-
Cancer Treatment Reviews Apr 2022Adjuvant and neoadjuvant breast cancer treatments can reduce breast cancer mortality but may increase mortality from other causes. Information regarding treatment... (Review)
Review
BACKGROUND
Adjuvant and neoadjuvant breast cancer treatments can reduce breast cancer mortality but may increase mortality from other causes. Information regarding treatment benefits and risks is scattered widely through the literature. To inform clinical practice we collated and reviewed the highest quality evidence.
METHODS
Guidelines were searched to identify adjuvant or neoadjuvant treatment options recommended in early invasive breast cancer. For each option, systematic literature searches identified the highest-ranking evidence. For radiotherapy risks, searches for dose-response relationships and modern organ doses were also undertaken.
RESULTS
Treatment options recommended in the USA and elsewhere included chemotherapy (anthracycline, taxane, platinum, capecitabine), anti-human epidermal growth factor 2 therapy (trastuzumab, pertuzumab, trastuzumab emtansine, neratinib), endocrine therapy (tamoxifen, aromatase inhibitor, ovarian ablation/suppression) and bisphosphonates. Radiotherapy options were after breast conserving surgery (whole breast, partial breast, tumour bed boost, regional nodes) and after mastectomy (chest wall, regional nodes). Treatment options were supported by randomised evidence, including > 10,000 women for eight treatment comparisons, 1,000-10,000 for fifteen and < 1,000 for one. Most treatment comparisons reduced breast cancer mortality or recurrence by 10-25%, with no increase in non-breast-cancer death. Anthracycline chemotherapy and radiotherapy increased overall non-breast-cancer mortality. Anthracycline risk was from heart disease and leukaemia. Radiation-risks were mainly from heart disease, lung cancer and oesophageal cancer, and increased with increasing heart, lung and oesophagus radiation doses respectively. Taxanes increased leukaemia risk.
CONCLUSIONS
These benefits and risks inform treatment decisions for individuals and recommendations for groups of women.
Topics: Breast Neoplasms; Chemotherapy, Adjuvant; Female; Humans; Mastectomy; Neoadjuvant Therapy; Tamoxifen
PubMed: 35367784
DOI: 10.1016/j.ctrv.2022.102375 -
BMJ (Clinical Research Ed.) Sep 2022To determine if margin involvement is associated with distant recurrence and to determine the required margin to minimise both local recurrence and distant recurrence in... (Meta-Analysis)
Meta-Analysis
OBJECTIVE
To determine if margin involvement is associated with distant recurrence and to determine the required margin to minimise both local recurrence and distant recurrence in early stage invasive breast cancer.
DESIGN
Prospectively registered systematic review and meta-analysis of literature.
DATA SOURCES
Medline (PubMed), Embase, and Proquest online databases. Unpublished data were sought from study authors.
ELIGIBILITY CRITERIA
Eligible studies reported on patients undergoing breast conserving surgery (for stages I-III breast cancer), allowed an estimation of outcomes in relation to margin status, and followed up patients for a minimum of 60 months. Patients with ductal carcinoma in situ only or treated with neoadjuvant chemotherapy or by mastectomy were excluded. Where applicable, margins were categorised as tumour on ink (involved), close margins (no tumour on ink but <2 mm), and negative margins (≥2 mm).
RESULTS
68 studies from 1 January 1980 to 31 December 2021, comprising 112 140 patients with breast cancer, were included. Across all studies, 9.4% (95% confidence interval 6.8% to 12.8%) of patients had involved (tumour on ink) margins and 17.8% (13.0% to 23.9%) had tumour on ink or a close margin. The rate of distant recurrence was 25.4% (14.5% to 40.6%) in patients with tumour on ink, 8.4% (4.4% to 15.5%) in patients with tumour on ink or close, and 7.4% (3.9% to 13.6%) in patients with negative margins. Compared with negative margins, tumour on ink margins were associated with increased distant recurrence (hazard ratio 2.10, 95% confidence interval 1.65 to 2.69, P<0.001) and local recurrence (1.98, 1.66 to 2.36, P<0.001). Close margins were associated with increased distant recurrence (1.38, 1.13 to 1.69, P<0.001) and local recurrence (2.09, 1.39 to 3.13, P<0.001) compared with negative margins, after adjusting for receipt of adjuvant chemotherapy and radiotherapy. In five studies published since 2010, tumour on ink margins were associated with increased distant recurrence (2.41, 1.81 to 3.21, P<0.001) as were tumour on ink and close margins (1.44, 1.22 to 1.71, P<0.001) compared with negative margins.
