Mild-to-severe traumatic brain injury in children: altered cytokines reflect severity.

BACKGROUND: Paediatric traumatic brain injury (TBI) is recognised to have significant longer-term neurocognitive effects. Childhood is a time of high risk for head injury. Functional recovery is variable with a combination of any or all of physical, cognitive and emotional impairment. Immune activation and alteration in cytokine levels are present following TBI which may differ from adults. METHODS: Pro- and anti-inflammatory cytokines including Interleukin (IL)-2, IL-4, IL-6, IL-8, IL-10, IL-17A, Tumor Necrosis Factor (TNF)-α and Interferon (IFN)-γ were examined at baseline and following in vitro treatment with endotoxin of whole blood, in the following children: severe TBI (sTBI: initial Glasgow coma scale(GCS) ≤ 8), mild TBI (mTBI; GCS 14/15) at 0-4d and at 10-14d post-TBI and compared to healthy age-matched controls. RESULTS: The study enrolled 208 children, including 110 with TBI cohort (n = 104 mild; 6 severe) and controls (n = 98). At baseline all children with TBI had increased IL-6. The mTBI group had significantly increased IFN-γ versus controls. In sTBI at baseline, IFN-γ was decreased compared to controls. At baseline IL-8, IL-10, IL-17A, and TNF-α were decreased in mTBI compared to controls. This persisted at 2 week post-mTBI. The AUC for detecting mTBI was 0.801 CI (0.73-086) using IL6/IL10 ratio. mTBI showed a greater fold change in IL-8 and TNF-α in response to endotoxin stimulation, a response that persisted at 2 weeks. Children with sTBI did not have a significant IL-6 response to endotoxin, but did show an increase in IL-17A. CONCLUSION: Children with all TBI including mTBI show altered cytokine profiles and altered endotoxin responses. Although cytokines increased in sTBI especially in response to endotoxin, suppressed responses were found in mTBI coupled with persistent immune dysfunction post-injury.

Traumatic Brain Injury in Children: Glial fibrillary Acidic Protein and Clinical Outcomes.

OBJECTIVES: Glial fibrillary acidic protein (GFAP) is a neuronal protein released after traumatic brain injury (TBI) and detectable in serum samples. GFAP correlates with symptom severity in adults and may be a marker of brain injury in children with milder symptoms or preverbal children. METHODS: GFAP was examined in children with severe TBI (initial Glasgow Coma Scale score <8), with mild TBI (Glasgow Coma Scale score 14/15), and at 0 to 4 and at 10 to 14 days after TBI and was compared with healthy age-matched controls. Mechanism, time points from injury, and symptoms were recorded. RESULTS: The study enrolled 208 children including 110 with TBI (n = 104 mild, 6 severe) and controls (n = 98). GFAP was higher in mild TBI than in controls and highest in the severe TBI cohort, with a maximum value at 6 hours from injury. Vomiting was significantly associated with higher GFAP levels, but no association was found with amnesia, loss of consciousness, and the Sports Concussion Assessment Tool. Children reporting >1-point changes from their preinjury functioning on the Post-Concussive Symptom Inventory had higher initial GFAP but not total Post-Concussive Symptom Inventory score changes. CONCLUSIONS: GFAP identifies children with TBI, even at the milder end of the spectrum, and is strongly associated with postinjury vomiting. It may be a useful marker of pediatric TBI; however, sampling is time critical.

Detrusor after-contraction on ambulatory urodynamics in symptomatic women.

