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Dystonia (Lausanne, Switzerland) 2022Blepharospasm is a type of dystonia where the diagnosis is often delayed because its varied clinical manifestations are not well recognized. The purpose of this study...
OBJECTIVE
Blepharospasm is a type of dystonia where the diagnosis is often delayed because its varied clinical manifestations are not well recognized. The purpose of this study was to provide a comprehensive picture of its clinical features including presenting features, motor features, and non-motor features.
METHODS
This was a two-part study. The first part involved a systematic literature review that summarized clinical features for 10,324 cases taken from 41 prior reports. The second part involved a summary of clinical features for 884 cases enrolled in a large multicenter cohort collected by the Dystonia Coalition investigators, along with an analysis of the factors that contribute to the spread of dystonia beyond the periocular region.
RESULTS
For cases in the literature and the Dystonia Coalition, blepharospasm emerged in the 50s and was more frequent in women. Many presented with non-specific motor symptoms such as increased blinking (51.9%) or non-motor sensory features such as eye soreness or pain (38.7%), photophobia (35.5%), or dry eyes (10.7%). Non-motor psychiatric features were also common including anxiety disorders (34-40%) and depression (21-24%). Among cases presenting with blepharospasm in the Dystonia Coalition cohort, 61% experienced spread of dystonia to other regions, most commonly the oromandibular region and neck. Features associated with spread included severity of blepharospasm, family history of dystonia, depression, and anxiety.
CONCLUSIONS
This study provides a comprehensive summary of motor and non-motor features of blepharospasm, along with novel insights into factors that may be responsible for its poor diagnostic recognition and natural history.
PubMed: 36248010
DOI: 10.3389/dyst.2022.10359 -
The Journal of Headache and Pain Mar 2022Vaccines against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) are used to reduce the risk of developing Coronavirus Disease 2019 (COVID-19). Despite the... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Vaccines against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) are used to reduce the risk of developing Coronavirus Disease 2019 (COVID-19). Despite the significant benefits in terms of reduced risk of hospitalization and death, different adverse events may present after vaccination: among them, headache is one of the most common, but nowadays there is no summary presentation of its incidence and no description of its main features.
METHODS
We searched PubMed and EMBASE covering the period between January 1 2020 and August 6, 2021, looking for record in English and with an abstract and using three main search terms (with specific variations): COVID-19/SARS-CoV-2; Vaccination; headache/adverse events. We selected manuscript including information on subjects developing headache after injection, and such information had to be derived from a structured form (i.e. no free reporting). Pooled estimates and 95% confidence intervals were calculated. Analyses were carried out by vaccine vs. placebo, by first vs. second dose, and by mRNA-based vs. "traditional" vaccines; finally, we addressed the impact of age and gender on post-vaccine headache onset.
RESULTS
Out of 9338 records, 84 papers were included in the review, accounting for 1.57 million participants, 94% of whom received BNT162b2 or ChAdOx1. Headache was generally the third most common AE: it was detected in 22% (95% CI 18-27%) of subjects after the first dose of vaccine and in 29% (95% CI 23-35%) after the second, with an extreme heterogeneity. Those receiving placebo reported headache in 10-12% of cases. No differences were detected across different vaccines or by mRNA-based vs. "traditional" ones. None of the studies reported information on headache features. A lower prevalence of headache after the first injection of BNT162b2 among older participants was shown.
CONCLUSIONS
Our results show that vaccines are associated to a two-fold risk of developing headache within 7 days from injection, and the lack of difference between vaccine types enable to hypothesize that headache is secondary to systemic immunological reaction than to a vaccine-type specific reaction. Some descriptions report onset within the first 24 h and that in around one-third of the cases, headache has migraine-like features with pulsating quality, phono and photophobia; in 40-60% of the cases aggravation with activity is observed. The majority of patients used some medication to treat headache, the one perceived as the most effective being acetylsalicylic acid.
