Blood Sampling Procedures Research Articles

Statistical analysis plan for the Petal trial: the effects of parental touch on relieving acute procedural pain in neonates

Background Infants undergo multiple clinically-required painful procedures during their time in hospital, and there is an increasing desire from both parents and clinical staff to have parents directly involved in their newborn’s pain relief. To avoid biases due to selective analysis and reporting, a clinical trial’s statistical analysis plan (SAP) should be finalised and registered prior to dataset lock and unblinding. Here, we outline the SAP for the Petal trial, which was registered on the ISRCTN registry prior to dataset lock and unblinding. Methods The Petal trial is a multicentre, individually randomised, parallel-group interventional superiority trial. The study involves in-patient neonates born at or after 35+0 weeks gestation with a postnatal age of ≤7 days, in two hospital research sites (John Radcliffe Hospital, Oxford, UK; Royal Devon and Exeter Hospital, Exeter, UK). The primary objective is to investigate the potential efficacy of a non-pharmacological parent-led stroking intervention on reducing the magnitude of neonates’ noxious stimulus-evoked brain activity. The primary outcome is the neonate’s brain activity recorded using electroencephalography (EEG) in response to a heel lance blood sampling procedure. Secondary outcomes include neonatal clinical pain scores and tachycardia, and parental anxiety. The study hypothesis is neonates’ pain responses and parents’ anxiety scores are lower in the intervention group. Randomisation will be via a minimisation algorithm to maintain balance in five prognostic factors. Conclusions Paediatric pain trials have been highlighted by regulatory bodies as an important and challenging topic, with interest increasing in brain imaging outcomes. The Petal trial, to which this SAP relates, is part of a larger effort of establishing a brain-based EEG outcome measure of infant pain for use in clinical trials. This SAP is thus likely to be of interest to those in academia, pharmaceutical companies, and regulatory bodies. Trial registration ClinicalTrials.gov: NCT04901611, 25/05/2021; ISRCTN: ISRCTN14135962, 23/08/2021).

A Systematic Review on Autism and Hyperserotonemia: State-of-the-Art, Limitations, and Future Directions.

Hyperserotonemia is one of the most studied endophenotypes in autism spectrum disorder (ASD), but there are still no unequivocal results about its causes or biological and behavioral outcomes. This systematic review summarizes the studies investigating the relationship between blood serotonin (5-HT) levels and ASD, comparing diagnostic tools, analytical methods, and clinical outcomes. A literature search on peripheral 5-HT levels and ASD was conducted. In total, 1104 publications were screened, of which 113 entered the present systematic review. Of these, 59 articles reported hyperserotonemia in subjects with ASD, and 26 presented correlations between 5-HT levels and ASD-core clinical outcomes. The 5-HT levels are increased in about half, and correlations between hyperserotonemia and clinical outcomes are detected in a quarter of the studies. The present research highlights a large amount of heterogeneity in this field, ranging from the characterization of ASD and control groups to diagnostic and clinical assessments, from blood sampling procedures to analytical methods, allowing us to delineate critical topics for future studies.

