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Alzheimer's Research & Therapy Feb 2022The NIA-AA research framework proposes a purely biological definition of Alzheimer's disease (AD). This implies that AD can be diagnosed based on biomarker...
BACKGROUND
The NIA-AA research framework proposes a purely biological definition of Alzheimer's disease (AD). This implies that AD can be diagnosed based on biomarker abnormalities, irrespective of clinical manifestation. While this brings opportunities, it also raises challenges. We aimed to provide an overview of considerations regarding the disclosure of AD pathology before the onset of dementia.
METHODS
A systematic literature review was conducted and reported according to PRISMA guidelines. We searched PubMed, Embase, APA PsycINFO, and Web of Science Core Collection (on 10 December 2020) for references on conveying AD biomarker results to individuals without dementia. Our query combined variations on the terms Alzheimer's disease, disclosure, or diagnosis, preclinical or prodromal, and biomarkers. Two reviewers independently screened the resulting 6860 titles and abstracts for eligibility and examined 162 full-text records for relevance. We included theoretical articles in English, on communicating amyloid and/or tau results to individuals with mild cognitive impairment, subjective cognitive decline, or normal cognition. MAXQDA-software was used for inductive data analysis.
RESULTS
We included 27 publications. From these, we extracted 26 unique considerations, which we grouped according to their primary relevance to a clinical, personal, or societal context. Clinical considerations included (lack of) validity, utility, and disclosure protocols. Personal considerations covered psychological and behavioral implications, as well as the right to (not) know. Finally, societal considerations comprised the risk of misconception, stigmatization, and discrimination. Overall, views were heterogeneous and often contradictory, with emphasis on harmful effects.
CONCLUSIONS
We found 26 diverse and opposing considerations, related to a clinical, personal, or societal context, which are relevant to diagnosing AD before dementia. The theoretical literature tended to focus on adverse impact and rely on common morality, while the motivation for and implications of biomarker testing are deeply personal. Our findings provide a starting point for clinicians to discuss biomarker-based diagnosis with their patients, which will become even more relevant in light of the conditional approval of a first disease-modifying drug for AD.
Topics: Alzheimer Disease; Amyloid; Biomarkers; Cognitive Dysfunction; Dementia; Disease Progression; Humans
PubMed: 35144684
DOI: 10.1186/s13195-022-00971-3 -
BMJ Open Dec 2017We conducted a systematic review of the available literature on deaths, injuries and permanent disability from rubber and plastic bullets, as well as from bean bag... (Review)
Review
OBJECTIVE
We conducted a systematic review of the available literature on deaths, injuries and permanent disability from rubber and plastic bullets, as well as from bean bag rounds, shot pellets and other projectiles used in arrests, protests and other contexts from 1 January 1990 until 1 June 2017.
DATA SOURCES
PubMed, Scopus, JSTOR and grey literature.
DATA SYNTHESIS
We report on descriptive statistics as well as data on injury severity, permanent disability and death. We analysed potential risk factors for injury severity, including the site of impact, firing distance and access to medical care.
RESULTS
Of 3228 identified articles, 26 articles met inclusion criteria. These articles included injury data on 1984 people, 53 of whom died as a result of their injuries. 300 people suffered permanent disability. Deaths and permanent disability often resulted from strikes to the head and neck (49.1% of deaths and 82.6% of permanent disabilities). Of the 2135 injuries in those who survived their injuries, 71% were severe, injuries to the skin and to the extremities were most frequent. Anatomical site of impact, firing distance and timely access to medical care were correlated with injury severity and risk of disability.
CONCLUSIONS
Kinetic impact projectiles (KIPs), often called rubber or plastic bullets, are used commonly in crowd-control settings. We find that these projectiles have caused significant morbidity and mortality during the past 27 years, much of it from penetrative injuries and head, neck and torso trauma. Given their inherent inaccuracy, potential for misuse and associated health consequences of severe injury, disability and death, KIPs do not appear to be appropriate weapons for use in crowd-control settings. There is an urgent need to establish international guidelines on the use of crowd-control weapons to prevent unnecessary injuries and deaths.
Topics: Crowding; Dissent and Disputes; Global Health; Humans; Law Enforcement; Trauma Severity Indices; Violence; Wounds, Gunshot
PubMed: 29255079
DOI: 10.1136/bmjopen-2017-018154 -
Contraception Sep 2016Postpartum women need effective contraception. Concerns have been raised that use of progestogen-only contraceptives (POCs) may affect breastfeeding performance and... (Review)
Review
BACKGROUND
Postpartum women need effective contraception. Concerns have been raised that use of progestogen-only contraceptives (POCs) may affect breastfeeding performance and infant health outcomes.
