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MedRxiv : the Preprint Server For... Mar 2024In this study the presence of uterine fibroids was significantly associated with an increased risk of development of hypertensive disorders of pregnancy even when...
CAPSULE
In this study the presence of uterine fibroids was significantly associated with an increased risk of development of hypertensive disorders of pregnancy even when accounting for age and BMI in meta-regression. This finding has potential implications for risk stratification and monitoring for hypertension during pregnancy in this population.
OBJECTIVE
To examine the association between uterine fibroids and the development of hypertensive disorders in pregnancy.
DATA SOURCES
Cochrane, Embase, PubMed, MEDLINE, Scopus, and Web of Science databases were searched from inception through April 2023.
STUDY SELECTION AND SYNTHESIS
Cohort, case-control, or case series studies including uterine fibroid status and hypertensive disorders of pregnancy status were included. The comparison group was pregnant women without uterine fibroids. Inverse-variance weighted random effects models were used to pool RR and OR estimates separately. Age and BMI were explored as potential sources of heterogeneity using inverse-variance weighted meta-regression.
MAIN OUTCOMES
Hypertensive disorders of pregnancy (HDP) defined as gestational hypertension, pre-eclampsia, eclampsia, superimposed preeclampsia, or hemolysis, elevated liver enzymes, and low platelets (HELLP) syndrome.
RESULTS
A total of 17 studies were included (Total N=1,374,395 participants, N=64,968 with uterine fibroids). Thirteen studies were retrospective cohorts and four were case-control studies. Women with uterine fibroids had a significantly higher risk of hypertensive disorders in pregnancy compared to women without uterine fibroids with RR 1.74 (95% CI 1.33-2.27, p<0.01), and OR 2.87 (95% CI 1.38-5.97, p<0.01), in cohort studies and case-control studies, respectively. In meta-regression analyses, age did not significantly change the positive association between uterine fibroids and hypertensive disorders in pregnancy.
CONCLUSION
Uterine fibroids were associated with an increased risk of hypertensive disorders of pregnancy when all available literature was synthesized, including when shared risk factors are examined in meta-regression analyses.
RELEVANCE
If confirmed in future studies, investigations into the mechanisms of this association are needed as this finding potentially has implications for risk stratification and monitoring for hypertensive disorders of pregnancy in this population.
TRIAL REGISTRATION
PROSPERO, ID # 331528.
PubMed: 38496589
DOI: 10.1101/2024.03.05.24303824 -
Cancer Medicine Mar 2024Due to encouraging pre-clinical data and supportive observational studies, there has been growing interest in applying cardiovascular drugs (including aspirin,... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Due to encouraging pre-clinical data and supportive observational studies, there has been growing interest in applying cardiovascular drugs (including aspirin, angiotensin-converting enzyme [ACE] inhibitors, statins, and metformin) approved to treat diseases such as hypertension, hyperlipidemia, and diabetes mellitus to the field of oncology. Moreover, given growing costs with cancer care, these medications have offered a potentially more affordable avenue to treat or prevent recurrence of cancer. We sought to investigate the anti-cancer effects of drugs repurposed from cardiology or anti-inflammatories to treat cancer. We specifically evaluated the following drug classes: HMG-CoA reductase inhibitors (statins), cyclo-oxygenase inhibitors, aspirin, metformin, and both angiotensin receptor blockers (ARBs) and angiotensin-converting enzyme inhibitors. We also included non-steroidal anti-inflammatory drugs (NSAIDs) because they exert a similar mechanism to aspirin by blocking prostaglandins and reducing inflammation that is thought to promote the development of cancer.
METHODS
We performed a systematic literature review using PubMed and Web of Science with search terms including "aspirin," "NSAID," "statin" (including specific statin drug names), "metformin," "ACE inhibitors," and "ARBs" (including specific anti-hypertensive drug names) in combination with "cancer." Searches were limited to human studies published between 2000 and 2023.
MAIN OUTCOMES AND MEASURES
The number and percentage of studies reported positive results and pooled estimates of overall survival, progression-free survival, response, and disease-free survival.
