Prevention Of Preterm Birth Research Articles

Preterm Birth: A Review of Its Early Diagnosis and Prevention

Preterm birth, a major global healthcare concern, is characterized by infants being born before completing 37 weeks of gestation. Accurate diagnosis and effective interventions are critical to managing this complex issue. This abstract provides an overview of the diagnosis and prevention of preterm birth, focusing on risk assessment, diagnostic techniques, and various interventions for mothers and newborns. The diagnostic process involves evaluating risk factors, clinical history, and the assessment of potential membrane rupture. Techniques such as speculum examination, the Nitrazine test, the Fern test, ultrasonography, and the Placental Alpha Microglobulin-1 test play vital roles in identifying membrane rupture and infection. Additional diagnostic markers include cervical ultrasonography and fetal fibronectin testing. Prevention strategies include lifestyle changes, maternal therapies, and antenatal interventions. Smoking cessation programs, low-dose aspirin, antenatal corticosteroid therapy, progesterone supplementation, magnesium sulfate, and antibiotic treatment are employed to reduce the risk of preterm birth. Cervical cerclage, another surgical intervention, is recommended in specific cases.
 For preterm newborns, immediate and effective care is vital. This includes thermal care, early breastfeeding, infection prevention, and respiratory distress syndrome management. These interventions are crucial in reducing infant mortality and morbidity associated with preterm birth. Efforts to diagnose and prevent preterm birth are essential in improving the well-being of both mothers and their newborns. A comprehensive approach, combining accurate diagnosis and effective interventions, can make a significant impact in reducing the burden of preterm birth on healthcare systems and families.
 Keywords: Preterm birth, infants, gestation, potential membrane rupture

Comparing Prophylactic Vaginal Progesterone & Cervical Cerclage In Preventing Preterm Birth: A Systematic Review

Preterm birth complicates at-risk singleton pregnancies, and this is associated with a poor prognosis for pregnant mothers. When comparing cervical cerclage to vaginal progesterone, the rationale is clear, but its effectiveness remains a mystery.It is the goal of this systematic review to shed further light on this well-known conundrum. To find research on preventive vaginal progesterone usage vs cervical cerclage, PubMed, PubMed Central, Medline, Science Direct, and Google Scholar were searched. There were three randomized control trials, three systematic reviews and meta-analyses, two cohort studies, and two conventional reviews. It was determined that both strategies for managing preterm delivery were equally effective in terms of preterm birth prevention when applied to pregnant women. We found that vaginal progesterone had less side effects than cervical cerclage, but it has no influence on a woman's ability to function and does not improve her life expectancy. The systematic reviews and randomized controlled studies unequivocally confirmed these findings. Cervical cerclage was shown to be more risky than preventive vaginal progesterone in a comprehensive study. However, prophylactic application of cervical cerclage still remains a superior treatment modality if serial transvaginal ultrasound scans are pointing towards cervical shortening. Therefore, more research is required to understand this relationship to identify populations at risk.

Investigating ticagrelor in a preclinical pipeline as a novel therapeutic to prevent preterm birth.

Preterm birth is the leading cause of perinatal morbidity and mortality, and new therapies that delay preterm birth and improve neonatal outcomes are urgently needed. This study investigates whether ticagrelor inhibits uterine contractility and inflammation in preclinical in vitro, ex vivo (human) and in vivo (mouse) studies, to explore the potential of repurposing ticagrelor for the prevention of preterm birth. Preterm birth remains a significant global health challenge, affecting approximately 10% of pregnancies and resulting in one million deaths globally every year. Tocolytic agents, used to manage preterm labour, have considerable limitations including lack of efficacy, and adverse side effects, emphasising the urgent need for innovative solutions. Here, we explore repurposing an antiplatelet cardioprotective drug, ticagrelor, as a potential treatment to prevent preterm birth. Ticagrelor has demonstrated pleiotropic actions beyond platelet inhibition, including relaxant effects on smooth muscle cells and anti-inflammatory effects in models of diabetes and sepsis. As preterm birth is underscored by inflammatory processes triggering uterine contractions, these actions position ticagrelor as an attractive candidate for prevention or delay of preterm birth. Utilising primary human myometrial tissue, human myometrial cells, and a mouse model of preterm birth, we investigated ticagrelor's potential as a safe and effective therapy for preterm birth. We showed that ticagrelor did not reduce the frequency or strength of spontaneous muscle contractions of ex vivo myometrial tissue nor did it reduce in vitro inflammation-induced contractility in myometrial cells. Additionally, ticagrelor did not exhibit the anticipated anti-inflammatory effects in myometrial cell culture experiments. In our mouse model of preterm birth, ticagrelor neither improved the preterm birth rate or fetal survival outcomes. Gene expression of pro-inflammatory cytokines and contraction-associated proteins in postpartum mouse uteri were unaltered by ticagrelor. In conclusion, ticagrelor is not a strong candidate to continue investigations in clinical trial for the treatment of preterm labour and prevention of preterm birth.

