Family Presence at the PICU Bedside: A Single-Center Retrospective Cohort Study.

OBJECTIVES: To determine factors associated with bedside family presence in the PICU and to understand how individual factors interact as barriers to family presence. DESIGN: Mixed methods study. SETTING: Tertiary children's hospital PICU. SUBJECTS: Five hundred twenty-three children of less than 18 years enrolled in the Seattle Children's Hospital Outcomes Assessment Program from 2011 to 2017. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Quantitative: Family was documented every 2 hours. Exposures included patient and illness characteristics and family demographic and socioeconomic characteristics. We used multivariable logistic regression to identify factors associated with presence of less than 80% and stratified results by self-reported race. Longer PICU length of stay (LOS), public insurance, and complex chronic conditions (C-CD) were associated with family presence of less than 80%. Self-reported race modified these associations; no factors were associated with lower bedside presence for White families, in contrast with multiple associations for non-White families including public insurance, C-CD, and longer LOS. Qualitative: Thematic analysis of social work notes for the 48 patients with family presence of less than 80% matched on age, LOS, and diagnosis to 48 patients with greater than or equal to 95% family presence. Three themes emerged: the primary caregiver's prior experiences with the hospital, relationships outside of the hospital, and additional stressors during the hospitalization affected bedside presence. CONCLUSIONS: We identified sociodemographic and illness factors associated with family bedside presence in the PICU. Self-reported race modified these associations, representing racism within healthcare. Family presence at the bedside may help identify families facing greater disparities in healthcare access.

Epidemiology of Intensive Care Admissions for Children in the US From 2001 to 2019.

Importance: Estimates of the number of US children receiving intensive care unit (ICU) care and ICU admission patterns over time are lacking. Objective: To determine how ICU admission patterns, use of critical care services, and the characteristics and outcomes of critically ill children have changed from 2001 to 2019. Design, Setting, and Participants: This population-based retrospective cohort study used data from the Healthcare Cost and Utilization Project's state inpatient databases from a total of 21 US states in 2001, 2004, 2010, 2016, and 2019. Hospitalized children aged 0 to 17 years, excluding newborns (during birth hospitalization), were included. Patients admitted to rehabilitation institutions or psychiatric hospitals were also excluded. Data were analyzed from July 2021 to December 2022. Exposures: Care in a nonneonatal ICU. Main Outcomes and Measures: From extracted patient data, International Classification of Diseases, Ninth Revision, Clinical Modification, and Tenth Revision, Clinical Modification, codes were used to identify diagnoses, comorbid conditions, organ failures, and mechanical ventilation. Generalized linear Poisson regression and the Cuzick test were used to evaluate trends. US Census data were used to generate age- and sex-adjusted national estimates of ICU admissions and costs. Results: Of 2 157 991 pediatric admissions, 275 656 (12.8%) included ICU care. The mean (SD) age was 6.43 (6.10) years; 121 894 individuals were female (44.2%), and 153 731 were male (55.8%). From 2001 to 2019, the prevalence of ICU care among hospitalized children increased from 10.6% to 15.5%. The percentage of ICU admissions in children's hospitals rose from 51.2% to 85.1% (relative risk [RR], 1.66; 95% CI, 1.64-1.68). The percentage of children admitted to an ICU with an underlying comorbidity increased from 46.2% to 57.0% (RR, 1.23; 95% CI, 1.22-1.25), and the percentage with preadmission technology dependence increased from 16.4% to 23.5% (RR, 1.44; 95% CI, 1.40-1.48). The prevalence of multiple organ dysfunction syndrome increased from 6.8% to 21.0% (RR, 3.12; 95% CI, 2.98-3.26), while mortality decreased from 2.5% to 1.8% (RR, 0.72; 95% CI, 0.66-0.79). Hospital length of stay increased by 0.96 days (95% CI, 0.73-1.18) for ICU admissions from 2001 to 2019. After inflation adjustment, total costs for a pediatric admission involving ICU care nearly doubled between 2001 and 2019. Nationally, an estimated 239 000 children were admitted to a US ICU in 2019, corresponding to $11.6 billion in hospital costs. Conclusions and Relevance: In this study, the prevalence of children receiving ICU care in the US increased, as did length of stay, technology use, and associated costs. The US health care system must be equipped to care for these children in the future.

