Risk of SARS-CoV-2 infection and COVID-19 prognosis with the use of renin–angiotensin–aldosterone system (RAAS) inhibitors: a systematic review

Abstract Background Angiotensin-converting-enzyme-2, being the receptor for SARS-CoV-2, is increased in the use of RAAS inhibitors. Therefore, concerns have been raised over risks of SARS-CoV-2 infection and poor prognosis of COVID-19 in persons with prior exposure to these drugs. This study aimed to systematically review available evidence for associations between exposure to RAAS inhibitors with susceptibility to SARS-CoV-2 infection and clinical outcomes in infected persons. It hopes to address the question on the effects of RAAS inhibitors on the risk of COVID-19 and its prognosis. Main body Search was conducted in the databases of PubMed, Scopus, Cochrane, Embase and MedRxiv.org from December 2019 to May 31, 2020, using relevant keywords. Additional articles were identified through hand-searching of reference lists. Studies that reported associations between positive tests to COVID-19 and use of RAAS inhibitors, and treatment outcomes of COVID-19 patients who had exposure to RAAS inhibitors were considered eligible. The Newcastle–Ottawa scale was used to assess risk of bias in individual studies. The review was conducted in line with Preferred Regulatory Items for Systematic Reviews and Meta-Analysis (PRISMA) guidelines 2009. From the 952 studies screened and 2 studies from reference hand-searching, 18 were reviewed. Four studies evaluated the risks for SARS-CoV-2 infection among RAAS inhibitors users, and 16 (including 2 of the 4 studies) evaluated the clinical outcomes associated with previous exposure to RAAS inhibitors. Conclusion Evidence does not suggest higher risks for SARS-CoV-2 infection or poor disease prognosis in the use of RAAS inhibitors. This suggests the continued use of RAAS inhibitors by patients with existing needs, which supports the position statements of American Heart Association and European societies for Cardiology.

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Prevalence of Cognitive Impairment and Dementia in Older Adults Living at High Altitude: A Systematic Review and Meta-Analysis

Dementia and Geriatric Cognitive Disorders ◽

10.1159/000514471 ◽

2021 ◽

pp. 1-11

Author(s):

Diego Urrunaga-Pastor ◽

Diego Chambergo-Michilot ◽

Fernando M. Runzer-Colmenares ◽

Josmel Pacheco-Mendoza ◽

Vicente A. Benites-Zapata

Keyword(s):

Older Adults ◽

Cognitive Impairment ◽

High Altitude ◽

Web Of Science ◽

Meta Analysis ◽

Cross Sectional ◽

Language Restriction ◽

Newcastle Ottawa Scale ◽

Meta Analyses ◽

Ottawa Scale

Introduction: Dementia is a chronic disease with a variable prevalence throughout the world; however, this could be higher at high-altitude populations. We aimed to summarize the prevalence of cognitive impairment and dementia in older adults living at high altitude. Methods: We searched in PubMed, Medline, Scopus, Web of Science, and Embase and included the studies published from inception to July 20, 2020, with no language restriction, which reported the frequency of cognitive impairment or dementia in older adults living at high-altitude populations. Random-effects meta-analyses were performed to calculate the overall prevalence and 95% confidence intervals (95% CI) of cognitive impairment and dementia. The risk of bias was evaluated using the Newcastle-Ottawa Scale (NOS) adapted for cross-sectional studies. Results: Six studies were included (3,724 participants), and 5 of the 6 included studies were carried out in Latin America. The altitude ranged from 1,783 to 3,847 m, the proportion of women included varied from 38.7 to 65.6%, and the proportion of participants with elementary or illiterate educational level ranged from 71.7 to 97.6%. The overall prevalence of cognitive impairment was 22.0% (95% CI: 8–40, I2: 99%), and the overall prevalence of dementia was 11.0% (95% CI: 6–17, I2: 92%). In a subgroup analysis according to the instrument used to evaluate cognitive impairment, the prevalence of cognitive impairment was 21.0% (95% CI: 5–42, I2: 99%) in the MMSE group while the prevalence was 29.0% (95% CI: 0–78) in the non-MMSE group. Conclusions: The prevalence of cognitive impairment and dementia in older adults living at high altitude is almost twice the number reported in some world regions.

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Hydroxychloroquine prophylaxis for preeclampsia, hypertension and prematurity in pregnant patients with systemic lupus erythematosus: A meta-analysis

Lupus ◽

10.1177/09612033211007199 ◽

2021 ◽

pp. 096120332110071

Author(s):

Jiaoniu Duan ◽

Dan Ma ◽

Xiaoting Wen ◽

Qianyu Guo ◽

Jinfang Gao ◽

...

