Community-Based Cluster-Randomized Trial to Reduce Opioid Overdose Deaths.

BACKGROUND: Evidence-based practices for reducing opioid-related overdose deaths include overdose education and naloxone distribution, the use of medications for the treatment of opioid use disorder, and prescription opioid safety. Data are needed on the effectiveness of a community-engaged intervention to reduce opioid-related overdose deaths through enhanced uptake of these practices. METHODS: In this community-level, cluster-randomized trial, we randomly assigned 67 communities in Kentucky, Massachusetts, New York, and Ohio to receive the intervention (34 communities) or a wait-list control (33 communities), stratified according to state. The trial was conducted within the context of both the coronavirus disease 2019 (Covid-19) pandemic and a national surge in the number of fentanyl-related overdose deaths. The trial groups were balanced within states according to urban or rural classification, previous overdose rate, and community population. The primary outcome was the number of opioid-related overdose deaths among community adults. RESULTS: During the comparison period from July 2021 through June 2022, the population-averaged rates of opioid-related overdose deaths were similar in the intervention group and the control group (47.2 deaths per 100,000 population vs. 51.7 per 100,000 population), for an adjusted rate ratio of 0.91 (95% confidence interval, 0.76 to 1.09; P = 0.30). The effect of the intervention on the rate of opioid-related overdose deaths did not differ appreciably according to state, urban or rural category, age, sex, or race or ethnic group. Intervention communities implemented 615 evidence-based practice strategies from the 806 strategies selected by communities (254 involving overdose education and naloxone distribution, 256 involving the use of medications for opioid use disorder, and 105 involving prescription opioid safety). Of these evidence-based practice strategies, only 235 (38%) had been initiated by the start of the comparison year. CONCLUSIONS: In this 12-month multimodal intervention trial involving community coalitions in the deployment of evidence-based practices to reduce opioid overdose deaths, death rates were similar in the intervention group and the control group in the context of the Covid-19 pandemic and the fentanyl-related overdose epidemic. (Funded by the National Institutes of Health; HCS ClinicalTrials.gov number, NCT04111939.).

Predictors of obstetric anal sphincter injury during waterbirth: a secondary analysis of a prospective observational study.

INTRODUCTION AND HYPOTHESIS: Obstetric anal sphincter injury (OASI) during childbirth is associated with urino-genital pain and dysfunction. Waterbirth is a popular birth choice for women, but controversy remains around the risk of OASI during waterbirth. This study reports on the incidence of OASI, and factors associated with OASI, for a cohort of women who gave birth in water. METHODS: This secondary analysis used prospectively collected data from 2,908 women who gave birth in water in a hospital setting. The incidence of OASI was calculated. Univariable and multivariable logistic regression analysis evaluated factors associated with OASI. RESULTS: The incidence of OASI was 1.9% (95% confidence interval (CI) 1.4, 2.4) for all women. In nulliparae it was higher (3.2%, 95% CI 2.3, 4.3) than in multiparae (0.9%, 95% CI 0.5, 1.4). In the multivariable analysis, two variables were associated with OASI; multiparity was negatively associated with OASI (adjusted odds ratio [aOR] 0.24, 95% CI 0.12, 0.50, p < 0.001), and birth weight was positively associated with OASI (aOR 1.001, 95% CI 1.000, 1.002, p = 0.02). A "hands-on" technique was used during only 13% of births. A birth position supporting a flexible sacrum did not influence OASI risk. CONCLUSIONS: A low incidence of OASI was found for this cohort of women. The low proportion of midwives using a hands-on technique suggests that it may not be required in waterbirth.

PALB2, CHEK2 and ATM rare variants and cancer risk: data from COGS.