OBJECTIVES
We investigated the clinical outcomes of breastfeeding duration, initiation of supplemental feeding and weaning, as well as infant outcomes including infant growth, health and development among breastfeeding women using POCs compared with breastfeeding women not using POCs.
SEARCH STRATEGY
We searched the PubMed database for all articles published from database inception through December 2014.
SELECTION CRITERIA
We included primary research studies of breastfeeding women of any age or parity who received POCs, including progestogen-only pills, injectables, implants or hormonal intrauterine devices (IUDs). The main outcomes were breastfeeding performance (as measured by initiation, continuation, frequency and exclusivity of breastfeeding) and infant health (as measured by growth, development or adverse health effects).
RESULTS
Forty-nine articles reporting on 47 different studies were identified that investigated the use of POCs in breastfeeding women and reported clinically relevant outcomes of infant growth, health or breastfeeding performance. Studies ranged from poor to fair methodological quality and generally failed to show negative effects of the use of POCs on breastfeeding outcomes or on infant growth or development. One randomized controlled trial (RCT) raises concerns that immediate insertion of the levonorgestrel IUD postpartum may be associated with poorer breastfeeding performance when compared with delayed insertion, although two other RCTs evaluating early etonogestrel implants compared with delayed initiation of implants or depot medroxyprogesterone acetate failed to find such an association.
CONCLUSION
The preponderance of evidence fails to demonstrate adverse breastfeeding outcomes or negative health outcomes in infants such as restricted growth, health problems or impaired development. Evidence newly added to this review was largely consistent with previous evidence.
Topics: Breast Feeding; Child Development; Contraception; Contraceptives, Oral, Hormonal; Drug Implants; Female; Humans; Infant; Intrauterine Devices; Levonorgestrel; Medroxyprogesterone Acetate; Progestins; Randomized Controlled Trials as Topic
PubMed: 26410174
DOI: 10.1016/j.contraception.2015.09.010 -
JACC. Cardiovascular Interventions Jan 2017This study sought to compare the 2-year outcomes between bioresorbable vascular scaffold (BVS) and everolimus-eluting metallic drug-eluting stent (EES). (Meta-Analysis)
Meta-Analysis Review
OBJECTIVES
This study sought to compare the 2-year outcomes between bioresorbable vascular scaffold (BVS) and everolimus-eluting metallic drug-eluting stent (EES).
BACKGROUND
The occurrence of very late stent/scaffold thrombosis (VLST) of BVS beyond 1 year after implantation is an increasing concern.
METHODS
We conducted a meta-analysis of 24 studies (BVS: n = 2,567 and EES: n = 19,806) reporting the 2-year outcomes of BVS and/or EES to compare the risk of BVS versus EES for stent/scaffold thrombosis (ST) and target lesion failure (TLF) in 7 comparative studies (3 randomized and 4 observational), and to estimate the pooled incidence rates of ST and TLF including additional 17 single-arm studies.
RESULTS
In the 7 comparative studies, the risk for VLST between 1 and 2 years was numerically higher in BVS than in EES (odds ratio [OR]: 2.03 [95% confidence interval (CI): 0.62 to 6.71]). The excess risk of BVS relative to EES for ST through 2 years was significant (OR: 2.08 [95% CI: 1.02 to 4.26]). The risk for TLF was neutral between BVS and EES. In the 24 studies, the pooled estimated incidence rates of VLST, and ST through 2 years were higher in BVS than in EES (0.240 [95% CI: 0.022 to 0.608]% vs. 0.003 [95% CI: 0.000 to 0.028]%, and 1.43 [95% CI: 0.67 to 2.41]% vs. 0.56 [95% CI: 0.43 to 0.70]%, respectively). The corresponding rates for TLF were comparable between BVS and EES (1.88 [95% CI: 1.30 to 2.55]% and 1.78 [95% CI: 1.17 to 2.49]% and 7.90 [95% CI: 6.26 to 9.69]% and 7.49 [95% CI: 5.86 to 9.29]%, respectively).
CONCLUSIONS
In this meta-analysis, BVS as compared with EES was associated with higher risk for VLST between 1 and 2 years and ST through 2 years.
