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The Australian Traumatic Brain Injury Initiative (AUS-TBI) aims to select a set of measures to comprehensively predict and assess outcomes following moderate-to-severe traumatic brain injury (TBI) across Australia. The aim of this article was to report on the implementation and findings of an evidence-based consensus approach to develop AUS-TBI recommendations for outcome measures following adult and pediatric moderate-to-severe TBI. Following consultation with a panel of expert clinicians, Aboriginal and Torres Strait Islander representatives and a Living Experience group, and preliminary literature searches with a broader focus, a decision was made to focus on measures of mortality, everyday functional outcomes, and quality of life. Standardized searches of bibliographic databases were conducted through March 2022. Characteristics of 75 outcome measures were extracted from 1485 primary studies. Consensus meetings among the AUS-TBI Steering Committee, an expert panel of clinicians and researchers and a group of individuals with lived experience of TBI resulted in the production of a final list of 11 core outcome measures: the Functional Independence Measure (FIM); Glasgow Outcome Scale-Extended (GOS-E); Satisfaction With Life Scale (SWLS) (adult); mortality; EuroQol-5 Dimensions (EQ5D); Mayo-Portland Adaptability Inventory (MPAI); Return to Work /Study (adult and pediatric); Functional Independence Measure for Children (WEEFIM); Glasgow Outcome Scale Modified for Children (GOS-E PEDS); Paediatric Quality of Life Scale (PEDS-QL); and Strengths and Difficulties Questionnaire (pediatric). These 11 outcome measures will be included as common data elements in the AUS-TBI data dictionary. Review Registration PROSPERO (CRD42022290954).

The Australian Traumatic Brain Injury Initiative (AUS-TBI) aims to develop a health informatics approach to collect data predictive of outcomes for persons with moderate-severe TBI across Australia. Central to this approach is a data dictionary; however, no systematic reviews of methods to define and develop data dictionaries exist to-date. This rapid systematic review aimed to identify and characterize methods for designing data dictionaries to collect outcomes or variables in persons with neurological conditions. Database searches were conducted from inception through October 2021. Records were screened in two stages against set criteria to identify methods to define data dictionaries for neurological conditions (International Classification of Diseases, 11th Revision: 08, 22, and 23). Standardized data were extracted. Processes were checked at each stage by independent review of a random 25% of records. Consensus was reached through discussion where necessary. Thirty-nine initiatives were identified across 29 neurological conditions. No single established or recommended method for defining a data dictionary was identified. Nine initiatives conducted systematic reviews to collate information before implementing a consensus process. Thirty-seven initiatives consulted with end-users. Methods of consultation were ?roundtable? discussion (n?=?30); with facilitation (n?=?16); that was iterative (n?=?27); and frequently conducted in-person (n?=?27). Researcher stakeholders were involved in all initiatives and clinicians in 25. Importantly, only six initiatives involved persons with lived experience of TBI and four involved carers. Methods for defining data dictionaries were variable and reporting is sparse. Our findings are instructive for AUS-TBI and can be used to further development of methods for defining data dictionaries.

The majority of traumatic encephalopathy syndrome (TES) cases have been reported in former contact sport athletes. This is the first case with TES in a 19-year-old male patient with progressive cognitive decline after daily domestic physical violence through repeated hits to the head for 15 years. The patient presented with a moderate depressive episode and progressive cognitive decline. Tau positron emission tomography (PET) with 220?MBq of [18F]PI-2620 revealed increased focal signal at the frontal and parietal white/gray matter border. Brain magnetic resonance imaging (MRI) showed a cavum septum pellucidum, reduced left-sided hippocampal volume, and a left midbrain lesion. Cerebrospinal fluid results showed elevated total and p-tau. Neurocognitive testing at admission showed memory deficits clearly below average, and hampered dysfunctions according to the slow processing speed with a low mistake rate, indicating the acquired, thus secondary, attentional deficits. We diagnosed the patient with a TES suggestive of chronic traumatic encephalopathy and classified him as having subtle/mild functional limitation with a most likely transition to mild dementia within the TES criteria. This report underlines child abuse as a relevant criterion in diagnosing TES in cases with repetitive hits to the head. In addition to clinical markers, we show the relevance of fluid tau biomarkers and tau-PET to support the diagnosis of TES according to the recently published diagnosis criteria for TES.

Previous studies have suggested that there are sex differences in the treatment and outcome of neurological emergencies; however, research identifying the role these sex differences play in the management of neurological emergencies is lacking. More knowledge of the way sex factors into the pathophysiology of neurological emergencies will be helpful in improving outcomes for these patients. The aim of this cross-sectional study was to assess the prevalence and management of neurological emergencies while evaluating sex differences in the diagnosis and treatment of these emergencies. We analyzed a cohort of 530 adult patients from four level 1 trauma centers over a period of 4 weeks who had a chief complaint of a neurological emergency, including seizures, cerebrovascular events, headache disorders, traumatic brain injuries, and central nervous system infections. Among patients with neurological emergencies, a significantly lower proportion of female patients underwent neurosurgery and were admitted to the intensive care unit compared to male patients, but there were no significant differences between sexes in the time of symptom onset, type of hospital transportation, amount of neuroimaging performed, admission rates, hospital length of stay, and disposition from the emergency department. Although female patients were more likely to have a chief complaint of headache compared to traumatic injuries in male patients, this was not statistically significant. A significantly higher proportion of female patients had health insurance coverage than male patients.

Purpose: Although health care systems aspire to deliver equitable care, practical tools that empower the health care workforce to weave equity throughout quality improvement (QI) processes are lacking. In this article, we report findings from context of use interviews that informed the development of a user-centered tool to support equity-focused QI. Methods: Semistructured interviews were conducted from February to April of 2019. Participants included 14 medical center administrators, departmental or service line leaders, and clinical staff involved in direct patient care from three Veterans Affairs (VA) Medical Centers within a single region. Interviews covered existing practices for monitoring health care quality (i.e., priorities, tasks, workflow, and resources) and explored how equity data might fit into current processes. Themes extracted through rapid qualitative analysis were used to draft initial functional requirements for a tool to support equity-focused QI. Results: Although the potential value of examining disparities in health care quality was clearly recognized, the data necessary for examining disparities were lacking for most quality measures. Interviewees also desired guidance on how inequities could be addressed through QI. The ways in which QI initiatives were selected, carried out, and supported also had important design implications for tools to support equity-focused QI. Discussion: The themes identified in this work guided the development of a national VA Primary Care Equity Dashboard to support equity-focused QI within VA. Understanding the ways in which QI was carried out across multiple levels of the organization provided a successful foundation upon which to build functional tools to support thoughtful engagement around equity in clinical settings.

