The use of the Panda-Nerve Block pain app in single-shot peripheral nerve block patients: a feasibility study.

PURPOSE: Peripheral nerve blocks (PNBs) provide excellent perioperative analgesia but can increase the risk of severe postoperative pain once the block wears off. Poor adherence to discharge instructions may increase this risk. Panda-Nerve Block (Panda) is an app that alerts the patient to assess their PNB, score their pain, and take scheduled pain medication. We assessed the usability and feasibility of Panda for assisting patients after receiving a PNB. METHODS: Twenty-nine patients tested Panda in three rounds, for two to seven days, postoperatively to assess and manage their pain and PNB. Feedback was provided via phone interview and the Computer System Usability Questionnaire (CSUQ). Additionally, each user's usage log was analyzed for parameters such as alert response times. Feasibility was determined by alert responses that occurred before the next alert, with a goal of greater than 50%. User adherence was measured as percentage compliance with alerts within one hour; usability and user satisfaction were determined from the CSUQ and interviews. RESULTS: A median [interquartile range (IQR)] of 68 [34-93]% responded before the next alert during the first 48 hr of app use, and 83 [54-92]% responded before the next alert with 87 [75-96]% of these within one hour. There were no significant differences in usage between rounds. Ninety-three percent of patients reported Panda to be easy to use and helpful, and 79% of patients would use Panda again. Critical themes included changes to the layout and appearance, clarification of the language of the PNB check, and requests for dynamic adjustments to the medication schedule based on user responses. CONCLUSION: Panda-Nerve Block is a feasible method for PNB patients to manage postoperative pain with a high response rate. Future work should include providing two-way communication for patients and clinicians and assessing its effect on pain outcomes. TRIAL REGISTRATION: www.clinicaltrials.gov (NCT03369392); registered 5 December 2017.

RéSUMé: OBJECTIF: Les blocs nerveux périphériques (BNP) procurent une excellente analgésie périopératoire mais peuvent augmenter le risque de douleur postopératoire élevée une fois que le bloc disparait. Un mauvais respect des instructions de congé pourrait augmenter ce risque. L'application Panda (Panda-Nerve Block) avertit le patient afin qu'il évalue son BNP, quantifie sa douleur, et prenne ses médicaments analgésiques prescrits. Nous avons évalué la facilité d'utilisation et la faisabilité de l'application Panda pour aider les patients ayant reçu un BNP. MéTHODE: Vingt-neuf patients ont testé l'application Panda en trois itérations de deux à sept jours après leur opération afin d'évaluer et de prendre en charge leur douleur et le BNP. Les rétroactions étaient partagées par entretien téléphonique et via le Questionnaire sur la convivialité du système informatique (CSUQ - Computer System Usability Questionnaire). En outre, le journal d'utilisation de chaque utilisateur a été analysé pour en étudier certains paramètres tels que les temps de réponse aux alertes. La faisabilité était déterminée par les réponses aux alertes survenant avant la prochaine alerte, avec un objectif de plus de 50 %. L'observance des utilisateurs était mesurée en tant que pourcentage de conformité aux alertes dans l'heure suivante; la facilité d'utilisation et la satisfaction des utilisateurs étaient déterminées à partir du CSUQ et des entretiens. RéSULTATS: En moyenne [écart interquartile (ÉIQ)], 68 [34­93] % des patients ont répondu avant la prochaine alerte au cours des premières 48 h d'utilisation de l'application, et 83 [54­92] % ont répondu avant la prochaine alerte, avec 87 [75­96] % de ces patients dans l'heure qui suivait. Il n'y a pas eu de différence significative dans l'utilisation entre les itérations. Quatre-vingt-treize pour cent des patients ont rapporté qu'ils trouvaient l'application Panda conviviale et utile, et 79 % l'utiliseraient à nouveau. Les critiques comprenaient des modifications de la disposition et de l'apparence de l'application, la clarification du langage lors des vérifications du BNP, et des demandes pour des ajustements dynamiques du traitement selon les réponses des utilisateurs. CONCLUSION: L'application Panda constitue une méthode possible de prise en charge de la douleur postopératoire pour les patients ayant reçu un BNP, avec un taux de réponse élevé. Les travaux futurs devraient inclure la fourniture d'une communication bidirectionnelle pour les patients et les cliniciens et l'évaluation de l'effet de l'utilisation de l'application sur des devenirs de douleur. ENREGISTREMENT DE L'éTUDE: www.clinicaltrials.gov (NCT03369392); enregistrée le 5 décembre 2017.

