Can we rely on adolescents to self-assess puberty stage? A systematic review and meta-analysis

2020 ◽  
Vol 105 (8) ◽  
pp. 2846-2856 ◽  
Author(s):  
Susan C Campisi ◽  
Josée D Marchand ◽  
Fahad Javaid Siddiqui ◽  
Muhammad Islam ◽  
Zulfiqar A Bhutta ◽  
...  
Keyword(s):  
Data Extraction ◽  
Meta Analysis ◽  
Pubertal Development ◽  
Tanner Stage ◽  
Pubic Hair ◽  
Cochrane Library ◽  
Self Assessment ◽  
Pubertal Stage ◽  
Tanner Staging ◽  
Stage 1

Abstract Context Clinicians, researchers, and global health advocates often include pubertal development in outcomes. However, assessments of pubertal stage can be challenging because of the sensitive nature and feasibility of clinical examinations, especially in larger settings. Objective To determine the accuracy of self-assessed Tanner staging when compared with physically assessed Tanner stages by a clinician. Data Sources MEDLINE, PubMed, Embase, Web of Science, Scopus, the Cochrane Library, CINAHL. Study Selection Studies were included if they reported 5 × 5 tables of self-assessment compared to clinician–assessment for the 5-stage Tanner scale. Data Extraction We extracted data to generate complete 5 × 5 tables for each study, including any subgroup eligible for the analysis, such as overweight/obese youth. Data Synthesis After screening, 22 studies representing 21,801 participants met our inclusion criteria for the meta-analysis. Overall agreement was moderate or substantial between the 2 assessments, with breast stage 1, female pubic hair 1, male pubic hair 1, and male pubic hair 5 having the highest agreement. When stages were collapsed into pre- (Tanner stage 1), in (stages 2,3), and completing (stages 4,5) puberty, levels of agreement improved, especially for pre- and completing pubertal development. Most included studies comprised Caucasian youth. More studies are needed which include a broader range of geographic and socioeconomic settings, as well as a greater diversity of racial/ethnic groups. Conclusions Self-assessment of puberty is most accurate when identifying Tanner stage 1, Tanner stage 5 and when development is categorized into prepuberty, in, and completing puberty phases. Use of self-assessment data should be structured accordingly. Protocol Registration PROSPERO # CRD42018100205

scholarly journals Urinary and salivary endocrine measurements to complement Tanner staging in studies of pubertal development

PLoS ONE ◽  
2021 ◽  
Vol 16 (5) ◽  
pp. e0251598
Author(s):  
Mandy Goldberg ◽  
Anna J. Ciesielski Jones ◽  
John A. McGrath ◽  
Christie Barker-Cummings ◽  
Deborah S. Cousins ◽  
...  
Keyword(s):  
Repeated Measures ◽  
Pubertal Development ◽  
Tanner Stage ◽  
Pubic Hair ◽  
Health Study ◽  
Final Visit ◽  
Tanner Staging ◽  
Non Invasive ◽  
Stage 1

Background Many studies investigating pubertal development use Tanner staging to assess maturation. Endocrine markers in urine and saliva may provide an objective, sensitive, and non-invasive method for assessing development. Objective Our objective was to examine whether changes in endocrine levels can indicate the onset of pubertal development prior to changes in self-rated Tanner stage. Methods Thirty-five girls and 42 boys aged 7 to 15 years were enrolled in the Growth and Puberty (GAP) study, a longitudinal pilot study conducted from 2007–2009 involving children of women enrolled in the Agricultural Health Study (AHS) in Iowa. We collected saliva and urine samples and assessed pubertal development by self-rated Tanner staging (pubic hair, breast development (girls), genital development (boys)) at three visits over six months. We measured dehydroepiandrosterone (DHEA) in saliva and creatinine-adjusted luteinizing hormone (LH), testosterone, follicle stimulating hormone (FSH), estrone 3-glucuronide (E13G) and pregnanediol 3-glucuronide (Pd3G) concentrations in first morning urine. We evaluated the relationships over time between Tanner stage and each biomarker using repeated measures analysis. Results Among girls still reporting Tanner breast stage 1 at the final visit, FSH levels increased over the 6-month follow-up period and were no longer lower than higher stage girls at the end of follow-up. We observed a similar pattern for testosterone in boys. By visit 3, boys still reporting Tanner genital stage 1 or pubic hair stage 1 had attained DHEA levels that were comparable to those among boys reporting Tanner stages 2 or 3. Conclusions Increasing concentrations of FSH in girls and DHEA and testosterone in boys over a 6-month period revealed the start of the pubertal process prior to changes in self-rated Tanner stage. Repeated, non-invasive endocrine measures may complement the more subjective assessment of physical markers in studies determining pubertal onset.