Keyword(s):

Lupus Erythematosus ◽

English Language ◽

Gestational Hypertension ◽

Meta Analysis ◽

Fetal Outcomes ◽

Pregnancy Hypertension ◽

Cochrane Database ◽

Newcastle Ottawa Scale ◽

Prospective Cohorts ◽

Ottawa Scale

Objectives This meta-analysis aimed to evaluate the effectiveness of HCQ in improving the maternal and fetal outcomes in pregnancies with SLE. Methods A literature search was conducted using PubMed, MEDLINE, EMBASE, and the Cochrane database for relevant English language articles, and Wanfang, CNKI and VIP for Chinese articles, from the databases’ inception to April 30, 2020. These studies compared the maternal and/or fetal outcomes between pregnant patients with SLE who were administered HCQ during pregnancy (HCQ+ group) and those who were not administered HCQ (HCQ− group). Two investigators extracted the data and assessed the quality using the Newcastle-Ottawa Scale (NOS) and GRADE criteria independently. Odds ratio (OR) and 95% confidence intervals (CIs) were calculated. All statistical analyses were conducted using the Stata 12.0 software. Results Nine studies involving 1132 pregnancies were included in the study (3 case controls, 2 prospective cohorts, 4 retrospective cohorts). Preeclampsia, gestational hypertension, and prematurity were significantly lower in the HCQ+ group than in the HCQ− group (OR 0.35, 95% CI 0.21–0.59), (OR 0.41, 95% CI 0.19–0.89) and (OR 0.55, 95% CI 0.36–0.86), respectively. There were no significant differences in the rates of HELLP Syndrome (OR 0.88, 95% CI 0.19–3.96), gestational diabetes (OR 2.3, 95% CI 0.44–12.12), thrombotic events (OR 0.26, 95% CI 0.05–1.51), spontaneous abortion (OR 1.77, 95% CI 0.96–3.26), premature rupture of membranes (OR 0.58, 95% CI 0.24–1.39), oligohydramnios (OR 0.90, 95% CI 0.38–2.14), live birth (OR 1.22, 95% CI 0.60–2.47), stillbirth (OR 1.00, 95% CI 0.50–2.00), congenital malformation (OR 0.53, 95% CI 0.14–2.04), low birth weight (OR 0.77, 95% CI 0.43–1.39), intrauterine distress (OR 1.07, 95% CI 0.41–2.76,), intrauterine growth restriction (OR 0.57, 95% CI 0.06–5.43), or five-minute APGAR score <7 (OR 0.72, 95% CI 0.20–2.58) between the two groups. Conclusions HCQ treatment during pregnancy could reduce the risk of preeclampsia, pregnancy hypertension and prematurity in SLE patients. The certainty of evidence is high but majority of the studies included are retrospective studies and not randomized controlled trials. Therefore, the multidisciplinary management of pregnant patients with SLE should promote HCQ use, irrespective of disease activity or severity.

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Clinical outcomes of cancer patients with COVID-19: A systematic review and meta-analysis.

Journal of Clinical Oncology ◽

10.1200/jco.2021.39.15_suppl.e18600 ◽

2021 ◽

Vol 39 (15_suppl) ◽

pp. e18600-e18600

Author(s):

Maryam Alasfour ◽

Salman Alawadi ◽

Malak AlMojel ◽

Philippos Apolinario Costa ◽

Priscila Barreto Coelho ◽

...

Keyword(s):