The relationship between systemic inflammation and secondary injury in traumatic brain injury (TBI) is complex. We investigated associations between inflammatory markers and clinical confirmation of TBI diagnosis and prognosis. The prospective TRACK-TBI Pilot (Transforming Research and Clinical Knowledge in Traumatic Brain Injury Pilot) study enrolled TBI patients triaged to head computed tomography (CT) and received blood draw within 24?h of injury. Healthy controls (HCs) and orthopedic controls (OCs) were included. Thirty-one inflammatory markers were analyzed from plasma. Area under the receiver operating characteristic curve (AUC) was used to evaluate discriminatory ability. AUC >0.7 was considered acceptable. Criteria included: TBI diagnosis (vs. OC/HC); moderate/severe vs. mild TBI (Glasgow Coma Scale; GCS); radiographic TBI (CT positive vs. CT negative); 3- and 6-month Glasgow Outcome Scale-Extended (GOSE) dichotomized to death/greater relative disability versus less relative disability (GOSE 1?4/5?8); and incomplete versus full recovery (GOSE

Pre-hospital resuscitation of critically injured patients traditionally includes supplemental oxygen therapy to address potential hypoxemia. The objective of this study was to explore the association between pre-hospital hypoxemia, hyperoxemia, and mortality in patients with traumatic brain injury (TBI) and traumatic shock. We hypothesized that both hypoxemia and hyperoxemia would be associated with increased mortality. We used the Resuscitation Outcomes Consortium Prospective Observational Prehospital and Hospital Registry for Trauma (ROC PROPHET) database of critically injured patients to identify a severe TBI cohort (pre-hospital Glasgow Coma Scale [GCS] 3?8) and a traumatic shock cohort (systolic blood pressure ?90?mm Hg and pre-hospital GCS >8). Arterial blood gas (ABG) obtained within 30?min of hospital arrival was required for inclusion. Patients with hypoxemia (PaO2 400?mm Hg) were compared to those with normoxemia (PaO2 80?400?mm Hg) with regard to the primary outcome measure of in-hospital mortality in both the TBI and traumatic shock cohorts. Multiple logistic regression was used to calculate odds ratios (ORs) after adjustment for multiple covariables. In addition, regression spline curves were generated to estimate the risk of death as a continuous function of PaO2 levels. A total of 1248 TBI patients were included, of whom 396 (32%) died before hospital discharge. Associations between hypoxemia and increased mortality (OR, 1.8; 95% confidence interval [CI], 1.2?2.8; p?=?0.008) and between hyperoxemia and decreased mortality (OR, 0.6; 95% CI, 0.4?0.9; p?=?0.018) were observed. A total of 582 traumatic shock patients were included, of whom 52 (9%) died before hospital discharge. No statistically significant associations were observed between in-hospital mortality and either hypoxemia (OR, 1.0; 95% CI, 0.4?2.4; p?=?0.987) or hyperoxemia (OR, 1.9; 95% CI, 0.6?5.7; p?=?0.269). Among patients with severe TBI but not traumatic shock, hypoxemia was associated with an increase of in-hospital mortality and hyperoxemia was associated with a decrease of in-hospital mortality.

The current approach to intracranial hypertension and brain tissue hypoxia is reactive, based on fixed thresholds. We used statistical machine learning on high-frequency intracranial pressure (ICP) and partial brain tissue oxygen tension (PbtO2) data obtained from the BOOST-II trial with the goal of constructing robust quantitative models to predict ICP/PbtO2 crises. We derived the following machine learning models: logistic regression (LR), elastic net, and random forest. We split the data set into 70?30% for training and testing and utilized a discrete-time survival analysis framework and 5-fold hyperparameter optimization strategy for all models. We compared model performances on discrimination between events and non-events of increased ICP or low PbtO2 with the area under the receiver operating characteristic (AUROC) curve. We further analyzed clinical utility through a decision curve analysis (DCA). When considering discrimination, the number of features, and interpretability, we identified the RF model that combined the most recent ICP reading, episode number, and longitudinal trends over the preceding 30?min as the best performing for predicting ICP crisis events within the next 30?min (AUC 0.78). For PbtO2, the LR model utilizing the most recent reading, episode number, and longitudinal trends over the preceding 30?min was the best performing (AUC, 0.84). The DCA showed clinical usefulness for wide risk of thresholds for both ICP and PbtO2 predictions. Acceptable alerting thresholds could range from 20% to 80% depending on a patient-specific assessment of the benefit-risk ratio of a given intervention in response to the alert.

In September 2020, the Department of Veterans Affairs (VA) launched a novel volunteer research registry to rapidly recruit eligible study participants for research on SARS-CoV-2 and COVID-19 vaccines and treatments at VA Medical Centers selected as study sites for COVID-19 clinical trials. Targeted multimedia outreach campaigns were used to recruit diverse populations, including those historically under-represented in medical research. By November 2022, 58,561 volunteers were enrolled in the registry, 19% of whom were women, 9% Hispanic/Latino, and 8% Black. The registry's strategic approach to outreach proved successful in recruiting diverse volunteers, with geotargeted e-mails recruiting the most diversity.

