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Journal of Anesthesia, Analgesia and... Dec 2022The leading cause of emergence delirium (ED) in children postoperatively is the exposure to inhalational anaesthetics. ED can occur immediately after waking from... (Review)
Review
The efficacy and safety of dexmedetomidine in preventing emergence delirium in paediatric patients following ophthalmic surgery: a systematic review and meta-analysis of randomised controlled trials.
BACKGROUND
The leading cause of emergence delirium (ED) in children postoperatively is the exposure to inhalational anaesthetics. ED can occur immediately after waking from anaesthesia, making patients generally uncooperative and agitated. Dexmedetomidine has sedative and analgesic effects and helps to reduce agitation and delirium and improve hemodynamic stability and the recovery of respiratory function; in addition to decreasing pain intensity, it is also well known for helping reduce nausea and vomiting.
OBJECTIVES
This updated systematic review meta-analysis investigate and summarise currently available evidence on the use of dexmedetomidine to prevent ED, reduce postoperative nausea and vomiting (PONV) and decrease the need for rescue analgesia in paediatric patients undergoing ophthalmic surgery.
METHODS
The medical databases EMBASE, PubMed and Cochrane Library were searched for randomised controlled trials published between January 2020 and August 2022 that used Dexmedetomidine in paediatric patients undergoing ophthalmic surgery. The protocol was prospectively registered with PROSPERO (CRD42022343622). The review was accomplished according to the 'Preferred Reporting Items for Systematic Reviews and Meta-Analyses', and the meta-analysis was conducted by using RevMan5.4. These studies examine the efficacy of dexmedetomidine in preventing ED in children undergo ophthalmic surgery. The Cochrane ROB-1 was used to assess risk of bias (ROB).
RESULTS
Eight studies comprised of 629 participants, of which 315 received dexmedetomidine and 314 placebos were examined. PAED score identified ED following surgery. A review and meta-analysis indicated that dexmedetomidine reduces ED incidence (RR = 0.39; 95% CI 0.25-0.62). Similarly, it reduces the use of rescue analgesia (RR = 0.38; 95% CI 0.25-0.57). However, dexmedetomidine did not help prevent PONV since no difference was found between groups (RR = 0.33; 95% CI 0.21-0.54).
CONCLUSION
This review showed that dexmedetomidine helped to reduce ED incidence in paediatric patients after ophthalmic surgery and reduced the need for rescue analgesia compared to placebo or other medications.
PubMed: 37386601
DOI: 10.1186/s44158-022-00079-y -
Journal of Current Ophthalmology 2022To conduct a systematic review and meta-analysis for estimating the prevalence of pediatric cataracts across Asia. (Review)
Review
PURPOSE
To conduct a systematic review and meta-analysis for estimating the prevalence of pediatric cataracts across Asia.
METHODS
A detailed literature search of PubMed, Embase, Web of Science, Cochrane Library, and Google Scholar databases, from 1990 to July 2021, was performed to include all studies reporting the prevalence of cataracts among children. Two researchers performed the literature search and screening of articles independently, and a third researcher critically reviewed the overall search and screening process to ensure the consistency. The JBI Critical Appraisal Checklist for studies reporting prevalence data was used to assess the methodological quality of the included studies.
RESULTS
Of the 496 identified articles, 35 studies with a sample size of 1,168,814 from 12 Asian countries were included in this analysis. The estimated pooled prevalence of pediatric cataracts in Asian children is 3.78 (95% confidence interval: 2.54-5.26)/10,000 individuals with high heterogeneity (I = 89.5%). The pooled prevalence by each country per 10,000 was 0.60 in Indonesia, 0.92 in Bangladesh, 1.47 in Iran, 2.01 in Bhutan, 3.45 in Laos, 3.68 in China, 4.27 in Thailand, 4.47 in India, 5.33 in Malaysia, 5.42 in Nepal, 9.34 in Vietnam, and 10.86 in Cambodia.
CONCLUSIONS
This study utilizes existing literature to identify the prevalence of cataracts in Asian children. Moreover, it highlights the need for more epidemiological studies with large sample sizes from other countries in Asia to accurately estimate the burden of disease.
