Antiplatelet therapy in pregnancy: A systematic review.

OBJECTIVE: To systematically review contemporary data on the safety of clopidogrel and newer antiplatelet agents in pregnant women, with particular attention to maternal and neonatal complications. METHODS: The review protocol was published via PROSPERO (ID 42020165235) and conducted in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA). Databases were searched using MeSH and free text terms encompassing the included antiplatelets, relevant indications, and pregnancy. Included studies reported the drug dose, the stage of pregnancy at which it was administered, and at least one primary or secondary outcome relating to pregnancy. The primary outcome was reporting of complications associated with antiplatelet use in pregnancy. RESULTS: The search yielded 5271 results. 39 publications were included, incorporating 42 live births. The mean age of women was 34.6 years. Seven different antiplatelet agents were described, clopidogrel being most frequent (n = 37). 14 women received antiplatelet therapy in the first trimester. 14 women had regional anaesthesia (12 while taking clopidogrel), all without complication. Two women developed bleeding post caesarean section. There were no recorded neonatal delivery complications. Two neonates had congenital anomalies not felt to be related to maternal antiplatelet use. CONCLUSIONS: This systematic review describes outcomes for both mothers and neonates when exposed to clopidogrel at varying durations throughout gestation, and does not suggest higher than acceptable risk, with a congenital anomaly rate comparable to background risk. Evidence for other antiplatelet agents remains limited. Regional anaesthesia should be offered, with recommendation to stop prior to delivery in line with national guidance and in the context of individualised decision making.

Association of Risk of Dementia With Direct Oral Anticoagulants Versus Warfarin Use in Patients With Non-valvular Atrial Fibrillation: A Systematic Review and Meta-analysis.

ABSTRACT: Atrial fibrillation (AF) is associated with an increased risk of dementia. Studies have shown the beneficial effects of anticoagulants in preventing dementia in this population. However, evidence around the use of direct oral anticoagulants (DOACs) versus warfarin in AF-related dementia prevention remains sparse. This systematic review and meta-analysis aimed to evaluate the use of DOACs versus warfarin in dementia prevention in this population. MEDLINE, EMBASE, PsycINFO, and the CENTRAL databases were systematically searched from its inception until May 2020. Nine studies (n = 611,069) were included for quantitative meta-analysis. DOACs use was associated with a lower risk of composite dementia outcomes compared with warfarin use [odds ratio (OR) 0.56, 95% confidence interval (CI) 0.34-0.94, P = 0.03]. No significant difference was found in subtypes of dementia (vascular dementia, Alzheimer's disease, and cognitive disorder) between both groups. No significant difference in the risk of composite dementia outcomes between the dabigatran and warfarin groups (OR 0.97, 95% CI 0.88-1.08, P = 0.61). Apixaban (OR 0.58, 95% CI 0.50-0.67, P < 0.00001) and rivaroxaban (OR 0.67, 95% CI 0.61-0.75, P < 0.00001) use were both associated with a significantly lower risk of composite dementia outcomes compared with warfarin use. Findings need to be interpreted with caution because of low certainty of evidence. In conclusion, this systematic review and meta-analysis of 9 comparative studies demonstrated the superiority of DOACs over warfarin in prevention of dementia in AF. Future prospective trials with adequate follow-up period are warranted to ascertain its causal relationship.

Prognostic significance of preinjury anticoagulation in patients with traumatic brain injury: A systematic review and meta-analysis.