Background: Ensuring enhanced delivery of care to women Veterans is a top Veterans Affairs (VA) priority; however, women are historically underrepresented in research that informs evidence-based health care. A primary barrier to women's participation is the inability to engage with research in person due to a number of documented challenges. The VA Million Veteran Program (MVP) is committed to increasing access for women Veterans to participate in research, thereby better understanding conditions specific to this population and how disease manifests differently in women compared to men. The goal of this work is to describe the results of the MVP Women's Campaign, an effort designed to increase outreach to and awareness of remote enrollment options for women Veterans. Materials and Methods: The MVP Women's Campaign launched two phases between March 2021 and April 2022: the Multimedia Phase leveraged a variety of strategic multichannel communication tactics and the Email Phase focused on direct email communication to women Veterans. The effect of the Multimedia Phase was determined using t-tests and chi-square tests, as well as logistic regression models to compare demographic subgroups. The Email Phase was evaluated using comparisons of the enrollment rate across demographic groups through a multivariate adjusted logistic regression model. Results: Overall, 4694 women Veterans enrolled during the MVP Women's Campaign (54% during the Multimedia Phase and 46% during the Email Phase). For the Multimedia Phase, the percentage of older women online enrollees increased, along with women from the southwest and western regions of the United States. Differences for women Veteran online enrollment across different ethnicity and race groups were not observed. During the Email Phase, the enrollment rate increased with age. Compared to White women Veterans, Blacks, Asians, and Native Americans were significantly less likely to enroll while Veterans with multiple races were more likely to enroll. Conclusion: The MVP Women's Campaign is the first large-scale outreach effort focusing on recruitment of women Veterans into MVP. The combination of print and digital outreach tactics and direct email recruitment resulted in over a fivefold increase in women Veteran enrollees during a 7-month period. Attention to messaging and communication channels, combined with a better understanding of effective recruitment methods for certain Veteran populations, allows MVP the opportunity to advance health and health care not only for women Veterans, but beyond. Lessons learned will be applied to increase other populations in MVP such as Blacks, Hispanics, Asians, Native Americans, younger Veterans, and Veterans with certain health conditions.

Therapeutic hypothermia for severe traumatic brain injury (TBI) has been repeatedly studied, but no past studies have assessed the detailed head computed tomography (CT) findings. We sought to investigate individual CT findings of severe TBI patients treated with targeted temperature management utilizing the head CT database obtained from the Brain Hypothermia study. Enrolled patients underwent either mild therapeutic hypothermia (32.0?C?34.0?C) or fever control (35.5?C?37.0?C). We assessed individual head CT images on arrival and after rewarming and investigated the correlations with outcomes. The initial CT data were available for 125 patients (hypothermia group?=?80, fever control group?=?45). Baseline characteristics and CT findings, such as hematoma thickness and midline shift, were similar in all aspects between the two groups. The favorable outcomes in the hypothermia and fever control groups were 38 (47.5%) and 24 (53.3%; p?=?0.53) for all 125 patients, respectively; 21 (46.7%) vs. 10 (38.5%; p?=?0.50) for 71 patients with acute subdural hematoma (SDH), respectively; and 12 (75.0%) vs. 4 (36.4%; p?=?0.045) in 27 young adults (?50 years) with acute SDH, respectively. There was a trend toward favorable outcomes for earlier time to reach 35.5?C (190 vs. 377?min, p?=?0.052) and surgery (155 vs. 180?min, p?=?0.096) in young patients with acute SDH. The second CT image revealed progression of the brain injury. This study demonstrated the potential benefits of early hypothermia in young patients with acute SDH, despite no difference in CT findings between the two groups. However, the small number of cases involved hindered the drawing of definitive conclusions. Future studies are warranted to validate the results.

Abstract Background Safe and accurate execution of surgeries to date mainly rely on preoperative plans generated based on preoperative imaging. Frequent intraoperative interaction with such patient images during the intervention is needed, which is currently a cumbersome process given that such images are generally displayed on peripheral two-dimensional (2D) monitors and controlled through interface devices that are outside the sterile filed. This study proposes a new medical image control concept based on a Brain Computer Interface (BCI) that allows for hands-free and direct image manipulation without relying on gesture recognition methods or voice commands. Method A software environment was designed for displaying three-dimensional (3D) patient images onto external monitors, with the functionality of hands-free image manipulation based on the user’s brain signals detected by the BCI device (i.e., visually evoked signals). In a user study, ten orthopedic surgeons completed a series of standardized image manipulation tasks to navigate and locate predefined 3D points in a Computer Tomography (CT) image using the developed interface. Accuracy was assessed as the mean error between the predefined locations (ground truth) and the navigated locations by the surgeons. All surgeons rated the performance and potential intraoperative usability in a standardized survey using a five-point Likert scale (1 = strongly disagree to 5 = strongly agree). Results When using the developed interface, the mean image control error was 15.51 mm (SD: 9.57). The user's acceptance was rated with a Likert score of 4.07 (SD: 0.96) while the overall impressions of the interface was rated as 3.77 (SD: 1.02) by the users. We observed a significant correlation between the users' overall impression and the calibration score they achieved. Conclusions The use of the developed BCI, that allowed for a purely brain-guided medical image control, yielded promising results, and showed its potential for future intraoperative applications. The major limitation to overcome was noted as the interaction delay.

Predicting and optimizing outcomes after traumatic brain injury (TBI) remains a major challenge because of the breadth of injury characteristics and complexity of brain responses. AUS-TBI is a new Australian Government?funded initiative that aims to improve personalized care and treatment for children and adults who have sustained a TBI. The AUS-TBI team aims to address a number of key knowledge gaps, by designing an approach to bring together data describing psychosocial modulators, social determinants, clinical parameters, imaging data, biomarker profiles, and rehabilitation outcomes in order to assess the influence that they have on long-term outcome. Data management systems will be designed to track a broad range of suitable potential indicators and outcomes, which will be organized to facilitate secure data collection, linkage, storage, curation, management, and analysis. It is believed that these objectives are achievable because of our consortium of highly committed national and international leaders, expert committees, and partner organizations in TBI and health informatics. It is anticipated that the resulting large-scale data resource will facilitate personalization, prediction, and improvement of outcomes post-TBI.

