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Journal of Oral Biology and... 2021Previous systematic reviews showed additional benefit of adjuvant bisphosphonates (BP) in the treatment of periodontitis. In contrast, it is unclear the effect of BP in... (Review)
Review
BACKGROUND
Previous systematic reviews showed additional benefit of adjuvant bisphosphonates (BP) in the treatment of periodontitis. In contrast, it is unclear the effect of BP in patients with diabetes and smokers, its pooled effect when administered locally or systemically is also unknown.
OBJECTIVES
This study aimed to systematically review the literature about the use of BP as adjuvant to nonsurgical scaling and root planning (SRP).
METHODOLOGY
This study followed the PRISMA guideline. This study included randomized clinical trials that administered locally or systemically BPs as adjuvant for periodontal treatment. Five databases were used. Meta-analyses were performed, using the pooled mean differences (MD) for clinical attachment level (CAL) and probing pocket depth (PPD). Standard mean difference (SMD) was used for radiographic assessment (RADIO). Subgroup analyses were performed for locally delivered meta-analyses, considering diabetes and smoking exposure.
RESULTS
Thirteen studies were included. It was showed MD of 1.52 mm (95%CI: 0.97-2.07) and 1.44 mm (95%CI: 1.08-1.79) for PPD reduction and CAL gain, respectively, for locally delivered BP. BP was not able to provide significant improvements in smokers (subgroup analysis) when considering CAL (MD: 1.37; 95%CI: -0.17-2.91) and PPD (MD: 1.35; 95%CI: -0.13-2.83). Locally delivered BP also improved significantly the RADIO assessments (SMD: 4.34; 95%CI: 2.94-5.74). MD for systemically administered BP was 0.40 mm (95%CI: 0.21-0.60), 0.51 mm (95%CI: 0.19-0.83) and 1.05 (95%CI: 0.80-1.31) for PPD, CAL and RADIO, respectively.
CONCLUSION
The administration of BP in adjunct to SRP may result in additional clinical effects.
PubMed: 33537188
DOI: 10.1016/j.jobcr.2021.01.008 -
The Cochrane Database of Systematic... Dec 2020Different bone-modifying agents like bisphosphonates and receptor activator of nuclear factor-kappa B ligand (RANKL)-inhibitors are used as supportive treatment in men... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Different bone-modifying agents like bisphosphonates and receptor activator of nuclear factor-kappa B ligand (RANKL)-inhibitors are used as supportive treatment in men with prostate cancer and bone metastases to prevent skeletal-related events (SREs). SREs such as pathologic fractures, spinal cord compression, surgery and radiotherapy to the bone, and hypercalcemia lead to morbidity, a poor performance status, and impaired quality of life. Efficacy and acceptability of the bone-targeted therapy is therefore of high relevance. Until now recommendations in guidelines on which bone-modifying agents should be used are rare and inconsistent.
OBJECTIVES
To assess the effects of bisphosphonates and RANKL-inhibitors as supportive treatment for prostate cancer patients with bone metastases and to generate a clinically meaningful treatment ranking according to their safety and efficacy using network meta-analysis.
SEARCH METHODS
We identified studies by electronically searching the bibliographic databases Cochrane Controlled Register of Trials (CENTRAL), MEDLINE, and Embase until 23 March 2020. We searched the Cochrane Library and various trial registries and screened abstracts of conference proceedings and reference lists of identified trials.
SELECTION CRITERIA
We included randomized controlled trials comparing different bisphosphonates and RANKL-inihibitors with each other or against no further treatment or placebo for men with prostate cancer and bone metastases. We included men with castration-restrictive and castration-sensitive prostate cancer and conducted subgroup analyses according to this criteria.
DATA COLLECTION AND ANALYSIS
Two review authors independently extracted data and assessed the quality of trials. We defined proportion of participants with pain response and the adverse events renal impairment and osteonecrosis of the jaw (ONJ) as the primary outcomes. Secondary outcomes were SREs in total and each separately (see above), mortality, quality of life, and further adverse events such as grade 3 to 4 adverse events, hypocalcemia, fatigue, diarrhea, and nausea. We conducted network meta-analysis and generated treatment rankings for all outcomes, except quality of life due to insufficient reporting on this outcome. We compiled ranking plots to compare single outcomes of efficacy against outcomes of acceptability of the bone-modifying agents. We assessed the certainty of the evidence for the main outcomes using the GRADE approach.