OBJECTIVES: To investigate the association between detrusor after-contraction and urodynamic parameters in a cohort of patients undergoing urodynamic studies by ambulatory monitoring. METHODS: All symptomatic adult female patients with non-neurogenic lower urinary tract dysfunction having ambulatory monitoring over the period January 1998 to January 2014 were included. Urodynamic traces were reviewed to identify detrusor after-contraction. Measured urodynamic variables were Qmax (mL/s), V(void) (mL) and P(det.Qmax) (cmH(2)O). Student's unpaired t-test was used to compare the mean of the variable in the detrusor after-contraction and non-detrusor after-contraction groups. RESULTS: We identified 331 women with a median age of 50 years (range 16-82). Detrusor after-contraction was seen after at least one void in 122 patients giving a prevalence of 37%. A total of 167 (51%) patients had detrusor overactivity. Diagnosis of detrusor overactivity was associated with the presence of detrusor after-contraction (P < 0.05). Overall, patients with detrusor after-contraction had a statistically higher mean P(det.Qmax) (32 vs 28 cmH(2)O, P = 0.04) and lower mean voided volume (300 vs 378 mL, P < 0.001). CONCLUSION: These findings suggest a relatively high prevalence of detrusor after-contraction during ambulatory monitoring, and an association between detrusor overactivity, V(void), P(det.Qmax) and detrusor after-contraction recorded during ambulatory monitoring. Therefore, a link between detrusor after-contractions and the syndrome of overactive bladder can be postulated.

Differences in urodynamic voiding variables recorded by conventional cystometry and ambulatory monitoring in symptomatic women.

OBJECTIVES: To determine whether there are differences in pressure and flow measurements between conventional cystometry (CONV) and ambulatory urodynamic monitoring (AMB) in women with overactive bladder syndrome and urinary incontinence. MATERIALS AND METHODS: Retrospective study which included female subjects who underwent both CONV (with saline filling medium) and AMB, separated by less than 24 months, not using medication active on the lower urinary tract and without history of prior pelvic surgery. Both tests were carried out in compliance with the International Continence Society standards. The paired Student's t test was used to compare continuous variables. Bland-Altman statistics were used to assess the agreement of each variable between both studies. RESULTS: Thirty women with a median (range) age of 50 (14 - 73) years met the inclusion criteria. AMB was carried out at a mean (SD) of 11 (6) months after CONV. Measurements of pves and pabd at the end of filling, and Qmax were significantly higher from AMB recordings. There were no differences in pdet at the end of filling, pdetQmax or pdetmax during voiding, nor significant difference in Vvoid. CONCLUSIONS: We provide previously undocumented comparative voiding data between CONV and AMB for patients who most commonly require both investigations. Our findings show higher values of Qmax but similar values of pdetQmax measured by AMB which may partly reflect an overall lower catheter caliber, physiological filling but perhaps also more 'normal' voiding conditions.

Survey of Laboratory Medicine's national response to the HSE cyberattack in the Republic of Ireland.

BACKGROUND: On Friday 14 May 2021, the Health Service Executive (HSE) was subjected to a serious cyberattack on their information technology (IT) infrastructure. Healthcare workers lost access to HSE-provided clinical and non-clinical IT systems, including laboratory systems. AIM: The aim of this national survey was to capture Laboratory Medicine's response across the Republic of Ireland during the HSE cyberattack. METHOD: An electronic survey developed using Microsoft Forms® was emailed on 24 September 2021 to 58 local representatives of the PeriAnalytic and Laboratory Medicine Society (PALMSoc). RESULTS: The survey was sent to 43 clinical laboratories across the Republic of Ireland. A total of 41 responses from 43 laboratories across all laboratory disciplines were received (95% response rate). From these, 55% did not have access to a functioning LIS, with 56% of these not having access to a LIS for greater than 2 weeks. A decrease in specimen requests received during this period was reported by 74% of laboratories, with 32% experiencing a reduction that lasted in excess of one month. Over half of the laboratories (55%) experienced a reduction of > 30% in requests, indicating that clinicians stopped investigating patients (87% reduction in primary care), further escalating the disruption to healthcare. CONCLUSION: The cyberattack burdened the HSE and laboratories at a time when healthcare staffs were coming to terms with the impact of the COVID-19 pandemic. Despite this, the survey confirms the agility of laboratory staff in meeting the demands placed on it during this time.

The CELTIC ranges project (comprehensive and effective laboratory test reference intervals for Irish children) methodology and results for renal profile tests in plasma on the Roche modularTM system.