Background: Phenotypic features and outcome differences between sexes have been reported in psoriatic arthritis (PsA). However, little is known about sex differences in effectiveness of biologics in clinical practice. Methods: Post hoc gender analysis of the CHRONOS, a multicenter, noninterventional, retroprospective Italian real-world study assessing 6-month and 1-year effectiveness of biologics for PsA. Results: Eligible patients were 399, 43.1% men. Sociodemographic characteristics, type of arthritis, baseline Disease Activity Score 28 joints (DAS28), and duration of biologic treatment were rather homogeneous. More men were overweight/obese and naive to biologics. The most frequently used biologics were TNF-inhibitors and secukinumab in both sexes. DAS28 responders were 72.7% (women) and 70.5% (men) at 6 months, and 68.0% in both sexes at 1 year. American College of Rheumatology (ACR) response showed a trend for men versus women to achieve more frequently ACR50 (32.6% vs. 26.5% at 6 months; 34.9% vs. 20.0% at 1 year) and ACR70 (22.3% vs. 12.4% at 6 months and 25.0% vs. 13.0% at 1 year). Global satisfaction with treatment at enrollment and after 6 months was slightly higher among men [mean (standard deviation) Treatment Satisfaction Questionnaire for Medication-9 (TSQM-9) score: 68.6 (18.6) and 69.9 (18.2), respectively] than women [65.3 (18.2), 66.2 (18.5)]. Conclusions: Overall response to biologics for PsA was rather favorable. With similar baseline disease severity, men appear to have a somewhat earlier and better response with higher treatment satisfaction.

The aims of this study are to describe the use of pharmaceutical venous thromboembolism (pVTE) prophylaxis in patients with traumatic brain injury (TBI) in Europe and study the association of pVTE prophylaxis with outcome. We included 2006 patients ?18 years of age admitted to the intensive care unit from the CENTER-TBI study. VTE events were recorded based on clinical symptoms. Variation between 54 centers in pVTE prophylaxis use was assessed with a multi-variate random-effect model and quantified with the median odds ratio (MOR). The association between pVTE prophylaxis and outcome (Glasgow Outcome Scale-Extended at 6 months) was assessed at center level with an instrumental variable analysis and at patient level with a multi-variate proportional odds regression analysis and a propensity-matched analysis. A time-dependent Cox survival regression analysis was conducted to determine the effect of pVTE prophylaxis on survival during hospital stay. The association between VTE prophylaxis and computed tomography (CT) progression was assessed with a logistic regression analysis. Overall, 56 patients (2%) had a VTE during hospital stay. The majority, 1279 patients (64%), received pVTE prophylaxis, with substantial between-center variation (MOR, 2.7; p?0.001). A moderate association with improved outcome was found at center level (odds ratio [OR], 1.2 [0.7?2.1]) and patient level (multi-variate adjusted OR, 1.4 [1.1?1.7], and propensity adjusted OR, 1.5 [1.1?2.0]), with similar results in subgroup analyses. Survival was higher with the use of pVTE prophylaxis (p?

This study aimed to report cancer incidence and mortality in a Brazilian human immunodeficiency virus (HIV) cohort of 31?years duration and compare cancer deaths with deaths due to noncancer causes. We also investigated risk factors for the development of acquired immunodeficiency syndrome (AIDS)-defining and non-AIDS-defining cancers. We searched for any information related to the diagnosis of cancer in a period ranging from 1989 to 2020. We also collected data on sociodemographic and clinical information and risk factors. Statistical analysis included parametric and nonparametric tests and the building of survival curves. We used the statistical software GraphPad software (version 9) and STATA software (version 14) for the elaboration of statistics. Fifty-five new cases of cancer occurred in a total of 677 HIV patients included in our cohort over 31?years, an incidence of 8.12%. The most important risk factors associated with cancer were smoking (p = 0.03), infection with oncoviruses like human papillomavirus (p < 0.001), and hepatitis C (p = 0.04). Eleven patients (1.6%) died from cancer. The most frequent diagnoses of fatal cancer were liver cancer and lymphoma (three cases each). The mean follow-up time of patients dying from cancer was 14?years; patients dying from noncancer causes were 24 (3.55%), and their mean follow-up time was 11?years. We had low overall mortality in our cohort of HIV patients (5.2%), mostly due to noncancer causes, which may be due to the fact that most of our patients begin follow-up asymptomatic. Cancer deaths were 31.4% of all deaths; half of those cancers were AIDS-defining.

Abstract Background The helicopter emergency services (HEMS) Benefit Score (HBS) is a nine-level scoring system developed to evaluate the benefits of HEMS missions. The HBS has been in clinical use for two decades in its original form. Advances in prehospital care, however, have produced demand for a revision of the HBS. Therefore, we developed the emergency medical services (EMS) Benefit Score (EBS) based on the former HBS. As reflected by its name, the aim of the EBS is to measure the benefits produced by the whole EMS systems to patients. Methods This is a four-round, web-based, international Delphi consensus study with a consensus definition made by experts from seven countries. Participants reviewed items of the revised HBS on a 5-point Likert scale. A content validity index (CVI) was calculated, and agreement was defined as a 70% CVI. Study included experts from seven European countries. Of these, 18 were prehospital expert panellists and 11 were in-hospital commentary board members. Results The first Delphi round resulted in 1248 intervention examples divided into ten diagnostic categories. After removing overlapping examples, 413 interventions were included in the second Delphi round, which resulted in 38 examples divided into HBS categories 3–8. In the third Delphi round, these resulted in 37 prehospital interventions, examples of which were given revised version of the score. In the fourth and final Delphi round, the expert panel was given an opportunity to accept or comment on the revised scoring system. Conclusions The former HBS was revised by a Delphi methodology and EBS developed to represent its structural purpose better. The EBS includes 37 exemplar prehospital interventions to guide its clinical use. Trial registration The study permission was requested and granted by Turku University Hospital (decision number TP2/010/18).