RESULTS
We reviewed 3094 titles and included 67 randomized clinical trials. The most common drugs that were tested were metformin (n = 21; 30.9%), celecoxib (n = 20; 29.4%), and simvastatin (n = 8; 11.8%). There was only one study that tested cardiac glycosides and none that studied ACE inhibitors. The most common tumor types were non-small-cell lung cancer (n = 19; 27.9%); breast (n = 8; 20.6%), colorectal (n = 7; 10.3%), and hepatocellular (n = 6; 8.8%). Most studies were conducted in a phase II trial (n = 38; 55.9%). Most studies were tested in metastatic cancers (n = 49; 72.1%) and in the first-line setting (n = 36; 521.9%). Four studies (5.9%) were stopped early because of difficulty with accrual. The majority of studies did not demonstrate an improvement in either progression-free survival (86.1% of studies testing progression-free survival) or in overall survival (94.3% of studies testing overall survival). Progression-free survival was improved in five studies (7.4%), and overall survival was improved in three studies (4.4%). Overall survival was significantly worse in two studies (3.8% of studies testing overall survival), and progression-free survival was worse in one study (2.8% of studies testing progression-free survival).
CONCLUSIONS AND RELEVANCE
Despite promising pre-clinical and population-based data, cardiovascular drugs and anti-inflammatory medications have overall not demonstrated benefit in the treatment or preventing recurrence of cancer. These findings may help guide future potential clinical trials involving these medications when applied in oncology.
Topics: Humans; Angiotensin-Converting Enzyme Inhibitors; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Carcinoma, Non-Small-Cell Lung; Angiotensin Receptor Antagonists; Lung Neoplasms; Randomized Controlled Trials as Topic; Anti-Inflammatory Agents, Non-Steroidal; Anti-Inflammatory Agents; Aspirin; Antihypertensive Agents; Metformin
PubMed: 38491813
DOI: 10.1002/cam4.7049 -
BJOG : An International Journal of... Mar 2024Chronic kidney disease (CKD) is associated with an increased risk of adverse pregnancy outcomes, but the risk at different stages of CKD (defined by estimated glomerular... (Review)
Review
BACKGROUND
Chronic kidney disease (CKD) is associated with an increased risk of adverse pregnancy outcomes, but the risk at different stages of CKD (defined by estimated glomerular filtration rate, eGFR) compared with women without CKD has not been quantified in large cohorts.
OBJECTIVES
To quantify the association between CKD and adverse pregnancy outcomes according to CKD definition, CKD stage and presence or absence of diabetes.
SEARCH STRATEGY
A systematic search of EMBASE and MEDLINE from inception to 5 January 2023.
SELECTION CRITERIA
English-language randomised controlled trials as well as cohort and case-control studies investigating adverse pregnancy outcomes in pregnant women with CKD.
DATA COLLECTION AND ANALYSIS
Two reviewers conducted independent data extractions. A random-effects model was used to estimate risk.
MAIN RESULTS
We included 19 studies with 3 251 902 women. Defining CKD using eGFR or serum creatinine produced results with greater effect size but wider confidence intervals. Compared with CKD stages 1-2, women with CKD stages 3-5 have a greater risk, but also greater imprecision in the risk estimate, of the following outcomes: pre-eclampsia (OR 55.18, 95% CI 2.63-1157.68, vs OR 24.74, 95% CI 1.75-348.70), preterm birth (OR 20.24, 95% CI 2.85-143.75, vs OR 8.18, 95% CI 1.54-43.46) and neonatal intensive care unit admission (OR 19.32, 95% CI 3.07-121.68, vs OR 9.77, 95% CI 2.49-38.39). Women with diabetic kidney disease, compared with women without diabetic kidney disease, have higher risks of maternal mortality, small-for-gestational-age neonates, pre-eclampsia and gestational hypertension.
CONCLUSIONS
There is heterogeneity in the definition of CKD in pregnancy. Future studies should consider ways to standardise its definition and measurement in pregnancy.