Mortality Rate ◽

Cancer Patients ◽

Clinical Outcomes ◽

Meta Analysis ◽

Small Sample ◽

Prediction Intervals ◽

Invasive Ventilation ◽

Newcastle Ottawa Scale ◽

Small Sample Sizes ◽

Meta Analyses

e18600 Background: Patients with coronavirus disease 2019 (COVID-19) and cancer have worse clinical outcomes compared to those without cancer. Primary studies have examined this population, but most had small sample sizes and conflicting results. Prior meta-analyses exclude most US and European data or only examine mortality. The present meta-analysis evaluates the prevalence of several clinical outcomes in cancer patients with COVID-19, including new emerging data from Europe and the US. Methods: A systematic search of PubMED, medRxiv, JMIR and Embase by two independent investigators included peer-reviewed papers and preprints up to July 8, 2020. The primary outcome was mortality. Other outcomes were ICU and non-ICU admission, mild, moderate and severe complications, ARDS, invasive ventilation, stable, and clinically improved rates. Study quality was assessed through the Newcastle–Ottawa scale. Random effects model was used to derive prevalence rates, their 95% confidence intervals (CI) and 95% prediction intervals (PI). Results: Thirty-four studies (N = 4,371) were included in the analysis. The mortality prevalence rate was 25.2% (95% CI: 21.1–29.7; 95% PI: 9.8-51.1; I 2 = 85.4), with 11.9% ICU admissions (95% CI: 9.2-15.4; 95% PI: 4.3-28.9; I 2= 77.8) and 25.2% clinically stable (95% CI: 21.1-29.7; 95% PI: 9.8-51.1; I 2 = 85.4). Furthermore, 42.5% developed severe complications (95% CI: 30.4-55.7; 95% PI: 8.2-85.9; I 2 = 94.3), with 22.7% developing ARDS (95% CI: 15.4-32.2; 95% PI: 5.8-58.6; I 2 = 82.4), and 11.3% needing invasive ventilation (95% CI: 6.7-18.4; 95% PI: 2.3-41.1; I 2 = 79.8). Post-follow up, 49% clinically improved (95% CI: 35.6-62.6; 95% PI: 9.8-89.4; I 2 = 92.5). All outcomes had large I 2 , suggesting high levels of heterogeneity among studies, and wide PIs indicating high variability within outcomes. Despite this variability, the mortality rate in cancer patients with COVID-19, even at the lower end of the PI (9.8%), is higher than the 2% mortality rate of the non-cancer with COVID-19 population, but not as high as what other meta-analyses conclude, which is around 25%. Conclusions: Patients with cancer who develop COVID-19 have a higher probability of mortality compared to the general population with COVID-19, but possibly not as high as previous studies have shown. A large proportion of them developed severe complications, but a larger proportion recovered. Prevalence of mortality and other outcomes published in prior meta-analyses did not report prediction intervals, which compromises the clinical utilization of such results.

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Sleep in youth with autism spectrum disorders: systematic review and meta-analysis of subjective and objective studies

Evidence-Based Mental Health ◽

10.1136/ebmental-2018-300037 ◽

2018 ◽

Vol 21 (4) ◽

pp. 146-154 ◽

Cited By ~ 23

Author(s):

Amparo Díaz-Román ◽

Junhua Zhang ◽

Richard Delorme ◽

Anita Beggiato ◽

Samuele Cortese

Keyword(s):

Systematic Review ◽

Autism Spectrum Disorders ◽

Evidence Synthesis ◽

Meta Analysis ◽

Autism Spectrum ◽

Newcastle Ottawa Scale ◽

Spectrum Disorders ◽

Sleep Alterations ◽

The Impact ◽

Ottawa Scale

BackgroundSleep problems are common and impairing in individuals with autism spectrum disorders (ASD). Evidence synthesis including both subjective (ie, measured with questionnaires) and objective (ie, quantified with neurophysiological tools) sleep alterations in youth with ASD is currently lacking.ObjectiveWe conducted a systematic review and meta-analysis of subjective and objective studies sleep studies in youth with ASD.MethodsWe searched the following electronic databases with no language, date or type of document restriction up to 23 May 2018: PubMed, PsycInfo, Embase+Embase Classic, Ovid Medline and Web of Knowledge. Random-effects models were used. Heterogeneity was assessed with Cochran’s Q and I2 statistics. Publication (small studies) bias was assessed with final plots and the Egger’s test. Study quality was evaluated with the Newcastle Ottawa Scale. Analyses were conducted using Review Manager and Comprehensive Meta-Analysis.FindingsFrom a pool of 3359 non-duplicate potentially relevant references, 47 datasets were included in the meta-analyses. Subjective and objective sleep outcome measures were extracted from 37 and 15 studies, respectively. Only five studies were based on comorbidity free, medication-naïve participants. Compared with typically developing controls, youth with ASD significantly differed in 10/14 subjective parameters and in 7/14 objective sleep parameters. The average quality score in the Newcastle-Ottawa Scale was 5.9/9.Discussion and clinical implicationsA number of subjective and, to a less extent, objective sleep alterations might characterise youth with ASD, but future studies should assess the impact of pharmacological treatment and psychiatric comorbidities.

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Quality of anticholinergic burden scales and their impact on clinical outcomes: a systematic review

European Journal of Clinical Pharmacology ◽

10.1007/s00228-020-02994-x ◽

2020 ◽

Author(s):

Angela Lisibach ◽

Valérie Benelli ◽

Marco Giacomo Ceppi ◽

Karin Waldner-Knogler ◽

Chantal Csajka ◽

...

