SIDE EFFECTS OF PTU AND MMI IN THE TREATMENT OF HYPERTHYROIDISM: A SYSTEMATIC REVIEW AND META-ANALYSIS

2020 ◽  
Vol 26 (2) ◽  
pp. 207-217 ◽  
Author(s):  
Wenshu Yu ◽  
Na Wu ◽  
Ling Li ◽  
Junwu Wang ◽  
Hong OuYang ◽  
...  
Keyword(s):  
Confidence Interval ◽  
Odds Ratio ◽  
Meta Analysis ◽  
Age Groups ◽  
Antithyroid Drug ◽  
Late Pregnancy ◽  
First Trimester ◽  
Group Differences ◽  
Antithyroid Drugs ◽  
The Impact

Objective: The present study aimed to investigate the adverse effects of the antithyroid drugs propylthiouracil (PTU) and methimazole (MMI)/carbimazole (CMZ) in treating hyperthyroidism. Methods: Qualitative analysis was performed for studies identified in a literature search up to April 20, 2019, and 30 studies were selected for meta-analysis. The study designs included case-control, randomized controlled, and retrospective cohort. Patients were in four age groups: childhood, gestating mothers, older adults, and other ages, and all were receiving PTU or MMI/CMZ. Adverse reactions to MMI/CMZ and PTU were evaluated and compared. Results: Odds of liver function injury were higher in the PTU group than in the MMI/CMZ group (odds ratio [OR], 2.40; 95% confidence interval [CI], 1.16 to 4.96; P = .02). Odds of elevated transaminase were much higher in the PTU group than in the MMI/CMZ group (OR, 3.96; 95% CI, 2.49 to 6.28; P<.00001). No significant between-group differences were found in odds of elevated bilirubin, agranulocytosis, rash, or urticaria; incidence of other adverse events; or in children. Odds of birth defects during the first trimester of pregnancy were higher in the MMI/CMZ group than in the PTU group (OR, 1.29; 95% CI, 1.09 to 1.53; P = .003). Conclusion: The impact of PTU on liver injury and transaminase levels is greater than that of MMI/CMZ, but no significant between-group differences are found in the drugs' effects on bilirubin, agranulocytosis and rash, urticaria, or in children. In treating pregnancy-related hyperthyroidism, PTU should be used in the first trimester and MMI reserved for use in late pregnancy. Abbreviations: ALT = alanine aminotransferase; ATD = antithyroid drug; CI = confidence interval; CMZ = carbimazole; GD = Graves disease; MMI = methimazole; MTU = methylthiouracil; NOS = Newcastle-Ottawa Scale; OR = odds ratio; PTU = propylthiouracil; RAI = radioactive iodine

A Method for Meta-Analysis of Epidemiological Studies

1988 ◽  
Vol 22 (10) ◽  
pp. 813-824 ◽  
Author(s):  
Thomas R. Einarson ◽  
J. Steven Leeder ◽  
Gideon Koren
Keyword(s):  
Confidence Interval ◽  
Odds Ratio ◽  
Meta Analysis ◽  
A Priori ◽  
Epidemiological Studies ◽  
Percent Confidence Interval ◽  
Case Control Studies ◽  
Chi Square ◽  
The Impact ◽  
Summary Odds Ratio

This article presents a stepwise approach for conducting a meta-analysis of epidemiological studies based on proposed guidelines. This systematic method is recommended for practitioners evaluating epidemiological studies in the literature to arrive at an overall quantitative estimate of the impact of a treatment. Bendectin is used as an illustrative example. Meta-analysts should establish a priori the purpose of the analysis and a complete protocol. This protocol should be adhered to, and all steps performed should be recorded in detail. To aid in developing such a protocol, we present methods the researcher can use to perform each of 22 steps in six major areas. The illustrative meta-analysis confirmed previous traditional narrative literature reviews that Bendectin is not related to teratogenic outcomes in humans. The overall summary odds ratio was 1.01 (χ2 = 0.05, p = 0.815) with a 95 percent confidence interval of 0.66–1.55. When the studies were separated according to study type, the summary odds ratio for cohort studies was 0.95 with a 95 percent confidence interval of 0.62–1.45. For case-control studies, the summary odds ratio was 1.27 with a 95 percent confidence interval of 0.83–1.94. The corresponding chi-square values were not statistically significant at the p = 0.05 level.