BACKGROUND: The CELTIC ranges project aims to deliver a comprehensive range of reference intervals for commonly ordered laboratory investigations suitable for use in an Irish population as well as enabling comparison with relevant international studies. In this paper, we describe our methodology used throughout the entire project and present paediatric reference intervals for renal profile tests in plasma (sodium, potassium, urea and creatinine). METHODS: 1023 children aged up to 17 years were recruited from our hospital's general practitioner paediatric phlebotomy clinic. Clinical chemistry analyses were performed on the Roche modular system and statistical analysis was completed in line with CLSI guideline EP28-A3c. RESULTS: The plasma reference interval for sodium for ages 0.45-16.99 years was 137-143 mmol/L in 1000 subjects (combined genders). For plasma potassium, the corresponding ranges between 1 and 16.99 years (combined genders) were 3.6-4.8 mmol/L. Apart from neonates and in keeping with other studies, age partitioning for electrolytes was not required. Data for plasma creatinine (enzymatic methodology) and urea is also presented and, as anticipated, required partitioning for both age and gender. CONCLUSIONS: Our renal profile findings are broadly consistent with those of international studies, for example, CALIPER, HAPPI, NORDIC, PRINCE and KiGGs. Moreover, the CELTIC ranges study is also based on over 1000 subjects whose samples were analysed on the widely used Roche modular analytics system. We also expect the findings will improve knowledge of children's metabolic health in Ireland.

Survey of laboratory medicine's national response to the Covid-19 pandemic in the Republic of Ireland.

BACKGROUND: The global SARS-CoV-2 pandemic placed Irish Laboratory Medicine services under sustained and massive strain. Rapid reconfiguration was required to introduce new assays at high capacity for diagnosis and monitoring of COVID-19, while maintaining existing services. AIM: The aim of this national survey was to capture Laboratory Medicine's response across the Republic of Ireland during the first wave of the COVID-19 pandemic. METHODS: An electronic survey developed using Microsoft Forms® was emailed on 5 October 2020 to 53 local representatives of the PeriAnalytic and Laboratory Medicine Society (PALMSoc), reaching 38 separate pathology departments in the country. RESULTS: A total of 45 responses from 38 laboratories were received (72% response rate) representing a range of departments and disciplines. Most laboratories (63%) introduced new tests, and in a time frame of less than 6 weeks (80%). Point-of-care testing (POCT) played a significant role in the response to COVID-19, with almost half of respondents (47%) reporting that additional equipment was introduced. Maintenance of the Quality Management System (QMS) proved challenging, with 60% of respondents indicating that not all aspects were sustained. When asked about changes to staff rostering, 98% of respondents reported that changes were made. All adjustments were made despite staffing challenges; only 18% of respondents described the staffing levels in their department as 100% prior to the onset of the first wave. CONCLUSIONS: This study confirms an agile and resilient response to the COVID-19 pandemic from Ireland's Laboratory Medicine services despite many economic and staffing challenges.

High anti-SARS-CoV-2 antibody seroprevalence in healthcare workers in an Irish university teaching hospital.

INTRODUCTION: Healthcare workers are at very high risk for SARS-CoV-2 exposure and infection. This study evaluated anti-SARS-CoV-2 seroprevalence in healthcare workers in a tertiary care hospital and then correlated seroprevalence with confirmed or suspected SARS-CoV-2 infection in this population since the onset of the COVID-19 pandemic. METHOD: The study was approved by our institution's Joint Research Ethics Committee in June 2020. All volunteers were provided with a consent form, an information leaflet and a questionnaire on the day before phlebotomy. Serum samples were collected from 1176 participants over a 3-month period and analysed using the Elecsys Anti-SARS-CoV-2 assay (Roche Diagnostics GmbH, Mannheim, Germany) which detects total antibodies against the nucleocapsid protein of SARs-COV-2. RESULTS: Overall anti-SARS-CoV-2 seroprevalence among participating healthcare workers was 17.9%. The rate of confirmed infection by real-time polymerase chain reaction molecular testing prior to participation was 12.2%. Of 211 participants who had a reactive antibody test result, 37% did not have COVID-19 infection confirmed at any point prior to participation in this study, either having had a swab which did not detect SARS-CoV-2 RNA or having never been tested. Seropositivity was the highest (30%) in the youngest quintile of age (20-29 years old). Staff with more patient contact had a higher seroprevalence of 19.5% compared to 13.4% in staff with less patient contact. CONCLUSION: This study demonstrates that a substantial proportion of SARS-CoV-2 infections in healthcare workers may be asymptomatic or subclinical and thus potentially represent a significant transmission risk to colleagues and patients.

