Neurological Complications of SARS-CoV-2 Infection in Children: A Systematic Review and Meta-Analysis

Abstract Background Knowledge about neurological complications of COVID-19 in children is limited due to the paucity of data in the existing literature. Some systematic reviews are available describing overall clinical features of COVID-19 in children and neurological complications of COVID-19 in adults. But to the best of our knowledge, no systematic review has been performed to determine neurological manifestations of COVID-19. Methods Six different electronic databases (MEDLINE, EMBASE, Web of Science, CENTRAL, medRxiv and bioRxiv) were searched for articles related to COVID-19 and neurological complications in children. Studies/case series reporting neurological manifestations of COVID-19 in patients aged ≤18 years, as well as case reports, as neurological complications appear to be rare. The pooled estimate of various non-specific and specific neurological manifestations was performed using a random effect meta-analysis. Results Twenty-one studies/case series and five case reports (3707 patients) fulfilled the eligibility criteria and were included in this systematic review, from a total of 460 records. Headache, myalgia and fatigue were predominant non-specific neurological manifestations, presenting altogether in 16.7% cases. Total of 42 children (1%) were found to have been reported with definite neurological complications, more in those suffering from a severe illness (encephalopathy—25, seizure—12, meningeal signs—17). Rare neurological complications were intracranial hemorrhage, cranial nerve palsy, Guillain–Barré syndrome and vision problems. All children with acute symptomatic seizures survived suggesting a favorable short-term prognosis. Conclusion Neurological complications are rare in children suffering from COVID-19. Still, these children are at risk of developing seizures and encephalopathy, more in those suffering from severe illness.

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Fronto-orbito-ethmoidal intradiploic meningiomas: A case study with systematic review

Surgical Neurology International ◽

10.25259/sni_386_2021 ◽

2021 ◽

Vol 12 ◽

pp. 485

Author(s):

Antonio Crea ◽

Gianluca Grimod ◽

Gianluca Scalia ◽

Mariarosaria Verlotta ◽

Lucio Mazzeo ◽

...

Keyword(s):

Systematic Review ◽

Case Reports ◽

Meta Analysis ◽

Case Series ◽

Complex Case ◽

Subtotal Resection ◽

Eligibility Criteria ◽

Orbital Roof ◽

Mesh Terms ◽

Almost All

Background: Primary intradiploic meningiomas, extra-axial tumors arising primarily in the skull, are rare. The authors reported a complex case of intradiploic intraosseous metaplastic meningioma of the left medial wall and orbital roof with the left frontal sinus invasion and left ethmoidal body bone substitution. The authors also conducted a systematic review concerning diagnosis and management of patients affected by purely calvarial intradiploic meningiomas along with a focus on fronto-orbito-ethmoidal ones. Methods: A literature search was conducted using PubMed and Scopus databases according to preferred reporting items for systematic reviews and meta-analysis statement and with the following Mesh terms: Intradiploic, intraosseous, calvarial, and meningioma. Eligibility criteria were limited by the nature of existing literature on intradiploic meningiomas, consisting of only case series, and case reports. Results: A total of 128 published studies were identified through our search. 41 studies were included in this systematic review, 59 patients with a female/male ratio of 1.2/1. The mean age of the patients is of 47.69 years (range 3–84 years). Only seven out of 59 patients (11.9%) presented a complex intradiploic meningioma located in fronto-orbito-ethmoidal region like our case. In almost all patients, a gross-total resection was performed (96.6%) and only in two patients (3.4%) a subtotal resection was achieved. Conclusion: The authors shared this successfully treated case to add to the overall clinical experience in the management of this rare subtype tumor, with the hope that more studies are conducted to further address the mechanism of intradiploic meningiomas development.

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Efficacy and Tolerability of Lacosamide in Lennox–Gastaut Syndrome: A Systematic Review and Meta-analysis

Journal of Neurosciences in Rural Practice ◽

10.1055/s-0041-1740580 ◽

2022 ◽

Author(s):

Prateek Kumar Panda ◽

Indar Kumar Sharawat ◽

Lesa Dawman ◽

Pragnya Panda ◽

Ananthanarayanan Kasinathan ◽

...