Topics: BNT162 Vaccine; COVID-19; Headache; Humans; SARS-CoV-2; Vaccination
PubMed: 35361131
DOI: 10.1186/s10194-022-01400-4 -
Medical Hypothesis, Discovery &... 2022The coronavirus disease 2019 (COVID-19) pandemic has been the most challenging health problem in the last 2 years. Post-COVID-19 multisystem inflammatory syndrome of... (Review)
Review
BACKGROUND
The coronavirus disease 2019 (COVID-19) pandemic has been the most challenging health problem in the last 2 years. Post-COVID-19 multisystem inflammatory syndrome of children (MIS-C) is a severe post-COVID-19 complication in pediatric patients. Ocular manifestations may be the first presentation of MIS-C, wherein prompt treatment may improve outcomes. In this systematic review, we aimed to summarize the acute and sub-acute ocular manifestations in pediatric patients with laboratory-confirmed COVID-19.
METHODS
We included all online primary studies, with no language restriction and published between January 1, 2019 and November 18, 2020, reporting any acute or sub-acute ocular manifestations in children with laboratory-confirmed COVID-19. PubMed/MEDLINE was searched using the following MeSH and Emtree terms: "eye," "ophthalmologic," "ocular," "vision," "conjunctivitis," "severe acute respiratory syndrome coronavirus 2," "SARS-CoV-2," "corona," "2019-nCoV," "COVID19," and "COVID." The eligibility and quality of the selected records were assessed by two independent reviewers as per the Cochrane Handbook for Systematic Review.
RESULTS
A total of 1,192 records were identified electronically. Seven papers were extracted from the reference lists of the eligible records. Thirty-six papers met the inclusion criteria and were categorized into two subgroups according to acute or sub-acute presentation of ocular manifestations. Among 463 pediatric patients with COVID-19, 72 (15.5%) had acute ocular manifestations. There was one patient with central retinal vein occlusion and another with photophobia and diplopia associated with meningoencephalitis. Among 895 pediatric patients with post-COVID-19 MIS-C, 469 (52.4%) had ocular manifestations, which only included non-purulent conjunctivitis.
CONCLUSIONS
Ocular manifestations have been reported in less than one-fifth of pediatric patients with acute COVID-19. Furthermore, conjunctivitis was the only ocular manifestation reported in half of the patients with MIS-C, and it may be missed easily due to its non-purulent nature. During the COVID-19 pandemic, pediatricians and health workers must remain vigilant for early detection of signs of this potentially fatal post-COVID-19 inflammatory syndrome.
PubMed: 37641695
DOI: 10.51329/mehdiophthal1440 -
Frontiers in Medicine 2021To evaluate the efficacy and safety of atropine for slowing myopia progression and to investigate whether the treatment effect remains constant with continuing...
To evaluate the efficacy and safety of atropine for slowing myopia progression and to investigate whether the treatment effect remains constant with continuing treatment. Studies were retrieved from MEDLINE, EMBASE, and the Cochrane Library from their inception to May 2021, and the language was limited to English. Randomized controlled trials (RCTs) and cohort studies involving atropine in at least one intervention and placebo/non-atropine treatment in another as the control were included and subgroup analysis based on low dose (0.01%), moderate dose (0.01%-<0.5%), and high dose (0.5-1.0%) were conducted. The Cochrane Collaboration and Newcastle-Ottawa Scale were used to evaluate the quality of RCTs and cohort studies, respectively. Twelve RCTs and fifteen cohort studies involving 5,069 children aged 5 to 15 years were included. The weighted mean differences in myopia progression between the atropine and control groups were 0.73 diopters (D), 0.67 D, and 0.35 D per year for high-dose, moderate-dose, and low-dose atropine, respectively (χ = 13.76; = 0.001, = 85.5%). After removing studies that provided extreme findings, atropine demonstrated a significant dose-dependent effect on both refractive change and axial elongation, with higher dosages of atropine resulting in less myopia progression ( = 0.85; = 0.004) and less axial elongation ( = -0.94; = 0.005). Low-dose atropine showed less myopia progression (-0.23 D; = 0.005) and less axial elongation (0.09 mm, < 0.001) in the second year than in the first year, whereas in high-dose atropine more axial elongation (-0.15 mm, = 0.003) was observed. The higher dose of atropine was associated with a higher incidence of adverse effects, such as photophobia with an odds ratio (OR) of 163.57, compared with an OR of 6.04 for low-dose atropine and 8.63 for moderate-dose atropine ( = 0.03). Both the efficacy and adverse effects of atropine are dose-dependent in slowing myopia progression in children. The efficacy of high-dose atropine was reduced after the first year of treatment, whereas low-dose atropine had better efficacy in a longer follow-up period.