Association of Socioeconomic Status With Postdischarge Pediatric Resource Use and Quality of Life.

OBJECTIVES: Socioeconomic factors may impact healthcare resource use and health-related quality of life, but their association with postcritical illness outcomes is unknown. This study examines the associations between socioeconomic status, resource use, and health-related quality of life in a cohort of children recovering from acute respiratory failure. DESIGN: Secondary analysis of data from the Randomized Evaluation of Sedation Titration for Respiratory Failure clinical trial. SETTING: Thirty-one PICUs. PATIENTS: Children with acute respiratory failure enrolled whose parent/guardians consented for follow-up. MEASUREMENTS AND MAIN RESULTS: Resource use included in-home care, number of healthcare providers, prescribed medications, home medical equipment, emergency department visits, and hospital readmission. Socioeconomic status was estimated by matching residential address to census tract-based median income. Health-related quality of life was measured using age-based parent-report instruments. Resource use interviews with matched census tract data (n = 958) and health-related quality of life questionnaires (n = 750/958) were assessed. Compared with high-income children, low-income children received care from fewer types of healthcare providers (ß = -0.4; p = 0.004), used less newly prescribed medical equipment (odds ratio = 0.4; p < 0.001), and had more emergency department visits (43% vs 33%; p = 0.04). In the youngest cohort (< 2 yr old), low-income children had lower quality of life scores from physical ability (-8.6 points; p = 0.01) and bodily pain/discomfort (+8.2 points; p < 0.05). In addition, health-related quality of life was lower in those who had more healthcare providers and prescribed medications. In older children, health-related quality of life was lower if they had prescribed medications, emergency department visits, or hospital readmission. CONCLUSIONS: Children recovering from acute respiratory failure have ongoing healthcare resource use. Yet, lower income children use less in-home and outpatient services and use more hospital resources. Continued follow-up care, especially in lower income children, may help identify those in need of ongoing healthcare resources and those at-risk for decreased health-related quality of life.

Food for all: designing sustainable and secure future seafood systems.

Food from the sea can make a larger contribution to healthy and sustainable diets, and to addressing hunger and malnutrition, through improvements in production, distribution and equitable access to wild harvest and mariculture resources and products. The supply and consumption of seafood is influenced by a range of 'drivers' including ecosystem change and ocean regulation, the influence of corporations and evolving consumer demand, as well as the growing focus on the importance of seafood for meeting nutritional needs. These drivers need to be examined in a holistic way to develop an informed understanding of the needs, potential impacts and solutions that align seafood production and consumption with relevant 2030 Sustainable Development Goals (SDGs). This paper uses an evidence-based narrative approach to examine how the anticipated global trends for seafood might be experienced by people in different social, geographical and economic situations over the next ten years. Key drivers influencing seafood within the global food system are identified and used to construct a future scenario based on our current trajectory (Business-as-usual 2030). Descriptive pathways and actions are then presented for a more sustainable future scenario that strives towards achieving the SDGs as far as technically possible (More sustainable 2030). Prioritising actions that not only sustainably produce more seafood, but consider aspects of access and utilisation, particularly for people affected by food insecurity and malnutrition, is an essential part of designing sustainable and secure future seafood systems. Supplementary Information: The online version contains supplementary material available at 10.1007/s11160-021-09663-x.

Correlation of integrated ERG/PTEN assessment with biochemical recurrence in prostate cancer.

INTRODUCTION: Prostate cancer is a heterogeneous disease, with a complex molecular landscape that evolves throughout disease progression. Common alterations in genes such as ERG and PTEN have been attributed to worse prognosis. This study aimed to further examine the clinical relevance of PTEN and ERG expression in a cohort of patients with prostate cancer post radical prostatectomy. METHODS: Tissue microarrays were constructed from 132 patients with prostate cancer from the Irish Prostate Cancer Research Consortium and University Hospital of Orebro, Sweden. Patients were divided into three groups - Group 1: biochemical recurrence, Group 2: no biochemical recurrence and Group 3: immediate progression after surgery. PTEN and ERG immunohistochemical analysis was performed and the association between expression levels and clinical parameters were compared. RESULTS: Pathological stage pT3 tumours were more common at borderline significantly higher levels amongst patients who biochemically recurred when compared to patients who did not recur after radical prostatectomy (p = 0.05). ERG and PTEN expression levels were compared separately and concurrently across all three patient groups. Lack of ERG expression was strongly associated with immediate progression after surgery (p = 0.029). Loss of/low PTEN trended towards an association with immediate progression, however this was not statistically significant (p = 0.066). CONCLUSION: In this study, negative ERG expression was strongly associated with immediate biochemical progression after radical prostatectomy. Moreover, a trend towards a relationship between aberrant PTEN expression and progression was observed. Additional studies with long-term follow up data may provide further clinical insight into the genomic heterogeneity in this population.

