-
ClinicoEconomics and Outcomes Research... 2023Currently approved biologic therapies for moderate-to-severe ulcerative colitis have well-established efficacy. However, many patients fail to respond or lose response,... (Review)
Review
BACKGROUND
Currently approved biologic therapies for moderate-to-severe ulcerative colitis have well-established efficacy. However, many patients fail to respond or lose response, leading to dose escalation or treatment switching.
OBJECTIVE
We sought to identify real-world evidence on dose escalation and treatment switching and associated clinical and economic outcomes among adults with ulcerative colitis treated with infliximab, adalimumab, golimumab, vedolizumab, ustekinumab, or tofacitinib.
METHODS
We conducted a systematic search of Embase, MEDLINE (up to 26 August 2020), and conference proceedings (2017-2020) for studies in adults with ulcerative colitis to assess clinical response and remission, colectomy, adverse events, and economic outcomes related to dose escalation and treatment switching.
RESULTS
In 56 studies, dose escalation and treatment switching involving infliximab and/or adalimumab were most frequently investigated. Rates of clinical response after dose escalation were 20-95% (1.8-36 months), clinical remission rates were 10-94% (1.8-36 months), colectomy rates were 0-33% (12-38 months), and adverse event rates were 0-18%. Treatment switching rates in 21 studies were 4-70% over 3-62 months, with switch due to loss of response rates of 4-35% over 12-62 months (7 studies). Up to 35% of patients underwent colectomy 12-120 weeks after switching, and 13-38% experienced adverse events. Data relating to economic outcomes were limited to tumor necrosis factor inhibitors, but demonstrated increased direct costs associated with both dose escalation and treatment switching.
CONCLUSION
Dose escalation and treatment switching are common with existing therapies. However, clinical response and remission rates vary, and a proportion of patients fail to achieve optimal clinical and economic outcomes. This highlights the need for more efficacious and durable treatments for patients with moderate-to-severe ulcerative colitis.
PubMed: 36855750
DOI: 10.2147/CEOR.S391413 -
International Ophthalmology Jun 2024This meta-analysis reviews the evidence for the risks and benefits associated with orthokeratology (OK) treatment compared with other methods of myopia control in... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
This meta-analysis reviews the evidence for the risks and benefits associated with orthokeratology (OK) treatment compared with other methods of myopia control in children and adults.
METHODS
A systematic search of Cochrane Central Register of Controlled Trials, Pubmed, Embase and Ovid was conducted from database inception to 22nd August 2021. Studies that reported on risks, visual and ocular biometric effects of OK in patients > 5 years of age with myopia (- 0.75 to - 6.00D) were included. Main outcomes are change in axial length and any adverse event.
RESULTS
Fourty-five papers were included in this systematic review and meta-analysis. The quality of data was variable and of moderate certainty, and selection bias likely skewed the results towards a relative benefit for OK. The rate of axial elongation in children was lower for OK treatment compared to other treatment modalities at one year (MD - 0.16 mm, 95% CI - 0.25 to - 0.07). Rate of change in axial length in children rebounded after OK discontinuation compared to participants who continued treatment (MD 0.10 mm, 95% CI 0.06 to 0.14). Adults and children wearing OK were up to 3.79 times more likely to experience an adverse event when compared with conventional contact lenses (OR 3.79, 95% CI 1.24 to ll.), though this evidence base is underdeveloped and requires additional well-designed studies for substantial conclusions to be drawn.
CONCLUSIONS
OK arrests myopia progression while in use, however, there remain unanswered questions about the optimal duration of treatment, discontinuation effects and long-term risk for adverse events.
Topics: Humans; Orthokeratologic Procedures; Myopia; Refraction, Ocular; Visual Acuity; Axial Length, Eye; Contact Lenses; Child; Risk Assessment
PubMed: 38904856
DOI: 10.1007/s10792-024-03175-w -
The Cochrane Database of Systematic... Dec 2021Chronic pelvic pain (CPP) is a common gynaecological condition accounting for 20% of all gynaecological referrals. There are wide ranges of causes with overlapping... (Review)
Review
BACKGROUND
Chronic pelvic pain (CPP) is a common gynaecological condition accounting for 20% of all gynaecological referrals. There are wide ranges of causes with overlapping symptomatology, therefore the management of the condition is a formidable challenge for clinicians. The aetiology of CPP is heterogeneous and in many cases, no clear diagnosis can be reached. It is in this scenario that the label of chronic pelvic pain syndrome (CPPS) can be applied. We defined women with CPPS as having a minimum duration of pain of at least 6 months, including with a diagnosis of pelvic congestion syndrome, but excluding pain caused by a condition such as endometriosis. Many surgical interventions have been tried in isolation or in conjunction with non-surgical interventions in the management with variable results. Surgical interventions are invasive and carry operative risks. Surgical interventions must be evaluated for their effectiveness prior to their prevalent use in the management of women with CPPS.