Previous SARS-CoV-2 Infection, Age, and Frailty Are Associated With 6-Month Vaccine-Induced Anti-Spike Antibody Titer in Nursing Home Residents.

OBJECTIVES: Older nursing home residents make up the population at greatest risk of morbidity and mortality from severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. No studies have examined the determinants of long-term antibody responses post vaccination in this group. DESIGN: Longitudinal cohort study. SETTING AND PARTICIPANTS: Residents from 5 nursing homes assessed before vaccination, and 5 weeks and 6 months post vaccination, with the BNT162b2 messenger RNA SARS-CoV-2 vaccine. METHODS: Comprehensive clinical assessment was performed, including assessment for comorbidity, frailty, and SARS-CoV-2 infection history. Serum nucleocapsid and anti-spike receptor binding domain (RBD) antibodies were analyzed at all timepoints. An in vitro angiotensin-converting enzyme (ACE2) receptor-spike RBD neutralization assay assessed serum neutralization capacity. RESULTS: Of 86 participants (81.1 ± 10.8 years; 65% female), just under half (45.4%; 39 of 86) had evidence of previous SARS-CoV-2 infection. All participants demonstrated a significant antibody response to vaccination at 5 weeks and a significant decline in this response by 6 months. SARS-CoV-2 infection history was the strongest predictor of antibody titer (log-transformed) at both 5 weeks [ß: 3.00; 95% confidence interval (CI): 2.32-3.70; P < .001] and 6 months (ß: 3.59; 95% CI: 2.89-4.28; P < .001). Independent of SARS-CoV-2 infection history, both age in years (ß: -0.05; 95% CI: -0.08 to -0.02; P < .001) and frailty (ß: -0.22; 95% CI: -0.33 to -0.11; P < .001) were associated with a significantly lower antibody titer at 6 months. Anti-spike antibody titers at both 5 weeks and 6 months significantly correlated with in vitro neutralization capacity. CONCLUSIONS AND IMPLICATIONS: In older nursing home residents, SARS-CoV-2 infection history was the strongest predictor of anti-spike antibody titers at 6 months, whereas age and frailty were independently associated with lower titers at 6 months. Antibody titers significantly correlated with in vitro neutralization capacity. Although older SARS-CoV-2 naïve nursing home residents may be particularly vulnerable to breakthrough SARS-CoV-2 infection, the relationship between antibody titers, SARS-CoV-2 infection, and clinical outcomes remains to be fully elucidated in this vulnerable population.

Monitoring and capturing patient identification errors in laboratory medicine.

BACKGROUND: Specimen labelling and patient identification are significant contributors to the rate of error in the preanalytical phase of laboratory medicine. This study aimed to investigate the prevalence and nature of preanalytical quality monitoring practices for patient identification and specimen labelling errors in Irish clinical laboratories. METHODS: A survey was developed by the Clinical Biochemistry Unit, Trinity College Dublin and the Irish External Quality Assessment Scheme (IEQAS), with the intention of gathering key information from each laboratory. Thirty-nine questions were organized into seven subsections covering general information, labelling requirements, information availability, rejection criteria, error monitoring, error reporting and interest in participation in an external quality assessment scheme. The survey was sent electronically to 63 laboratory quality managers at 55 laboratories in Ireland. RESULTS: A total of 39 responses (61% response rate) provided information on 94 separate laboratory departments or disciplines. Laboratories reported varying practices and requirements for labelling specimens and all accepted handwritten preprinted request forms. All (100%) respondents had defined rejection criteria both for specimen labelling and request form completion. Unsurprisingly, the rejection criteria differed between the various laboratory disciplines. Almost all respondents provided information to clinical staff on labelling requirements, but just over half provided training on the same. A large percentage of laboratories (74%) monitored the rate of specimen-labelling errors; however, only 46% had defined target limits for acceptable rates of error. CONCLUSION: The survey observed a wide variation in collection, recording and monitoring of errors but also confirmed significant interest in improving preanalytical monitoring and data collection.

