Efficacy and safety of intravenous immunoglobulins for the treatment of viral encephalitis: a systematic literature review

Abstract Background For most viral encephalitides, therapy is merely supportive. Intravenous immunoglobulins (IVIG) have been used as a prophylactic and therapeutic approach. We conduct a systematic review on the safety and efficacy of IVIG in viral encephalitis. Methods We conducted a systematic review assessing PubMed, Cochrane Database, Biosis Previews and the ClinicalTrials.gov website to identify all reports on patients with viral encephalitis treated with IVIG as of May 31, 2019. The main outcomes assessed were therapeutic efficacy and safety. For an increased homogeneity of the population, atypical viral infections were excluded, as were reports on prophylactic IVIG use, intrathecal application of immunoglobulins, or use of antibody-enriched IVIG-preparations. Data were extracted from published studies. Descriptive statistics were used. Results We included a total of 44 studies (39 case reports). The case reports cover a total of 53 patients. Our search retrieved two prospective and three retrospective studies. These show heterogeneous results as to the efficacy of IVIG therapy. Only one study reports a significant association between IVIG-use and death (odds ratio 0.032; 95% confidence interval 0.0033–0.3024; p = 0.0027). None of the studies report significant differences in the number of serious adverse events. Conclusion Data on the efficacy of IVIG-therapy is heterogeneous. While it seems generally safe, evident superiority compared to supportive treatment has not been demonstrated so far. Future trials should also investigate the optimal dosing and timing of IVIG and their benefit in the immunosuppressed.

Download Full-text

Favipiravir for the treatment of patients with COVID-19: a systematic review and meta-analysis

BMC Infectious Diseases ◽

10.1186/s12879-021-06164-x ◽

2021 ◽

Vol 21 (1) ◽

Author(s):

Toshie Manabe ◽

Dan Kambayashi ◽

Hiroyasu Akatsu ◽

Koichiro Kudo

Keyword(s):

Systematic Review ◽

Clinical Improvement ◽

Odds Ratio ◽

Meta Analysis ◽

Viral Clearance ◽

Efficacy And Safety ◽

Duration Of Treatment ◽

Comparator Group ◽

Cochrane Database ◽

High Utility

Abstract Background Favipiravir possesses high utility for treating patients with COVID-19. However, research examining the efficacy and safety of favipiravir for patients with COVID-19 is limited. Methods We conducted a systematic review of published studies reporting the efficacy of favipiravir against COVID-19. Two investigators independently searched PubMed, the Cochrane Database of Systematic Reviews, MedRxiv, and ClinicalTrials.gov (inception to September 2020) to identify eligible studies. A meta-analysis was performed to measure viral clearance and clinical improvement as the primary outcomes. Results Among 11 eligible studies, 5 included a comparator group. Comparing to the comparator group, the favipiravir group exhibited significantly better viral clearance on day 7 after the initiation of treatment (odds ratio [OR] = 2.49, 95% confidence interval [CI] = 1.19–5.22), whereas no difference was noted on day 14 (OR = 2.19, 95% CI = 0.69–6.95). Although clinical improvement was significantly better in the favipiravir group on both days 7 and 14, the improvement was better on day 14 (OR = 3.03, 95% CI = 1.17–7.80) than on day 7 (OR = 1.60, 95% CI = 1.03–2.49). The estimated proportions of patients with viral clearance in the favipiravir arm on days 7 and 14 were 65.42 and 88.9%, respectively, versus 43.42 and 78.79%, respectively, in the comparator group. The estimated proportions of patients with clinical improvement on days 7 and 14 in the favipiravir group were 54.33 and 84.63%, respectively, compared with 34.40 and 65.77%, respectively, in the comparator group. Conclusions Favipiravir induces viral clearance by 7 days and contributes to clinical improvement within 14 days. The results indicated that favipiravir has strong possibility for treating COVID-19, especially in patients with mild-to-moderate illness. Additional well-designed studies, including examinations of the dose and duration of treatment, are crucial for reaching definitive conclusions.

