An Educational Intervention for Infusion Center Nurses to Improve Their Confidence in Identification and Management of Immunotherapy Adverse Events, Based on Changes in Pre- and Post-test scores: A Quality Improvement Project

BACKGROUND: Immunotherapy is a treatment that uses the body’s immune system to fight diseases. It is used for the management of many conditions but is mainly utilized in cancer treatment. Immunotherapy has been shown to improve quality of life and increase survival rates in metastatic disease. A major limitation of immunotherapy are the adverse events (AE), or adverse effects, that may cause a delay in treatment, lead to hospitalization, or in extreme cases, mortality. In this study the terms adverse events and adverse effects will be used interchangeably. DESIGN: Pre- and post-test survey design. METHODS: Data was collected from a sample of 23 Infusion Center nurses following an education intervention on identification and management of immunotherapy adverse events, using the Oncology Nurse Immunotherapy Confidence Survey (ONICS) instrument modified for this QI project. RESULTS: The pre- and post-test scores revealed a 39% increase in Infusion Centers nurses’ confidence regarding identification and management of immunotherapy adverse events shown. These findings were established as statically significant (p \u3e 0.0001). CONCLUSIONS: Novice nurses and experienced nurses new to the Oncology specialty would most benefit from this intervention. Department orientation policies can be reviewed and modified based on the data from this project to improve the quality of patient care

Preoperative Education Regarding the Enhanced Recovery After Surgery (ERAS) Guideline for Colorectal Surgical Patients: A Quality Improvement Project

BACKGROUND: Advancements in colorectal surgeries can be attributed to the adoption of the Enhanced Recovery After Surgery (ERAS) clinical guideline, which is a system of perioperative interventions bundled together cohesively to enhance a patient’s surgical experience, especially their post-operative recovery. One of the first interventions that initiates the ERAS process is the delivery of patient education before surgery. However, there are currently no standardizations on the kind of content or method of delivery for this education. PURPOSE: This Quality Improvement (QI) project determined the effects of a private, in-person, educational program discussing in detail the ERAS guideline adopted by their treating facility and the patient’s active role in the recovery process. An enhanced quality of recovery for these colorectal surgical patients was evaluated by measures of an early return to normal activities of daily living (ADLs), symptom incidence, levels of anxiety, and patient satisfaction when compared to patients who receive usual care. METHODS: A multivariate, repeated measures design was used, which followed the Plan, Do, Study, and Act (PDSA) model. The sample consisted of ten participants who were scheduled for colorectal surgery at a community medical center. Participants were given code numbers where odd numbered participants received the educational intervention and even numbered participants represented the usual care, control group. After informed consent, a Demographic and Clinical Data form was completed for each participant. The Quality of Recovery- 40 (QoR-40) questionnaire was administered to the intervention and usual care groups at two time points: upon hospital discharge and one week following hospital discharge. Descriptive analysis was used to identify trends in the Demographic and Clinical Data forms, while changes in the scores on the QoR-40 questionnaires was measured by independent and paired t-tests. RESULTS: A two-tailed paired t-test analyzed the difference in mean scores of the intervention group on Discharge Day and One-week Post-Discharge, revealing statistical significance with a t-score (5) = 3.9198 and p-value = 0.0173. Another two-tailed paired t-test analyzed the difference in mean scores of the control group on Discharge Day and One-week Post-Discharge, revealing statistical significance by a t-score (5) = 2.9994 and a p-value = 0.004. However, completing a one-tailed independent t-test on Discharge Day scores between the intervention and control group revealed no statistical significance as demonstrated by t-score (5) = 0.6551, and a p-value = 0.5308 (p\u3e0.05). Another one-tailed independent t-test on One-week Post-Discharge scores between the intervention and control group revealed no statistical significance as demonstrated by a t-score (5) = 1.2421, and a p-value = 0.2494. DISCUSSION: The results of this QI project indicate that for elective colorectal surgical patients, education regarding the ERAS guideline is not required to enhance their surgical recovery, measured by an early return to ADLs, decreases postoperative symptoms, decreased levels of anxiety, and overall increased patient satisfaction. Further research is needed to study the effects of different preoperative educational material to determine what content is most influential on patients’ surgical recovery

