Y chromosome linked UTY modulates sex differences in valvular fibroblast methylation in response to nanoscale extracellular matrix cues.

Aortic valve stenosis (AVS) is a progressive disease wherein males develop valve calcification relative to females that develop valve fibrosis. Valvular interstitial cells (VICs) aberrantly activate to myofibroblasts during AVS, driving the fibrotic valve phenotype in females. Myofibroblasts further differentiate into osteoblast-like cells and secrete calcium nanoparticles, driving valve calcification in males. We hypothesized the lysine demethylase UTY (ubiquitously transcribed tetratricopeptide repeat containing, Y-linked) decreases methylation uniquely in response to nanoparticle cues in the valve extracellular matrix to promote an osteoblast-like phenotype. Here, we describe a bioinspired hydrogel cell culture platform to interrogate how nanoscale cues modulate sex-specific methylation states in VICs activating to myofibroblasts and osteoblast-like cells. We found UTY (ubiquitously transcribed tetratricopeptide repeat containing, Y-linked) modulates VIC phenotypes in response to nanoscale cues uniquely in males. Overall, we reveal a novel role of UTY in the regulation of calcification processes in males during AVS progression.

Telemedicine Service Adoption During the COVID-19 Pandemic: Physicians' Experience from Nigeria.

Introduction: Telemedicine practice experiences during the COVID-19 pandemic have not been well documented in resource-constrained settings, such as Nigeria. We set out to assess knowledge, attitude, and factors associated with telemedicine practice during the COVID-19 lockdown, as well as physician experiences in Kano, Nigeria. Methods: We employed a mixed-methods approach, utilizing structured questionnaires administered to 246 physicians, followed by in-depth interviews with a purposive subsample of 20 individuals. The data were analyzed using logistic regression and the framework approach. Results: Overall, 65.0% of the respondents demonstrated moderate to good knowledge of telemedicine. Before COVID, only 47.6% (n = 117) reported practicing telemedicine, compared with 77.2% (n = 190) during the COVID lockdown (p < 0.05). Factors associated with telemedicine practice included having at least 5 years of work experience, working in pediatrics, undergoing senior residency training, receiving formal telemedicine training, possessing good knowledge of telemedicine, and having a positive attitude toward it. The odds of engaging in telemedicine practice were four times higher (adjusted odds ratio = 4.10, 95% confidence interval: 1.79-9.40) for those who practiced it before the pandemic. Challenges identified included knowledge and skill gaps, slow internet connectivity, unstable electricity, and inadequate equipment. Conclusion: To enhance telemedicine practice in resource-limited settings, it is important to focus on strengthening information and communication infrastructure, providing comprehensive clinician training, implementing careful patient selection processes, and improving practice guidelines.

Early recognition of pulmonary complications of sickle cell disease.

Sickle cell disease (SCD) is an inherited hematological disorder with multiple-organ involvement. The pulmonary complications of SCD are associated with significant morbidity and mortality. This article presents an important review of acute and chronic pulmonary complications, including acute chest syndrome, pneumonia, pulmonary thromboembolism, pulmonary fat embolism, chronic sickle cell lung disease, and pulmonary hypertension, in patients with SCD. Bronchial asthma and obstructive sleep apnea in relation to SCD are discussed in this article. Early recognition of pulmonary complications leads to early therapeutic interventions and improvement of the overall treatment outcome.

"I Would Rather Take the Vaccine Than Undergo Weekly Testing": Correlates of Health Workers' Support for COVID-19 Vaccine Mandates.

This study examined the support for vaccine mandates and uptake among clinical and non-clinical staff at a tertiary hospital in northern Nigeria, focusing on variation of survey responses based on job position, socio-demographic characteristics, and perceived risk of infection with severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2). Using an explanatory, sequential, mixed-methods design and deploying a pragmatic paradigm, 370 healthcare workers were administered structured questionnaires. This was followed by in-depth interviews with a sub-sample of respondents to further clarify the responses regarding support for the coronavirus disease 2019 (COVID-19) vaccine mandate. Findings demonstrated that less than one-half of respondents supported the COVID-19 mandate, and only one in three had received the recommended COVID-19 vaccine doses. Support for the vaccine mandate and vaccine uptake were predicted by profession, work experience, number of children, health status, and risk perception. Support for the vaccine mandate was ascribed to ethical and professional duty, whereas opposition was associated with respect for autonomy and human rights. This study documents the need to enhance support for vaccine mandates and uptake among healthcare workers through sustainable strategies, as Nigeria's healthcare workers are considered a source of trust and role models for the rest of society.

