on the relationship between MCAT scores and medical school performance or medical board licensing exam measures. Moderator variables, participant characteristics, and medical school performance/medical board licensing exam measures were extracted and reviewed separately by three reviewers using a standardized protocol. RESULTS: Medical school performance measures from 11 studies and medical board licensing examinations from 18 studies, for a total of 23 studies, were selected. A random-effects model meta-analysis of weighted effects sizes (r) resulted in (1) a predictive validity coefficient for the MCAT in the preclinical years of r = 0.39 (95% confidence interval [CI], 0.21-0.54) and on the USMLE Step 1 of r = 0.60 (95% CI, 0.50-0.67); and (2) the biological sciences subtest as the best predictor of medical school performance in the preclinical years (r = 0.32 95% CI, 0.21-0.42) and on the USMLE Step 1 (r = 0.48 95% CI, 0.41-0.54). CONCLUSIONS: The predictive validity of the MCAT ranges from small to medium for both medical school performance and medical board licensing exam measures. The medical profession is challenged to develop screening and selection criteria with improved validity that can supplement the MCAT as an important criterion for admission to medical schools.

Achievement↗

PubMed1999

Meta-analysis of genome searches.

We have developed a method for meta-analysis of genome scans which allows systematic integration of data from published results. The Genome Search Meta-analysis method (GSMA) uses a non-parametric ranking method to identify genetic regions that show consistently increased sharing statistics or lod scores. The GSMA ranks genetic regions according to the lod score or p-value achieved in each scan. The summed rank across studies is compared to its probability distribution assuming ranks are randomly assigned. The GSMA can confirm evidence for regions highlighted in the original genome scans, and identify novel regions, which did not reach significance in any scan. In this paper, the GSMA was applied to four genome screens in multiple sclerosis and across 11 screens from autoimmune disorders. The GSMA is appropriate for studies with different family ascertainment, markers, and statistical analysis methods. The method increases the power to detect individual linkages in a clinically homogeneous dataset and has the potential to detect susceptibility loci in clinically distinct diseases which show involvement of common pathogenetic pathways.

Autoimmune Diseases↗

PubMed1994

Corticosteroids and peptic ulcer: meta-analysis of adverse events during steroid therapy.

OBJECTIVES: This meta-analysis was performed to determine whether corticosteroid therapy induces the development of peptic ulcer and other putative complications of steroid therapy. DESIGN: A retrospective investigation in which we analysed all the randomized, double-blind, controlled trials (RDBCT) in which steroids had been administered that we were able to identify. The number of episodes of peptic ulcer, dermatological effects, sepsis, diabetes, hypertension, osteoporosis, psychosis and tuberculosis reported in both the placebo and steroid groups were compared. SETTING: The international medical literature was analysed for any RDBCT in which any steroid or ACTH had been administered in any dosage for any duration, and any putative complication of steroid therapy was reported. SUBJECTS: Of 1857 articles, 93 satisfied our requirements and were analysed by the meta-analytic techniques of Peto, DerSimonian and Laird. A total of 6602 patients were included. MAIN OUTCOME MEASURES: The relative frequencies of each of these eight 'complications' were compared in the placebo and steroid groups using conventional statistics and meta-analysis. The relative frequencies of 'annualized' subgroups of patients who received treatment for 1 to 7 days, 1 week to 1 month, 1 to 3 months and more than 3 months, were similarly analysed. RESULTS: Nine of 3267 patients in the placebo group (0.3%) and 13 of 3335 patients in the steroid group (0.4%) were reported to develop peptic ulcer (P > 0.05). The dermatological cosmetic effects of steroid therapy were observed more frequently in the steroid group (P < 0.001), as was diabetes (P < 0.001), hypertension (P < 0.01) and psychosis (P < 0.001). Sepsis, osteoporosis and tuberculosis all occurred more frequently in the steroid than in the placebo group, but the differences are not statistically significant. CONCLUSIONS: Peptic ulcer is a rare complication of corticosteroid therapy that should not be considered a contraindication when steroid therapy is indicated.