Keyword(s):

Systematic Review ◽

Adverse Events ◽

Seizure Frequency ◽

Retrospective Studies ◽

Case Reports ◽

Random Effect ◽

Random Effect Model ◽

Case Series ◽

Eligibility Criteria ◽

Serious Adverse Events

Abstract Purpose Lennox–Gastaut syndrome (LGS) is one of the most difficult to treat childhood-onset epileptic encephalopathies. There is growing evidence that lacosamide is safe and efficacious in patients and adults with refractory epilepsy. However, the evidence regarding the efficacy of lacosamide in LGS is controversial so far. We aimed to evaluate the efficacy and tolerability of lacosamide in patients with LGS. Methods We conducted a systematic review on MEDLINE, EMBASE, COCHRANE CENTRAL, Google Scholar, and Web of Science, collating all available literature till July 31, 2020. The qualitative review included case reports, case series, and both controlled/uncontrolled trials as well as retrospective studies, but for determining pooled estimates, we only included studies with a sample size of 5 or more. The primary outcome was the efficacy of lacosamide in patients with LGS. Clinical variables related to efficacy and adverse events attributed to lacosamide were extracted from each publication. The pooled estimate of variables related to these parameters was performed using a random-effect model. Results Of the 68 items identified by the search, 14 were reviewed as full-text. Eleven articles including two prospective and six retrospective studies fulfilled eligibility criteria and described outcomes in 81 patients (42 adults, 39 children, 60% male, range—1.4–61 years). On average, 35.2%, 27.9%, 7.3%, and 29.4% patients had > 50% reduction, < 50% reduction, no change, and worsening of seizure frequency, respectively. Although 36% of patients had adverse events like somnolence, behavioral abnormalities including irritability, aggressiveness, nausea, tremor, memory problems, dizziness, gastrointestinal discomfort, vomiting, and weight loss, no serious adverse events were noted. Conclusion The evidence available in the current literature is not sufficient to support or refute the use of lacosamide in patients with LGS. Although it is one of the possible therapeutic options worth exploring in patients with LGS, caution is still necessary, as there are reports of worsening of seizure frequency in some patients.

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Characteristic Cerebral Venous Thrombosis (CVT) in COVID-19: A Systematic Review

Ulum Islamiyyah ◽

10.33102/uij.vol33no1.298 ◽

2021 ◽

pp. 140-148

Author(s):

Sulistyani ◽

Iwan Setiawan ◽

Titian Rakhma ◽

Burhannudin Ichsan

Keyword(s):

Systematic Review ◽

Venous Thrombosis ◽

Cerebral Venous Thrombosis ◽

Virus Disease ◽

Case Reports ◽

Meta Analysis ◽

Case Series ◽

Eligibility Criteria ◽

Online Databases ◽

D Dimer

Cerebral venous thrombosis (CVT) is one of the diagnoses reported in coronavirus disease 2019 (COVID-19 patients). Meanwhile, the severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) infection has the potential to cause endothelial dysfunction, increase thrombin generation and inhibit fibrinolysis. This causes hyper coagulopathy, with the potential to become CVT. Therefore, this study aims to determine the characteristics of CVT cases in COVID-19 patients. This systematic review refers to the PRISMA (Preferred Reporting Items for Systematic Review and Meta-analysis) guidelines. The articles were obtained systematically from online databases, Pubmed, Science Direct, as well as Google Scholar, using the search keywords ("COVID 19" OR "SARS-CoV-2 infection" OR "COVID-19 virus disease" OR "2019-nCoV infection" OR "coronavirus disease 2019" OR "coronavirus disease-19" OR "2019- nCoV disease "OR" COVID-19 virus infection") AND" cerebral venous thrombosis " as well as " cerebral venous thrombosis ". After deduplication, eligibility criteria selection and critical assessment on journals, the study reviewed eight patients from four case reports and two case series. According to the characterization, CVT patients with COVID-19 had a mean age of 42.4 years, were mostly male, tended to be cryptogenic, as well as varied neurological symptoms, and increased D-Dimer in most cases. All patients showed CVT features on imaging and were treated using mostly anticoagulants. Five out of the eight patients (50%) died.

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Mechanical thrombectomy in pediatric stroke: systematic review, individual patient data meta-analysis, and case series

Journal of Neurosurgery Pediatrics ◽

10.3171/2019.5.peds19126 ◽

2019 ◽

Vol 24 (5) ◽

pp. 558-571 ◽

Cited By ~ 3

Author(s):

Kartik Bhatia ◽

Hans Kortman ◽

Christopher Blair ◽

Geoffrey Parker ◽

David Brunacci ◽

...