Chemical and molecular tools to probe biological sex differences at multiple length scales.

Biological sex differences are observed at multiple different length scales and across organ systems. Gaps in knowledge remain regarding our understanding of how molecular, cellular, and environmental factors contribute to physiological sex differences. Here, we provide our perspective on how chemical and molecular tools can be leveraged to explore sex differences in biology at the molecular, intracellular, extracellular, tissue, and organ length scales. We provide examples where chemical and molecular tools were used to explore sex differences in the cardiovascular, nervous, immune, and reproductive systems. We also provide a future outlook where chemical and molecular tools can be applied to continue investigating sex differences in biology, with the ultimate goal of addressing inequities in biomedical research and approaches to clinical treatments.

HIV self-testing and repeat testing in pregnancy and postpartum in Northern Nigeria.

OBJECTIVE: Incident HIV infections in pregnant and breastfeeding mothers pose significant challenges to prevention of mother-to-child HIV transmission efforts in sub-Saharan Africa. We identified the predictors of willingness to self-test for HIV when retesting in pregnancy and postpartum among antenatal clients in a tertiary hospital in Northern Nigeria. METHODS: Structured and validated questionnaires were administered to a cross section of antenatal attendees (n = 370) in March 2021. Willingness to self-test and adjusted odds ratios of potential predictors were generated from logistic regression models. RESULTS: Of the 317 respondents who agreed to repeat HIV test during pregnancy, 29.3% (n = 93) were willing to self-test. Similarly, of those (n = 350) willing to retest after delivery, 27.4% (n = 96) were willing to self-test. Willingness to self-test during pregnancy was higher among respondents who were multiparous (2-4 births) (adjusted odds ratio, aOR = 2.40, 95% confidence interval CI, 1.14-6.43), employed (aOR = 1.49, 95% CI, 1.13-4.53) and those with at least secondary education (aOR = 2.96, 95% CI, 1.43-11.47). In contrast, willingness to self-test was lower among those who were unaware of the husband's HIV status (aOR = 0.05, 95% CI, 0.02-0.13). Willingness to self-test after delivery was higher among respondents who were married (aOR = 15.41, 95% CI, 3.04-78.2), multiparous (aOR = 2.01, 95% CI, 1.27-5.63), employed (aOR = 1.59, 95% CI, 1.08-2.35) and had at least to secondary education (aOR = 6.12, 95% CI, 1.36-27.47). In contrast, willingness to self-test postpartum was lower among those who booked late (≥29 weeks) (aOR = 0.11, 95% CI, 0.022-0.52), those who were unaware of the risk of HIV transmission during breastfeeding (aOR = 0.29, 95% CI, 0.12-0.68) and participants who were unaware of the husband's HIV status (aOR = 0.076, 95% CI, 0.03-0.19). CONCLUSION: Willingness to self-test for HIV in pregnancy and postpartum was low in this population and was influenced by risk perception, socio-demographic and obstetric attributes. Communication interventions and training of potential mentor mothers among early adopters could improve self-testing in this group and similar settings.

Patient Satisfaction With Quality of Care at the Kingdom of Saudi Arabia.

Background The emergency department (ED) is the first contact of many individuals who require acute health services. This study was the first to be conducted among patients in different regions of Saudi Arabia to determine patient satisfaction with emergency healthcare services using the Arabic version of the Echelle de Qualité des Soins en Hospitalisation (EQS-H). Methodology This cross-sectional study was conducted among 2,997 patients admitted to the ED in different hospitals in different regions of Saudi Arabia. The study was based on a self-reported questionnaire validated to assess the satisfaction of patients with ED healthcare services called EQS-H. In this study, we used an Arabic version of the questionnaire. Statistical analyses were performed using R version 3.6.3. Results The study was conducted among 2,997 patients (36.7% males and 63.3% females). Regarding region, respondents from the central region represented one-third of the sample (31.7%), followed by respondents from the western, eastern, and southern regions (24.1%, 16.9%, and 14.6%, respectively). Statistical analysis showed that the average percentage score for the clarity of information was significantly higher in the central region than in other regions and was lowest in the eastern region. Individuals aged 26-35 years (B = -2.54 and P < 0.05), male sex (B = -1.63 and P < 0.05), Saudis (B = -3.81 and P < 0.05), longer ED length of stay (LOS) (B = -2.19 and P < 0.001), worse perceived health state, and lower life satisfaction scale scores were significantly associated with lower levels of satisfaction with ED services. Perceived improvement is the strongest predictor of satisfaction. Conclusion Moderate satisfaction levels were reported in both the clarity of information domain and relationship with staff domain among patients admitted to EDs in different regions of Saudi Arabia, with better results in the central region.