BIOCHEMICAL PARAMETERS OF BLOOD OF LABORATORY ANIMALS IN CASE OF PROLONGED CONTACT WITH THE RESEARCH MATERIAL

The purpose of this study was to determine the biochemical parameters of blood of laboratory animals in prolonged contact with the experimental material
 Materials and methods. An experimental study was conducted in the laboratories and vivarium of the State Institution "Institute of Spine and Joint Pathology named after Prof. M.I. Sitenko" on 28 white laboratory rats aged 6 months with a body weight of 200 to 250 grams. The animals were randomly divided into two groups: a control group (14 rats) and an experimental group (14 rats), which were exposed to dental glass ionomer cement at a dose of 1.0 mg/kg. Toxic effects were evaluated for 1 month. The blood sampling procedure included tail vein dilation, disinfection, tail fixation, and blood collection. The study was conducted in special conditions with full feeding.
 Results. The study found no significant negative effects of prolonged use of dental glass ionomer cement (GIC) on kidney function. Analysis of diuresis, urea and creatinine levels in urine and blood serum showed no statistically significant differences between males and females. No sugar, ketones, or protein were detected in the animals' urine. Serum creatinine levels were (65.47±4.6) μmol/l in males and (63.38±7.1) μmol/l in females, while serum urea levels were (4.84±0.47) μmol/l in males and (4.67±0.42) μmol/l in females. Urinary urea levels were (374.35±20.7) mmol/l in males and (371.15±22.3) mmol/l in females.
 Conclusions. The obtained results of the study indicate statistically significant deviations in the studied indicators of the functional state of the kidneys both in males and females after prolonged use of dental glass-inomer cement based on polyacrylate carboxylate. The presence of sugar, ketones and protein was not detected in the urine of the animals. The analysis of serum creatinine levels showed no statistically significant differences between the conditions, and serum urea levels did not differ between them either. Thus, it can be concluded that the use of glass-inomer cement has no negative effect on the functional state of the kidneys in the studied animals.

Effectiveness of nesting positioning and Yakson touch on physiological, behavioral state and pain caused by blood sampling procedures in preterm neonates

PurposeThis quasi-experimental study aimed to evaluate the effectiveness of nesting positioning and Yakson touch on physiological, behavioral state and pain caused by blood sampling procedures in preterm neonates. MethodsA purposive sample of 60 preterm neonates, were randomly divided into two equal groups: control and study. Data were collected using a preterm neonates' physiological parameters assessment tool, the Premature Infant pain profile (PIPP) and Anderson behavioral state scale. ResultsPreterm neonates' mean Premature Infant pain profile (PIPP) scores declined to 3.733 ± 0.94, 9.26 ± 2.14 and 4.400 ± 1.16 in the study group before, during and immediately after blood sampling respectively compared to the control group which was 4.066 ± 1.08, 11.833 ± 2.39 and 5.466 ± 0. Statistically significant differences were observed in the physiological parameters between the two groups during and immediately after the blood sampling procedure. Also, a remarkable decrease in preterm neonates' mean behavioral state score was noticed in the study group before, during and immediately after blood sampling compared to control group with highly significant statistical difference (p = 0.0001). ConclusionNesting positioning combined with Yakson touch help to stabilize the physiological parameters and lowering behavioral state in addition to pain levels of blood sampling procedure in the preterm neonates.

Observational Study on Adherence to modified Clinical and Laboratory Standard Institute H3-A6 Guidelines on Blood Sampling Procedures

Background: The accuracy of clinical laboratory results is paramount for effective patient diagnosis and treatment. However, errors in the pre-analytical phase, particularly during phlebotomy, significantly impact the reliability of laboratory data. With the Clinical and Laboratory Standards Institute (CLSI) guidelines serving as a benchmark for best practices in blood collection, adherence to these standards is crucial for minimizing errors. Objective: This study aimed to assess compliance with modified CLSI guidelines in phlebotomy procedures within a healthcare setting and identify the most prevalent errors in the pre-analytical phase that could compromise patient safety and the integrity of laboratory results. Methods: Conducted at the Combined Military Hospital Lahore from January to March 2023, this observational study scrutinized phlebotomy practices across three distinct healthcare settings: emergency department, outpatient department, and clinical wards. A structured checklist, adapted from the European Federation for Clinical Chemistry and Laboratory Medicine (EFLM) guidelines and aligned with local modifications, was employed to evaluate compliance in 20 specific areas of phlebotomy practice. A total of 285 phlebotomies were observed by specialized staff, with data analyzed using SPSS version 25 to compare error frequencies and compliance rates across different settings and among various healthcare professionals. Results: The study revealed an overall compliance rate of 88% for identified request forms, 76% for patient identification according to local guidelines, and 66% for proper hand sanitization. However, significant errors were identified in checking for potential complications of venipuncture (34% compliance), with tubes being clearly under or overfilled (46% compliance), and in verifying that patients were prepared for phlebotomy (46% compliance). The error frequency varied across settings, with the highest discrepancies observed in the emergency department. Differences in compliance rates between laboratory staff and nurses were statistically significant in key areas, including patient identification (p<0.001) and tube labeling (p=0.081). Conclusion: The study highlights a critical need for improving adherence to CLSI guidelines within phlebotomy practices to enhance patient safety and the accuracy of laboratory results. Targeted educational and training interventions are essential for addressing the identified gaps in compliance, particularly in patient identification, sample volume control, and verification of patient preparation for phlebotomy.