Inverse Relationship Between Physical Activity, Adiposity, and Arterial Stiffness in Healthy Middle-Aged Subjects.

BACKGROUND: Several obesity related factors are reported to exacerbate premature arterial stiffening, including inactivity and metabolic disarray. The aim of the current study was to investigate the relationship between physical activity, arterial stiffness and adiposity using objective methods. To further explore the role of adiposity in this complex process, obesity associated anthropometric and humoral biomarkers were measured. METHODS: Seventy-nine healthy, lifelong nonsmoking subjects were recruited. Habitual physical activity was measured using accelerometry. Arterial stiffness [augmentation index (AIx) and pulse wave velocity (PWV)] was measured using tonometry. Body composition was estimated using bioimpedence. Adipose associated biomarkers, leptin and adiponectin, were also measured. RESULTS: Sedentary time was significantly associated with AIx (r = 0.38, P < .001), PWV (r = 0.33, P < .01), body fat composition (r = 0.40, P < .001) and age (r = 0.30, P < .01). Moderate-to-vigorous physical activity (MVPA) was inversely correlated with AIx (r = -0.28, P < .05), body fat composition (r = -0.30, P < .01), postprandial insulin (r = -0.35, P < .01), and leptin/adiponectin ratio (r = -0.28, P < .05). MVPA, body fat composition, and postprandial insulin remained independent predictors of AIx but not PWV. CONCLUSION: The more time healthy individuals spend being sedentary, the greater their body fat and arterial stiffness. Conversely higher activity levels are associated with reduced body fat and less arterial stiffness.

Navigating the cultural geography of indigenous peoples' attitude toward genetic research: the Ohana (family) heart project.

BACKGROUND: Little is known about the burden of heart failure among indigenous populations, including Native Hawaiians (NH). Recent concerns about genetic research in the NH community resonate with similar concerns raised by American Indian, Alaskan Native and Canadian First Nations communities and have raised questions about the best way to proceed with studies involving biological specimens. OBJECTIVE: To help us plan a study to investigate disparities in heart failure incidence and outcomes in a NH community, we performed a qualitative study to examine the community's expectations for heart failure research that includes the collection of biological specimens. METHODS: Eighty-five NH with a personal or family history of heart failure, who lived in a geographically isolated community in the state of Hawai'i participated in 1 of 16 semi-structured interviews. Interviews were conducted in a standard manner, with open-ended questions designed to explore their expectations for a heart failure research study that included the collection of biological specimens. Interviews were analyzed thematically through iterative readings and coding. RESULTS: four key themes regarding heart failure research with the use of biological specimens characterized their expectations: (a) Need to foster trust between investigator and community; (b) Establish a partnership with the community to identify needs and goals; (c) Need for mutual benefit to investigator and community; (d) Identification of a key voice to represent the community. Participants expressed strong support for research. However, the strength of that support was directly related to the strength of the relationship between the research team and the community. The collection of biological specimens for genetic analyses was not an explicit concern or barrier per se. CONCLUSIONS: It appears feasible to conduct a heart failure research study that includes the collection of biological samples. However, success will likely require addressing the community's expectations, including the need for a long-term partnership built on trust and mutual benefit, and a key voice to represent the community.