"They have produced a vaccine, but we doubt if COVID-19 exists": correlates of COVID-19 vaccine acceptability among adults in Kano, Nigeria.

Vaccination is a critical tool in the global response to the COVID-19 pandemic. Yet, COVID-19 vaccine hesitancy has not been well explored in parts of Nigeria. We assessed the predictors of acceptability of the COVID-19 vaccine and identified reasons for vaccine hesitancy among adults in urban Kano, northern Nigeria. Using a mixed-methods design, we administered structured questionnaires to a cross-section of adults (n = 446), complemented with 20 in-depth interviews. Binary logistic regression and the framework approach were used to analyze the data. About one-half (51.1%, n = 228) of the respondents were willing to take the COVID-19 vaccine. Vaccine acceptance was higher among older respondents (≥30 years) (adjusted Odds Ratio (aOR) = 1.76, 95% Confidence Interval (CI): 1.14-2.99 (≥30 vs. <30), higher-income earners (≥30,000 Naira) (aOR = 2.06, 95%CI:1.12-3.80, ≥30,000 vs. <30,000), and those with a history of a chronic medical disorder (aOR = 1.90, 95%CI:1.06-3.72). Vaccine acceptance was also higher in persons with high risk perception (aOR = 1.61, 95%CI:1.13-2.81, high vs. low), those who were unconcerned about vaccine safety (aOR = 1.71, 95%CI:1.13-3.55), and those who were not worried about efficacy (aOR = 2.02, 95%CI:1.14-4.11) and infertility-related rumors (aOR = 1.98, 95%CI:1.24-3.18). Themes revealed doubts about the existence of COVID-19, mistrust for authorities, and popular credence to rumors and conspiracy theories. In conclusion, COVID-19 vaccine acceptance was sub-optimal and influenced by respondent's age, income, co-morbidities, risk perception, and concerns about vaccine safety, efficacy, and rumors. Context-specific, evidence-based risk communication strategies and trust-building measures could boost vaccine confidence in similar settings.

Application of a postnatal prediction model of survival in CDH in the era of fetal therapy.

Background: The disease severity in patients with a congenital diaphragmatic hernia (CDH) is highly variable. To compare patient outcomes, set up clinical trials and come to severity-based treatment guidelines, a performant prediction tool early in neonatal life is needed.Objective: The primary purpose of this study was to validate the CDH study group (SG) prediction model for survival in neonates with CDH, including patients who had fetal therapy. Secondary, we aimed to assess its predictive value for early morbidity.Methods: This is a retrospective single-center study at the University Hospitals Leuven on all infants with a diagnosis of CDH live-born between April 2002 and December 2016. The prediction model of the CDHSG was applied to evaluate its performance in determining mortality risk. Besides, we examined its predictive value for early morbidity parameters, including duration of ventilation, respiratory support on day 30, time to full enteral feeding and length of hospital stay.Results: The CDHSG prediction model predicted survival well, with an area under the curve of 0.796 (CI: 0.720-0.871). It had poor value in predicting infants who needed respiratory support on day 30 (area under the curve (AUC) 0.606; CI: 0.493-0.719), and correlated poorly with duration of ventilation, time to full enteral feeding and length of hospital stay.Conclusion: The CDHSG prediction model was in our hands also a useful tool in predicting mortality in neonates with CDH in the fetal treatment era. Correlation with early morbidity was poor.RationaleObjectives: (1) Validation of the CDHSG prediction model for survival in a cohort of neonates with CDH, in whom fetal endoscopic tracheal occlusion was applied according to the severity of lung hypoplasia. (2) Evaluation of performance of the model in the prediction of early morbidity.Main results: (1) Confirmation of the predictive value of the model for survival in neonates with CDH in the era of fetal therapy. (2) No correlation of the model with early morbidity parameters.

