The Choice of Population and Outcomes in Neonatal Trials on Hyperbilirubinemia: Are They Relevant? An Analysis of Cochrane Neonatal Reviews

Neonatology ◽  
2020 ◽  
pp. 1-7
Author(s):  
Nai Ming Lai ◽  
Shaun Wen Huey Lee ◽  
Sheng Xuan Wai ◽  
Zhi Wei Teh ◽  
Min Yao Chan ◽  
...  
Keyword(s):  
High Risk ◽  
Primary Outcome ◽  
Serum Bilirubin ◽  
Surrogate Marker ◽  
Low Risk ◽  
Use Of Resources ◽  
Cochrane Reviews ◽  
High Risk Populations ◽  
High Risk Infants ◽  
Event Rates

<b><i>Background:</i></b> Neonates with jaundice are usually managed according to their serum bilirubin despite an unclear overall correlation between bilirubin levels and patient-important outcomes (PIOs) such as kernicterus spectrum disorder (KSD). <b><i>Objectives:</i></b> We examined data from Cochrane Neonatal reviews to assess whether conditions that constituted KSD were included as key outcomes and how commonly they occurred in the population studied. <b><i>Methods:</i></b> We identified Cochrane reviews, published till November 2017 that evaluated interventions for neonatal jaundice (NNJ). We extracted the following information at the review and study levels: included population, outcomes assessed (in particular, whether PIOs such as KSD were listed as the primary outcomes), as well as their cumulative incidence in the reviews. <b><i>Results:</i></b> Out of 311 reviews, 11 evaluated interventions for NNJ with 78 randomized controlled trials (RCTs) included. Among the reviews, a total number of 148 outcomes were predefined and 30 (20.3%) were PIOs related to KSD, with 11 (36.7%) listed as primary outcomes. Among the 78 included RCTs (total participants = 8,232), 38 (48.7%) enrolled predominantly high-risk and 40 (51.3%) enrolled predominantly low-risk population. A total number of 431 outcomes were reported, and 40 (9.2%) were PIOs related to KSD (of which 37 were from studies with high-risk infants), with 13 (32.5%) listed as primary outcome. Cumulatively, no infant developed KSD across all studies. <b><i>Conclusions:</i></b> There is suboptimal representation of PIOs such as KSD in neonatal trials and Cochrane reviews on NNJ. Over half of the trials included populations with very low risk of KSD, which does not represent judicious use of resources. Amidst our continued search for a more reliable surrogate marker for NNJ, studies should evaluate the whole spectrum KSD alongside serum bilirubin in high-risk populations with sufficiently significant event rates, as this will make the trial methodologically feasible, with findings that will impact the population concerned.

Precursor lesions of oesophageal cancer in a low-risk population in China: Comparison with high-risk populations

1984 ◽  
Vol 34 (5) ◽  
pp. 599-602 ◽  
Author(s):  
M. Crespi ◽  
N. Muńoz ◽  
A. Grassi ◽  
Shen Qiong ◽  
Wang Kuo Jing ◽  
...  
Keyword(s):  
High Risk ◽  
Oesophageal Cancer ◽  
Low Risk ◽  
Precursor Lesions ◽  
Risk Population ◽  
High Risk Populations

The Prevalence of the Human Papillomavirus in Cervix and Vagina in Low-risk and High-risk Populations

2004 ◽  
Vol 36 (6-7) ◽  
pp. 456-459 ◽  
Author(s):  
Marc Baay ◽  
Veronique Verhoeven ◽  
Kristien Wouters ◽  
Filip Lardon ◽  
Pierre Van Damme ◽  
...  
Keyword(s):  
Human Papillomavirus ◽  
High Risk ◽  
Low Risk ◽  
High Risk Populations

scholarly journals Assessing the risk of performance and detection bias in Cochrane reviews as a joint domain is less accurate compared to two separate domains

2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Ognjen Barcot ◽  
Matija Boric ◽  
Svjetlana Dosenovic ◽  
Livia Puljak
Keyword(s):  
High Risk ◽  
Risk Of Bias ◽  
Low Risk ◽  
Single Domain ◽  
Similar Proportion ◽  
Detection Bias ◽  
Cochrane Reviews ◽  
Outcome Type ◽  
Performance Bias ◽  
Made In