CONCLUSIONS
Involved or close pathological margins after breast conserving surgery for early stage, invasive breast cancer are associated with increased distant recurrence and local recurrence. Surgeons should aim to achieve a minimum clear margin of at least 1 mm. On the basis of current evidence, international guidelines should be revised.
SYSTEMATIC REVIEW REGISTRATION
CRD42021232115.
Topics: Breast; Breast Neoplasms; Female; Humans; Margins of Excision; Mastectomy; Mastectomy, Segmental; Neoplasm Recurrence, Local
PubMed: 36130770
DOI: 10.1136/bmj-2022-070346 -
Journal of Plastic, Reconstructive &... Nov 2022Because of improved aesthetic results, immediate breast reconstruction has become the most widely used timing of reconstruction following mastectomy. Many studies report... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Because of improved aesthetic results, immediate breast reconstruction has become the most widely used timing of reconstruction following mastectomy. Many studies report complication rates between immediate and delayed reconstructions at certain medical institutions, but no systematic reviews exist to summarize the literature. This systematic review was conducted to assess the outcomes in women who underwent immediate versus delayed breast reconstruction following mastectomy for breast cancer.
METHODS
Cochrane, PubMed, and EMBASE electronic databases were screened, and data were extracted from included studies. The clinical outcomes assessed were surgical complications, length of postoperative hospital stay, and reoperation rate.
RESULTS
A total of 30 studies met the inclusion criteria for the review and provided enough data to be included in the meta-analysis (14,034 patients). Women receiving immediate breast reconstruction were significantly more likely to experience surgical complications (OR 1.30, 95% CI 1.03, 1.65; p = 0.03). Sensitivity analysis showed that women receiving immediate reconstruction were also more likely to experience infection (OR 1.41, 95% 1.04, 1.92; p = 0.03) and hematoma/seroma (OR 2.01, 95% CI 1.27-3.17; p = 0.003). Furthermore, a separate sensitivity analysis showed no significant differences in reported outcomes when comparing studies whose patient cohorts received post-mastectomy radiation therapy (PMRT).
CONCLUSIONS
This study provides evidence that immediate breast reconstruction generally increases the risk of complications in comparison with delayed reconstruction. Additional prospective and observational studies are needed to determine the role of PMRT and reconstruction surgical technique in the incidence of complications between immediate and delayed reconstructions.
Topics: Humans; Female; Mastectomy; Breast Neoplasms; Prospective Studies; Mammaplasty; Seroma; Postoperative Complications; Radiotherapy, Adjuvant; Retrospective Studies
PubMed: 36202732
DOI: 10.1016/j.bjps.2022.08.029 -
Breast Cancer (Tokyo, Japan) Jul 2020The present review evaluated health-related quality of life (HR-QoL) outcomes in surgical breast cancer survivors who received breast reconstruction (BR),... (Comparative Study)
Comparative Study Meta-Analysis
Health-related quality of life following breast reconstruction compared to total mastectomy and breast-conserving surgery among breast cancer survivors: a systematic review and meta-analysis.
The present review evaluated health-related quality of life (HR-QoL) outcomes in surgical breast cancer survivors who received breast reconstruction (BR), breast-conservation surgery (BCS) or mastectomy (M), and whether HR-QoL domains across generic and disease/surgery-specific questionnaires are compatible. Six electronic databases were searched for appropriate observational studies. Standardized scores for different HR-QoL domains in the BR, BCS, and M treatment groups were extracted from each study for the purpose of a meta-analysis. Using Stata version 14.0, a random-effects meta-analysis model was adopted for each outcome variable to estimate the effect size, 95% CI-confidence intervals, and statistical significance. Sixteen of the 18 eligible studies with BR (n = 1474) and BCS (n = 2612) or M (n = 1458) groups were included in the meta-analysis. The BR group exhibited a better physical health (k = 12; 0.1, 95% CI 0.04, 0.24) and body image (k = 12; 0.50, 95% CI 0.10, 0.89) than the M group. However, the two groups exhibited comparable social health (k = 13; 0.1, 95% CI -0.07, 0.37), emotional health (k = 13; -0.08, 95% CI - 0.41, 0.25), global health (k = 7; 0.1, 95% CI - 0.01, 0.27), and sexual health (k =11; 0.2, 95% CI - 0.02,0.57). There was no clear evidence of the superiority of BR to BCS for all the six domains. These results suggest that HR-QoL outcomes in BR and BCS groups are better than the M group. Therefore, women opting for BR or BCS are likely to report fairly better HR-QoL outcomes than M. However, due to the significant heterogeneity observed in most BR versus BCS outcomes, developing a unified questionnaire incorporating both breast/surgery-specific and generic HR-QoL domains is warranted.