Self-assessment of pubertal development in a puberty cohort

2018 ◽  
Vol 31 (7) ◽  
pp. 763-772 ◽  
Author(s):  
Andreas Ernst ◽  
Lea Lykke B. Lauridsen ◽  
Nis Brix ◽  
Camilla Kjersgaard ◽  
Jørn Olsen ◽  
...  
Keyword(s):  
Clinical Examination ◽  
Pubertal Development ◽  
Tanner Stage ◽  
Weighted Kappa ◽  
Pubic Hair ◽  
Kappa Statistics ◽  
Random Errors ◽  
Rater Agreement ◽  
Self Assessment ◽  
Tanner Staging

Abstract Background We evaluated the inter-rater agreement between self-assessed Tanner staging and clinical examination and the intra-individual agreement of self-assessed information on various puberty markers in late adolescents from the longitudinal nationwide Puberty Cohort, a sub-cohort of the Danish National Birth Cohort (DNBC). Methods We invited 715 children from the ongoing Puberty Cohort between June 2016 and January 2017. In total, 366 children (51%) returned an add-on questionnaire identical to the questionnaire used to collect information on puberty markers, including Tanner staging, in the Puberty Cohort. Of these, 197 (54%) also participated in a clinical examination with Tanner staging. We used percentage agreement and weighted kappa statistics to evaluate the inter-rater and intra-individual agreement. Results Due to late entry, more than 75% of children were Tanner stage 4 or above at clinical examination. In girls, the inter-rater agreement for pubic hair and breast staging was 54% and 52%, respectively, yielding weighted kappas of fair strength. In boys, pubic hair and genital staging agreed in 55% and 33%, respectively, corresponding to weighted kappas of fair to moderate strength. Boys tended to underestimate genitalia staging consistently. The intra-individual agreement on Tanner staging was 75–77% in girls and 69% in boys, whereas the intra-individual agreement on axillary hair and acne was above 92%. Conclusions Self-assessment of late stages of pubertal development may be misclassified, leading to random errors in studies of puberty timing. However, self-assessment continues to serve as an important time- and cost-saving tool in large prospective puberty cohorts.

scholarly journals Twenty-Four-Hour Profiles of Luteinizing Hormone, Follicle-Stimulating Hormone, Testosterone, and Estradiol Levels: A Semilongitudinal Study throughout Puberty in Healthy Boys*

1997 ◽  
Vol 82 (2) ◽  
pp. 541-549 ◽  
Author(s):  
Kerstin Albertsson-Wikland ◽  
Sten Rosberg ◽  
Birgitta Lannering ◽  
Leo Dunkel ◽  
Gunnar Selstam ◽  
...  
Keyword(s):  
Diurnal Rhythm ◽  
Pubertal Development ◽  
Tanner Stage ◽  
Testicular Volume ◽  
Early Puberty ◽  
Pubertal Stage ◽  
Pubertal Stages ◽  
Prepubertal Boys ◽  
Stage 1 ◽  
Estradiol Levels