This study aimed to determine whether magnetic resonance imaging (MRI) white matter hyperintensities (WMHs) are associated with symptom reporting and/or cognitive performance in 1202 active-duty service members with prior single or multiple mild traumatic brain injury (mTBI). Patients with mTBI evaluated at the National Intrepid Center of Excellence (NICoE) at Walter Reed National Military Medical Center (WRNMMC) were divided into those with (n?=?632) and without (n?=?570) WMHs. The groups were compared on several self-report scales including the Neurobehavioral Symptom Inventory (NSI), Post-Traumatic Stress Disorder (PTSD) Checklist-Civilian Version (PCL-C), Satisfaction with Life Scale (SWLS), and Short Form-36 Health Survey (SF-36). They were also compared on several neuropsychological measures, including tests of attention, working memory, learning and memory, executive functioning, and psychomotor functioning. After correction for multiple comparisons, there were no significant differences between the two groups on any self-reported symptom scale or cognitive test. When comparing a subgroup with the highest (20+) WMH burden (n?=?60) with those with no WMHs (n?=?60; matched on age, education, sex, race, rank, and TBI number), only SF-36 Health Change significantly differed between the subgroups; the multiple WMH subgroup reported worsening health over the past year (t[53]?=?3.52, p?=?0.001, d?=?0.67) compared with the no WMH subgroup. These findings build on prior research suggesting total WMHs are not associated with significant changes in self-reported symptoms or cognitive performance in patients with a remote history of mTBI. As such, clinicians are encouraged to use caution when reporting such imaging findings.

Glial fibrillary acidic protein (GFAP) and ubiquitin carboxyl-terminal hydrolase L1 (UCH-L1) may aid in the evaluation of traumatic brain injury (TBI). The objective of this analysis was to compare GFAP and UCH-L1 values measured using a handheld device compared with a core laboratory platform. We analyzed plasma samples from patients with TBI and healthy controls enrolled in the Transforming Research and Clinical Knowledge in TBI (TRACK-TBI) cohort study. GFAP and UCH-L1 were measured twice in each subject using prototype assays, first with the Abbott i-STAT? handheld device, and second with the Abbott ARCHITECT? platform. We then quantified the agreement in biomarker values obtained using these two methods. GFAP and UCH-L1 were measured twice in 570 and 572 samples, respectively. GFAP values measured by the ARCHITECT platform (median 143.3 [interquartile range (IQR): 19.8?925.8] pg/mL) were higher than values measured by the i-STAT (median 116.0 [IQR: 9.2?856.5] pg/mL). GFAP values from the two platforms were strongly correlated (p?=?0.985). Similarly, UCH-L1 values measured by the ARCHITECT platform (median 163.9 [IQR: 82.5?412.4] pg/mL) were higher than values measured by the i-STAT (median 122.5 [IQR: 63.0?297.3] pg/mL). UCH-L1 values from the two platforms were strongly correlated (p?=?0.933). Passing-Bablok regression equations were developed to estimate the relationship between the two platforms, specifically to predict i-STAT values from the ARCHITECT platform. GFAP and UCH-L1 values measured using the prototype assays on the Abbott i-STAT and ARCHITECT platforms are strongly correlated and values from either platform may be converted to the other.

Youth and young adults who previously experienced foster care are prone to negative life events, such as physical injuries, and adverse childhood experiences (ACE), such as abuse, neglect, and household dysfunction. The purpose of the present study was to identify the prevalence of traumatic brain injury (TBI), ACE, and poor sustained attention and the associations of these events in this group of vulnerable persons. Participants completed standardized questionnaires on the prevalence of self-reported TBI (TBI) and ACE and performed the Sustained Attention to Response Task (SART) test to measure sustained attention. Chi-squared and Kruskal-Wallis rank-sum tests were used to assess demographic differences and associations between TBI and ACE. Sustained attention was assessed using analysis of variance and linear modeling. Seventy-one participants?46 youth and young adults who previously experienced foster care (vulnerable group) and 25 age-matched healthy controls?completed the standardized questionnaires. Analyses indicated that vulnerable participants reported markedly higher rates of TBI and ACE than healthy controls. Vulnerable persons with TBI reported significantly higher Total ACE scores (p?=?0.02), were more likely to have a history of family dysfunction (p?=?0.02), and were more likely to have lived with a mentally ill guardian (p?=?0.01) than vulnerable persons with no TBI. TBI was significantly associated with Total Errors (p?=?0.001 and p?=?0.02) and Omission Errors (p?0.001 and p?=?0.01) in all participants and in vulnerable participants, respectively, after adjusting for education level.

Polytrauma and traumatic brain injury (TBI) frequently co-occur and outcomes are routinely measured by the Glasgow Outcome Scale-Extended (GOSE). Polytrauma may confound GOSE measurement of TBI-specific outcomes. Adult patients with TBI from the prospective Transforming Research and Clinical Knowledge in Traumatic Brain Injury Pilot (TRACK-TBI Pilot) study had presented to a Level 1 trauma center after injury, received head computed tomography (CT) within 24?h, and completed the GOSE at 3 months and 6 months post-injury. Polytrauma was defined as an Abbreviated Injury Score (AIS) ?3 in any extracranial region. Univariate regressions were performed using known GOSE clinical cutoffs. Multi-variable regressions were performed for the 3- and 6-month GOSE, controlling for known demographic and injury predictors. Of 361 subjects (age 44.9???18.9 years, 69.8% male), 69 (19.1%) suffered polytrauma. By Glasgow Coma Scale (GCS) assessment, 80.1% had mild, 5.8% moderate, and 14.1% severe TBI. On univariate logistic regression, polytrauma was associated with increased odds of moderate disability or worse (GOSE ?6; 3 month odds ratio [OR]?=?2.57 [95% confidence interval (CI): 1.50-4.41; 6 month OR?=?1.70 [95% CI: 1.01-2.88]) and death/severe disability (GOSE ?4; 3 month OR?=?3.80 [95% CI: 2.03-7.11]; 6 month OR?=?3.33 [95% CI: 1.71-6.46]). Compared with patients with isolated TBI, more polytrauma patients experienced a decline in GOSE from 3 to 6 months (37.7 vs. 24.7%), and fewer improved (11.6 vs. 22.6%). Polytrauma was associated with greater univariate ordinal odds for poorer GOSE (3 month OR?=?2.79 [95% CI: 1.73-4.49]; 6 month OR?=?1.73 [95% CI: 1.07-2.79]), which was conserved on multi-variable ordinal regression (3 month OR?=?3.05 [95% CI: 1.76-5.26]; 6 month OR?=?2.04 [95% CI: 1.18-3.42]). Patients with TBI with polytrauma are at greater risk for 3- and 6-month disability compared with those with isolated TBI. Methodological improvements in assessing TBI-specific disability, versus disability attributable to all systemic injuries, will generate better TBI outcomes assessment tools.

