Reflex strategy to ensure accurate total testosterone results from consumer initiated, self-collected capillary samples.

BACKGROUND: Self-collected capillary samples are convenient for direct access testing (DAT), but exogenous testosterone use may cause falsely elevated total testosterone (TT) results. We designed a quality assurance workflow to differentiate between accurate or erroneous supraphysiological TT concentrations. METHODS: Clinical samples with TT > 1500 ng/dL were reflexed to luteinizing hormone (LH) and follicle stimulating hormone (FSH) and screened for exogenous testosterone use. Samples (n = 120) with normal TT were reflexed to LH/FSH as a control. RESULTS: A total of 8572 TT samples were evaluated, of which 533 (6.2 %) had TT > 1500 ng/dL and were reflexed. Of these, 441 (82.7 %) had significantly decreased LH/FSH (<0.85/<0.7mIU/mL, respectively), 72 (13.5 %) had normal or borderline normal LH/FSH, and 20 (3.8 %) had insufficient plasma volume. In patients with TT > 1500 ng/dL, injectable exogenous testosterone use was most commonly accompanied by significantly decreased LH/FSH, while topical testosterone use was most commonly accompanied by detectable LH/FSH. Control samples were almost all (99.2 %) within or above the LH/FSH reference intervals. Unique patients ordered 351 TT tests where at least one TT result was > 1500 ng/dL. Based on TT and LH/FSH results, we hypothesized that patients were intermittently or consistently overusing exogenous testosterone, resolved elevated TT with recollection, or repeatedly contaminated their sample. CONCLUSION: Self-collected capillary specimens are acceptable for TT testing. A quality assurance reflex to LH/FSH can determine the validity of supraphysiological TT results in a consumer initiated/DAT population.

Bronchopulmonary dysplasia and carbon dioxide retention.

AIM: The aim of this study was to determine the pre-discharge carbon dioxide (CO2 ) levels of preterm neonates with bronchopulmonary dysplasia (BPD) requiring ongoing nasal cannulae oxygen therapy and who were ready for discharge home. METHODS: We studied a retrospective cohort of infants born <30 weeks gestational age (GA) at ≥36 weeks corrected GA who had established BPD requiring ongoing nasal cannulae oxygen therapy and were ready for discharge home. Neonates were born and admitted between May 2014 and December 2018. Demographic data at the time of birth and at the time of the last blood gas sampled were collected. RESULTS: One hundred five neonates had median GA of 26.1 weeks and birth weight of 775 g. Median (IQR) CO2 level was 54 (49-58) mmHg. Ninety-nine (94%) neonates had CO2 levels exceeding the normal range and 91 (87%) neonates had a CO2 between 45 and 65 mmHg. CONCLUSION: Ninety-four per cent of neonates <30 weeks GA at ≥36 weeks corrected GA requiring ongoing nasal cannulae oxygen therapy for established BPD, who were ready for discharge home, have CO2 levels outside of normocapnia (35-45 mmHg), with 87% having CO2 levels between 45 and 65 mmHg.

Thresholds for blood transfusion in extremely preterm infants: A review of the latest evidence from two large clinical trials.

There are two recently completed large randomized clinical trials of blood transfusions in the preterm infants most at risk of requiring them. Liberal and restrictive strategies were compared with composite primary outcome measures of death and neurodevelopmental impairment. Infants managed under restrictive guidelines fared no worse in regard to mortality and neurodevelopment in early life. The studies had remarkably similar demographics and used similar transfusion guidelines. In both, there were fewer transfusions in the restrictive arm. Nevertheless, there were large differences between the studies in regard to transfusion exposure with almost 3 times the number of transfusions per participant in the transfusion of prematures (TOP) study. Associated with this, there were differences between the studies in various outcomes. For example, the combined primary outcome of death or neurodevelopmental impairment was more likely to occur in the TOP study and the mortality rate itself was considerably higher. Whilst the reasons for these differences are likely multifactorial, it does raise the question as to whether they could be related to the transfusions themselves? Clearly, every effort should be made to reduce exposure to transfusions and this was more successful in the Effects of Transfusion Thresholds on Neurocognitive Outcomes (ETTNO) study. In this review, we look at factors which may explain these transfusion differences and the differences in outcomes, in particular neurodevelopment at age 2 years. In choosing which guidelines to follow, centers using liberal guidelines should be encouraged to adopt more restrictive ones. However, should centers with more restrictive guidelines change to ones similar to those in the studies? The evidence for this is less compelling, particularly given the wide range of transfusion exposure between studies. Individual centers already using restrictive guidelines should assess the validity of the findings in light of their own transfusion experience. In addition, it should be remembered that the study guidelines were pragmatic and acceptable to a large number of centers. The major focus in these guidelines was on hemoglobin levels which do not necessarily reflect tissue oxygenation. Other factors such as the level of erythropoiesis should also be taken into account before deciding whether to transfuse.