The evaluation of smartphone versions of the visual analogue scale and numeric rating scale as postoperative pain assessment tools: a prospective randomized trial.

PURPOSE: The Pain assessment using a novel digital application (Panda) is a smartphone application that contains the digital versions of the visual analogue scale (VAS-100) and numeric rating scale (NRS-11). This study aimed to investigate if the Panda versions of these two pain scales are equivalent to the paper versions in adult patients. METHODS: This was a prospective, randomized, cross-over-controlled trial of subjects aged 19-75 yr undergoing procedures with anticipated post-surgical pain. Each subject used both the Panda and paper versions of VAS-100 or NRS-11 pain scores after emergence from anesthesia and after meeting postanesthesia care unit (PACU) discharge criteria. Correlations between the two tools were analyzed, and Bland-Altman agreement was calculated. The smartphone and paper versions were considered equivalent at each time point if the differences (and their 95% confidence interval [CI]) between them were less than 20 points for the VAS-100 and 2.1 for NRS-11. RESULTS: The two versions of the VAS-100 correlated strongly after emergence (Pearson's r = 0.93; P < 0.001) and upon meeting discharge criteria (r = 0.94; P < 0.001); the mean (standard deviation [SD]) Panda score after emergence was 35 (27) compared with the paper score of 37 (26) (mean difference, - 2; 95% CI, - 22 to 19). The mean (SD) VAS-100 Panda score upon meeting discharge criteria was 21 (20) compared with the paper score of 23 (21) (mean difference, - 2; 95% CI, - 17 to 13). For the NRS-11, Panda again correlated strongly with the original tool scores after emergence (r = 0.93; P < 0.001) and upon meeting discharge criteria (r = 0.96; P < 0.001); the mean (SD) Panda and paper scores after emergence were both 4 (3) (mean difference, 0.05; 95% CI, - 1.87 to 1.96). The mean (SD) NRS-11 Panda and paper scores upon meeting PACU discharge criteria were both 3 (2) (mean difference, - 0.08; 95% CI, - 1.41 to 1.26). CONCLUSION: Following emergence from anesthesia in adult patients, the digital Panda version of the NRS-11, but not the VAS-100, is equivalent to the validated paper version. In those who are ready for discharge from the PACU, the digital Panda versions of both the VAS-100 and NRS-11 agreed adequately and can be used in place of the original paper versions.

BRAF mutation in papillary thyroid cancer-Prevalence and clinical correlation in a South-East Asian cohort.

OBJECTIVE: BRAF mutation is the commonest mutation seen in papillary thyroid cancer (PTC), but its prevalence and clinical significance vary across countries. We aim to evaluate the prevalence and clinico-pathological correlation of BRAF mutation in PTC patients at our centre. STUDY DESIGN: Retrospective cohort study of 75 consecutive archival thyroid specimens, whereby BRAF mutation was detected using a polymerase chain reaction (PCR) technique and correlated with clinical and pathological features and outcomes. SETTING: Tertiary university hospital in Singapore. PARTICIPANTS: A total of 75 consecutive histologically proven archival thyroid specimens from patients who underwent thyroidectomy for PTC were accrued for this study. MAIN OUTCOME MEASURES: Main outcome is to determine the prevalence of the BRAF mutation in our South-East Asian population. Secondary aim is to correlate the mutational status with adverse pathological features like histological variants, multi-focality, lymphovascular invasion and extra-thyroidal extension, clinical features like demographics, TNM stage, recurrence and survival, as well as treatment details like type of surgery performed and radioiodine doses. RESULTS: BRAF mutation was detected in 56% (42/75) of PTC. All but one BRAF-mutated PTC had the BRAFV600E mutation. BRAF-mutated tumours were associated with an advanced T-stage (P = 0.049) and were more likely to have a central neck dissection (P = 0.036). There was no significant correlation between BRAF mutation status and clinical outcomes. CONCLUSION: The prevalence of BRAF mutation is 56%. BRAF mutation-positive tumours were associated with locally advanced disease, but not poorer survival.