PubMed: 38488268
DOI: 10.1111/1471-0528.17807 -
Annals of Medicine and Surgery (2012) Mar 2024This study aimed to analyze the Vaccine Adverse Event Reporting System (VAERS) database and systematically review the literature to provide a comprehensive analysis of...
Reversible cerebral vasoconstriction syndrome and posterior reversible encephalopathy syndrome following vaccination: analysis of the VAERS database and systematic review.
OBJECTIVES
This study aimed to analyze the Vaccine Adverse Event Reporting System (VAERS) database and systematically review the literature to provide a comprehensive analysis of reversible cerebral vasoconstriction syndrome (RCVS) and posterior reversible encephalopathy syndrome (PRES) secondary to vaccination.
METHODS
The authors analyzed the VAERS database and conducted a systematic review following PRISMA guidelines. The inclusion criteria for VAERS data were a score of ≥3 on the RCVS score and/or radiographic findings consistent with the diagnosis of RCVS or PRES. The systematic review was registered with PROSPERO.
RESULTS
Our combined data set included 29 cases (9 RCVS and 20 PRES). Most cases were women (72.4%) with a mean age of 50.7 years (SD 19.4 years). Most cases were associated with COVID-19 mRNA vaccines (58.6% Moderna, 20.7% Pfizer). Hypertension (37.9%), hyperlipidemia (13.7%), chronic kidney disease (CKD) (10.3%), and end-stage renal disease (6.8%) were common comorbidities. Furthermore, 20.6% (6/29) of cases were on immunosuppression therapy for various reasons. The mean time to symptom onset was 10.49 days after vaccination (SD 18.60), and the mean duration of hospitalization was 7.42 days (SD 5.94). The symptoms reported the most frequently were headache (41.3%), elevated blood pressure (31.0%), and emesis (17.2%). Typical radiographic findings included T2/FLAIR hyperintensities affecting the parieto-occipital lobes, indicative of vasogenic and/or cytotoxic edema.
CONCLUSIONS
This study provides a comprehensive analysis of postvaccine RCVS and PRES. Both disease states were seen most often in those with pre-existing risk factors such as female sex, age over 50, hypertension, renal disease, and immunosuppression. Vaccines and their associated immune response may cause endothelial dysfunction leading to cerebral vasospasm and loss of cerebral autoregulation. However, further research is required to understand the underlying pathophysiological mechanisms. Despite the associations found, the absolute risk of these syndromes remains extremely low compared to the immense benefits of vaccination.
PubMed: 38463101
DOI: 10.1097/MS9.0000000000001407 -
American Journal of Obstetrics &... Apr 2024This study aimed to synthesize the available evidence on probiotic administration during pregnancy for the prevention of preeclampsia and its effects on related... (Meta-Analysis)
Meta-Analysis Review
OBJECTIVE
This study aimed to synthesize the available evidence on probiotic administration during pregnancy for the prevention of preeclampsia and its effects on related maternal, fetal, and newborn outcomes.
DATA SOURCES
Six databases were systematically searched for eligible studies, namely Ovid MEDLINE, Embase, CINAHL, Cochrane, Global Index Medicus, and the Maternity and Infant Care Database, from inception to August 2, 2023.
STUDY ELIGIBILITY CRITERIA
Randomized controlled trials that evaluated the effects of probiotic administration on women during any stage of pregnancy were eligible for inclusion.
METHODS
The protocol was registered with the International Prospective Register of Systematic Reviews under identifier CRD42023421613. Evaluating study eligibility, extracting data, assessing risk of bias (ROB-2 tool), and rating certainty (Grading of Recommendations, Assessment, Development and Evaluations) were conducted independently by 2 authors. The primary outcomes were incidence of preeclampsia, eclampsia, and maternal mortality. A meta-analysis was performed, and the results were reported as risk ratios with 95% confidence intervals.