An exploratory assessment of serum biomarkers of post-cardiac arrest syndrome in children.

AIM: We hypothesized that serum biomarkers of inflammation including chemokine, cytokine, pituitary hormones, and growth factors following cardiac arrest in children would independently associate with 6-month neurologic outcome. METHODS: In this prospective observational single center study of children with in-hospital and out-of-hospital cardiac arrest surviving to intensive care unit admission, serum was obtained twice per 24 h period between 0 h and 96 h and once at approximately 196 h post-cardiac arrest. Inflammatory mediators, hormones, and growth factors were analyzed by Luminex Multiplex Bead Immunoassay. We recorded demographics, resuscitation characteristics, and Pediatric Cerebral Performance Category (PCPC) at 6 months. We analyzed the association and area under the curve (AUC) of biomarker levels with favorable (PCPC 1-3) or unfavorable (PCPC 4-6, or >1 increase from baseline) outcome. RESULTS: Forty-two children (50% female; median age of 2.5 [IQR: 0.4-10.2]) were enrolled and 18 (42%) died prior to 6-month follow up. Receiver operator curves for initial levels of ciliary neurotrophic factor (CNTF, AUC 0.84, 95% CI 0.73-0.96, p < 0.001) and interleukin (IL-17, AUC 0.84, 95% CI 0.73-0.97, p < 0.001) best classified favorable versus unfavorable 6-month outcome. In multivariable analysis, initial levels of CNTF and IL-17 remained associated with 6-month PCPC. Peak levels of interferon-γ-inducible protein 10 (IP-10), CNTF, and hepatocyte growth factor (HGF) were also independently associated with outcome. CONCLUSION: Increased serum concentrations of CNTF and IL-17 associated with unfavorable 6-month neurologic outcome of children surviving cardiac arrest. Further investigation of the prognostic utility and roles of CNTF and IL-17 in the pathophysiology of post-cardiac arrest syndrome are warranted. This project is registered with clinicaltrials.gov (NCT00797680) as "Duration of Hypothermia for Neuroprotection after Pediatric Cardiac Arrest: A Randomized, Controlled Trial".

Psychosocial burden and out-of-pocket costs in patients with atopic dermatitis in Ireland.

Atopic dermatitis (AD) is one of the most common inflammatory skin diseases in the developed world, affecting 1-3% of the adult population in Europe. This inflammatory disease can have a marked impact on affected individuals, leading to significant impairment in physical wellbeing and quality of life (QoL). The aim of this study was to investigate the psychosocial impact and financial burden of AD on patients in Ireland. To increase our understanding of the psychosocial and financial aspects of AD disease burden in the Irish population, an online survey was designed. The survey was launched by the Irish Skin Foundation, and included questions focusing on disease severity, disease control, psychosocial impact, interrupted sleep, missed work and school days, and financial cost. The survey showed that the impact of AD on QoL was profound. The survey demonstrated that 85% of adults described interrupted sleep, 70% reported social anxiety, 65% avoid exercise and sports, 52% avoid social activities, 52% avoid sexual intimacy and 43% feel they are depressed as a result of their AD. Approximately one-quarter of those surveyed can spend up to €2300 annually on over-the-counter, prescription and alternative treatments. This study has shown the significant impact AD has on patients living in Ireland. It also highlights that out-of-pocket costs for patients is higher compared with previous studies across European countries.

Global, regional, and national sepsis incidence and mortality, 1990-2017: analysis for the Global Burden of Disease Study.