Abstract To follow and correlate gonadotropin and sex steroid changes throughout puberty, 24-h profiles of LH, FSH, testosterone, and estradiol were taken on several occasions for between 2–9.5 yr in 12 healthy boys, aged 8.7–18.2 yr. Serum concentrations of LH and FSH were measured every 20 min, whereas testosterone and estradiol were measured every 2–4 h during the 24-h period. The prepubertal boys (Tanner stage 1) were subdivided into two groups: Pre 1, with a testicular volume of 1–2 mL, and Pre 2, with a testicular volume of 3 mL. Pubertal stages were classified, according to testicular volume, as early puberty (pubertal stage 2; 4–9 mL), midpuberty (pubertal stages 3–4; 10–15 mL), and late puberty (pubertal stage 5; ≥16 mL). Mean levels of LH and FSH increased with pubertal development, although the increase in LH was greater than that in FSH. These increases were due to elevated basal levels of LH and FSH as well as to increases in the number of peaks and the peak amplitudes of LH. No diurnal rhythm was found in boys at stage Pre 1. Thereafter, a clear diurnal rhythm appeared for LH, and later in puberty, an ultradian rhythm was superimposed, as shown by time-sequence analyses. A diurnal rhythm also existed for FSH, but was much less marked than that for LH despite a clear covariation between LH and FSH, as shown from cross-correlation studies. Testosterone also showed diurnal variations from the late prepubertal stage, followed by increasing levels during both day and night in puberty. We conclude that during puberty, gonadotropin levels rise differently for LH and FSH, which may be due to the development of differences in feedback mechanisms. Despite covariation between LH and FSH, only LH showed a clear diurnal variation. In parallel, nocturnal variations in testosterone and estradiol were found. Changes in mean levels of LH, testosterone, and estradiol as well as their mean daytime and nighttime levels follow each other from the prepubertal stages to late puberty.

scholarly journals Prevalence of retinopathy in prediabetes: protocol for a systematic review and meta-analysis

BMJ Open ◽  
2021 ◽  
Vol 11 (1) ◽  
pp. e040997
Author(s):  
Varo Kirthi ◽  
Paul Nderitu ◽  
Uazman Alam ◽  
Jennifer Evans ◽  
Sarah Nevitt ◽  
...  
Keyword(s):  
Systematic Review ◽  
Diabetic Retinopathy ◽  
Data Extraction ◽  
Meta Analysis ◽  
International Diabetes Federation ◽  
Current Data ◽  
Risk Of Bias ◽  
Fundus Photography ◽  
Primary Data ◽  
Cochrane Library

IntroductionThere is growing evidence of a higher than expected prevalence of retinopathy in prediabetes. This paper presents the protocol of a systematic review and meta-analysis of retinopathy in prediabetes. The aim of the review is to estimate the prevalence of retinopathy in prediabetes and to summarise the current data.Methods and analysisThis protocol is developed in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses Protocols (PRISMA-P) guidelines. A comprehensive electronic bibliographic search will be conducted in MEDLINE, EMBASE, Web of Science, Cumulative Index to Nursing and Allied Health Literature (CINAHL), Google Scholar and the Cochrane Library. Eligible studies will report prevalence data for retinopathy on fundus photography in adults with prediabetes. No time restrictions will be placed on the date of publication. Screening for eligible studies and data extraction will be conducted by two reviewers independently, using predefined inclusion criteria and prepiloted data extraction forms. Disagreements between the reviewers will be resolved by discussion, and if required, a third (senior) reviewer will arbitrate.The primary outcome is the prevalence of any standard features of diabetic retinopathy (DR) on fundus photography, as per International Clinical Diabetic Retinopathy Severity Scale (ICDRSS) classification. Secondary outcomes are the prevalence of (1) any retinal microvascular abnormalities on fundus photography that are not standard features of DR as per ICDRSS classification and (2) any macular microvascular abnormalities on fundus photography, including but not limited to the presence of macular exudates, microaneurysms and haemorrhages. Risk of bias for included studies will be assessed using a validated risk of bias tool for prevalence studies. Pooled estimates for the prespecified outcomes of interest will be calculated using random effects meta-analytic techniques. Heterogeneity will be assessed using the I2 statistic.Ethics and disseminationEthical approval is not required as this is a protocol for a systematic review and no primary data are to be collected. Findings will be disseminated through peer-reviewed publications and presentations at national and international meetings including Diabetes UK, European Association for the Study of Diabetes, American Diabetes Association and International Diabetes Federation conferences.PROSPERO registration numberCRD42020184820.

scholarly journals Effectiveness of Antalgic Therapies in Patients with Vertebral Bone Metastasis: A Protocol for a Systematic Review and Meta-Analysis

2021 ◽  
Vol 18 (8) ◽  
pp. 3991
Author(s):  
Antonio Jose Martin-Perez ◽  
María Fernández-González ◽  
Paula Postigo-Martin ◽  
Marc Sampedro Pilegaard ◽  
Carolina Fernández-Lao ◽  
...  
Keyword(s):  
Systematic Review ◽  
Bone Metastasis ◽  
Data Extraction ◽  
Meta Analysis ◽  
Risk Of Bias ◽  
Cochrane Library ◽  
Pharmacological Intervention ◽  
Vertebral Metastasis ◽  
Randomized Controlled Clinical Trials