MAIN RESULTS
Twenty-five trials fulfilled our inclusion criteria. Twenty-one trials could be considered in the quantitative analysis, of which six bisphosphonates (zoledronic acid, risedronate, pamidronate, alendronate, etidronate, or clodronate) were compared with each other, the RANKL-inhibitor denosumab, or no treatment/placebo. By conducting network meta-analysis we were able to compare all of these reported agents directly and/or indirectly within the network for each outcome. In the abstract only the comparisons of zoledronic acid and denosumab against the main comparator (no treatment/placebo) are described for outcomes that were predefined as most relevant and that also appear in the 'Summary of findings' table. Other results, as well as results of subgroup analyses regarding castration status of participants, are displayed in the Results section of the full text. Treatment with zoledronic acid probably neither reduces nor increases the proportion of participants with pain response when compared to no treatment/placebo (risk ratio (RR) 1.46, 95% confidence interval (CI) 0.93 to 2.32; per 1000 participants 121 more (19 less to 349 more); moderate-certainty evidence; network based on 4 trials including 1013 participants). For this outcome none of the trials reported results for the comparison with denosumab. The adverse event renal impairment probably occurs more often when treated with zoledronic acid compared to treatment/placebo (RR 1.63, 95% CI 1.08 to 2.45; per 1000 participants 78 more (10 more to 180 more); moderate-certainty evidence; network based on 6 trials including 1769 participants). Results for denosumab could not be included for this outcome, since zero events cannot be considered in the network meta-analysis, therefore it does not appear in the ranking. Treatment with denosumab results in increased occurrence of the adverse event ONJ (RR 3.45, 95% CI 1.06 to 11.24; per 1000 participants 30 more (1 more to 125 more); high-certainty evidence; 4 trials, 3006 participants) compared to no treatment/placebo. When comparing zoledronic acid to no treatment/placebo, the confidence intervals include the possibility of benefit or harm, therefore treatment with zoledronic acid probably neither reduces nor increases ONJ (RR 1.88, 95% CI 0.73 to 4.87; per 1000 participants 11 more (3 less to 47 more); moderate-certainty evidence; network based on 4 trials including 3006 participants). Compared to no treatment/placebo, treatment with zoledronic acid (RR 0.84, 95% CI 0.72 to 0.97) and denosumab (RR 0.72, 95% CI 0.54 to 0.96) may result in a reduction of the total number of SREs (per 1000 participants 75 fewer (131 fewer to 14 fewer) and 131 fewer (215 fewer to 19 fewer); both low-certainty evidence; 12 trials, 5240 participants). Treatment with zoledronic acid and denosumab likely neither reduces nor increases mortality when compared to no treatment/placebo (zoledronic acid RR 0.90, 95% CI 0.80 to 1.01; per 1000 participants 48 fewer (97 fewer to 5 more); denosumab RR 0.93, 95% CI 0.77 to 1.11; per 1000 participants 34 fewer (111 fewer to 54 more); both moderate-certainty evidence; 13 trials, 5494 participants). Due to insufficient reporting, no network meta-analysis was possible for the outcome quality of life. One study with 1904 participants comparing zoledronic acid and denosumab showed that more zoledronic acid-treated participants than denosumab-treated participants experienced a greater than or equal to five-point decrease in Functional Assessment of Cancer Therapy-General total scores over a range of 18 months (average relative difference = 6.8%, range -9.4% to 14.6%) or worsening of cancer-related quality of life.
AUTHORS' CONCLUSIONS
When considering bone-modifying agents as supportive treatment, one has to balance between efficacy and acceptability. Results suggest that Zoledronic acid likely increases both the proportion of participants with pain response, and the proportion of participants experiencing adverse events However, more trials with head-to-head comparisons including all potential agents are needed to draw the whole picture and proof the results of this analysis.