BACKGROUND: Sepsis is life-threatening organ dysfunction due to a dysregulated host response to infection. It is considered a major cause of health loss, but data for the global burden of sepsis are limited. As a syndrome caused by underlying infection, sepsis is not part of standard Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) estimates. Accurate estimates are important to inform and monitor health policy interventions, allocation of resources, and clinical treatment initiatives. We estimated the global, regional, and national incidence of sepsis and mortality from this disorder using data from GBD 2017. METHODS: We used multiple cause-of-death data from 109 million individual death records to calculate mortality related to sepsis among each of the 282 underlying causes of death in GBD 2017. The percentage of sepsis-related deaths by underlying GBD cause in each location worldwide was modelled using mixed-effects linear regression. Sepsis-related mortality for each age group, sex, location, GBD cause, and year (1990-2017) was estimated by applying modelled cause-specific fractions to GBD 2017 cause-of-death estimates. We used data for 8·7 million individual hospital records to calculate in-hospital sepsis-associated case-fatality, stratified by underlying GBD cause. In-hospital sepsis-associated case-fatality was modelled for each location using linear regression, and sepsis incidence was estimated by applying modelled case-fatality to sepsis-related mortality estimates. FINDINGS: In 2017, an estimated 48·9 million (95% uncertainty interval [UI] 38·9-62·9) incident cases of sepsis were recorded worldwide and 11·0 million (10·1-12·0) sepsis-related deaths were reported, representing 19·7% (18·2-21·4) of all global deaths. Age-standardised sepsis incidence fell by 37·0% (95% UI 11·8-54·5) and mortality decreased by 52·8% (47·7-57·5) from 1990 to 2017. Sepsis incidence and mortality varied substantially across regions, with the highest burden in sub-Saharan Africa, Oceania, south Asia, east Asia, and southeast Asia. INTERPRETATION: Despite declining age-standardised incidence and mortality, sepsis remains a major cause of health loss worldwide and has an especially high health-related burden in sub-Saharan Africa. FUNDING: The Bill & Melinda Gates Foundation, the National Institutes of Health, the University of Pittsburgh, the British Columbia Children's Hospital Foundation, the Wellcome Trust, and the Fleming Fund.

PICU-Based Rehabilitation and Outcomes Assessment: A Survey of Pediatric Critical Care Physicians.

OBJECTIVES: Characterize current practices for PICU-based rehabilitation, and physician perceptions and attitudes, barriers, resources, and outcome assessment in contemporary PICU settings. DESIGN: International, self-administered, quantitative, cross-sectional survey. SETTING: Online survey distributed from March 2017 to April 2017. PATIENTS OR SUBJECTS: Pediatric critical care physicians who subscribed to email distribution lists of the Pediatric Acute Lung Injury and Sepsis Investigators, the Pediatric Neurocritical Care Research Group, or the Prevalence of Acute Critical Neurological Disease in Children: A Global Epidemiological Assessment study group, and visitors to the World Federation of Pediatric Intensive and Critical Care Societies website. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Of the 170 subjects who began the survey, 148 completed it. Of those who completed the optional respondent information, most reported working in an academic medical setting and were located in the United States. The main findings were 1) a large majority of PICU physicians reported working in institutions with no guidelines for PICU-based rehabilitation, but expressed interest in developing and implementing such guidelines; 2) despite this lack of guidelines, an overwhelming majority of respondents reported that their current practices would involve consultation of multiple rehabilitation services for each case example provided; 3) PICU physicians believed that additional research evidence is needed to determine efficacy and optimal implementation of PICU-based rehabilitation; 4) PICU physicians reported significant barriers to implementation of PICU-based rehabilitation across centers; and 5) low routine assessment of long-term functional outcomes of PICU patients, although some centers have developed multidisciplinary follow-up programs. CONCLUSIONS: Physicians lack PICU-based rehabilitation guidelines despite great interest and current practices involving a high degree of PICU-based rehabilitation consultation. Data are needed to identify best practices and necessary resources in the delivery of ICU-based multidisciplinary rehabilitation and long-term functional outcomes assessment to optimize recovery of children and families affected by critical illness.

The educational preparation of nurses in a developing economy and patient mortality.