Download Full-text

Intravenous Immunoglobulins for Refractory Status Epilepticus: A Scoping Systematic Review of the Pediatric Literature

Journal of Pediatric Neurology ◽

10.1055/s-0037-1603594 ◽

2017 ◽

Vol 15 (06) ◽

pp. 305-315

Author(s):

M. Matuszczak ◽

J. Teitelbaum ◽

C. Kazina ◽

L. Gillman ◽

F. Zeiler

Keyword(s):

Systematic Review ◽

Status Epilepticus ◽

Pediatric Patients ◽

Ivig Therapy ◽

Intravenous Immunoglobulins ◽

Refractory Status Epilepticus ◽

Neurological Deficits ◽

Cochrane Library ◽

Refractory Status ◽

Grade Methodology

AbstractOur goal was to perform a scoping systematic review of the literature on the use of intravenous immunoglobulins (IVIGs) for refractory status epilepticus (RSE) in pediatric patients. Articles from MEDLINE, BIOSIS, EMBASE, Global Health, Healthstar, Scopus, Cochrane Library, the International Clinical Trials Registry Platform, ClinicalTrials.gov (inception to June 2016), reference lists of relevant articles, and gray literature were searched. The strength of evidence was adjudicated using both the Oxford and Grading of Recommendation Assessment Development and Education (GRADE) methodology by two independent reviewers. We identified 21 original articles. Eighty-seven pediatric patients were described as having received IVIG therapy for RSE. The mean age was 7.8 years (range: 2–17.5 years). Seizure response occurred in 14 of the 87 patients (16.1%), with 3 (3.4%) and 11 (12.6%) displaying partial and complete responses, respectively. Seventy-three of the 87 patients (83.9%) failed to display any seizure response to IVIG therapy. No complications related to IVIG therapy were recorded. The majority of patients had moderate to severe neurological deficits upon follow-up. Oxford level 4, GRADE D evidence exists to suggest little to no impact on seizure control in pediatric autoimmune RSE. Routine use of IVIG for pediatric RSE cannot be recommended at this time and should be considered experimental.

Download Full-text

Cutaneous neonatal Langerhans cell histiocytosis: a systematic review of case reports

F1000Research ◽

10.12688/f1000research.17664.1 ◽

2019 ◽

Vol 8 ◽

pp. 13

Author(s):

Victoria Venning ◽

Evelyn Yhao ◽

Elizabeth Huynh ◽

John W. Frew

Keyword(s):

Systematic Review ◽

Langerhans Cell Histiocytosis ◽

Case Reports ◽

Systemic Disease ◽

Langerhans Cell ◽

Multiple Lesions ◽

Risk Of Mortality ◽

Cochrane Database ◽

Chi Squared ◽

Worse Prognosis

Background: Cutaneous langerhans cell histiocytosis (LCH) is a rare disorder characterized by proliferation of cells with phenotypical characteristics of Langerhans cells. Although some cases spontaneously resolve, no consistent variables have been identified that predict which cases will manifest with systemic disease later in childhood. Methods: A systematic review (Pubmed, Embase, Cochrane database and all published abstracts from 1946-2018) was undertaken to collate all reported cases of cutaneous LCH in the international literature. This study was registered with PROSPERO (CRD42016051952). Descriptive statistics and correlation analyses were undertaken. Bias was analyzed according to GRADE criteria. Results: A total of 83 articles encompassing 128 cases of cutaneous LCH were identified. Multiple lesions were weakly associated with an increased length of survival (R=0.304 (p<0.05)), Worse prognosis was associated with internal organ involvement with a statistically significant chi squared statistic (χ2=14.96, 2DF p<0.001) and an elevated odds ratio ((OR)= 12.30 95% CI=2.67-56.74). Vesicular lesions (OR=10.8 95% CI=2.83-41.26), but not ulceration (OR=0.53 95% CI 0.12-2.05) were associated with greater risk of mortality. Conclusions: Congenital and neonatal LCH most commonly presents as multiple lesions in multiple anatomical sites at birth. Significant differences, including the associations of mortality with lesion morphology and number were seen in this neonatal cohort compared to overall pediatric LCH. These findings require validation in a large prospective cohort.