Keyword(s):

Side Effects ◽

Clinical Outcomes ◽

Validation Studies ◽

Multiple Scales ◽

Meta Analysis ◽

Anticholinergic Drug ◽

Burden Scale ◽

Newcastle Ottawa Scale ◽

Anticholinergic Burden

Abstract Purpose Older people are at risk of anticholinergic side effects due to changes affecting drug elimination and higher sensitivity to drug’s side effects. Anticholinergic burden scales (ABS) were developed to quantify the anticholinergic drug burden (ADB). We aim to identify all published ABS, to compare them systematically and to evaluate their associations with clinical outcomes. Methods We conducted a literature search in MEDLINE and EMBASE to identify all published ABS and a Web of Science citation (WoS) analysis to track validation studies implying clinical outcomes. Quality of the ABS was assessed using an adapted AGREE II tool. For the validation studies, we used the Newcastle-Ottawa Scale and the Cochrane tool Rob2.0. The validation studies were categorized into six evidence levels based on the propositions of the Oxford Center for Evidence-Based Medicine with respect to their quality. At least two researchers independently performed screening and quality assessments. Results Out of 1297 records, we identified 19 ABS and 104 validations studies. Despite differences in quality, all ABS were recommended for use. The anticholinergic cognitive burden (ACB) scale and the German anticholinergic burden scale (GABS) achieved the highest percentage in quality. Most ABS are validated, yet validation studies for newer scales are lacking. Only two studies compared eight ABS simultaneously. The four most investigated clinical outcomes delirium, cognition, mortality and falls showed contradicting results. Conclusion There is need for good quality validation studies comparing multiple scales to define the best scale and to conduct a meta-analysis for the assessment of their clinical impact.

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Metabolic Syndrome and Its Components in Patients with COVID-19: Severe Acute Respiratory Syndrome (SARS) and Mortality. A Systematic Review and Meta-Analysis

Journal of Cardiovascular Development and Disease ◽

10.3390/jcdd8120162 ◽

2021 ◽

Vol 8 (12) ◽

pp. 162

Author(s):

Sergio Rico-Martín ◽

Julián F. Calderón-García ◽

Belinda Basilio-Fernández ◽

María Zoraida Clavijo-Chamorro ◽

Juan F. Sánchez Muñoz-Torrero

Keyword(s):

Systematic Review ◽

Metabolic Syndrome ◽

Severe Acute Respiratory Syndrome ◽

Meta Analysis ◽

Risk Of Bias ◽

Newcastle Ottawa Scale ◽

Abstract Screening ◽

The Relationship ◽

Metabolic Comorbidities ◽

Ottawa Scale

Recent meta-analysis studies have reported that metabolic comorbidities such as diabetes, obesity, dyslipidaemia and hypertension are associated with higher risk of severe acute respiratory syndrome (SARS) and mortality in patients with COVID-19. This meta-analysis aims to investigate the relationship between metabolic syndrome (MetS) and its components with SARS and mortality in COVID-19 patients. Methods: A systematic search was conducted in the several databases up until 1 September 2021. Primary observational longitudinal studies published in peer review journals were selected. Two independent reviewers performed title and abstract screening, extracted data and assessed the risk of bias using the Newcastle–Ottawa Scale. Results: The random effects meta-analysis showed that MetS was significantly associated with SARS with a pooled OR (95% CI) of 3.21 (2.88–3.58) and mortality with a pooled OR (95% CI) of 2.32 (1.16–4.63). According to SARS, the pooled OR for MetS was 2.19 (1.71–2.67), p < 0.001; significantly higher than the hypertension component. With regard to mortality, although the pooled OR for MetS was greater than for its individual components, no significant differences were observed. Conclusions: this meta-analysis of cohort studies, showed that MetS is better associated to SARS and mortality in COVID-19 patients than its individual components.