BACKGROUND: Most studies have reported that higher levels (baccalaureate degree) of educational attainment by nurses are associated with lower levels of patient mortality. Researchers working in developed economies (e.g. North America and Europe) have almost exclusively conducted these studies. The value of baccalaureate nurse education has not been tested in countries with a developing economy. METHOD: A retrospective observational study conducted in seven hospitals. Patient mortality was the main outcome of interest. Anonymized data were extracted from nurses and patients from two different administrative sources and linked using the staff identification number that exists in both systems. We used bivariate logistic regression models to test the association between mortality and the educational attainment of the admitting nurse (responsible for assessment and care planning). RESULTS: Data were extracted for 11 918 (12, 830 admissions) patients and 7415 nurses over the first 6 months of 2015. The majority of nurses were educated in South Asia and just over half were educated to at least bachelor degree level. After adjusting for confounding and clustering, nurse education was not found to be associated with mortality. IMPLICATIONS FOR NURSING AND HEALTH POLICY: Our observations may suggest that in a developing economy, the academic level of nurses' education is not associated with a reduction in patient mortality. Findings should be interpreted with considerable caution but do challenge widely held assumptions about the value of baccalaureate-prepared nurses. Further research focused on nursing education in developing economies is required to inform health policy and planning.

A photonumeric scale for the assessment of atrophic facial photodamage.

BACKGROUND: Photonumeric scales have consistently shown superiority over descriptive equivalents. They have the advantage of providing a consistent visual frame of reference by minimizing variability in perception and subjectivity. A photonumeric scale to assess hypertrophic facial photodamage already exists. However, there is currently no objective measure for atrophic facial photodamage. To address this, we have devised a nine-point photonumeric standardized scale. OBJECTIVES: To design, test and validate a photonumeric scale for the assessment of atrophic facial photodamage against a descriptive scale for the same indication. METHODS: A pool of 393 facial photographs (en face and 45° oblique) from 131 individuals with atrophic facial photodamage was created. Five photographic standards were selected and assigned grades zero through to eight, where zero is no photodamage and eight is severe atrophic photodamage, thus making a nine-point scale. Twenty photographs spanning the entire range of values were selected to test the scale. Testing was performed alongside a descriptive equivalent. A panel of 10 dermatologists, 10 nondermatology clinicians and 14 dermatology scientists marked the two scales; marking was repeated 1 week later. RESULTS: There was a significantly greater agreement between the graders using the photonumeric scale than the descriptive scale (kappa values 0·71 and 0·37 with standardized errors of 0·57 and 0·17, respectively) with no significant difference in repeatability between the two methods (P < 0·05). CONCLUSIONS: The study describes a new photonumeric scale for atrophic photodamage. This would be a useful adjunct in both the clinical and research settings.

Stressors affecting nursing students in Pakistan.

AIM: To determine factors contributing to stress experienced by preregistration nursing students in Pakistan, using the Stressors in Nursing Students scale. The aim was to explore the psychometric properties of this instrument and to investigate the effect of a range of demographic variables on the perception of stressors in nursing students. BACKGROUND: Nursing is a stressful profession, and nursing students may experience more stress due to competing demands and challenges of nursing education, assessment, placements and worries about employment prospects. METHODS: In this cross-sectional survey, data from 726 nursing students from 11 schools of nursing in Karachi, Pakistan, were collected using a questionnaire. Data were analysed using descriptive as well inferential statistics. An exploratory factor analysis was also conducted. RESULTS: There was no apparent factor structure to the Stressors in Nursing Students scale, unlike in previous studies. The total score on the Stressors in Nursing Students scale was related to gender with males scoring higher. The score generally increased over 4 years of the programme, and students in private schools of nursing scored higher than those in public schools of nursing. CONCLUSION: Nursing students in Pakistan do not appear to differentiate between different stressors, and this may be due to cultural differences in the students and to the structure of the programme and the articulation between the academic and clinical aspects. Likewise, cultural reasons may account for differences between stress experienced by male and female students. IMPLICATIONS FOR NURSING AND POLICY: The fact that scores on the Stressors in Nursing Students scale increased over 4 years of the programme and males scored higher than females should alert nursing schools and policymakers related to nursing education and workforce to pay attention to prevent attrition from nursing programmes.

An Intensive, Simulation-Based Communication Course for Pediatric Critical Care Medicine Fellows.