PubMed: 35096861
DOI: 10.3389/fmed.2021.756398 -
Frontiers in Neurology 2021By reviewing the existing clinical studies about visual snow (VS) as a symptom or as part of visual snow syndrome (VSS), we aim at improving our understanding of VSS...
By reviewing the existing clinical studies about visual snow (VS) as a symptom or as part of visual snow syndrome (VSS), we aim at improving our understanding of VSS being a network disorder. Patients with VSS suffer from a continuous visual disturbance resembling the view of a badly tuned analog television (i.e., VS) and other visual, as well as non-visual symptoms. These symptoms can persist over years and often strongly impact the quality of life. The exact prevalence is still unknown, but up to 2.2% of the population could be affected. Presently, there is no established treatment, and the underlying pathophysiology is unknown. In recent years, there have been several approaches to identify the brain areas involved and their interplay to explain the complex presentation. We collected the clinical and paraclinical evidence from the currently published original studies on VS and its syndrome by searching PubMed and Google Scholar for the term visual snow. We included original studies in English or German and excluded all reviews, case reports that did not add new information to the topic of this review, and articles that were not retrievable in PubMed or Google Scholar. We grouped the studies according to the methods that were used. Fifty-three studies were found for this review. In VSS, the clinical spectrum includes additional visual disturbances such as excessive floaters, palinopsia, nyctalopia, photophobia, and entoptic phenomena. There is also an association with other perceptual and affective disorders as well as cognitive symptoms. The studies that have been included in this review demonstrate structural, functional, and metabolic alterations in the primary and/or secondary visual areas of the brain. Beyond that, results indicate a disruption in the pre-cortical visual pathways and large-scale networks including the default mode network and the salience network. The combination of the clinical picture and widespread functional and structural alterations in visual and extra-visual areas indicates that the VSS is a network disorder. The involvement of pre-cortical visual structures and attentional networks might result in an impairment of "filtering" and prioritizing stimuli as top-down process with subsequent excessive activation of the visual cortices when exposed to irrelevant external and internal stimuli. Limitations of the existing literature are that not all authors used the ICHD-3 definition of the VSS. Some were referring to the symptom VS, and in many cases, the control groups were not matched for migraine or migraine aura.
PubMed: 34671311
DOI: 10.3389/fneur.2021.724072 -
Acta Ophthalmologica Feb 2022To systematically review the literature on the treatment of vernal keratoconjunctivitis (VKC) in children and young adults and conduct comparative efficacy analysis on...
PURPOSE
To systematically review the literature on the treatment of vernal keratoconjunctivitis (VKC) in children and young adults and conduct comparative efficacy analysis on clinical signs and symptoms using network meta-analyses.
METHODS
We systematically searched the databases PubMed/MEDLINE, EMBASE, Cochrane Central and Web of Science on 21 October 2019 for randomized controlled trials (RCT). Studies considered had patients with VKC < 20 years of age randomized into either intervention (any medical intervention) or comparator (active treatment, placebo treatment or non-treatment control), where pre-defined outcomes (data from ≥2 weeks and as close as possible to 2 months) of symptoms (itching, tearing, photophobia and foreign body sensation) and signs (hyperaemia, punctate keratitis, Horner-Trantas dots and macropapillae) were reported. Risk of bias within studies was evaluated using the Cochrane risk of bias tool. Comparisons were made using network meta-analyses.