Keyword(s):

Systematic Review ◽

Ischemic Stroke ◽

Acute Ischemic Stroke ◽

Mechanical Thrombectomy ◽

Case Reports ◽

Meta Analysis ◽

Case Series ◽

Neurological Outcomes

OBJECTIVEThe role of mechanical thrombectomy in pediatric acute ischemic stroke is uncertain, despite extensive evidence of benefit in adults. The existing literature consists of several recent small single-arm cohort studies, as well as multiple prior small case series and case reports. Published reports of pediatric cases have increased markedly since 2015, after the publication of the positive trials in adults. The recent AHA/ASA Scientific Statement on this issue was informed predominantly by pre-2015 case reports and identified several knowledge gaps, including how young a child may undergo thrombectomy. A repeat systematic review and meta-analysis is warranted to help guide therapeutic decisions and address gaps in knowledge.METHODSUsing PRISMA-IPD guidelines, the authors performed a systematic review of the literature from 1999 to April 2019 and individual patient data meta-analysis, with 2 independent reviewers. An additional series of 3 cases in adolescent males from one of the authors’ centers was also included. The primary outcomes were the rate of good long-term (mRS score 0–2 at final follow-up) and short-term (reduction in NIHSS score by ≥ 8 points or NIHSS score 0–1 at up to 24 hours post-thrombectomy) neurological outcomes following mechanical thrombectomy for acute ischemic stroke in patients < 18 years of age. The secondary outcome was the rate of successful angiographic recanalization (mTICI score 2b/3).RESULTSThe authors’ review yielded 113 cases of mechanical thrombectomy in 110 pediatric patients. Although complete follow-up data are not available for all patients, 87 of 96 (90.6%) had good long-term neurological outcomes (mRS score 0–2), 55 of 79 (69.6%) had good short-term neurological outcomes, and 86 of 98 (87.8%) had successful angiographic recanalization (mTICI score 2b/3). Death occurred in 2 patients and symptomatic intracranial hemorrhage in 1 patient. Sixteen published thrombectomy cases were identified in children < 5 years of age.CONCLUSIONSMechanical thrombectomy may be considered for acute ischemic stroke due to large vessel occlusion (ICA terminus, M1, basilar artery) in patients aged 1–18 years (Level C evidence; Class IIb recommendation). The existing evidence base is likely affected by selection and publication bias. A prospective multinational registry is recommended as the next investigative step.

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Neurological symptoms, manifestations, and complications associated with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and coronavirus disease 19 (COVID-19)

Journal of Neurology ◽

10.1007/s00415-021-10406-y ◽

2021 ◽

Author(s):

Biyan Nathanael Harapan ◽

Hyeon Joo Yoo

Keyword(s):

Severe Acute Respiratory Syndrome ◽

Case Reports ◽

Case Series ◽

Altered Mental Status ◽

Neurological Complications ◽

Neurological Symptoms ◽

Neurological Manifestations ◽

Fisher Syndrome ◽

Novel Coronavirus ◽

The Impact

AbstractSevere acute respiratory syndrome coronavirus 2 (SARS-CoV-2), a novel coronavirus, is responsible for the outbreak of coronavirus disease 19 (COVID-19) and was first identified in Wuhan, China in December 2019. It is evident that the COVID-19 pandemic has become a challenging world issue. Although most COVID-19 patients primarily develop respiratory symptoms, an increasing number of neurological symptoms and manifestations associated with COVID-19 have been observed. In this narrative review, we elaborate on proposed neurotropic mechanisms and various neurological symptoms, manifestations, and complications of COVID-19 reported in the present literature. For this purpose, a review of all current published literature (studies, case reports, case series, reviews, editorials, and other articles) was conducted and neurological sequelae of COVID-19 were summarized. Essential and common neurological symptoms including gustatory and olfactory dysfunctions, myalgia, headache, altered mental status, confusion, delirium, and dizziness are presented separately in sections. Moreover, neurological manifestations and complications that are of great concern such as stroke, cerebral (sinus) venous thrombosis, seizures, meningoencephalitis, Guillain–Barré syndrome, Miller Fisher syndrome, acute myelitis, and posterior reversible encephalopathy syndrome (PRES) are also addressed systematically. Future studies that examine the impact of neurological symptoms and manifestations on the course of the disease are needed to further clarify and assess the link between neurological complications and the clinical outcome of patients with COVID-19. To limit long-term consequences, it is crucial that healthcare professionals can early detect possible neurological symptoms and are well versed in the increasingly common neurological manifestations and complications of COVID-19.