BACKGROUND: The rarity of mutations in PALB2, CHEK2 and ATM make it difficult to estimate precisely associated cancer risks. Population-based family studies have provided evidence that at least some of these mutations are associated with breast cancer risk as high as those associated with rare BRCA2 mutations. We aimed to estimate the relative risks associated with specific rare variants in PALB2, CHEK2 and ATM via a multicentre case-control study. METHODS: We genotyped 10 rare mutations using the custom iCOGS array: PALB2 c.1592delT, c.2816T>G and c.3113G>A, CHEK2 c.349A>G, c.538C>T, c.715G>A, c.1036C>T, c.1312G>T, and c.1343T>G and ATM c.7271T>G. We assessed associations with breast cancer risk (42 671 cases and 42 164 controls), as well as prostate (22 301 cases and 22 320 controls) and ovarian (14 542 cases and 23 491 controls) cancer risk, for each variant. RESULTS: For European women, strong evidence of association with breast cancer risk was observed for PALB2 c.1592delT OR 3.44 (95% CI 1.39 to 8.52, p=7.1×10-5), PALB2 c.3113G>A OR 4.21 (95% CI 1.84 to 9.60, p=6.9×10-8) and ATM c.7271T>G OR 11.0 (95% CI 1.42 to 85.7, p=0.0012). We also found evidence of association with breast cancer risk for three variants in CHEK2, c.349A>G OR 2.26 (95% CI 1.29 to 3.95), c.1036C>T OR 5.06 (95% CI 1.09 to 23.5) and c.538C>T OR 1.33 (95% CI 1.05 to 1.67) (p≤0.017). Evidence for prostate cancer risk was observed for CHEK2 c.1343T>G OR 3.03 (95% CI 1.53 to 6.03, p=0.0006) for African men and CHEK2 c.1312G>T OR 2.21 (95% CI 1.06 to 4.63, p=0.030) for European men. No evidence of association with ovarian cancer was found for any of these variants. CONCLUSIONS: This report adds to accumulating evidence that at least some variants in these genes are associated with an increased risk of breast cancer that is clinically important.

Identification of independent association signals and putative functional variants for breast cancer risk through fine-scale mapping of the 12p11 locus.

BACKGROUND: Multiple recent genome-wide association studies (GWAS) have identified a single nucleotide polymorphism (SNP), rs10771399, at 12p11 that is associated with breast cancer risk. METHOD: We performed a fine-scale mapping study of a 700 kb region including 441 genotyped and more than 1300 imputed genetic variants in 48,155 cases and 43,612 controls of European descent, 6269 cases and 6624 controls of East Asian descent and 1116 cases and 932 controls of African descent in the Breast Cancer Association Consortium (BCAC; http://bcac.ccge.medschl.cam.ac.uk/ ), and in 15,252 BRCA1 mutation carriers in the Consortium of Investigators of Modifiers of BRCA1/2 (CIMBA). Stepwise regression analyses were performed to identify independent association signals. Data from the Encyclopedia of DNA Elements project (ENCODE) and the Cancer Genome Atlas (TCGA) were used for functional annotation. RESULTS: Analysis of data from European descendants found evidence for four independent association signals at 12p11, represented by rs7297051 (odds ratio (OR) = 1.09, 95 % confidence interval (CI) = 1.06-1.12; P = 3 × 10(-9)), rs805510 (OR = 1.08, 95 % CI = 1.04-1.12, P = 2 × 10(-5)), and rs1871152 (OR = 1.04, 95 % CI = 1.02-1.06; P = 2 × 10(-4)) identified in the general populations, and rs113824616 (P = 7 × 10(-5)) identified in the meta-analysis of BCAC ER-negative cases and BRCA1 mutation carriers. SNPs rs7297051, rs805510 and rs113824616 were also associated with breast cancer risk at P < 0.05 in East Asians, but none of the associations were statistically significant in African descendants. Multiple candidate functional variants are located in putative enhancer sequences. Chromatin interaction data suggested that PTHLH was the likely target gene of these enhancers. Of the six variants with the strongest evidence of potential functionality, rs11049453 was statistically significantly associated with the expression of PTHLH and its nearby gene CCDC91 at P < 0.05. CONCLUSION: This study identified four independent association signals at 12p11 and revealed potentially functional variants, providing additional insights into the underlying biological mechanism(s) for the association observed between variants at 12p11 and breast cancer risk.