Awake prone positioning for COVID-19 patients at Eka Kotebe General Hospital, Addis Ababa, Ethiopia: A prospective cohort study

Objectives: The objectives of the study were to evaluate the benefit of awake prone positioning in COVID-19 patients hospitalized at Eka Kotebe General Hospital, Addis Ababa, Ethiopia.Materials and Methods: Consecutive patients with COVID-19 who require supplemental oxygen to maintain oxygen saturation of ≥90% during the month of October 2020 were enrolled. Structured questionnaires were employed to collect data. Admission oxygen saturation was recorded for each patient before and after their first proning session. Analysis of descriptive and comparison statistics was done using SPSS version 25.Results: A total of 61 patients were included in the study. The mean age (+SD) for the cohort was 55.4 (+16.9) years. The average duration of proning was 5+2.5 h/session and 8+6 h/day. The average oxygen saturation before proning was 89% (SD 5.2) and 93% (SD 2.8) 1 h after proning (P < 0.001); supplemental oxygen requirements significantly decreased with prone ventilation, before proning: FiO2 0.33 (+0.14) versus 1 h after prone ventilation: FiO2 0.31 (+0.13) (P < 0.001). Oxygen improvement with prone ventilation was not associated with duration of illness or total prone position hours. When assessed at 28 days after admission, 55.7% (n = 34) had been discharged home, 1.6% (n = 1) had died, and 42.6 (n = 26) were still hospitalized.Conclusion: Awake prone positioning demonstrated improved oxygen saturation in our oxygen requiring COVID-19 patients. Even though further studies are needed to support causality and determine the effect of proning on disease severity and mortality, early institution of prone ventilation in appropriate oxygen requiring COVID-19 patients should be encouraged

Removal of pertechnetate from simulated nuclear waste streams using supported zerovalent

The application of nanoparticles of predominantly zerovalent iron (nanoiron), either unsupported or supported, to the separation and reduction of pertechnetate anions (TcO 4 -) from complex waste mixtures was investigated as an alternative approach to current waste-processing schemes. Although applicable to pertechnetate-containing waste streams in general, the research discussed here was directed at two specific potential applications at the U.S. Department of Energy's Hanford Site: (1) the direct removal of pertechnetate from highly alkaline solutions, typical of those found in Hanford tank waste, and (2) the removal of dilute pertechnetate from near-neutral solutions, typical of the eluate streams from commercial organic ion-exchange resins that may be used to remediate Hanford tank wastes. It was envisioned that both applications would involve the subsequent encapsulation of the loaded sorbent material into a separate waste form. A high surface area (>200 m 2 /g) base-stable, nanocrystalline zirconia was used as a support for nanoiron for tests with highly alkaline solutions, while a silica gel support was used for tests with near-neutral solutions. It was shown that after 24 h of contact time, the high surface area zirconia supported nanoiron sorbent removed about 50% (K d ) 370 L/kg) of the pertechnetate from a pH 14 tank waste simulant containing 0.51 mM TcO 4 -and large concentrations of Na + , OH -, NO 3 -, and CO 3 2-for a phase ratio of 360 L simulant per kg of sorbent. It was also shown that after 18 h of contact time, the silica-supported nanoiron removed >95% pertechnetate from a neutral pH eluate simulant containing 0.076 mM TcO 4 -for a phase ratio of 290 L/kg. It was determined that in all cases, nanoiron reduced the Tc(VII) to Tc(IV), or possibly to Tc(V), through a redox reaction. Finally, it was demonstrated that a mixture of 20 mass % of the solid reaction products obtained from contacting zirconia-supported nanoiron with an alkaline waste solution containing Re(VII), a surrogate for Tc(VII), with 80 mass % alkali borosilicate based frit heat-treated at 700°C for 4 h sintered into an easily handled glass composite waste form

Early Detection of Ovarian Cancer using the Risk of Ovarian Cancer Algorithm with Frequent CA125 Testing in Women at Increased Familial Risk – Combined Results from Two Screening Trials