Abstract Background Exposure to hypothermia is somehow unavoidable when a baby comes to life. This is the reason why any possible effort should be made by every caregiver involved during birth, from labour to transfer into the maternity ward, to reduce it. Hypothermia has widely shown to be related to several neonatal problems, and the risks are more relevant when the babies are born prematurely. Method An observational study was conducted in April 2016 to assess the current practises to avoid hypothermia at birth in 20 Italian neonatal units. Each unit introduced local improvements in clinical practice and the same observational study was repeated 1 year later. Results A total of 4722 babies were analysed. An overall increase in adherence to local and international recommendations emerged from our study. Significant differences between 2016 and 2017 were found in regard to neonatal temperature at nursery entry (36.3 °C vs 36.5 °C, respectively, p 60″ (48.1% vs 68.1%, respectively, p 60′ (56.3% vs 60.9, respectively, p = 0.03). Statistical correlations with the risk of hypothermia were found for delivery room (OR 0.88 (CI 95%0.83–0.94), p

BackgroundCountdown to 2015 was a multi-institution consortium tracking progress towards Millennium Development Goals (MDGs) 4 and 5. Case studies to explore factors contributing to progress (or lack of progress) in reproductive, maternal, newborn and child health (RMNCH) were undertaken in: Afghanistan, Bangladesh, China, Ethiopia, Kenya, Malawi, Niger, Pakistan, Peru, and Tanzania. This paper aims to identify cross-cutting themes on how and why these countries achieved or did not achieve MDG progress.MethodsApplying a standard evaluation framework, analyses of impact, coverage and equity were undertaken, including a mixed methods analysis of how these were influenced by national context and coverage determinants (including health systems, policies and financing).ResultsThe majority (7/10) of case study countries met MDG-4 with over two-thirds reduction in child mortality, but none met MDG-5a for 75 % reduction in maternal mortality, although six countries achieved >75 % of this target. None achieved MDG-5b regarding reproductive health. Rates of reduction in neonatal mortality were half or less that for post-neonatal child mortality. Coverage increased most for interventions administered at lower levels of the health system (e.g., immunisation, insecticide treated nets), and these experienced substantial political and financial support. These interventions were associated with ~30-40 % of child lives saved in 2012 compared to 2000, in Ethiopia, Malawi, Peru and Tanzania. Intrapartum care for mothers and newborns -- which require higher-level health workers, more infrastructure, and increased community engagement -- showed variable increases in coverage, and persistent equity gaps. Countries have explored different approaches to address these problems, including shifting interventions to the community setting and tasks to lower-level health workers.ConclusionsThese Countdown case studies underline the importance of consistent national investment and global attention for achieving improvements in RMNCH. Interventions with major global investments achieved higher levels of coverage, reduced equity gaps and improvements in associated health outcomes. Given many competing priorities for the Sustainable Development Goals era, it is essential to maintain attention to the unfinished RMNCH agenda, particularly health systems improvements for maternal and neonatal outcomes where progress has been slower, and to invest in data collection for monitoring progress and for rigorous analyses of how progress is achieved in different contexts.

Abstract Background Non-specific neck pain and headache are major economic and individual burden in office-workers. The aim of this study is to investigate the effect of a multi-component intervention combining workstation ergonomics, health promotion information group workshops, neck exercises, and an app to enhance intervention adherence to assess possible reductions in the economic and individual burden of prevalent and incident neck pain and headache in office workers. Methods/design This study is a stepped wedge cluster-randomized controlled trial. Eligible participants will be any office-worker aged 18–65 years from two Swiss organisations in the Cantons of Zurich and Aargau, working more than 25 h a week in predominantly sedentary office work and without serious health conditions of the neck. One hundred twenty voluntary participants will be assigned to 15 clusters which, at randomly selected time steps, switch from the control to the intervention group. The intervention will last 12 weeks and comprises workstation ergonomics, health promotion information group workshops, neck exercises and an adherence app. The primary outcome will be health-related productivity losses (presenteeism, absenteeism) using the Work Productivity and Activity Impairment Questionnaire. Secondary outcomes are neck disability and pain (measured by the Neck Disability Index, and muscle strength and endurance measures), headache (measured by the short-form headache impact test), psychosocial outcomes (e.g. job-stress index, Fear-Avoidance Beliefs Questionnaire), workplace outcomes (e.g. workstation ergonomics), adherence to intervention, and additional measures (e.g. care-seeking). Measurements will take place at baseline, 4 months, 8 months, and 12 months after commencement. Data will be analysed on an intention to treat basis and per protocol. Primary and secondary outcomes will be examined using linear mixed-effects models. Discussion To the authors’ knowledge, this study is the first that investigates the impact of a multi-component intervention combining current evidence of effective interventions with an adherence app to assess the potential benefits on productivity, prevalent and incident neck pain, and headache. The outcomes will impact the individual, their workplace, as well as private and public policy by offering evidence for treatment and prevention of neck pain and headache in office-workers. Trial registration ClinicalTrials.gov, NCT04169646 . Registered 15 November 2019 - Retrospectively registered.

Abstract Background Eating disorders are serious conditions which are increasing in prevalence internationally. The causes of these conditions are complex and incompletely understood, and clinical presentations can vary over time. The complexity of these conditions can also complicate treatment. Therefore, stepped care treatment comprising a hierarchy of interventions, including access to day treatment programs (DTPs), is recommended. While studies have examined patient outcomes and provided narrative accounts of these programs, no published studies describe DTP development. This study aims to address this gap by examining development and implementation of a DTP from service providers and patients’ perspectives. Methods This study utilised a mixed-methods design to examine the design and implementation of a publicly funded, closed group DTP in Australia. Data from service records and documents were analysed, alongside interviews with patients and interview and focus groups with service providers conducted between June 2016 and July 2017. Quantitative data were analysed using descriptive statistics. Qualitative data were analysed using the Framework Approach. Results Seventeen service providers (n = 4 in managerial and n = 13 clinical positions, with clinical experience of 3 months to 20 years) and 11 patients (100% F, 17-33 years) were interviewed. The service providers reported that implementation was a stressful undertaking due to tight timeframes to achieve multiple tasks. Patients had diverse opinions regarding the DTP content and the group treatment experience. Despite this, all patients reported benefits from attending the DTP, varying from improvements in mood, weight gain, development of personal skills and strengths, to living independently. For further benefit, patients suggested that programs could be shaped and targets towards differing patient groups, with fewer breaks throughout treatment. Conclusions Designing and implementing a DTP is a challenge and can be a time-intensive undertaking, however the result can be beneficial for both service providers and patients. The closed group format was beneficial in creating a supportive environment, though may have led to increases in additional eating disordered behaviours. While the current structure of this DTP may require reconsideration, organisations considering implementing a new DTP may find usefulness in the overall design described in this study, alongside learning from the issues experienced.