Perbedaan Efektivitas Terapi Audiovisual Dan Coolpack Terhadap Tingkat Nyeri Pada Prosedur Pengambilan Darah Anak Usia Pra Sekolah

Pain is an unpleasant sensory-nervous response experience associated with tissue damage. Pain in children during invasive procedures that are not handled properly can make them uncooperative and refuse action, which can hinder the treatment process. Long-term effects that can arise if a child's pain is not reduced or treated are the psychological and physical stress suffered by the child, such as insomnia, depression, changes in appetite, and fatigue. Efforts to overcome pain during blood sampling procedures include audiovisual therapy and cool packs. This study aims to analyze the differences in the effectiveness of audiovisual therapy and cool packs on pain levels during blood sampling procedures in preschool children. This research is quantitative with a quasi-experimental two-group posttest design. The number of samples in this study was 44 respondents, who were divided into two groups using the consecutive sampling technique. Based on the Mann- Whitney test, the results showed that there were differences in the effectiveness of audiovisual therapy and cool packs on pain levels in blood sampling procedures for preschool children, with a p-value of 0.000 (<0.05). Audiovisual therapy and cool packs can be used as nursing actions to reduce pain during blood sampling procedures in preschool children.

Optical blood glucose non-invasive detection and its research progress.

Blood glucose concentration is an important index for the diagnosis of diabetes, its self-monitoring technology is the method for scientific diabetes management. Currently, the typical household blood glucose meters have achieved great success in diabetes management, but they are discrete detection methods, and involve invasive blood sampling procedures. Optical detection technologies, which use the physical properties of light to detect the glucose concentration in body fluids non-invasively, have shown great potential in non-invasive blood glucose detection. This article summarized and analyzed the basic principles, research status, existing problems, and application prospects of different optical glucose detection technologies. In addition, this article also discusses the problems of optical detection technology in wearable sensors and perspectives on the future of non-invasive blood glucose detection technology to improve blood glucose monitoring in diabetic patients.

Goldfish or aquatic turtle? Impact of two animal assisted interventions on children's pain, anxiety, and fear during IV catheterization: A randomized controlled trial

PurposeThis study aimed to determine the effect of goldfish and aquatic turtle nursing interventions on children's pain, anxiety, and fear during IV catheter insertion. Design and methodsThe randomized controlled trial included 98 children (control group = 32, goldfish group = 33, aquatic turtle group = 33) aged 5–6 years, attending outpatient clinic for blood sampling and catheterisation procedures. Pain was measured using the Wong Baker Facial Pain Scale, anxiety was measured using the Child Anxiety Scale-State, and child fear was measured using the Child Fear Scale, before, during, and after catheterization. ResultsWhen analyzing the pain, anxiety, and fear findings, no statistical difference was found between the scores of the mother, child, and researcher before the procedure. During the catheterization procedure, the pain, anxiety, and fear scores of the children in the fish and turtle groups increased statistically less than those in the control group. When analyzing the post-procedure findings, the pain, anxiety, and fear scores of the control group were similar to those before the procedure. In the fish and turtle groups, anxiety and fear scores were statistically the lowest (p < 0.05). ConclusionIt can be concluded that animal-assisted practices reduce anxiety and fear during and after the catheterization procedures while diverting attention from pain. Practice implicationsGoldfish or aquatic turtle intervention improve children's attitudes toward pain, anxiety, and fear during IV catheter insertion. Pediatric nurses could consider incorporating, such as the animal assisted intervention, into their clinical practice to reduce the pain, anxiety, and fear experienced by children during medical/nursing procedures.