Differences in urodynamic voiding variables recorded by conventional cystometry and ambulatory monitoring in symptomatic women

Objectives To determine whether there are differences in pressure and flow measurements between conventional cystometry (CONV) and ambulatory urodynamic monitoring (AMB) in women with overactive bladder syndrome and urinary incontinence. Materials and Methods Retrospective study which included female subjects who underwent both CONV (with saline filling medium) and AMB, separated by less than 24 months, not using medication active on the lower urinary tract and without history of prior pelvic surgery. Both tests were carried out in compliance with the International Continence Society standards. The paired Student’s t test was used to compare continuous variables. Bland-Altman statistics were used to assess the agreement of each variable between both studies. Results Thirty women with a median (range) age of 50 (14 - 73) years met the inclusion criteria. AMB was carried out at a mean (SD) of 11 (6) months after CONV. Measurements of pves and pabd at the end of filling, and Qmax were significantly higher from AMB recordings. There were no differences in pdet at the end of filling, pdetQmax or pdetmax during voiding, nor significant difference in Vvoid. Conclusions We provide previously undocumented comparative voiding data between CONV and AMB for patients who most commonly require both investigations. Our findings show higher values of Qmax but similar values of pdetQmax measured by AMB which may partly reflect an overall lower catheter caliber, physiological filling but perhaps also more ‘normal’ voiding conditions. .

Are conventional pressure-flow measurements dependent upon filled volume?

OBJECTIVE: To determine, in a prospective study, whether detrusor pressure (p(det.Qmax)) and maximum urinary flow rate (Q(max)) measurements obtained after filling to maximum cystometric capacity (MCC) differ from those obtained with filling restricted to average voided volume (V(void)), as standard protocols for pressure flow studies (PFS) mandate bladder filling until the subject has a strong desire to void, which aids standardization but further divorces the test from real-life experience. PATIENTS AND METHODS: After calculating the appropriate sample size, 84 patients attending for PFS with an adequately completed 3-day frequency-volume chart were recruited. Each underwent two consecutive PFS with filling to MCC and average V(void) in a random order, and measurements of p(det.Qmax) and Q(max) were compared. For men, the agreement for a diagnosis of obstruction between the tests was also assessed. RESULTS: Complete data were obtained from 76 (90%) of the patients, with a mean (range) age of 64 (20-94) years. The mean (sd) difference between MCC and average V(void) was 134 (113) mL (P < 0.01). There were no significant differences between estimates of Q(max), at - 0.1 (3) mL/s (P = 0.75), and of p(det.Qmax), at - 1 (13) cmH(2)O (P = 0.91), obtained within each patient. For men there was 91% agreement (32 of 35) in the classification of obstruction. CONCLUSIONS: Restriction of filling to the average V(void) during PFS allows a closer approximation to normal voiding and results in no clinically relevant change to the value of standard pressure-flow measurements or alters individual classification of obstruction.

Can bladder outflow obstruction be diagnosed from pressure flow analysis of voiding initiated by involuntary detrusor overactivity?

PURPOSE: We investigated whether a diagnosis of bladder outflow obstruction could be established from pressure flow analysis of a void initiated by involuntary detrusor overactivity. MATERIALS AND METHODS: A total of 79 men with lower urinary tract symptoms were identified prospectively. In each subject 2 sequential pressure flow studies were performed during the same session. Pressure flow data were recorded during a voluntary void and voiding initiated by involuntary detrusor overactivity. Pressure flow parameters were compared using the paired t test and differences in classification according to the International Continence Society nomogram were analyzed using the chi-square test. RESULTS: The maximum flow rate showed no significant difference between voluntary voiding and voiding initiated by involuntary detrusor overactivity. Detrusor pressure at maximum flow showed a slight, statistically significant but not clinically significant increase during voiding initiated by involuntary detrusor overactivity. However, the diagnostic classification remained unchanged in 64 of 79 men (80%). In no case was the diagnosis altered from bladder outflow obstruction to nonobstruction or vice versa when comparing the 2 pressure flow studies. There were significant increases in maximum detrusor pressure and detrusor pressure at the initiation of voiding during voiding initiated by involuntary detrusor overactivity. CONCLUSIONS: This study demonstrates that increased detrusor pressure observed during voiding subsequent to detrusor overactivity does not change the diagnostic classification in 80% of men. The results provide evidence that bladder outflow obstruction can be reliably diagnosed based on pressure flow parameters recorded during voiding initiated by involuntary detrusor overactivity.