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Acta Ophthalmologica Sep 2021Effectiveness of ocriplasmin for vitreomacular traction (VMT) varies depending on the presence of common ocular conditions and patient selection criteria. We carried out... (Meta-Analysis)
Meta-Analysis
PURPOSE
Effectiveness of ocriplasmin for vitreomacular traction (VMT) varies depending on the presence of common ocular conditions and patient selection criteria. We carried out a systematic literature review and meta-analysis of ocriplasmin studies conducted in real-world settings (RWS) and compared outcomes with those from randomized controlled trials (RCTs).
METHODS
We included prospective and retrospective studies from RWS documenting effectiveness of ocriplasmin in patients with VMT with or without MH, and RCTs of ocriplasmin versus control. Key end-points were vitreomacular adhesion resolution (VMAR), nonsurgical MH closure, need for vitrectomy and safety. We conducted meta-regression on pooled results to evaluate effects of baseline covariates and study design on outcomes.
RESULTS
Thirty RWS (2402 patients) and 5 RCTs (737 patients) were included epiretinal membrane (ERM) and broad VMA were more prevalent in RCTs. Primary VMAR, vitrectomy and MH closure rates were comparable between RWS and RCTs. Rates of nsVMAR were significantly higher in RWS than RCTs (odds ratio 1.66; 95% confidence interval [CI]: 1.18-2.34). nsVMAR rates were inversely associated with ERM prevalence (odds ratio 0.20; 95% CI: 0.08-0.51). Compared with the recent OASIS trial, RWS reported a higher incidence of new/worsening subretinal fluid cases and less photophobia, photopsia, vitreous floaters, electroretinogram abnormalities and MH progression.
CONCLUSIONS
Ocriplasmin was significantly more effective in achieving nsVMAR in RWS than in RCTs. Lower ERM prevalence in RWS was the single significant explanatory variable for this difference. Conclusions on ocriplasmin safety in RWS are limited due to inconsistent reporting.
Topics: Fibrinolysin; Humans; Intravitreal Injections; Peptide Fragments; Randomized Controlled Trials as Topic; Retinal Diseases; Tomography, Optical Coherence; Visual Acuity
PubMed: 33369248
DOI: 10.1111/aos.14686 -
European Journal of Ophthalmology Feb 2024To estimate the effect of atropine eyedrops at different concentrations for myopia control in children. (Review)
Review
PURPOSE
To estimate the effect of atropine eyedrops at different concentrations for myopia control in children.
METHODS
We conducted a Bayesian random-effects network meta-analysis based on randomized controlled trials (RCT). Primary outcomes include changes in spherical equivalent error (SER) and changes in axial length (AL), mean difference (MD) together with 95% credible interval (CrI) were used to evaluate the efficacy.
RESULTS
28 RCTs (6608 children) were included in this review. Comparing ten atropine eyedrops (0.0025%, 0.005%, 0.01%, 0.02%, 0.025%, 0.05%, 0.1%, 0.25%, 0.5% and 1% concentrations) with the placebo, the MDs and 95%CrIs of changes in SER are -0.006 (-0.269, 0.256) D, 0.216 (-0.078, 0.508) D, 0.146 (0.094, 0.199) D, 0.167 (0.039, 0.297) D, 0.201 (0.064, 0.341) D, 0.344 (0.251, 0.440) D, 0.255 (0.114, 0.396) D, 0.296 (0.140, 0.452) D, 0.331 (0.215, 0.447) D, and 0.286 (0.195, 0.337) D, respectively. The MDs and 95%CrIs of changes in AL are -0.048 (-0.182, 0.085) mm, -0.078 (-0.222, 0.066) mm, -0.095 (-0.130, -0.060) mm, -0.096 (-0.183, -0.009) mm, -0.083 (-0.164, -0.004) mm, -0.114 (-0.176, -0.056) mm, -0.134 (-0.198, -0.032) mm, -0.174 (-0.315, -0.061) mm, -0.184 (-0.291, -0.073) mm, and -0.171 (-0.203, -0.097) mm, respectively.Whether evaluated by SER or AL, 1% concentration ranks first in efficacy, but the risk of photophobia is 17 times higher than 0.01% concentration.