Introduction Congenital heart defects (CHD) are one of the most commonly diagnosed congenital malformations in fetuses and newborns. The aim of the study was to determine whether inter-pregnancy interval (IPI), maternal age or number of pregnancies had any influence on the recurrence of congenital heart disease in subsequent pregnancies. Material and methods We found in our database 144 women with subsequent pregnancies after CHD in a previous pregnancy. Each woman was selected according to the eligibility and exclusion criteria. Medical history as well as obstetrics history were recorded. Comparisons of groups with and without a recurrence of CHD were performed. We calculated hazard ratios for recurrence of CHD. We also performed analysis of the impact of confounding variables: maternal age and parity. Missing data were excluded from the analysis. Smoking habits as well as socio-demographic characteristics were not evaluated in this study. Results A higher risk of recurrence of CHD correlated with a shorter IPI, with a median of 11 months compared with 24 months for the group of healthy fetuses in subsequent pregnancy. The results were statistically significant. Parity was proven to be an important confounder of the study. Multivariable analysis including parity and maternal age did not affect the confidence intervals of hazard ratios for IPI. Conclusions The optimal IPI to reduce the risk of recurrence of CHD is 24 months. Shorter intervals are related to a higher risk of recurrence of CHD in the next pregnancy and are independent on the age of the woman and parity.

Abstract Background Perioperative anaemia leads to impaired oxygen supply with a risk of vital organ ischaemia. In healthy and fit individuals, anaemia can be compensated by several mechanisms. Elderly patients, however, have less compensatory mechanisms because of multiple co-morbidities and age-related decline of functional reserves. The purpose of the study is to evaluate whether elderly surgical patients may benefit from a liberal red blood cell (RBC) transfusion strategy compared to a restrictive transfusion strategy. Methods The LIBERAL Trial is a prospective, randomized, multicentre, controlled clinical phase IV trial randomising 2470 elderly (≥ 70 years) patients undergoing intermediate- or high-risk non-cardiac surgery. Registered patients will be randomised only if Haemoglobin (Hb) reaches ≤9 g/dl during surgery or within 3 days after surgery either to the LIBERAL group (transfusion of a single RBC unit when Hb ≤ 9 g/dl with a target range for the post-transfusion Hb level of 9–10.5 g/dl) or the RESTRICTIVE group (transfusion of a single RBC unit when Hb ≤ 7.5 g/dl with a target range for the post-transfusion Hb level of 7.5–9 g/dl). The intervention per patient will be followed until hospital discharge or up to 30 days after surgery, whichever occurs first. The primary efficacy outcome is defined as a composite of all-cause mortality, acute myocardial infarction, acute ischaemic stroke, acute kidney injury (stage III), acute mesenteric ischaemia and acute peripheral vascular ischaemia within 90 days after surgery. Infections requiring iv antibiotics with re-hospitalisation are assessed as important secondary endpoint. The primary endpoint will be analysed by logistic regression adjusting for age, cancer surgery (y/n), type of surgery (intermediate- or high-risk), and incorporating centres as random effect. Discussion The LIBERAL-Trial will evaluate whether a liberal transfusion strategy reduces the occurrence of major adverse events after non-cardiac surgery in the geriatric population compared to a restrictive strategy within 90 days after surgery. Trial registration ClinicalTrials.gov (identifier: NCT03369210).

Abstract Background Despite the positive outcomes of the use of noninvasive positive pressure ventilation (NPPV) in patients with acute exacerbation of chronic obstructive pulmonary disease (AECOPD), NPPV fails in approximately 15% of patients with AECOPD, possibly because the inspiratory pressure delivered by conventional low-intensity NPPV is insufficient to improve ventilatory status for these patients. High-intensity NPPV, a novel form that delivers high inspiratory pressure, is believed to more efficiently augment alveolar ventilation than low-intensity NPPV, and it has been shown to improve ventilatory status more than low-intensity NPPV in stable AECOPD patients. Whether the application of high-intensity NPPV has therapeutic advantages over low-intensity NPPV in patients with AECOPD remains to be determined. The high-intensity versus low-intensity NPPV in patients with AECOPD (HAPPEN) study will examine whether high-intensity NPPV is more effective for correcting hypercapnia than low-intensity NPPV, hence reducing the need for intubation and improving survival. Methods/design The HAPPEN study is a multicenter, two-arm, single-blind, prospective, randomized controlled trial. In total, 600 AECOPD patients with low to moderate hypercapnic respiratory failure will be included and randomized to receive high-intensity or low-intensity NPPV, with randomization stratified by study center. The primary endpoint is NPPV failure rate, defined as the need for endotracheal intubation and invasive ventilation. Secondary endpoints include the decrement of arterial carbon dioxide tension from baseline to 2 h after randomization, in-hospital and 28-day mortality, and 90-day survival. Patients will be followed up for 90 days after randomization. Discussion The HAPPEN study will be the first randomized controlled study to investigate whether high-intensity NPPV better corrects hypercapnia and reduces the need for intubation and mortality in AECOPD patients than low-intensity NPPV. The results will help critical care physicians decide the intensity of NPPV delivery to patients with AECOPD. Trial registration ClinicalTrials.gov, NCT02985918. Registered on 7 December 2016.