Factors associated with successful extubation following the first course of systemic dexamethasone in ventilator-dependent preterm infants with or at risk of developing bronchopulmonary dysplasia.

OBJECTIVES: We aimed to identify factors present at the start of an initial course of systemic dexamethasone that would be associated with successful extubation in mechanically ventilated neonates <30 weeks gestational age (GA) with or at risk of developing bronchopulmonary dysplasia (BPD). METHODS: We studied a retrospective cohort of neonates (23+0 -29+6 weeks GA), with or at risk of developing BPD, prescribed their first course of systemic dexamethasone to aid in extubation from mechanical ventilation. The data collected only pertained to the first course of dexamethasone. Neonates given dexamethasone for airway edema were not included. The primary outcome of interest was successful extubation (i.e., extubated within 14 days of starting dexamethasone and remaining extubated for at least 7 days). Binary logistic regression was employed. RESULTS: A total of 287 neonates were included. Each additional week of GA at birth led to a 1.53 increase in the odds of successful extubation (95% CI: 1.122-2.096, p < 0.01). Higher average fraction of inspired oxygen (FiO2 ) requirements in the preceding 24 h resulted in a 0.94 decrease in the odds of successful extubation (p < 0.05) and higher mean airway pressure (MAP) resulted in 0.76 decrease in odds of successful extubation (p < 0.01). CONCLUSIONS: Mechanically ventilated neonates with or at risk of developing BPD, born at <30 week GA and initiated on dexamethasone to facilitate extubation, had a lower likelihood of successful extubation by Day 14 if they had younger GA at birth, and at the time of commencing steroids had higher MAPs and had higher oxygen requirements.

Efficacy of standard- vs reduced-dose insulin for treatment of hyperkalemia: A quasi-experiment.

PURPOSE: Hyperkalemia more commonly affects patients with a glomerular filtration rate of less than 60 mL/min. Using intravenous (IV) insulin to shift potassium intracellularly may cause hypoglycemia, requiring additional treatment or longer hospitalization. Literature on insulin dosing in this context is limited, with one previous study indicating that 5 units of IV insulin might be as effective and result in less hypoglycemia than the standard dose of 10 units of IV insulin. The hyperkalemia treatment pathway at our institution was revised in May 2018 to include a reduced-dose option (5 units of insulin) for patients with end-stage renal disease. This study aimed to compare the prevalence of hypoglycemia between patients who received standard-dose vs reduced-dose IV insulin. METHODS: This single-center, retrospective, quasi-experimental study evaluated the impact of revision of the hyperkalemia treatment pathway by assessing rates of hypoglycemia during the 6 months before and after implementation of the revised pathway. The primary endpoint was prevalence of hypoglycemia, defined as a blood glucose level of less than or equal to 70 mg/dL. RESULTS: There was no statistically significant difference in the occurrence of hypoglycemia when comparing the pre- and postimplementation groups (36 [17.7%] patients vs 34 [18.7%] patients; P = 0.7924). The postimplementation group had a statistically significant lower reduction in potassium levels after treatment than the preimplementation group (mean [interquartile range], -0.9 [-1.3, -0.5] mEq/L vs -0.6 [-1.2, -0.2] mEq/L; P = 0.0095). Baseline potassium levels were similar between the groups. CONCLUSION: Administration of reduced-dose IV insulin for treatment of hyperkalemia was significantly less effective in lowering serum potassium levels and did not decrease prevalence of hypoglycemia. When accounting for potential confounders, the only variable that was associated with hypoglycemia was pretreatment glucose level.

Gentamicin Dosing in Neonates with Normal Renal Function: Trough and Peak Levels.