CONCLUSIONS
0.01% or higher concentration atropine eyedrops are effective for myopia control, while 0.0025% and 0.005% concentrations may not. As the concentration increases, the effect tends to increase, 1% concentration may have the strongest effect.
PubMed: 38377951
DOI: 10.1177/11206721241229317 -
CNS Drugs May 2020Ubrogepant is a small molecular calcitonin gene-related peptide receptor antagonist that is used for the acute treatment of migraine. (Meta-Analysis)
Meta-Analysis
BACKGROUND
Ubrogepant is a small molecular calcitonin gene-related peptide receptor antagonist that is used for the acute treatment of migraine.
OBJECTIVE
The aim was to conduct a meta-analysis to systematically evaluate the efficacy and safety of ubrogepant for the treatment of episodic migraine compared with placebo in the adult population.
METHODS
We systematically searched PubMed, EMBASE, and the Cochrane Library Central Register of Controlled Trials for relevant randomized clinical trials, from the earliest available date to November 10, 2019, to evaluate the efficacy and safety of short-term ubrogepant use. Inclusion criteria were (1) randomized clinical trial; (2) enrolled adult participants diagnosed with episodic migraine; (3) compared ubrogepant with placebo at doses that were evaluated in phase III clinical trials; (4) enrolled more than 100 patients in each group; and (5) provided any information on primary or secondary outcomes. Trials were excluded if their participants were diagnosed with chronic migraine.
RESULTS
A total of three multicenter, randomized clinical trials with 3326 patients were included. Ubrogepant use was associated with a significantly higher percentage of patients with pain freedom (ubrogepant 20.8%; placebo 12.6%; relative risk [RR] 1.65, 95% confidence interval [CI] 1.38-1.98) and absence of the most bothersome migraine-associated symptoms (ubrogepant 37.3%; placebo 27.6%; RR 1.35, 95% CI 1.20-1.53) at 2 h post-dose compared with placebo. Ubrogepant increased the rate of absence of migraine-associated symptoms at 2 h post-dose compared with placebo (photophobia: RR 1.30 [95% CI 1.18-1.44], I = 49%; phonophobia: RR 1.20 [95% CI 1.11-1.29]; nausea: RR 1.07 [95% CI 1.02-1.13]), and patients were more likely to function normally at 2 h post-dose compared with placebo (RR 1.30 [95% CI 1.16-1.45]). No significant difference was found for treatment-related adverse events within 48 h or 30 days for ubrogepant compared with placebo (48 h: RR 1.07 [95% CI 0.85-1.35]; 30 days: RR 1.03 [95% CI 0.79-1.34]). Subgroup analysis demonstrated that compared to placebo, ubrogepant led to greater rates of freedom from pain at 2 h with 25-mg, 50-mg, and 100-mg doses and absence of the most bothersome symptoms with 50-mg and 100-mg doses.
CONCLUSIONS
The use of ubrogepant as an acute treatment of episodic migraine in adults led to a greater percentage of freedom from pain and absence of the most bothersome symptoms at 2 h post-dose. Short-term use of ubrogepant was not related to an increased risk for adverse events. Further studies are needed to evaluate efficacy and safety for long-term use and in specific subgroups of patients.
Topics: Adult; Calcitonin Gene-Related Peptide Receptor Antagonists; Humans; Migraine Disorders; Pyridines; Pyrroles; Randomized Controlled Trials as Topic
PubMed: 32193827
DOI: 10.1007/s40263-020-00715-7 -
European Journal of Medical Genetics Oct 2023Autosomal recessive keratitis-ichthyosis-deafness syndrome (KIDAR MIM #242150) is a very rare disorder caused by pathogenic loss-of-function variants in the AP1B1 gene....