OBJECTIVES
To review the effectiveness and safety of surgical interventions in the management of women with CPPS.
SEARCH METHODS
We searched the Cochrane Gynaecology and Fertility Group (CGF) Specialised Register of Controlled Trials, CENTRAL, MEDLINE, Embase and PsycINFO, on 23 April 2021 for any randomised controlled trials (RCT) for surgical interventions in women with CPPS. We also searched the citation lists of relevant publications, two trial registries, relevant journals, abstracts, conference proceedings and several key grey literature sources.
SELECTION CRITERIA
RCTs with women who had CPPS. The review authors were prepared to consider studies of any surgical intervention used for the management of CPPS. Outcome measures were pain rating scales, adverse events, psychological outcomes, quality of life (QoL) measures and requirement for analgesia.
DATA COLLECTION AND ANALYSIS
Two review authors independently evaluated studies for inclusion and extracted data using the forms designed according to Cochrane guidelines. For each included trial, we collected information regarding the method of randomisation, allocation concealment, blinding, data reporting and analyses. We reported pooled results as mean difference (MDs) or odds ratios (OR) and 95% confidence interval (CI) by the Mantel-Haenszel method. If similar outcomes were reported on different scales, we calculated the standardised mean difference (SMD). We applied GRADE criteria to judge the overall certainty of the evidence.
MAIN RESULTS
Four studies met our inclusion criteria involving 216 women with CPP and no identifiable cause. Adhesiolysis compared to no surgery or diagnostic laparoscopy We are uncertain of the effect of adhesiolysis on pelvic pain scores postoperatively at three months (MD -7.3, 95% CI -29.9 to 15.3; 1 study, 43 participants; low-certainty evidence), six months (MD -14.3, 95% CI -35.9 to 7.3; 1 study, 43 participants; low-certainty evidence) and 12 months postsurgery (MD 0.00, 95% CI -4.60; 1 study, 43 participants; very low-certainty evidence). Adhesiolysis may improve both the emotional wellbeing (MD 24.90, 95% CI 7.92 to 41.88; 1 study, 43 participants; low-certainty evidence) and social support (MD 23.90, 95% CI -1.77 to 49.57; 1 study, 43 participants; low-certainty evidence) components of the Endometriosis Health Profile-30, and both the emotional component (MD 32.30, 95% CI 13.16 to 51.44; 1 study, 43 participants; low-certainty evidence) and the physical component of the 12-item Short Form (MD 22.90, 95% CI 10.97 to 34.83; 1 study, 43 participants; low-certainty evidence) when compared to diagnostic laparoscopy. We are uncertain of the safety of adhesiolysis compared to comparator groups due to low-certainty evidence and lack of structured adverse event reporting. No studies reported on psychological outcomes or requirements for analgesia. Laparoscopic uterosacral ligament ablation or resection compared to diagnostic laparoscopy/other treatment We are uncertain of the effect of laparoscopic uterosacral ligament/nerve ablation (LUNA) or resection compared to other treatments postoperatively at three months (OR 1.26, 95% CI 0.40 to 3.93; 1 study, 51 participants; low-certainty evidence) and six months (MD -2.10, 95% CI -4.38 to 0.18; 1 study, 74 participants; very low-certainty evidence). At 12 months post-surgery, we are uncertain of the effect of LUNA on the rate of successful treatment compared to diagnostic laparoscopy. One study of 56 participants found no difference in the effect of LUNA on non-cyclical pain (P = 0.854) or dyspareunia (P = 0.41); however, there was a difference favouring LUNA on dysmenorrhea (P = 0.045) and dyschezia (P = 0.05). We are also uncertain of the effect of LUNA compared to vaginal uterosacral ligament resection on pelvic pain at 12 months (MD 2.00, 95% CI 0.47 to 3.53; 1 study, 74 participants; very low-certainty evidence). We are uncertain of the safety of LUNA or resection compared to comparator groups due to the lack of structured adverse event reporting. Women undergoing LUNA may require more analgesia postoperatively than those undergoing other treatments (P < 0.001; 1 study, 74 participants). No studies reported psychological outcomes or QoL.