Purpose: Women at familial/genetic ovarian cancer risk often undergo screening despite unproven efficacy. Research suggests each woman has her own CA125 baseline; significant increases above this level may identify cancers earlier than standard 6- to 12-monthly CA125 > 35 U/mL. Experimental Design: Data from prospective Cancer Genetics Network and Gynecologic Oncology Group trials, which screened 3,692 women (13,080 woman-screening years) with a strong breast/ovarian cancer family history or BRCA1/2 mutations, were combined to assess a novel screening strategy. Specifically, serum CA125 q3 months, evaluated using a risk of ovarian cancer algorithm (ROCA), detected significant increases above each subject's baseline, which triggered transvaginal ultrasound. Specificity and positive predictive value (PPV) were compared with levels derived from general population screening (specificity 90%, PPV 10%), and stage-at-detection was compared with historical high-risk controls. Results: Specificity for ultrasound referral was 92% versus 90% ( P = 0.0001), and PPV was 4.6% versus 10% ( P > 0.10). Eighteen of 19 malignant ovarian neoplasms [prevalent = 4, incident = 6, risk-reducing salpingo-oophorectomy (RRSO) = 9] were detected via screening or RRSO. Among incident cases (which best reflect long-term screening performance), three of six invasive cancers were early-stage (I/II; 50% vs. 10% historical BRCA1 controls; P = 0.016). Six of nine RRSO-related cases were stage I. ROCA flagged three of six (50%) incident cases before CA125 exceeded 35 U/mL. Eight of nine patients with stages 0/I/II ovarian cancer were alive at last follow-up (median 6 years). Conclusions: For screened women at familial/genetic ovarian cancer risk, ROCA q3 months had better early-stage sensitivity at high specificity, and low yet possibly acceptable PPV compared with CA125 > 35 U/mL q6/q12 months, warranting further larger cohort evaluation. Clin Cancer Res; 23(14); 3628-37. ©2017 AACR

Autologous chondrocyte implantation-derived synovial fluids display distinct responder and non-responder proteomic profiles

Hulme, Charlotte H. & Wilson, Emma L. - Equal contributorsBackground Autologous chondrocyte implantation (ACI) can be used in the treatment of focal cartilage injuries to prevent the onset of osteoarthritis (OA). However, we are yet to understand fully why some individuals do not respond well to this intervention. Identification of a reliable and accurate biomarker panel that can predict which patients are likely to respond well to ACI is needed in order to assign the patient to the most appropriate therapy. This study aimed to compare the baseline and mid-treatment proteomic profiles of synovial fluids (SFs) obtained from responders and non-responders to ACI. Methods SFs were derived from 14 ACI responders (mean Lysholm improvement of 33 (17–54)) and 13 non-responders (mean Lysholm decrease of 14 (4–46)) at the two stages of surgery (cartilage harvest and chondrocyte implantation). Label-free proteome profiling of dynamically compressed SFs was used to identify predictive markers of ACI success or failure and to investigate the biological pathways involved in the clinical response to ACI. Results Only 1 protein displayed a ≥2.0-fold differential abundance in the preclinical SF of ACI responders versus non-responders. However, there is a marked difference between these two groups with regard to their proteome shift in response to cartilage harvest, with 24 and 92 proteins showing ≥2.0-fold differential abundance between Stages I and II in responders and non-responders, respectively. Proteomic data has been uploaded to ProteomeXchange (identifier: PXD005220). We have validated two biologically relevant protein changes associated with this response, demonstrating that matrix metalloproteinase 1 was prominently elevated and S100 calcium binding protein A13 was reduced in response to cartilage harvest in non-responders. Conclusions The differential proteomic response to cartilage harvest noted in responders versus non-responders is completely novel. Our analyses suggest several pathways which appear to be altered in non-responders that are worthy of further investigation to elucidate the mechanisms of ACI failure. These protein changes highlight many putative biomarkers that may have potential for prediction of ACI treatment success

