Opioid use disorder in pediatric populations: considerations for perioperative pain management and precision opioid analgesia.

INTRODUCTION: Opioids are commonly used for perioperative analgesia, yet children still suffer high rates of severe post-surgical pain and opioid-related adverse effects. Persistent and severe acute surgical pain greatly increases the child's chances of chronic surgical pain, long-term opioid use, and opioid use disorder. AREAS COVERED: Enhanced recovery after surgery (ERAS) protocols are often inadequate in treating a child's severe surgical pain. Research suggests that 'older' and longer-acting opioids such as methadone are providing better methods to treat acute post-surgical pain. Studies indicate that lower repetitive methadone doses can decrease the incidence of chronic persistent surgical pain (CPSP). Ongoing research explores genetic components influencing severe surgical pain, inadequate opioid analgesia, and opioid use disorder. This new genetic research coupled with better utilization of opioids in the perioperative setting provides hope in personalizing surgical pain management, reducing pain, opioid use, adverse effects, and helping the fight against the opioid pandemic. EXPERT OPINION: The opioid and analgesic pharmacogenomics approach can proactively 'tailor' a perioperative analgesic plan to each patient based on underlying polygenic risks. This transition from population-based knowledge of pain medicine to individual patient knowledge can transform acute pain medicine and greatly reduce the opioid epidemic's socioeconomic, personal, and psychological strains globally.

Effect of Guest Solvents on the Ionic Conductivity and Electrochemical Performance of Metal-Organic Framework-Based Magnesium Semi-Solid Electrolytes.

Developing suitable electrolytes is crucial for the advancement of rechargeable magnesium batteries. Recently, metal-organic frameworks (MOFs) have shown a great interest in the field of solid electrolytes for metal ion batteries. However, the ionic conductivity as well as the electrolyte stability in the presence of Mg electrodes are shown to be strongly dependent on the guest solvent used to solvate Mg salts in MOFsSEs. Our measurements showed that full evacuation of the MOF structure before semi-solid electrolytes (sSEs) preparation is crucial for achieving relatively low Mg overpotentials regardless of the ionic conductivity values. Moreover, the behavior of the anode/MOFsSEs interfaces (MOF: α-Mg3 [HCOO]6 ; Mg salt : MgCl2 -Mg[TFSI]2 (1 : 1 wt %); guest solvent: acetone, DMF, DEG, DME and tetraglyme) was investigated by EIS, CV and galvanostatic measurements. The current comparative study of the electrochemical deposition processes of magnesium from MOFsSEs revealed that magnesium deposition/dissolution reactions vary depending on the MOF structure, the guest anion species as well as the nature of the guest solvents.

Always ask your pharmacist: Using the media to enhance student drug information skills.

BACKGROUND AND PURPOSE: Social media is a source for information and misinformation, including healthcare information. Pharmacy students are trained to critically assess health information literature; however, this does not typically extend into assessing claims made on social media platforms. Students were asked to evaluate social media claims to provide a patient-specific recommendation and response. EDUCATIONAL ACTIVITY AND SETTING: Each student was given one of five media claims and asked to assess the validity of the claim to create a response and a recommendation for a provider and a patient. Students were placed in small groups for a verbal presentation of all the claims and a facilitator-led discussion about the pharmacist's role in healthcare information. FINDINGS: Students responded to the media claims and were able to support or reject the validity of the statements. They also created a variety of patient-facing informational documents. SUMMARY: The inclusion of questions derived from media sources is a unique way to incorporate drug information skills that is relevant to real-world practice.

Determination of albuterol and montelukast post-expiry drug strength by HPLC.

Background: Knowing the level of active ingredients in an expired drug is a matter of concern irrespective of its final disposition. This is also a matter of national security and defense as it has important implications on the nation's stockpile of prescription medications. Current literature has limited information about the strength of expired medications and any relevant trends. Objective: To utilize high performance liquid chromatography (HPLC) to determine the strength of selected drugs for asthma and chronic obstructive pulmonary disease (COPD) as a class of therapeutic agents commonly used in free clinics. Methods: Samples from expired lots of montelukast and albuterol pharmaceutical products were analyzed for their levels of their respective active ingredients. Two HPLC methods were developed, validated, and applied to achieve this goal. Quantitative analysis of each drug was performed using two different reversed phase C18 columns with a linear gradient of acetonitrile in 0.1% aqueous formic acid at a flow rate of 1 mL/min for both methods. Detection wavelength for montelukast and albuterol was 280 and 277 nm, respectively. Results: Expiry dates of analyzed batches ranged from 2003 to 2019. Despite the extended time range beyond expiry dates, levels of both drugs were relatively consistent and exceeded 90% of the listed strength in most analyzed lots. Conclusions: Our results introduce a new perspective towards reducing the financial burden resulting from disposal of expired medications with retained strength. They also offer supporting evidence to extend the use of out-of-date montelukast and albuterol preparations at home and in free clinics.