RESULTS
A total of 29 trials (7735 pregnant women) met the eligibility criteria. There was heterogeneity across the trials in the population of enrolled women and the type of probiotic tested (20 different strains), although most used oral administration. Probiotics may make no difference to the risk of preeclampsia (risk ratio, 1.14; 95% confidence interval, 0.84-1.53; 11 trials; 2401 women; low certainty evidence), preterm birth at <37 weeks' gestation (risk ratio, 0.93; 95% confidence interval, 0.66-1.30; 18 trials, 4016 women; low certainty evidence), or gestational age at delivery (mean difference, -0.03 weeks [≈0.2 days]; 95% confidence interval, -0.16 to 0.10 weeks [≈ -1.1 to 0.7 days]; 13 trials, 2194 women; low certainty evidence). It is difficult to assess the effects of probiotics on other secondary outcomes because the evidence was of very low certainty, however, no benefits or harms were observed.
CONCLUSION
Limited evidence suggests that probiotic supplementation does not affect the risk for preeclampsia. Further high-quality trials are needed to definitively assess the benefits and possible harms of probiotic supplementation during pregnancy. There is also a lack of data from trials that included women who were undernourished or who experienced microbial dysbiosis and for whom probiotic supplementation might be useful.
Topics: Humans; Probiotics; Pregnancy; Pre-Eclampsia; Female; Infant, Newborn; Pregnancy Outcome; Randomized Controlled Trials as Topic; Maternal Mortality; Premature Birth
PubMed: 38447676
DOI: 10.1016/j.ajogmf.2024.101322 -
Frontiers in Psychiatry 2024Burnout is a public health problem with various health consequences, among which cardiovascular disease is the most investigated but still under debate. Our objective...
BACKGROUND
Burnout is a public health problem with various health consequences, among which cardiovascular disease is the most investigated but still under debate. Our objective was to conduct a systematic review and meta-analysis on the influence of burnout on cardiovascular disease.
METHODS
Studies reporting risk (odds ratio, relative risk, and hazard ratio) of cardiovascular disease following burnout were searched in PubMed, PsycINFO, Cochrane, Embase, and ScienceDirect. We performed a random-effect meta-analysis stratified by type of cardiovascular disease and searched for putative influencing variables. We performed sensitivity analyses using the most adjusted models and crude risks.
RESULTS
We included 25 studies in the systematic review and 9 studies in the meta-analysis (4 cross-sectional, 4 cohort, and 1 case-control study) for a total of 26,916 participants. Burnout increased the risk of cardiovascular disease by 21% (OR = 1.21, 95% CI 1.03 to 1.39) using the most adjusted risks and by 27% (OR = 1.27, 95% CI 1.10 to 1.43) using crude risks. Using stratification by type of cardiovascular disease and the most adjusted risks, having experienced burnout significantly increased the risk of prehypertension by 85% (OR = 1.85, 95% CI 1.00 to 2.70) and cardiovascular disease-related hospitalization by 10% (OR = 1.10, 95% CI 1.02 to 1.18), whereas the risk increase for coronary heart disease (OR = 1.79, 95% CI 0.79 to 2.79) and myocardial infarction (OR = 1.78, 95% CI 0.85 to 2.71) was not significant. Results were also similar using crude odds ratio. The risk of cardiovascular disease after a burnout was not influenced by gender. Insufficient data precluded other meta-regressions.
CONCLUSIONS
Burnout seems to increase the risk of cardiovascular disease, despite the few retrieved studies and a causality weakened by cross-sectional studies. However, numerous studies focused on the pathophysiology of cardiovascular risk linked to burnout, which may help to build a preventive strategy in the workplace.
PubMed: 38439796
DOI: 10.3389/fpsyt.2024.1326745 -
International Urology and Nephrology Jul 2024Intradialytic hypertension affects 5-15% of hemodialysis patients, yet relevant studies are relatively scarce. It is also associated with higher interdialytic blood... (Meta-Analysis)
Meta-Analysis Review
PURPOSE
Intradialytic hypertension affects 5-15% of hemodialysis patients, yet relevant studies are relatively scarce. It is also associated with higher interdialytic blood pressure. Beta-blockers can be preferred as antihypertensive drugs due to their superior blood pressure control, decreased risk of cardiovascular events, improved endothelial cell function, and decreased noradrenaline levels. Through this study, beta-blocker antihypertensive effects in intra- and interdialytic hypertension were analyzed.