Topics: Body Image; Breast; Breast Neoplasms; Cancer Survivors; Female; Humans; Mammaplasty; Mastectomy, Segmental; Mastectomy, Simple; Quality of Life; Surveys and Questionnaires
PubMed: 32162181
DOI: 10.1007/s12282-020-01076-1 -
Medicine Dec 2020Studies have shown that manual lymphatic drainage (MLD) has a beneficial effect on lymphedema related to breast cancer surgery. However, whether MLD reduces the risk of... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Studies have shown that manual lymphatic drainage (MLD) has a beneficial effect on lymphedema related to breast cancer surgery. However, whether MLD reduces the risk of lymphedema is still debated. The purpose of this systematic review and meta-analysis was to summarize the current evidence to assess the effectiveness of MLD in preventing and treating lymphedema in patients after breast cancer surgery.
METHODS
From inception to May 2019, PubMed, EMBASE, and Cochrane Library databases were systematically searched without language restriction. We included randomized controlled trials (RCTs) that compared the treatment and prevention effect of MLD with a control group on lymphedema in breast cancer patients. A random-effects model was used for all analyses.
RESULTS
A total of 17 RCTs involving 1911 patients were included. A meta-analysis of 8 RCTs, including 338 patients, revealed that MLD did not significantly reduce lymphedema compared with the control group (standardized mean difference (SMD): -0.09, 95% confidence interval (CI): [-0.85 to 0.67]). Subgroup analysis was basically consistent with the main analysis according to the research region, the publication year, the sample size, the type of surgery, the statistical analysis method, the mean age, and the intervention time. However, we found that MLD could significantly reduce lymphedema in patients under the age of 60 years (SMD: -1.77, 95% CI: [-2.23 to -1.31]) and an intervention time of 1 month (SMD: -1.77, 95% CI: [-2.23 to -1.30]). Meanwhile, 4 RCTs including, 1364 patients, revealed that MLD could not significantly prevent the risk of lymphedema (risk ratio (RR): 0.61, 95% CI: [0.29-1.26]) for patients having breast cancer surgery.
CONCLUSIONS
Overall, this meta-analysis of 12 RCTs showed that MLD cannot significantly reduce or prevent lymphedema in patients after breast cancer surgery. However, well-designed RCTs with a larger sample size are required, especially in patients under the age of 60 years or an intervention time of 1 month.
Topics: Breast Neoplasms; Humans; Lymphedema; Manual Lymphatic Drainage; Mastectomy; Randomized Controlled Trials as Topic
PubMed: 33285693
DOI: 10.1097/MD.0000000000023192 -
Quality of Life Research : An... Apr 2022To determine the efficacy of physical therapy interventions on quality of life (QoL) and pain severity in post-mastectomy pain syndrome (PMPS). (Meta-Analysis)
Meta-Analysis
Efficacy of physical therapy interventions on quality of life and upper quadrant pain severity in women with post-mastectomy pain syndrome: a systematic review and meta-analysis.
PURPOSE
To determine the efficacy of physical therapy interventions on quality of life (QoL) and pain severity in post-mastectomy pain syndrome (PMPS).
METHODS
Multiple databases were searched from database inception to October 2020. Searches were limited to human studies published in either English or Chinese in peer-reviewed journals with full text available for randomized controlled trials conducted on females. Trials comparing the effectiveness of physical therapy interventions against control conditions on QoL and pain were included.