BACKGROUND: Traumatic brain injury (TBI) is a leading cause of injury-related deaths and neurological disability globally. Considering the widespread anticoagulant use among the aging population, we aimed to perform a systematic review and meta-analysis to evaluate the prognostic significance of preinjury anticoagulation in TBI patients. METHODS: This systematic review was conducted according to a predefined protocol (International Prospective Register of Systematic Reviews CRD42020192323). In compliance with Preferred Reporting Items for Systematic Reviews and Meta-Analyses and Meta-Analysis of Observational Studies in Epidemiology standards, a structured electronic database search was undertaken to identify all observational studies comparing preinjury anticoagulation with no preinjury anticoagulation in TBI patients. The primary outcome measure was overall mortality. The secondary outcome measures comprised in-hospital mortality, length of hospital stay, length of intensive care unit stay, need for neurosurgical procedure, and number of patients discharged home. All outcome data were analyzed using random effects modeling. RESULTS: Twelve comparative studies enrolling a total of 4,417 patients were included. Preinjury anticoagulation was associated with higher risk of overall mortality (odds ratio [OR], 2.39; 95% confidence interval [CI], 1.63-3.50, p < 0.00001), in-hospital mortality (OR, 2.47; 95% CI, 1.56-3.93, p = 0.0001), and longer length of intensive care unit stay (mean difference, 1.06; 95% CI, 0.54-1.57; p < 0.0001) compared with no preinjury anticoagulation. No statistical difference was observed in length of hospital stay (mean difference, -2.15; 95% CI, -5.36 to 1.05, p = 0.19), need for neurosurgical procedure (OR, 1.30; 95% CI, 0.70-2.44; p = 0.41), and discharged home (OR, 0.76; 95% CI, 0.55-1.04; p = 0.09) between the two groups. CONCLUSION: Preinjury anticoagulation is a powerful prognosticator of mortality in TBI patients. This highlights the need for dedicated triage and trauma team activation protocols considering earlier intervention and more aggressive imaging in all anticoagulated patients. Future studies should focus on strategies that can potentially reduce the risk of mortality in this population. The prognostic significance of direct oral anticoagulants versus warfarin remains unanswered. LEVEL OF EVIDENCE: Systematic review and meta-analysis of observational studies, level III.

Effect of perioperative regional anesthesia on cancer recurrence: A meta-analysis of randomized controlled trials.

BACKGROUND: Studies have reported that general anesthesia (GA), especially volatile agents were associated with higher cancer recurrence rate after cancer resection surgery. However, the effect of supplementary regional anesthesia (RA) in reducing the use of anesthetic agents on oncological outcomes remains unclear. The primary aim of this meta-analysis was to examine the effect of adjunctive use of RA on the cancer recurrence rate in adults undergoing cancer resection surgery. METHODS: MEDLINE, EMBASE and CENTRAL were systematically searched for randomized control trials (RCTs) from its inception until April 2020. RESULTS: Six RCTs (n = 3139 patients) were included. In comparison to the GA alone, our meta-analysis demonstrated no significant difference in the cancer recurrence rate in patients who received the adjunctive use of RA in the routine care of GA (3 studies, n = 2380 patients; odds ratio 0.93, 95%CI 0.63-1.39, ρ = 0.73, certainty of evidence = very low). Our review also showed no significant difference in cancer-related mortality (2 studies, n = 545; odds ratio 1.20, 95%CI 0.83-1.74, ρ = 0.33, certainty of evidence = low), all-cause mortality (3 studies, n = 2653; odds ratio 0.98, 95%CI 0.69-1.39, ρ = 0.89, certainty of evidence = low) and duration of cancer-free survival (2 studies, n = 659; mean difference 0.00 years, 95%CI -0.25-0.25, ρ = 1.00, certainty of evidence = high). CONCLUSION: This meta-analysis concluded that the adjunctive use of RA in the routine care of GA did not reduce cancer recurrence rate in cancer resection surgery. However, this finding needs to be interpreted with caution due to low level of evidence, substantial heterogeneity and potential risk of bias across the included studies. STUDY REGISTRATION NUMBER: CRD42020171368.

Effect of regional anaesthesia only versus general anaesthesia on cancer recurrence rate: A systematic review and meta-analysis with trial sequential analysis.