Download Full-text

Efficacy and safety of Anaferon for children and Anaferon for the prevention and treatment of influenza and other acute respiratory viral infections: systematic review and meta-analysis

Russian Medical Inquiry ◽

10.32364/2587-6821-2021-5-5-335-347 ◽

2021 ◽

Vol 5 (5) ◽

pp. 335-347

Author(s):

N.A. Geppe ◽

◽

A.L. Zaplatnikov ◽

E.G. Kondyurina ◽

O.I. Afanasieva ◽

...

Keyword(s):

Systematic Review ◽

Therapeutic Efficacy ◽

Disease Duration ◽

Viral Infections ◽

Respiratory Infections ◽

Meta Analysis ◽

Acute Respiratory Infections ◽

Efficacy And Safety ◽

Prevention And Treatment ◽

Respiratory Viral Infections

Aim: to evaluate the efficacy and safety of Anaferon and Anaferon for children for the prevention and treatment of of acute respiratory viral infections (ARVI)/influenza using meta-analysis. Patients and Methods: the meta-analysis included data from 11 randomized clinical trials (RCTs) involving 3079 patients aged 1 month to 69 years, of which: 1729 people were included in the meta-analysis of the preventive drugs efficacy, 1550 patients — in the meta-analysis of the therapeutic efficacy of Anaferon for children. The evaluation of the therapeutic efficacy was conducted according to the criteria "disease duration" and/or "fever duration", the evaluation of the preventive efficacy was conducted according to the criterion "the proportion of patients not falling ill with ARVI/influenza". The safety was evaluated taking into account the number of adverse events (AEs). Statistical methods included the exact Fisher criterion, the Student criterion, fixed and random effects models, the Z-test, the Cochrane-Mantel-Hensel criterion, Cochrane Q-statistics and the I2 coefficient, the Breslow-Day test, the calculation of relative risk (RR), odds ratios (OR) and their 95% confidence intervals (CI). Results: according to the criterion "the proportion of patients not falling ill with ARVI/influenza", the RR of Anaferon for children was 1.2 [95% CI 1.2; 1.3] with an OR of 2.2 [95% CI 1.7; 2.9], while for Anaferon, the RR was 6.7 [95% CI 3.8; 11.8] with an OR of 20.1 [95% CI 9.2; 44.0]. At the same time, the proportion of patients without ARVI/influenza during Anaferon intake exceeded that in the absence of preventive intervention by almost 8 times, and during Anaferon for children intake — 1.3 times vs. placebo. When evaluating the therapeutic effect of Anaferon for children, it was found that the average disease duration was 1.4 times shorter than during placebo intake, and was 4.71±2.53 days (p<0,001). The average fever duration was 2.19±1.21 days vs. 3.22±1.81 days during placebo intake (p<0,001). According to the criterion "disease duration", the weighted average effect value was 1.05 [95% CI 0.44; 1.67], according to the criterion "fever duration" — 0.97 [95% CI 0.61; 1.33] (p<0.001, p-value of the two-tailed Z-test; random effects model). The therapeutic efficacy of Anaferon for children did not depend on the etiology of ARVI, the symptoms, and the presence of comorbidity (asthma). The total number of AEs is similar to those in the comparison group. Conclusion: the conducted review and meta-analysis concerning the efficacy and safety of Anaferon and Anaferon for children for the treatment and prevention of ARVI/influenza allow us to conclude the following: 1) Anaferon for children is effective and safe for the treatment of influenza and other acute respiratory infections, regardless of the pathogen and the presence of comorbidity (asthma); 2) Anaferon and Anaferon for children are effective and safe for the prevention of acute respiratory infections/influenza, including patients with concomitant bronchopulmonary pathology and frequently ill children. KEYWORDS: ARVI, influenza, prevention, treatment, meta-analysis, Anaferon, Anaferon for children. FOR CITATION: Geppe N.A., Zaplatnikov A.L., Kondyurina E.G. et al. Efficacy and safety of Anaferon for children and Anaferon for the prevention and treatment of influenza and other acute respiratory viral infections: systematic review and meta-analysis. Russian Medical Inquiry. 2021;5(5):335–347 (in Russ.). DOI: 10.32364/2587-6821-2021-5-5-335-347.