Health education to diabetic patients before the start of Ramadan: Experience from a teaching hospital in Dammam.

BACKGROUND AND OBJECTIVE: Studies have shown that pre-Ramadan structured educational program for patients with diabetes mellitus (DM) is beneficial. In this study, our aim was to evaluate the degree of adherence of treating physicians to such programs and their influence on the patient's knowledge and behavior. MATERIALS AND METHODS: This cross-sectional study was carried out on adult patients with DM attending a university hospital, who were observed while fasting during Ramadan 1436/2015. Data was collected using a questionnaire-based interview. Baseline characteristics were obtained, and patients were asked whether they had had pre-Ramadan education or not and who the provider was. Patients' knowledge of the components of the recommended structured pre-Ramadan educational program was also tested. Comparison between patients who had the education and those who did not was done using Chi-square test and independent samples Student's t-test; p ≤ 0.05 was considered statistically significant. RESULTS: A total of 298 patients with type 1 or type 2 DM were included in the study; 75.5% of the patients were aged 40 years or older. Only 30% had pre-Ramadan education delivered mainly by diabetic educators or the treating physicians (52% and 44%, respectively). Patients who had the education were younger (mean age: 45.6 ± 17.4 vs. 50.3 ± 14.4, respectively, p = 0.0048), had higher educational qualifications, were more likely to be employed, and self-monitored their blood glucose more frequently (p = 0.0001). There was no difference between the two groups with regard to their knowledge of diet and exercise. CONCLUSION: The adherence to the pre-Ramadan educational program by the treating physician was low. It is necessary to increase the awareness about the importance of these programs among health-care professionals. The programs should target the less educated, the unemployed, and older patients.

The role of intervention mapping in designing disease prevention interventions: A systematic review of the literature.

OBJECTIVE: To assess the role of Intervention Mapping (IM) in designing disease prevention interventions worldwide. METHODS: Systematic search and review of the relevant literature-peer-reviewed and grey-was conducted using the Preferred Reporting Items for Systematic Reviews and Meta-analysis (PRISMA) guidelines. FINDINGS: Only five of the twenty two included studies reviewed were RCTs that compared intervention using IM protocol with placebo intervention, and provided the outcomes in terms of percentage increase in the uptake of disease-prevention programmes, and only one of the five studies provided an effect measure in the form of relative risk (RR = 1.59, 95% CI = 1.08-2.34, p = 0.02). Of the five RCTs, three were rated as strong evidences, one as a medium evidence and one as a weak evidence, and they all reported statistically significant difference between the two study groups, with disease prevention interventions that have used the intervention mapping approach generally reported significant increases in the uptake of disease-prevention interventions, ranging from 9% to 28.5% (0.0001 ≤ p ≤ 0.02), On the other hand, all the 22 studies have successfully identified the determinants of the uptake of disease prevention interventions that is essential to the success of disease prevention programmes. CONCLUSION: Intervention Mapping has been successfully used to plan, implement and evaluate interventions that showed significant increase in uptake of disease prevention programmes. This study has provided a good understanding of the role of intervention mapping in designing disease prevention interventions, and a good foundation upon which subsequent reviews can be guided.

Does crown/implant ratio influence the survival and marginal bone level of short single implants in the mandibular molar? A preliminary investigation consisting of 12 patients.

Crown/implant (C/I) ratio has been proven to not affect the survival of the implants; however, it is also a fact that no evidence exists with regard to the use of single short implants in the mandibular molar. The aim of this study was to determine whether the crown/implant ratios of single implant-supported fixed restorations on implants of 6-8 mm in the mandibular molar have an impact on the implant survival and marginal bone maintenance. Twelve short dental implants (6-8 mm) were installed and restored with single crowns, loaded after 3 months of healing. The restorations were divided according to crown-to-implant ratio into two groups: Group 1: C/I < 2.0 and Group 2: C/I ≧ 2.0. Alveolar bone loss was measured using CBCT scan, taken at the implant placement and after 12 months follow-up from loading. Reduced implant/crown ratio shown no statistic significant differences on implant survival and the alveolar bone level compared with recommended implant/crown ratio. Within the limitation of this study, it can be concluded that reduced C/I ratio could be used as a substitute for recommended C/I ratio in severely mandibular atrophic residual alveolar ridges.

Pierre Robin sequence: Management of respiratory and feeding complications during the first year of life in a tertiary referral centre.

