Gastrointestinal manifestations of COVID-19 in children: a systematic review and meta-analysis

ObjectivesTo summarise the published evidence on the gastrointestinal manifestations of COVID-19 in children and to determine the prevalence of gastrointestinal symptoms.MethodsIn this systematic review and meta-analysis, we searched PubMed, Embase, CINAHL and the WHO’s database of publications on novel coronavirus. We included English language studies that had described original demographic and clinical characteristics of children diagnosed with COVID-19 and reported on the presence or absence of gastrointestinal symptoms. Meta-analysis was conducted using the random-effects model. The pooled prevalence of gastrointestinal symptoms was expressed as proportion and 95% CI.ResultsThe search identified 269 citations. Thirteen studies (nine case series and four case reports) comprising data for 284 patients were included. Overall, we rated four studies as having a low risk of bias, eight studies as moderate and one study as high risk of bias. In a meta-analysis of nine studies, comprising 280 patients, the pooled prevalence of all gastrointestinal symptoms was 22.8% (95% CI 13.1% to 35.2%; I2=54%). Diarrhoea was the most commonly reported gastrointestinal symptom followed by vomiting and abdominal pain.ConclusionsNearly a quarter of children with COVID-19 have gastrointestinal symptoms. It is important for clinicians to be aware of the gastrointestinal manifestation of COVID-19.PROSPERO registration numberCRD42020177569.

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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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Characteristics of COVID-19 recurrence: a systematic review and meta-analysis

10.1101/2020.09.05.20189134 ◽

2020 ◽

Author(s):

Tung Hoang

Keyword(s):

Systematic Review ◽

Case Reports ◽

Meta Analysis ◽

Disease Onset ◽

Case Series ◽

Final Analysis ◽

Disease Recurrence ◽

Pooled Prevalence ◽

Epidemiological Characteristics

AbstractBackgroundPrevious studies reported the recurrence of coronavirus disease 2019 (COVID-19) among discharge patients. This study aimed to examine the characteristic of COVID-19 recurrence cases by performing a systematic review and meta-analysis.MethodsA systematic search was performed in PubMed and Embase and gray literature up to September 17, 2020. A random-effects model was applied to obtain the pooled prevalence of disease recurrence among recovered patients and the prevalence of subjects underlying comorbidity among recurrence cases. The other characteristics were calculated based on the summary data of individual studies.ResultsA total of 41 studies were included in the final analysis, we have described the epidemiological characteristics of COVID-19 recurrence cases. Of 3,644 patients recovering from COVID-19 and being discharged, an estimate of 15% (95% CI, 12% to 19%) patients was re-positive with SARS-CoV-2 during the follow-up. This proportion was 14% (95% CI, 11% to 17%) for China and 31% (95% CI, 26% to 37%) for Korea. Among recurrence cases, it was estimated 39% (95% CI, 31% to 48%) subjects underlying at least one comorbidity. The estimates for times from disease onset to admission, from admission to discharge, and from discharge to RNA positive conversion were 4.8, 16.4, and 10.4 days, respectively.ConclusionThis study summarized up-to-date evidence from case reports, case series, and observational studies for the characteristic of COVID-19 recurrence cases after discharge. It is recommended to pay attention to follow-up patients after discharge, even if they have been in quarantine.

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Frequency of neurological manifestations in COVID-19: a systematic review and meta-analysis of 350 studies

10.1101/2021.04.20.21255780 ◽

2021 ◽

Author(s):

Shubham Misra ◽

Kavitha Kolappa ◽

Manya Prasad ◽

Divya Radhakrishnan ◽

Kiran T Thakur ◽

...

Keyword(s):