scholarly journals The impact of atrial fibrillation type on the risks of thromboembolic recurrence, mortality and major haemorrhage in patients with previous stroke: A systematic review and meta-analysis of observational studies

2020 ◽  
Vol 5 (2) ◽  
pp. 155-168
Author(s):  
Antonia Mentel ◽  
Terence J Quinn ◽  
Alan C Cameron ◽  
Kennedy R Lees ◽  
Azmil H Abdul-Rahim
Keyword(s):  
Atrial Fibrillation ◽  
Systematic Review ◽  
Confidence Interval ◽  
Odds Ratio ◽  
Observational Studies ◽  
Meta Analysis ◽  
Major Haemorrhage ◽  
Risk Of Bias ◽  
Previous Stroke ◽  
The Impact

Introduction There is conflicting evidence on the impact of atrial fibrillation (AF) type, i.e. non-paroxysmal AF or paroxysmal AF, on thromboembolic recurrence. The consensus of risk equivalence is greatly based on historical evidence, focussing on initial stroke risks. We conducted a systematic review and meta-analysis to describe the impact of AF type on the risk of thromboembolic recurrence, mortality and major haemorrhage in patients with previous stroke. Methods We systematically searched four multidisciplinary databases from inception to December 2018. We selected observational studies investigating clinical outcomes in patients with ischaemic stroke and AF, stratified by AF type. We assessed all included studies for risk of bias using the ‘Risk of Bias In Non-randomised Studies – of Exposures’ tool. The Comprehensive Meta-Analysis Software was used to calculate odds ratios from crude event rates. Results After reviewing 14,127 citations, we selected 108 studies for full-text screening. We extracted data from a total of 26 studies, reporting outcomes on 23,054 patients. Overall, risk of bias was moderate. The annual incidence rates of thromboembolism in patients with non-paroxysmal AF and paroxysmal AF were 7.1% (95% confidence interval: 4.2–11.7) and 5.2% (95% confidence interval: 3.2–8.2), respectively. The odds ratio for thromboembolism in patients with non-paroxysmal AF versus paroxysmal AF was 1.47 (95% confidence interval: 1.08–1.99, p = 0.013). The annual mortality rates in patients with non-paroxysmal AF and paroxysmal AF were 20.0% (95% confidence interval: 13.2–28.0) and 10.1% (95% confidence interval: 5.4–17.3), respectively, and odds ratio was 1.90 (95% confidence interval: 1.43–2.52, p < 0.001). There was no difference in rates of major haemorrhage, odds ratio  = 1.01 (95% confidence interval: 0.61–1.69, p = 0.966). Conclusion In patients with prior stroke, non-paroxysmal AF is associated with significantly higher risk of thromboembolic recurrence and mortality than paroxysmal AF. Although current guidelines make no distinction between non-paroxysmal AF and paroxysmal AF for secondary stroke prevention, future guidance and risk stratification tools may need to consider this differential risk (PROSPERO ID: CRD42019118531).

Revascularisation in older adult patients with non-ST-segment elevation acute coronary syndrome: effect and impact on 6-month mortality

2019 ◽  
Vol 9 (4) ◽  
pp. 358-366 ◽  
Author(s):  
Alfredo Bardaji ◽  
José A Barrabés ◽  
Aida Ribera ◽  
Héctor Bueno ◽  
Antonio Fernández-Ortiz ◽  
...  
Keyword(s):  
Acute Coronary Syndrome ◽  
Confidence Interval ◽  
Older Adult ◽  
Odds Ratio ◽  
Meta Analysis ◽  
Two Stage ◽  
St Segment Elevation ◽  
Coronary Syndrome ◽  
St Segment ◽  
The Impact