PubMed: 36147271
DOI: 10.4103/joco.joco_339_21 -
The Cochrane Database of Systematic... Nov 2021A rhegmatogenous retinal detachment (RRD) is a separation of the neurosensory retina from the retinal pigment epithelium caused by a full-thickness break associated with... (Review)
Review
BACKGROUND
A rhegmatogenous retinal detachment (RRD) is a separation of the neurosensory retina from the retinal pigment epithelium caused by a full-thickness break associated with vitreous traction. While pneumatic retinopexy (PR), scleral buckle (SB), and vitrectomy are all well-received surgical interventions for eyes with RRD, their relative effectiveness has remained controversial.
OBJECTIVES
To assess the effectiveness and safety of PR versus SB or PR versus a combination treatment of SB and vitrectomy for people with RRD and to summarize any data on economic measures and quality of life.
SEARCH METHODS
We searched CENTRAL; which contains the Cochrane Eyes and Vision Trials Register; 2021, Issue 3); Ovid MEDLINE; Ovid Embase; and four other databases on 11 March 2021. We used no date or language restrictions in the electronic searches for trials.
SELECTION CRITERIA
We included all randomized or quasi-randomized controlled trials comparing the effectiveness of PR versus SB (with or without vitrectomy) for eyes with RRD.
DATA COLLECTION AND ANALYSIS
After screening for eligibility, two review authors independently extracted study characteristics, methods, and outcomes. We followed systematic review standards as set by Cochrane.
MAIN RESULTS
In this update, we identified and included one new randomized controlled trial. Together with two trials from the 2015 version of the review, we included three trials (276 eyes of 274 participants) comparing the effectiveness of PR versus SB. None compared PR versus a combined treatment of SB and vitrectomy. Of the three trials, one was a small study (published in 1996) with 20 participants (20 eyes) enrolled in Ireland and followed for a mean of 16 months; the second (published in 1989) included 196 participants (198 eyes) in the US followed for at least six months, and the third (published in 2021) was conducted in Italy and enrolled 58 participants (58 eyes) with a follow-up of 12 months. Overall, poor reporting quality resulted in unclear or high risks of bias. We found low-certainty evidence that PR may achieve retinal reattachment slightly less often than SB (risk ratio [RR] 0.91, 95% confidence interval [CI] 0.81 to 1.02; I = 0%; 3 studies, 276 eyes). Eyes undergoing PR may also display a higher risk of recurrent retinal detachment (low-certainty evidence), but the RR estimates were very imprecise (RR 1.70, 95% CI 0.97 to 2.98; I = 0%; 3 studies, 276 eyes). All three studies described the final visual acuity (VA) after the two procedures. However, the results were reported using different metrics and could not be combined. One study (196 participants) reported the proportion of eyes with a final VA of 20/40 or greater and favored PR (RR 1.31, 95% CI 1.04 to 1.65; low-certainty evidence), whereas in the 2021 study, both groups showed an improvement in final VA and there was no evidence of a difference between the two (mean difference [MD] -0.03, 95% CI -0.25 to 0.19; low-certainty evidence). No study reported data on quality of life or economic measures. Postoperative safety outcomes generally favored PR versus SB (low/very low-certainty evidence); however, there was considerable uncertainty regarding the risk of any operative ocular adverse events (RR 0.55 CI 0.28 to 1.11; 276 eyes), glaucoma (RR 0.31, 95% CI 0.01 to 7.46; 198 eyes), macular pucker (RR 0.65, 95% CI 0.20 to 2.11; 256 eyes), proliferative vitreoretinopathy (RR 0.94, 95% CI 0.30 to 2.96; 276 eyes), and persistent diplopia (RR 0.24, 95% CI 0.03 to 2.09; 256 eyes). Eyes undergoing PR experienced fewer postoperative cataract developments (RR 0.40, 95% CI 0.21 to 0.75; 153 eyes), choroidal detachments (RR 0.17, 95% CI 0.05 to 0.57; 198 eyes), and myopic shift (RR 0.03, 95% CI 0.01 to 0.10; 256 eyes).
AUTHORS' CONCLUSIONS
The current update confirms the findings of the previous review. PR may result in lower rates of reattachment and higher rates of recurrence than SB, but carries a lower burden of postoperative complications. The effects of these two procedures on other functional outcomes and quality of life remain uncertain. The available evidence remains insufficient and of low quality.