Systematic Review ◽

Disease Severity ◽

Meta Analysis ◽

Case Series ◽

Risk Of Bias ◽

Cochrane Library ◽

Neurological Manifestations ◽

Pooled Prevalence ◽

Prevalence Estimates ◽

Acute Confusion

SummaryObjectiveTo summarize the frequency of neurological manifestations reported in COVID-19 patients and investigate the association of these manifestations with disease severity and mortality.DesignSystematic review and meta-analysisEligibility criteriaStudies enrolling consecutive COVID-19 patients (probable or confirmed) presenting with neurological manifestations.Data sourcesPubMed, Medline, Cochrane library, clinicaltrials.gov and EMBASE from 31st December 2019 to 15th December 2020.Data extraction and analysisTwo authors independently screened titles and abstracts retrieved by literature search. Risk of bias was examined using Joanna Briggs Institute (JBI) scale. A random-effects meta-analysis was performed, and pooled prevalence and 95% Confidence Intervals (CI) were calculated for neurological manifestations. Odds ratio (OR) and 95%CI were calculated to determine the association of neurological manifestations with disease severity and mortality. Presence of heterogeneity was assessed using I-square, meta-regression, and subgroup analyses. Statistical analyses were conducted in R version 3.6.2.ResultsOf 2,455 citations, 350 studies were included in this review, providing data on 145,634 COVID-19 patients, 89% of whom were hospitalized. Forty-one neurological manifestations (24 symptoms and 17 diagnoses) were identified. Pooled prevalence of the most common neurological symptoms included: fatigue (32%), myalgia (20%), taste impairment (21%), smell impairment (19%) and headache (13%). A low risk of bias was observed in 85% of studies; studies with higher risk of bias yielded higher prevalence estimates. Stroke was the most common neurological diagnosis (pooled prevalence-2%). In COVID-19 patients aged >60, the pooled prevalence of acute confusion/delirium was 34% and the presence of any neurological manifestations in this age group was associated with mortality (OR 1.80; 95%CI 1.11 to 2.91).ConclusionsUp to one-third of COVID-19 patients analysed in this review experienced at least one neurological manifestation. One in 50 patients experienced stroke. In those over 60, more than one-third had acute confusion/delirium; the presence of neurological manifestations in this group was associated with near doubling of mortality. Results must be interpreted keeping in view the limitations of observational studies and associated bias.Systematic review registrationPROSPERO CRD42020181867.What is already known on this topicThe frequency of neurological manifestations including fatigue, myalgia, taste and smell impairments, headache and dizziness in COVID-19 patients has been reported in a few systematic reviews and meta-analyses. However, considerable heterogeneity has been observed in terms of methodological quality of the studies, severity of the disease, mean age and hospitalization status of the patients. The evidence regarding the frequency of neurological diagnoses including stroke, encephalitis, Guillain Barré syndrome (GBS) is also limited to case reports and case series and no data exists thus far on the pooled prevalence estimates for neurological diagnoses in COVID-19 patients.What this study addsTo the best of the authors’ knowledge, this is the largest systematic review and meta-analysis to date (including 350 studies with data on 145,634 cases) summarizing the evidence on the frequency of the full spectrum of neurological manifestations in COVID-19 patients in the overall, young and elderly populations. For the first time, our review reports the pooled prevalence of stroke in COVID-19 patients. Risk of bias, old age and disease severity were potential determinants of the frequency and nature of neurological manifestations as well as its association with mortality. Our review also highlights the need to develop reporting standards for studies describing the frequency of clinical features. Moreover, we note that this will be the first systematic review and meta-analysis on this subject to include studies reported in all languages.

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Prevalence, clinical characteristics and treatment outcomes of HIV and SARS-CoV-2 co-infection: a systematic review and meta-analysis

10.1101/2020.05.31.20118497 ◽

2020 ◽

Author(s):

Joseph Baruch Baluku ◽

Ronald Olum ◽

Curthbert Agolor ◽

Josephine Nakakande ◽

Laura Russell ◽

...

Keyword(s):

Clinical Characteristics ◽

English Language ◽

Case Reports ◽

Meta Analysis ◽

Grey Literature ◽

Random Effect ◽

Case Series ◽

Comorbid Condition ◽

Hiv Viral Load ◽

Pooled Prevalence

ABSTRACTObjectivesTo determine the prevalence, clinical characteristics and outcomes of HIV and severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) co-infection.MethodsWe searched Medline, Embase, Cochrane and Web of Science databases and grey literature for studies reporting epidemiological and clinical data of patients with HIV and SARS-CoV-2 co-infection. Eligible studies were all observational or interventional studies and commentaries in English language that reported patient data on HIV/SARS-CoV-2 co-infection. We used random effect meta-analysis to determine the pooled prevalence and mortality.ResultsOf the 17 eligible studies, there were 3 retrospective cohorts, 1 survey, 5 case series, 7 case reports and 1 commentary that reported on a total of 146 HIV infected individuals. The pooled prevalence of HIV among individuals with SARS-CoV-2 infection was 1.0% (95% CI: 0.0 – 3.0, I2 = 79.3%, p = 0.01), whereas the prevalence of SARS-CoV-2 among HIV patients was 0.68% (95% CI: 0.34 – 1.34).There were 110 (83.8%) HIV/ SARS-CoV-2 co-infected males, and the age (range) of the co-infected was 30 – 60 years. A total of 129 (97.0%) were anti-retroviral therapy experienced, and 113 (85.6%) had a suppressed HIV viral load. The CD4 count (range) was 298 – 670 cells/mm3 (n = 107). The commonest symptoms were fever (73.5%, n = 75) and cough (57.8%, n = 59). Sixty-two (65.3%) patients had at least one other comorbid condition, of which hypertension (26.4%, n = 38) was the commonest. Chest radiological imaging abnormalities were found in 46 (54.1%) cases. Twenty-eight cases (56.0%) were reported as mild. Recovery occurred in 120 (88.9%) cases, and the pooled mortality was 9% (95% CI: 3.0 – 15.0, I2 = 25.6%, p = 0.24).ConclusionThe prevalence of HIV/SARS-CoV-2 co-infection was low. The clinical characteristics and outcomes of HIV/SARS-CoV-2 co-infection are comparable to those reported among HIV negative SARS-CoV-2 cases.