Performance evaluation of Cepheid Xpert Norovirus kit with a user-modified protocol.

The Cepheid Xpert® Norovirus kit automates sample processing, nucleic acid extraction, and real-time reverse transcription polymerase chain reactions (RT-PCRs) to detect norovirus genogroups I (GI) and II (GII). Eighty-five stool samples collected between February 2015 and May 2017 were used to compare the performance of a user-modified Xpert assay against a clinically validated laboratory-developed test (LDT). Of the 85 samples, 54 were previously archived in -80°C freezer. The remaining 31 were fresh samples tested concurrently with the LDT. The results of all samples tested using the Xpert kit and LDT were found to be concordant, including 12 GI- and 42 GII-positive samples, 1 GI and GII coinfection, and 30 negative samples. Comparison of the assays showed perfect concordance with a kappa coefficient score of 1.00 (95%CI from 1.00 to 1.00). Of the 30 negative stool samples tested, three samples were positive for rotavirus detected using an immunochromatographic assay, with no cross-reactivity shown in both LDT and Xpert assays. In-run sample processing control of the Xpert assay for all negative samples tested showed no/minor inhibition. Compared to the LDT, the Xpert assay produced similar or better Ct values for detection. It also showed better mitigation of PCR inhibition in stool sample testing.

Epidemiology of GB virus type C among patients infected with HIV in Singapore.

Several studies have shown that individuals co-infected with GB virus type C (GBV-C), and human immunodeficiency virus (HIV) have slower progression to acquired immunodeficiency syndrome (AIDS) and a prolonged lifespan, compared to those infected with only HIV. In Singapore, despite the steadily increasing number of HIV infections in recent years, there are no studies documenting the extent of GBV-C/HIV co-infection in this group of patients. To fill this dearth of information, two GBV-C screening assays was performed on 80 archived HIV-1-positive samples from the National University Hospital. The overall prevalence of GBV-C co-infection among patients infected with HIV in this study was 10% (8/80). Phylogenetic analysis of the eight dual-infection cases revealed that genotypes 3 (4/8, 50%) and 2a (2/8, 25%) were the main genotypes circulating among these Singaporean HIV patients. One case each of genotypes 2b (1/8, 12.5%) and 4 (1/8, 12.5%), which have not been described previously in Singapore, were identified. These findings hint at the complex epidemiology of GBV-C in different patient groups and a larger study would be needed to characterize, and understand the potential clinical impact of GBV-C co-infection on the patients.

Rapid prenatal diagnosis of common beta-thalassemia mutations in Southeast Asia using pyrosequencing.

OBJECTIVE: Current methods of prenatal diagnosis to detect beta-thalassemia are Sanger sequencing and reverse dot blot. These methods are time-consuming and can prolong assay turnaround time. We aim to develop a sensitive and rapid method to detect 27 beta-thalassemia mutations using pyrosequencing. METHOD: Pyrosequencing primer pairs and sequencing primers were designed to detect 27 most common beta-thalassemia mutations found in Singapore. Pyrosequencing was performed on 191 DNA samples with known beta-thalassemia mutations isolated from 143 peripheral blood and 48 prenatal samples (seven chorionic villus biopsies, 26 cultured amniocytes, 15 uncultured amniocytes). All mutations were validated with Sanger sequencing. RESULTS: Pyrosequencing identified 210 alleles with beta-thalassemia mutations and 82 alleles without mutations with 100% sensitivity (lower 95% confidence interval [CI], 97.8%) and 100% specificity (lower 95% CI, 94.4%). All pyrosequences were concordant with Sanger-based sequences. Pyrosequencing was able to detect DNA concentrations as low as 2 ng, obviating the need for cell culture in volume-restricted samples. Sample receipt-to-report assay turnaround times were 16 to 18 h (Sanger sequencing) and 4 to 6 h (pyrosequencing). CONCLUSION: Pyrosequencing is a rapid and sensitive method to detect common beta-thalassemia mutations without the need for cell culture, thus reducing the assay turnaround time.