Topics: Humans; Quality of Life; Randomized Controlled Trials as Topic; Retina; Retinal Detachment; Scleral Buckling; Vitrectomy
PubMed: 34762741
DOI: 10.1002/14651858.CD008350.pub3 -
BMC Ophthalmology Mar 2023Vitiligo is a disorder characterized by loss of epidermal melanocytes, resulting in depigmented macules and patches. While the relationship between ocular pathology and...
Vitiligo is a disorder characterized by loss of epidermal melanocytes, resulting in depigmented macules and patches. While the relationship between ocular pathology and vitiligo has been demonstrated in conditions such as Vogt-Koyanagi-Harada and Alezzandrini syndromes, the ocular associations of non-syndromic vitiligo are incompletely understood. We conducted a systematic review to comprehensively describe the structural and functional changes seen in the eyes of patients with vitiligo, to identify patients at heightened risk for ocular disease, and to provide an approach to management of ocular manifestations of vitiligo. Overall, the strongest link between vitiligo and ocular pathology seems to lie with dry eye disease and pigmentary abnormalities of various ocular structures, especially the retinal pigment epithelium. Normal-tension glaucoma may also be more prevalent in the vitiligo population. The available literature did not provide conclusive evidence for increased risk of cataracts or uveitis. Aside from the impact of symptomatic dry eye disease, it seems unlikely that there are significant functional consequences of these ocular manifestations such as impaired visual acuity or visual fields.
Topics: Humans; Vitiligo; Uveomeningoencephalitic Syndrome; Eye; Uveitis; Cataract
PubMed: 36973683
DOI: 10.1186/s12886-023-02777-9 -
Journal of Current Ophthalmology 2022To determine the global prevalence and common causes of visual impairment (VI) and blindness in children. (Review)
Review
PURPOSE
To determine the global prevalence and common causes of visual impairment (VI) and blindness in children.
METHODS
In this meta-analysis, a structured search strategy was applied to search electronic databases including PubMed, Scopus, and Web of Science, as well as the list of references in the selected articles to identify all population-based cross-sectional studies that concerned the prevalence of VI and blindness in populations under 20 years of age up to January 2018, regardless of the publication date and language, gender, region of residence, or race. VI was reported based on presenting visual acuity (PVA), uncorrected visual acuity (UCVA), and best corrected visual acuity (BCVA) of equal to 20/60 or worse in the better eye. Blindness was reported as visual acuity worse than 20/400 in the better eye.
RESULTS
In the present study, 5711 articles were identified, and the final analyses were done on 80 articles including 769,720 people from twenty-eight different countries. The prevalence of VI based on UCVA was 7.26% (95% confidence interval [CI]: 4.34%-10.19%), PVA was 3.82% (95% CI: 2.06%-5.57%), BCVA was 1.67% (95% CI 0.97%-2.37%), and blindness was 0.17% (95% CI: 0.13%-0.21%). Refractive errors were the most common cause of VI in the subjects of selected articles (77.20% [95% CI: 73.40%-81.00%]). The prevalence of amblyopia was 7.60% (95% CI: 05.60%-09.10%) and congenital cataract was 0.60% (95% CI: 0.3%-0.9%).
CONCLUSION
Despite differences in the definition of VI and blindness, based on PVA, 3.82%, and based on BCVA, 1.67% of the examined samples suffer from VI.
PubMed: 35620376
DOI: 10.4103/joco.joco_135_21 -
Eye (London, England) Nov 2021To systematically review studies on refractive error after phacovitrectomy and phacoemulsification and to investigate factors associated with larger error. (Meta-Analysis)
Meta-Analysis
PURPOSE
To systematically review studies on refractive error after phacovitrectomy and phacoemulsification and to investigate factors associated with larger error.
MATERIALS AND METHODS
A literature search was performed using PUBMED and EMBASE until May 2020. The articles were included in the study if they reported data about refractive error as the difference in spherical equivalent between actual vs. target refraction in patients who underwent phacovitrectomy and phacoemulsification according to the type of biometry (ultrasound or optical). An inverse variance meta-analysis technique was used to pool errors; standard deviations (SDs), which are an expression of random error, were reported descriptively as median and range of the 95% coefficient of reproducibility (95% CR: 1.96 SD).