Abstract Background Initially, the Cochrane risk of bias (RoB) tool had a domain for “blinding of participants, personnel and outcome assessors”. In the 2011 tool, the assessment of blinding was split into two domains: blinding of participants and personnel (performance bias) and blinding of outcome assessors (detection bias). The aims of this study were twofold; first, to analyze the frequency of usage of the joint blinding domain (a single domain for performance and detection bias), and second, to assess the proportion of adequate assessments made in the joint versus single RoB domains for blinding by comparing whether authors’ RoB judgments were supported by explanatory comments in line with the Cochrane Handbook recommendations. Methods We extracted information about the assessment of blinding from RoB tables (judgment, comment, and whether it was specified which outcome type; e.g., objective, subjective) of 729 Cochrane reviews published in 2015-2016. In the Cochrane RoB tool, judgment (low, unclear or high risk) needs to be accompanied by a transparent comment, in which authors provide a summary justifying RoB judgment, to ensure transparency in how these judgments were reached. We reassessed RoB based on the supporting comments reported in Cochrane RoB tables, in line with instructions from the Cochrane Handbook. Then, we compared our new assessments to judgments made by Cochrane authors. We compared the frequency of adequate judgments in reviews with two separate domains for blinding versus those with a joint domain for blinding. Results The total number of assessments for performance bias was 6918, with 8656 for detection bias and 3169 for the joint domain. The frequency of adequate assessments was 74% for performance bias, 78% for detection bias, and 59% for the joint domain. The lowest frequency of adequate assessments was found when Cochrane authors judged low risk – 47% in performance bias, 62% in detection bias, and 31% in the joint domain. The joint domain and detection bias domain had a similar proportion of specified outcome types (17% and 18%, respectively). Conclusions Splitting joint RoB assessment about blinding into two domains was justified because the frequency of adequate judgments was higher in separate domains. Specification of outcome types in RoB domains should be further scrutinized.

THE EFFECT OF BUFFERED AND NON-BUFFERED ACD BLOOD ON ELECTROLYTE AND ACID-BASE HOMEOSTASIS DURING EXCHANGE TRANSFUSION

PEDIATRICS ◽  
1968 ◽  
Vol 41 (4) ◽  
pp. 802-814
Author(s):  
W. E. Pierson ◽  
Cynthia T. Barrett ◽  
T. K. Oliver
Keyword(s):  
High Risk ◽  
Exchange Transfusion ◽  
Low Risk ◽  
Acid Base ◽  
High Risk Infants

Exchange transfusions have been performed using buffered and non-buffered ACD blood. In 15 low risk infants receiving unbuffered blood, severe acidosis occurred in one during the transfusion. Other investigators have recently observed similar findings. In contrast, when blood was buffered prior to exchange transfusion in 26 high risk infants (i.e., with cardiorespiratory insufficiency), acidemia did not occur. Since the mortality of exchange transfusion is increased in infants with cardiorespiratory insufficiency, it appears that buffered ACD blood will lessen the risks. It is recommended that, ACD blood is used for exchange transfusion in any infant, the blood should be buffered immediately prior to transfusion using 10 mM of 1.0-1.2 M THAM.

Comparison of infant heart rate assessment by auscultation, ECG and oximetry in the delivery room

2018 ◽  
Vol 103 (5) ◽  
pp. F490-F492 ◽  
Author(s):  
Madeleine C Murphy ◽  
Laura De Angelis ◽  
Lisa K McCarthy ◽  
Colm Patrick Finbarr O’Donnell
Keyword(s):  
Heart Rate ◽  
High Risk ◽  
Pulse Oximetry ◽  
Clinical Assessment ◽  
Newborn Infants ◽  
Mean Difference ◽  
Low Risk ◽  
Delivery Room ◽  
Reasonable Accuracy ◽  
High Risk Infants