Metagenomic investigation of 16S rRNA marker gene samples to analyze the role of race, ethnicity, and location in preterm birth: A comprehensive vaginal microbiome meta-analysis

The vaginal microbiome is essential to women's reproductive health and numerous studies have demonstrated that any microbial dysbiosis can increase the risk of Preterm Birth (PTB). The present study utilized an integrated computational methodology to conduct a meta-analysis of PTB vaginal microbiome samples from women of different racial, ethnic, and geographical locations, across multiple studies derived from public repositories. Taxonomic classification, functional profiling, and statistical analysis of the PTB samples revealed that Finegoldia, Haemophilus, and Lactobacillus showed the highest variation in their microbial abundances while the Sensory system pathway, Substance dependence pathway, and Circulatory system pathway showed the highest variation in their expression levels based on race, ethnicity, and locations respectively. All of these factors cause subsequent variations in the etiology of PTB across the aforementioned demographic attributes. LEfSE and ANCOM-BC approaches were performed to identify race, ethnicity, and geographic location-specific microbial biomarkers. To the best of our knowledge, our work is one of the first to provide a detailed analysis of the complex delineations between socioeconomic constructs of race and ethnicity at a global scale, considering the eight racial groups and the geographical location of the participants who faced PTB. We believe these findings will have significant implications for the development of more targeted and efficacious strategies for the prevention and treatment of PTB.

Diving into CDC pregnancy data in the United States: longitudinal study and interactive application.

Preterm birth (PTB) is a major determinant of neonatal mortality, morbidity, and childhood disability. In this article, we present a longitudinal analysis of the risk factors associated with PTB and how they have varied over the years: starting from 1968 when the CDC first started, reporting the natality data, up until 2021. Along with this article, we are also releasing an RShiny web application that will allow for easy consumption of this voluminous dataset by the research community. Further, we hope this tool can aid clinicians in the understanding and prevention of PTB. This study used the CDC Natality data from 1968 to 2021 to analyze trends in PTB outcomes across the lens of various features, including race, maternal age, education, and interval length between pregnancies. Our interactive RShiny web application, CDC NatView, allows users to explore interactions between maternal risk factors and maternal morbidity conditions and the aforementioned features. Our study demonstrates how CDC data can be leveraged to conduct a longitudinal analysis of natality trends in the United States. Our key findings reveal an upward trend in late PTBs, which is concerning. Moreover, a significant disparity exists between African American and White populations in terms of PTB. These disparities persist in other areas, such as education, body-mass index, and access to prenatal care later in pregnancy. Another notable finding is the increase in maternal age over time. Additionally, we confirm that short interpregnancy intervals (IPIs) are a risk factor for PTBs. To facilitate the exploration of pregnancy risk factors, infections, and maternal morbidity, we developed an open-source RShiny tool called CDC NatView. This software offers a user-friendly interface to interact with and visualize the CDC natality data, which constitutes an invaluable resource. In conclusion, our study has shed light on the rise of late PTBs and the persistent disparities in PTB rates between African American and White populations in the US. The increase in maternal age and the confirmation of a short IPI as a risk factor for PTB are noteworthy findings. Our open-source tool, CDC NatView, can be a valuable resource for further exploration of the CDC natality data to enhance our understanding of pregnancy risk factors and the interaction of PTB outcomes and maternal morbidities.