RESULTS
Twenty-one studies (197,353 eyes) were included. The mean error obtained using optical biometry was negligible for phacoemulsification (0.04 D, 95% CI: -0.04 to 0.12; 8 studies, 587 eyes) and was consistent with larger datasets using mixed biometric methods (0.02, 95% CI -0.07 to 0.04; 5 studies, 194,522 eyes). A trend towards hyperopia was found with ultrasound biometry after phacoemulsification (+0.21 D, 0.00-0.42 D; 7 studies, 394 eyes). Mean error after phacovitrectomy was clinically insignificant with optical biometry (-0.10 D, -0.22 to 0.02;, 8 studies, 453 eyes), and) and a mild myopic shift was possible with ultrasound biometry (-0.39 D, 95% CI: -0.68 to -0.09 D; 6 studies, 529 eyes). The 95% CR was greater and more variable with ultrasound biometry in patients who underwent phacovitrectomy (median 1.75 D, range 0.47-2.5) while it was consistent and lower with optical biometry in patients who underwent phacoemulsification (median 0.96 D, range 0.60-1.2]).
CONCLUSIONS
Phacovitrectomy causes a mild myopic shift compared to phacoemulsification, which is clinically relevant only with ultrasound biometry. Furthermore, our review provides estimates of fixed and random error for postoperative vs. target spherical equivalent as a continuous variable, that is easy to use as benchmark for quality assurance.
Topics: Benchmarking; Biometry; Cataract; Humans; Lens Implantation, Intraocular; Lenses, Intraocular; Refractive Errors; Reproducibility of Results; Retina; Vitrectomy
PubMed: 33420421
DOI: 10.1038/s41433-020-01381-1 -
The Cochrane Database of Systematic... Jun 2023Cataract is the leading cause of blindness in the world and, as such, cataract surgery is one of the most commonly performed operations globally. Surgical techniques... (Review)
Review
BACKGROUND
Cataract is the leading cause of blindness in the world and, as such, cataract surgery is one of the most commonly performed operations globally. Surgical techniques have changed dramatically over the past half century with associated improvements in outcomes and safety. Femtosecond lasers can be used to perform the key steps in cataract surgery, such as corneal incisions, lens capsulotomy and fragmentation. The potential advantage of femtosecond laser-assisted cataract surgery (FLACS) is greater precision and reproducibility of these steps compared to manual techniques. The disadvantages are the costs associated with FLACS technology.
OBJECTIVES
To compare the effectiveness and safety of FLACS with standard ultrasound phacoemulsification cataract surgery (PCS) by gathering evidence from randomised controlled trials (RCTs).
SEARCH METHODS
We searched the Cochrane Central Register of Controlled Trials (CENTRAL; which contains the Cochrane Eyes and Vision Trials Register; 2022, Issue 5); Ovid MEDLINE; Ovid Embase; LILACS; the ISRCTN registry; ClinicalTrials.gov; the WHO ICTRP and the US Food and Drug Administration (FDA) website. We did not use any date or language restrictions in the electronic searches for trials. We last searched the electronic databases on 10 May 2022.
SELECTION CRITERIA
We included RCTs where FLACS was compared to PCS.
DATA COLLECTION AND ANALYSIS
Three review authors independently screened the search results, assessed risk of bias and extracted data using the standard methodological procedures expected by Cochrane. The primary outcome for this review was intraoperative complications in the operated eye, namely anterior capsule, and posterior capsule tears. The secondary outcomes included corrected distance visual acuity (CDVA), quality of vision (as measured by any validated patient-reported outcome measure (PROM)), postoperative cystoid macular oedema complications, endothelial cell loss and cost-effectiveness. We assessed the certainty of the evidence using GRADE.
