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Frontiers in Immunology 2024The objective of this study is to evaluate the risk of secondary autoimmune diseases in multiple sclerosis (MS) patients treated with alemtuzumab (ALZ) through a... (Meta-Analysis)
Meta-Analysis
BACKGROUND AND PURPOSE
The objective of this study is to evaluate the risk of secondary autoimmune diseases in multiple sclerosis (MS) patients treated with alemtuzumab (ALZ) through a meta-analysis.
METHODS
PubMed, Web of Science, OVID, EMBASE, and Cochrane central register of controlled trials were searched. Information and data were screened and extracted by 2 researchers. The obtained data were analyzed using the R software meta package. Quality assessment was conducted using the Newcastle-Ottawa Scale (NOS). The causes of heterogeneity were analyzed using subgroup analysis and sensitivity analysis. Publication bias was evaluated using funnel plots and Egger's test.
RESULTS
The search retrieved a total of 3530 papers from the databases. After screening, a total of 37 studies were included in the meta-analysis. The analysis results indicate that the pooled incidence rate of overall secondary autoimmune events (SAEs) in the included studies was 0.2824 [0.2348, 0.3300] (I²=94%, p<0.01). The overall incidence of autoimmune thyroid events (ATE) was 0.2257 [0.1810, 0.2703] (I²=94%, p<0.01). Among them, the rate of serious autoimmune thyroid events (SATE) was 0.0541 [0.0396, 0.0687] (I²=0%, p=0.44). The incidence rates of different thyroid events were as follows: Graves' disease (GD), 0.2266 [0.1632, 0.2900] (I²=83%, p<0.01); Hashimoto thyroiditis (HT), 0.0844 [0.0000, 0.2262] (I²=81%, p=0.02); Hashimoto thyroiditis with hypothyroidism (HTwH), 0.0499 [0.0058, 0.0940] (I²=37%, p=0.21); fluctuating thyroid dysfunction (FTD), 0.0219 [0.0015, 0.0424] (I²=0%, p=0.40); transient thyroiditis (TT), 0.0178 [0.0062, 0.0295] (I²=0%, p=0.94). The overall incidence of hematological events was 0.0431 [0.0274, 0.0621] (I²=70%, p<0.01). The incidence rates from high to low were as follows: lymphopenia, 0.0367 [0.0000, 0.0776] (I²=81%, p=0.02); Idiopathic thrombocytopenic purpura (ITP), 0.0258 [0.0199, 0.0323] (I²=25%, p=0.15); Hemolytic anemia (HA), 0.0177 [0.0081, 0.0391] (I²=29%, p=0.23); pancytopenia, 0.0136 [0.0000, 0.0314] (I²=0%, p=0.67); Neutropenia, 0.0081 [0.0000, 0.0183] (I²=0%, p=0.42). After excluding thyroid and hematological diseases, the combined incidence of other related SAEs was 0.0061 [0.0014, 0.0109] (I²=50%, p=0.02). The incidence of each disease ranked from highest to lowest as: skin psoriasis (SP), 0.0430 [0.0000, 0.0929] (I²=0%, p=0.57); alopecia areata (AA), 0.0159 [0.0024, 0.0372] (I²=19%, p=0.29); vitiligo, 0.0134 [0.0044, 0.0223] (I²=0%, p=0.81); inflammatory atrichia (IA), 0.0103 [0.0000, 0.0232] (I²=0%, p=0.43); chronic urticaria (CU), 0.0107 [0.0000, 0.0233] (I²=0%, p=0.60); and nephropathy, 0.0051 [0.0000, 0.0263] (I²=62%, p=0.02).
CONCLUSION
The occurrence of secondary autoimmune diseases in patients with MS treated with ALZ is noteworthy, particularly in the form of thyroid events and hematological events. Clinicians should monitor the overall condition of patients promptly for early management and avoid delayed diagnosis and treatment.
SYSTEMATIC REVIEW REGISTRATION
inplasy.com/inplasy-2024-4-0048/, identifier INPLASY202440048.
Topics: Humans; Alemtuzumab; Multiple Sclerosis; Autoimmune Diseases; Incidence; Hashimoto Disease
PubMed: 38690271
DOI: 10.3389/fimmu.2024.1343971 -
British Journal of Anaesthesia Jan 2023
Epileptiform discharges, electrographic seizures, and electroclinical seizures during paediatric sevoflurane anaesthesia: a systematic review and proposal for standard definitions.