Autosomal recessive keratitis-ichthyosis-deafness syndrome (KIDAR MIM #242150) is a very rare disorder caused by pathogenic loss-of-function variants in the AP1B1 gene. So far, nine patients have been reported in the literature and more clinical descriptions are essential to further delineate the phenotype of KIDAR. Here we report a new patient with KIDAR and compare the clinical findings with those from the other published cases with molecular confirmation. We describe a 14-year-old male born to non-consanguineous parents with unremarkable family history. The patient had fetal ascites, neonatal pancreatic insufficiency with consequent failure to thrive, feeding difficulties, recurrent infections and sepsis. The skin examination was remarkable for an ichthyosis with conspicuous palmoplantar keratoderma, sparse and brittle hair with alopecia on the vertex and slight bilateral ectropion. He had short stature, thin build, frontal bossing, small teeth and prominent abdomen. Additional features were congenital profound bilateral sensorineural deafness, photosensitivity and photophobia. Mild global developmental delay was noted. Persistent mild anemia, neutropenia, thrombocytopenia, and low serum copper, ceruloplasmin and growth hormone were also present. Brain magnetic resonance imaging (MRI) showed cerebral atrophy and thin corpus callosum. Genetic testing revealed a homozygous deletion in the AP1B1 gene, possibly including the same exons as a previously reported deletion. Comparing the phenotypes of all reported individuals, they are highly concordant and major features are enteropathy with feeding difficulties, failure to thrive, ichthyosis, palmoplantar keratoderma, sensorineural deafness and sparse and brittle hair. Here we report other features present in more than one patient that could be part of the phenotypic spectrum and suggest copy number variation analysis to be performed alongside sequencing of the AP1B1 gene in case of suspicion.
PubMed: 37657632
DOI: 10.1016/j.ejmg.2023.104827 -
The International Journal of... Jun 2024The efficacy of ubrogepant 50 mg versus 100 mg daily for migraine remained controversial. We conducted a systematic review and meta-analysis to compare the efficacy... (Meta-Analysis)
Meta-Analysis
The efficacy of ubrogepant 50 mg versus 100 mg daily for migraine remained controversial. We conducted a systematic review and meta-analysis to compare the efficacy and safety of ubrogepant 50 mg versus 100 mg daily on treatment in migraine patients. We have searched PubMed, EMbase, Web of science, EBSCO, Cochrane library databases and SCOPUS through 21 March 2022 for randomized controlled trials (RCTs) assessing the effect of ubrogepant 50 mg versus 100 mg on treatment efficacy in migraine patients. This meta-analysis was performed using the random-effect model. Three RCTs were included in the meta-analysis. Overall, compared with ubrogepant 100 mg in migraine patients, ubrogepant 50 mg obtained comparable pain freedom at 2 h (OR = 0.86; 95% CI = 0.64-1.15; = 0.310), sustained pain freedom 2-24 h (OR = 0.76; 95% CI = 0.54-1.07; = 0.110), photophobia absence at 2 h (OR = 0.80; 95% CI = 0.63-1.02; = 0.070), phonophobia absence at 2 h (OR = 1.07; 95% CI = 0.82-1.40; = 0.620) and nausea absence at 2 h (OR = 1.02; 95% CI = 0.79-1.32; = 0.880). In terms of safety, adverse events were found to be increased in ubrogepant 100 mg as compared to ubrogepant 50 mg (OR = 0.81; 95% CI = 0.67-0.99; = 0.040), and there was no statistical difference of serious adverse events between two groups (OR = 0.87; 95% CI = 0.40-1.91; = 0.720). Ubrogepant 50 mg and 100 mg may be equally effective to alleviate migraine, but ubrogepant 100 mg led to increase incidence of adverse events.