Clinical assessment of an infant’s heart rate (HR) in the delivery room (DR) has been reported to be inaccurate. We compared auscultation of the HR using a stethoscope with electrocardiography (ECG) and pulse oximetry (PO) for determining the HR in 92 low-risk newborn infants in the DR. Caregivers auscultated the HR while masked to the HR on the monitor. Auscultation underestimated ECG HR (mean difference (95% CI) by −9 (−15 to –2) beats per minute (bpm)) and PO HR (mean difference (95% CI) by −5 (−12 to 2) bpm). The median (IQR) time to HR by auscultation was 14 (10–18) s. As HR was determined quickly and with reasonable accuracy by auscultation in low-risk newborns, study in high-risk infants is warranted.

scholarly journals Using HMGB1 Protein as a Surrogate Marker for Lung Cancer in High‐Risk Populations

2020 ◽  
Vol 34 (S1) ◽  
pp. 1-1
Author(s):  
Breanna Cole ◽  
Eric Jeffords ◽  
Glenn E. Simmons
Keyword(s):  
Lung Cancer ◽  
High Risk ◽  
Surrogate Marker ◽  
Hmgb1 Protein ◽  
High Risk Populations

Relationship of Serum Bilirubin Levels to Ototoxicity and Deafness in High-Risk Low-Birth-Weight Infants

PEDIATRICS ◽  
1985 ◽  
Vol 76 (3) ◽  
pp. 351-354
Author(s):  
L. S. de Vries ◽  
S. Lary ◽  
L. M.S. Dubowitz
Keyword(s):  
Birth Weight ◽  
High Risk ◽  
Preterm Infants ◽  
Bilirubin Level ◽  
Serum Bilirubin ◽  
Sensorineural Deafness ◽  
Serum Bilirubin Level ◽  
Low Birth Weight Infants ◽  
High Risk Infants ◽  
L 14

During a 4-year period, 12 premature infants, all less than 34 weeks of gestation and all with a bilirubin level above 240 µmol/L (14 mg/dL) were determined to have bilateral sensorineural deafness. In order to investigate how far the hyperbilirubinemia or any associated factor might have been a causative factor, all infants of 34 weeks of gestation or less who had a serum bilirubin level above 240 µmol/L were investigated. For a period of 4 years, 99 infants meeting these criteria were classified as high risk or low risk on the basis of perinatal risk factors. Eight of the 22 high-risk infants with birth weight less than 1,500 g, but only two of 43 high-risk infants with birth weight greater than 1,500 g were deaf (P &lt; .05). The deaf infants were also matched with infants of normal hearing who had similar bilirubin levels and the same number of adverse perinatal factors. The mean duration of hyperbilirubinemia was significantly longer in the deaf infants (P &lt; .02), and they appeared to have a greater number of acidotic episodes while they were hyperbilirubinemic. These findings suggest that in healthy preterm infants with birth weight greater than 1,500 g, high bilirubin levels carry little risk, whereas a serum bilirubin level greater than 240 µmol/L in highrisk preterm infants with birth weight of 1,500 g or less is associated with a high risk of deafness.

THE DEVELOPMENT OF HIGH-RISK INFANTS IN LOW-RISK FAMILIES

1989 ◽  
pp. 81-137
Author(s):  
Deborah L. Holmes ◽  
Jill Nagy Reich ◽  
James S. Gyurke
Keyword(s):  
High Risk ◽  
Low Risk ◽  
High Risk Infants

APPLICATION of EUTOS SCORE IN CHRONIC Myeloid LEUKEMIA AFFECTING VERY Elderly (>75 years) PATIENTS

Blood ◽  
2011 ◽  
Vol 118 (21) ◽  
pp. 1686-1686
Author(s):  
Simona Sica ◽  
Massimo Breccia ◽  
Francesco Autore ◽  
Roberto Latagliata ◽  
Elisabetta Abruzzese ◽  
...  
Keyword(s):  
High Risk ◽  
Risk Group ◽  
Prognostic Score ◽  
Surrogate Marker ◽  
Cytogenetic Response ◽  
Small Sample ◽  
Low Risk ◽  
Banding Technique ◽  
Complete Cytogenetic Response ◽  
Eutos Score