There is no systematic review that has identified existing studies evaluating the pharmacological and non-pharmacological intervention for pain management in patients with bone metastasis. To fill this gap in the literature, this systematic review with meta-analysis aims to evaluate the effectiveness of different antalgic therapies (pharmacological and non-pharmacological) in the improvement of pain of these patients. To this end, this protocol has been written according to the Preferred Reporting Items for Systematic review and Meta-Analysis Protocols (PRISMA-P) and registered in PROSPERO (CRD42020135762). A systematic search will be carried out in four international databases: Medline (Via PubMed), Web of Science, Cochrane Library and SCOPUS, to select the randomized controlled clinical trials. The Risk of Bias Tool developed by Cochrane will be used to assess the risk of bias and the quality of the identified studies. A narrative synthesis will be used to describe and compare the studies, and after the data extraction, random effects model and a subgroup analyses will be performed according to the type of intervention, if possible. This protocol aims to generate a systematic review that compiles and synthesizes the best and most recent evidence on the treatment of pain derived from vertebral metastasis.

Urinary gonadotropin measurements by enhanced luminometric assays (LIA) for the evaluation of pubertal development

2021 ◽  
Vol 0 (0) ◽  
Author(s):  
And Demir ◽  
Adem Aydın ◽  
Atilla Büyükgebiz ◽  
Ulf-Håkan Stenman ◽  
Matti Hero
Keyword(s):  
Healthy Subjects ◽  
Reliable Method ◽  
Pubertal Development ◽  
High Sensitivity ◽  
Tanner Stage ◽  
Time Resolved ◽  
Stage 1 ◽  
Sensitive Detection Technique ◽  
Serum And Urine

Abstract Objectives Determination of LH in urine has proved to be a reliable method for evaluation of pubertal development. The human LH assay based on time-resolved immunofluorometric (IFMA) technology (AutoDELFIA, PerkinElmer, Wallac) has been found to be suitable for this purpose thanks to its high sensitivity but other assays have not been evaluated. We have analyzed our data obtained by another potentially sensitive detection technique, enhanced luminometric assay (LIA) with the objective of finding a viable alternative to IFMA since these may not be available in the future. Methods LIA was used to measure LH and FSH in serum and urine samples from 100 healthy subjects of each Tanner stage and both genders, whose pubertal development has been determined. Results Urinary gonodotropin concentrations measured by LIA correlated well with Tanner stage [(r=0.93 for girls, r=0.81 for boys; p<0.01 for LH) and (r=0.81 for girls, r=0.73 for boys; p<0.01 for FSH)]. LIA determinations revealed the increase in U-LH concentrations during the transition from Tanner stage 1–2 in both girls and boys (p<0.001), whereas U-FSH and S-LH were able to detect the increase from Tanner stage 1–2 only in boys or girls, respectively (both p<0.001). Conclusions Measurement of urinary gonadotropin concentrations by LIA may be useful for the evaluation of overall pubertal development and also in the detection of transition from prepuberty to puberty.

Executive functions in children with heart disease: a systematic review and meta-analysis

2021 ◽  
pp. 1-9
Author(s):  
William M. Jackson ◽  
Nicholas Davis ◽  
Johanna Calderon ◽  
Jennifer J. Lee ◽  
Nicole Feirsen ◽  
...  
Keyword(s):  
Systematic Review ◽  
Executive Functions ◽  
Data Extraction ◽  
Meta Analysis ◽  
Executive Dysfunction ◽  
Cochrane Library ◽  
Planning Problem ◽  
Healthy Controls ◽  
Cross Sectional ◽  
Increased Risk