Common genetic variants in the CLDN2 and PRSS1-PRSS2 loci alter risk for alcohol-related and sporadic pancreatitis

Pancreatitis is a complex, progressively destructive inflammatory disorder. Alcohol was long thought to be the primary causative agent, but genetic contributions have been of interest since the discovery that rare PRSS1, CFTR, and SPINK1 variants were associated with pancreatitis risk. We now report two significant genome-wide associations identified and replicated at PRSS1-PRSS2 (1×10-12) and x-linked CLDN2 (p < 1×10-21) through a two-stage genome-wide study (Stage 1, 676 cases and 4507 controls; Stage 2, 910 cases and 4170 controls). The PRSS1 variant affects susceptibility by altering expression of the primary trypsinogen gene. The CLDN2 risk allele is associated with atypical localization of claudin-2 in pancreatic acinar cells. The homozygous (or hemizygous male) CLDN2 genotype confers the greatest risk, and its alleles interact with alcohol consumption to amplify risk. These results could partially explain the high frequency of alcohol-related pancreatitis in men – male hemizygous frequency is 0.26, female homozygote is 0.07

Breast cancer risk variants at 6q25 display different phenotype associations and regulate ESR1, RMND1 and CCDC170.

We analyzed 3,872 common genetic variants across the ESR1 locus (encoding estrogen receptor α) in 118,816 subjects from three international consortia. We found evidence for at least five independent causal variants, each associated with different phenotype sets, including estrogen receptor (ER(+) or ER(-)) and human ERBB2 (HER2(+) or HER2(-)) tumor subtypes, mammographic density and tumor grade. The best candidate causal variants for ER(-) tumors lie in four separate enhancer elements, and their risk alleles reduce expression of ESR1, RMND1 and CCDC170, whereas the risk alleles of the strongest candidates for the remaining independent causal variant disrupt a silencer element and putatively increase ESR1 and RMND1 expression.This is the author accepted manuscript. The final version is available from Nature Publishing Group via http://dx.doi.org/10.1038/ng.352

Polygenic Risk Scores for Prediction of Breast Cancer and Breast Cancer Subtypes

Stratification of women according to their risk of breast cancer based on polygenic risk scores (PRSs) could improve screening and prevention strategies. Our aim was to develop PRSs, optimized for prediction of estrogen receptor (ER)-specific disease, from the largest available genome-wide association dataset and to empirically validate the PRSs in prospective studies. The development dataset comprised 94,075 case subjects and 75,017 control subjects of European ancestry from 69 studies, divided into training and validation sets. Samples were genotyped using genome-wide arrays, and single-nucleotide polymorphisms (SNPs) were selected by stepwise regression or lasso penalized regression. The best performing PRSs were validated in an independent test set comprising 11,428 case subjects and 18,323 control subjects from 10 prospective studies and 190,040 women from UK Biobank (3,215 incident breast cancers). For the best PRSs (313 SNPs), the odds ratio for overall disease per 1 standard deviation in ten prospective studies was 1.61 (95%CI: 1.57-1.65) with area under receiver-operator curve (AUC) = 0.630 (95%CI: 0.628-0.651). The lifetime risk of overall breast cancer in the top centile of the PRSs was 32.6%. Compared with women in the middle quintile, those in the highest 1% of risk had 4.37- and 2.78-fold risks, and those in the lowest 1% of risk had 0.16- and 0.27-fold risks, of developing ER-positive and ER-negative disease, respectively. Goodness-of-fit tests indicated that this PRS was well calibrated and predicts disease risk accurately in the tails of the distribution. This PRS is a powerful and reliable predictor of breast cancer risk that may improve breast cancer prevention programs.NovartisEli Lilly and CompanyAstraZenecaAbbViePfizer UKCelgeneEisaiGenentechMerck Sharp and DohmeRocheCancer Research UKGovernment of CanadaArray BioPharmaGenome CanadaNational Institutes of HealthEuropean CommissionMinistère de l'Économie, de l’Innovation et des Exportations du QuébecSeventh Framework ProgrammeCanadian Institutes of Health Researc