Topics: Humans; Migraine Disorders; Nausea; Pain; Pyridines; Pyrroles; Treatment Outcome
PubMed: 35999672
DOI: 10.1080/00207454.2022.2090351 -
CNS & Neurological Disorders Drug... Jun 2024Recently, US Food and Drug Administration (FDA) has approved calcitonin gene-related peptide receptor antagonists (rimegepant, and ubrogepant), and selective serotonin... (Meta-Analysis)
Meta-Analysis
Safety and Efficacy of Calcitonin Gene-related Peptide Receptor Antagonists and Selective Serotonin Receptor Agonist in the Management of Migraine: A Systematic Review and Meta-analysis.
BACKGROUND
Recently, US Food and Drug Administration (FDA) has approved calcitonin gene-related peptide receptor antagonists (rimegepant, and ubrogepant), and selective serotonin receptor agonists (lasmiditan) in the management of migraine. However, the exact safety and efficacy profile of these drugs is unclear so far.
METHODS
The study's primary objective was to determine the exact safety and efficacy profile. The overall estimate was calculated in terms of risk ratios using a suitable model. The subgroup analysis was also performed to check the effect of individual drugs on the outcome, whereas sensitivity analysis was performed to check the effects of outliers on the outcome. All the analyses were performed using Rev Man 5. The drugs have shown significant improvement in efficacy parameters (pain freedom, most bothersome symptoms, phonophobia, nausea, and photophobia).
RESULTS
The subgroup analysis results have shown significant improvement in all efficacy parameters in the rimegepant and ubrogepant groups. The effect of ubrogepant on safety parameters was found to be non-significant, indicating a better safety profile of ubrogepant than lasmiditan.
CONCLUSION
The sensitivity analysis results have shown no effect of outliers on the efficacy parameters. Based on the available evidence, recently approved drugs are effective in the treatment of migraine, however, associated with few adverse drug reactions.
PubMed: 38847252
DOI: 10.2174/0118715273304677240529062909 -
Advances in Therapy Dec 2020Use of triptans for acute treatment of migraine is associated with insufficient efficacy and/or tolerability in approximately 30-40% of people. We conducted a systematic...
INTRODUCTION
Use of triptans for acute treatment of migraine is associated with insufficient efficacy and/or tolerability in approximately 30-40% of people. We conducted a systematic literature review (SLR) to synthesize definitions, terminology, subsequent treatment outcomes, and characteristics associated with this subpopulation.
METHODS
A comprehensive SLR was conducted to identify studies, published from Jan 1995 to May 2019, which focused on insufficient efficacy and/or tolerability to triptans.
RESULTS
Thirty-five publications were identified, of which 22 described randomized controlled trials and open-label studies, and 13 described observational studies. Across studies, multiple objectives and a high amount of variability in methodologies and outcomes were noted. The most commonly applied measures of efficacy were headache pain freedom and pain relief at 2 h. Ten studies assessed efficacy of switching or optimizing treatment in patients with historical insufficient efficacy or tolerability to previous triptan treatment and demonstrated varying levels of success. Factors associated with increased risk of triptan insufficient efficacy included severe baseline headache severity, photophobia, phonophobia, nausea, and depression.
CONCLUSIONS
Irrespective of the methodology or definition used to identify people with insufficient efficacy and/or tolerability to triptans, study results support the assertion that a high unmet need remains for effective acute treatment of migraine.
Topics: Administration, Oral; Adult; Female; Humans; Male; Middle Aged; Migraine Disorders; Nausea; Pain Management; Randomized Controlled Trials as Topic; Serotonin Receptor Agonists; Severity of Illness Index; Treatment Outcome; Tryptamines
PubMed: 32990921
DOI: 10.1007/s12325-020-01494-9 -
Headache Jun 2024Hemicrania continua is a primary unilateral headache characterized by ipsilateral parasympathetic and sympathetic autonomic features. A key diagnostic criterion is its... (Review)
Review
BACKGROUND
Hemicrania continua is a primary unilateral headache characterized by ipsilateral parasympathetic and sympathetic autonomic features. A key diagnostic criterion is its dramatic response to indomethacin treatment; however, various vascular or structural abnormalities have been reported to cause secondary hemicrania continua, presenting with clinical features similar to those of the primary headache presentation.