Genetic variation in mitotic regulatory pathway genes is associated with breast tumor grade.

Mitotic index is an important component of histologic grade and has an etiologic role in breast tumorigenesis. Several small candidate gene studies have reported associations between variation in mitotic genes and breast cancer risk. We measured associations between 2156 single nucleotide polymorphisms (SNPs) from 194 mitotic genes and breast cancer risk, overall and by histologic grade, in the Breast Cancer Association Consortium (BCAC) iCOGS study (n = 39 067 cases; n = 42 106 controls). SNPs in TACC2 [rs17550038: odds ratio (OR) = 1.24, 95% confidence interval (CI) 1.16-1.33, P = 4.2 × 10(-10)) and EIF3H (rs799890: OR = 1.07, 95% CI 1.04-1.11, P = 8.7 × 10(-6)) were significantly associated with risk of low-grade breast cancer. The TACC2 signal was retained (rs17550038: OR = 1.15, 95% CI 1.07-1.23, P = 7.9 × 10(-5)) after adjustment for breast cancer risk SNPs in the nearby FGFR2 gene, suggesting that TACC2 is a novel, independent genome-wide significant genetic risk locus for low-grade breast cancer. While no SNPs were individually associated with high-grade disease, a pathway-level gene set analysis showed that variation across the 194 mitotic genes was associated with high-grade breast cancer risk (P = 2.1 × 10(-3)). These observations will provide insight into the contribution of mitotic defects to histological grade and the etiology of breast cancer.

Prevalence of BRCA1 and BRCA2 germline mutations in patients with triple-negative breast cancer.

Triple-negative breast cancers (TNBC) lack expression of oestrogen, progesterone and HER2 receptors. The gene expression profiles of TNBCs are similar to those of breast tumours in women with BRCA1 mutations. Reports to date indicate that up to 20 % of TNBC patients harbour germline BRCA mutations; however, the prevalence of BRCA mutations in TNBC patients varies widely between countries and from study to study. We studied 774 women with triple-negative breast cancer, diagnosed on average at age 58.0 years. Samples of genomic DNA were provided by the Australian Breast Cancer Tissue Bank (ABCTB) (439 patients) and by the Department of Genetics and Pathology of the Pomeranian Medical University (335 patients). The entire coding regions and the exon-intron boundaries of BRCA1 and BRCA2 were amplified and sequenced by next-generation sequencing. We identified a BRCA1 or BRCA2 mutation in 74 of 774 (9.6 %) triple-negative patients. The mutation prevalence was 9.3 % in Australia and was 9.9 % in Poland. In both countries, the mean age of diagnoses of BRCA1 mutation carriers was significantly lower than that of non-carriers, while the age of onset of BRCA2 mutation carriers was similar to that of non-carriers. In the Australian cohort, 59 % of the mutation-positive patients did not have a family history of breast or ovarian cancer, and would not have qualified for genetic testing. The triple-negative phenotype should be added as a criterion to genetic screening guidelines.

Genome-wide association study identifies 25 known breast cancer susceptibility loci as risk factors for triple-negative breast cancer.