OBJECTIVES: There is growing evidence on the influence of general anaesthesia (GA) in promoting the proliferation of cancer cells. The benefits of regional anaesthesia (RA) on cancer recurrence rate in cancer surgery remains unclear in the literature. The primary objective of this review was to examine the effect of RA on the incidence of post-operative cancer recurrence rate in cancer resection surgery. DESIGN: Systematic review and meta-analysis with trial sequential analysis. DATA SOURCES: Medline, EMBASE and CENTRAL were systematically searched from its inception until April 2020. ELIGIBILITY CRITERIA: All randomized control trials and observational studies comparing RA only versus GA in cancer resection surgery were included. Case report, case series and editorials were excluded. RESULTS: Ten retrospective observational studies (n = 9708; 4567 GA vs 5141 RA) were included for qualitative and quantitative meta-analysis. In comparison to GA, RA was not significantly associated with a lower cancer recurrence rate in cancer resection surgery (odds ratio 1.01, 95% CI 0.67 to 1.53, p = 0.95, certainty of evidence = very low). However, the trial sequential analysis for cancer recurrence rate was inconclusive. Our analysis demonstrated no significant difference between the RA and GA groups in the overall survival rate (odds ratio 1.51, 95% CI 0.65 to 3.51, p = 0.34, certainty of evidence = very low), time to cancer recurrence (mean difference 1.45 months, 95% CI -8.69 to 11.59, p = 0.78, certainty of evidence = very low), cancer-related mortality (odds ratio 1.79, 95% CI 0.57 to 5.62, p = 0.32, certainty of evidence = very low). CONCLUSIONS: Given the low level of evidence and underpowered trial sequential analysis, our review neither support nor oppose that the use of RA was associated with lower incidence of cancer recurrence rate than GA in cancer resection surgery. TRIAL REGISTRATION: CRD42020163780.

The effect of preinjury anticoagulation on mortality in trauma patients: A systematic review and meta-analysis.

OBJECTIVES: To assess the effect of preinjury anticoagulation on mortality in trauma patients. METHODS: A search of electronic information sources was conducted to identify all observational studies comparing preinjury anticoagulation with no preinjury anticoagulation in trauma patients. The primary outcome measure was overall mortality (overall mortality, in-hospital mortality and 30-day mortality). The secondary outcome measures included the length of hospital stay, length of intensive care unit (ICU) stay, incidence of intracranial haemorrhage (ICH), and need for operation. Fixed effect or random effects modelling was applied as appropriate to calculate pooled outcome data. RESULTS: Nineteen comparative studies enrolling a total of 1,365,446 patients were included. Preinjury anticoagulation was associated with higher risk of overall mortality (OR 2.12, 95%CI 1.79 - 2.51, p < 0.00001), in-hospital mortality (OR 2.04, 95%CI 1.66 - 2.52, p < 0.00001), ICH (OD 1.99, 95%CI 1.61 - 2.45, p < 0.00001), and shorter length of hospital stay (MD 0.50, 95%CI 0.03 - 0.97, p = 0.04) in comparison to no preinjury anticoagulation. We found no difference between the two groups in 30-day mortality (OR 1.61, 95%CI 0.91 - 2.85, p = 0.10), length of ICU stay (MD 0.62, 95%CI -0.13 - 1.36, p = 0.11), and need for operation (OR 1.73, 95%CI 0.71 - 4.20, p = 0.23). The quality of the available evidence was moderate. CONCLUSION: Preinjury anticoagulation is a significant predictor of mortality in trauma patients. Future studies should focus on strategies required to reduce such a significant risk of mortality in these high-risk patients. This may include adaptation of primary, secondary and tertiary trauma surveys for patients on preinjury anticoagulation.

Flash glucose monitoring (FGM): A clinical review on glycaemic outcomes and impact on quality of life.

Flash glucose monitoring (FGM) is widely accepted as an alternative means to conventional finger prick test for measuring glucose level in individuals with diabetes mellitus. In this clinical review, we endeavour to draw all available clinical evidence on the usage and efficacy of FGM from research trials and observational studies in real-world settings. We aim to explore its clinical efficacy and impact on quality of life (QoL) in the diabetic population. In terms of clinical outcomes, use of FGM is associated with a significant reduction in glycated haemoglobin A1c (HbA1c) level, notably in patients with suboptimal glycaemic control prior to commencement of FGM and reduction in time spent in hypoglycaemia. FGM demonstrated non-inferiority in device accuracy when compared to other well-established CGMs available in the market. Patients have reported improved QoL and treatment satisfaction measured by validated objective scores after consistent use of FGM. This results in a positive impact on patient psychosocial wellbeing and ultimately enhances patient compliance and optimisation of glycaemic control. Evaluation of QoL and patient reported outcome measures (PROMs) will require a standardised approach to allow comparability of the results and evidence.