RESULTS
Eighteen trials were included in the review. The pooled analysis of the four exercise trials revealed a significant effect of the intervention on general [standardized mean difference [SMD]: 0.87 (95%CI: 0.36, 1.37); p = 0.001], physical [SMD: 0.34 (95%CI: 0.01, 0.66); p = 0.044], and mental health components [SMD: 0.27 (95%CI: 0.03, 0.51); p = 0.027] of QoL compared with the control condition. Meta-analyses of six exercise trials, two myofascial release trials, and two acupuncture trials revealed a significant improvement in pain severity in the treatment group than in the control group. However, meta-analyses of two studies revealed a non-significant effect of compression therapy compared to control on pain severity.
CONCLUSION
Our meta-analyses found that exercise is beneficial for improving the QoL and pain severity of women with PMPS. Future studies are needed to determine the optimal parameters for exercise interventions designed to improve QoL and pain severity in women with PMPS. The effect of acupuncture, myofascial release, and compression therapy remains inconclusive, and future research is required to validate the effect of these interventions on PMPS.
Topics: Breast Neoplasms; Chronic Pain; Female; Humans; Mastectomy; Pain Measurement; Physical Therapy Modalities; Quality of Life
PubMed: 34185226
DOI: 10.1007/s11136-021-02926-x -
The Lancet. Oncology May 2013The body of evidence related to breast-cancer-related lymphoedema incidence and risk factors has substantially grown and improved in quality over the past decade. We... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
The body of evidence related to breast-cancer-related lymphoedema incidence and risk factors has substantially grown and improved in quality over the past decade. We assessed the incidence of unilateral arm lymphoedema after breast cancer and explored the evidence available for lymphoedema risk factors.
METHODS
We searched Academic Search Elite, Cumulative Index to Nursing and Allied Health, Cochrane Central Register of Controlled Trials (clinical trials), and Medline for research articles that assessed the incidence or prevalence of, or risk factors for, arm lymphoedema after breast cancer, published between Jan 1, 2000, and June 30, 2012. We extracted incidence data and calculated corresponding exact binomial 95% CIs. We used random effects models to calculate a pooled overall estimate of lymphoedema incidence, with subgroup analyses to assess the effect of different study designs, countries of study origin, diagnostic methods, time since diagnosis, and extent of axillary surgery. We assessed risk factors and collated them into four levels of evidence, depending on consistency of findings and quality and quantity of studies contributing to findings.
FINDINGS
72 studies met the inclusion criteria for the assessment of lymphoedema incidence, giving a pooled estimate of 16.6% (95% CI 13.6-20.2). Our estimate was 21.4% (14.9-29.8) when restricted to data from prospective cohort studies (30 studies). The incidence of arm lymphoedema seemed to increase up to 2 years after diagnosis or surgery of breast cancer (24 studies with time since diagnosis or surgery of 12 to <24 months; 18.9%, 14.2-24.7), was highest when assessed by more than one diagnostic method (nine studies; 28.2%, 11.8-53.5), and was about four times higher in women who had an axillary-lymph-node dissection (18 studies; 19.9%, 13.5-28.2) than it was in those who had sentinel-node biopsy (18 studies; 5.6%, 6.1-7.9). 29 studies met the inclusion criteria for the assessment of risk factors. Risk factors that had a strong level of evidence were extensive surgery (ie, axillary-lymph-node dissection, greater number of lymph nodes dissected, mastectomy) and being overweight or obese.
INTERPRETATION
Our findings suggest that more than one in five women who survive breast cancer will develop arm lymphoedema. A clear need exists for improved understanding of contributing risk factors, as well as of prevention and management strategies to reduce the individual and public health burden of this disabling and distressing disorder.
FUNDING
The National Breast Cancer Foundation, Australia.
Topics: Breast Neoplasms; Female; Humans; Incidence; Lymph Node Excision; Lymphedema; Mastectomy; Odds Ratio; Overweight; Prevalence; Risk Assessment; Risk Factors; Time Factors; Upper Extremity
PubMed: 23540561
DOI: 10.1016/S1470-2045(13)70076-7 -
Journal of Cancer Survivorship :... Apr 2021Manual lymphatic drainage (MLD) massage is widely accepted as a conservative treatment for lymphedema. This systematic review aims to examine the methodologies used in... (Review)
Review
PURPOSE
Manual lymphatic drainage (MLD) massage is widely accepted as a conservative treatment for lymphedema. This systematic review aims to examine the methodologies used in recent research and evaluate the effectiveness of MLD for those at-risk of or living with lymphedema.