Statement of Retraction: Matched sample comparison of intramuscular versus vaginal micronized progesterone for prevention of preterm birth

Statement of Retraction: Matched sample comparison of intramuscular versus vaginal micronized progesterone for prevention of preterm birth

A Guide to Measuring and Interpreting Omega-3 (n-3) Fatty Acid Status in Relation to Health

Dietary fats can play a role in life-long health outcomes. The role of polyunsaturated fatty acids (PUFA) in health and disease has been a keen focus of researchers for over 50 years. Recently the focus of this research has turned to the beneficial role of the omega-3 (n-3) PUFA on health outcomes including heart disease and the prevention of preterm birth. From the standpoint of clinical practice, there has been a call for reliable screening tests that can predict risk. Two tests, both involving the measurement of n-3 PUFA in blood or its fractions, have become prominent, namely, the ‘omega-3 index’ as a predictor of cardiovascular disease risk and the ‘total n-3’ pregnancy test as a predictor of risk of premature birth. We provide an overview for pathologists, clinicians and nutritionists of the methodology and terminology related to the n-3 biomarkers to aid their interpretation of proposed cut-point values for health risk.

Cervical Pessary for Prevention of Preterm Birth in Individuals With a Short Cervix: The TOPS Randomized Clinical Trial

(Abstracted from JAMA 2023;330(4):340–348) Preterm delivery remains a public health issue, affecting many pregnant patients and their infants each year. There are a number of causes and associations with preterm delivery, with some that are identifiable and treatable and some that are not; one association that has been well established is the connection between preterm birth (PTB) and a short cervix.

269 Stress-reducing interventions in pregnancy for prevention of preterm birth: a systematic review and meta-analysis.

269 Stress-reducing interventions in pregnancy for prevention of preterm birth: a systematic review and meta-analysis.

Analysis of cases of premature rupture of membranes and preterm births to identify effective management measures to prevent them

Aim: Based on retrospective analysis recognize the key factors of development of premature childbirth and elaborate highly specific criteria for individual prognosis to improve perinatal outcomes. Materials and Methods: A retrospective analysis of the birth histories of 250 women and their newborns with spontaneous preterm births at 22-36 weeks was conducted using archival data from the department for pregnant women with obstetric pathology of the State Institution “Institute of Pediatrics, Obstetrics and Gynecology named by academician OM Lukianova of the National Academy of Medical Sciences of Ukraine” Results: Important risk factors for premature rupture of membranes (PROM) in preterm pregnancy include the presence of sexually transmitted diseases (χ2=31.188, p=0.001), bacterial vaginosis (χ2=30.913, p=0.0001), a history of abortion and/or preterm birth (χ2=16.62, p=0.0002), SARS during pregnancy (χ2=16.444, p=0.0002), chronic adnexitis in anamnesis (χ2=11.522, p=0.0031), inflammatory cervical disease (χ2=11.437, p=0.0032), anaemia (χ2=10.815, p=0.0044), isthmic-cervical insufficiency (ІСІ) (χ2=10.345, p=0.0057), chronic pyelonephritis with exacerbation (χ2=9.16, p=0.01), smoking during pregnancy (χ2=10.815, p=0.0044). Conclusions: The results of a retrospective analysis of 250 cases of preterm birth at 22 to 36 weeks allowed us to identify ways to effectively use existing diagnostic measures to determine readiness for pregnancy and the possibility of prolonging pregnancy to the viability of the newborn. Ways to improve the prevention of preterm birth and the design of further research were identified.

620 Childhood outcomes of multiples prenatally exposed to progesterone for the prevention of preterm birth

620 Childhood outcomes of multiples prenatally exposed to progesterone for the prevention of preterm birth

Conceptual framework for preterm birth review in San Francisco.

Preterm birth persists as a leading cause of infant mortality and morbidity despite decades of intervention effort. Intervention null effects may reflect failure to account for social determinants of health (SDH) or jointly acting risk factors. In some communities, persistent preterm birth trends and disparities have been consistently associated with SDH such as race/ethnicity, zip code, and housing conditions. Health authorities recommend conceptual frameworks for targeted action on SDH and precision public health approaches for preterm birth prevention. We document San Francisco, California's experience identifying the need, rationale, methods, and pilot work for developing a conceptual framework for preterm birth review (PTBR) in San Francisco. The PTBR conceptual framework is intended to enable essential public health services in San Francisco that prevent a range of preterm birth phenotypes by guiding plans for data collection, hypothesis testing, analytical methods, reports, and intervention strategy. Key elements of the PTBR conceptual framework are described including, 10 domains of SDH, 9 domains at the whole person level, such as lived experience and health behaviors, 8 domains at the within-person level, such as biomarkers and clinical measures, 18 preterm birth phenotypes, and the interconnections between domains. Assumptions for the PTBR conceptual framework were supported by a scoping review of literature on SDH effects on preterm birth, health authority consensus reports, and PTBR pilot data. Researcher and health authority interest in each of the domains warrants the framework to prompt systematic consideration of variables in each proposed domain. PTBR pilot data, illustrated in heatmaps, confirm the feasibility of data collection based on the framework, prevalence of co-occurring risk factors, potential for joint effects on specific preterm birth phenotypes, and opportunity for intervention to block SDH effects on preterm birth. The proposed PTBR conceptual framework has practical implications for specifying (1) population groups at risk, (2) grids or heatmap visualization of risk factors, (3) multi-level analyses, and (4) multi-component intervention design in terms of patterns of co-occurring risk factors. Lessons learned about PTBR data collection logistics, variable choice, and data management will be incorporated into future work to build PTBR infrastructure based on the PTBR conceptual framework.