Triple-negative (TN) breast cancer is an aggressive subtype of breast cancer associated with a unique set of epidemiologic and genetic risk factors. We conducted a two-stage genome-wide association study of TN breast cancer (stage 1: 1529 TN cases, 3399 controls; stage 2: 2148 cases, 1309 controls) to identify loci that influence TN breast cancer risk. Variants in the 19p13.1 and PTHLH loci showed genome-wide significant associations (P < 5 × 10(-) (8)) in stage 1 and 2 combined. Results also suggested a substantial enrichment of significantly associated variants among the single nucleotide polymorphisms (SNPs) analyzed in stage 2. Variants from 25 of 74 known breast cancer susceptibility loci were also associated with risk of TN breast cancer (P < 0.05). Associations with TN breast cancer were confirmed for 10 loci (LGR6, MDM4, CASP8, 2q35, 2p24.1, TERT-rs10069690, ESR1, TOX3, 19p13.1, RALY), and we identified associations with TN breast cancer for 15 additional breast cancer loci (P < 0.05: PEX14, 2q24.1, 2q31.1, ADAM29, EBF1, TCF7L2, 11q13.1, 11q24.3, 12p13.1, PTHLH, NTN4, 12q24, BRCA2, RAD51L1-rs2588809, MKL1). Further, two SNPs independent of previously reported signals in ESR1 [rs12525163 odds ratio (OR) = 1.15, P = 4.9 × 10(-) (4)] and 19p13.1 (rs1864112 OR = 0.84, P = 1.8 × 10(-) (9)) were associated with TN breast cancer. A polygenic risk score (PRS) for TN breast cancer based on known breast cancer risk variants showed a 4-fold difference in risk between the highest and lowest PRS quintiles (OR = 4.03, 95% confidence interval 3.46-4.70, P = 4.8 × 10(-) (69)). This translates to an absolute risk for TN breast cancer ranging from 0.8% to 3.4%, suggesting that genetic variation may be used for TN breast cancer risk prediction.

A meta-analysis of genome-wide association studies of breast cancer identifies two novel susceptibility loci at 6q14 and 20q11.

Genome-wide association studies (GWAS) of breast cancer defined by hormone receptor status have revealed loci contributing to susceptibility of estrogen receptor (ER)-negative subtypes. To identify additional genetic variants for ER-negative breast cancer, we conducted the largest meta-analysis of ER-negative disease to date, comprising 4754 ER-negative cases and 31 663 controls from three GWAS: NCI Breast and Prostate Cancer Cohort Consortium (BPC3) (2188 ER-negative cases; 25 519 controls of European ancestry), Triple Negative Breast Cancer Consortium (TNBCC) (1562 triple negative cases; 3399 controls of European ancestry) and African American Breast Cancer Consortium (AABC) (1004 ER-negative cases; 2745 controls). We performed in silico replication of 86 SNPs at P ≤ 1 × 10(-5) in an additional 11 209 breast cancer cases (946 with ER-negative disease) and 16 057 controls of Japanese, Latino and European ancestry. We identified two novel loci for breast cancer at 20q11 and 6q14. SNP rs2284378 at 20q11 was associated with ER-negative breast cancer (combined two-stage OR = 1.16; P = 1.1 × 10(-8)) but showed a weaker association with overall breast cancer (OR = 1.08, P = 1.3 × 10(-6)) based on 17 869 cases and 43 745 controls and no association with ER-positive disease (OR = 1.01, P = 0.67) based on 9965 cases and 22 902 controls. Similarly, rs17530068 at 6q14 was associated with breast cancer (OR = 1.12; P = 1.1 × 10(-9)), and with both ER-positive (OR = 1.09; P = 1.5 × 10(-5)) and ER-negative (OR = 1.16, P = 2.5 × 10(-7)) disease. We also confirmed three known loci associated with ER-negative (19p13) and both ER-negative and ER-positive breast cancer (6q25 and 12p11). Our results highlight the value of large-scale collaborative studies to identify novel breast cancer risk loci.

Choosing Midwifery - The perceptions and experiences of Black, Asian and Minority Ethnic applicants to midwifery programmes: A mixed methods study.