Topics: Absorbable Implants; Aged; Cardiovascular Agents; Coronary Artery Disease; Coronary Thrombosis; Drug-Eluting Stents; Everolimus; Female; Humans; Incidence; Kaplan-Meier Estimate; Male; Metals; Middle Aged; Odds Ratio; Percutaneous Coronary Intervention; Propensity Score; Prosthesis Design; Risk Assessment; Risk Factors; Time Factors; Treatment Outcome
PubMed: 28057284
DOI: 10.1016/j.jcin.2016.10.027 -
European Journal of Preventive... Jul 2018Aims The association between progestin-only contraceptive (POC) use and the risk of various cardiometabolic outcomes has rarely been studied. We performed a systematic... (Meta-Analysis)
Meta-Analysis
Aims The association between progestin-only contraceptive (POC) use and the risk of various cardiometabolic outcomes has rarely been studied. We performed a systematic review and meta-analysis to determine the impact of POC use on cardiometabolic outcomes including venous thromboembolism, myocardial infarction, stroke, hypertension and diabetes. Methods and results Nineteen observational studies (seven cohort and 12 case-control) were included in this systematic review. Of those, nine studies reported the risk of venous thromboembolism, six reported the risk of myocardial infarction, six reported the risk of stroke, three reported the risk of hypertension and two studies reported the risk of developing diabetes with POC use. The pooled adjusted relative risks (RRs) for venous thromboembolism, myocardial infarction and stroke for oral POC users versus non-users based on the random effects model were 1.06 (95% confidence interval (CI) 0.70-1.62), 0.98 (95% CI 0.66-1.47) and 1.02 (95% CI 0.72-1.44), respectively. Stratified analysis by route of administration showed that injectable POC with a RR of 2.62 (95% CI 1.74-3.94), but not oral POCs (RR 1.06, 95% CI 0.7-1.62), was associated with an increased risk of venous thromboembolism. A decreased risk of venous thromboembolism in a subgroup of women using an intrauterine levonorgestrel device was observed with a RR of 0.53 (95% CI 0.32-0.89). No effect of POC use on blood pressure was found, but there was an indication for an increased risk of diabetes with injectable POCs, albeit non-significant. Conclusions This systematic review and meta-analysis suggests that oral POC use is not associated with an increased risk of developing various cardiometabolic outcomes, whereas injectable POC use might increase the risk of venous thromboembolism.
Topics: Administration, Oral; Adolescent; Adult; Aged; Cardiovascular Diseases; Contraceptives, Oral, Hormonal; Diabetes Mellitus; Drug Implants; Female; Humans; Injections; Middle Aged; Progestins; Risk Assessment; Risk Factors; Venous Thromboembolism; Young Adult
PubMed: 29745237
DOI: 10.1177/2047487318774847 -
Graefe's Archive For Clinical and... Feb 2023Neovascular glaucoma (NVG) is characterised by neovascularisation of the angle and therefore elevated intraocular pressure (IOP). This results in progressive optic... (Meta-Analysis)
Meta-Analysis
PURPOSE
Neovascular glaucoma (NVG) is characterised by neovascularisation of the angle and therefore elevated intraocular pressure (IOP). This results in progressive optic neuropathy and loss of visual acuity. Treatment aims to reduce IOP in order to prevent optic nerve damage. A systematic review was completed synthesising results from randomised control trials (RCTs) comparing interventions for the management of NVG and their efficacy and safety.
METHODS
Data was sourced from Web of Science, Embase and Medline after 1st January 2000. The primary outcome measures were mean IOP at follow-up and success rate. The secondary outcomes included mean IOP lowering medications and total complications. A meta-analysis was completed on comparative studies using Revman (version 5.4).
RESULTS
For the two studies comparing Ahmed glaucoma valve (AGV) + pan-retinal photocoagulation (PRP) vs AGV + PRP + intra-vitreal bevacizumab (IVB), there was no difference in mean IOP or odds of success from the meta-analysis. From the 4 studies examining the utilisation of anti-vascular endothelial growth factor (anti-VEGF), one study showed lower mean IOP at 1 (p = 0.002) and 3 months (p = 0.033) for IVB vs sham injection. In the 2 studies studying transcleral diode laser (TDL), there were no significant findings. From the 4 studies looking at trabeculectomy (trab), lower mean IOP at 6 (p = 0.001), 9 (p = 0.01), 12 (p = 0.02) and 18 months (p = 0.004) was shown for intra-vitreal ranibizumab (IVR) + PRP + visco-trabeculectomy vs IVR + PRP + trab, and a significantly lower mean IOP was present in the Baerveldt group vs trab at 6 months (p = 0.03). In the 2 studies investigating the AGV, there was a lower mean IOP at 1 month (p = 0.01) in the AGV + triamcinolone (TCA) group. The risk of bias was low for 4 studies, high for 4 studies and 6 studies had some concerns.