Although revascularisation in non-ST-segment elevation acute coronary syndrome (NSTEACS) is associated with better outcomes, its impact in older adult patients is unclear. This is a retrospective analyses of three national NSTEACS registries conducted during the past decade in Spain. Patients aged 75 years and older were included: DESCARTES (DES; year 2002; n=534), MASCARA (MAS; 2005; n=1736) and DIOCLES (DIO; 2012; n=593). The adjusted association between revascularisation and total (inhospital and 6-month) mortality was estimated by two-stage meta-analysis (pooled effect across the three registries with inverse-variability weights) and one-stage meta-analysis (multilevel model with random effects across studies). The impact of revascularisation was assessed comparing the observed and the expected mortality based on a logistic regression model in the pooled database. Although revascularisation was associated with a lower risk of mortality in meta-analyses (two-stage: odds ratio 0.44, 95% confidence interval 0.29–0.67; one-stage: odds ratio 0.54, 95% confidence interval 0.36–0.81) and the revascularisation rate increased steadily from 2002 (DES 14.2%) to 2012 (DIO 43.7%), its impact was not patent across registries, probably because this increase was concentrated in low and medium-risk GRACE strata (tertile 1, 2 and 3: MAS 59%, 20% and 6%; DIO 64%, 39% and 19%, respectively). In conclusion, a consistent increase of revascularisation in NSTEACS in older adults was not followed by a decrease in mortality at 6 months, probably because the impact of this strategy is limited to the higher risk population, the stratum with the lowest revascularisation rate in real life.

Does Time-to-Chemotherapy Impact the Outcomes of Resected Ovarian Cancer? Meta-analysis of Randomized and Observational Data

2017 ◽  
Vol 27 (2) ◽  
pp. 274-280 ◽  
Author(s):  
Pedro Luiz Serrano Usón ◽  
Diogo Diniz Gomes Bugano ◽  
Monique Sedlmaier França ◽  
Yuri Philippe Pimentel Vieira Antunes ◽  
Patricia Taranto ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Confidence Interval ◽  
Odds Ratio ◽  
Meta Analysis ◽  
Disease Recurrence ◽  
Curative Intent ◽  
Platinum Based Chemotherapy ◽  
Definition Of ◽  
Optimal Debulking ◽  
The Impact

ObjectivesThis study is a meta-analysis of prior publications evaluating the impact of time-to-chemotherapy (TTC) on disease recurrence and survival 3 years after the original surgery.MethodsWe performed a meta-analysis of studies published in PubMed (1950–2016) as of April 2016. Inclusion criteria were as follows: randomized controlled trials and prospective or retrospective cohorts that included patients with ovarian cancer who had undergone surgery with curative intent and use of adjuvant chemotherapy. We compared rates of disease recurrence and death according to the TTC (“early” vs “delayed”) using a random-effects model and performed a metaregression to evaluate the impact of covariates on these outcomes.ResultsOf 239 abstracts in the original search, 12 were considered eligible. The cutoffs used for TTC were between 20 and 40 days. All studies used a platinum-based chemotherapy, and the rates of patients with suboptimal resection varied from 33% to 70%. A longer TTC was not associated with higher rates of disease recurrence (odds ratio, 0.89; 95% confidence interval, 0.63–1.24) or death at 3 years (odds ratio, 1.06; 95% confidence interval, 0.9–1.24). There was no evidence of significant publication bias (Egger test P = 0.472), but data were heterogeneous (I2 = 64.3%). Metaregression showed that the percentage of patients with suboptimal surgery and values used as cutoff to define “delayed” chemotherapy combined were a significant source of bias (residual I2 = 0%).ConclusionsIn our analysis, TTC after surgery for ovarian cancer with curative intent was not associated with higher risk of disease recurrence or death. However, this association was influenced by the rate of optimal debulking and definition of “late” initiation of chemotherapy, so we must be careful when applying these data to patients with complete resection.

scholarly journals Protective Effects of Statins Administration in European and North American Patients Infected with COVID-19: A Meta-analysis

2021 ◽  
Author(s):  
Mairi Pucci ◽  
Diletta Onorato ◽  
Giovanni Carpene ◽  
Brandon Michael Henry ◽  
Fabian Sanchis-Gomar ◽  
...  
Keyword(s):  
Confidence Interval ◽  
Statin Therapy ◽  
Odds Ratio ◽  
Meta Analysis ◽  
Protective Role ◽  
Favorable Effect ◽  
Current Evidence ◽  
Severe Illness ◽  
Protective Effects ◽  
Time Data