OBJECTIVE: Effective communication among providers, families, and patients is essential in critical care but is often inadequate in the PICU. To address the lack of communication education pediatric critical care medicine fellows receive, the Children's Hospital of Pittsburgh PICU developed a simulation-based communication course, Pediatric Critical Care Communication course. Pediatric critical care medicine trainees have limited prior training in communication and will have increased confidence in their communication skills after participating in the Pediatric Critical Care Communication course. DESIGN: Pediatric Critical Care Communication is a 3-day course taken once during fellowship featuring simulation with actors portraying family members. SETTING: Off-site conference space as part of a pediatric critical care medicine educational curriculum. SUBJECTS: Pediatric Critical Care Medicine Fellows. INTERVENTIONS: Didactic sessions and interactive simulation scenarios. MEASUREMENTS AND MAIN RESULTS: Prior to and after the course, fellows complete an anonymous survey asking about 1) prior instruction in communication, 2) preparedness for difficult conversations, 3) attitudes about end-of-life care, and 4) course satisfaction. We compared pre- and postcourse surveys using paired Student t test. Most of the 38 fellows who participated over 4 years had no prior communication training in conducting a care conference (70%), providing bad news (57%), or discussing end-of-life options (75%). Across all four iterations of the course, fellows after the course reported increased confidence across many topics of communication, including giving bad news, conducting a family conference, eliciting both a family's emotional reaction to their child's illness and their concerns at the end of a child's life, discussing a child's code status, and discussing religious issues. Specifically, fellows in 2014 reported significant increases in self-perceived preparedness to provide empathic communication to families regarding many aspects of discussing critical care, end-of-life care, and religious issues with patients' families (p < 0.05). The majority of fellows (90%) recommended that the course be required in pediatric critical care medicine fellowship. CONCLUSIONS: The Pediatric Critical Care Communication course increased fellow confidence in having difficult discussions common in the PICU. Fellows highly recommend it as part of PICU education. Further work should focus on the course's impact on family satisfaction with fellow communication.

International Survey of Critically Ill Children With Acute Neurologic Insults: The Prevalence of Acute Critical Neurological Disease in Children: A Global Epidemiological Assessment Study.

OBJECTIVE: The international scope of critical neurologic insults in children is unknown. Our objective was to assess the prevalence and outcomes of children admitted to PICUs with acute neurologic insults. DESIGN: Prospective study. SETTING: Multicenter (n = 107 PICUs) and multinational (23 countries, 79% in North America and Europe). PATIENTS: Children 7 days to 17 years old admitted to the ICU with new traumatic brain injury, stroke, cardiac arrest, CNS infection or inflammation, status epilepticus, spinal cord injury, hydrocephalus, or brain mass. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: We evaluated the prevalence and outcomes of children with predetermined acute neurologic insults. Child and center characteristics were recorded. Unfavorable outcome was defined as change in pre-post insult Pediatric Cerebral Performance Category score greater than or equal to 2 or death at hospital discharge or 3 months, whichever came first. Screening data yielded overall prevalence of 16.2%. Of 924 children with acute neurologic insults, cardiac arrest (23%) and traumatic brain injury (19%) were the most common. All-cause mortality at hospital discharge was 12%. Cardiac arrest subjects had highest mortality (24%), and traumatic brain injury subjects had the most unfavorable outcomes (49%). The most common neurologic insult was infection/inflammation in South America, Asia, and the single African site but cardiac arrest in the remaining regions. CONCLUSIONS: Neurologic insults are a significant pediatric international health issue. They are frequent and contribute substantial morbidity and mortality. These data suggest a need for an increased focus on acute critical neurologic diseases in infants and children including additional research, enhanced availability of clinical resources, and the development of new therapies.

Improving multivariable prostate cancer risk assessment using the Prostate Health Index.

OBJECTIVES: To analyse the clinical utility of a prediction model incorporating both clinical information and a novel biomarker, p2PSA, in order to inform the decision for prostate biopsy in an Irish cohort of men referred for prostate cancer assessment. PATIENTS AND METHODS: Serum isolated from 250 men from three tertiary referral centres with pre-biopsy blood draws was analysed for total prostate-specific antigen (PSA), free PSA (fPSA) and p2PSA. From this, the Prostate Health Index (PHI) score was calculated (PHI = (p2PSA/fPSA)*√tPSA). The men's clinical information was used to derive their risk according to the Prostate Cancer Prevention Trial (PCPT) risk model. Two clinical prediction models were created via multivariable regression consisting of age, family history, abnormality on digital rectal examination, previous negative biopsy and either PSA or PHI score, respectively. Calibration plots, receiver-operating characteristic (ROC) curves and decision curves were generated to assess the performance of the three models. RESULTS: The PSA model and PHI model were both well calibrated in this cohort, with the PHI model showing the best correlation between predicted probabilities and actual outcome. The areas under the ROC curve for the PHI model, PSA model and PCPT model were 0.77, 0.71 and 0.69, respectively, for the prediction of prostate cancer (PCa) and 0.79, 0.72 and 0.72, respectively, for the prediction of high grade PCa. Decision-curve analysis showed a superior net benefit of the PHI model over both the PSA model and the PCPT risk model in the diagnosis of PCa and high grade PCa over the entire range of risk probabilities. CONCLUSION: A logical and standardized approach to the use of clinical risk factors can allow more accurate risk stratification of men under investigation for PCa. The measurement of p2PSA and the integration of this biomarker into a clinical prediction model can further increase the accuracy of risk stratification, helping to better inform the decision for prostate biopsy in a referral population.