Laparoscopic prepregnancy transabdominal cerclage: operative and pregnancy outcomes for a novel technique of suture placement using port closure device

Trans-abdominal cerclage (TAC) is an effective surgical intervention for preterm birth prevention. Placement of cervical suture using port closure device for pre-pregnancy laparoscopic abdominal cerclage has been used at our unit in recent years. We report operative and pregnancy outcomes for pre-pregnancy laparoscopic abdominal cerclage using the port closure device compared to traditional approach.For pre-pregnancy laparoscopic TAC(n=52), the port closure device approach is associated with lower blood loss at surgery and hospital length of stay (0.95+-4.4 mls vs 5.4+-15.7mls, p=0.007; 0.0(0.0-0.0) days vs 1.0(0.0-1.0) days, p<0.001). There were also trends towards shorter operating times (41.4+-15.3 minutes versus 50.1+-18.0, p=0.167) and lower peri-operative complications (0.0%, 0/21 vs 16.1%, 5/31, p=0.065) compared to traditional technique. There was no significant difference between the port closure device technique and traditional approach in rates of preterm birth rate in subsequent pregnancy (0.0%,0/9 vs 22.6%,7/39, p=0.248).Novel use of the port closure device for suture placement at pre-pregnancy laparoscopic cerclage for preterm birth prevention. This technique is associated with lower blood loss and length of stay, has trends in shorter operating times and peri-operative complications and similar rates of preterm birth.

A genome-wide and candidate gene association study of preterm birth in Korean pregnant women.

Preterm birth (PTB) refers to delivery before 37 weeks of gestation. Premature neonates exhibit higher neonatal morbidity and mortality rates than term neonates; therefore, it is crucial to predict and prevent PTB. Advancements enable the prediction and prevention of PTB using genetic approaches, especially by investigating its correlation with single nucleotide polymorphisms (SNPs). We aimed to identify impactive and relevant SNPs for the prediction of PTB via whole-genome sequencing analyses of the blood of 31 pregnant women with PTB (n = 13) and term birth (n = 18) who visited the Ewha Womans University Mokdong Hospital from November 1, 2018 to February 29, 2020. A genome-wide association study was performed using PLINK 1.9 software and 256 SNPs were selected and traced through protein-protein interactions. Moreover, a validation study by genotyping was performed on 60 other participants (preterm birth, n = 30; term birth, n = 30) for 25 SNPs related to ion channel binding and receptor complex pathways. Odds ratios were calculated using additive, dominant, and recessive genetic models. The risk of PTB in women with the AG allele of rs2485579 (gene name: RYR2) was significantly 4.82-fold increase, and the risk of PTB in women with the AG allele of rs7903957 (gene name: TBX5) was significantly 0.25-fold reduce. Our results suggest that rs2485579 (in RYR2) can be a genetic marker of PTB, which is considered through the association with abnormal cytoplasmic Ca2+ concentration and dysfunctional uterine contraction due to differences of RYR2 in the sarcoplasmic reticulum.