AbstractSevere acute respiratory syndrome coronavirus 2 has spread rapidly throughout the world, becoming an overwhelming global health emergency. The array of injuries caused by this virus is broad and not limited to the respiratory system, but encompassing also extensive endothelial and systemic tissue damage. Since statins effectively improve endothelial function, these drugs may have beneficial effects in patients with coronavirus disease 2019 (COVID-19). Therefore, this investigation aimed to provide an updated overview on the interplay between statins and COVID-19, with particular focus on their potentially protective role against progression toward severe or critical illness and death. A systematic electronic search was performed in Scopus and PubMed up to present time. Data on statins use and COVID-19 outcomes especially in studies performed in Europe and North America were extracted and pooled. A total of seven studies met our inclusion criteria, totaling 2,398 patients (1,075 taking statins, i.e., 44.8%). Overall, statin usage in Western patients hospitalized with COVID-19 was associated with nearly 40% lower odds of progressing toward severe illness or death (odds ratio: 0.59; 95% confidence interval: 0.35–0.99). After excluding studies in which statin therapy was started during hospital admission, the beneficial effect of these drugs was magnified (odds ratio: 0.51; 95% confidence interval: 0.41–0.64). In conclusion, although randomized trials would be necessary to confirm these preliminary findings, current evidence would support a favorable effect of statins as adjuvant therapy in patients with COVID-19. Irrespective of these considerations, suspension of statin therapy seems highly unadvisable in COVID-19 patients.

scholarly journals Adherence to antihypertensive medications and associated factors among hypertensive patients in Ethiopia: Systematic review and meta-analysis

2020 ◽  
Vol 8 ◽  
pp. 205031212098245
Author(s):  
Assefa Tola Gemeda ◽  
Lemma Demissie Regassa ◽  
Adisu Birhanu Weldesenbet ◽  
Bedasa Taye Merga ◽  
Nanti Legesse ◽  
...  
Keyword(s):  
Systematic Review ◽  
Medication Adherence ◽  
Confidence Interval ◽  
Odds Ratio ◽  
Associated Factors ◽  
Antihypertensive Medication ◽  
Meta Analysis ◽  
Group Analysis ◽  
Hypertensive Patients ◽  
Pooled Prevalence

The foundation of controlling hypertension is adherence to antihypertensive medication adherence. This systematic review and meta-analysis aimed to assess the magnitude and associated factors of adherence to antihypertensive medication among adult hypertensive patients in Ethiopia. A comprehensible bibliographic searching was conducted from PubMed, EMBASE, Scopus, and Web of Science core collection. All published and unpublished studies that had been accessible before 31 May 2020, and written in English were eligible. Joanna Briggs Institute assessment tool was used to evaluate the quality of the findings of the included studies. Stata software 16.0 was used to analyze the data. Study-specific estimates were pooled to determine the overall prevalence estimate across studies using a random-effects meta-analysis model. Publication bias and heterogeneity were checked. Fourteen studies with a total of 4938 hypertensive patients were included in the final systematic review and meta-analysis. The pooled prevalence of medication adherence among hypertensive patients in Ethiopia was 65.41% (95% confidence interval: 58.91–71.91). Sub-group analysis shown that the pooled prevalence of medication adherence was the highest (69.07%, 95% confidence interval: 57.83–80.31, I2 = 93.51) among studies using questionnaire technique whereas the lowest in Morisky Medication Adherence Scale eight-items (60.66%, 95% confidence interval: 48.92–72.40, I2 = 97.16). Moreover, medication adherence was associated with the presence of comorbidities (pooled odds ratio = 0.23, 95% confidence interval: 0.07–0.38, p = 0.030, I2 = 54.9%) and knowledge about the disease and its management (pooled odds ratio = 2.98, 95% confidence interval: 1.72–4.24, p = 0.04, I2 = 55.55%) but not with place of residence (pooled odds ratio = 1.22, 95% confidence interval: 0.51–1.93, p = 0.00, I2 = 76.9%). Despite a lack of uniformity among included studies, adherence to antihypertensive medication among the hypertensive population in Ethiopia was moderate. The presence of comorbidities and/or complications reduced the odds of adherence whereas having good knowledge about the disease increased chance of medication adherence among hypertensive patients.