A quality control procedure for central venous blood sampling based on potassium concentrations

Abstract Objectives To evaluate the extent of agreement between two blood collection methods for electrolytes, central venous blood sampling by the push-pull technique versus venipuncture, and to mitigate errors in blood sampling by a potassium-based quality control procedure. Methods A comparative within-subject study was carried out for adult patients in the intensive care unit. Intraclass correlation coefficients (ICCs) were used to estimate concordance, and Bland–Altman analysis and clinically acceptable limits were used to compare the equivalence of the two methods. An in-house checklist was designed to identify errors made by nurses throughout central venous blood sampling by the push-pull technique, the corrective training and quality control procedure were conducted, and the rate of errors, incidence of hemolysis and distribution of potassium concentrations were comparatively analyzed for the quality of central venous blood sampling before and after the quality control procedure. Results All the ICCs of 220 paired blood samples displayed excellent reliability, except for potassium. Most of the electrolyte variables were within the clinically acceptable limits, and the results showed that the potassium concentrations did not seem to sufficiently affect clinical decision-making. A total of 30 nurses accepted 90 observations before and after the quality control procedure, and the results showed that blood exposure and repeated disconnections of the line in the push-pull technique were always the main problems throughout the process of central venous blood sampling. In addition, after improvement, the number of patients with hypokalemia or hyperkalemia tended to decrease, but the difference was not statistically significant. For all of the blood samples, only three push-pull paired samples received hemolysis notice. Conclusions Central venous blood sampling by the push-pull technique could be an acceptable substitute for most electrolytes via venipuncture, but caution should be exercised for potassium-based quality control procedures.

Basal gonadotropin levels combine with pelvic ultrasound and pituitary volume: a machine learning diagnostic model of idiopathic central precocious puberty

ObjectiveThe current diagnosis of central precocious puberty (CPP) relies on the gonadotropin-releasing hormone analogue (GnRHa) stimulation test, which requires multiple invasive blood sampling procedures. The aim of this study was to construct machine learning models incorporating basal pubertal hormone levels, pituitary magnetic resonance imaging (MRI), and pelvic ultrasound parameters to predict the response of precocious girls to GnRHa stimulation test.MethodsThis retrospective study included 455 girls diagnosed with precocious puberty who underwent transabdominal pelvic ultrasound, brain MRI examinations and GnRHa stimulation testing were retrospectively reviewed. They were randomly assigned to the training or internal validation set in an 8:2 ratio. Four machine learning classifiers were developed to identify girls with CPP, including logistic regression, random forest, light gradient boosting (LightGBM), and eXtreme gradient boosting (XGBoost). The accuracy, sensitivity, specificity, positive predictive value, negative predictive value, area under receiver operating characteristic (AUC) and F1 score of the models were measured.ResultsThe participates were divided into an idiopathic CPP group (n = 263) and a non-CPP group (n = 192). All machine learning classifiers used achieved good performance in distinguishing CPP group and non-CPP group, with the area under the curve (AUC) ranging from 0.72 to 0.81 in validation set. XGBoost had the highest diagnostic efficacy, with sensitivity of 0.81, specificity of 0.72, and F1 score of 0.80. Basal pubertal hormone levels (including luteinizing hormone, follicle-stimulating hormone, and estradiol), averaged ovarian volume, and several uterine parameters were predictors in the model.ConclusionThe machine learning prediction model we developed has good efficacy for predicting response to GnRHa stimulation tests which could help in the diagnosis of CPP.

The Effect of Tucaresol on Translational MRI Estimates of Cerebral Physiology in Townes SCD Mice