Topics: Child; Humans; Sevoflurane; Seizures; Anesthesia; Electroencephalography
PubMed: 36333161
DOI: 10.1016/j.bja.2022.09.021 -
Dermatology and Therapy Jun 2021Distinct skin lesions associated with coronavirus disease 2019 (COVID-19) have been described, but data regarding their time of onset during the COVID-19 course are... (Review)
Review
INTRODUCTION
Distinct skin lesions associated with coronavirus disease 2019 (COVID-19) have been described, but data regarding their time of onset during the COVID-19 course are scant. Our objective was to systematically review the studies reporting the time of onset of selected skin lesions with respect to the reported onset of the COVID-19 core symptoms.
METHODS
A comprehensive search of studies published before 21 January 2021 was performed on MEDLINE via PubMed database using a predefined strategy to identify relevant articles.
RESULTS
Out of 354 references, 87 were selected, reporting a total of 895 patients with skin lesions associated with COVID-19. The most frequent pattern was exanthema (n = 430, 48%), followed by vascular (n = 299, 33%), urticarial (n = 105, 12%) and others (n = 66, 7%). Skin lesions occurred more frequently in the first 4 weeks from the COVID-19 onset (n = 831, 92%), whereas prodromal or late lesions were rarer (n = 69, 8%). The urticarial and exanthema patterns were more frequent in the first 2 weeks. About the vascular pattern some differences were noted among its subtypes. Livedoid lesions occurred mainly in the first 2 weeks, while chilblain-like lesions between weeks 2 and 4. Purpuric/petechial lesions were equally distributed during the first 4 weeks. Several skin manifestations did not fall into the pattern classification, including erythema multiforme, generalized pruritus, Kawasaki disease and others.
CONCLUSION
The diversity in the time of onset of skin lesions as well as their polymorphic nature likely reflects the diversity of the pathogenetic underlying mechanisms.
PROSPERO DATABASE REGISTRATION NUMBER
CRD42021236331.
PubMed: 33811315
DOI: 10.1007/s13555-021-00526-8 -
Oro-facial mucocutaneous manifestations of Coronavirus Disease-2019 (COVID-19): A systematic review.PloS One 2022We reviewed the prevalence, the likely aetiopathogenesis, and the management of oro-facial mucocutaneous manifestations of Coronavirus Disease-2019 (COVID-19), caused by...
We reviewed the prevalence, the likely aetiopathogenesis, and the management of oro-facial mucocutaneous manifestations of Coronavirus Disease-2019 (COVID-19), caused by the Severe Acute Respiratory Syndrome Coronavirus -2 (SARS-CoV-2). English language manuscripts searched using standard databases yielded 26 articles that met the inclusion criteria. In total, 169 cases (75 females; 94 males) from 15 countries with a spectrum of COVID-19 severities were reviewed. Gustatory perturbations were prevalent in over 70%. Mucocutaneous manifestations were reported predominantly on the tongue, palate, buccal mucosa, gingivae, and lips and included ulcers, blisters, erosions, papillary hyperplasia, macules, glossitis, and mucositis. Ulcerative lesions, present in over 50 percent, were the most common oral manifestation. Lesions resembling candidal infections, with burning mouth, were prevalent in 19%. Petechiae and angina bullosa were generally seen, subsequent to COVID-19 therapies, in 11%. Ulcerated, necrotic gingivae were documented in severely ill with poor oral hygiene. These manifestations, present across the COVID-19 disease spectrum, were commonly associated with the immunosuppressed state and/ or the concurrent antimicrobial/steroidal therapies. In summary, a wide variety of orofacial mucocutaneous lesions manifest in COVID-19. They are likely to be secondary to the disease-associated immune impairment and/or pharmaco-therapy rather than a direct result of SARS-CoV-2 infection per se.
Topics: COVID-19; Female; Humans; Male; SARS-CoV-2
PubMed: 35648785
DOI: 10.1371/journal.pone.0265531 -
Journal of Neurotrauma Apr 2019Diffusion tensor imaging is a magnetic resonance imaging technique that is uniquely capable of detecting microstructural tissue damage in mild and moderate traumatic... (Comparative Study)
Comparative Study Meta-Analysis
Comparing Region of Interest versus Voxel-Wise Diffusion Tensor Imaging Analytic Methods in Mild and Moderate Traumatic Brain Injury: A Systematic Review and Meta-Analysis.