METHODS
Systematic review and meta-analysis were performed following PRISMA guidelines. We registered our PROSPERO protocol (Registration ID: CRD42023446184) and included relevant full-text clinical trials or RCTs from 2008 to 2023 with predetermined keywords and criteria from multiple databases including PUBMED, COCHRANE, SCOPUS, and citation searching. Seven eligible articles were included in this review study.
RESULTS
Four studies with 82 participants for intradialytic hypertension evaluation were included. Meta-analysis showed a decrease in SBP in intradialytic hypertensive patients after beta-blocker intervention, with a significant estimated mean difference of - 15.19 mmHg (P < 0.00001; 95% CI - 19.47 to - 10.91). Supporting previous data, SBP remains constant between pre- and post-dialysis with beta-blocker therapy, with an insignificant estimated mean difference of - 2.72 mmHg (P = 0.29; 95% CI - 7.80 to 2.36). Whereas five studies with 142 participants were included for interdialytic hypertension evaluation. Meta-analysis shows a significant decrease in SBP before to after therapy, with an estimated mean difference of - 10.92 (P < 0.0001; 95% CI - 16.33 to - 5.51).
CONCLUSION
Beta-blocker treatment resulted in significant reductions in post-hemodialysis systolic blood pressure among intra- and interdialytic hypertensive patients.
Topics: Humans; Adrenergic beta-Antagonists; Hypertension; Renal Dialysis; Treatment Outcome
PubMed: 38424373
DOI: 10.1007/s11255-024-03973-2 -
Archives of Gynecology and Obstetrics May 2024Preeclampsia is a major cause of health problems for both pregnant women and unborn babies worldwide. However, the underlying causes of preeclampsia are not fully... (Review)
Review
PURPOSE
Preeclampsia is a major cause of health problems for both pregnant women and unborn babies worldwide. However, the underlying causes of preeclampsia are not fully understood, leading to limited effective treatments. The goal of this study is to enhance our knowledge of its causes, devise prevention strategies, and develop treatments.
METHODS
We performed a systematic literature search. Six models regarding the pathogenesis of preeclampsia are discussed in this review.
RESULTS
This review focuses on the latest advancements in understanding preeclampsia's origins. Preeclampsia is a complex condition caused by various factors, processes, and pathways. Reduced blood flow and oxygen to the uterus and placenta, heightened inflammatory reactions, immune imbalances, altered genetic changes, imbalanced blood vessel growth factors, and disrupted gut bacteria may contribute to its development.
CONCLUSION
Preeclampsia is thought to result from the interplay of these factors.
Topics: Pregnancy; Female; Humans; Pre-Eclampsia; Placenta; Uterus
PubMed: 38421424
DOI: 10.1007/s00404-024-07393-6 -
Blood Pressure and Heart Rate Variability and the Impact on Pregnancy Outcomes: A Systematic Review.Journal of the American Heart... Mar 2024Long-term (visit-to-visit) blood pressure variability (BPV) and heart rate variability (HRV) outside pregnancy are associated with adverse cardiovascular outcomes. Given...
BACKGROUND
Long-term (visit-to-visit) blood pressure variability (BPV) and heart rate variability (HRV) outside pregnancy are associated with adverse cardiovascular outcomes. Given the limitations of relying solely on blood pressure level to identify pregnancies at risk, long-term (visit-to-visit) BPV or HRV may provide additional diagnostic/prognostic counsel. To address this, we conducted a systematic review to examine the association between long-term BPV and HRV in pregnancy and adverse maternal and perinatal outcomes.