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Prevalence of Sarcopenia and Its Association With Diabetes: A Meta-Analysis of Community-Dwelling Asian Population

Frontiers in Medicine ◽

10.3389/fmed.2021.681232 ◽

2021 ◽

Vol 8 ◽

Author(s):

Seung Min Chung ◽

Jun Sung Moon ◽

Min Cheol Chang

Keyword(s):

Data Extraction ◽

Meta Analysis ◽

Asian Population ◽

The Elderly ◽

Community Dwelling ◽

Geriatric Population ◽

Newcastle Ottawa Scale ◽

Diabetic Population ◽

Ottawa Scale

Purpose: Sarcopenia is a major disease affecting mortality and quality of life in the elderly population. We performed a meta-analysis of studies on the community-dwelling population to investigate the prevalence of sarcopenia and its association with diabetes.Methods: Databases were searched for studies published up to February 3, 2021, reporting the prevalence of sarcopenia in patients with and without diabetes. Data extraction and quality assessment were performed according to the Newcastle-Ottawa scale.Results: Six articles were included in the systematic review. All the patients were Asian, aged ≥60 years (women 53.4%), and the diabetic and non-diabetic population was 1,537 and 5,485, respectively. In all six studies, the Asian Working Group for Sarcopenia criteria were used to diagnose sarcopenia. The prevalence of sarcopenia was 15.9% in diabetics and 10.8% in non-diabetics. Diabetics showed a significantly higher risk of sarcopenia than non-diabetics (pooled OR = 1.518, 95% CI = 1.110 to 2.076, Z-value = 2.611, p = 0.009).Conclusion: Among the Asian community-dwelling geriatric population, the prevalence of sarcopenia was significantly higher in diabetics than in non-diabetics. These results suggest that strategies for the management of sarcopenia are required in Asian elderly patients, especially with diabetes.

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Efficacy and safety of tocilizumab in the management of COVID-19: A systematic review and meta-analysis of observational studies

10.1101/2021.01.27.21250599 ◽

2021 ◽

Author(s):

Gollapalle L Viswanatha ◽

CH K V L S N Anjana Male ◽

Hanumanthappa Shylaja

Keyword(s):

Systematic Review ◽

Meta Analysis ◽

Standard Of Care ◽

Efficacy And Safety ◽

Risk Of Mortality ◽

Significant Difference ◽

Newcastle Ottawa Scale ◽

Soc Control ◽

Ottawa Scale

AbstractBackgroundThis systematic review and meta-analysis was aimed to evaluate the efficacy and safety of tocilizumab (TCZ) in treating severe coronavirus disease 2019 (COVID-19).MethodsThe electronic search was performed using PubMed, Scopus, CENTRAL, and Google scholar to identify the retrospective observational reports. The studies published from 01 January 2020 to 30th September 2020. Participants were hospitalized COVID-19 patients. Interventions included tocilizumab versus placebo/standard of care. The comparison will be between TCZ versus standard of care (SOC)/placebo. Inconsistency between the studies was evaluated with I2 and quality of the evidences were evaluated by Newcastle-Ottawa scale.ResultsBased on the inclusion criteria there were 24 retrospective studies involving 5686 subjects were included. The outcomes of the meta-analysis have revealed that the TCZ has reduced the mortality (M-H,RE-OR −0.11(−0.18 to −0.04) 95% CI, p =0.001, I2 =88%) and increased the incidences of super-infections (M-H, RE-OR 1.49(1.13 to 1.96) 95% CI, p=0.004, I2=47%). However, there is no significant difference in ICU admissions rate (M-H, RE-OR −0.06(−0.23 to 0.12), I2=93%), need of MV (M-H, RE-OR of 0.00(−0.06 to 0.07), I = 74%), LOS (IV −2.86(−0.91 to 3.38), I2=100%), LOS-ICU (IV: −3.93(−12.35 to 4.48), I2=100%), and incidences of pulmonary thrombosis (M-H, RE-OR 1.01 (0.45 to 2.26), I2=0%) compared to SOC/control.ConclusionBased on cumulative low to moderate certainty evidence shows that TCZ could reduce the risk of mortality in hospitalized patients. However, there is no statistically significant difference observed between the TCZ and SOC/control groups in other parameters.

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Diabetes as a risk factor for incident peripheral arterial disease in women compared to men: a systematic review and meta-analysis

Cardiovascular Diabetology ◽

10.1186/s12933-020-01130-4 ◽

2020 ◽

Vol 19 (1) ◽

Cited By ~ 1

Author(s):

Alyssa Z. Chase-Vilchez ◽

Isaac H. Y. Chan ◽

Sanne A. E. Peters ◽

Mark Woodward

Keyword(s):