Diffusion tensor imaging is a magnetic resonance imaging technique that is uniquely capable of detecting microstructural tissue damage in mild and moderate traumatic brain injuries (TBIs). To date, it remains unknown if two common analytic techniques, region of interest (ROI) versus voxel-wise (VW) analyses, detect injury in similar locations. The purpose of this systematic review and meta-analysis was to directly compare the regions of abnormality elucidated by each method. Twenty-seven ROI and 11 VW studies met our inclusion criteria. Our ROI meta-analysis identified 11 regions, including the splenium of the corpus callosum, where fractional anisotropy (FA) was significantly decreased in TBI patients, compared with controls. Likewise, we identified higher mean diffusivity/apparent diffusivity constant in the genu, body, and splenium of the corpus callosum. Alternatively, our VW analysis identified one region of high FA in the right superior longitudinal fasciculus and seven regions of low FA, with the two largest located in the corpus callosum. High mean diffusivity and high radial diffusivity, both in the right inferior longitudinal fasciculus, also was revealed by our VW analysis. Moreover, we have shown that the magnitude of damage in the corpus callosum revealed by ROI analysis (z = -3.15) is greater than that demonstrated by VW analysis (z = -1.41). Overall, this study indicates that both ROI and VW analytic methods are sensitive to low FA in the corpus callosum; however, the ROI method has more power to detect the full extent of tissue abnormality in the corpus callosum. More research utilizing standardized methods and reporting is essential to fully characterize the extent to which ROI and VW analyses can concordantly detect other locations of pathology in mild and moderate TBI patients.
Topics: Brain Concussion; Brain Injuries, Traumatic; Diffusion Tensor Imaging; Humans; Image Interpretation, Computer-Assisted; Neuroimaging
PubMed: 30375271
DOI: 10.1089/neu.2018.5838 -
Annals of Translational Medicine Jun 2022We conducted this meta-analysis to investigate the efficacy and safety of caplacizumab in patients with thrombotic thrombocytopenic purpura (TTP). TTP is a potentially...
Comparison of the efficacy and safety of caplacizumab versus placebo in thrombotic thrombocytopenic purpura: a meta-analysis and systematic review based on randomized controlled trials.
BACKGROUND
We conducted this meta-analysis to investigate the efficacy and safety of caplacizumab in patients with thrombotic thrombocytopenic purpura (TTP). TTP is a potentially fatal disorder characterized by systemic microvascular thrombosis.
METHODS
Randomized controlled trials (RCTs) were conducted from PubMed, Embase, Cochrane Library and Web of Science, China National Knowledge Infrastructure (CNKI), VIP and Wanfang databases. RCTs of caplacizumab treatment for TPP were mainly included. Data from eligible studies were extracted and analyzed using relative effect sizes versus placebo use. The Cochrane bias assessment tool was used to assess the risk of bias of included studies, and the assessment results were presented graphically in Revman5.3.
RESULTS
Four RCTs with a total of 416 patients were included, all of which were of high quality. Caplacizumab was associated with improvements in platelet counts normalization time [weighted mean difference (WMD) -1.18, 95% confidence interval (CI): -2.55 to 0.19, I=69.9%, P=0.036], plasma exchange (PE) time (WMD -2.97, 95% CI: -4.44 to -1.50, I=8.2%, P=0.163) and hospital stay (WMD -2.88, 95% CI: -4.56 to -1.21, I=48.7%, P=0.036). In addition, the occurrence of adverse events was also investigated. The difference in mortality between the two groups was not statistically significant [relative risk (RR) 0.56, 95% CI: 0.18 to 1.72, I=22.7%, P=0.275], relapse (RR 0.68, 95% CI: 0.13 to 3.49, I=78.3%, P=0.01), or major thrombotic events (RR 1.01, 95% CI: 0.65 to 1.57, I=43.4%, P=0.151).
CONCLUSIONS
Caplacizumab shortens the platelet normalization time, PE time, and hospital stay in patients with TTP, and did not significantly increase the risk of adverse events. These results indicate that caplacizumab treatment provides significant benefits to patients with TTP. Even though this is evidence from RCTs, few original studies were included, so more multicenter RCTs are required.