Topics: Adult; Alendronate; Antineoplastic Agents, Hormonal; Bisphosphonate-Associated Osteonecrosis of the Jaw; Bone Density Conservation Agents; Bone Neoplasms; Clodronic Acid; Denosumab; Diphosphonates; Etidronic Acid; Humans; Male; Network Meta-Analysis; Pamidronate; Prostatic Neoplasms; Prostatic Neoplasms, Castration-Resistant; Quality of Life; RANK Ligand; Randomized Controlled Trials as Topic; Risedronic Acid; Zoledronic Acid
PubMed: 33270906
DOI: 10.1002/14651858.CD013020.pub2 -
Frontiers in Endocrinology 2020Bisphosphonates (BPs) are first-line therapy for osteoporosis. Adherence is usually low in chronic, asymptomatic diseases, but gastrointestinal (GI) side-effects can... (Meta-Analysis)
Meta-Analysis
INTRODUCTION
Bisphosphonates (BPs) are first-line therapy for osteoporosis. Adherence is usually low in chronic, asymptomatic diseases, but gastrointestinal (GI) side-effects can also contribute to low adherence in BP therapy and may necessitate a review by a gastroenterologist with or without gastroscopy.
AIMS
Our meta-analysis aims to determine the risk of severe GI adverse events due to oral BP therapy in osteoporotic patients.
METHODS
A systematic search was conducted in three databases up to September 2020 for randomized controlled trials (RCTs) detailing GI adverse events in adults with osteoporosis on BP compared to placebo. Risk ratios (RRs) with 95% confidence intervals (CI) were calculated for non-severe and severe adverse events indicating endoscopic procedure with the random-effects model. Statistical heterogeneity was assessed using chi and I statistics.
RESULTS
Forty-two RCTs with 39,047 patients with 9,999 non-severe and 1,503 severe GI adverse events were included. The incidence of non-severe and severe adverse events ranged between 0.3-54.9 and 0-10.3%, respectively. There was no difference between BP and control groups in terms of the risk of non-severe or severe side effects: RR=1.05 (CI: 0.98-1.12), I = 48.1%, and RR=1.01 (CI: 0.92-1.12), I = 0.0%, respectively. Subgroup analysis of the most commonly used BP, once-weekly alendronate 70 mg, revealed an association between bisphosphonates and the risk of non-severe GI adverse events, RR=1.16 (CI: 1.00-1.36), I = 40.7%, while the risk of severe GI side effects was not increased in this subgroup, RR=1.20 (CI: 0.83-1.74), I = 0.0%.
CONCLUSION
Our results show that bisphosphonates do not increase the risk of severe GI adverse events. However, the marked variability of the screening for side effects in the included studies, and the fact that in most of the studies GI diseases were exclusion criteria limits the strenght of evidence of our results. The conclusions drawn from the meta-analysis are therefore restricted to selected populations, and the results must be interpreted with caution.
Topics: Administration, Oral; Bone Density Conservation Agents; Diphosphonates; Gastrointestinal Diseases; Humans; Osteoporosis; Publication Bias
PubMed: 33240217
DOI: 10.3389/fendo.2020.573976 -
Journal of Dental Research Apr 2021The objective of this study was to assess clinical measurements related to the effectiveness of bisphosphonate (BP) administration as a supplement to conventional dental... (Meta-Analysis)
Meta-Analysis
The objective of this study was to assess clinical measurements related to the effectiveness of bisphosphonate (BP) administration as a supplement to conventional dental treatment in patients free of bone-related diseases using a network meta-analysis. Only randomized controlled trials (RCTs) were included that provided dental clinical measurements on human patients treated with BPs with or without similar untreated controls or treated with placebo. Information sources included a systematic search of 17 electronic databases up to August 2020, complemented by manual searches. Risk of bias assessment was performed with the revised Cochrane risk of bias tool for randomized trials (RoB 2.0). Extracted measurements were pooled according to time of evaluation. The random-effects model by DerSimonian and Laird was used to calculate mean differences (MDs) and the respective 95% confidence intervals (CIs). Seven RCTs were included in the network meta-analysis, assessing 391 subjects reporting on periodontal treatment effects after 2 to 12 mo of BP administration. BP treatment was associated with significant improvement of most clinical measurements, compared with BP-naive controls. According to the network ranking, alendronate was more efficient in improvement of probing depth and clinical attachment gain when compared to zoledronate or alendronate/risedronate. Similarly, the local application of alendronate as a gel was more effective than the oral administration. A long-term analysis of the pharmaceutical effects was not possible due to insufficient data. The current review, performed according to existing guidelines, included only RCTs and, through appropriate statistical analyses, provided precise estimates for most assessed outcomes. However, no adverse effects or long-term treatment results were analyzed due to inadequate pertinent data. BP administration seems to be beneficial in the short term for the treatment of periodontal diseases, mainly through controlling periodontal inflammation.