Application of two different nasal CPAP levels for the treatment of respiratory distress syndrome in preterm infants-"The OPTTIMMAL-Trial"-Optimizing PEEP To The IMMAture Lungs: study protocol of a randomized controlled trial.

BACKGROUND: Nasal continuous positive airway pressure (CPAP) applies positive end-expiratory pressure (PEEP) and has been shown to reduce the need for intubation and invasive mechanical ventilation in very low birth weight infants with respiratory distress syndrome. However, CPAP failure rates of 50% are reported in large randomized controlled trials. A possible explanation for these failure rates is the application of insufficient low levels of PEEP during nasal CPAP treatment to maintain adequate functional residual capacity shortly after birth. The optimum PEEP level to treat symptoms of respiratory distress in very low birth weight infants has not been assessed in clinical studies. The aim of the study is to compare two different PEEP levels during nasal CPAP treatment in preterm infants. METHODS: In this randomized multicenter trial, 216 preterm infants born at 26 + 0-29 + 6 gestational weeks will be allocated to receive a higher (6-8 cmH2O) or a lower (3-5 cmH2O) PEEP during neonatal resuscitation and the first 120 h of life. The PEEP level within each group will be titrated throughout the intervention based on the FiO2 (fraction of inspired oxygen concentration) requirements to keep oxygenation within the target range. The primary outcome is defined as the need for intubation and mechanical ventilation for > 1 h or being not ventilated but reaching one of the two pre-defined CPAP failure criteria (FiO2 > 0.5 for > 1 h or pCO2 ≥ 70 mmHg in two consecutive blood gas analyses at least 2 h apart). DISCUSSION: Based on available data from the literature, the optimum level of PEEP that most effectively treats respiratory distress syndrome in preterm infants is unknown, since the majority of large clinical trials applied a wide range of PEEP levels (4-8 cmH2O). The rationale for our study hypothesis is that the early application of a higher PEEP level will more effectively counteract the collapsing properties of the immature and surfactant-deficient lungs and that the level of inspired oxygen may serve as a surrogate marker to guide PEEP titration. Finding the optimum noninvasive continuous distending pressure during early nasal CPAP is required to improve CPAP efficacy and as a consequence to reduce the exposure to ventilator-induced lung injury and the incidence of chronic lung disease in this vulnerable population of very preterm infants. TRIAL REGISTRATION: drks.de DRKS00019940 . Registered on March 13, 2020.

A Neonate with an Unusual Midline Defect and Cardiovascular Anomaly.

We present a female neonate with a sternal cleft (SC) and additional aortic aneurysm who presented with respiratory failure. Stabilization of the SC was achieved by using the xyphoid process as an autologous graft bridging the upper part of the SC. We conclude that a step-wise correction of the SC with the use of an autologous graft may improve respiratory function, and should be considered when complete surgical correction is not feasible.

Vital Signs and Physiologic Derangement in Patients With Thoracic Trauma in Iraq and Afghanistan.

BACKGROUND: Triage is the act of stratifying the need for medical attention. Effective triage must account for injury patterns and severity. Personnel making triage decisions must also consider the patients' physiologic states. Vital signs can possibly be used to assess for the presence of physiological derangements such as coagulopathy, acidosis, or a significant base deficit. Providers could use this knowledge to assist with triage at casualty collection points where laboratory studies or point of care testing may not be available. METHODS: With institutional approval, data were extracted from the Joint Theater Trauma Registry for all patients with thoracic trauma between 2002 and 2012. Patients were identified by International Statistical Classification of Diseases and Related Health Problems, 9th Revision (ICD-9) codes. Heart rate (HR), systolic blood pressure (SBP), and pulse pressure were correlated with coagulopathy (international normalization ratio ≥ 1.5), acidosis (pH < 7.2) or an elevated base deficit (>6) on admission. Sensitivity, specificity, positive predictive values, negative predictive values, and odds ratios were calculated. FINDINGS: HR > 100, SBP < 90, or pulse pressure <30 were associated with an increased risk for acidosis (odds ratio 3.06 [95% confidence interval 2.48-3.78], 4.72 [3.85-5.78], and 2.73 [2.15-3.48], respectively), coagulopathy (2.21 [1.72-2.83], 4.55 [3.57-5.80], and 2.73 [2.15-3.48], respectively), and base deficit >6 (2.17 [1.88-2.50], 3.48 [2.87-4.22], and 2.22 [1.78-2.77], respectively). HR was a moderately sensitive marker (0.74), whereas SBP was a specific marker (0.93). DISCUSSION: SBP < 90 is an effective marker for ruling in physiologic derangement after thoracic trauma. HR > 100 was associated with over twice the odds for physiologic derangement. Vital signs can be used to assess for physiologic derangement in the population studied and may help in triage.

