scholarly journals The adverse effects of bisphosphonates in breast cancer: A systematic review and network meta-analysis

PLoS ONE ◽  
2021 ◽  
Vol 16 (2) ◽  
pp. e0246441
Author(s):  
Christopher Jackson ◽  
Alexandra L. J. Freeman ◽  
Zśofia Szlamka ◽  
David J. Spiegelhalter

Background Bisphosphonate drugs can be used to improve the outcomes of women with breast cancer. Whilst many meta-analyses have quantified their potential benefits for patients, attempts at comprehensive quantification of potential adverse effects have been limited. We undertook a meta-analysis with novel methodology to identify and quantify these adverse effects. Methods We systematically reviewed randomised controlled trials in breast cancer where at least one of the treatments was a bisphosphonate (zoledronic acid, ibandronate, pamidronate, alendronate or clodronate). Neoadjuvant, adjuvant and metastatic settings were examined. Primary outcomes were adverse events of any type or severity (excluding death). We carried out pairwise and network meta-analyses to estimate the size of any adverse effects potentially related to bisphosphonates. In order to ascertain whether adverse effects differed by individual factors such as age, or interacted with other common adjuvant breast cancer treatments, we examined individual-level patient data for one large trial, AZURE. Findings We identified 56 trials that reported adverse data, which included a total of 29,248 patients (18,301 receiving bisphosphonate drugs versus 10,947 not). 24 out of the 103 different adverse outcomes analysed showed a statistically and practically significant increase in patients receiving a bisphosphonate drug compared with those not (2 additional outcomes that appeared statistically significant came only from small studies with low event counts and no clinical suspicion so are likely artifacts). Most of these 24 are already clinically recognised: ‘flu-like symptoms, fever, headache and chills; increased bone pain, arthralgia, myalgia, back pain; cardiac events, thromboembolic events; hypocalcaemia and osteonecrosis of the jaw; as well as possibly stiffness and nausea. Oral clodronate appeared to increase the risk of vomiting and diarrhoea (which may also be increased by other bisphosphonates), and there may be some hepatotoxicity. Four additional potential adverse effects emerged for bisphosphonate drugs in this analysis which have not classically be recognised: fatigue, neurosensory problems, hypertonia/muscle spasms and possibly dysgeusia. Several symptoms previously reported as potential side effects in the literature were not significantly increased in this analysis: constipation, insomnia, respiratory problems, oedema or thirst/dry mouth. Individual patient-level data and subgroup analysis revealed little variation in side effects between women of different ages or menopausal status, those with metastatic versus non-metastatic cancer, or between women receiving different concurrent breast cancer therapies. Conclusions This meta-analysis has produced estimates for the absolute frequencies of a range of side effects significantly associated with bisphosphonate drugs when used by breast cancer patients. These results show good agreement with previous literature on the subject but are the first systematic quantification of side effects and their severities. However, the analysis is limited by the availability and quality of data on adverse events, and the potential for bias introduced by a lack of standards for reporting of such events. We therefore present a table of adverse effects for bisphosphonates, identified and quantified to the best of our ability from a large number of trials, which we hope can be used to improve the communication of the potential harms of these drugs to patients and their healthcare providers.

Nutrients ◽  
2018 ◽  
Vol 10 (12) ◽  
pp. 1886 ◽  
Author(s):  
Vincenza Gianfredi ◽  
Daniele Nucci ◽  
Angela Abalsamo ◽  
Mattia Acito ◽  
Milena Villarini ◽  
...  