Download Full-text

Impact of COVID-19 on the placental pathology of pregnant women and their infants: A systematic review protocol

10.31219/osf.io/3f8j7 ◽

2020 ◽

Author(s):

Irina Oltean ◽

Dina El Demellawy

Keyword(s):

Systematic Review ◽

Pregnant Women ◽

Clinical Outcomes ◽

Viral Infections ◽

Case Reports ◽

Case Series ◽

Cell Mediated Immunity ◽

Case Control Studies ◽

Antibody Testing ◽

Adverse Pregnancy

Pregnant women are susceptible to viral infections due to physiological changes such as cell-mediated immunity. No severe adverse pregnancy or neonatal outcomes have been consistently reported in COVID-19 positive pregnancy cases. There are controversies around the role of COVID-19 in pregnancy. A systematic review was conducted to examine clinical maternal and neonatal clinical outcomes. Studies were included if they reported COVID-19 infection among pregnant women and/or COVID-19 positive neonates as validated by positive antibody testing or viral testing using Polymerase Chain Reaction. Case series, case reports, case-control studies, and comparative studies were included. 837 records were identified, resulting in 525 records for level I screening. 41 were included after full-text review. Results suggest elevated rates of ICU admission, gestational diabetes, preeclampsia, C-sections, pre-term birth, and CRP in comparison to pregnant women without SARS-CoV-2. Careful monitoring of pregnancies with SARS-CoV-2 to minimize adverse clinical outcomes is recommended.

Download Full-text

Efficacy and safety of convalescent plasma for severe COVID-19 based on evidence in other severe respiratory viral infections: a systematic review and meta-analysis

Canadian Medical Association Journal ◽

10.1503/cmaj.200642 ◽

2020 ◽

Vol 192 (27) ◽

pp. E745-E755 ◽

Cited By ~ 11

Author(s):

Niveditha Devasenapathy ◽

Zhikang Ye ◽

Mark Loeb ◽

Fang Fang ◽

Borna Tadayon Najafabadi ◽

...

Keyword(s):

Systematic Review ◽

Viral Infections ◽

Meta Analysis ◽

Efficacy And Safety ◽

Respiratory Viral Infections

Download Full-text

Efficacy and safety of pharmacological cachexia interventions: systematic review and network meta-analysis

BMJ Supportive & Palliative Care ◽

10.1136/bmjspcare-2020-002601 ◽

2020 ◽

pp. bmjspcare-2020-002601

Author(s):

Manit Saeteaw ◽

Phitjira Sanguanboonyaphong ◽

Jukapun Yoodee ◽

Kaitlyn Craft ◽

Ratree Sawangjit ◽

...

Keyword(s):