Targeting both rs12979860 and rs8099917 polymorphisms with a single-tube high-resolution melting assay for IL28b genotyping.

A rapid, duplex, high-resolution melting interleukin-28B gene (IL28B) genotyping assay, targeting both rs12979860 and rs8099917 polymorphisms, was developed and validated using 30 DNA samples from healthy volunteers. A linkage study on 300 healthy Singaporeans showed variable haplotypes. When the assay was applied to plasma DNA from 50 hepatitis C virus genotype-1 (HCV-1)-infected patients, five compound heterozygous types were detected.

A diagnostic polymerase chain reaction assay for Zika virus.

Zika virus (ZIKV) is a mosquito-borne flavivirus. Infection results in a dengue-like illness with fever, headache, malaise, and a maculopapular rash. Nearly all cases are mild and self-limiting but in 2007, a large outbreak of ZIKV was reported from the island of Yap (in Micronesia, northwest of Indonesia). Singapore is already endemic for dengue, and its impact on public health and economic burden is significant. Other dengue-like infections (e.g., Chikungunya virus) are present. Yet only 10% of reported dengue cases have laboratory confirmation. The identification and control of other dengue-like, mosquito-transmitted infections is thus important for the health of Singapore's population, as well as its economy. Given that ZIKV shares the same Aedes mosquito vector with both dengue and Chikungunya, it is possible that this virus is present in Singapore and causing some of the mild dengue-like illness. A specific and sensitive one-step, reverse transcription polymerase chain reaction (RT-PCR) with an internal control (IC) was designed and tested on 88 archived samples of dengue-negative, Chikungunya-negative sera from patients presenting to our hospital with a dengue-like illness, to determine the presence of ZIKV in Singapore. The assay was specific for detection of ZIKV and displayed a lower limit of detection (LoD) of 140 copies viral RNA/reaction when tested on synthetic RNA standards prepared using pooled negative patient plasma. Of the 88 samples tested, none were positive for ZIKV RNA, however, the vast majority of these were from patients admitted to hospital and further study may be warranted in community-based environments.

A universal influenza A and B duplex real-time RT-PCR assay.

A high throughput universal influenza A and B duplex real-time RT-PCR was developed to meet effectively the heightened surveillance and diagnostic needs essential in managing influenza infections and outbreaks. Primers and probes, designed to target highly conserved regions of the matrix protein of influenza A and the nucleoprotein of influenza B, were optimized using the high-throughput LightCycler 480 II system. Analytical sensitivity and specificity were characterized using RNA transcripts diluted serially, archived non-influenza respiratory viruses, and proficiency test samples. Eighty-nine clinical samples were tested in parallel against existing influenza A and B monoplex assays. Once validated, the duplex assay was applied prospectively on 2,458 clinical specimens that were later subtyped. In April 2011, the emergence of an influenza B variant necessitated the inclusion of an additional modified probe for influenza B and revalidation of the revised protocol. The lower detection limits of the assay were 50 copies/PCR. There was no cross-reactivity against any non-influenza respiratory virus and all proficiency testing materials were identified correctly. The parallel testing revealed a 98.9% overall agreement. Routine application of the assay revealed high sensitivity and specificity for the detection of influenza A/H1N1/2009, A/H3N2 and influenza B. Assay C(q) values correlated well between the pre- and post-revision protocols for influenza A (r(2) = 0.998) and B (r(2) = 0.999). The revised protocol detected three additional novel influenza B variant cases in 200 specimens reported previously as influenza B negative. This in-house assay offers a highly sensitive and specific option for laboratories seeking to expand their influenza testing capacity.