OBJECTIVES: To review early clinical manifestations of Pierre Robin sequence (PRS) and their management during the first year of life in the University Hospitals Leuven. METHODS: Retrospective series of 48 patients with PRS born between 2001 and 2011 and treated at a tertiary referral hospital. Review of the current literature about management of respiratory and breathing difficulties in the early life of PRS patients. RESULTS: Of our cleft palate patients 15.3% presented with PRS. A syndrome was diagnosed in 14.6%, associated anomalies without a syndromic diagnosis in 56.3% and isolated PRS in 29.2% of the cases. Mortality rate directly related to PRS was 2.1%. Respiratory difficulties were observed in 83.3% and feeding difficulties in 95.6% of the patients. Respiratory problems were addressed in a conservative way in 75%, in a non-surgical invasive way in 42.5% and in a surgical way in 12.5%. A statistically significant relationship between the association of a syndrome or other anomalies, and a higher need for resuscitation and invasive treatment were found (chi-square test, p-values=0.019 and 0.034). Feeding difficulties were managed conservatively in 91.3%, invasively in 80.4% and surgically in 15.2%. CONCLUSIONS: PRS is frequently associated with other abnormalities or syndromes. Therefore routine screening for associated anomalies in neonates with PRS is recommendable. Respiratory and feeding complications are highly frequent and possibly severe, particularly in patients with associated anomalies or syndromes, and should be recognized and addressed appropriately in an early stage. There is a potential role for the nasopharyngeal airway in reducing the need for the more traditional surgical interventions for respiratory problems.

Correlation of observed-to-expected total fetal lung volume with intrathoracic organ herniation on magnetic resonance imaging in fetuses with isolated left-sided congenital diaphragmatic hernia.

OBJECTIVES: To assess using fetal magnetic resonance imaging (MRI) the relationship between the position of the stomach as well as the volume of herniation of organs into the thorax, and the observed-to-expected total fetal lung volume (o/e-TFLV), as a measure of pulmonary hypoplasia, in fetuses with isolated left-sided congenital diaphragmatic hernia (LCDH). METHODS: This was a single-center retrospective study using archived MR images from fetuses > 20 weeks' gestation evaluated for isolated LCDH over an 11-year period between July 2002 and September 2013. We retrieved data on the gestational age at MRI, o/e-TFLV and liver position. Images were also reviewed by a single operator to determine retrospectively the position of the stomach as well as the proportion of the total thorax volume occupied by the herniated fetal liver, stomach and other viscera. Following confirmation of reproducibility, we assessed the correlation of intrathoracic organ volumes and stomach position with o/e-TFLV. RESULTS: The study included 205 fetuses which underwent a total of 259 MR examinations. The reproducibility of organ volume measurements was excellent (intraclass correlation coefficient range, 0.928-0.997). The average time spent to obtain intrathoracic organ volumes ranged from 2.28 to 5.13 min. Of all herniated organ-to-thoracic volume ratios, the liver-to-thoracic volume ratio had the strongest correlation with o/e-TFLV (ρ = -0.429, P<0.0001). Stomach volume did not correlate, although, when categorized by the position and extent of stomach herniation, there was an inverse relationship to o/e-TFLV. No intrathoracic organ-to-thoracic volume ratio was related to gestational age. CONCLUSIONS: We observed in fetuses with isolated LCDH an inverse relationship between lung volume and the amount of liver herniated as well as the position of the stomach in the chest.

Bone graft substitutes for articular support and metaphyseal comminution: what are the options?

Subchondral and metaphyseal bone defects pose a great challenge for the Orthopaedic surgeon not only because the support for the articular surface has been lost but also because the mechanism for the nourishment of articular cartilage through the subchondral plate is distorted. A number of options are available to the surgeons, none of them perfect. Autografting has an appreciable high rate of harvest site morbidity, allograft is associated with infection transmission and host immunologic response. These realities have stimulated interest in supplying bone replacement materials (demineralised bone matrix, synthetic bone substitutes, bone morphogenic proteins). This paper presents the indications and applications of bone substitutes for metaphyseal defects and subchondral support in orthopaedic trauma.

High-resolution perineal ultrasound of a paraurethral cyst in a neonate (2008: 8b).

We present high-resolution ultrasonography of a paraurethral cyst, a rare cause of an interlabial mass in a newborn. Although not always performed in these cases, ultrasonographic evaluation is an easily performed examination in assessment of the final diagnosis and therapeutic decisions.