PubMed: 35845542
DOI: 10.21037/atm-22-2847 -
The Cochrane Database of Systematic... Oct 2014Hereditary ataxia syndromes can result in significant speech impairment, a symptom thought to be responsive to treatment. The type of speech impairment most commonly... (Review)
Review
BACKGROUND
Hereditary ataxia syndromes can result in significant speech impairment, a symptom thought to be responsive to treatment. The type of speech impairment most commonly reported in hereditary ataxias is dysarthria. Dysarthria is a collective term referring to a group of movement disorders affecting the muscular control of speech. Dysarthria affects the ability of individuals to communicate and to participate in society. This in turn reduces quality of life. Given the harmful impact of speech disorder on a person's functioning, treatment of speech impairment in these conditions is important and evidence-based interventions are needed.
OBJECTIVES
To assess the effects of interventions for speech disorder in adults and children with Friedreich ataxia and other hereditary ataxias.
SEARCH METHODS
On 14 October 2013, we searched the Cochrane Neuromuscular Disease Group Specialized Register, CENTRAL, MEDLINE, EMBASE, CINAHL Plus, PsycINFO, Education Resources Information Center (ERIC), Linguistics and Language Behavior Abstracts (LLBA), Dissertation Abstracts and trials registries. We checked all references in the identified trials to identify any additional published data.
SELECTION CRITERIA
We considered for inclusion randomised controlled trials (RCTs) or quasi-RCTs that compared treatments for hereditary ataxias with no treatment, placebo or another treatment or combination of treatments, where investigators measured speech production.
DATA COLLECTION AND ANALYSIS
Two review authors independently selected trials for inclusion, extracted data and assessed the risk of bias of included studies using the standard methodological procedures expected by The Cochrane Collaboration. The review authors collected information on adverse effects from included studies. We did not conduct a meta-analysis as no two studies utilised the same assessment procedures within the same treatment.
MAIN RESULTS
Fourteen clinical trials, involving 721 participants, met the criteria for inclusion in the review. Thirteen studies compared a pharmaceutical treatment with placebo (or a low dose of the intervention), in heterogenous groups of degenerative cerebellar ataxias. Three compounds were studied in two trials each: a levorotatory form of 5-hydroxytryptophan (L-5HT), idebenone and thyrotropin-releasing hormone tartrate (TRH-T); each of the other compounds (riluzole, varenicline, buspirone, betamethasone, coenzyme Q10 with vitamin E, α-tocopheryl quinone and erythropoietin) were studied in one trial. The 14th trial, involving a mixed group of participants with spinocerebellar ataxia, compared the effectiveness of nonspecific physiotherapy and occupational therapy within an inpatient hospital setting to no treatment. No studies utilised traditional speech therapies. We defined the primary outcome measure in this review as the percentage change (improvement) in overall speech production immediately following completion of the intervention or later, measured by any validated speech assessment tool. None of the trials included speech as a primary outcome or examined speech using any validated speech assessment tool. Eleven studies reported speech outcomes derived from a subscale embedded within disease rating scales. The remaining three studies used alternative assessments to measure speech, including mean time to produce a standard sentence, a subjective rating of speech on a 14-point analogue scale, patient-reported assessment of the impact of dysarthria on activities of daily living and acoustic measures of syllable length. One study measured speech both subjectively as part of a disease rating scale and with further measures of speech timing. Three studies utilised the Short Form-36 Health Survey (SF-36) and one used the Child Health Questionnaire as measures of general quality of life. A further study utilised the Functional Independence Measure to assess functional health.Five studies reported statistically significant improvement on an overall disease rating scale in which a speech subscale was included. Only three of those studies provided specific data on speech performance; all were comparisons with placebo. Improvements in overall disease severity were observed with α-tocopheryl quinone; however, no significant changes were found on the speech subscale in a group of individuals with Friedreich ataxia. A statistically significant improvement in speech according to a speech disorders subscale was observed with betamethasone. Riluzole was found to have a statistically significant effect on speech in a group of participants with mixed hereditary, sporadic and unknown origin ataxias. No significant differences were observed between treatment and placebo in any other pharmaceutical study. A statistically significant improvement in functional independence occurred at the end of the treatment period in the rehabilitation study compared to the delayed treatment group but these effects were not present 12 to 24 weeks after treatment. Of the four studies that assessed quality of life, none found a significant effect. A variety of minor adverse events were reported for the 13 pharmaceutical therapies, including gastrointestinal side effects and nausea. Serious adverse effects were reported in two participants in one of the L-5HT trials (participants discontinued due to gastrointestinal effects), and in four participants (three taking idebenone, one taking placebo) in the idebenone studies. Serious adverse events with idebenone were gastrointestinal side effects and, in people with a previous history of these events, chest pain and idiopathic thrombocytopenic purpura. The rehabilitation study did not report any adverse events.We considered six studies to be at high risk of bias in some respect. We suspected inadequate blinding of participants or assessors in four studies and poor randomisation in a further two studies. There was a high risk of reporting bias in two studies and attrition bias in four studies. Only one study had a low risk of bias across all criteria. Taken together with other limitations of the studies relating to the validity of the measurement scales used, we downgraded the quality of the evidence for many of the outcomes to low or very low.