AUTHORS' CONCLUSIONS
We are uncertain about the benefit of adhesiolysis or LUNA in management of pain in women with CPPS based on the current literature. There may be a QoL benefit to adhesiolysis in improving both emotional wellbeing and social support, as measured by the validated QoL tools. It was not possible to synthesis evidence on adverse events as these were only reported narratively in some studies, in which none were observed. With the inadequate objective assessment of adverse events, especially long-term adverse events, associated with adhesiolysis or LUNA for CPPS, there is currently little to support these interventions for CPPS.
Topics: Chronic Pain; Endometriosis; Female; Humans; Laparoscopy; Pelvic Pain; Quality of Life
PubMed: 34923620
DOI: 10.1002/14651858.CD008212.pub2 -
Frontiers in Immunology 2023To present the pooled quantitative evidence of baseline characteristics and clinical outcomes of tocilizumab (TCZ) in patients with refractory Takayasu arteritis (TAK). (Meta-Analysis)
Meta-Analysis
OBJECTIVE
To present the pooled quantitative evidence of baseline characteristics and clinical outcomes of tocilizumab (TCZ) in patients with refractory Takayasu arteritis (TAK).
METHODS
A comprehensive systematic review and meta-analysis was performed on all available studies retrieved from the MEDLINE, Embase, and Cochrane databases, using TCZ in patients with refractory TAK. We applied the commands and in Stata Software to pool overall estimates of continuous data and binomial data, respectively. A random-effects model was recruited for analysis.
RESULTS
Nineteen studies with 466 patients were included in this meta-analysis. The mean age at implementation of TCZ was 34.32 years. Female sex and Numano Type V were the most prominent baseline characteristics. During the 12-month follow-up when receiving TCZ treatment, pooled CRP was 1.17 mg/L (95% confidence interval [CI] -0.18-2.52), pooled ESR was 3.54 mm/h (95% CI 0.51-6.58), and pooled glucocorticoid dose was 6.26 mg/d (95% CI 4.24-8.27). Approximately 76% (95% CI 58-87%) of patients achieved a decrease in glucocorticoid dosage. Meanwhile, patients with TAK had a remission rate of 79% (95% CI 69-86%), a relapse rate of 17% (95% CI 5-45%), an imaging progress rate of 16% (95% CI 9-27%), and a retention rate of 68% (95% CI 50-82%). Adverse events occurred in 16% (95% CI 5-39%) of patients, and infection was the most common adverse event, with a rate of 12% (95% CI 5-28%).
CONCLUSION
TCZ treatment can provide favorable outcomes in terms of inflammatory markers, steroid-sparing effects, clinical response, drug retention and minimizing adverse effects for patients with refractory TAK.
Topics: Humans; Female; Adult; Glucocorticoids; Takayasu Arteritis; Treatment Outcome; Antibodies, Monoclonal, Humanized
PubMed: 36845158
DOI: 10.3389/fimmu.2023.1084558 -
Cancer Treatment Reviews Apr 2024Cancer-related pain often requires opioid treatment with opioid-induced constipation (OIC) as its most frequent gastrointestinal side-effect. Both for prevention and... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Cancer-related pain often requires opioid treatment with opioid-induced constipation (OIC) as its most frequent gastrointestinal side-effect. Both for prevention and treatment of OIC osmotic (e.g. polyethylene glycol) and stimulant (e.g. bisacodyl) laxatives are widely used. Newer drugs such as the peripherally acting µ-opioid receptor antagonists (PAMORAs) and naloxone in a fixed combination with oxycodone have become available for the management of OIC. This systematic review and meta-analysis aims to give an overview of the scientific evidence on pharmacological strategies for the prevention and treatment of OIC in cancer patients.
METHODS
A systematic search in PubMed, Embase, Web of Science and the Cochrane Library was completed from inception up to 22 October 2022. Randomized and non-randomized studies were systematically selected. Bowel function and adverse drug events were assessed.