The Arabin cervical pessary for the prevention of preterm birth in twin-to-twin transfusion syndrome treated by fetoscopic laser coagulation: a multicenter randomized controlled trial

BackgroundMiscarriage and preterm birth are leading causes of loss and disability in monochorionic twins following laser treatment for twin-twin transfusion syndrome. ObjectiveWe investigated the use of the cervical pessary to reduce preterm birth before 32 weeks in monochorionic diamniotic twin pregnancies after fetal surgery for twin-twin transfusion syndrome. Study designIn this open-label multicenter randomized trial pregnant women carrying monochorionic diamniotic twins requiring fetoscopic laser coagulation for twin-twin transfusion syndrome were randomly assigned in a 1:1 ratio to pessary placement or conservative management. The primary outcome was birth before 32 weeks. Secondary outcomes were birth before 28, 30, 34 or 37 weeks, preterm rupture of membranes, fetal and neonatal survival, and a composite of maternal and neonatal complications. The estimated sample size was 364 patients, with 182 cases in each arm of the study. The analysis was performed according to the intention-to-treat principle. Two interim analyses were planned. ResultsThe trial was stopped prematurely after the first planned interim analysis for futility. One hundred thirty-seven women were included in the analysis, 67 in the pessary and 70 in the conservative management group. A preterm birth before 32 weeks occurred in 27/67 women (40.3%) in the pessary group and in 25/70 women (35.7%) in the conservative management group (aOR, 1.19; 95%CI, 0.58-2.47, P=.63). No significant differences between groups were observed in the rate of deliveries before 28, 30, 34 and 37 weeks, respectively. Overall survival to delivery was 91.2% (125/137) for at least one twin and 70.8% (97/137) for both twins, with no differences between groups. Neonatal survival at 30 days was 76.5% (208/272). There were no differences between groups in maternal or neonatal morbidity. ConclusionIn monochorionic diamniotic twin pregnancies requiring fetal therapy for twin-twin transfusion syndrome, routine use of cervical pessary did not reduce the rate of preterm delivery before 32 weeks.

Deciphering a critical role of uterine epithelial SHP2 in parturition initiation at single cell resolution

The timely onset of female parturition is a critical determinant for pregnancy success. The highly heterogenous maternal decidua has been increasingly recognized as a vital factor in setting the timing of labor. Despite the cell type specific roles in parturition, the role of the uterine epithelium in the decidua remains poorly understood. This study uncovers the critical role of epithelial SHP2 in parturition initiation via COX1 and COX2 derived PGF2α leveraging epithelial specific Shp2 knockout mice, whose disruption contributes to delayed parturition initiation, dystocia and fetal deaths. Additionally, we also show that there are distinct types of epithelium in the decidua approaching parturition at single cell resolution accompanied with profound epithelium reformation via proliferation. Meanwhile, the epithelium maintains the microenvironment by communicating with stromal cells and macrophages. The epithelial microenvironment is maintained by a close interaction among epithelial, stromal and macrophage cells of uterine stromal cells. In brief, this study provides a previously unappreciated role of the epithelium in parturition preparation and sheds lights on the prevention of preterm birth.

Progesterone and Treatment for Preterm Birth: Past, Present and Future

Abstract: Preterm birth (PTB) remains a leading cause of neonatal morbidity and mortality in the United States and worldwide. Efforts to predict and delay preterm birth have been largely unsuccessful thus far. This paper seeks to illuminate the history and relevant discoveries regarding the role of progesterone in the prevention of PTB, which includes maintaining quiescence of the myometrium and counteracting cervical ripening. We will review the outcomes and methodologies of recent clinical trials, which have led to debate over the efficacy of progesterone in delaying PTB among at-risk women. The aim of this paper is to explore the historical and scientific basis for progestin treatments in the prevention of PTB, briefly discuss the results of recent clinical trials, and suggest direction for future research.

Preconception laparoscopic cervical cerclage for prevention of mid-trimester pregnancy loss and preterm birth: A 6-year study