AIM: to explore recruitment to UK midwifery programmes from the perspective of applicants from Black, Asian and Minority Ethnic (BAME) groups and describe the perceptions and experiences of the application process for these applicants and those from white backgrounds. BACKGROUND: Midwifery in the Global North is an overwhelmingly white profession. This lack of diversity has been cited as a factor in the poorer outcomes experienced by women from non-white backgrounds. There is a need for midwifery programmes to recruit and support more ethnically and racially diverse cohorts if this situation is to be addressed. Very little is currently known about the recruitment experiences of midwifery applicants. DESIGN: A mixed methods study comprising a survey and individual interview or focus group. The study was conducted between September 2020 and March 2021 in three universities in South East England. Participants comprised 440 applicants to midwifery programmes and 13 current or recently qualified BAME midwifery students. FINDINGS: Although many survey findings in respect to choosing a midwifery programme were broadly similar between candidates from BAME and non-BAME backgrounds, some trends were noted. More BAME applicants cited school/college rather than family as encouraging. More BAME applicants also indicated that they would consider issues of diversity when selecting a place of study, and BAME respondents appeared less likely to consider location and university life. Survey and focus group findings combined may indicate deficits in social capital available to BAME midwifery applicants. Focus group findings in particular suggest multiple experiences of challenge and inequity at all stages of the application process, together with a perception that midwifery is a niche and white profession. Applicants value proactive support from universities and would appreciate increased diversity, opportunities for mentorship and an individualised approach to recruitment. CONCLUSIONS: BAME applicants to midwifery can face additional challenges which have an impact on their ability to secure a place. There is a need to reposition midwifery as an inclusive and welcoming option for people from all backgrounds and to develop equitable recruitment processes that value a range of skills and life experiences.

Applied risk mapping and spatial analysis of address-level decedent data to inform opioid overdose interventions: The Massachusetts HEALing Communities Study.

BACKGROUND: Death certificate data provide powerful and sobering records of the opioid overdose crisis. In Massachusetts, where address-level decedent data are publicly available upon request, mapping and spatial analysis of fatal overdoses can provide valuable insights to inform prevention interventions. We describe how we used this approach to support a community-level intervention to reduce opioid-involved overdose mortality. METHODS: We developed a method to clean and geocode decedent data that substituted injury locations (the likely location of fatal overdoses) for deaths recorded in hospitals. After geomasking for greater privacy protection, we created maps to visualize the spatial distribution of decedent residence addresses, alone and juxtaposed with drive and walk-time distances to opioid treatment programs (OTPs), and place of death by overdose address. We used spatial statistical analyses to identify locations with significant clusters of overdoses. RESULTS: In the 8 intervention communities, 785 individuals died from opioid-involved overdoses between 2017 and 2020. We found that 19.7% of fatal overdoses were recorded in hospitals, 50.2% occurred at the decedent's residence, and 30.1% at another location. We identified overdose hotspots in study communities. By juxtaposing decedent residence data with drive- and walk-time analyses, we highlighted actionable spatial gaps in access to OTP treatment. CONCLUSION: To better understand local fatal opioid overdose risk environments and inform the development of community-level prevention interventions, we used publicly available address-level decedent data to conduct nuanced spatial analyses. Our approach can be replicated in other jurisdictions to inform overdose prevention responses.

Development of a data entry auditing protocol and quality assurance for a tissue bank database.

Human transcription error is an acknowledged risk when extracting information from paper records for entry into a database. For a tissue bank, it is critical that accurate data are provided to researchers with approved access to tissue bank material. The challenges of tissue bank data collection include manual extraction of data from complex medical reports that are accessed from a number of sources and that differ in style and layout. As a quality assurance measure, the Breast Cancer Tissue Bank (http:\\www.abctb.org.au) has implemented an auditing protocol and in order to efficiently execute the process, has developed an open source database plug-in tool (eAuditor) to assist in auditing of data held in our tissue bank database. Using eAuditor, we have identified that human entry errors range from 0.01% when entering donor's clinical follow-up details, to 0.53% when entering pathological details, highlighting the importance of an audit protocol tool such as eAuditor in a tissue bank database. eAuditor was developed and tested on the Caisis open source clinical-research database; however, it can be integrated in other databases where similar functionality is required.

Factors Associated With Normal Physiologic Birth for Women Who Labor In Water: A Secondary Analysis of A Prospective Observational Study.