Sickle Cell Disease (SCD) is characterized by severe hemolytic anemia and low Hct. This contributes to elevated cerebral cerebrometabolic strain, as evidenced by increased cerebral blood flow (CBF), increased blood oxygen extraction fraction (OEF), and increased incidence of silent cerebral infarct. Recent reports have shown that approved and experimental therapies ameliorate these physiological indicators of strain in SCD patients using advanced MRI-based techniques (Fields, et al., Blood, 2019; Hulbert, et al., Blood 2022), but the effect on these same MRI endpoints has not been demonstrated in animal models of SCD. The purpose of this work was to perform these same measurements in Townes SCD mice treated with tucaresol, which is known to increase the oxygen affinity hemoglobin, thus building a translational platform for non-invasive assessment of these endpoints to support characterization of novel therapies and their relationship to cerebrometabolic strain that leads to end organ damage in the brain. All animal procedures were performed under an IACUC-approved protocol. Forty-three male Townes SCD mice were assigned to two treatment groups (n=21 / 22, mean age = 8.1±0.8 / 8.4 ±0.6 weeks, mean weight = 26±2 / 26±2 g). Animals were anesthetized and scanned on a 9.4 T Bruker MRI scanner at MGH. CBF was measured using a pseudo-continuous arterial spin labeling sequence (pCASL) (Hirschler, et al., NMR in Biomedicine, 2018), and OEF was estimated from a T2 measurement in the superior sagittal sinus using a TRUST sequence (Wei, et al., Magn. Reson. Med., 2018) and a hematocrit measure which was taken from a tail vein bleed immediately following the scan. Following anesthesia recovery from the first imaging timepoint, animals were placed in cages according to group assignment and drinking water was replaced by one of two masked dosing solutions. prepared off-site by an independent team, containing either 1.14 mM tucaresol or pH and color-matched water. The tucaresol concentration was chosen to approximate an oral dose of 60 mg/kg/day comparable to a clinical dose and be consistent with previous studies. After two weeks of ad lib exposure to the dosing solutions, the scanning and blood sampling procedure was repeated. A terminal cardiac punch was also performed under anesthesia to assess tucaresol blood exposure. Due to technical challenges Hct measures were not performed in the first five animals from each group, and two animals had Hct measures at only the second timepoint. CBF is reported in whole bilateral striatum. Whole blood analysis revealed tucaresol exposures of 0.1-0.6 mM in the active arm. While still within the range for hemoglobin modification, the exposures were similar but somewhat lower than the exposures of 0.5-1.6 mM reported from oral gavage at 30 mg/kg twice per day in SCD mice (Knee et al. Blood, 2016). Table 1 shows CBF, Hct, and OEF values at baseline and after two weeks of dosing for each group. OEF values assume arterial oxygen saturation of 1. Spaghetti plots in figure 1 display changes in these values for individual animals. CBF elevations are observed very early in clinical SCD populations and begin to plateau as the disease progresses, but OEF has been shown to increase as the disease progresses (Juttukunda, et al., J. Magn. Reson. Imaging, 2019). As a result, therapeutic interventions in advanced disease may be expected to first affect OEF, with decreases in CBF to follow. That may, in part explain why a treatment effect was observed with OEF and not with CBF. Additionally, the proximity of the labeling plane of inflowing arterial blood to the brain tissue being perfused and the high carotid artery flow rate in these animals means that the CBF measure by pCASL MRI is considerably more challenging in mice than in humans. The sensitivity of MRI-derived OEF to therapeutic intervention in mice is similar to what has been reported in SCD patients, where elevated OEF is particularly associated with regions of the brain at highest risk for developing silent infarct. CBF and OEF are currently being evaluating for an approved HbS modifier (NCT05228821). The ability to use the same techniques in both mice and humans to non-invasively and quantitatively demonstrate the amelioration of the cerebrophysiological compensatory measures that precede end CNS organ damage is a valuable step in characterizing potential benefit of novel therapeutics beyond standard regulatory endpoints associated with pain crises.

LC-MS/MS method for quantitative profiling of ketone bodies, α-keto acids, lactate, pyruvate and their stable isotopically labelled tracers in human plasma: An analytical panel for clinical metabolic kinetics and interactions