RESULTS
We identified 39 studies with data on 2046 individuals. Twenty-three studies were eligible for quantitative analyses. None were systemic therapy. Temporal trend analysis showed that an initial focus on topical mast cell stabilizers turned to a focus on calcineurin inhibitors and a more diverse variety of pharmacological strategies. Studies varied in population, treatment duration and quality. The quantitative analysis revealed that efficacy of different therapies differed substantially across important clinical signs and symptoms, but there was a general trend of superior efficacy when using topical corticosteroids with stronger efficacy of the more potent corticosteroids.
CONCLUSION
We provide an overview of RCTs comparing the efficacy of treatments for VKC in children and young adults, which we find differs across symptoms and signs. Overall, we saw a general trend of superior efficacy with topical corticosteroids. However, our findings highlight the need for better studies, consensus on core outcomes and potential for individualized therapy.
Topics: Adult; Anti-Inflammatory Agents, Non-Steroidal; Child; Conjunctivitis, Allergic; Glucocorticoids; Humans; Immunosuppressive Agents; Network Meta-Analysis
PubMed: 33779061
DOI: 10.1111/aos.14858 -
Headache Feb 2021To review the acute migraine clinical trial literature and provide a summary of the endpoints and outcomes used in such trials.
BACKGROUND/OBJECTIVE
To review the acute migraine clinical trial literature and provide a summary of the endpoints and outcomes used in such trials.
METHOD
A systematic literature review, following a prespecified (but unregistered) protocol developed to adhere to recommendations of the Preferred Reporting Items for Systematic Reviews and Meta-Analyses, was conducted to understand endpoints and outcomes used in acute migraine clinical trials. Predefined terms were searched in PubMed to locate clinical trials assessing acute migraine treatments. Final database search was conducted on October 28, 2019. Identified publications were reviewed against established inclusion and exclusion criteria to determine eligibility. Data related to general trial design characteristics, sample characteristics, and outcomes and endpoints reported in each publication were extracted from eligible publications. Descriptive summaries of design features, sample characteristics, and the endpoints and outcomes employed across publications were constructed. Outcomes are presented within four broad categories: (a) pain-related outcomes (pain relief, pain freedom, etc.), (b) associated symptoms (nausea, photophobia, etc.), (c) disability/impairment/impact, (d) patient-reported outcome measures (PROMs, general health and migraine/headache-specific). Endpoint types were categorized within three broad categories: (a) change from baseline, (b) fixed timepoint, and (c) responder definitions (e.g., 50% reduction). This review focuses on a subset of recent (1998 or later) randomized and blinded publications evaluating drugs or medical devices.
RESULTS
Of 1567 publications found through the initial search and reference section reviews, 705 met criteria and were included for data extraction. Inter-rater agreement kappas for the descriptive variables extracted had an average kappa estimate of 0.86. The more recent, randomized and blinded pharmaceutical and medical device article subset includes 451 publications (451/705, 63.9%). The outcomes and endpoints varied substantially across trials, ranging from pain relief or freedom, freedom from or relief of migraine-associated symptoms, use of acute or rescue medication, and various other PROMs, including measures of satisfaction and quality of life. Within the recent randomized and blinded article subset, most articles examined ≥1 pain-related outcome (430/451, 95.3%). Of the publications that examined pain, outcomes most often used were pain relief (310/430, 72.1%), pain freedom (279/430, 64.9%), and headache recurrence (202/43,051, 47.0%) or rescue medication use (278/430, 64.9%). Associated symptoms such as nausea, photophobia, and phonophobia were more frequently measured (299/451, 66.3%) compared to most bothersome associated symptom (16/451, 3.5%), as it is a new addition to regulatory guidance. Over one-third of eligible publications examined disability/impairment (186/451, 41.2%) or ≥1 PROM (159/451, 35.3%). The definition of the endpoints used (e.g., change from baseline, fixed timepoint comparisons, categorization of "responders" to treatment based on wide variety of "responder definitions") also differed substantially across publications.