Comparison of pandemic (H1N1) 2009 and seasonal influenza viral loads, Singapore.

Mean viral loads for patients with pandemic (H1N1) 2009 were ≈1 log10 times lower than those for patients with seasonal influenza within the first week after symptom onset. Neither pandemic nor seasonal influenza viral loads correlated with clinical severity of illness. No correlation was found between viral loads and concurrent illness.

Laboratory Verification of a BRCA1 and BRCA2 Massively Parallel Sequencing Assay from Wet Bench to Bioinformatics for Germline DNA Analysis.

Introduction A robust genetic test for BRCA1 and BRCA2 genes is necessary for the diagnosis, prognosis, and treatment of patients with hereditary breast and ovarian cancer. We evaluated a commercial amplicon-based massively parallel sequencing (MPS) assay, BRCA MASTR Plus on the MiSeq platform, for germline BRCA genetic testing. Methods This study was performed on 31 DNA from cell lines and proficiency testing samples to establish the accuracy of the assay. A reference cell line DNA, NA12878 was used to determine the reproducibility of the assay. Discordant MPS result was resolved orthogonally by the current gold-standard Sanger sequencing method. Results The analytical accuracy, sensitivity, and specificity for variant detection were 93.55, 92.86, and 100.00%, respectively. Both sequencing depth and variant allele frequencies were highly reproducible by comparing the NA12878 DNA tested in three separate runs. The single discordant result, later confirmed by Sanger sequencing was due to the inability of the MASTR Reporter software to identify a 40-bp deletion in BRCA1 . Conclusion The BRCA MASTR Plus assay on the MiSeq platform is accurate and reproducible for germline BRCA genetic testing, making it suitable for use in a clinical diagnostic laboratory. However, Sanger sequencing may still serve as a confirmatory method to improve diagnostic capability of the MPS assay.

Perceived Challenges to Routine Uptake of the Ankle Brachial Index within Primary Care Practice.

(1) Introduction: The ankle-brachial index (ABI) is the most widely used method of diagnosing peripheral arterial disease (PAD). However, the uptake of ABIs has been reported to be low in primary care settings across different various healthcare settings; however, this is yet to be investigated within the Canadian context. (2) Objective: Therefore, we sought to assess the rates of ABI usage as well as perceived barriers among primary care practitioners (PCPs) in Toronto, Canada. (3) Methods: A modified questionnaire was electronically sent to 257 PCPs in the Greater Toronto Area (GTA). Questions pertained to frequency, feasibility, utility, and barriers associated with ABI usage in clinical practice. Responses were collected and tallied. (4) Results: A total of 52 PCPs completed the questionnaire. 79% of PCPs did not routinely perform ABIs within their clinical practice, and 56% deemed ABI usage as unfeasible. Constraints in time and staff personnel, as well as complexity of ABI result interpretation, were cited as the major perceived barriers to ABI usage. The overwhelming majority of PCPs viewed alternative forms of diagnosis, such as a blood test for PAD, as being preferable to ABI, as such an approach would enhance diagnostic simplicity and efficiency. (5) Conclusion: ABI usage rates are poor within primary care practices in Toronto, Canada. Alternative approaches for diagnosing PAD may result in greater adoption rates among PCPs and therefore improve the identification of patients with PAD.

Viral loads of herpes simplex virus in clinical samples--a 5-year retrospective analysis.