Urinary propofol metabolites in early life after single intravenous bolus.

BACKGROUND: /st> Propofol clearance is lower in neonates than in adults and displays extensive interindividual variability, in part explained by postmenstrual age (PMA) and postnatal age (PNA). Since propofol is almost exclusively cleared metabolically, urinary propofol metabolites were determined in early life and compared with similar observations reported in adults. METHODS: /st> Twenty-four hours urine collections were sampled after a single i.v. bolus of propofol (3 mg kg(-1)) in neonates undergoing procedural sedation. Clinical characteristics (PMA, PNA, weight, and cardiopathy) were recorded. Urine metabolites [propofol glucuronide (PG), 1- and 4-quinol glucuronide (QG)] were quantified using high-pressure liquid chromatography. Urine recovery (% administered dose) and the contribution of PG and QG to urinary elimination were calculated. Data were reported by median and range, analysed by Mann-Whitney U or Spearman's rank. RESULTS: /st> Eleven neonates (median PNA 11 days, PMA 38 weeks) were included. Median propofol metabolite recovery was 64% (range 34-98%). PG contributed 34% (range 8-67%) and QG 65% (range 33-92%). There was no significant correlation between either PMA, PNA, or cardiopathy and propofol metabolites. Compared with adults, the contribution of PG (34% vs 77%) was lower and the contribution of QG (65% vs 22%) was higher in neonates. CONCLUSIONS: /st> Propofol metabolism in neonates differs from adults, reflecting the age-dependent limited glucuronidation capacity. Hydroxylation to quinol metabolites already contributes to propofol metabolism. These differences likely explain the PMA- and PNA-dependent reduced propofol clearance in neonates.

The use of duplex doppler ultrasound in a case of multifocal hepatic hemangioma.

A one-month-old girl presented with multiple cutaneous hemangiomas, abnormal weight gain, hepatomegaly, and symptoms of bleeding disorder. Abdominal ultrasound and CT revealed a multifocal hypervascular hepatic tumor and signs of vascular overload. Biopsy confirmed the presence of an infantile hepatic hemangioma. Conservative treatment with high dose steroids showed regression of the hepatic lesions and the signs of vascular congestion. Ultrasound was used for follow-up and its role in treatment monitoring is discussed in this manuscript.

Developmental pharmacology: neonates are not just small adults...

Neonatal drug dosing needs to be based on the physiological characteristics of the newborn and the pharmacokinetic parameters of the drug. Size-related changes can in part be modelled based on allometry and relates to the observation that metabolic rate relates to weight by a kg 0.75 trend. Until adult metabolic activity has been reached, ontogeny, i.e. isoenzyme-specific maturation and maturation of renal clearance also contributes to drug metabolism, making isoenzyme-specific documentation of maturation necessary. Changes in body composition and ontogeny are most prominent in neonates. The body fat content (/kg) is markedly lower and the body water content (/kg) is markedly higher in neonates. These findings have an impact on the distribution volume of both lipophilic and hydrophilic drugs. Drugs are cleared either by metabolism or elimination. While the first is mainly hepatic, the second route is mainly renal. Both hepatic metabolism and renal clearance display maturation in early life although other covariables (e.g. polymorphisms, co-administration of drugs, first pass metabolism, disease characteristics) further contribute to the interindividual variability in drug disposition. Documentation of these maturational processes based on in vivo 'case' studies is of value since these drug-specific observations can subsequently be extrapolated to other drugs which are either already being prescribed or even considered for use in neonates by the introduction of these observations in 'generic physiologically-based pharmacokinetic' models.

Both postnatal and postmenstrual age contribute to the interindividual variability in tramadol glucuronidation in neonates.

INTRODUCTION: Although of pharmacokinetic and -dynamic relevance, data on ontogeny of UDP-glucuronosyltransferase (UGT) activity in neonates are scant. We therefore wanted to assess the impact of both postnatal and postmenstrual age (PNA/PMA) on the interindividual variability of glucuronidation to overall tramadol urinary elimination in neonates. METHODS: O-demethyl tramadol (M1) and M1-glucuronide (M1G) were determined in 24 hour urine collections during continuous intravenous tramadol administration in neonates. Glucuronidation fraction (%) was calculated by the ratio of M1G to the sum of M1G and M1 free (M1total). Fractions (%) in early (