MAIN RESULTS
We included 42 RCTs conducted in Europe, North America, South America and Asia, which enrolled a total of 7298 eyes of 5831 adult participants. Overall, the studies were at unclear or high risk of bias. In 16 studies the authors reported financial links with the manufacturer of the laser platform evaluated in their studies. Thirteen of the studies were within-person (paired-eye) studies with one eye allocated to one procedure and the other eye allocated to the other procedure. These studies were reported ignoring the paired nature of the data. There was low-certainty evidence of little or no difference in the odds of developing anterior capsular tears when comparing FLACS and PCS (Peto odds ratio (OR) 0.83, 95% confidence interval (CI) 0.40 to 1.72; 5835 eyes, 27 studies) There was one fewer anterior capsule tear per 1000 operations in the FLACS group compared with the PCS group (95% CI 4 fewer to 3 more). There was low-certainty evidence of lower odds of developing posterior capsular tears with FLACS compared to PCS (Peto OR 0.50, 95% CI 0.25 to 1.00; 5767 eyes, 26 studies). There were four fewer posterior capsule tears per 1000 operations in the FLACS group compared with the PCS group (95% CI 6 fewer to same). There was moderate-certainty evidence of a very small advantage for the FLACS arm with regard to CDVA at six months or more follow-up, (mean difference (MD) -0.01 logMAR, 95% CI -0.02 to 0.00; 1323 eyes, 7 studies). This difference is equivalent to 1 logMAR letter between groups and is not thought to be clinically important. From the three studies (1205 participants) reporting a variety of PROMs (Cat-PROMS, EQ-5D, EQ-SD-3L, Catquest9-SF and patient survey) up to three months following surgery, there was moderate-certainty evidence of little or no difference in the various parameters between the two treatment arms. There was low-certainty evidence of little or no difference in the odds of developing cystoid macular oedema when comparing FLACS and PCS (Peto OR 0.84, 95% CI 0.56 to 1.28; 4441 eyes, 18 studies). There were three fewer cystoid macular oedema cases per 1000 operations in the FLACS group compared with the PCS group (95% CI 10 fewer to 6 more). In one study the incremental cost-effectiveness ratio (ICER) (cost difference divided by quality-adjusted life year (QALY) difference) was GBP £167,620 when comparing FLACS to PCS. In another study, the ICER was EUR €10,703 saved per additional patient who had treatment success with PCS compared to FLACS. Duration ranged from three minutes in favour of FLACS to eight minutes in favour of PCS (I = 100%, 11 studies) (low-certainty evidence). There was low-certainty evidence of little or no important difference in endothelial cell loss when comparing FLACS with PCS (MD 12 cells per mm in favour of FLACS, 95% CI -40 to 64; 1512 eyes, 10 studies). AUTHORS' CONCLUSIONS: This review of 42 studies provides evidence that there is probably little or no difference between FLACS and PCS in terms of intraoperative and postoperative complications, postoperative visual acuity and quality of life. Evidence from two studies suggests that FLACS may be the less cost-effective option. Many of the included studies only investigated very specific outcome measures such as effective phacoemulsification time, endothelial cell count change or aqueous flare, rather than those directly related to patient outcomes. Standardised reporting of complications and visual and refractive outcomes for cataract surgery would facilitate future synthesis, and guidance on this has been recently published.
Topics: Humans; Phacoemulsification; Macular Edema; Cataract Extraction; Cataract; Lasers
PubMed: 37369549
DOI: 10.1002/14651858.CD010735.pub3 -
Journal of Contemporary Brachytherapy Jun 2021The aim of this study was to evaluate the efficacy and vision-threatening complications of brachytherapy with ruthenium-106 (Ru) plaque to treat uveal melanoma. (Review)
Review
PURPOSE
The aim of this study was to evaluate the efficacy and vision-threatening complications of brachytherapy with ruthenium-106 (Ru) plaque to treat uveal melanoma.
MATERIAL AND METHODS
A literature review was performed based on results from searching PubMed, Embase, Web of Science, Scopus, and Cochrane databases, using the following key words: "choroidal melanoma", "uveal melanoma", "brachytherapy", and "ruthenium-106". We included studies performed on more than 30 patients since 1986, reporting on local control rate, complications rate, mean radiation dose, and mean tumor thickness. The cumulative analysis was performed using Metaprop command of Stata v.16, and meta-regression was conducted based on mean tumor thickness and mean radiation dose to tumor's apex.
RESULTS
Twenty-one retrospective studies were selected, involving 3,913 patients treated primarily with Ru plaque brachytherapy. The range of radiation dose to tumor apex was from 70 Gy to 250 Gy. The local control rate following brachytherapy ranged from 59% to 98%, and the overall weighted mean of local control was 84%. However, the heterogeneity between studies' reports was remarkable ( = 95.40%). Meta-regression based on tumor thickness and mean dose of radiation to the apex showed that the studies' heterogeneity was minimally related to the difference in mean tumor size ( = 92%). The correlation between larger tumor size and lower local control rate was statistically significant (-value = 0.024). There was no significant correlation between the mean radiation dose and local control rate (-value = 0.679). The most commonly reported complications were cataract and radiation-related retinopathy.