Phantomless calibration of CT scans for measurement of BMD and bone strength-Inter-operator reanalysis precision.

Patient-specific phantomless calibration of computed tomography (CT) scans has the potential to simplify and expand the use of pre-existing clinical CT for quantitative bone densitometry and bone strength analysis for diagnostic and monitoring purposes. In this study, we quantified the inter-operator reanalysis precision errors for a novel implementation of patient-specific phantomless calibration, using air and either aortic blood or hip adipose tissue as internal calibrating reference materials, and sought to confirm the equivalence between phantomless and (traditional) phantom-based measurements. CT scans of the spine and hip for 25 women and 15 men (mean±SD age of 67±9years, range 41-86years), one scan per anatomic site per patient, were analyzed independently by two analysts using the VirtuOst software (O.N. Diagnostics, Berkeley, CA). The scans were acquired at 120kVp, with a slice thickness/increment of 3mm or less, on nine different CT scanner models across 24 different scanners. The main parameters assessed were areal bone mineral density (BMD) at the hip (total hip and femoral neck), trabecular volumetric BMD at the spine, and vertebral and femoral strength by finite element analysis; other volumetric BMD measures were also assessed. We found that the reanalysis precision errors for all phantomless measurements were ≤0.5%, which was as good as for phantom calibration. Regression analysis indicated equivalence of the phantom- versus phantomless-calibrated measurements (slope not different than unity, R2≥0.98). Of the main parameters assessed, non-significant paired mean differences (n=40) between the two measurements ranged from 0.6% for hip areal BMD to 1.1% for mid-vertebral trabecular BMD. These results indicate that phantom-equivalent measurements of both BMD and finite element-derived bone strength can be reliably obtained from CT scans using patient-specific phantomless calibration.

Down Syndrome: Gestational Age-Related Neonatal Anthropometrics for Germany.

BACKGROUND: Neonates with Down syndrome (DS) weigh less, are smaller and have increased first-year mortality, especially if born small for gestational age (GA). DS-specific GA-related neonatal anthropometrics for Germany are lacking. OBJECTIVES: To construct reference tables and centile curves for birth weight (g), crown-heel length (cm) and head circumference (cm) by sex and GA for German DS neonates. METHODS: Retrospective anthropometric data from live-born singleton DS neonates born in Germany from January 1966 to June 2010 were collected using standardized questionnaires and patient records. Reference tables were created based on means and standard deviations. The 3rd, 10th, 25th, 50th, 75th, 90th and 97th centile curves were constructed and smoothed using running medians and Cole's LMS method. RESULTS: Anthropometric measurements were obtained for 1,304 DS neonates [males/females: 713/591 (54.7%/45.3%)]. Reference tables and centile charts were constructed from 3,542 (males/females: 1,932/1,610) observations for GA 32-41 weeks. Compared with general-population newborns, prematurity was increased (21.1 vs. 6.3%) at GA 32-36 weeks. Term-born (GA 40 weeks) male and female DS neonates were 352.5 and 223.5 g lighter and 1.5 and 1.4 cm smaller than general-population neonates, and head circumference was also 1.4 and 1.5 cm smaller, respectively. CONCLUSION: This is the first study to report GA-related, sex-specific reference tables and centile charts of birth weight, length and head circumference for DS neonates born in Germany. Compared with the general German population, DS newborns are more frequently born prematurely, weigh less, are smaller and have a smaller head circumference at birth.

Prevalence of Poor Bone Quality in Women Undergoing Spinal Fusion Using Biomechanical-CT Analysis.