Abstract Context: People with CHD are at increased risk for executive functioning deficits. Meta-analyses of these measures in CHD patients compared to healthy controls have not been reported. Objective: To examine differences in executive functions in individuals with CHD compared to healthy controls. Data sources: We performed a systematic review of publications from 1 January, 1986 to 15 June, 2020 indexed in PubMed, CINAHL, EMBASE, PsycInfo, Web of Science, and the Cochrane Library. Study selection: Inclusion criteria were (1) studies containing at least one executive function measure; (2) participants were over the age of three. Data extraction: Data extraction and quality assessment were performed independently by two authors. We used a shifting unit-of-analysis approach and pooled data using a random effects model. Results: The search yielded 61,217 results. Twenty-eight studies met criteria. A total of 7789 people with CHD were compared with 8187 healthy controls. We found the following standardised mean differences: −0.628 (−0.726, −0.531) for cognitive flexibility and set shifting, −0.469 (−0.606, −0.333) for inhibition, −0.369 (−0.466, −0.273) for working memory, −0.334 (−0.546, −0.121) for planning/problem solving, −0.361 (−0.576, −0.147) for summary measures, and −0.444 (−0.614, −0.274) for reporter-based measures (p < 0.001). Limitations: Our analysis consisted of cross-sectional and observational studies. We could not quantify the effect of collinearity. Conclusions: Individuals with CHD appear to have at least moderate deficits in executive functions. Given the growing population of people with CHD, more attention should be devoted to identifying executive dysfunction in this vulnerable group.

scholarly journals Risk of dementia in gout and hyperuricaemia: a meta-analysis of cohort studies

BMJ Open ◽  
2021 ◽  
Vol 11 (6) ◽  
pp. e041680
Author(s):  
Shu-Yue Pan ◽  
Rui-Juan Cheng ◽  
Zi-Jing Xia ◽  
Qiu-Ping Zhang ◽  
Yi Liu
Keyword(s):  
Cohort Studies ◽  
Quality Assessment ◽  
Publication Bias ◽  
Data Extraction ◽  
Meta Analysis ◽  
Sensitivity Analyses ◽  
Cochrane Library ◽  
Crystal Formation ◽  
Medical Subject Headings ◽  
Eligibility Criteria

ObjectivesGout, characterised by hyperuricaemia with monosodium urate crystal formation and inflammation, is the most common inflammatory arthritis in adults. Recent studies have found that elevated uric acid levels are related to the occurrence of dementia. We conducted a study to investigate the association between dementia and gout or hyperuricaemia.DesignSystematic review and meta-analysis of cohort studies.Data sourcesStudies were screened from inception to 28 June 2019 by searching Medline, Embase and the Cochrane Library databases.Eligibility criteriaCohort studies comparing the risk of dementia in patients with gout and hyperuricaemia versus non-gout and non-hyperuricaemia controls were enrolled.Data extraction and analysisTwo reviewers separately selected studies and extracted data using the Medical Subject Headings without restriction on languages or countries. The adjusted HRs were pooled using the DerSimonian and Laird random effects model. Sensitivity analyses were conducted to evaluate the stability of the results. Publication bias was evaluated using Egger’s and Begg’s tests. Quality assessment was performed according to the Newcastle-Ottawa Scale.ResultsFour cohort studies that met the inclusion criteria were included in our meta-analysis. We found that gout and hyperuricaemia did not increase the risk of dementia, with a pooled HR of 0.94 (95% CI 0.69 to 1.28), but might decrease the risk of Alzheimer’s disease (AD), with a pooled HR of 0.78 (95% CI 0.64 to 0.95). There was little evidence of publication bias. Quality assessment of the included studies was high (range: 6–8 points).ConclusionsOur study shows that gout and hyperuricaemia do not increase the risk of dementia. However, gout and hyperuricaemia might have a protective effect against AD. Due to the limited number of research articles, more investigations are needed to demonstrate the potential relationship between dementia and gout or hyperuricaemia.

Comparing adolescent self staging of pubertal development with hormone biomarkers

2021 ◽  
Vol 0 (0) ◽  
Author(s):  
Nana-Hawa Yayah Jones ◽  
Jane C. Khoury ◽  
Yingying Xu ◽  
Nicholas Newman ◽  
Heidi J. Kalkwarf ◽  
...  
Keyword(s):  
Least Squares ◽  
Pubertal Development ◽  
Dehydroepiandrosterone Sulfate ◽  
Pubic Hair ◽  
Birth Cohort Study ◽  
Physical Examinations ◽  
Environment Study ◽  
Hair Development ◽  
Stage 1 ◽  
Self Examination