METHODS
The electronic databases Embase, PubMed, CINAHL Complete and Cochrane Central Register of Controlled Trials were searched using relevant terms. Studies comparing MLD with another intervention or control in patients at-risk of or with lymphedema were included. Studies were critically appraised with the PEDro scale.
RESULTS
Seventeen studies with a total of 867 female and two male participants were included. Only studies examining breast cancer-related lymphedema were identified. Some studies reported positive effects of MLD on volume reduction, quality of life and symptom-related outcomes compared with other treatments, while other studies reported no additional benefit of MLD as a component of complex decongestive therapy. In patients at-risk, MLD was reported to reduce incidence of lymphedema in some studies, while others reported no such benefits.
CONCLUSIONS
The reviewed articles reported conflicting findings and were often limited by methodological issues. This review highlights the need for further experimental studies on the effectiveness of MLD in lymphedema.
IMPLICATIONS FOR CANCER SURVIVORS
There is some evidence that MLD in early stages following breast cancer surgery may help prevent progression to clinical lymphedema. MLD may also provide additional benefits in volume reduction for mild lymphedema. However, in moderate to severe lymphedema, MLD may not provide additional benefit when combined with complex decongestive therapy.
Topics: Breast Neoplasms; Female; Humans; Lymphedema; Male; Manual Lymphatic Drainage; Mastectomy; Quality of Life
PubMed: 32803533
DOI: 10.1007/s11764-020-00928-1 -
The Cochrane Database of Systematic... Mar 2018Metastatic breast cancer is not a curable disease, but women with metastatic disease are living longer. Surgery to remove the primary tumour is associated with an... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Metastatic breast cancer is not a curable disease, but women with metastatic disease are living longer. Surgery to remove the primary tumour is associated with an increased survival in other types of metastatic cancer. Breast surgery is not standard treatment for metastatic disease, however several recent retrospective studies have suggested that breast surgery could increase the women's survival. These studies have methodological limitations including selection bias. A systematic review mapping all randomised controlled trials addressing the benefits and potential harms of breast surgery is ideal to answer this question.
OBJECTIVES
To assess the effects of breast surgery in women with metastatic breast cancer.
SEARCH METHODS
We conducted searches using the MeSH terms 'breast neoplasms', 'mastectomy', and 'analysis, survival' in the following databases: the Cochrane Breast Cancer Specialised Register, CENTRAL, MEDLINE (by PubMed) and Embase (by OvidSP) on 22 February 2016. We also searched ClinicalTrials.gov (22 February 2016) and the WHO International Clinical Trials Registry Platform (24 February 2016). We conducted an additional search in the American Society of Clinical Oncology (ASCO) conference proceedings in July 2016 that included reference checking, citation searching, and contacting study authors to identify additional studies.
SELECTION CRITERIA
The inclusion criteria were randomised controlled trials of women with metastatic breast cancer at initial diagnosis comparing breast surgery plus systemic therapy versus systemic therapy alone. The primary outcomes were overall survival and quality of life. Secondary outcomes were progression-free survival (local and distant control), breast cancer-specific survival, and toxicity from local therapy.
DATA COLLECTION AND ANALYSIS
Two review authors independently conducted trial selection, data extraction, and 'Risk of bias' assessment (using Cochrane's 'Risk of bias' tool), which a third review author checked. We used the GRADE tool to assess the quality of the body of evidence. We used the risk ratio (RR) to measure the effect of treatment for dichotomous outcomes and the hazard ratio (HR) for time-to-event outcomes. We calculated 95% confidence intervals (CI) for these measures. We used the random-effects model, as we expected clinical or methodological heterogeneity, or both, among the included studies.
MAIN RESULTS
We included two trials enrolling 624 women in the review. It is uncertain whether breast surgery improves overall survival as the quality of the evidence has been assessed as very low (HR 0.83, 95% CI 0.53 to 1.31; 2 studies; 624 women). The two studies did not report quality of life. Breast surgery may improve local progression-free survival (HR 0.22, 95% CI 0.08 to 0.57; 2 studies; 607 women; low-quality evidence), while it probably worsened distant progression-free survival (HR 1.42, 95% CI 1.08 to 1.86; 1 study; 350 women; moderate-quality evidence). The two included studies did not measure breast cancer-specific survival. Toxicity from local therapy was reported by 30-day mortality and did not appear to differ between the two groups (RR 0.99, 95% CI 0.14 to 6.90; 1 study; 274 women; low-quality evidence).