INTRODUCTION: Research to understand factors associated with normal physiologic birth (unassisted vaginal birth, spontaneous labor onset without epidural analgesia, spinal, or general anesthetic, without episiotomy) is required. Laboring and/or giving birth in water has been shown to be associated with a high proportion of physiologic birth but with little understanding of factors that may influence this outcome. This study explored factors associated with normal physiologic birth for women who labored in water. METHODS: We conducted a secondary analysis of a UK-based prospective observational study of 8064 women at low risk of childbirth complications who labored in water. Consecutive women were recruited from birth settings in England, Scotland, and Northern Ireland. Planned place of birth, maternal characteristics, intrapartum events, and maternal and neonatal outcomes were measured. Univariable and multivariable logistic regression modelling explored factors associated with normal physiologic birth. RESULTS: In total, 5758 (71.4%) of women who labored in water had a normal physiologic birth. Planned birth in the community (adjusted odds ratio [aOR], 2.58; 95% CI, 2.22-2.99) or at an alongside midwifery unit (aOR, 1.21; 95% CI, 1.04-1.41) was positively associated with normal physiologic birth compared with planned birth in an obstetric unit. Duration of second stage (aOR, 0.66; 95% CI, 0.62-0.70), duration in the pool [aOR, 0.93; 95% CI, 0.90-0.96), and birth weight of the neonate (aOR, 0.74; 95% CI, 0.65-0.85) were negatively associated with normal physiologic birth. Parity was not associated with normal physiologic birth in multivariate analyses. DISCUSSION: Our findings largely reflected wider research, both in and out of water. We found midwifery-led birth settings may increase the likelihood of normal physiologic birth among healthy women who labor in water, irrespective of parity. This association supports growing evidence demonstrating the importance of planned place of birth on reducing intervention rates and adds to research on labor and birth in water.

Pharmacists' perceptions on real-time prescription monitoring (RTPM) systems - a cross-sectional survey.

Background: Real-time prescription monitoring (RTPM) systems are an effective tool to help health practitioners monitor opioid use and reduce opioid-related harm but little has been reported about the support required by pharmacists to engage with them effectively in practice. Objective: To evaluate the current understanding and perceptions of Western Australian pharmacists regarding RTPM systems and opioid-related harm, and investigate their self-reported training and support requirements prior to RTPM system implementation. Methods: This cross-sectional, prospective study involved an online Qualtrics survey distributed to Western Australian community or hospital pharmacists involved in dispensing and patient-centred roles via local professional pharmacy newsletters and social media. Data collection included demographic information, responses to authentic case scenarios and Likert-scale questions regarding perceptions and training requirements of a RTPM system, pain management and opioid-related harm. Descriptive analysis was utilised. Result: Sixty-two pharmacists responded to the questionnaire. Most (58/61; 95.1%) had a positive attitude towards RTPM systems, but only 33/61 (54.1%) reported being prepared for its implementation. Perceived barriers to successful implementation included lack of remuneration (46/60; 76.6%), conflict with prescribers (40/60; 66.7%), increased workload (37/60; 61.7%), staff safety concerns (34/60; 56.7%) and lack of knowledge regarding RTPM systems (32/60; 53.3%). Even though most participants were satisfied with training previously received, over 90% reported requiring further training and education, especially regarding RTPM systems (51/57; 96.2%) and opioid-related harm (56/57; 98.2%). Conclusion: Among a small sample of participants, there was a strong positivity regarding the value of RTPM systems and a high degree of receptiveness to further training in preparation for RTPM implementation.

Trends in Pediatric Candidemia: Epidemiology, Anti-Fungal Susceptibility, and Patient Characteristics in a Children's Hospital.