Viral loads of herpes simplex virus (HSV) are not monitored usually for the effective clinical management of HSV-related diseases. However, recently, there has been more interest about the typical HSV levels in clinical specimens, and how such data may improve understanding of the behavior of this virus in such clinical presentations, particularly in immunocompromised patients, where more prolonged therapy using higher doses of antiviral drugs may be required. Using an in-house quantitative HSV-1/HSV-2 polymerase chain reaction assay, an observational, retrospective 5-year analysis of diagnostic, quantitative HSV-1 and HSV-2 DNA levels was conducted. The results (all in median log(10) DNA copies/ml), including perhaps the first quantitative comparison of cerebrospinal fluid (CSF) HSV viral loads, were as follows: CSF: HSV-1, 3.40 (range 2.30-8.98) versus HSV-2, 3.60 (range 2.31-6.86) (P=0.559); plasma: HSV-1, 3.20 (range 2.23-5.51) versus HSV-2, 3.20 (range 3.18-3.41) (P=0.905); genital swabs: HSV-1, 6.79 (range 2.28-8.48) versus HSV-2, 6.97 (range 3.40-9.66) (P=0.810); oral swabs: HSV-1, 7.28 (range 2.46-10.04) versus HSV-2, 5.62 (range 4.60-6.63) (P=0.529). Note that with the samples usually collected for HSV testing (i.e., CSF, plasma, oral, and genital swabs) there was no significant difference in the viral loads between HSV-1 and HSV-2 types, nor between immunocompetent and immunocompromised patients for each of these different HSV types. Indeed, even between immunocompromised patients with similar diseases, for these samples, the HSV loads were found to vary considerably. These findings may therefore limit the usefulness of monitoring HSV loads in everyday clinical practice.

Cytokeratin 19 regulates endoplasmic reticulum stress and inhibits ERp29 expression via p38 MAPK/XBP-1 signaling in breast cancer cells.

Cytokeratin 19 (CK19) is widely used as a biomarker for the detection of disseminated tumor cells in blood and bone marrow, and its positivity is considered as an independent prognostication indicator in cancer patients. However, its role in breast cancer progression remains unknown. We had established a stable CK19-expressing clone in the CK19-negative BT549 human breast cancer cell line and found that CK19 expression in the BT549 cells caused cell cycle arrest, reduced cell motility and increased drug resistance. Further study revealed that CK19 expression regulated endoplasmic reticulum (ER) stress signaling by up-regulating p38/RNA-dependent protein kinase-like ER kinase (PERK)/p-eIF2alpha and 78 kDa glucose-regulated protein (Bip/GRP78), and down-regulating focal adhesion kinase (FAK). The level of ER protein 29 (ERp29) was shown to be decreased in the CK19-expressing BT549 cells by proteomic analyses and verified by Western blotting and RT-PCR. Pharmacological inhibition of p38 signaling by its specific inhibitor SB203580 or knockdown of p38 and transcription factor XBP-1 by siRNA in BT549/CK19 and MDA-MB-231 cells revealed that p38/XBP-1 signaling negatively regulated ERp29 expression. Our results indicated that CK19 modulates ER stress signaling and contributes to cell survival and dormancy in breast cancer cells.

Noninvasive prenatal exclusion of haemoglobin Bart's using foetal DNA from maternal plasma.

OBJECTIVE: Prenatal diagnosis of alpha-thalassaemia requires invasive testing associated with a risk of miscarriage. Cell-free foetal DNA in maternal plasma presents an alternative source of foetal genetic material for noninvasive prenatal diagnosis. We aimed to exclude HbBart's noninvasively by detection of unaffected paternal alleles in maternal plasma using quantitative fluorescence PCR (QF-PCR). METHOD: Microsatellite markers (16PTEL05, 16PTEL06) within the breakpoint regions of -(SEA), -(FIL) and -(THAI) deletions were analysed using QF-PCR of maternal plasma from 30 families. In this blinded study, genotypes were confirmed using conventional PCR. Maternal plasma from two known cases of HbBart's were also analysed. RESULTS: HbBart's was excluded in 10 out of 30 (33.3%, 95% CI, 17.3-52.8%) mothers by identifying the presence of nondeleted paternally inherited fetal alleles; either only 16PTEL05 (n = 1) or only 16PTEL06 (n = 4), or both (n = 5), and confirmed through direct analysis of fetal DNA. Paternally inherited foetal alleles of 16PTEL05 and 16PTEL06 were not detected in maternal plasma of the two known HbBarts cases. False negatives were excluded with the detection of paternally inherited fetal control marker, D21S1270 in maternal plasma. CONCLUSION: We show proof-of-principle that such a test can accurately exclude HbBart's in the foetus by identifying the nondeleted paternally inherited fetal alleles in maternal plasma in one out of three pregnancies, avoiding invasive testing in these pregnancies.