AUTHORS' CONCLUSIONS
There is insufficient and low or very low quality evidence from either RCTs or observational studies to determine the effectiveness of any treatment for speech disorder in any of the hereditary ataxia syndromes.
Topics: Friedreich Ataxia; Humans; Randomized Controlled Trials as Topic; Speech; Speech Disorders; Spinocerebellar Degenerations
PubMed: 25348587
DOI: 10.1002/14651858.CD008953.pub2 -
British Journal of Haematology Feb 2020Persistent immune thrombocytopenia (ITP) patients require second-line treatments, for which information on clinical outcomes are lacking. A systematic review and network... (Meta-Analysis)
Meta-Analysis
Persistent immune thrombocytopenia (ITP) patients require second-line treatments, for which information on clinical outcomes are lacking. A systematic review and network meta-analysis (NMA) were conducted. Only randomised controlled trials (RCT) of second-line drugs in adult persistent ITP patients with platelet response, platelet count, any bleeding or serious adverse events (SAE) outcome were eligible. Twelve RCTs (n = 1313) were included in NMA. For platelet response outcome, eltrombopag and romiplostin were the best relative to placebo; the former had a non-significant advantage [risk ratio (RR) = 1·10 (95% confidence interval: 0·46, 2·67)]. Both treatments were superior to rituximab and recombinant human thrombopoietin (rhTPO)+rituximab, with corresponding RRs of 4·56 (1·89, 10·96) and 4·18 (1·21, 14·49) for eltrombopag; 4·13 (1·56, 10·94) and 3·79 (1·02, 14·09) for romiplostim. For platelet count, romiplostim ranked highest, followed by eltrombopag, rhTPO+rituximab, and rituximab. For bleeding, rituximab had lowest risk, followed by eltrombopag and romiplostim. For SAEs, rhTPO+rituximab had highest risk, followed by rituximab, eltrombopag and romiplostim. From clustered ranking, romiplostim had the best balance between short-term efficacy and SAEs, followed by eltrombopag. In conclusion, romiplostim and eltrombopag may yield high efficacy and safety. Rituximab may not be beneficial due to lower efficacy and higher complications compared with the thrombopoietin receptor agonists. RCTs with long-term clinical outcomes are required.
Topics: Adult; Benzoates; Drug Therapy, Combination; Female; Humans; Hydrazines; Male; Platelet Count; Prospective Studies; Purpura, Thrombocytopenic, Idiopathic; Pyrazoles; Randomized Controlled Trials as Topic; Receptors, Fc; Recombinant Fusion Proteins; Rituximab; Thrombopoietin
PubMed: 31423574
DOI: 10.1111/bjh.16161 -
BMC Pediatrics Mar 2024Intravenous immunoglobulin (IVIg) is a first-line treatment for children with newly diagnosed immune thrombocytopenia (ITP). Higher doses of IVIg are associated with a... (Meta-Analysis)
Meta-Analysis
Can low-dose intravenous immunoglobulin be an alternative to high-dose intravenous immunoglobulin in the treatment of children with newly diagnosed immune thrombocytopenia: a systematic review and meta-analysis.