Abstract Abstract 1686 The Eutos score has recently been published as a new prognostic score in CML because of its prognostic ability and its simplicity in the imatinib era. It maintains the percent of basophils and the spleen size and it eliminates three other laboratory values and the variable of the age, that is usually important in the prognosis of almost all the diseases. This score was able to predict the probability of achieving a complete cytogenetic response (CCgR) within 18 months, which is the most solid and confirmed surrogate marker of survival in CML treated with imatinib. Thus we reviewed the cases of CML affecting individuals > 75 years and we apply the Eutos score and compare results with classic Sokal risk. We collected 221 patients from 29 of the major Italian hematological centers for diagnosis and treatment of CML. Because of the lack of data for the calculation of the scores in 84 patients, 137 patients were evaluable. The M: F ratio was 70: 67, the median age was of 78 years (range 75–89). Patients aged >75 years as expected showed frequently comorbidities (cardiovascular, respiratory, renal, oncologic ones). The distribution according to the Sokal score was: 3 patients in the low risk group, 95 patients in the intermediate risk group and 39 patients in the high risk group. As expected, there were only few patients in the low Sokal risk group aged >75 years in demonstration of the importance of the age in this score. Calculating Eutos score we have identified only 6 patients with a high score, whereas the remaining 131 patients were in the low risk group. The group with high Eutos risk score included 5 males and 1 female; their median age was 77 years (range 75–78), at the onset their median white blood cell count was 33.840/mmc (range 29.500–300.000), platelet count was 1.443.000/mmc (range 453.000–4.849.000), their median level of hemoglobin was 8.8 g/dl (range 7.7–13.9). All of them showed percent of basophils>12%, whereas at physical examination splenomegaly was usually moderate with no hepatomegaly. Due to the small sample of patients in the high Eutos score statistical analysis was not feasible but we tried to correlate baseline informations to the outcome. Not all the high Eutos risk patients were in the high Sokal risk group (3 patients were in the high Sokal risk group and 3 were in the intermediate one) none was in the low Sokal risk group. All but one patients in the high risk Eutos score were treated with imatinib in early chronic phase of CML. Then we considered the complete cytogenetic response (CCyR) at 18 months, performed through conventional cytogenetic analysis on bone marrow cells by G-banding technique. This has been chosen for the validation of the Eutos score as a solid early surrogate marker of outcome. The overall rate of CCyR was 100% in the low Sokal risk group, 63% in the intermediate Sokal risk group and 69% in the high Sokal risk group; the same type of response was 67% in the low Eutos risk group and 50% in the high Eutos risk group (Table 1). In the high Eutos risk group, 2 patients achieved CCyR, 1 patient achieved MMR, 2 patients did not achieve it and 1 patient was not evaluable. Two patients died because of comorbidities (relapse of colon cancer and cardio-respiratory insufficiency) at 19 and 39 months of follow up. Resistance to imatinib was registered in 17 out of 131 patients (13%) in the low Eutos risk and in 3 out of 6 patients (50%) in the high Eutos risk. In our series of CML patients >75 years, high Eutos score was infrequent (4.38%). Moving from Sokal to Eutos score, patients were largely reallocated as low risk Eutos score. It is not clear whether the low frequency of high risk Eutos might be attributed to a early diagnosis of CML in this subset of patients with age-related comorbidities requiring frequent laboratory exams. In view of the ability to predict CCyR at 18 months, Eutos score validation in the setting of elderly patients with CML could be relevant to clinical practice.Table 1Distribution of patients according Sokal and Eutos scoreN° patients% CCyRSOKALLow risk3100%Intermediate risk9563%High risk3969%EUTOSLow risk13167%High risk650% Disclosures: Russo Rossi: Novartis: Honoraria; Bristol Myers Squibb: Honoraria. Rosti:Novartis: Consultancy; Bristol Myers Squibb: Consultancy; Novartis: Research Funding; Novartis: Honoraria; Bristol Myers Squibb: Honoraria.

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