METHODS AND RESULTS
Databases were searched from inception to May 2023 for studies including pregnant women, with sufficient blood pressure or heart rate measurements to calculate any chosen measure of BPV or HRV. Studies were excluded that reported short-term, not long-term, variability. Adjusted odds ratios were extracted. Eight studies (138 949 pregnancies) reporting BPV met our inclusion criteria; no study reported HRV and its association with pregnancy outcomes. BPV appeared to be higher in women with hypertension and preeclampsia specifically, compared with unselected pregnancy cohorts. Greater BPV was associated with significantly more adverse pregnancy outcomes, particularly maternal (gestational hypertension [odds ratio range, 1.40-2.15], severe hypertension [1.40-2.20]), and fetal growth (small-for-gestational-age infants [1.12-1.32] or low birth weight [1.18-1.39]). These associations were independent of mean blood pressure level. In women with hypertension, there were stronger associations with maternal outcomes but no consistent pattern for perinatal outcomes.
CONCLUSIONS
Future work should aim to confirm whether BPV could be useful for risk stratification prospectively in pregnancy, and should determine the optimal management path for those women identified at increased risk of adverse outcomes.
Topics: Female; Humans; Pregnancy; Blood Pressure; Heart Rate; Hypertension; Hypertension, Pregnancy-Induced; Pre-Eclampsia; Pregnancy Outcome
PubMed: 38410988
DOI: 10.1161/JAHA.123.032636 -
BMC Pregnancy and Childbirth Feb 2024Maternal near-miss (MNM) is defined by the World Health Organization (WHO) working group as a woman who nearly died but survived a life-threatening condition during... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Maternal near-miss (MNM) is defined by the World Health Organization (WHO) working group as a woman who nearly died but survived a life-threatening condition during pregnancy, childbirth, or within 42 days of termination of pregnancy due to getting quality of care or by chance. Despite the importance of the near-miss concept in enhancing quality of care and maternal health, evidence regarding the prevalence of MNM, its primary causes and its determinants in Africa is sparse; hence, this study aimed to address these gaps.
METHODS
A systematic review and meta-analysis of studies published up to October 31, 2023, was conducted. Electronic databases (PubMed/Medline, Scopus, Web of Science, and Directory of Open Access Journals), Google, and Google Scholar were used to search for relevant studies. Studies from any African country that reported the magnitude and/or determinants of MNM using WHO criteria were included. The data were extracted using a Microsoft Excel 2013 spreadsheet and analysed by STATA version 16. Pooled estimates were performed using a random-effects model with the DerSimonian Laired method. The I test was used to analyze the heterogeneity of the included studies.
RESULTS
Sixty-five studies with 968,555 participants were included. The weighted pooled prevalence of MNM in Africa was 73.64/1000 live births (95% CI: 69.17, 78.11). A high prevalence was found in the Eastern and Western African regions: 114.81/1000 live births (95% CI: 104.94, 123.59) and 78.34/1000 live births (95% CI: 67.23, 89.46), respectively. Severe postpartum hemorrhage and severe hypertension were the leading causes of MNM, accounting for 36.15% (95% CI: 31.32, 40.99) and 27.2% (95% CI: 23.95, 31.09), respectively. Being a rural resident, having a low monthly income, long distance to a health facility, not attending formal education, not receiving ANC, experiencing delays in health service, having a previous history of caesarean section, and having pre-existing medical conditions were found to increase the risk of MNM.
CONCLUSION
The pooled prevalence of MNM was high in Africa, especially in the eastern and western regions. There were significant variations in the prevalence of MNM across regions and study periods. Strengthening universal access to education and maternal health services, working together to tackle all three delays through community education and awareness campaigns, improving access to transportation and road infrastructure, and improving the quality of care provided at service delivery points are key to reducing MNM, ultimately improving and ensuring maternal health equity.
Topics: Pregnancy; Female; Humans; Maternal Death; Near Miss, Healthcare; Cesarean Section; Maternal Mortality; Pregnancy Complications; Africa
PubMed: 38368373
DOI: 10.1186/s12884-024-06325-1