Abstract Background Obstetric haemorrhage, sepsis and pregnancy hypertension account for more than 50% of maternal deaths worldwide. Early detection and effective management of these conditions relies on vital signs. The Microlife® CRADLE Vital Sign Alert (VSA) is an easy-to-use, accurate device that measures blood pressure and pulse. It incorporates a traffic-light early warning system that alerts all levels of healthcare provider to the need for escalation of care in women with obstetric haemorrhage, sepsis or pregnancy hypertension, thereby aiding early recognition of haemodynamic instability and preventing maternal mortality and morbidity. The aim of the trial was to determine whether implementation of the CRADLE intervention (the Microlife® CRADLE VSA device and CRADLE training package) into routine maternity care in place of existing equipment will reduce a composite outcome of maternal mortality and morbidity in low- and middle-income country populations. Methods The CRADLE-3 trial was a stepped-wedge cluster-randomised controlled trial of the CRADLE intervention compared to routine maternity care. Each cluster crossed from routine maternity care to the intervention at 2-monthly intervals over the course of 20 months (April 2016 to November 2017). All women identified as pregnant or within 6 weeks postpartum, presenting for maternity care in cluster catchment areas were eligible to participate. Primary outcome data (composite of maternal death, eclampsia and emergency hysterectomy per 10,000 deliveries) were collected at 10 clusters (Gokak, Belgaum, India; Harare, Zimbabwe; Ndola, Zambia; Lusaka, Zambia; Free Town, Sierra Leone; Mbale, Uganda; Kampala, Uganda; Cap Haitien, Haiti; South West, Malawi; Addis Ababa, Ethiopia). This trial was informed by the Medical Research Council guidance for complex interventions. A process evaluation was undertaken to evaluate implementation in each site and a cost-effectiveness evaluation will be undertaken. Discussion All aspects of this protocol have been evaluated in a feasibility study, with subsequent optimisation of the intervention. This trial will demonstrate the potential impact of the CRADLE intervention on reducing maternal mortality and morbidity in low-resource settings. It is anticipated that the relatively low cost of the intervention and ease of integration into existing health systems will be of significant interest to local, national and international health policy-makers. Trial registration ISCRTN41244132. Registered on 2 February 2016. Prospective protocol modifications have been recorded and were communicated to the Ethics Committees and Trials Committees. The adapted Standard Protocol Items: Recommendations for Interventional Trials (SPIRIT) Checklist and the SPIRIT Checklist are attached as Additional file 1.

Background: Currently, evidence about the long-term consequences of COVID-19 on return to work and health-related quality of life (HRQoL) is limited. We evaluated return to work and its associations with baseline characteristics and physical and mental recovery over time in patients up to 1 year after hospitalization for COVID-19. Secondly, we aimed to evaluate the association between return to work and health-related quality of life (HRQoL). Methods: CO-FLOW, a multicenter prospective cohort study, enrolled adult participants hospitalized for COVID-19, aged ≥ 18 years within 6 months after hospital discharge. Return to work and HRQoL were collected at 3, 6, and 12 months after hospital discharge using the iMTA Productivity Cost Questionnaire and the 36-Item Short Form Health Survey, respectively. Data were collected between July 1, 2020, and September 1, 2022. Generalized estimating equations with repeated measurements were used to assess outcomes over time. Results: In the CO-FLOW study, 371 participants were employed pre-hospitalization. At 3, 6, and 12 months post-discharge, 50% (170/342), 29% (92/317), and 15% (44/295) of participants had not returned to work, and 21% (71/342), 21% (65/317), and 16% (48/295) only partially, respectively. ICU admission (adjusted odds ratio (95% confidence interval): 0.17 (0.10 to 0.30), p < 0.001), persistent fatigue (0.93 (0.90 to 0.97), p < 0.001), female sex (0.57 (0.36 to 0.90), p = 0.017), and older age (0.96 (0.93 to 0.98), p < 0.001) were independently associated with no return to work. ICU patients required a longer time to return to work than non-ICU patients. Patients who did not return or partially returned to work reported lower scores on all domains of HRQoL than those who fully returned. Conclusions: One year after hospitalization for COVID-19, only 69% of patients fully returned to work, whereas 15% did not return and 16% partially returned to work. No or partial return to work was associated with reduced HRQoL. This study suggests that long-term vocational support might be needed to facilitate return to work. Trial registration: World Health Organization International Clinical Trials Registry Platform NL8710. [ABSTRACT FROM AUTHOR]

Abstract Background Countdown to 2015 was a multi-institution consortium tracking progress towards Millennium Development Goals (MDGs) 4 and 5. Case studies to explore factors contributing to progress (or lack of progress) in reproductive, maternal, newborn and child health (RMNCH) were undertaken in: Afghanistan, Bangladesh, China, Ethiopia, Kenya, Malawi, Niger, Pakistan, Peru, and Tanzania. This paper aims to identify cross-cutting themes on how and why these countries achieved or did not achieve MDG progress. Methods Applying a standard evaluation framework, analyses of impact, coverage and equity were undertaken, including a mixed methods analysis of how these were influenced by national context and coverage determinants (including health systems, policies and financing). Results The majority (7/10) of case study countries met MDG-4 with over two-thirds reduction in child mortality, but none met MDG-5a for 75 % reduction in maternal mortality, although six countries achieved >75 % of this target. None achieved MDG-5b regarding reproductive health. Rates of reduction in neonatal mortality were half or less that for post-neonatal child mortality. Coverage increased most for interventions administered at lower levels of the health system (e.g., immunisation, insecticide treated nets), and these experienced substantial political and financial support. These interventions were associated with ~30–40 % of child lives saved in 2012 compared to 2000, in Ethiopia, Malawi, Peru and Tanzania. Intrapartum care for mothers and newborns -- which require higher-level health workers, more infrastructure, and increased community engagement -- showed variable increases in coverage, and persistent equity gaps. Countries have explored different approaches to address these problems, including shifting interventions to the community setting and tasks to lower-level health workers. Conclusions These Countdown case studies underline the importance of consistent national investment and global attention for achieving improvements in RMNCH. Interventions with major global investments achieved higher levels of coverage, reduced equity gaps and improvements in associated health outcomes. Given many competing priorities for the Sustainable Development Goals era, it is essential to maintain attention to the unfinished RMNCH agenda, particularly health systems improvements for maternal and neonatal outcomes where progress has been slower, and to invest in data collection for monitoring progress and for rigorous analyses of how progress is achieved in different contexts.

An amendment to this paper has been published and can be accessed via the original article.