CONCLUSION
This is the first meta-analysis of RCTs in the management of neovascular glaucoma. The lack of high-quality evidence contributes to the lack of consensus in managing NVG. Our results highlight modern treatment strategies and the need for better powered RCTs with long-term follow-up in order to establish optimal treatment modalities and true patient outcomes.
Topics: Humans; Glaucoma, Neovascular; Intraocular Pressure; Consensus; Glaucoma; Ranibizumab; Bevacizumab; Glaucoma Drainage Implants; Treatment Outcome; Randomized Controlled Trials as Topic
PubMed: 35939118
DOI: 10.1007/s00417-022-05785-5 -
Journal of Clinical Medicine Apr 2024This systematic review aimed to evaluate the impact of antiresorptive drug therapy on osseointegrated dental implants and the association with medication-related... (Review)
Review
This systematic review aimed to evaluate the impact of antiresorptive drug therapy on osseointegrated dental implants and the association with medication-related osteonecrosis of the jaw (MRONJ). A systematic search, including a computer search of several databases with specific keywords, a reference search, and a manual search of four key maxillofacial journals were performed. Relevant articles were then evaluated and those that fulfilled the five predetermined criteria were chosen to enter the final review. A total of 445 implants in 135 subjects were included in the eight studies analyzed in the final review. The failure rate of dental implants after antiresorptive medication in the included studies was 23%, with 83% of failures attributed to MRONJ. The average time from antiresorptive drug initiation to MRONJ development was approximately 34 months, ranging from 3 months to 16 years. The majority of MRONJ cases were classified as stage 2, and all sites showed either complete healing or substantial mucosal coverage after treatment. This review highlights the significant impact of antiresorptive drugs on osseo- integrated implants, with MRONJ identified as a leading cause of implant failure. The potential role of peri-implantitis as a trigger for MRONJ is emphasized. Regular monitoring and maintaining good periodontal health, especially within the first three years of antiresorptive drug therapy initiation, are crucial for implant success. Physicians and dentists should provide comprehensive information to patients prescribed with antiresorptive drugs, emphasizing the need for an awareness of the risks of MRONJ in the context of osseointegrated implants. A longer term of follow-up is recommended to identify and manage MRONJ around dental implants in an early manner.
PubMed: 38610856
DOI: 10.3390/jcm13072091 -
Journal of Biomaterials Applications Feb 2020Medical devices made of polydioxanone (a synthetic biodegradable polymer) have been available since the early 1980s. However, no review regarding their performance and...
BACKGROUND
Medical devices made of polydioxanone (a synthetic biodegradable polymer) have been available since the early 1980s. However, no review regarding their performance and safety has been published.
OBJECTIVE
This systematic review intends to review and assess commercially available polydioxanone implants and their safety and performance in patients.
METHODS
We searched for approved polydioxanone implants in several Food and Drug Administration databases. Then, we performed a literature search for publications and clinical trials where polydioxanone devices were implanted in patients. This search was performed on MEDLINE, Embase, Scopus and other databases. Safety and performance of polydioxanone implants in patients were assessed and compared with the implantation of non-polydioxanone devices, when possible, based on scoring systems developed by the authors that analyse surgical site infection rates, inflammatory reaction rates, foreign body response, postoperative pain and fever.
RESULTS
Food and Drug Administration databases search revealed that 48 implants have been approved since 1981, with 1294 adverse reactions or product malfunction in the last decade and 16 recalls. A total of 49 clinical trials and 104 scientific publications were found. Polydioxanone sutures and meshes/plates had low rates of surgical site infection, inflammatory reaction, foreign body response and postoperative fever. Polydioxanone clips/staples reported high rates of surgical site infection, postoperative fever and pain, with sub-optimal clinical performance and poor safety rates. The remaining implants identified showed high levels of safety and performance. Safety scores of polydioxanone implants and non-polydioxanone alternatives are similar. Polydioxanone monofilament sutures perform better than non-polydioxanone alternatives but performance did not differ with remaining polydioxanone implant types.