Intravenous immunoglobulin (IVIg) is a first-line treatment for children with newly diagnosed immune thrombocytopenia (ITP). Higher doses of IVIg are associated with a more insupportable financial burden to pediatric patients' families and may produce more adverse reactions. Whether low-dose IVIg (LD-IVIg) can replace high-dose IVIg (HD-IVIg) has yet to be established. We conducted a comprehensive literature search from the establishment of the database to May 1, 2023, and eventually included 22 RCTs and 3 cohort studies compared different dosages of IVIg. A total of 1989 patients were included, with 991 patients in the LD-IVIg group and 998 patients in the HD-IVIg group. Our results showed no significant differences between the two groups in the effective rate (LD-IVIg: 91% vs. HD-IVIg: 93%; RR: 0.99; 95%CI: 0.96-1.02) and the durable remission rate (LD-IVIg: 65% vs. HD-IVIg: 67%; RR: 0.97; 95%CI: 0.89-1.07). Similar results were also found in the time of platelet counts (PC) starting to rise (MD: 0.01, 95%CI: -0.06-0.09), rising to normal (MD: 0.16, 95%CI: -0.03-0.35), and achieving hemostasis (MD: 0.11, 95%CI: -0.02-0.23) between the two groups. Subgroup analysis showed the effective rate of 0.6 g/kg was equal to 1 g/kg subgroup (91%) but higher than 0.8 g/kg subgroup (82%), and a combination with glucocorticoid may contribute to effect enhancement (combined with glucocorticoid: 91% vs. IVIg alone: 86%) whether combined with dexamethasone (92%) or methylprednisolone (91%). Besides, the incidence rate of adverse reactions in the LD-IVIg group (3%) was significantly lower than the HD-IVIg group (6%) (RR: 0.61; 95%CI: 0.38-0.98). So low-dose IVIg (≤ 1 g/kg) is effective, safe, and economical, which can replace high-dose IVIg (2 g/kg) as an initial treatment. This systematic review was registered in PROSPERO (CRD42022384604).
Topics: Child; Humans; Purpura, Thrombocytopenic, Idiopathic; Immunoglobulins, Intravenous; Glucocorticoids; Platelet Count; Methylprednisolone
PubMed: 38515126
DOI: 10.1186/s12887-024-04677-3 -
Orphanet Journal of Rare Diseases Nov 2019Acquired thrombotic thrombocytopenic Purpura (aTTP) is a life-threatening ultra-orphan disease with a reported annual incidence between 1.5 and 6.0 cases per million in...
BACKGROUND
Acquired thrombotic thrombocytopenic Purpura (aTTP) is a life-threatening ultra-orphan disease with a reported annual incidence between 1.5 and 6.0 cases per million in Europe and mainly affecting otherwise young and healthy adults aged 40 years on average. The goal of this study was to assess the incidence of aTTP in Germany.
METHODS
A systematic review was performed to determine the published evidence on the aTTP epidemiology in Germany. To obtain additional evidence on the proportion of aTTP cases within the national Thrombotic Microangiopathy (TMA) population a hospital-level study was performed, using a retrospective data collection approach. Diagnosis of aTTP was confirmed if ADAMTS13 level were < 10% and/or the medical records explicitly mentioned aTTP diagnosis. The aggregated hospital data were then projected to the national level using logistic regression techniques.
RESULTS
The systematic literature search did not provide incidence estimates of aTTP in Germany. Eight centers (≈27% of the top 30 TMA hospitals) delivered data according to a predefined data collection form. On average (year 2014-2016) a total number of 172 aTTP episodes per year was projected (95% confidence interval [95%CI]: 132-212). The majority were newly diagnosed aTTP cases (n = 121; 95%CI: 105-129), and 51 were recurrent aTTP cases (95%CI: 27-84). The average annual projected incidence (year 2014-2016) of aTTP episodes was 2.10 per million inhabitants in Germany (95%CI: 1.60-2.58).
CONCLUSIONS
The determined annual incidence of newly diagnosed aTTP cases and the overall annual incidence of aTTP episodes in Germany confirm the ultra-orphan character of aTTP. An external validation against international registries (France, UK and USA) shows that our findings are quite comparable with those international incidence rates.
Topics: Adult; Female; Germany; Hospitals; Humans; Incidence; Logistic Models; Male; Purpura, Thrombotic Thrombocytopenic
PubMed: 31730475
DOI: 10.1186/s13023-019-1240-0