Candida bloodstream infections (CBSIs) have decreased among pediatric populations in the United States, but remain an important cause of morbidity and mortality. Species distributions and susceptibility patterns of CBSI isolates diverge widely between children and adults. The awareness of these patterns can inform clinical decision-making for empiric or pre-emptive therapy of children at risk for candidemia. CBSIs occurring from 2006-2016 among patients in a large children's hospital were analyzed for age specific trends in incidence rate, risk factors for breakthrough-CBSI, and death, as well as underlying conditions. Candida species distributions and susceptibility patterns were evaluated in addition to the anti-fungal agent use. The overall incidence rate of CBSI among this complex patient population was 1.97/1000 patient-days. About half of CBSI episodes occurred in immunocompetent children and 14% in neonatal intensive care unit (NICU) patients. Anti-fungal resistance was minimal: 96.7% of isolates were fluconazole, 99% were micafungin, and all were amphotericin susceptible. Liposomal amphotericin was the most commonly prescribed anti-fungal agent included for NICU patients. Overall, CBSI-associated mortality was 13.7%; there were no deaths associated with CBSI among NICU patients after 2011. Pediatric CBSI characteristics differ substantially from those in adults. The improved management of underlying diseases and antimicrobial stewardship may further decrease morbidity and mortality from CBSI, while continuing to maintain low resistance rates among Candida isolates.

Building Research Support Capacity across Human Health Biobanks during the COVID-19 Pandemic.

Human health biobanks are forms of research infrastructure that supply biospecimens and associated data to researchers, and therefore juxtapose the activities of clinical care and biomedical research. The discipline of biobanking has existed for over 20 years and is supported by several international professional societies and dedicated academic journals. However, despite both rising research demand for human biospecimens, and the growth of biobanking as an academic discipline, many individual biobanks continue to experience sustainability challenges. This commentary will summarize how the COVID-19 pandemic is creating new challenges and opportunities for both the health biobanking sector and the supporting discipline of biobanking. While the challenges for biobanks may be numerous and acute, there are opportunities for both individual biobanks and the discipline of biobanking to embrace change such that biobanks can continue to support and drive biomedical research. We will therefore describe numerous practical steps that individual biobanks and/or the discipline of biobanking can take to survive and possibly thrive in response to the COVID-19 pandemic.

Practice Improvement for Standardized Evaluation and Management of Acute Tracheitis in Mechanically Ventilated Children.

There is no consensus definition for ventilator-associated tracheitis and limited evidence to guide diagnosis and treatment. To improve acute tracheitis evaluation and management, this quality improvement project aimed to (1) improve the appropriateness of tracheal aspirate cultures while decreasing the number of unnecessary cultures by 20% and (2) decrease antibiotic use for acute tracheitis not consistent with local guidelines by 20% over 12 months among pediatric patients requiring mechanical ventilation. METHODS: All patients admitted to the Medical Intensive Care Unit requiring mechanical ventilation via an artificial airway were included. Tracheal aspirate sampling criteria, technique, and minimum intervals were standardized. Primary outcome measures were the number of tracheal aspirate cultures obtained per 100 ETT/tracheostomy days and ventilator-associated antibiotic days per 100 ETT/tracheostomy days. Improvement cycles included: Implementation of tracheal aspirate sampling criteria, sampling technique standardization, limiting repeat cultures to >72-hour intervals, and standardizing empiric antibiotic therapy. RESULTS: Tracheal aspirate culture rate decreased from 10.70 to 7.10 cultures per 100 ETT/tracheostomy days (P < 0.001). Cultures meeting sampling criteria increased from 28% to 80%. Ventilator-associated antibiotic use decreased from 24.88 to 7.30 ventilator-associated antibiotic days per 100 ETT/tracheostomy days. There were no associated increases in ventilator-associated events or days of mechanical ventilation. CONCLUSIONS: Implementation of standardized criteria for tracheal aspirate sampling, improved tracheal aspirate sampling technique, limiting repeat tracheal aspirate cultures, and utilizing standardized antibiotic treatment guidelines safely decreased resource utilization and antibiotic use among critically ill children requiring mechanical ventilation.

Stewardship Intervention to Optimize Central Venous Catheter Utilization in Critically Ill Children.