Systematic Review ◽

Adverse Events ◽

Meta Analysis ◽

Total Body Weight ◽

Megestrol Acetate ◽

High Dose ◽

Efficacy And Safety ◽

Pharmacological Interventions ◽

Serious Adverse Events ◽

Significant Difference

AimsRandomised controlled trials (RCTs) demonstrated benefits of pharmacological interventions for cachexia in improving weight and appetite. However, comparative efficacy and safety are not available. We conducted a systematic review and network meta-analysis (NMA) to evaluate the relative efficacy and safety of pharmacological interventions for cachexia.MethodsPubMed, EmBase, Cochrane, and ClinicalTrials.gov were searched for RCTs until October 2019. Key outcomes were total body weight (TBW) improvement, appetite (APP) score and serious adverse events. Two reviewers independently extracted data and assessed risk of bias. NMA was performed to estimate weight gain and APP score increase at 8 weeks, presented as mean difference (MD) or standardised MD with 95% CI.Results80 RCTs (10 579 patients) with 12 treatments were included. Majority is patients with cancer (7220). Compared with placebo, corticosteroids, high-dose megestrol acetate combination (Megace_H_Com) (≥400 mg/day), medroxyprogesterone, high-dose megestrol acetate (Megace_H) (≥400 mg/day), ghrelin mimetic and androgen analogues (Androgen) were significantly associated with MD of TBW of 6.45 (95% CI 2.45 to 10.45), 4.29 (95% CI 2.23 to 6.35), 3.18 (95% CI 0.94 to 5.41), 2.66 (95% CI 1.47 to 3.85), 1.73 (95% CI 0.27 to 3.20) and 1.50 (95% CI 0.56 to 2.44) kg. For appetite improvement, Megace_H_Com, Megace_H and Androgen significantly improved standardised APP score, compared with placebo. There is no significant difference in serious adverse events from all interventions compared with placebo.ConclusionsOur findings suggest that several pharmacological interventions have potential to offer benefits in treatment of cachexia especially Megace_H and short-term use corticosteroids. Nonetheless, high-quality comparative studies to compare safety and efficacy are warranted for better management of cachexia.

Download Full-text

The effects of caffeine in adults with neurogenic orthostatic hypotension: a systematic review

Clinical Autonomic Research ◽

10.1007/s10286-021-00814-5 ◽

2021 ◽

Author(s):

Jake Ryan Gibbon ◽

James Frith

Keyword(s):

Systematic Review ◽

Blood Pressure ◽

Orthostatic Hypotension ◽

Case Reports ◽

Meta Analysis ◽

Evidence Base ◽

Original Research ◽

Neurogenic Orthostatic Hypotension ◽

Serious Adverse Events ◽

Evidence Based Treatments

Abstract Purpose To systematically review the evidence base for the effectiveness and safety of caffeine for the treatment of neurogenic orthostatic hypotension in adults. Methods Eight electronic databases were searched in January 2021. Original research studies or case reports involving adults with neurogenic orthostatic hypotension were included if caffeine was an intervention and outcomes included symptoms, blood pressure or adverse effects. Relevant studies were screened and underwent qualitative analysis. Insufficient reporting precluded meta-analysis. Results Five studies were identified: four crossover studies and one case report summation. Study size ranged from 5 to 16 participants. Participants had neurogenic orthostatic hypotension, with a mean standing systolic blood pressure of 86 mmHg. Two studies evaluated caffeine alone. Three studies administered caffeine in combination with ergotamine. Caffeine dose ranged from 100 to 300 mg. Nature and timing of outcomes measured varied between studies, with measurements being recorded from 30 to 480 min after intervention. Caffeine/ergotamine improved symptoms in one study and reduced orthostatic blood pressure drop in two studies. Caffeine/ergotamine increased seated blood pressure in three studies, whilst the results for caffeine alone were inconsistent. No serious adverse events were reported. All studies demonstrated high risk of bias. Conclusion Caffeine should only be considered as a treatment for adults with neurogenic orthostatic hypotension when evidence-based treatments have been exhausted. Systematic review registration PROSPERO ID: CRD42020124589. Date of registration: 30/10/2020

Download Full-text

Medical Management of Patients After Atypical Femur Fractures: a Systematic Review and Recommendations From the European Calcified Tissue Society

The Journal of Clinical Endocrinology & Metabolism ◽

10.1210/clinem/dgz295 ◽

2019 ◽

Vol 105 (5) ◽

pp. 1682-1699 ◽

Cited By ~ 1

Author(s):

Denise M van de Laarschot ◽

Malachi J McKenna ◽

Bo Abrahamsen ◽

Bente Langdahl ◽

Martine Cohen-Solal ◽

...