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Risk of colectomy after conservative treatment of diverticulitis of the left hemicolon complicated by abdominal or pelvic abscess: protocol of a systematic review and meta-analysis

BMJ Open ◽

10.1136/bmjopen-2020-042350 ◽

2020 ◽

Vol 10 (12) ◽

pp. e042350

Author(s):

Maximilian Sohn ◽

Ayman Agha ◽

Igors Iesalnieks ◽

Anna Tiefes ◽

Alfred Hochrein ◽

...

Keyword(s):

Systematic Review ◽

Emergency Surgery ◽

Case Reports ◽

Acute Diverticulitis ◽

Meta Analysis ◽

Case Series ◽

Pelvic Abscess ◽

Risk Of Bias ◽

Cochrane Central Register ◽

Review Manager

IntroductionAcute diverticulitis of the sigmoid colon is increasingly treated by a non-operative approach. The need for colectomy after recovery from a flare of acute diverticulitis of the left colon, complicated diverticular abscess is still controversial. The primary aim of this study is to assess the risk of interval emergency surgery by systematic review and meta-analysis.Methods and analysisThe systematic review and meta-analysis will be conducted in accordance to the Preferred Reporting Items for Systematic Review and Meta-Analysis Protocols statement. PubMed/MEDLINE, Cochrane Central Register of Controlled Trials and EMBASE will be screened for the predefined searching term: (Diverticulitis OR Diverticulum) AND (Abscess OR pelvic abscess OR pericolic abscess OR intraabdominal abscess) AND (surgery OR operation OR sigmoidectomy OR drainage OR percutaneous drainage OR conservative therapy OR watchful waiting). All studies published in an English or German-speaking peer-reviewed journal will be suitable for this analysis. Case reports, case series of less than five patients, studies without follow-up information, systematic and non-systematic reviews and meta-analyses will be excluded. Primary endpoint is the rate of interval emergency surgery. Using the Review Manager Software (Review Manager/RevMan, V.5.3, Copenhagen, The Nordic Cochrane Centre, The Cochrane Collaboration, 2012) meta-analysis will be pooled using the Mantel-Haenszel method for random effects. The Risk of Bias in Non-randomized Studies of Interventions tool will be used to assess methodological quality of non-randomised studies. Risk of bias in randomised studies will be assessed using the Cochrane developed RoB 2-tool.Ethics and disseminationAs no new data are being collected, ethical approval is exempt for this study. This systematic review is to provide a new insight on the need for surgical treatment after a first attack of acute diverticulitis, complicated by intra-abdominal or pelvic abscesses. The results of this study will be presented at national and international meetings and published in a peer-reviewed journal.PROSPERO registration numberCRD42020164813.

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Psychological and Behavioral Impact of Lockdown and Quarantine Measures for COVID-19 Pandemic on Children, Adolescents and Caregivers: A Systematic Review and Meta-Analysis

Journal of Tropical Pediatrics ◽

10.1093/tropej/fmaa122 ◽

2020 ◽

Author(s):

Prateek Kumar Panda ◽

Juhi Gupta ◽

Sayoni Roy Chowdhury ◽

Rishi Kumar ◽

Ankit Kumar Meena ◽

...

Keyword(s):