An important area within clinical research is in vivo metabolism of ketone bodies (β-hydroxybutyrate and acetoacetate) and in connection metabolites that may affect their production and/or cellular transport such as the keto-acids from the branched-chain amino acids, lactate and pyruvate. To determine in vivo metabolite turnover, availability of accurate and sensitive methods for analyzing the plasma concentrations of these metabolites and their stable isotopically labeled enrichments is mandatory. Therefore, the present study describes a high-performance liquid chromatography-tandem mass spectrometry (LC-MS/MS) method for simultaneous analysis of ketone bodies, α-keto acids, lactate, pyruvate, and their tracer enrichments in humans using 2 different derivatization techniques with 4-bromo-N-methylbenzylamine and O-benzylhydroxylamine as derivatization reagents, and 1-ethyl-3-dimethylaminopropyl carbodiimide as coupling compound followed by a single LC-MS/MS run. The method was validated for matrix effects, linearity, accuracy, precision, recovery, stability, and enrichment (ratio) analysis of a stable isotopically labelled analytes (tracers) continuously infused in humans divided by the unlabeled endogenous analyte (tracee) that makes it possible to quantify the analyte in vivo synthesis and degradation rates. The applied parallel derivatization procedure yielded good sensitivity for all analytes of interest and their tracers. Despite the double derivatization method, mixing the ethyl acetate portions at the final stage made it possible to simultaneously analyze all compounds in a single LC-MS/MS run. Moreover, the liquid chromatography method was optimized to robustly quantify the keto acids derived from leucine (α-keto-isocaproic acid) and isoleucine (α-keto-β-methylvaleric acid), the compounds with similar chemical structure and identical molecular weights. The presented method is designed and validated for human plasma. However, care should be taken in blood sampling and processing procedures as well as quick freezing and storage at −80 °C due to the instability of especially acetoacetate.

Dried Blood Spots (DBS): A suitable alternative to using whole blood samples for diagnostic testing of visceral leishmaniasis in the post-elimination era.

Serum or whole blood collection, processing, transport and storage still present significant challenges in low resource settings where mass surveillance is required to sustain disease elimination. Therefore, in this study, we explored the diagnostic efficacy of dried blood spots (DBS) as a minimally invasive and potentially cost-effective alternative sampling technique to whole blood sampling procedures for subsequent detection of Leishmania donovani antibodies or DNA. Archived serum, DNA samples from whole blood of visceral leishmaniasis (VL) cases and healthy controls, and DBS from corresponding cases and controls, were used. Both molecular and serological assays were optimized to detect L. donovani antibodies or DNA in DBS elute and results were compared against those obtained with whole blood. Serological assays (both rK28 ELISA and rK39 ELISA) of DBS samples showed sensitivity and specificity of 100% and had excellent agreement with results from whole blood samples (kappa value ranged from 0.98-1). Bland-Altman analysis of OD values from rK28-ELISA with DBS elute and patients' serum showed an excellent agreement (ICC = 0.9) whereas a good agreement (ICC = 0.8) was observed in the case of rK39-ELISA. However, qPCR and RPA of DBS samples had a diminished sensitivity of 76% and 68%, respectively, and poor agreement was observed with the whole blood samples. Our results demonstrate that DBS offer excellent diagnostic efficiency for serological assays and represent a viable alternative to whole blood sampling procedures.

A Novel Tourniquet with an Alarm System, Replaceable Components, and The Ability to Adjust Pressure and Detect Body Temperature for Medical Applications

A tourniquet is a practical device in the medical field that is employed to collect blood and prevent bleeding in medical centers. The need for a durable tourniquet with leveled pressure adjustment capabilities, which indicates the time, can be used for both blood collection and control of intense bleeding, and has replaceable components in case of damage is strongly felt. Thus, developing a tourniquet with the aforementioned features is highly beneficial. The designed tourniquet includes four main parts (end hook, strap, main clip, and pin), and the other three parts are mounted on the strap. This tourniquet has a unique strap design and a sturdy lock and fastener, a body temperature detection sensor, a pressure adjustment section at four levels, a timer with an alarm, buttons (pins) to open the strap, a linen pad, and a special end hook (with an end clamp). The proposed time warning tourniquet with replaceable components has the ability to adjust the pressure, detect the temperature, and create local pressure, and therefore, can boost the performance of the medical staff during blood sampling and bleeding control procedures.