RESULTS
Twenty trials (prevention: five RCTs and three cohort studies; treatment: ten RCTs and two comparative cohort studies) were included in the review. Regarding the prevention of OIC, three RCTs compared laxatives with other laxatives, finding no clear differences in effectivity of the laxatives used. One cohort study showed a significant benefit of magnesium oxide compared with no laxative. One RCT found a significant benefit for the PAMORA naldemedine compared with magnesium oxide. Preventive use of oxycodone/naloxone did not show a significant difference in two out of three other studies compared to oxycodone or fentanyl. A meta-analysis was not possible. Regarding the treatment of OIC, two RCTs compared laxatives, of which one RCT found that polyethylene glycol was significantly more effective than sennosides. Seven studies compared an opioid antagonist (naloxone, methylnaltrexone or naldemedine) with placebo and three studies compared different dosages of opioid antagonists. These studies with opioid antagonists were used for the meta-analysis. Oxycodone/naloxone showed a significant improvement in Bowel Function Index compared to oxycodone with laxatives (MD -13.68; 95 % CI -18.38 to -8.98; I = 58 %). Adverse drug event rates were similar amongst both groups, except for nausea in favour of oxycodone/naloxone (RR 0.51; 95 % CI 0.31-0.83; I = 0 %). Naldemedine (NAL) and methylnaltrexone (MNTX) demonstrated significantly higher response rates compared to placebo (NAL: RR 2.07, 95 % CI 1.64-2.61, I = 0 %; MNTX: RR 3.83, 95 % CI 2.81-5.22, I = 0 %). With regard to adverse events, abdominal pain was more present in treatment with methylnaltrexone and diarrhea was significantly more present in treatment with naldemedine. Different dosages of methylnaltrexone were not significantly different with regard to both efficacy and adverse drug event rates.
CONCLUSIONS
Magnesium oxide and naldemedine are most likely effective for prevention of OIC in cancer patients. Naloxone in a fixed combination with oxycodone, naldemedine and methylnaltrexone effectively treat OIC in cancer patients with acceptable adverse events. However, their effect has not been compared to standard (osmotic and stimulant) laxatives. More studies comparing standard laxatives with each other and with opioid antagonists are necessary before recommendations for clinical practice can be made.
Topics: Humans; Laxatives; Analgesics, Opioid; Narcotic Antagonists; Constipation; Oxycodone; Opioid-Induced Constipation; Magnesium Oxide; Cohort Studies; Naloxone; Polyethylene Glycols; Neoplasms; Drug-Related Side Effects and Adverse Reactions; Quaternary Ammonium Compounds; Naltrexone
PubMed: 38452708
DOI: 10.1016/j.ctrv.2024.102704 -
Prehospital and Disaster Medicine Oct 2022Global climate change (global warming) has been identified as the primary factor responsible for the observed increase in frequency and severity of wildfires (also known... (Review)
Review
INTRODUCTION
Global climate change (global warming) has been identified as the primary factor responsible for the observed increase in frequency and severity of wildfires (also known as bushfires in some countries) throughout the majority of the world's vegetated environments. This trend is predicted to continue, causing significant adverse health effects to nearby residential populations and placing a potential strain on local emergency departments (EDs).
STUDY OBJECTIVE
The aim of this literature review was to identify papers relating to wildfires and their impact on EDs, specifically patient presentation characteristics, resource utilization, and patient outcomes.
METHOD
This integrative literature review was guided by the Preferred Reporting Items of Systematic Reviews and Meta-Analysis (PRISMA) guidelines for data collection, and Whittemore and Knafl's framework for data analysis. Data were collected from OvidSP, MEDLINE, DARE, CINAHL, PubMed, and Scopus databases. Various Medical Subject Headings (MeSH) and keywords identified papers relevant to wildfires/bushfires and EDs.
RESULTS
Literature regarding the relationship between ED presentations and wildfire events, however, is primarily limited to studies from the United States and Australia and indicates particulate matter (PM) is principally linked to adverse respiratory and cardiovascular outcomes. Observable trends in the literature principally included a significant increase in respiratory presentations, primarily with a lag of one to two days from the initial event. Respiratory and cardiovascular studies that stratified results by age indicated individuals under five, over 65, or those with pre-existing conditions formed the majority of ED presentations.