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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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Systematic review to investigate the safety of induction and augmentation of labour among pregnant women with iron-deficiency anaemia

BMJ Open ◽

10.1136/bmjopen-2018-021793 ◽

2018 ◽

Vol 8 (12) ◽

pp. e021793 ◽

Cited By ~ 1

Author(s):

Kathryn Bunch ◽

Nia Roberts ◽

Marian Knight ◽

Manisha Nair

Keyword(s):

Systematic Review ◽

Iron Deficiency ◽

Pregnant Women ◽

Iron Deficiency Anaemia ◽

Case Reports ◽

Case Series ◽

Severe Anaemia ◽

Risk Of Bias ◽

Deficiency Anaemia ◽

Increased Risk

ObjectiveTo conduct a systematic review to investigate the safety of induction and/or augmentation of labour compared with spontaneous-onset normal labour among pregnant women with iron-deficiency anaemia.DesignSystematic review.SettingStudies from all countries, worldwide.PopulationPregnant women with iron-deficiency anaemia at labour and delivery.InterventionAny intervention related to induction and/or augmentation of labour.Outcome measuresPrimary: Postpartum haemorrhage (PPH), heart failure and maternal death. Secondary: Emergency caesarean section, hysterectomy, admission to intensive care unit.MethodWe searched 10 databases, including Medline and Embase, from database inception to 1 October 2018. We included all study designs except cross-sectional studies without a comparator group, case reports, case series, ecological studies, and expert opinion. The searches were conducted by a healthcare librarian and two authors independently screened and reviewed the studies. We used the Grading of Recommendations, Assessment, Development and Evaluations (GRADE) approachto ascertain risk of bias and conducted a narrative synthesis.ResultsWe identified 3217 journal articles, 223 conference papers, 45 dissertations and 218 registered trials. Ten articles were included for full-text review and only one was found to fulfil the eligibility criteria. This was a retrospective cohort study from India, which showed that pregnant women with moderate and severe anaemia could have an increased risk of PPH if they underwent induction and/or augmentation of labour, but the evidence was weak (graded as ‘high risk of bias’).ConclusionThe best approach is to prevent anaemia, but a large number of women in low-to-middle-income countries present with severe anaemia during labour. In such women, appropriate peripartum management could prevent complications and death. Our review showed that at present we do not know if induction and augmentation of labour is safe in pregnant women with iron-deficiency anaemia and further research is required.PROSPERO registration numberCRD42015032421.

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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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Prevalence of smoking in adults with spinal cord stimulators: a systematic review and meta-analysis

Regional Anesthesia and Pain Medicine ◽

10.1136/rapm-2019-100996 ◽

2020 ◽

Vol 45 (3) ◽

pp. 214-218

Author(s):

W Michael Hooten ◽

Rajat N Moman ◽

Jodie Dvorkin ◽

E Morgan Pollard ◽

Robalee Wonderman ◽

...

Keyword(s):

Systematic Review ◽

Spinal Cord ◽

Smoking Status ◽

Meta Analysis ◽

Vascular Diseases ◽

Risk Of Bias ◽

Future Research ◽

Cross Sectional ◽

Prevalence Studies ◽

Pooled Prevalence

BackgroundSmoking adversely impacts pain-related outcomes of spinal cord stimulation (SCS). However, the proportion of SCS patients at risk of worse outcomes is limited by an incomplete knowledge of smoking prevalence in this population. Thus, the primary aim of this systematic review is to determine the prevalence of smoking in adults with chronic pain treated with SCS.MethodsA comprehensive search of databases from 1 January 1980 to 3 January 2019 was conducted. Eligible study designs included (1) randomized trials; (2) prospective and retrospective cohort studies; and (3) cross-sectional studies. The risk of bias was assessed using a tool specifically developed for prevalence studies. A total of 1619 records were screened, 19 studies met inclusion criteria, and the total number of participants was 10 838.ResultsThirteen studies had low or moderate risk of bias, and six had a high risk of bias. All 19 studies reported smoking status and the pooled prevalence was 38% (95% CI 30% to 47%). The pooled prevalence in 6 studies of peripheral vascular diseases was 56% (95% CI 42% to 69%), the pooled prevalence of smoking in 11 studies of lumbar spine diagnoses was 28% (95% CI 20% to 36%) and the pooled prevalence in 2 studies of refractory angina was 44% (95% CI 31% to 58%).ConclusionsThe estimated prevalence of smoking in SCS patients is 2.5 times greater than the general population. Future research should focus on development, testing and deployment of tailored smoking cessation treatments for SCS patients.