Breast cancer (BC) is the most common cancer in women and several factors are involved in its onset. Green tea (GT) has been shown to have potential beneficial effects on different types of cancer. The aim of this review was to evaluate the association between GT regular consumption and risk of BC in women. The risk of BC recurrence and risk of BC in relation to menopausal status were also evaluated. A literature search of PubMed, Scopus, and Web of Science was conducted. Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines were followed to perform the systematic review and meta-analysis. Full texts were downloaded for 40 studies; however, only 13 records were included in the meta-analysis. Eight were cohort studies and five were case-control studies. The pooled sample consisted of 163,810 people. An inverse statistically significant relationship between GT and BC risk, with an Odds Ratio (OR) = 0.85 ((95% CI = 0.80–0.92), p = 0.000)), was found. Egger’s linear regression test did not show a potential publication bias (intercept 0.33, t = 0.40, p = 0.695), which was also confirmed by the symmetry of the funnel plot. Moreover, no high statistical heterogeneity (Chi2 = 31.55, df = 13, I2 = 58.79%, p = 0.003) was found. The results of this meta-analysis showed a potential protective effect of GT consumption on BC, especially for BC recurrence.


2020 ◽  
Vol 41 (Supplement_2) ◽  
Author(s):  
B Hirsh-Raccah ◽  
A Yanovsky ◽  
V Rotshild ◽  
H Danenberg ◽  
R Eliaz ◽  
...  

Abstract Background Lipid lowering therapy may be associated with impaired cognitive function. The association between the use of Proprotein Convertase Subtilisin/Kexin Type 9 (PCSK9) inhibitors and the risk of neurocognitive adverse effects remains unclear. Purpose To assess the neurocognitive safety of PCSK9 inhibitors using meta-analysis and meta-regression of randomized controlled trials (RCTs). Methods PubMed (MEDLINE), Embase and Cochrane library were searched. RCTs that reported assessments of neurocognitive outcomes of participants using PCSK9 inhibitors, with a duration of follow up of at least six months were included. The results of the search were screened by two independent reviewers. Any disagreements were resolved by consensus. The research was conducted and reported in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) extension statement for meta-analyses. Results were pooled using random-effects models. The primary safety outcome of this analysis was defined as the reported incidence of neurocognitive adverse effects. Results Results of 21 trials were included in the analysis. Among 59,733 patients, 31,611 were treated with PCSK9 inhibitors. No significant difference in the incidence of neurocognitive side effects between the treatment and control groups was identified (RR=1.01, 95% CI: 0.86–1.19, I2=3%). Same results were seen in separate analysis for each of the medicines (Alirocumab- RR=0.88, 95% CI: 0.72–1.08, I2=0%, Evolocumab- RR=1.42, 95% CI: 0.74–2.73, I2=55%). In a meta-regression analysis there was no statistically significant association between the assessed and the risk for neurocognitive side effects. Conclusions Pooled results of our meta-analysis and meta-regression clearly show that the exposure to PCSK9 inhibitors is not associated with an increased risk of neurocognitive adverse events. Due to the increasing proportion of patients using lipid-lowering therapy these results are positively reassuring. However, more data from long-term outcomes studies is needed to further evaluate the effect of longer exposure to PCSK9 inhibitors Funding Acknowledgement Type of funding source: None


2018 ◽  
pp. 64-69
Author(s):  
E. I. Kovalenko ◽  
I. B. Kononenko ◽  
A. V. Snegovoi ◽  
O. P. Grebennikova ◽  
L. V. Manzyuk

Hormonal therapy is a highly effective and well tolerable treatment of hormone-responsive breast cancer. However, it has some side effects that can affect quality of life and lead to treatment discontinuation. Common side effects of tamoxifen and aromatase inhibitors are discussed in this article: menopausal, gynecological symptoms, cardiovascular and musculoskeletal adverse events. Some of them are preventable and manageable. In order to maintain good quality of life during treatment the oncologists should pay more attention to the side effects that lead to it’s deterioration and not be too anxious about insignificant ones.


2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Ran Liu ◽  
Kun Zhang ◽  
Qiu-yu Tong ◽  
Guang-wei Cui ◽  
Wen Ma ◽  
...  