STUDY DESIGN: Retrospective, cross-sectional analysis of vertebral bone quality in spine-fusion patients at a single medical center. OBJECTIVE: To characterize the prevalence of osteoporosis and fragile bone strength in a spine-fusion population of women with an age range of 50 years to 70 years. Fragile bone strength is defined as the level of vertebral strength below which a patient is at as high a risk of future vertebral fracture as a patient having bone density-defined osteoporosis. SUMMARY OF BACKGROUND DATA: Poor bone quality--defined here as the presence of either osteoporosis or fragile bone strength--is a risk factor for spine-fusion patients that often goes undetected but can now be assessed preoperatively by additional postprocessing of computed tomography (CT) scans originally ordered for perioperative clinical assessment. METHODS: Utilizing such perioperative CT scans for a cohort of 98 women (age range: 51-70 yr) about to undergo spine fusion, we retrospectively used a phantomless calibration technique and biomechanical-CT postprocessing analysis to measure vertebral trabecular bone mineral density (BMD) (in mg/cm³) and by nonlinear finite element analysis, vertebral compressive strength (in Newtons, N) in the L1 or L2 vertebra. Preestablished validated threshold values were used to define the presence of osteoporosis (trabecular BMD of 80 mg/cm³ or lower) and fragile bone strength (vertebral strength of 4500 N or lower). RESULTS: Fourteen percent of the women tested positive for osteoporosis, 27% tested positive for fragile bone strength, and 29% were classified as having poor bone quality (either osteoporosis or fragile bone strength). Over this narrow age range, neither BMD nor vertebral strength were significantly correlated with age, weight, height, or body mass index (P values 0.14-0.97 for BMD; 0.13-0.51 for strength). CONCLUSION: Poor bone quality appears to be common in women between ages 50 years and 70 years undergoing spinal fusion surgery. LEVEL OF EVIDENCE: 3.

Acute kidney injury with hypoxic respiratory failure.

A 27-year-old Caucasian man was transferred from a remote clinic with acute kidney injury for the prior 7-10 days preceded by gastroenteritis. His kidney biopsy showed non-specific mesangiopathic glomerular changes, minimal tubulointerstitial disease without sclerosis, crescents, nor evidence of vasculitis. On his third hospital day, he developed acute hypoxic respiratory failure requiring intubation and mechanical ventilation. Pulmonary renal syndromes ranked highest on his differential diagnosis. He was extubated after 2 days of mechanical ventilation and after pulse dose steroids. His lung biopsy showed pulmonary capillaritis. Our case describes a patient with clinically appearing renopulmonary syndrome, but found to have pulmonary capillaritis, a rare form of lung disease that may also cause acute kidney injury.

Assessment of incident spine and hip fractures in women and men using finite element analysis of CT scans.

Finite element analysis of computed tomography (CT) scans provides noninvasive estimates of bone strength at the spine and hip. To further validate such estimates clinically, we performed a 5-year case-control study of 1110 women and men over age 65 years from the AGES-Reykjavik cohort (case = incident spine or hip fracture; control = no incident spine or hip fracture). From the baseline CT scans, we measured femoral and vertebral strength, as well as bone mineral density (BMD) at the hip (areal BMD only) and lumbar spine (trabecular volumetric BMD only). We found that for incident radiographically confirmed spine fractures (n = 167), the age-adjusted odds ratio for vertebral strength was significant for women (2.8, 95% confidence interval [CI] 1.8 to 4.3) and men (2.2, 95% CI 1.5 to 3.2) and for men remained significant (p = 0.01) independent of vertebral trabecular volumetric BMD. For incident hip fractures (n = 171), the age-adjusted odds ratio for femoral strength was significant for women (4.2, 95% CI 2.6 to 6.9) and men (3.5, 95% CI 2.3 to 5.3) and remained significant after adjusting for femoral neck areal BMD in women and for total hip areal BMD in both sexes; fracture classification improved for women by combining femoral strength with femoral neck areal BMD (p = 0.002). For both sexes, the probabilities of spine and hip fractures were similarly high at the BMD-based interventional thresholds for osteoporosis and at corresponding preestablished thresholds for "fragile bone strength" (spine: women ≤ 4500 N, men ≤ 6500 N; hip: women ≤ 3000 N, men ≤ 3500 N). Because it is well established that individuals over age 65 years who have osteoporosis at the hip or spine by BMD criteria should be considered at high risk of fracture, these results indicate that individuals who have fragile bone strength at the hip or spine should also be considered at high risk of fracture.

[A qualitative assessment of the impact of a specialist nurse in outpatient urology consultations]. / Objectivation de l'impact qualitatif d'une infirmière référente en consultation d'urologie.