Effects of high and low doses of methimazole in patients with Graves' thyrotoxicosis

1987 ◽  
Vol 116 (1_Suppl) ◽  
pp. S312-S317 ◽  
Author(s):  
G. Benker ◽  
D. Reinwein ◽  
H. Creutzig ◽  
H. Hirche ◽  
W. D. Alexander ◽  
...  
Keyword(s):  
Antithyroid Drug ◽  
Drug Dosage ◽  
Antithyroid Drugs ◽  
Graves Disease ◽  
Duration Of Treatment ◽  
Disease Heterogeneity ◽  
Remission Rates ◽  
Set Up ◽  
The Many ◽  
The Impact

Abstract. In spite of the long-established use of antithyroid drugs, there are many unsettled questions connected with this treatment of Graves' disease. There is a lack of controlled prospective trials studying the results of antithyroid drug therapy while considering the many variables such as disease heterogeneity, regional differences, drug dosage and duration of treatment. Therefore, a multicenter study has been set up in order to compare the effects of two fixed doses of methimazole (10 vs 40 mg) with thyroid hormone supplementation on the clinical, biochemical and immunological course of Graves' disease and on remission rates. Experience accumulated so far suggests that treatment is safe using either 10 or 40 mg of methimazole. While there is a tendency for an advantage of the higher dose within the first weeks (higher effectiveness in controlling hyperthyroidism), this difference is not significant. The impact of dosage on remission rates remains to be shown.

scholarly journals POS0774 INFLUENZA INFECTION AS A TRIGGER FOR SYSTEMIC LUPUS ERYTHEMATOSUS FLARES RESULTING IN HOSPITALIZATION

2021 ◽  
Vol 80 (Suppl 1) ◽  
pp. 641.1-641
Author(s):  
Y. B. Joo ◽  
Y. J. Park
Keyword(s):  
Systemic Lupus Erythematosus ◽  
Confidence Interval ◽  
Lupus Erythematosus ◽  
Influenza Infection ◽  
Age Groups ◽  
Case Series ◽  
Incidence Rates ◽  
Systemic Lupus ◽  
Control Interval ◽  
The Impact

Background:Infections have been associated with a higher risk of systemic lupus erythematosus (SLE) flares, but the impact of influenza infection on SLE flares has not been evaluated.Objectives:We evaluated the association between influenza infection and SLE flares resulting in hospitalization.Methods:SLE flares resulting in hospitalization and influenza cases were ascertained from the Korean national healthcare insurance database (2014-2018). We used a self-controlled case series design. We defined the risk interval as the first 7 days after the influenza index date and the control interval was defined as all other times during the observation period of each year. We estimated the incidence rates of SLE flares resulting in hospitalization during the risk interval and control interval and compared them using a Poisson regression model.Results:We identified 1,624 influenza infections among the 1,455 patients with SLE. Among those, there were 98 flares in 79 patients with SLE. The incidence ratio (IR) for flares during the risk interval as compared with the control interval was 25.75 (95% confidence interval 17.63 – 37.59). This significantly increased the IRs for flares during the risk interval in both women (IR 27.65) and men (IR 15.30), all age groups (IR 17.00 – 37.84), with and without immunosuppressive agent (IR 24.29 and 28.45, respectively), and with and without prior respiratory diseases (IR 21.86 and 26.82, respectively).Conclusion:We found significant association between influenza infection and SLE flares resulting in hospitalization. Influenza infection has to be considered as a risk factor for flares in all SLE patients regardless of age, sex, medications, and comorbidities.References:[1]Kwong, J. C. et al. Acute Myocardial Infarction after Laboratory-Confirmed Influenza Infection. N Engl J Med 2018:378;345-353.Table 1.Incidence ratios for SLE flares resulting in hospitalization after influenza infectionRisk intervalIncidence ratio95% CIDuring risk interval for 7 days / control interval25.7517.63 – 37.59Days 1-3 / control interval21.8114.71 – 32.35Days 4-7 / control interval7.563.69 – 15.47SLE, systemic lupus erythematosus; CI, confidence intervalDisclosure of Interests:None declared

scholarly journals Impact of patient and public involvement on enrolment and retention in clinical trials: systematic review and meta-analysis

BMJ ◽  
2018 ◽  
pp. k4738 ◽  
Author(s):  
Joanna C Crocker ◽  
Ignacio Ricci-Cabello ◽  
Adwoa Parker ◽  
Jennifer A Hirst ◽  
Alan Chant ◽  
...  
Keyword(s):  
Systematic Review ◽  
Clinical Trial ◽  
Clinical Trials ◽  
Lived Experience ◽  
Odds Ratio ◽  
Public Involvement ◽  
Meta Analysis ◽  
Patient And Public Involvement ◽  
Retention Rates ◽  
The Impact