Topics: Bone Diseases; Diphosphonates; Humans; Network Meta-Analysis; Periodontal Diseases; Zoledronic Acid
PubMed: 33208008
DOI: 10.1177/0022034520972945 -
Expert Review of Clinical Pharmacology Jan 2021: Postmenopausal osteoporosis carries a high risk of fractures, which decrease quality of life and are associated with high morbidity, mortality, and economic burden.... (Comparative Study)
Comparative Study Meta-Analysis
: Postmenopausal osteoporosis carries a high risk of fractures, which decrease quality of life and are associated with high morbidity, mortality, and economic burden. The best pharmacological treatment options to manage and prevent osteoporotic fractures remain still unclear. The present study investigated the efficacy and safety of the most commonly employed drugs in the management of postmenopausal osteoporosis. : Only RCTs comparing different drugs for the management of postmenopausal osteoporosis were included. Data from 76 RCTs (205,011 patients) were collected. The mean follow-up was 27.6 ± 14.9 months. : Denosumab reported the lowest rate of non-vertebral fractures (LOR -1.57), Romosozumab the lowest rate of vertebral fractures (LOR 1.99), and Ibandronate the lowest rate of hip fractures (LOR0.18). Serious adverse events resulted in the lowest in the Raloxifene group (LOR 3.11), while those leading to study discontinuation were lowest in the Romosozumab cohort (LOR 2.65). : Denosumab resulted in most effective, particularly in reducing the occurrence of non-vertebral fractures. Romosozumab and Ibandronate resulted best to prevent, respectively, vertebral fractures and hip fractures. Adverse events leading to study discontinuation were less frequent in the Romosozumab and Denosumab groups, while Raloxifene and Alendronate showed a lower incidence of serious adverse events overall. : I, Bayesian network meta-analysis of RCTs.
Topics: Bone Density Conservation Agents; Female; Humans; Osteoporosis, Postmenopausal; Osteoporotic Fractures; Quality of Life; Randomized Controlled Trials as Topic
PubMed: 33183112
DOI: 10.1080/17512433.2021.1851192 -
Clinical Oral Investigations Dec 2020The aim of this article was to perform a systematic review on the effectiveness of local adjuvant therapies in the treatment of aggressive periodontitis (AgP), now...
OBJECTIVES
The aim of this article was to perform a systematic review on the effectiveness of local adjuvant therapies in the treatment of aggressive periodontitis (AgP), now reported as periodontitis grade C.
MATERIALS AND METHODS
The authors selected randomized clinical trials of AgP patients who received local therapy as adjuvants to non-surgical periodontal with a duration of at least 90 days. Seven databases were searched up to January 2020. The gain in clinical attachment level (CAL) and reduction of probing depth (PD) were the outcomes of interest.
RESULTS
Of the 3583 studies found, only five articles were included in the qualitative analysis. Among the substances analyzed, only 1.2 mg of simvastatin gel (SMV) (1.2 mg/0.1 ml), 1% of alendronate gel (ALN) (10 mg/ml), and 25% metronidazole gel (MTZ) (Elyzol) showed a significant decrease in the probing depth when compared with their respective control groups. The gain CAL was shown using 1.2 mg SMV gel (1.2 mg/0.1 ml) and 1% ALN gel (10 mg/ml).
CONCLUSION
Although 1.2 mg SMV gel (1.2 mg/0.1 ml), 1% ALN gel (10 mg/ml), and 25% MTZ gel (Elyzol) have shown better results, local therapies adjuvant to SRP the data found were limited. Future clinical studies with appreciable methodological quality should be conducted.
CLINICAL RELEVANCE
Despite some benefits of local delivery therapy, up to now, it has not been possible to prove the efficacy of local therapy as an adjunct to standard treatment of AgP (periodontitis grade C).
Topics: Aggressive Periodontitis; Alendronate; Chronic Periodontitis; Dental Scaling; Humans; Periodontal Index; Root Planing
PubMed: 33070281
DOI: 10.1007/s00784-020-03631-8 -
Archives of Osteoporosis Oct 2020A local management algorithm and practice recommendations for the management of osteoporosis in Egyptian males were developed after assessing the applicability of...