Absence of developmental toxicity in a canine model after infusion of a hemoglobin-based oxygen carrier: Implications for risk assessment.

Bovine-derived hemoglobin-based oxygen carriers (HBOCs) have been investigated for use in humans (HBOC-201) and approved for veterinary medicine (HBOC-301). We infused pregnant beagles with HBOC-201 to test whether HBOC-induced developmental toxicity previously observed in rats would occur in a species devoid of an inverted visceral yolk sac (invVYS). Phase 1 assessed developmental toxicity of 6g/kg HBOC-201 on gestational day (GD) 21. Phase 2 investigated single infusions of 6g/kg HBOC-201 on one of GDs 21, 25, 29 or 33. Phase 3 studied multiple sequential infusions on GDs 21, 23,25,27,29, 31, and 33 at 0.52g/kg/day (3.6g/kg total dose). Mild to moderate maternal toxicity occurred in all phases. There was an unequivocal absence of developmental toxicity in all phases. Overall, our hypothesis that HBOC, which interferes with the function of the invVYS, would not affect the offspring in dogs was supported. The implications relative to human risk are discussed.

Commercialized biomarkers: new horizons in prostate cancer diagnostics.

Limitations with current clinical tools available for diagnosis and prognosis of prostate cancer (PCa) have resulted in overdiagnosis and costly overtreatment, which is affecting the outcomes and quality of life of men. The biotech industry is investing significant resources into developing more specific biomarkers for PCa detection and patient stratification that would greatly advance the decision-making processes behind PCa management and treatment. In this review, we focus on those biomarkers that have been translated into commercial tests available to clinicians. Since these tests aim to fill specific gaps during the decision-making process of PCa management, we have grouped them based on the clinical question they claim to address, that is, improved PCa screening, false-negative biopsy dilemma, prognostic tests following a positive biopsy and tests predicting relapse/metastases after surgery. We evaluate each test with respect to its development, platform, clinical validation, biomatrix, regulatory approval status and cost.

Prostate cancer risk assessment tools in an unscreened population.

OBJECTIVE: To compare the prostate cancer prevention trial risk calculator (PCPT-RC) and European randomized study of screening for prostate cancer risk calculator (ERSPC-RC) in a unique unscreened population from the West of Ireland. PATIENTS AND METHODS: Data was prospectively recorded for all 556 consecutive men who underwent prostate biopsy at our institution as part of the Rapid Access Prostate Assessment Clinic program in Ireland. The estimated probabilities of detecting prostate cancer and high-grade disease were calculated using the PCPT and ERSPC risk calculators. For each calculator the discriminative ability, calibration and clinical utility was assessed. RESULTS: Prostate cancer was detected in 49% and high-grade prostate cancer in 34% of men. Receiver operating characteristic curve analysis demonstrated that the PCPT-RCs outperformed the ERSPC-RCs for the prediction of prostate cancer areas underneath the ROC curve (AUC 0.628 vs. 0.588, p = 0.0034) and for the prediction of high-grade prostate cancer (AUC 0.792 vs. 0.690, p = 0.0029). Both risk calculators generally over-predicted the risk of prostate cancer and high-grade disease across a wide range of predicted probabilities. Decision curve analysis suggested greater net benefit using the PCPT-RCs in this population. CONCLUSIONS: Multivariable nomograms can further aid patient counselling for early prostate cancer detection. In unscreened men from Western Ireland, the PCPT-RCs provided better discrimination for overall prostate cancer and high-grade disease compared to the ERSPC-RC. However, both tools overpredicted the risk of cancer detection on biopsy, and it is possible that a different set of predictive variables may be more useful in this population.