Adrenal Cortex Hormones↗

PubMed2006

Genetic variation in IL6 gene and type 2 diabetes: tagging-SNP haplotype analysis in large-scale case-control study and meta-analysis.

Interleukin-6 (IL-6, gene symbol IL6) is a proinflammatory cytokine. High circulating IL-6 levels have been associated with insulin resistance and greater risk of type 2 diabetes. Using a linkage disequilibrium (LD)-based approach, we sought to investigate the associations of the common polymorphisms comprehensively defining the genetic variability at the IL6 locus with diabetes risk. We conducted a case-control study of 2691 cases of type 2 diabetes (1692 women and 999 men) and 3237 control subjects (2238 women and 999 men) from the Nurses' Health Study and the Health Professional Follow-up Study. Pairwise LD analysis indicated that all the IL6 polymorphisms (rs2069827, rs1800797, rs1800795, rs1554606, rs2069849, rs2069861 and rs1818879) were in strong LD. We did not find significant associations between IL6 polymorphisms and the risk of type 2 diabetes in women or men, individually or in haplotypes. In addition, none of the IL6 polymorphisms was significantly associated with the plasma levels of IL-6 in the control subjects. Our meta-analysis of 5383 diabetes case and 12 069 controls indicated a null association between the best-studied 5' promoter polymorphism--174G>C (rs1800795)--and diabetes risk. Diversity in adiposity, age and sex could not account for the heterogeneity across different studies. In summary, the data in this study do not support substantial associations between the common polymorphisms in IL6 gene and circulating IL-6 levels and the risk of type 2 diabetes.

Adult↗

PubMed2004

Therapeutic effects of hyaluronic acid on osteoarthritis of the knee. A meta-analysis of randomized controlled trials.

BACKGROUND: The magnitude of the therapeutic effects of intra-articular injection of hyaluronic acid on osteoarthritis of the knee is still in question. The aim of this meta-analysis was to elucidate the therapeutic efficacy and safety of intra-articular injection of hyaluronic acid for osteoarthritis of the knee. METHODS: We conducted a meta-analysis of twenty blinded randomized controlled trials that compared the therapeutic effect of intra-articular injection of hyaluronic acid with that of intra-articular injection of a placebo to treat osteoarthritis of the knee. The outcome end points were classified into three categories: pain with activities, pain without activities, and function. The outcome measures of the efficacy of hyaluronic acid were the mean differences in the efficacy scores between the hyaluronic acid and placebo groups. The outcome measure of the safety of hyaluronic acid was the relative risk of adverse events. RESULTS: Intra-articular injection of hyaluronic acid can decrease symptoms of osteoarthritis of the knee. We found significant improvements in pain and functional outcomes with few adverse events. However, there was significant between-study heterogeneity in the estimates of the efficacy of hyaluronic acid. Subgroup analysis and meta-regression analysis showed that lower methodological quality such as a single-blind or single-center design resulted in higher estimates of hyaluronic acid efficacy, that introduction of acetaminophen as an escape analgesic in the trial resulted in lower estimates of hyaluronic acid efficacy, and that patients older than sixty-five years of age and those with the most advanced radiographic stage of osteoarthritis (complete loss of the joint space) were less likely to benefit from intra-articular injection of hyaluronic acid. CONCLUSIONS: This meta-analysis confirmed the therapeutic efficacy and safety of intra-articular injection of hyaluronic acid for the treatment of osteoarthritis of the knee. Additional well-designed randomized controlled trials with high methodological quality are needed to resolve the continued uncertainty about the therapeutic effects of different types of hyaluronic acid products on osteoarthritis of the knee in various clinical situations and patient populations. LEVEL OF EVIDENCE: Therapeutic study, Level II-3b (systematic review; nonhomogeneous Level-I studies). See Instructions to Authors for a complete description of levels of evidence.

Activities of Daily Living↗