ObjectiveTo evaluate surgical results and pregnancy outcomes of preconception laparoscopic cervical cerclage (LCC) in women with cervical insufficiency. Study designWe conducted an observational study in consecutive women who had preconception LCC. Data was prospectively collected from 55 women at high risk of second trimester miscarriage and extreme preterm delivery due to cervical insufficiency who underwent pre-conception LCC between January 2017 – December 2021. This included patient demographics and relevant obstetric & gynaecological history, previous cervical cerclage, operative complications and subsequent pregnancy outcomes. All women included in study had at least one previous unsuccessful transvaginal cervical cerclage. The surgeries were conducted in private tertiary hospital in Hyderabad, India. The follow-up was until December 2022. The primary outcome was neonatal survival. Surgical morbidity and complications were also recorded. ResultsThere were 49 pregnancies of which 46 progressed beyond first trimester. 4.34 % (2/46) were delivered between 28 and 33 weeks due to preterm premature rupture of membranes (PPROM). 13.04 % (6/46) including 5 women with pregnancy complications and one with unicornuate uterus needed delivery between 34 and 36 weeks. 82.60 % (38/46) women were delivered at or beyond 37 weeks of pregnancy. In those who carried pregnancy beyond first trimester, live-birth rate and neonatal survival rate were 100 %. All neonates had favourable outcome with no long-term morbidity. There were no intraoperative or immediate postoperative complications. Two women had long-term complication in the form of tape erosion needing further surgery. ConclusionsThis study provides evidence that LCC improves pregnancy outcomes significantly in those with cervical weakness, without increasing the safety risk.

Primary prevention with vaginal chlorhexidine before 16 weeks reduces the incidence of preterm birth: results of the Preterm Labor Prevention Using Vaginal Antiseptics study

Preterm labor is one of the leading causes of perinatal death and is currently considered a syndrome with many causes. One of the most important causes of preterm birth is ascending infection from bacterial vaginosis. Chlorhexidine has proven to be effective against bacterial vaginosis and against bacterial biofilms without affecting gestation. We aimed to evaluate the effectiveness of a universal primary prevention strategy for preterm birth using intravaginal chlorhexidine applied before 16 weeks (Preterm Labor Prevention Using Vaginal Antiseptics study). We performed a prospective observational study with 2 cohorts of pregnant women that were assigned either to prevention of preterm birth by means of intravaginal chlorhexidine (Cum Laude Chlorhexidine, chlorhexidine digluconate 0.2%) before 16 weeks (n=413), or to no treatment following the usual hospital protocol (n=704). Primary outcomes were the incidence of spontaneous preterm birth before 34 and 37 weeks; the incidence of preterm birth before 34 and 37 weeks, including inductions for premature rupture of membranes; and the incidence of preterm birth before 34 and 37 weeks, including any indication for termination of pregnancy. Both cohorts were compared using Mann-Whitney and Fisher tests. Finally, a multivariable analysis, including the odds ratio was performed, adjusting for clinical parameters, to evaluate the importance of the different determinants in the prediction of preterm birth. In pregnancies treated with chlorhexidine, the incidences of spontaneous preterm birth; preterm birth, including induction for premature rupture of membranas; and preterm birth, including any indication for termination of pregnancy were at 34 and 37 weeks: 0% and 0%, 0.24% and 1.69, and 2.90% and 3.15%, respectively; whereas in nontreated pregnancies, these incidences were 9% and 11%, 12% and 23%, and 35% and 43%, respectively. According to the multivariable analysis, the incidence of preterm birth among women treated with chlorhexidine before 16 weeks was halved (Odds ratio, 0.52; P<.05). Universal treatment with vaginal chlorhexidine before 16 weeks reduces the incidence of preterm birth, especially before 34 weeks.

Randomized controlled trials: not always the “gold standard” for evidence in obstetrics and gynecology

Randomized Controlled Trials (RCTs) are considered the "gold standard" for therapeutic interventions, and it is not uncommon for sweeping changes in medical practice to follow positive results from such trials. However, RCTs are not without their limitations. Physicians frequently view RCTs as infallible, while they tend to dismiss evidence derived from sources other than RCTs as less credible or reliable. In several situations in obstetrics & gynecology, there are no RCTs to help guide the clinician. In these circumstances, it is important to evaluate the entire body of evidence including observational studies, rather than to dismiss interventions altogether simply because no RCTs exist. RCTs and observational studies should be viewed as complementary to each other rather than at odds with each other. Some reversals in widely adopted clinical practice have recently been implemented following subsequent studies that contradicted the outcomes of major RCTs; the most notable of these being the withdrawal from the market of 17-hydroxyprogesterone caproate for preterm birth prevention. Such reversals could potentially have been averted if the inherent limitations of RCTs were carefully considered prior to implementing these universal practice changes. This Clinical Opinion underscores the limitations of an exclusive reliance on RCTs while disregarding other evidence in determining how best to care for patients. Solutions are proposed that advocate that clinicians adopt a more balanced perspective that considers the entirety of the available medical evidence as well as the individual patient characteristics, needs, and wishes.