Systematic Review ◽

Sleep Disturbance ◽

Behavioral Problems ◽

Meta Analysis ◽

Random Effect ◽

Psychological Problems ◽

Psychological State ◽

Eligibility Criteria ◽

Behavioral Abnormalities ◽

Anxiety Depression

Abstract Background During the current ongoing COVID-19 pandemic, psychological problems like anxiety, depression, irritability, mood swings, inattention and sleep disturbance are fairly common among quarantined children in several studies. A systematic review of these publications to provide an accurate burden of these psychiatric/behavioral problems is needed for planning mitigating measures by the health authorities. Methods Different electronic databases (MEDLINE, EMBASE, Web of Science, CENTRAL, medRxiv and bioRxiv) were searched for articles describing psychological/behavioral complications in children/adolescents with/without pre-existing behavioral abnormalities and their caregivers related to the COVID-19 pandemic. Only original articles with/without comparator arms and a minimum sample size of 50 were included in the analysis. The pooled estimate of various psychological/behavioral problems was calculated using a random-effect meta-analysis. Results Fifteen studies describing 22 996 children/adolescents fulfilled the eligibility criteria from a total of 219 records. Overall, 34.5%, 41.7%, 42.3% and 30.8% of children were found to be suffering from anxiety, depression, irritability and inattention. Although the behavior/psychological state of a total of 79.4% of children was affected negatively by the pandemic and quarantine, at least 22.5% of children had a significant fear of COVID-19, and 35.2% and 21.3% of children had boredom and sleep disturbance. Similarly, 52.3% and 27.4% of caregivers developed anxiety and depression, respectively, while being in isolation with children. Conclusion Anxiety, depression, irritability, boredom, inattention and fear of COVID-19 are predominant new-onset psychological problems in children during the COVID-19 pandemic. Children with pre-existing behavioral problems like autism and attention deficit hyperactivity disorder have a high probability of worsening of their behavioral symptoms.

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COVID-19 and Influenza Co-infection: A Systematic Review and Meta-Analysis

Frontiers in Medicine ◽

10.3389/fmed.2021.681469 ◽

2021 ◽

Vol 8 ◽

Author(s):

Masoud Dadashi ◽

Saeedeh Khaleghnejad ◽

Parisa Abedi Elkhichi ◽

Mehdi Goudarzi ◽

Hossein Goudarzi ◽

...

Keyword(s):

Systematic Review ◽

Case Reports ◽

Influenza Infection ◽

Meta Analysis ◽

Clinical Manifestations ◽

Case Series ◽

Influenza Viruses ◽

Original Research ◽

Respiratory Pathogens ◽

Prevalence Studies

Background and Aim: Co-infection of COVID-19 with other respiratory pathogens which may complicate the diagnosis, treatment, and prognosis of COVID-19 emerge new concern. The overlap of COVID-19 and influenza, as two epidemics at the same time can occur in the cold months of the year. The aim of current study was to evaluate the rate of such co-infection as a systematic review and meta-analysis.Methods: A systematic literature search was performed on September 28, 2019 for original research articles published in Medline, Web of Science, and Embase databases from December 2019 to September 2020 using relevant keywords. Patients of all ages with simultaneous COVID-19 and influenza were included. Statistical analysis was performed using STATA 14 software.Results: Eleven prevalence studies with total of 3,070 patients with COVID-19, and 79 patients with concurrent COVID-19 and influenza were selected for final evaluation. The prevalence of influenza infection was 0.8% in patients with confirmed COVID-19. The frequency of influenza virus co-infection among patients with COVID-19 was 4.5% in Asia and 0.4% in the America. Four prevalence studies reported the sex of patients, which were 30 men and 31 women. Prevalence of co-infection with influenza in men and women with COVID-19 was 5.3 and 9.1%, respectively. Eight case reports and 7 case series with a total of 123 patients with COVID-19 were selected, 29 of them (16 men, 13 women) with mean age of 48 years had concurrent infection with influenza viruses A/B. Fever, cough, and shortness of breath were the most common clinical manifestations. Two of 29 patients died (6.9%), and 17 out of 29 patients recovered (58.6%). Oseltamivir and hydroxychloroquine were the most widely used drugs used for 41.4, and 31% of patients, respectively.Conclusion: Although a low proportion of COVID-19 patients have influenza co-infection, however, the importance of such co-infection, especially in high-risk individuals and the elderly, cannot be ignored. We were unable to report the exact rate of simultaneous influenza in COVID-19 patients worldwide due to a lack of data from several countries. Obviously, more studies are needed to evaluate the exact effect of the COVID-19 and influenza co-infection in clinical outcomes.

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Abstract 181: A Systematic Review of Interventions to Increase tPA Administration

Stroke ◽

10.1161/str.47.suppl_1.181 ◽

2016 ◽

Vol 47 (suppl_1) ◽

Author(s):

Mollie McDermott ◽

Lesli E Skolarus ◽

James F Burke

Keyword(s):