Abstract Background Acupuncture for post-stroke depression (PSD) has been evolving, but uncertainty remains. To assess the existing evidence from randomized clinical trials (RCTs) of acupuncture for PSD, we sought to draw conclusions by synthesizing RCTs. Methods An exhaustive literature search was conducted in seven electronic databases from their inception dates to April 19, 2020, to identify systematic reviews (SRs) and meta-analyses (MAs) on this topic. The primary RCTs included in the SRs/MAs were identified. We also conducted a supplementary search for RCTs published from January 1, 2015, to May 12, 2020. Two reviewers extracted data separately and pooled data using RevMan 5.3 software. The quality of evidence was critically appraised with the Grades of Recommendation, Assessment, Development and Evaluation (GRADE) system. Results A total of 17 RCTs involving 1402 patients were included. Meta-analysis showed that participants who received a combination of acupuncture and conventional treatments exhibited significantly lower scores on the HAM-D17, HAM-D24 and HAM-D (MD, − 5.08 [95% CI, − 6.48 to − 3.67], I2 = 0%), (MD, − 9.72 [95% CI, − 14.54 to − 4.91], I2 = 65%) and (MD, − 2.72 [95% CI, − 3.61 to − 1.82], respectively) than those who received conventional treatment. However, there was no significant difference in acupuncture versus antidepressants in terms of the 17-item, 24-item and HAM-D scales (MD, − 0.43 [95% CI, − 1.61 to 0.75], I2 = 51%), (MD, − 3.09 [95% CI, − 10.81 to 4.63], I2 = 90%) and (MD, − 1.55 [95% CI, − 4.36 to 1.26], I2 = 95%, respectively). For adverse events, acupuncture was associated with fewer adverse events than antidepressants (RR, 0.16 [95% CI, 0.07 to 0.39], I2 = 35%), but there was no significant difference in the occurrence of adverse events between the combination of acupuncture and conventional treatments versus conventional treatments (RR, 0.63 [95% CI, 0.21 to 1.83], I2 = 38%). The quality of evidence was low to very low due to the substantial heterogeneity among the included studies. Conclusions The current review indicates that acupuncture has greater effect on PSD and better safety profile than antidepressants, but high-quality evidence evaluating acupuncture for PSD is still needed.


BMJ Open ◽  
2017 ◽  
Vol 7 (9) ◽  
pp. e017868
Author(s):  
Joey S.W. Kwong ◽  
Sheyu Li ◽  
Wan-Jie Gu ◽  
Hao Chen ◽  
Chao Zhang ◽  
...  

IntroductionEffective selection of coronary lesions for revascularisation is pivotal in the management of symptoms and adverse outcomes in patients with coronary artery disease. Recently, instantaneous ‘wave-free’ ratio (iFR) has been proposed as a new diagnostic index for assessing the severity of coronary stenoses without the need of pharmacological vasodilation. Evidence of the effectiveness of iFR-guided revascularisation is emerging and a systematic review is warranted.Methods and analysisThis is a protocol for a systematic review of randomised controlled trials and controlled observational studies. Electronic sources including MEDLINE via Ovid, Embase, Cochrane databases and ClinicalTrials.gov will be searched for potentially eligible studies investigating the effects of iFR-guided strategy in patients undergoing coronary revascularisation. Studies will be selected against transparent eligibility criteria and data will be extracted using a prestandardised data collection form by two independent authors. Risk of bias in included studies and overall quality of evidence will be assessed using validated methodological tools. Meta-analysis will be performed using the Review Manager software. Our systematic review will be performed according to the guidance from the Cochrane Handbook for Systematic Reviews of Interventions and the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) statement.Ethics and disseminationEthics approval is not required. Results of the systematic review will be disseminated as conference proceedings and peer-reviewed journal publication.Trial registration numberThis protocol is registered in the International Prospective Register of Systematic Reviews (PROSPERO), registration number CRD42017065460.


2018 ◽  
Vol 10 (4) ◽  
pp. 387-405 ◽  
Author(s):  
C. J. Bennett ◽  
R. E. Walker ◽  
M. L. Blumfield ◽  
J. Ma ◽  
F. Wang ◽  
...  