CONCLUSION
Key learnings from this review included the need for effective and targeted community advisory programs/procedures, prior to and during wildfire events, as well as pre-event planning, development, and robust resilience strategies for EDs.
Topics: Climate Change; Databases, Factual; Disasters; Emergency Service, Hospital; Humans; United States; Wildfires
PubMed: 35875982
DOI: 10.1017/S1049023X22001054 -
Cardiovascular Revascularization... Apr 2022To assess the safety and efficacy of the Amplatzer Septal Occluder in the closure of secundum type atrial septal defects. (Meta-Analysis)
Meta-Analysis
OBJECTIVES
To assess the safety and efficacy of the Amplatzer Septal Occluder in the closure of secundum type atrial septal defects.
BACKGROUND
The Amplatzer Septal Occluder (ASO; Abbott, St. Paul, MN) is an FDA-approved device for percutaneous closure of secundum type atrial septal defects (ASD). Previous small cohort trials have shown a favorable safety and technical efficacy profile.
METHODS
We conducted a systemic review and meta-analysis of all prospective case series and controlled trials that evaluated the ASO's safety and implant efficacy. The primary endpoint was the technical success rate of implantations. Secondary outcomes included proportions of arrhythmias and embolism specific-adverse events.
RESULTS
We included a total of 12 studies with 2972 patients. The ratio of device implantation was 2:1 by sex [female: male]. Pooled technical success rate of implantation was 98% (95% CI: 0.968-0.990, P < 0.01). The cumulative adverse event rate was 5.1% (95% CI: 0.035-0.068, P < 0.01), which included arrhythmia and embolism specific adverse event rates of 1.8% (95% CI: 0.007-0.032, P < 0.01) and 0.7% (95% CI: 0.002-0.013, P < 0.01), respectively. Sensitivity analysis did not significantly affect pooled outcomes for success rate and adverse events; both forest plot and Begg's and Egger's regression tests supported symmetricity.
CONCLUSION
A high likelihood of technical success can be expected when implanting the ASO in secundum type ASDs. Adverse event rates are expected for one in twenty patients, and thus, our results support the safe use of ASO in secundum type ASDs closure.
CONDENSED ABSTRACT
The AMPLATZER Septal Occluder is an FDA-approved device for percutaneous closure of secundum type atrial septal defects (ASD). We conducted a systemic review and meta-analysis of all prospective case series and controlled trials that evaluated the ASO's safety and implant efficacy. We included a total of 12 studies with 2972 patients. Pooled technical success rate of implantation was 98% (P < 0.01). The cumulative adverse event rate was 5.1% (P < 0.01), 1.8% (P < 0.01) rate of arrhythmias, and 0.7% (P < 0.01) rate of embolisms. A high likelihood of technical success can be expected with a low rate of adverse events.
Topics: Cardiac Catheterization; Cohort Studies; Female; Heart Septal Defects, Atrial; Humans; Male; Septal Occluder Device; Treatment Outcome
PubMed: 34183276
DOI: 10.1016/j.carrev.2021.06.002 -
Frontiers in Immunology 2023Conventional treatment techniques have limited efficacy and more side effects in the treatment of prurigo nodularis. The better alternative treatment option for better...
BACKGROUND
Conventional treatment techniques have limited efficacy and more side effects in the treatment of prurigo nodularis. The better alternative treatment option for better outcomes of the disease is dupilumab.
OBJECTIVE
The objective of this study was to systematically review dupilumab-related treatment outcomes in prurigo nodularis.
METHODS
Several databases like Embase, PubMed, Web of Science, and Cochrane library were searched for data acquisition on October 8, 2022. Based on Preferred Reporting Items for Systematic Reviews and Meta-analyses guidelines, 24 publications were included in this study.
RESULTS
After 4,12,16 and more than 16 weeks of dupilumab treatment, 8.3% (n=5/60), 34.4% (n=11/32), 3.6% (n=2/56), and 45.3% (n=29/64) of patients had complete remission, respectively. In addition, 85.0% (n=51/60), 59.4% (n=19/32), 83.9% (n=47/56), and 43.8% (n=28/64) had partial remission, respectively. Moreover, 6.7% (n=4/60), 6.3% (n=2/32), 12.5% (n=7/56), and 10.9% (n=7/64) showed no remission, respectively, and significant reduction of numeric rating scale itch intensity (from 9.0 to 4.9, 2.1, 2.8, 0.9) was attained. There were no serious adverse events observed during treatment, but the most common event observed was conjunctivitis (12.6%, n=15/119).