OBJECTIVE
We reviewed the literature to compile secondary hemicrania continua cases, highlighting the importance of imaging during the evaluation. Additionally, we also contributed our three cases to the existing studies.
METHODS
We conducted a review of articles from the PubMed and EMBASE databases that described reported cases of secondary hemicrania continua, covering the period from 1993 to 2021. Our review included detailed patient information, signs, and symptoms of hemicrania continua, as well as information on indomethacin usage and headache resolution (if pertinent).
RESULTS
Secondary hemicrania continua can result from a remarkably diverse range of structural and vascular lesions, yet clinical reports on long-term follow-up are lacking. Notably, cases may exhibit a classical response to indomethacin, emphasizing the importance of neuroimaging in excluding secondary cases. Our search yielded 41 cases meeting our criteria. We excluded six cases that were not treated with indomethacin or were unresponsive to it. Additionally, we present three cases that highlight the necessity of neuroimaging in evaluating hemicrania continua, along with short- and long-term clinical outcomes following indomethacin and lesion-directed treatments. Case 1 presented with daily right-sided headaches and cranial autonomic symptoms. Her pain completely resolved with indomethacin use. Neuroimaging of the brain revealed a laterally directed saccular aneurysm of the right internal carotid artery. Case 2 presented with continuous left-sided unilateral headaches with superimposed exacerbations. She complained of left-sided photophobia with a dull sensation in the left ear. Her symptoms decreased after 2 weeks of indomethacin use. Neuroimaging of the head indicated a benign tumor with mass effect into the left lateral medulla and inferior cerebellar peduncle. Case 3 presented with a right side-locked headache with daily, severe superimposed exacerbations. She had photophobia in the right eye and a right-sided Horner's syndrome, along with tearing during her exacerbations. Neuroimaging of the brain revealed a pituitary tumor and her pain completely resolved with indomethacin.
CONCLUSION
Hemicrania continua is a rare headache disorder that can be either primary or secondary. Importantly, response to indomethacin can still occur in secondary hemicrania continua. Thus, neuroimaging should be considered to rule out underlying structural etiology in all cases, regardless of their clinical responsiveness to indomethacin therapy.
Topics: Female; Humans; Anti-Inflammatory Agents, Non-Steroidal; Indomethacin; Neuroimaging
PubMed: 38780233
DOI: 10.1111/head.14728 -
Arquivos Brasileiros de Oftalmologia Sep 2019This systematic review aimed to assess the effectiveness of using preservative-free artificial tears versus preserved lubricants for the treatment of dry eyes in... (Meta-Analysis)
Meta-Analysis
This systematic review aimed to assess the effectiveness of using preservative-free artificial tears versus preserved lubricants for the treatment of dry eyes in Universidade Federal de Alagoas (PROSPERO 2018 CRD42018089933). Online databases were searched (LILACS, EMBASE, MEDLINE, and CENTRAL) from inception to April 2018; references from included papers were also searched. The following keywords were used: lubricants OR artificial tears OR artificial tears, lubricants AND dry eye OR dry eye syndrome OR syndromes, dry eye OR dry eyes. Among the 2028 electronic search results, 29 full papers were retrieved and four were considered relevant. The number of participants from these studies ranged from 15 to 76. Meta-analysis was possible for the following outcomes: score of symptoms according to the Ocular Surface Disease Index - Allergan (OSDI), tear secretion rate using the Schirmer test, tear evaporation rate using the tear film breakup time test, burning, foreign body sensation, and photophobia. No statistically significant difference was observed between the two groups, and no side effects were attributed to the interventions. Evidence proving that preservative-free artificial tears are more effective than preserved artificial tears is lacking.
Topics: Bias; Dry Eye Syndromes; Female; Humans; Lubricant Eye Drops; Male; Ophthalmic Solutions; Preservatives, Pharmaceutical; Tears
PubMed: 31508669
DOI: 10.5935/0004-2749.20190097