CONCLUSION
Acute migraine clinical trials exhibit a large amount of variability in outcomes and endpoints used, in addition to the variability in how outcomes and endpoints were used from trial-to-trial. There were some common elements across trials that align with guidance from the International Headache Society, the Food and Drug Administration and other regulatory agencies (e.g., assessing pain and associated symptoms, 2-hour post-treatment). Other aspects of acute migraine clinical trial design did not follow guidance. For example, multi-item PROMs intended to measure constructs (e.g., scales) are rarely used, the use of pain-related outcomes is inconsistent, some associated symptom assessments are idiosyncratic, and the timing of the assessment of primary endpoints is variable. The development of a core set of outcomes and endpoints for acute migraine clinical trials that are patient-centered and statistically robust could improve the conduct of individual trials, facilitate cross-trial comparisons, and better support informed treatment decisions by healthcare professionals and patients.
Topics: Acute Disease; Clinical Trials as Topic; Humans; Migraine Disorders; Outcome Assessment, Health Care
PubMed: 33611818
DOI: 10.1111/head.14067 -
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 -
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 -
The Cochrane Database of Systematic... Aug 2020Traumatic eye complaints account for 3% of all hospital emergency department visits. The most common traumatic injury to the eye is blunt trauma, which accounts for 30%... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Traumatic eye complaints account for 3% of all hospital emergency department visits. The most common traumatic injury to the eye is blunt trauma, which accounts for 30% of these visits. Blunt trauma frequently leads to traumatic iridocyclitis, thus causing anterior uveitis. Iridocyclitis frequently causes tearing, photophobia, eye pain, and vision loss. These symptoms are a result of the inflammatory processes and ciliary spasms to iris muscles and sphincter. The inflammatory process is usually managed with topical corticosteroids, while the ciliary spasm is blunted by dilating the pupils with topical mydriatic agents, an adjuvant therapy. However, the effectiveness of mydriatic agents has not been quantified in terms of reduction of ocular pain and visual acuity loss.
OBJECTIVES
To evaluate the effectiveness and safety of topical mydriatics as adjunctive therapy to topical corticosteroids for traumatic iridocyclitis.
SEARCH METHODS
We searched the Cochrane Central Register of Controlled Trials (CENTRAL) which contains the Cochrane Eyes and Vision Trials Register (2019, issue 6); Ovid MEDLINE; Embase.com; Cumulative Index to Nursing and Allied Health Literature (CINAHL) Plus; PubMed; ClinicalTrials.gov and the World Health Organization (WHO) International Clinical Trials Registry Platform (ICTRP). We did not use any date or language restrictions in the electronic search for trials. We last searched the electronic databases on 12 June 2019.
SELECTION CRITERIA
We planned to include randomized controlled trials (RCTs) that compared topical mydriatic agents in conjunction with topical corticosteroid therapy versus topical corticosteroids alone, in participants with traumatic iridocyclitis.
DATA COLLECTION AND ANALYSIS
Two review authors (JH, MK) independently screened titles and abstracts, then full-text reports, against eligibility criteria. We planned to have two authors independently extract data from included studies. We resolved differences in opinion by discussion.
MAIN RESULTS
There were no eligible RCTs that compared the interventions of interest in people with traumatic iridocyclitis.
AUTHORS' CONCLUSIONS
We did not find any evidence from RCTs about the efficacy of topical mydriatic agents as an adjunctive therapy with topical corticosteroids for treating traumatic iridocyclitis. In the absence of these types of studies, we cannot draw any firm conclusions. Controlled trials that compare the combined use of topical mydriatic agents and corticosteroid drops against standard corticosteroid drops alone, in people with traumatic iridocyclitis are required. These may provide evidence about the efficacy and risk of topical mydriatic drops as adjuvant therapy for traumatic iridocyclitis.
PubMed: 35659470
DOI: 10.1002/14651858.CD013260.pub2