Systematic Review ◽

Public Education ◽

Small Sample Size ◽

Case Reports ◽

Meta Analysis ◽

Experimental Studies ◽

Fixed Effect Model ◽

Small Sample ◽

Eligibility Criteria ◽

Design Elements

Introduction: Rates of tPA administration remain low nationally and globally despite its demonstrated efficacy. We performed a systematic review and meta-analysis of interventions to increase the rate of tPA administration. Methods: We searched PubMed and EMBASE to identify all studies (excluding case reports) published between 1995 and January 8, 2015 documenting interventions to increase the utilization of tPA. We screened each study with pre-specified inclusion and exclusion criteria. Design elements and study data were extracted from eligible studies. The principal summary measure was the percentage change in rate of tPA administration. Fixed and random effects meta-analytic models were built to summarize the effect of intervention compared to control as well as intervention subtypes. Results: Our search yielded 1457 results of which 25 met eligibility criteria. We identified 13 pre-post studies and 11 randomized or quasi-experimental studies. Included studies utilized EMS (n=14), telemedicine (n=6), and public education (n=5). Intervention settings included urban (n=13), rural (n=4), and combined (n=4). In a fixed effect model, tPA administration was significantly higher in the intervention arm across all studies that limited enrollment to ischemic stroke patients (n=14) with a risk ratio (RR) of 1.71. Interventions involving EMS were associated with an increased rate of tPA administration with a RR of 1.51, (95% CI: 1.43-1.59, p<0.0001); promoting public education RR = 2.62, (95% CI: 1.54-4.43, p<0.01); and utilizing telemedicine RR = 2.97, (95% CI: 2.61-3.39, p<0.0001). Conclusions: Interventions to increase tPA use appear to have considerable efficacy. Comparative inferences between intervention types are limited by small sample size and intervention heterogeneity.

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Effect of pragmatic versus explanatory interventions on medication adherence in people with cardiometabolic conditions: a systematic review and meta-analysis

BMJ Open ◽

10.1136/bmjopen-2019-036575 ◽

2020 ◽

Vol 10 (7) ◽

pp. e036575

Author(s):

Claire Fitzpatrick ◽

Clare Gillies ◽

Samuel Seidu ◽

Debasish Kar ◽

Ekaterini Ioannidou ◽

...

Keyword(s):

Systematic Review ◽

Medication Adherence ◽

Real World ◽

Meta Analysis ◽

Random Effect ◽

Routine Care ◽

Outcome Data ◽

Eligibility Criteria ◽

Novel Approach ◽

Explanatory Trials

ObjectiveTo synthesise findings from randomised controlled trials (RCTs) of interventions aimed at increasing medication adherence in individuals with type 2 diabetes (T2DM) and/or cardiovascular disease (CVD). And, in a novel approach, to compare the intervention effect of studies which were categorised as being more pragmatic or more explanatory using the Pragmatic-Explanatory Continuum Indicator Summary-2 (PRECIS-2) tool, to identify whether study design affects outcomes. As explanatory trials are typically held under controlled conditions, findings from such trials may not be relatable to real-world clinical practice. In comparison, pragmatic trials are designed to replicate real-world conditions and therefore findings are more likely to represent those found if the intervention were to be implemented in routine care.DesignSystematic review and meta-analysis.Data sourcesOvid Medline, Ovid Embase, Web of Science and CINAHL from 1 January 2013 to 31 December 2018.Eligibility criteria for selecting studiesRCTs lasting ≥3 months (90 days), involving ≥200 patients in the analysis, with either established CVD and/or T2DM and which measured medication adherence. From 4403 citations, 103 proceeded to full text review. Studies published in any language other than English and conference abstracts were excluded.Main outcome measureChange in medication adherence.ResultsOf 4403 records identified, 34 studies were considered eligible, of which 28, including 30 861 participants, contained comparable outcome data for inclusion in the meta-analysis. Overall interventions were associated with an increase in medication adherence (OR 1.57 (95% CI: 1.33 to 1.84), p<0.001; standardised mean difference 0.24 (95% CI: −0.10 to 0.59) p=0.101). The effectiveness of interventions did not differ significantly between studies considered pragmatic versus explanatory (p=0.598), but did differ by intervention type, with studies that included a multifaceted rather than a single-faceted intervention having a more significant effect (p=0.010). The analysis used random effect models and used the revised Cochrane Risk of Bias Tool to assess study quality.ConclusionsIn this meta-analysis, interventions were associated with a significant increase in medication adherence. Overall multifaceted interventions which included an element of education alongside regular patient contact or follow-up showed the most promise. Effectiveness of interventions between pragmatic and explanatory trials was comparable, suggesting that findings can be transferred from idealised to real-word conditions.PROSPERO registration numberCRD42017059460.

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