AbstractDespite many interventions aiming to reduce excessive gestational weight gain (GWG), it is currently unclear the impact on infant anthropometric outcomes. The aim of this review was to evaluate offspring anthropometric outcomes in studies designed to reduce GWG. A systematic search of seven international databases, one clinical trial registry and three Chinese databases was conducted without date limits. Studies were categorised by intervention type: diet, physical activity (PA), lifestyle (diet + PA), other, gestational diabetes mellitus (GDM) (diet, PA, lifestyle, metformin and other). Meta-analyses were reported as weighted mean difference (WMD) for birthweight and birth length, and risk ratio (RR) for small for gestational age (SGA), large for gestational age (LGA), macrosomia and low birth weight (LBW). Collectively, interventions reduced birthweight, risk of macrosomia and LGA by 71 g (WMD: −70.67, 95% CI −101.90 to −39.43,P<0.001), 16% (RR: 0.84, 95% CI 0.73–0.98,P=0.026) and 19% (RR: 0.81, 95% CI 0.69–0.96,P=0.015), respectively. Diet interventions decreased birthweight and LGA by 99 g (WMD −98.80, 95% CI −178.85 to −18.76,P=0.016) and 65% (RR: 0.35, 95% CI 0.17–0.72,P=0.004). PA interventions reduced the risk of macrosomia by 51% (RR: 0.49, 95% CI 0.26–0.92,P=0.036). In women with GDM, diet and lifestyle interventions reduced birthweight by 211 and 296 g, respectively (WMD: −210.93, 95% CI −374.77 to −46.71,P=0.012 and WMD:−295.93, 95% CI −501.76 to −90.10,P=0.005, respectively). Interventions designed to reduce excessive GWG lead to a small reduction in infant birthweight and risk of macrosomia and LGA, without influencing the risk of adverse outcomes including LBW and SGA.


2012 ◽  
Vol 23 (5) ◽  
pp. 1130-1137 ◽  
Author(s):  
J. Cortes ◽  
V. Calvo ◽  
N. Ramírez-Merino ◽  
J. O'Shaughnessy ◽  
A. Brufsky ◽  
...  

2000 ◽  
Vol 18 (6) ◽  
pp. 1220-1229 ◽  
Author(s):  
Timothy J. Whelan ◽  
Jim Julian ◽  
Jim Wright ◽  
Alejandro R. Jadad ◽  
Mark L. Levine

PURPOSE: Recent randomized trials in women with node-positive breast cancer who received systemic treatment report that locoregional radiation therapy improves survival. Previous trials failed to detect a difference in survival that results from its use. A systematic review of randomized trials that examine the effectiveness of locoregional radiation therapy in patients treated by definitive surgery and adjuvant systemic therapy was conducted. METHODS: Randomized trials published between 1967 and 1999 were identified through MEDLINE database, CancerLit database, and reference lists of relevant articles. Relevant data was abstracted. The results of randomized trials were pooled using meta-analyses to estimate the effect of treatment on any recurrence, locoregional recurrence, and mortality. RESULTS: Eighteen trials that involved a total of 6,367 patients were identified. Most trials included both pre- and postmenopausal women with node-positive breast cancer treated with modified radical mastectomy. The type of systemic therapy received, sites irradiated, techniques used, and doses of radiation delivered varied between trials. Data on toxicity were infrequently reported. Radiation was shown to reduce the risk of any recurrence (odds ratio, 0.69; 95% confidence interval [CI], 0.58 to 0.83), local recurrence (odds ratio, 0.25; 95% CI, 0.19 to 0.34), and mortality (odds ratio, 0.83; 95% CI, 0.74 to 0.94). CONCLUSION: Locoregional radiation after surgery in patients treated with systemic therapy reduced mortality. Several questions remain on how these results should be translated into current-day clinical practice.


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