Cardiovascular Disease ◽

Risk Factor ◽

Relative Risk ◽

Meta Analysis ◽

Arterial Disease ◽

Excess Risk ◽

Newcastle Ottawa Scale ◽

Peripheral Arterial ◽

Meta Analyses ◽

Ottawa Scale

Abstract Aims/hypothesis Previous meta-analyses have suggested that diabetes confers a greater excess risk of coronary heart disease, stroke, vascular dementia, and heart failure in women compared to men. While the underlying mechanism that explains such greater excess risk is unknown, in the current meta-analysis we hypothesized that we would find a similar sex difference in the relationship between diabetes and peripheral arterial disease (PAD). Methods PubMed MEDLINE, the Cochrane Database of Systematic Reviews, and Embase were systematically searched for prospective population-based cohort studies, with no restriction on publication date, language, or country. We included studies that reported the relative risk (RR), and its variability, for incident PAD associated with diabetes in both sexes. We excluded studies that did not adjust at least for age, and in which participants had pre-existing PAD. In cases where sex-specific results were not reported, study authors were contacted. Random-effects meta-analyses with inverse variance weighting were used to obtain summary sex-specific RRs and the women: men ratio of RRs for PAD. The Newcastle–Ottawa scale was used to assess study quality. Results Data from seven cohorts, totalling 2071,260 participants (49.8% women), were included. The relative risk for incident PAD associated with diabetes compared with no diabetes was 1.96 (95% CI 1.29–2.63) in women and 1.84 (95% CI 1.29–2.86) in men, after adjusting for potential confounders. The multiple-adjusted RR ratio was 1.05 (95% CI 0.90–1.22), with virtually no heterogeneity between studies (I2 = 0%). All studies scored 6–8, on the Newcastle–Ottawa scale of 0–9, indicating good quality. Eleven of the 12 studies that met review inclusion criteria did not report sex-specific relative risk, and these data were collected through direct correspondence with the study authors. Conclusion/interpretation Consistent with other studies, we found evidence that diabetes is an independent risk factor for PAD. However, in contrast to similar studies of other types of cardiovascular disease, we did not find evidence that diabetes confers a greater excess risk in women compared to men for PAD. More research is needed to explain this sex differential between PAD and other forms of CVD, in the sequelae of diabetes. In addition, we found that very few studies reported the sex-specific relative risk for the association between diabetes and PAD, adding to existing evidence for the need for improved reporting of sex-disaggregated results in cardiovascular disease research.

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Cranial Base Angle in Patients With Cleft Lip and Palate—A Systematic Review and Meta-Analysis

The Cleft Palate-Craniofacial Journal ◽

10.1177/10556656211053545 ◽

2021 ◽

pp. 105566562110535

Author(s):

Chandnee Murugan ◽

Vignesh Kailasam

Keyword(s):

Systematic Review ◽

Cleft Lip ◽

Cleft Lip And Palate ◽

Meta Analysis ◽

Cranial Base ◽

Class I ◽

Base Angle ◽

Registration Number ◽

Newcastle Ottawa Scale ◽

Ottawa Scale

Background: Diverse findings have been reported for the cranial base angle (CBA) in patients with CLP (cleft lip and palate) and non-CLP controls. Objective: The aim of this study is to assess and evaluate the CBA in patients with CLP and non-CLP controls. Methods: Data from PubMed, OVID Technologies, Inc., Cochrane, Literatura Latino-Americana e do Caribe em Ciências da Saúde (LILACS), Scopus, Web of Science, and EMBASE for Excerpta Medica dataBASE (EMBASE) with relevant terms was extracted until December 31, 2020. Inclusion criteria were data of patients with non-syndromic unilateral cleft lip and palate (UCLP) and bilateral cleft lip and palate (BCLP). In the case of UCLP and BCLP, patients with craniofacial syndromes were excluded. The study proposal was registered with PROSPERO (Registration number: CRD42021228632). Results: Fifteen studies with a total of 2032 participants were included for the systematic review and 14 studies with a total of 1972 participants were included for the meta-analysis. The risk of bias was assessed using the Modified Newcastle Ottawa scale under seven domains by two authors. Thirteen studies were graded as “good” and two as “satisfactory.” The CBA in patients with CLP were greater than the non CLP Class I controls in six of the 15 studies. CBA was greater in patients with CLP than non-CLP controls by 1.21° (95% CI of 0.19-2.22). Meta-analysis reported considerable heterogeneity (I2 = 86%). Anterior (ACB) and posterior cranial base (PCB) lengths were shorter in patients with CLP than in the non-cleft Class I controls by 2.14 mm (95% CI of 0.99-3.30) and 2.06 mm (95% CI of 1.52-2.60), respectively. Conclusion: Most studies were graded as good. Patients with CLP had greater CBA and shorter ACB and PCB lengths when compared to non-CLP controls.

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