CONCLUSIONS
Dupilumab has definite effectiveness and safety in prurigo nodularis treatment.
SYSTEMATIC REVIEW REGISTRATION
https://www.crd.york.ac.uk/PROSPERO, identifier (CRD42022365802).
Topics: Humans; Prurigo; Pruritus; Antibodies, Monoclonal, Humanized; Treatment Outcome
PubMed: 36742321
DOI: 10.3389/fimmu.2023.1092685 -
Therapeutic Advances in Drug Safety 2019Poor oral hygiene is strongly associated with oral and systemic diseases. Alongside mechanical tooth cleaning, the adjunctive use of mouthrinses has been widely... (Review)
Review
BACKGROUND
Poor oral hygiene is strongly associated with oral and systemic diseases. Alongside mechanical tooth cleaning, the adjunctive use of mouthrinses has been widely advocated. Although research on the efficacy of various mouthrinse formulations is very active, there are a lack of conclusive data regarding their adverse effects.
METHODS
We undertook a systematic review in accordance wih PRISMA guidelines of electronic databases of clinical trials of any duration with daily home use of mouthwashes, presenting clinical and subjective side effects (PROSPERO registration: CRD42016054037).
RESULTS
After evaluating 614 titles and abstracts, 154 studies were selected for full-text analysis; 85 final papers were included. Based on the active ingredient in the test product, nine categories were created: cetyl pyridinium chloride, essential oils, chlorhexidine, triclosan, natural products, diclofenac, fluorides, delmopinol, and miscellaneous active substances. Most of the studies were of short duration (less than 6 months) with a defective 'methods' description; the reporting of adverse events often being overlooked. Both local morphological (oral mucosa and dental-crown staining, mucosal lesions) and functional (taste modifications, abnormal oral sensation) alterations were reported. Tooth staining was the most commonly listed adverse event, but it was quantitatively assessed only in a very small number of papers; most studies relied on patient reports. Staining was time associated; the longer the study, the higher its reported incidence and severity.
CONCLUSIONS
The reduced report of side effects may partly be due to a lack of an objective measure and lack of general guidelines that demand studies report their adverse events. The most frequently reported adverse effect was teeth staining. As in most studies, the effect was associated with trial duration; clinical trials should be of sufficient duration. New investigations meeting the suggested criteria of a minimal duration of 6 months should be planned.
PubMed: 31579502
DOI: 10.1177/2042098619854881 -
European Archives of... Feb 2020To review types and frequencies of adverse events (AE) associated with bone-conduction hearing implants (BCHIs) and active middle-ear implants (aMEIs) as reported in the...
PURPOSE
To review types and frequencies of adverse events (AE) associated with bone-conduction hearing implants (BCHIs) and active middle-ear implants (aMEIs) as reported in the literature.
METHODS
Cochrane, PubMed, and EMBASE libraries were searched for primary articles in English or German language that reported on adverse events following BCHI or aMEI implantation, included at least five patients and were published between 1996 and 2016. Study characteristics, demographics, and counts of adverse events were tabulated and analyzed within the R statistical programming environment.
RESULTS
Following assessment of the reporting quality of adverse events, we present a brief guideline that potentially improves AE reporting in this field of research. For the full dataset, we summarize study-level adverse event frequencies in terms of ratio of events to ears (REE) by AE groups and by device. For a subset of studies, we also report cumulative incidence (risk) for minor- and major adverse-events by device and by device groups.
CONCLUSIONS
Data analyzed in this review show that: (1) the reporting quality of adverse events associated with BCHI and aMEIs is often very low; (2) adverse events associated with BCHI and aMEIs are qualitatively different and not equally frequent among devices; (3) state-of-the-art implantable BCHIs and aMEIs are a safe treatment option for hearing loss.
Topics: Adult; Cochlear Implants; Hearing Aids; Hearing Loss; Humans; Ossicular Prosthesis; Prosthesis Implantation
PubMed: 31749056
DOI: 10.1007/s00405-019-05727-8