Abstract Objectives Physical examinations to characterize pubertal maturation may be unacceptable for children enrolled in research studies. Studies confirm the utility of pubertal self staging for research, but there has been limited comparison of self examination with hormone biomarkers. Our objective was to assess concordance of pubertal self staging with hormone biomarkers of puberty. Methods Participants were enrolled in the Health Outcomes and Measures of the Environment Study, a longitudinal pregnancy and birth cohort study. At age 12 years, 139 females and 112 males completed pubertal self staging including breast and pubic hair development in females and pubic hair development in males. No clinical physical examination was performed. Hormone concentrations were measured in 102 females and 96 males including serum dehydroepiandrosterone sulfate, luteinizing hormone, and follicle-stimulating hormone in all; estradiol in females; and testosterone in males. Results Estradiol was significantly associated with female breast stage, even when adjusted for BMI, with geometric least squares means (95%CI) of 13.2 (8.7, 20.2), 38.3 (29.9, 49.1), 59.4 (39.8, 88.6), and 81.2 (45.6, 144) pg/mL for breast stage 1–2, 3, 4, and 5, respectively. Testosterone was significantly associated with male pubic hair stage, with adjusted geometric least squares means (95%CI) of 37.6 (19.9, 71.1), 43.4 (27.7, 68.3), 126 (78.4, 203), 275 (146, 521), and 559 (237, 1319) ng/dL for pubic hair stage 1, 2, 3, 4, and 5, respectively. Conclusions Self assessed pubertal development was positively associated with hormonal biomarkers of puberty.

Comparison between Ologen implant and Mitomycin C in trabeculectomy: A Systematic Review and Meta-Analysis

2019 ◽  
Author(s):  
Xiaoyan Liu ◽  
Yali Du ◽  
Min Lei ◽  
Leyi Zhuang ◽  
Peng Lv
Keyword(s):  
Adverse Events ◽  
Success Rate ◽  
Data Extraction ◽  
Meta Analysis ◽  
Collagen Matrix ◽  
Current Evidence ◽  
Cochrane Library ◽  
Significant Difference ◽  
Mean Differences ◽  
Alternative Choice

Abstract Objective To evaluate the effectiveness and safety of the biodegradable collagen matrix (Ologen) implant in trabeculectomy. Research design and methods We searched Pubmed, Cochrane library, Embase and Web of Science databases to find studies that met our pre-stated inclusion criteria. Reference lists of retrieved articles were also reviewed. The search was finished by February 2019. Study selection, data extraction, quality assessment, and data analyses were performed according to the Cochrane standards. Either a fixed or a random-effects model was used to calculate the overall combined risk estimates. The efficacy measures were the weighted mean differences (WMDs) for the intraocular pressure reduction (IOPR) and the glaucoma medications reduction, the odds ratio (OR) for the success rate and adverse events. Results Fifteen randomized controlled trials involved 682 eyes were included in the meta-analysis. There were no statistically differences between two groups in the IOPR at any time postoperatively. The MD of the IOPR was [MD= -0.45,95% Confidence Interval (CI), (-2.36,1.46), P=0.65] at one day, [MD= -0.82,95% CI, (-1.97, 0.33), P=0.16] at one week, [MD= -1.33, 95% CI,(-3.12, 0.47), P=0.15] at one month, [MD= 0.11,95% CI, (-1.87, 2.08), P=0.92] at three months, [MD= -0.60,95% CI, (-2.27, 1.06), P=0.48] at six months, [MD= -0.33,95% CI, (-1.99, 1.32), P=0.69] at one year, [MD= -0.13,95% CI, (-1.90, 1.65), P=0.89] at two years, [MD= 2.54,95% CI, (-2.83, 7.90), P=0.35] at three years, [MD= 3.04,95% CI, (-3.95, 10.03), P=0.39] at five years. There was no statistically significant difference between the Ologen groups and MMC groups concerned the complete success rate [OR=1.19, 95%CI, (0.83, 1.71), P=0.35]. With regard to the adverse events, no obvirously significance was observed. Seven studies reported the change of antiglaucoma medications. We found that the change of antiglaucoma medications is higher in MMC groups than that in Ologen groups [MD=-0.18, 95%CI, (-0.33, -0.03), P=0.02]. There is no significant difference in complications between the two groups. Conclusions From the current evidence, Ologen may be an alternative choice for trabeculectomy when considering the efficacy and safety. However, MMC might be the preferred choice concerned cost-effectiveness.

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