UNLABELLED
A local management algorithm and practice recommendations for the management of osteoporosis in Egyptian males were developed after assessing the applicability of current international recommendations and the cost effectiveness of local drugs. A systematic review and sensitivity analyses augmented the quality of the research efforts.
PURPOSE
Osteoporosis affects both men and women; however, no local recommendations for the condition are available for the male population. Therefore, this study was undertaken to produce recommendations for men based on the applicability of current international recommendations and the cost effectiveness of local drugs.
METHODS
The International Osteoporosis Foundation website, EMBASE, and SUMSEARCH-2 databases were searched to identify all guidelines that included recommendations for males. Regional and international guidelines were then appraised using the Advancing Guideline Development, Reporting, and Evaluation in Healthcare-II tool. A cost-effectiveness analysis was conducted using the perspective of an uninsured patient, international outcomes, and local costs. Recommendations were then formulated using the Grading of Recommendations Assessment, Development and Evaluation guidelines, and symbolic representations.
RESULTS
Twenty-six guidelines were found. Only one of the guidelines focused entirely on males, with the remainder making inferences based on recommendations for females. Six regional guidelines were mainly of low quality. Alendronate was considered to be the most cost-effective drug, while teriparatide was found to be unaffordable.
CONCLUSION
Recommendations for men with osteoporosis are based on that of women, and the topic lacks exploration in the Middle East. International recommendations and other guidelines were evaluated and adopted to create guidance for the management of osteoporosis in men for application in Egypt.
Topics: Algorithms; Cost-Benefit Analysis; Databases, Factual; Egypt; Female; Humans; Male; Osteoporosis
PubMed: 33037516
DOI: 10.1007/s11657-020-00830-4 -
Medicine Oct 2020The goal of this study was to review relevant randomized controlled trials or case-control studies to determine the clinical efficacy of minodronate in the treatment of... (Meta-Analysis)
Meta-Analysis
BACKGROUND
The goal of this study was to review relevant randomized controlled trials or case-control studies to determine the clinical efficacy of minodronate in the treatment of osteoporosis.
METHOD
The relevant studies were identified on PubMed, Cochrane, and Embase databases using appropriate keywords. Pertinent sources in the literature were also reviewed, and all articles published through October 2019 were considered for inclusion. For each study, we assessed odds ratios, mean difference, and 95% confidence interval (95% CI) to evaluate and synthesize outcomes.
RESULT
Thirteen studies comprising 3740 patients were included in this study. Compared with other drugs, minodronate significantly decreased N-telopeptide of type I collagen/creatinine (weighted mean difference [WMD]: -13.669, 95% confidence interval [CI]: -23.108 to -4.229), bone alkaline phosphatase (BAP) (WMD: -1.26, 95% CI: -2.04 to -0.47) and tartrate-resistant acid phosphatase 5b (WMD: -154.11, 95% CI: -277.85 to -30.37). Minodronate combined with other drugs would significantly decrease BAP (WMD: -3.10, 95% CI: -5.20 to -1.00) than minodronate. Minodronate-naïve would significantly decrease BAP (WMD: -3.00, 95% CI: -5.47 to 0.53) and tartrate-resistant acid phosphatase 5b (WMD: -128.20, 95% CI: -198.11 to -58.29) than minodronate-switch. The incidence of vertebral fracture was significantly decreased in the minodronate group than the other drugs (relative risk: 0.520, 95% CI: 0.363-0.744).
CONCLUSION
Minodronate has better clinical efficacy in the treatment of osteoporosis than other drugs (alendronate, risedronate, raloxifene, or eldecalcitol).
Topics: Aged; Aged, 80 and over; Alendronate; Alkaline Phosphatase; Bone Density Conservation Agents; Case-Control Studies; Collagen Type I; Creatinine; Diphosphonates; Drug Therapy, Combination; Female; Humans; Imidazoles; Male; Middle Aged; Osteoporosis; Raloxifene Hydrochloride; Randomized Controlled Trials as Topic; Risedronic Acid; Spinal Fractures; Tartrate-Resistant Acid Phosphatase; Treatment Outcome; Vitamin D
PubMed: 33019463
DOI: 10.1097/MD.0000000000022542 -
Journal of Bone Metabolism Aug 2020The present study performed a systematic review and meta-analysis of clinical trials using bisphosphonates for bone demineralization in human immunodeficiency virus...