We aimed to describe utilization and indication(s) for long-term central venous catheters (CVCs) in a pediatric intensive care unit (PICU) and identify potential strategies to decrease CVC utilization. METHODS: We conducted a single-center prospective quality improvement initiative at a 30-bed PICU in a large, freestanding, academic children's hospital. We created an electronic report to identify patients with an indwelling CVC for 7 days and older (defined as long term). We discussed the ongoing need for each long-term CVC with PICU clinicians at weekly interdisciplinary structured "CVC stewardship rounds." We then made recommendations around expedited removal of CVCs. We conducted multiple Plan-Do-Study-Act cycles to categorize CVC indications, identify modifiable factors, and educate PICU clinicians. We hypothesized that CVC stewardship rounds would decrease long-term CVC utilization in our PICU. RESULTS: From October 2016 to September 2017, 607 long-term CVCs were eligible for the stewardship intervention. Compared to the preintervention period, we recorded a significant increase in peripherally inserted central catheters and a decrease in nontunneled CVCs (P < 0.001). Most patients had single- or double-lumen CVCs in both the preintervention and intervention periods (86% and 91%, respectively). The utilization of overall long-term CVC devices, and those with modifiable indications, decreased during the intervention period. CONCLUSIONS: A single-center QI intervention focused on PICU CVC stewardship was associated with a decrease in CVC utilization.

Central venous catheter bundle adherence: Kamishibai card (K-card) rounding for central-line-associated bloodstream infection (CLABSI) prevention.

OBJECTIVE: To institute facility-wide Kamishibai card (K-card) rounding for central venous catheter (CVC) maintenance bundle education and adherence and to evaluate its impact on bundle reliability and central-line-associated bloodstream infection (CLABSI) rates. DESIGN: Quality improvement project. SETTING: Inpatient units at a large, academic freestanding children's hospital. PARTICIPANTS: Data for inpatients with a CVC in place for ≥1 day between November 1, 2017 and October 31, 2018 were included. INTERVENTION: A K-card was developed based on 7 core elements in our CVC maintenance bundle. During monthly audits, auditors used the K-cards to ask bedside nurses standardized questions and to conduct medical record documentation reviews in real time. Adherence to every bundle element was required for the audit to be considered "adherent." We recorded bundle reliability prospectively, and we compared reliability and CLABSI rates at baseline and 1 year after the intervention. RESULTS: During the study period, 2,321 K-card audits were performed for 1,051 unique patients. Overall maintenance bundle reliability increased significantly from 43% at baseline to 78% at 12 months after implementation (P < .001). The hospital-wide CLABSI rate decreased from 1.35 during the 12-month baseline period to 1.17 during the 12-month intervention period, but the change was not statistically significant (incidence rate ratio [IRR], 0.87; 95% confidence interval [CI], 0.60-1.24; P = .41). CONCLUSIONS: Hospital-wide CVC K-card rounding facilitated standardized data collection, discussion of reliability, and real-time feedback to nurses. Maintenance bundle reliability increased after implementation, accompanied by a nonsignificant decrease in the CLABSI rate.

Toward a Synergistic Operating Model for Westmead Research Hub Biobanks: A Questionnaire Study.

Standardization and sustainability are ideals within the biobanking world, and the demand for high-quality well-annotated specimens is growing just as rapidly as the ever-increasing precision and throughput of today's high-tech scientific methods. In the state of New South Wales (NSW) in Australia, the state government has allocated significant funding toward this requirement in recent years, with the launch of the NSW Health Statewide Biobank in central Sydney in 2017, and the introduction of the voluntary NSW Biobank Certification Program, and Consent Toolkit. For new and established biobanks, the influence of these new resources has been twofold: first they have provided valuable guidance for moving toward standardized practices and raising the bar for biobanking quality standards; second, they have brought to the forefront the challenges of sustainability and transitioning to a certification standard of biobanking. In Westmead, ∼20 km from Sydney's central business district, the Westmead Research Hub has responded to these challenges with a collaborative biobanking project initiated in 2015. As the site of almost 30 individual biobanks, and to inform a pilot project of central biobank services, a questionnaire was developed and administered to all of the biobanks. This article reports on the results from the questionnaire and the rationale for subsequent initiation of a core biobanking facility.