AbstractObjectiveTo investigate the impact of patient and public involvement (PPI) on rates of enrolment and retention in clinical trials and explore how this varies with the context and nature of PPI.DesignSystematic review and meta-analysis.Data sourcesTen electronic databases, including Medline, INVOLVE Evidence Library, and clinical trial registries.Eligibility criteriaExperimental and observational studies quantitatively evaluating the impact of a PPI intervention, compared with no intervention or non-PPI intervention(s), on participant enrolment and/or retention rates in a clinical trial or trials. PPI interventions could include additional non-PPI components inseparable from the PPI (for example, other stakeholder involvement).Data extraction and analysisTwo independent reviewers extracted data on enrolment and retention rates, as well as on the context and characteristics of PPI intervention, and assessed risk of bias. Random effects meta-analyses were used to determine the average effect of PPI interventions on enrolment and retention in clinical trials: main analysis including randomised studies only, secondary analysis adding non-randomised studies, and several exploratory subgroup and sensitivity analyses.Results26 studies were included in the review; 19 were eligible for enrolment meta-analysis and five for retention meta-analysis. Various PPI interventions were identified with different degrees of involvement, different numbers and types of people involved, and input at different stages of the trial process. On average, PPI interventions modestly but significantly increased the odds of participant enrolment in the main analysis (odds ratio 1.16, 95% confidence interval and prediction interval 1.01 to 1.34). Non-PPI components of interventions may have contributed to this effect. In exploratory subgroup analyses, the involvement of people with lived experience of the condition under study was significantly associated with improved enrolment (odds ratio 3.14v1.07; P=0.02). The findings for retention were inconclusive owing to the paucity of eligible studies (odds ratio 1.16, 95% confidence interval 0.33 to 4.14), for main analysis).ConclusionsThese findings add weight to the case for PPI in clinical trials by indicating that it is likely to improve enrolment of participants, especially if it includes people with lived experience of the health condition under study. Further research is needed to assess which types of PPI work best in particular contexts, the cost effectiveness of PPI, the impact of PPI at earlier stages of trial design, and the impact of PPI interventions specifically targeting retention.Systematic review registrationPROSPERO CRD42016043808.

Prognostic Value of Brain Magnetic Resonance Imaging in Neonatal Hypoxic-Ischemic Encephalopathy: A Meta-analysis

2017 ◽  
Vol 32 (13) ◽  
pp. 1065-1073 ◽  
Author(s):  
Iván Sánchez Fernández ◽  
J. Leon Morales-Quezada ◽  
Samuel Law ◽  
Paggie Kim
Keyword(s):  
Confidence Interval ◽  
Odds Ratio ◽  
Prognostic Value ◽  
Meta Analysis ◽  
Brain Mri ◽  
Brain Magnetic Resonance Imaging ◽  
Hypoxic Ischemic Encephalopathy ◽  
Resonance Imaging ◽  
Neonatal Brain ◽  
Ischemic Encephalopathy

Objective: To quantify the prognostic value of neonatal brain magnetic resonance imaging (MRI) in neonatal hypoxic-ischemic encephalopathy. Methods: Meta-analysis of studies with ≥35-week neonates with hypoxic-ischemic encephalopathy who underwent brain MRI within age 4 weeks and had neurodevelopmental follow-up for at least 12 months. Results: An abnormal neonatal brain MRI was more frequent among patients with unfavorable neurodevelopmental outcome: odds ratio = 18.2 (95% confidence interval: 9.4-34.9), P <.0001. The prognostic value of neonatal brain MRI in moderate hypoxic-ischemic encephalopathy had an odds ratio of 17.7 (95% confidence interval: 5.3-59.3) and in severe hypoxic-ischemic encephalopathy, the odds ratio was 125.0 (95% confidence interval: 2.0-7917.1). Therapeutic hypothermia did not change the prognostic value of neonatal brain MRI (odds ratio for hypothermia, 14.0 [95% confidence interval: 3.1-63.6], vs no hypothermia, 18.1 [95% confidence interval: 10.0-33.1], P = .7525). Conclusion: Neonatal brain MRI provides prognostic information on outcome beyond early infancy in hypoxic-ischemic encephalopathy and therapeutic hypothermia does not change its prognostic value.

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