Priority Outcomes in Critically Ill Children: A Patient and Parent Perspective.

BACKGROUND: Outcomes in pediatric critical care research are typically selected by the researcher. OBJECTIVES: (1) To identify outcomes prioritized by patients and their families following a critical illness and (2) to determine the overlap between patient-centered and researcher-selected study outcomes. METHODS: An exploratory descriptive qualitative study nested within a longitudinal cohort study conducted in 2 pediatric intensive care units (PICUs). Participants were purposively sampled from the primary cohort to ensure adequate demographic representation. Qualitative descriptive approaches based on naturalistic observation were used to collect data and analyze results. Data were coded by using the International Classification of Functioning, Disability, and Health Children and Youth (ICF-CY) framework. RESULTS: Twenty-one participants were interviewed a mean of 5.1 months after PICU discharge. Outcomes fell into 2 categories: patient-centered and family-centered. In the former, diagnosis, survival, and prognosis were key priorities during the acute critical illness. Once survival appears possible, functioning (physical, cognitive, and emotional), and factors that influence recovery (ie, rehabilitation, environment, and quality of life) are prioritized. Family-centered outcomes consisted of parents' psychosocial functioning and experience of care. Patient-centered outcomes were covered well by the selected study measures of functioning, but not by the clinical outcome measures. CONCLUSION: Functioning and quality of life are key patient-centered outcomes during recovery from critical illness. These are not well captured by end points typically used in PICU studies. These results justify the importance of patient- and family-centered outcomes in PICU research and a need to determine how these outcomes can be comprehensively measured.

The National Palliative Care Research Center: Ten Years of Promoting and Developing Research in Palliative Care.

BACKGROUND: The evidence base to support high-quality clinical care and number of scientists available to develop this evidence base are inadequate. OBJECTIVE: To describe the first 10 years of the National Palliative Care Research Center's (NPCRC) programs and their outcomes. DESIGN: Established in 2005, NPCRC was created in direct response to the recommendations of the Institute of Medicine. Specifically, NPCRC was created to expand the palliative care evidence-based needed for both health policy and clinical practice by supporting research scientists, stimulating research and innovation, and creating a community of researchers focused on the needs of persons with serious illness and their families. MEASUREMENTS: Subsequent grant funding following NPCRC investment (web searches of NIH Research Portfolio Online Reporting Tools [RePORT], Veterans Administration and Patient Centered Outcomes Research Institute [PCORI] grant databases, grantee on-line surveys, and grantee annual reports) promotions (grantee on-line surveys and annual reports), publications (PubMed searches), and NPCRC participant satisfaction (grantee questionnaires). RESULTS: As of July 2017, NPCRC has funded 47 junior investigators representing over 10 disciplines. These investigators have leveraged NPCRC's $7.8 million investment into 52 federal grants totaling $74.8 million dollars and 69 foundation grants totaling $16 million. Thirty-five grants ($5.8 million) have been awarded to experienced investigators, resulting in additional grant funding of $104.5 million dollars ($78.5 million federal, $26 million nonfederal). Satisfaction with NPCRC's program has been uniformly high and policy efforts have resulted in enhanced federal funding opportunities in palliative care research. CONCLUSIONS: NPCRC's focus on people and infrastructure in conjunction with a top-down bottom-up strategy has been critical in improving the palliative care evidence base.