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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 -
Cureus Mar 2023This systematic scoping review aims to answer questions related to the main characteristics of primary headache, the need for neuroimaging, and the presence of red flags... (Review)
Review
This systematic scoping review aims to answer questions related to the main characteristics of primary headache, the need for neuroimaging, and the presence of red flags in these patients. A review of prospective studies including the MEDLINE/PubMed, Scopus, LILACS, and SCIELO databases, as well as the grey literature, was conducted. The methodological quality of the selected investigations was also assessed. Six investigations met the selection criteria. The mean age of people with primary headache was less than 43 years, with ages ranging from 39 to 46 years. Most of the studies reported the presence of nausea/vomiting, between 12% and 60% of the patients studied. To a lesser extent, there was also the presence of intense and moderate pain, loss of consciousness, stiff neck, presence of aura, and photophobia. The most frequent diagnoses were unspecified headache, migraine, and tension headache. The studies did not recommend neuroimaging and no red flags were reported. Primary headache occurred more frequently in women, in those under 46 years of age with a history of migraine and similar episodes. Moreover, the presence of red flags and the need for neuroimaging in patients with primary headaches were not evidenced.
PubMed: 37065368
DOI: 10.7759/cureus.36131 -
Survey of Ophthalmology 2023Congenital aniridia is a rare, panocular disorder with a main phenotypic characteristic of a partial or complete absence of the iris existing alongside other ocular...
Congenital aniridia is a rare, panocular disorder with a main phenotypic characteristic of a partial or complete absence of the iris existing alongside other ocular morbidities such as cataract, keratopathy, optic nerve and foveal hypoplasia, and nystagmus. The iris abnormality, however, often leads to symptoms such as photophobia, glare, and decreased visual acuity, as well as cosmetic dissatisfaction. Current management options for the iris deficit include colored iris contact lenses, corneal tattooing, and tinted contact lenses. Symptoms arising from small iris defects can be resolved with surgical management using micro-tying suture techniques such as McCannel or Siepser. Currently, larger iris defects can be treated with artificial iris implants. New prosthetic options range from colored intraocular lenses to flexible custom-made silicone iris implants. With a range of therapeutic options available and given the challenges of multiple comorbidities in aniridia, we evaluate the literature relating to the use of artificial iris implants in congenital aniridia, with a focus on the different surgical implantation techniques, the clinical outcomes achieved, complications occurred, and risk of bias of the studies included.
Topics: Humans; Visual Acuity; Aniridia; Iris; Lenses, Intraocular; Prosthesis Implantation; Vision Disorders
PubMed: 36379301
DOI: 10.1016/j.survophthal.2022.11.001 -
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 -
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 -
Medicine Sep 2023The last few decades have witnessed an appalling rise in several emerging and re-emerging viral and zoonotic outbreaks. Amongst those emerging zoonosis, one of the...
BACKGROUND
The last few decades have witnessed an appalling rise in several emerging and re-emerging viral and zoonotic outbreaks. Amongst those emerging zoonosis, one of the diseases which is gaining popularity these days and has been declared as public health emergency of international concern by the world health organization, is human monkeypox virus (HMPX). Proper understanding of the clinical spectrum of the disease is of paramount importance for early diagnosis and treatment. In this review, we aimed to study and quantify the neurological manifestations of HMPX virus infection.
METHODS
Any study, released prior to April 13, 2023, that reported neurological manifestations in patients infected by HMPX virus were reviewed systematically on PubMed, Scopus, Google Scholar, and Cochrane Library using the PRISMA (Preferred Reporting Items for Systematic review and Meta-Analysis) statement.
RESULTS
Our systematic review included data from 22 eligible studies: 10 cohort studies, 3 cross sectional studies, one retrospective study, 5 case series, and 2 case reports. The most commonly reported neurological manifestations of HMPX were headache (48.84%), myalgia (27.50%), fatigue (17.73%), and photophobia (4.43%). Uncommonly, HMPX can also present with visual deficit (0.57%), seizure (0.34%), encephalitis (0.8%), dizziness (0.34%), encephalomyelitis (0.23%), coma (0.11%), and transverse myelitis (0.11%).
DISCUSSIONS
Monkeypox virus usually presents with self-limiting painful rash, lymphadenitis, and fever, complications like secondary skin infection, eye problems and pneumonia can be life threatening, carrying a case fatality rate of 1% to 10%. Neurological manifestations are not uncommon and can further add-on to morbidity and mortality.
Topics: Humans; Coinfection; Cross-Sectional Studies; Mpox (monkeypox); Monkeypox virus; Public Health; Retrospective Studies
PubMed: 37657009
DOI: 10.1097/MD.0000000000034664 -
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 -
Preventive Medicine Reports Feb 2024COVID-19 caused by SARS-CoV-2, commonly presents with symptoms such as fever and shortness of breath but can also affect other organs. There is growing evidence pointing... (Review)
Review
INTRODUCTION
COVID-19 caused by SARS-CoV-2, commonly presents with symptoms such as fever and shortness of breath but can also affect other organs. There is growing evidence pointing to potential eye complications. In this article, we aim to systematically review the ocular manifestations of COVID-19.
METHODS
We conducted a systematic review to explore the ocular manifestations of COVID-19. We searched online databases including PubMed, Embase, Scopus, and Web of Science up to September 4, 2023. After a two-stage screening process and applying inclusion/exclusion criteria, eligible articles were advanced to the data extraction phase. The PRISMA checklist and Newcastle-Ottawa Scale (NOS) were used for quality and bias risk assessments.
RESULTS
We selected and extracted data from 42 articles. Most of the studies were cross-sectional (n = 33), with the highest number conducted in Turkey (n = 10). The most frequent ocular manifestation was conjunctivitis, reported in 24 articles, followed by photophobia, burning, chemosis, itching, and ocular pain. Most studies reported complete recovery from these manifestations; however, one study mentioned visual loss in two patients.
CONCLUSION
In general, ocular manifestations of COVID-19 appear to resolve either spontaneously or with supportive treatments. For more severe cases, both medical treatment and surgery have been employed, with the outcomes suggesting that complete recoveries are attainable.
PubMed: 38375172
DOI: 10.1016/j.pmedr.2024.102608 -
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