Association of obstructive sleep apnea and postoperative cardiac complications: A systematic review and meta-analysis with trial sequential analysis.

OBJECTIVES: The repetitive hypoxic and hypercapnia events of obstructive sleep apnea (OSA) are believed to adversely affect cardiopulmonary function, which make them vulnerable to a higher incidence of postoperative complications. The primary aim of this systematic review and meta-analysis was to examine the association of OSA and the composite endpoints of postoperative cardiac or cerebrovascular complications in adult undergoing non-cardiac surgery. DATA SOURCES: MEDLINE, EMBASE and CENTRAL were systematically searched from its inception until May 2019. REVIEW METHODS: All observational studies were included. RESULTS: Twenty-two studies (n = 3,033,814; 184,968 OSA vs 2,848,846 non-OSA) were included for quantitative meta-analysis. In non-cardiac surgery, OSA was significantly associated with a higher incidence of the composite endpoints of postoperative cardiac or cerebrovascular complications (odd ratio: 1.44, 95%CI: 1.17 to 1.78, ρ = 0.007, trial sequential analysis = conclusive; certainty of evidence = very low). In comparison to non-OSA, OSA patients were reported to have nearly 2.5-fold risk of developing pulmonary complications (odd ratio: 2.52, 95%CI: 1.92 to 3.31, ρ < 0.001, certainty of evidence = very low), postoperative delirium (odd ratio: 2.45, 95%CI: 1.50 to 4.01, ρ < 0.001, certainty of evidence = low) and acute kidney injury (odd ratio: 2.41, 95%CI: 1.93 to 3.02, ρ < 0.001, certainty of evidence = very low). CONCLUSIONS: This meta-analysis of 22 comparative studies demonstrated that OSA is a potential risk factor to postoperative adverse complications in adults undergoing non-cardiac surgery. However, the conclusions need to be interpreted with caution due to the nature of included observational studies with significant heterogeneity and low quality of evidence. PROSPERO: CRD42019136564.

Real World Patterns of Antimicrobial Use and Microbiology Investigations in Patients with Sepsis outside the Critical Care Unit: Secondary Analysis of Three Nation-Wide Point Prevalence Studies.

Recent description of the microbiology of sepsis on the wards or information on the real-life antibiotic choices used in sepsis is lacking. There is growing concern of the indiscriminate use of antibiotics and omission of microbiological investigations in the management of septic patients. We performed a secondary analysis of three annual 24-h point-prevalence studies on the general wards across all Welsh acute hospitals in years 2016-2018. Data were collected on patient demographics, as well as radiological, laboratory and microbiological data within 48-h of the study. We screened 19,453 patients over the three 24 h study periods and recruited 1252 patients who fulfilled the entry criteria. 775 (64.9%) patients were treated with intravenous antibiotics. Only in 33.65% (421/1252) of all recruited patients did healthcare providers obtain blood cultures; in 25.64% (321/1252) urine cultures; in 8.63% (108/1252) sputum cultures; in 6.79% (85/1252) wound cultures; in 15.25% (191/1252) other cultures. Out of the recruited patients, 59.1% (740/1252) fulfilled SEPSIS-3 criteria. Patients with SEPSIS-3 criteria were significantly more likely to receive antibiotics than the non-septic cohort (p < 0.0001). In a multivariable regression analysis increase in SOFA score, increased number of SIRS criteria and the use of the official sepsis screening tool were associated with antibiotic administration, however obtaining microbiology cultures was not. Our study shows that antibiotics prescription practice is not accompanied by microbiological investigations. A significant proportion of sepsis patients are still at risk of not receiving appropriate antibiotics treatment and microbiological investigations; this may be improved by a more thorough implementation of sepsis screening tools.