CONCLUSIONS
Although the studies' heterogeneity was high, in a prescription dose ranging from 70 Gy to 250 Gy to the tumor apex, Ru brachytherapy seems to be successful in local control of uveal melanoma. The efficacy of Ru in controlling uveal melanomas decreased with the increase in tumor thickness. However, these outcomes should be verified in randomized comparative studies.
PubMed: 34122577
DOI: 10.5114/jcb.2021.106191 -
Frontiers in Medicine 2021To evaluate whether dry eye deteriorates after phacoemulsification cataract surgery, and to explore the influential factors. Studies published before February 2020...
To evaluate whether dry eye deteriorates after phacoemulsification cataract surgery, and to explore the influential factors. Studies published before February 2020 indexed on PubMed and the Cochrane Central Register of Controlled Trials were retrieved. A meta-analysis, including meta-regression, a sensitivity analysis, and a subgroup analysis, were performed. Twenty studies with 2,247 eyes were included in the meta-analysis, dry eye-related parameters were investigated preoperatively and 1 month postoperatively. Patients with pre-existing meibomian gland dysfunction (MGD) had worsened subjective symptoms of dry eye (1.31, 95% confidence interval (CI) [0.66, 1.95], < 0.0001), a reduced tear break-up time (BUT) (-2.27, 95% CI [-2.66, -1.88], < 0.0001), and a worse corneal fluorescein staining (CFS) score (0.75, 95% CI [0.5, 1.0], < 0.0001) after phacoemulsification cataract surgery, whereas in the general population, the subjective symptoms score and CFS remained unchanged and BUT decreased slightly after surgery. Patients without diabetes showed significantly reduced total tear secretion after phacoemulsification cataract surgery (-1.25, 95% CI [-1.62, -0.88], < 0.0001). Dry eye generally remained unchanged 1 month after phacoemulsification cataract surgery. Notably, worsened symptoms and signs of dry eye were observed more frequently in patients with pre-existing MGD. Patients without diabetes were more susceptible to reduced tearing postoperatively. Identifier: PERSPERO (2020: CRD42020203316).
PubMed: 34307395
DOI: 10.3389/fmed.2021.649030 -
Frontiers in Medicine 2023Many eye diseases, such as diabetic retinopathy (DR), age-related macular degeneration (AMD), and cataracts are preventable and treatable with lifestyle. The objective...
Many eye diseases, such as diabetic retinopathy (DR), age-related macular degeneration (AMD), and cataracts are preventable and treatable with lifestyle. The objective of this review is to assess the most recent research on the ideal dietary approach to prevent or support the treatment of DR, AMD, and cataracts, as well as to construct a food pyramid that makes it simple for people who are at risk of developing these pathologies to decide what to eat. The food pyramid presented here proposes what should be consumed every day: 3 portions of low glycemic index (GI) grains (for fiber and zinc content), 5 portions (each portion: ≥200 g/day) of fruits and vegetables (spinach, broccoli, zucchini cooked, green leafy vegetables, orange, kiwi, grapefruit for folic acid, vitamin C, and lutein/zeaxanthin content, at least ≥42 μg/day, are to be preferred), extra virgin olive (EVO) oil (almost 20 mg/day for vitamin E and polyphenols content), nuts or oil seeds (20-30 g/day, for zinc content, at least ≥15.8 mg/day); weekly: fish (4 portions, for omega-3 content and eicosapentaenoic acid (EPA) + docosahexaenoic acid (DHA) 0.35-1.4 g/day), white meat (3 portions for vitamin B12 content), legumes (2 portions for vegetal proteins), eggs (2 portions for lutein/zeaxanthin content), light cheeses (2 portions for vitamin B6 content), and almost 3-4 times/week microgreen and spices (saffron and curcumin). At the top of the pyramid, there are two pennants: one green, which indicates the need for personalized supplementation (if daily requirements cannot be met through diet, omega-3, and L-methylfolate supplementation), and one red, which indicates that certain foods are prohibited (salt and sugar). Finally, 3-4 times per week, 30-40 min of aerobic and resistance exercises are required.
PubMed: 37324128
DOI: 10.3389/fmed.2023.1168560