AUTHORS' CONCLUSIONS
Based on existing evidence from two randomised clinical trials, it is not possible to make definitive conclusions on the benefits and risks of breast surgery associated with systemic treatment for women diagnosed with metastatic breast cancer. Until the ongoing clinical trials are finalised, the decision to perform breast surgery in these women should be individualised and shared between the physician and the patient considering the potential risks, benefits, and costs of each intervention.
Topics: Breast Neoplasms; Combined Modality Therapy; Female; Humans; Mastectomy; Neoplasm Metastasis; Prognosis; Randomized Controlled Trials as Topic
PubMed: 29542106
DOI: 10.1002/14651858.CD011276.pub2 -
The Cochrane Database of Systematic... Jun 2013A variety of estimates of the benefits and harms of mammographic screening for breast cancer have been published and national policies vary. (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
A variety of estimates of the benefits and harms of mammographic screening for breast cancer have been published and national policies vary.
OBJECTIVES
To assess the effect of screening for breast cancer with mammography on mortality and morbidity.
SEARCH METHODS
We searched PubMed (22 November 2012) and the World Health Organization's International Clinical Trials Registry Platform (22 November 2012).
SELECTION CRITERIA
Randomised trials comparing mammographic screening with no mammographic screening.
DATA COLLECTION AND ANALYSIS
Two authors independently extracted data. Study authors were contacted for additional information.
MAIN RESULTS
Eight eligible trials were identified. We excluded a trial because the randomisation had failed to produce comparable groups.The eligible trials included 600,000 women in the analyses in the age range 39 to 74 years. Three trials with adequate randomisation did not show a statistically significant reduction in breast cancer mortality at 13 years (relative risk (RR) 0.90, 95% confidence interval (CI) 0.79 to 1.02); four trials with suboptimal randomisation showed a significant reduction in breast cancer mortality with an RR of 0.75 (95% CI 0.67 to 0.83). The RR for all seven trials combined was 0.81 (95% CI 0.74 to 0.87). We found that breast cancer mortality was an unreliable outcome that was biased in favour of screening, mainly because of differential misclassification of cause of death. The trials with adequate randomisation did not find an effect of screening on total cancer mortality, including breast cancer, after 10 years (RR 1.02, 95% CI 0.95 to 1.10) or on all-cause mortality after 13 years (RR 0.99, 95% CI 0.95 to 1.03).Total numbers of lumpectomies and mastectomies were significantly larger in the screened groups (RR 1.31, 95% CI 1.22 to 1.42), as were number of mastectomies (RR 1.20, 95% CI 1.08 to 1.32). The use of radiotherapy was similarly increased whereas there was no difference in the use of chemotherapy (data available in only two trials).
AUTHORS' CONCLUSIONS
If we assume that screening reduces breast cancer mortality by 15% and that overdiagnosis and overtreatment is at 30%, it means that for every 2000 women invited for screening throughout 10 years, one will avoid dying of breast cancer and 10 healthy women, who would not have been diagnosed if there had not been screening, will be treated unnecessarily. Furthermore, more than 200 women will experience important psychological distress including anxiety and uncertainty for years because of false positive findings. To help ensure that the women are fully informed before they decide whether or not to attend screening, we have written an evidence-based leaflet for lay people that is available in several languages on www.cochrane.dk. Because of substantial advances in treatment and greater breast cancer awareness since the trials were carried out, it is likely that the absolute effect of screening today is smaller than in the trials. Recent observational studies show more overdiagnosis than in the trials and very little or no reduction in the incidence of advanced cancers with screening.
Topics: Adult; Aged; Breast Neoplasms; Cause of Death; Diagnostic Errors; Female; Humans; Mammography; Mass Screening; Mastectomy; Middle Aged; Pamphlets; Patient Education as Topic; Randomized Controlled Trials as Topic
PubMed: 23737396
DOI: 10.1002/14651858.CD001877.pub5