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Intralesional cryotherapy for hypertrophic scars and keloids: a review

Scars Burns & Healing ◽

10.1177/2059513117702162 ◽

2017 ◽

Vol 3 ◽

pp. 205951311770216 ◽

Cited By ~ 5

Author(s):

Ciaran P O’Boyle ◽

Holleh Shayan-Arani ◽

Maha Wagdy Hamada

Keyword(s):

English Language ◽

Meta Analysis ◽

Case Series ◽

Evidence Base ◽

Treatment Modalities ◽

Hypertrophic Scars ◽

Published Evidence ◽

Keloid Scarring ◽

Comparative Trials ◽

Scar Reduction

Introduction: Hypertrophic and keloid scarring remain notoriously troublesome for patients to tolerate and frustratingly difficult for clinicians to treat. Many different treatment modalities exist, signifying the failure of any method to achieve consistently excellent results. Intralesional cryotherapy is a relatively recent development that uses a double lumen needle, placed through the core of a keloid or hypertrophic scar, to deliver nitrogen vapour, which freezes the scar from its core, outwards. Methods: This article provides a comprehensive review of the literature on intralesional cryotherapy for hypertrophic scars and keloids. A systematic review or meta-analysis was not possible, since the existing articles did not permit this. Results: A search of English language, peer-reviewed literature was carried out. The evidence base was found to be low (level 4). In addition, much of the published evidence comes from a very few groups. Despite this, consistent findings from case series suggest that the technique is safe and achieves good scar reduction with very few treatments. Adverse effects include depigmentation, recurrence and pain. Pain and recurrence appear to be uncommon and depigmentation may be temporary. Discussion: Well-constructed, prospectively recruited comparative trials are absent from the literature. These are strongly encouraged, in order to strengthen general confidence in this technique and in the repeatability of outcomes reported thus far.

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Proton pump inhibitors do not increase the risk of dementia: a systematic review and meta-analysis of prospective studies

Diseases of the Esophagus ◽

10.1093/dote/doaa041 ◽

2020 ◽

Vol 33 (10) ◽

Author(s):

Madhav Desai ◽

Venkat Nutalapati ◽

Sachin Srinivasan ◽

Jihan Fathallah ◽

Chandra Dasari ◽

...

Keyword(s):

Systematic Review ◽

Proton Pump ◽

Prospective Studies ◽

Case Reports ◽

Meta Analysis ◽

Case Series ◽

Extensive Literature ◽

Meta Regression

SUMMARY Published studies have reported variable results on the association between duration of proton pump inhibitor (PPI) use and the risk of dementia. An extensive literature search was performed in PubMed, Embase, Google Scholar, and Cochrane for studies examining the risk of cognitive decline and dementia among PPI users versus non-PPI users in prospective studies. Retrospective database linkage studies, case reports, case series, editorials, uncontrolled cohort studies, cross-sectional studies, and review articles were excluded. Primary outcome was pooled hazard rate (HR) of any dementia among PPI users compared with non-PPI users. Secondary outcomes were pooled HR of Alzheimer’s dementia (AD) and risk with long-term PPI follow-up (more than 5 years) studies. Meta-analysis outcomes, heterogeneity (I2), and meta-regression (for the effect of covariates) were derived by statistical software R and Open meta-analyst. A total of six studies (one RCT and five prospective) with 308249 subjects, average age of 75.8 ± 5.2 years, and follow-up of 5 (range 1.5–11) years were included in the analysis. Pooled HR of any dementia was 1.16 (n = 6, 95% confidence interval (CI) = 0.86–1.47). Results remained unchanged when only studies with long-term PPI use (more than 5 years) were analyzed (n = 4, pooled HR 1.10, 95% CI 0.66–1.53). Finally, the pooled HR for AD was 1.06 (n = 3, 95% CI 0.70–1.41). There was substantial heterogeneity among inclusion studies (I2 = 93%). Meta-regression did not demonstrate a significant role of age at study start (P = 0.1) or duration of PPI use (P = 0.62) to incident dementia. The results of this systematic review and meta-analysis do not show a significant relationship between PPI use and dementia in prospective studies with at least a 5-year follow-up.

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