Fast in Action to Reduce Rejection (FARR): Pre-Analytical Errors in Blood Sampling Procedures by the Nurses

The pre-analytical errors are the major source of mistakes in laboratory diagnostics referring to all of the inappropriate performances before the specimens are measured by the analyzers2,such as improper sample collection, transport delays, illegible handwriting on requisition, wrong or missing identification, haemolysed, clotted 14 and quantity not sufficient (QNS) samples, wrong vacutainer selection, inappropriate blood to anticoagulant ratio and so on. However, it has been reported that the pre-analytical phase is error-prone which may lead to repeated sampling, inaccurate test results, delay in diagnosis, and may jeopardize patient safety which may potentially compromise patient care and clinical outcomes 7. This review examines pre-analytical errors, their causes, their impact on lab results, and strategies for creating clear classification systems to reduce these errors among nurses. Errors, often by trained staff nurses, highlight the need for regular competency tests and an active detection system to enhance lab testing reliability and quality. The study focused on identifying and categorizing errors 8 during phlebotomy collection. It aimed to mitigate these errors, which though not catastrophic, signalled system failures. The campaign successfully reduced errors from 368 to 287 after starting in response to a high error count in July 2022. The campaign also led to a shift from open to closed blood collection methods, including improved aseptic techniques. More than 1,000 nurses adopted this change, demonstrating a positive impact on maintaining sample quality and reducing errors. Overall, the campaign achieved remarkable success in addressing pre-analytical blood sample errors.

Statistical analysis plan for the Petal trial: the effects of parental touch on relieving acute procedural pain in neonates

Background: Infants undergo multiple clinically-required painful procedures during their time in hospital, and there is an increasing desire from both parents and clinical staff to have parents directly involved in their newborn’s pain relief. The Petal trial is a multicentre randomised controlled trial to investigate the effect of parental touch prior to a clinically-required heel lance on neonatal pain responses and parental anxiety. To avoid biases due to selective analysis and reporting, a clinical trial’s statistical analysis plan (SAP) should be finalised and registered prior to dataset lock and unblinding. Here, we outline the SAP for the Petal trial, which was registered on the ISRCTN registry prior to dataset lock and unblinding. The SAP is written in line with best practice guidelines to provide sufficient detail for reproducibility. Methods: The primary outcome is the neonate’s brain activity recorded using electroencephalography (EEG) in response to a heel lance blood sampling procedure. In this superiority trial, the primary objective is to investigate the potential efficacy of a parent-led non-pharmacological analgesic intervention on reducing the magnitude of neonates’ noxious stimulus-evoked brain activity. Secondary outcomes include neonatal clinical pain scores and tachycardia, and parental anxiety. Conclusions: Paediatric pain trials have been highlighted by regulatory bodies as an important and challenging topic, with interest increasing in brain imaging outcomes. The Petal trial, to which this SAP relates, is part of a larger effort of establishing a brain-based EEG outcome measure of infant pain for use in clinical trials. This SAP is thus likely to be of interest to those in academia, pharmaceutical companies, and regulatory bodies. We hope this SAP will help establish a foundation for the use of brain imaging outcomes in neonatal pain clinical trials, on which best practices can be built. Trial registration: ClinicalTrials.gov: NCT04901611, 25/05/2021; ISRCTN: ISRCTN14135962, 23/08/2021).

Patient Centric Microsampling to Support Paxlovid Clinical Development: Bridging and Implementation.

Nirmatrelvir is a potent and selective severe acute respiratory syndrome-coronavirus 2 (SARS-CoV-2) main protease inhibitor. Nirmatrelvir co-packaged with ritonavir (as PAXLOVID) received US Food and Drug Administration (FDA) Emergency Use Authorization (EUA) on December 22, 2021, as an oral treatment for coronavirus disease 2019 (COVID-19) and subsequent new drug application approval on May 25, 2023. Pharmacokinetic (PK) capillary blood sampling at-home using Tasso-M20 micro-volumetric sampling device was implemented in the program, including three phase II/III outpatient and several clinical pharmacology studies supporting the EUA. The at-home sampling complemented venous blood sampling procedures to enrich the PK dataset, to decrease the need for patients' site visit for PK sampling, and to allow different sampling approaches for flexibility and convenience. To demonstrate concordance/equivalence, bridging between venous plasma and Tasso dried blood results was conducted by comparing concentrations and derived PK parameters from both sampling approaches. In addition, a two-compartment population PK model was utilized to bridge the plasma and Tasso data by estimating the PK parameters using blood-to-plasma ratio as a slope parameter. Operational challenges were successfully managed to implement at-home PK sampling in global phase II/III trials. Sample quality was generally very good with less than 3% samples deemed as "not usable" from over 800 samples collected in all the studies. Experience gained from sites and patients will guide future broader implementations.