CONCLUSIONS
Although polydioxanone clips/staples should be implanted with caution and monitored carefully, in general, safety and performance scores of other polydioxanone implants did not differ from non-polydioxanone alternatives. This review will be a useful reference for researchers and industries developing new polydioxanone medical devices.
Topics: Absorbable Implants; Biocompatible Materials; Device Approval; Humans; Inflammation; Medical Device Recalls; Polydioxanone
PubMed: 31771403
DOI: 10.1177/0885328219888841 -
PloS One 2013Intravitreal agents have replaced observation in macular edema in central (CRVO) and grid laser photocoagulation in branch retinal vein occlusion (BRVO). We conducted a... (Review)
Review
BACKGROUND
Intravitreal agents have replaced observation in macular edema in central (CRVO) and grid laser photocoagulation in branch retinal vein occlusion (BRVO). We conducted a systematic review to evaluate efficacy and safety outcomes of intravitreal therapies for macular edema in CRVO and BRVO.
METHODS AND FINDINGS
MEDLINE, Embase, and the Cochrane Library were systematically searched for RCTs with no limitations of language and year of publication. 11 RCTs investigating anti-VEGF agents (ranibizumab, bevacizumab, aflibercept) and steroids (triamcinolone, dexamethasone implant) with a minimum follow-up of 1 year were evaluated.
EFFICACY CRVO
Greatest gain in visual acuity after 12 months was observed both under aflibercept 2 mg: +16.2 letters (8.5 injections), and under bevacizumab 1.25 mg: +16.1 letters (8 injections). Ranibizumab 0.5 mg improved vision by +13.9 letters (8.8 injections). Triamcinolone 1 mg and 4 mg stabilized visual acuity at a lower injection frequency (-1.2 letters, 2 injections).
BRVO
Ranibizumab 0.5 mg resulted in a visual acuity gain of +18.3 letters (8.4 injections). The effect of dexamethasone implant was transient after 1.9 implants in both indications.
SAFETY
Serious ocular adverse events were rare, e.g., endophthalmitis occurred in 0.0-0.9%. Major differences were found in an indirect comparison between steroids and anti-VEGF agents for cataract progression (19.8-35.0% vs. 0.9-7.0%) and in required treatment of increased intraocular pressure (7.0-41.0% vs. none). No major differences were identified in systemic adverse events.
CONCLUSIONS
Anti-VEGF agents result in a promising gain of visual acuity, but require a high injection frequency. Dexamethasone implant might be an alternative, but comparison is impaired as the effect is temporary and it has not yet been tested in PRN regimen. The ocular risk profile seems to be favorable for anti-VEGF agents in comparison to steroids. Because comparative data from head-to-head trials are missing currently, clinicians and patients should carefully weigh the benefit-harm ratio.
Topics: Humans; Intravitreal Injections; Macular Edema; Patient Safety; Retinal Vein Occlusion; Risk Assessment
PubMed: 24205253
DOI: 10.1371/journal.pone.0078538 -
Biomolecules Mar 2022Cochlear implantation initiates an inflammatory cascade in which both acute insertion trauma and chronic foreign body reaction lead to intracochlear fibrosis and loss of... (Review)
Review
Cochlear implantation initiates an inflammatory cascade in which both acute insertion trauma and chronic foreign body reaction lead to intracochlear fibrosis and loss of residual hearing. Several strategies have been proposed to attenuate the local reactive process after implantation, including intracochlear drug delivery. The present study gives an overview of what is being investigated in the field of inner ear therapeutics and cochlear implant surgery. The aim is to evaluate its potential benefit in clinical practice. A systematic search was conducted in PubMed, Embase, and Cochrane Library databases identifying comparative prospective studies examining the effect of direct inner ear drug application on mechanical cochlear trauma. Both animal and human studies were considered and all studies were assessed for quality according to the validated risk of bias tools. Intracochlear administration of drugs is a feasible method to reduce the local inflammatory reaction following cochlear implantation. In animal studies, corticosteroid use had a significant effect on outcome measures including auditory brainstem response, impedance, and histological changes. This effect was, however, only durable with prolonged drug delivery. Significant differences in outcome were predominantly seen in studies where the cochlear damage was extensive. Six additional reports assessing non-steroidal agents were found. Overall, evidence of anti-inflammatory effects in humans is still scarce.
Topics: Animals; Cochlear Implantation; Cochlear Implants; Ear, Inner; Hearing; Prospective Studies
PubMed: 35454118
DOI: 10.3390/biom12040529