BACKGROUND AND OBJECTIVE: Gentamicin is commonly used in neonates, and it requires drug concentration monitoring. The objective of this study was to determine the extent of high trough (≥ 2 mg/l) and therapeutic peak serum gentamicin concentrations (5-12 mg/l) using our current gentamicin regimen and to adjust the dosing regimen accordingly and reassess. METHODS: This was a prospective cohort study of neonates, with normal renal function, who were prescribed gentamicin. Group 1: March 2014-July 2017-gentamicin intravenous (IV) 2.5 mg/kg given every 36 h if < 30 weeks gestational age (GA) and every 24 h if ≥ 30 weeks GA; Group 2: August 2019-February 2020-gentamicin IV 3.5 mg/kg given every 36 h if < 30 weeks GA and every 24 h if ≥ 30 weeks GA. We assessed the number of neonates with aberrant trough and peak serum gentamicin concentrations. RESULTS: Forty-eight neonates < 30 weeks GA and 34 ≥ 30 weeks GA were given 2.5 mg/kg gentamicin. Eleven (23%) neonates < 30 weeks GA and four (13%) ≥ 30 weeks GA had subtherapeutic peak concentrations (< 5 mg/l); none had supratherapeutic (> 12 mg/l) or toxic trough concentrations (≥ 2 mg/l). Forty-four neonates < 30 weeks GA and 54 ≥ 30 weeks GA were given 3.5 mg/kg gentamicin. Eighty-four (86%) had non-toxic trough concentrations (< 2 mg/l). One (1%) < 30 weeks GA neonate had subtherapeutic (< 5 mg/l) and one (1%) neonate ≥ 30 weeks GA had supratherapeutic (> 12 mg/l) peak concentrations. CONCLUSIONS: Gentamicin regimen of 2.5 mg/kg given every 36 h for neonates < 30 weeks GA and every 24 h for neonates ≥ 30 weeks GA was suboptimal at achieving therapeutic gentamicin peak. Increasing the dosage to 3.5 mg/kg achieved therapeutic peak concentrations in 98% and non-toxic trough concentrations in 86% of all neonates (prior to dose interval adjustment).

Ventilation settings in preterm neonates with ventilator-dependant, evolving bronchopulmonary dysplasia.

OBJECTIVE: The only guidance in the literature on which tidal volumes to use when ventilating babies with, or at high risk of, bronchopulmonary dysplasia (BPD) suggests using very large volume breaths of around 8-12 mL/kg and low rates (10-20 breaths per min) to achieve adequate gas exchange, whilst acknowledging there are no data to validate these strategies. The aim of this retrospective, observational, cohort study was to identify the mechanical ventilation settings that are used, and what carbon dioxide (CO2) levels were achieved, in neonates with ventilator-dependant evolving BPD. METHODS: This retrospective cohort study included neonates born <30 weeks GA admitted to the Grantley Stable Neonatal Unit between May 2014 and December 2018. Included ventilator-dependant neonates with evolving BPD ventilated on either or all days 28, 42 and 56 of life. RESULTS: A total of 105 neonates were included, all were between 23 and 28.5 weeks GA. The median (IQR) GA was 25.1 (24.2-26.5) weeks and BW 708 (608-809) grams. Neonates who required conventional mechanical ventilation (CMV) at each of the three time-points had median tidal volumes ranging between 4.5 and 4.7 mL/kg, median ventilator rates of 35-50 and MAPs of 10-11 cmH2O. For those neonates requiring HFOV, median MAPs ranged from 14 to 18 cmH2O and tidal volumes from 1.4 to 2.2 mL/kg to achieve adequate ventilation and oxygenation. CONCLUSIONS: Neonates with ventilator-dependant evolving BPD were ventilated either with CMV using tidal volumes of around 4-5 mL/kg, or HFOV using tidal volumes around 1-2 mL/kg, which achieves adequate ventilation and blood gas results.

Progress toward delisting a Great Lakes Area of Concern: the role of integrated research and monitoring in the Hamilton Harbour Remedial Action Plan.

The goal of restoring environmental health and qualities to Hamilton Harbour Great Lakes Area of Concern, an embayment at the western end of Lake Ontario, is considered to be achievable by the year 2015. Restoring Hamilton Harbour is a dynamic process that relies heavily on research and monitoring to direct remediation efforts. Three principle means of coordinating this research and monitoring include: research and monitoring workshops; a monitoring catalogue outlining both government and nongovernment initiatives; and an annual report written by a local community group. These tools increase the effectiveness of remedial actions by: (i) improving stakeholders' ability to track trends; (ii) allowing program decision-makers to utilize adaptive management techniques to continuously modify programs based on new results; (iii) integrating interdisciplinary fields, and (iv) increasing accountability. This paper describes in detail these tools used for coordinating research and monitoring in implementing the Remedial Action Plan of the Hamilton Harbour Great Lakes Area of Concern, along with lessons learned to assist other implementers who are considering similar programs.