AIM: This paper presents the results of a prospective study of outpatient urology consultations designed to provide evidence of the benefits of using a specialist nurse to improve quality of care. METHODS: 135 patients (95 men and 40 women) were included in the study. Urinary disorders were defined using the International Classification of Functioning, Disability and Health (ICF), developed by the World Health Organization (WHO). The activity/ participation component was studied from a communication perspective before and after the urology consultation. Scores were obtained using a visual analogue scale (VAS). The VAS was also used to assess the role of the nurse as a facilitator (environmental factors component). A statistical analysis was performed on the population, as was an analysis of variance (ANOVA) of the activity/participation component. RESULTS: The participants were aged between 4years 10 months and 96years (m = 63.29; standard deviation (SD) = 19.71). The median score for the urological disorders was 2. An analysis of variance of the two questions relating to the activity/participation component indicated a significant difference between the two groups (F = 6.4172; p < 0.001). A third question was used to assess the environmental factors component (nurse as facilitator), with a mean VAS score of97.79% (SD= 4.67). CONCLUSION: The purpose of this prospective study was to conduct a qualitative assessment of the impact of involving a specialist nurse in outpatient urology consultations. The study demonstrated that the qualitative impact of using a specialist nurse as a facilitator (environmental factors component) is extremely important for the participatory dimension of communication, particularly in terms of understanding medical information.

The most altruistic living organ donor: a best friend.

Living organ donors are growing in number and account for a substantial proportion of organs transplanted. Types of living organ donors include family members, anonymous donors, and friends. Although familial donation is the most common form of living organ donation, anonymous donation and donation among friends are gaining popularity. Society has placed living organ donors at the top of the altruistic ladder. However, one's altruistic motives for living organ donation may be affected by the type of relationship he or she has with the organ recipient. Although family relationships are close, pressure and coercion from family members may make informed consent difficult. Anonymous donors do not have the pressure associated with a familial donation, but psychological and self-worth issues may influence their choice to donate. Friendship incorporates the close relationships associated with familial donation and the freedom associated with anonymous donation. Using Aristotle's definition of true friendship, the author argues that best friends are the only true altruistic living organ donors and therefore may be preferable to family donors or anonymous donors.

Age-dependence of femoral strength in white women and men.

Although age-related variations in areal bone mineral density (aBMD) and the prevalence of osteoporosis have been well characterized, there is a paucity of data on femoral strength in the population. Addressing this issue, we used finite-element analysis of quantitative computed tomographic scans to assess femoral strength in an age-stratified cohort of 362 women and 317 men, aged 21 to 89 years, randomly sampled from the population of Rochester, MN, and compared femoral strength with femoral neck aBMD. Percent reductions over adulthood were much greater for femoral strength (55% in women, 39% in men) than for femoral neck aBMD (26% in women, 21% in men), an effect that was accentuated in women. Notable declines in strength started in the mid-40s for women and one decade later for men. At advanced age, most of the strength deficit for women compared with men was a result of this decade-earlier onset of strength loss for women, this factor being more important than sex-related differences in peak bone strength and annual rates of bone loss. For both sexes, the prevalence of "low femoral strength" (<3000 N) was much higher than the prevalence of osteoporosis (femoral neck aBMD T-score of -2.5 or less). We conclude that age-related declines in femoral strength are much greater than suggested by age-related declines in femoral neck aBMD. Further, far more of the elderly may be at high risk of hip fracture because of low femoral strength than previously assumed based on the traditional classification of osteoporosis.

Degenerative and regenerative processes involved in midgut pseudotumor formation in the stick insect (Carausius morosus).

Spontaneous and experimentally induced pseudotumor formation in Carausius morosus impairs the midgut tissue homeostasis. Spontaneous pseudotumor formation begins by the break down of a single or a small group of columnar cells (CCs) and is followed by the degeneration of neighboring CCs. There are not only marked similarities but also decisive differences between normal dying CCs in healthy specimens and the degeneration of CCs leading to pseudotumors: in both cases, the apical cell parts with the nucleus are extruded into the midgut lumen, but only during of pseudotumor formation an "amorphous substance" originates from the basal parts of the CCs. Hemocytes are attracted to this substance and form a nodule-like aggregation, which is responsible for the phenotype of pseudotumors. Pseudotumor infestation has also an impact on the midgut nidi, which consist of an intestinal stem cell and several CC progenitor cells. In healthy specimens only one progenitor cell per nidus differentiates at a time, but, several to all progenitor cells differentiate simultaneously in pseudotumor-infested specimens. Extirpation of the ingluvial ganglion in healthy specimens results in an immediate onset of pseudotumor formation and a dramatic acceleration of pseudotumor growth. Importantly, the ultrastructural characteristics of spontaneous and experimentally induced pseudotumors are identical. This supports the idea that the stomatogastric nervous system plays an integral role in the maintenance of midgut tissue homeostasis.