Use of Bisphosphonates, Calcium and Vitamin D for Bone Demineralization in Patients with Human Immunodeficiency Virus/Acquired Immune Deficiency Syndrome: A Systematic Review and Meta-Analysis of Clinical Trials.
BACKGROUND
The present study performed a systematic review and meta-analysis of clinical trials using bisphosphonates for bone demineralization in human immunodeficiency virus (HIV) patients.
METHODS
A comprehensive literature search was performed from January 2004 to January 2020 considering the bone mineral density (BMD) of the lumbar spine (LS) as the main outcome. Out of 214 titles that met criteria, 9 studies fulfilled the selection criteria.
RESULTS
A total of 394 patients were identified, and they were allocated into 2 groups: the intervention group (200 patients), to whom a combination of alendronate or zoledronate with calcium and vitamin D was administered; and control group (194 patients), to whom only calcium and vitamin D was administered. Clinical profile and indicators of bone metabolism of the participants were evaluated regarding effect size, homogeneity, and consistency. No substantial heterogeneity between the groups was found for the baseline variables, and there was high consistency to the main outcome. The meta-analysis shows a significant difference in post-treatment BMD, favoring the intervention over the control treatment. The intervention improved LS density up to 0.227 g/cm², raising the average to the levels of general population. Adverse effects related to intervention were fever immediately after zoledronate administration and gastrointestinal complaints during alendronate usage. Other adverse effects were barely reported and poorly connected to intervention by studies' authors, despite all of them have been successfully resolved.
CONCLUSIONS
This study provides evidence that BMD post-treatment is better in HIV patients who used bisphosphonates combined with calcium and vitamin D.
PubMed: 32911582
DOI: 10.11005/jbm.2020.27.3.175 -
Orthopaedic Surgery Aug 2020To assess the effectiveness and safety of oral bisphosphonates in increasing bone mineral density (BMD), reducing fractures, and improving clinical function in patients... (Meta-Analysis)
Meta-Analysis
OBJECTIVE
To assess the effectiveness and safety of oral bisphosphonates in increasing bone mineral density (BMD), reducing fractures, and improving clinical function in patients with osteogenesis imperfecta (OI).
METHODS
Studies were eligible for inclusion if they were randomized controlled trials of directly comparing oral bisphosphonate therapy with placebo-group in OI patients. Data synthesis regarding to bone mineral density as measured by dual-energy X-ray absorptiometry (DEXA), decreased fracture incidence, change in biochemical markers of bone and mineral metabolism, bone histology, growth, bone pain, quality of life, and others were assessed, and meta-analysis done when possible.
RESULTS
From 98 potential references and six randomized controlled studies a total of 263 participants receiving oral bisphosphonates and 143 placebo treatments contributed data to meta-analysis. Pooled meta-analysis of three studies suggested that there was significant difference between bisphosphonate treated group and placebo in number of patients with at least one fracture (mean difference 0.53, 95% confidence interval 0.32-0.89, P = 0.02). Pooled meta-analysis of two studies suggested that significant difference was noted between bisphosphonate treated group and placebo in mean percentage change in spine BMD (T-score) (mean difference 28.43, 95% confidence interval 7.09-49.77, P = 0.009). The similar effect was shown in the term of mean change (Z-score) in spine BMD.
CONCLUSIONS
Significant improvement in lumbar areal BMD in patients affected with OI has been shown when treated with oral bisphosphonates, even though only a small population was enrolled. We cannot draw a definite conclusion that the increase in BMD can be translated into fracture reduction and clinical functional improvement. The optimal method, dose, type, initiation, and duration of oral bisphosphonates therapy still remains unclear. Well-designed, adequately-powered, placebo-controlled RCTs investigating the effects of oral bisphosphonates on fractures reduction and improvement in quality of life in both children and adults are studied here.
Topics: Bone Density; Bone Density Conservation Agents; Diphosphonates; Fractures, Bone; Humans; Osteogenesis Imperfecta; Randomized Controlled Trials as Topic
PubMed: 32589343
DOI: 10.1111/os.12611