Keyword(s):

Systematic Review ◽

Case Reports ◽

Evidence Synthesis ◽

Fragility Fractures ◽

Serious Adverse Events ◽

Naive Patient ◽

Femur Fractures ◽

Atypical Femur Fractures ◽

Calcified Tissue ◽

Radiological Healing

Abstract Context Atypical femur fractures (AFFs) are serious adverse events associated with bisphosphonates and often show poor healing. Evidence acquisition We performed a systematic review to evaluate effects of teriparatide, raloxifene, and denosumab on healing and occurrence of AFF. Evidence synthesis We retrieved 910 references and reviewed 67 papers, including 31 case reports, 9 retrospective and 3 prospective studies on teriparatide. There were no RCTs. We pooled data on fracture union (n = 98 AFFs on teriparatide) and found that radiological healing occurred within 6 months of teriparatide in 13 of 30 (43%) conservatively managed incomplete AFFs, 9 of 10 (90%) incomplete AFFs with surgical intervention, and 44 of 58 (75%) complete AFFs. In 9 of 30 (30%) nonoperated incomplete AFFs, no union was achieved after 12 months and 4 (13%) fractures became complete on teriparatide. Eight patients had new AFFs during or after teriparatide. AFF on denosumab was reported in 22 patients, including 11 patients treated for bone metastases and 8 without bisphosphonate exposure. Denosumab after AFF was associated with recurrent incomplete AFFs in 1 patient and 2 patients of contralateral complete AFF. Eight patients had used raloxifene before AFF occurred, including 1 bisphosphonate-naïve patient. Conclusions There is no evidence-based indication in patients with AFF for teriparatide apart from reducing the risk of typical fragility fractures, although observational data suggest that teriparatide might result in faster healing of surgically treated AFFs. Awaiting further evidence, we formulate recommendations for treatment after an AFF based on expert opinion.

Download Full-text

Coronavirus infection in neonates: a systematic review

Archives of Disease in Childhood - Fetal and Neonatal Edition ◽

10.1136/archdischild-2020-319837 ◽

2020 ◽

pp. fetalneonatal-2020-319837

Author(s):

Daniele Trevisanuto ◽

Francesco Cavallin ◽

Maria Elena Cavicchiolo ◽

Martina Borellini ◽

Serena Calgaro ◽

...

Keyword(s):

Systematic Review ◽

Spontaneous Breathing ◽

Respiratory Infections ◽

Case Reports ◽

Gastrointestinal Symptoms ◽

Case Series ◽

Final Analysis ◽

Good Prognosis ◽

Cochrane Database ◽

The Impact

ObjectiveTo summarise currently reported neonatal cases of SARS-CoV-2 infection.MethodsA search strategy was designed to retrieve all articles published from 1 December 2019 to 12 May 2020, by combining the terms ‘coronavirus’ OR ‘covid’ OR ‘SARS-CoV-2’) AND (‘neonat*’ OR ‘newborn’) in the following electronic databases: MEDLINE/Pubmed, Scopus, Web of Science, MedRxiv, the Cochrane Database of Systematic Review and the WHO COVID-19 database, with no language restrictions. Quality of studies was evaluated by using a specific tool for assessment of case reports and/or case series.ResultsTwenty-six observational studies (18 case reports and 8 case series) with 44 newborns with confirmed SARS-CoV-2 infection were included in the final analysis. Studies were mainly from China and Italy. Half of neonates had a documented contact with the infected mother and one out of three infected neonates was admitted from home. Median age at diagnosis was 5 days. One out of four neonates was asymptomatic, and the remaining showed mild symptoms typical of acute respiratory infections and/or gastrointestinal symptoms. The majority of neonates were left in spontaneous breathing (room air) and had good prognosis after a median duration of hospitalisation of 10 days.ConclusionsMost neonates with SARS-CoV-2 infection were asymptomatic or presented mild symptoms, generally were left in spontaneous breathing and had a good prognosis after median 10 days of hospitalisation. Large epidemiological and clinical cohort studies, as well as the implementation of collaborative networks, are needed to improve the understanding of the impact of SARS-CoV-2 infection in neonates.

Download Full-text