Direct costs of blood drawings with pre-analytical errors in tertiary paediatric hospital care.

Blood drawings is a common hospital procedure involving laboratory and clinical disciplines that is important for the diagnosis and management of illnesses in children. Blood drawings with pre-analytical error (PAE) can lead to increased costs for hospitals and healthcare organisations. The direct cost of blood drawings after a PAE is not fully understood in paediatric hospital care. The aim of this study was to estimate the average direct cost of PAE per year and per 10,000 blood drawings in tertiary paediatric care. A cost analysis using a bottom-up approach was conducted on the basis of combined information from the hospital's laboratory register for the period 2013-2014 and clinical in-ward observations at a tertiary children's referral hospital in Sweden, the Astrid Lindgren Children's Hospital. For the analysis, we hypothesised the re-collection of all blood drawings with PAE and included the average costs of the sampling materials, the time of the healthcare personnel, the laboratory analyses, and in-ward premises based on the time spent on the blood sampling procedure. The annual cost of PAE was estimated to be 74,267 euros per 54,040 blood drawings, which corresponds to 13,756 euros per 10,000 blood drawings or 1.5 euros per draw. The personnel cost represented 60.1% (45,261 euros per year) of the cost due to PAE, followed by costs for hospitalisation (25.2%), laboratory analyses (8.1%), and materials (5.7%). PAEs lead to substantial increases in the costs in tertiary paediatric hospital care. If these PAEs can be avoided, costs related to the re-collection of blood drawings with PAE may be re-allocated to other health-promoting activities for children visiting hospital institutions.

Scribbling and doodling: social representations by children expressed in drawings, regarding the experience of blood sampling

The scope of this article was to identify the social representations of children in a municipal public school in Rio de Janeiro, with respect to the blood sampling procedure and to discuss the social representations that emerge, in the light of the performance of the family health team in carrying out this procedure. Moscovisci's method/theory of analysis of social representations based on a qualitative approach was used. For data collection, the projective technique of the esthetic production scene and the student's speech was used. The results were grouped into four categories: 1) structural dimensions involved in the blood sampling procedure; 2) dimension of the human component and its interface in the blood sampling procedure; 3) the psycho-emotional dimension portrayed in the blood sampling procedure; and 4) blood sampling: the importance for student health. With respect to the importance of blood sampling, we highlight the perception of students regarding the importance of actions aimed at prevention and health care promotion.

Regulation of Pancreatic TXNIP-Insulin Expression Levels after Bariatric Surgery Using Diabetic Rodent Model.

The purpose of this study was to investigate the effect of bariatric surgery on pancreatic thioredoxin-interacting protein (TXNIP) and insulin expression levels. The research question is does bariatric surgery induce changes in the pancreatic TXNIP level, given that TXNIP has been proposed as a key glucose control factor? Using nondiabetic and diabetic rats, we investigated whether our streptozotocin-induced diabetic rat models exhibited changes in pancreatic TXNIP regulation. Following this confirmation, we randomly divided the diabetic rats into the following three groups: the gastric bypass group (n = 16), pair-fed group (n = 10), and sham group (n = 10). Preoperatively and 3 weeks postoperatively, all the rats underwent an oral glucose tolerance test, insulin tolerance test, and blood sampling procedures for hormonal analysis. The TXNIP messenger ribonucleic acid (mRNA) and protein expression levels were significantly lower in the gastric bypass group than in the other groups. Regarding the gastric bypass group, the pancreatic mRNA expression levels of microRNA-204 (miR-204) and MafA were significantly lower and higher, respectively, than in the other groups. Furthermore, the levels of pancreatic insulin expression at the mRNA and protein levels were also significantly higher in the gastric bypass group than in the other groups. Bariatric surgery significantly improved glucose control and regulated the pancreatic insulin production pathways of TXNIP, miR-204, and MafA. The regulation of TXNIP, miR-204, and MafA might play an important role in the mechanism of diabetes remission following bariatric surgery.