Education provision in community setting increases engagement with bowel cancer screening.

In the United Kingdom, colorectal carcinoma (CRC) is the third most prevalent and second most lethal cancer, accounting for 1 in 10 cancer deaths. To address this health burden, the NHS implemented a national screening programme to detect traces of blood in the stool of those at highest risk of CRC - men and women aged over 60. Preliminary data showed that the screening programme reduced CRC death by 16% overall and 23% in those who had returned their kit, highlighting the importance of patient engagement. Worryingly, recent data has indicated that engagement with the screening programme has begun to decline. Many GP surgeries are failing to achieve the 75% quota set by the Quality and Outcomes Framework, with London performing least favourably within the UK. To address this, we set up an educational intervention at a London GP practice, targeting misconceptions and anxieties associated with bowel screening and CRC in general, to assess whether this would improve patients' confidence in returning a stool sample as suggested by previous studies. Our results came to promising conclusions, but we remain cautious that our preliminary findings are subject to confounding influences which prevent conclusion of a causal relationship.

Freestanding Dialysis Facility Quality Incentive Program Scores and Mortality Among Incident Dialysis Patients in the United States.

RATIONALE & OBJECTIVE: The Centers for Medicare & Medicaid Services introduced the Quality Incentive Program (QIP) along with the bundled payment reform to improve the quality of dialysis care in the United States. The QIP has been criticized for using easily obtained laboratory indicators without patient-centered measures and for a lack of evidence for an association between QIP indicators and patient outcomes. This study examined the association between dialysis facility QIP performance scores and survival among patients after initiation of dialysis. STUDY DESIGN: Retrospective cohort study. SETTING & PARTICIPANTS: Study participants included 84,493 patients represented in the US Renal Disease System's patient-level data who had initiated dialysis between January 1, 2013, and December 1, 2013, and who did not, during the first 90 days after dialysis initiation, die, receive a transplant, or become lost to follow-up. Patients were followed up for the study outcome through March 31, 2014. PREDICTOR: Dialysis facility QIP scores. OUTCOME: Mortality. ANALYTICAL APPROACH: Using a unique facility identifier, we linked Medicare freestanding dialysis facility data from 2015 with US Renal Disease System patient-level data. Kaplan-Meier product limit estimator was used to describe the survival of study participants. Cox proportional hazards regression was used to assess the multivariable association between facility performance scores and patient survival. RESULTS: Excluding patients who died during the first 90 days of dialysis, 11.8% of patients died during an average follow-up of 5 months. Facilities with QIP scores<45 (HR, 1.39; 95% CI, 1.15-1.68) and 45 to<60 (HR, 1.21; 95% CI, 1.10-1.33) had higher patient mortality rates than facilities with scores≥90. LIMITATIONS: Because the Centers for Medicare & Medicaid Services have revised QIP criteria each year, the findings may not relate to years other than those studied. CONCLUSIONS: Dialysis facilities characterized by lower QIP scores were associated with higher rates of patient mortality. These findings need to be replicated to assess their consistency over time.

Assessment of Label-Free Quantification in Discovery Proteomics and Impact of Technological Factors and Natural Variability of Protein Abundance.

We evaluated the state of label-free discovery proteomics focusing especially on technological contributions and contributions of naturally occurring differences in protein abundance to the intersample variability in protein abundance estimates in this highly peptide-centric technology. First, the performance of popular quantitative proteomics software, Proteome Discoverer, Scaffold, MaxQuant, and Progenesis QIP, was benchmarked using their default parameters and some modified settings. Beyond this, the intersample variability in protein abundance estimates was decomposed into variability introduced by the entire technology itself and variable protein amounts inherent to individual plants of the Arabidopsis thaliana Col-0 accession. The technical component was considerably higher than the biological intersample variability, suggesting an effect on the degree and validity of reported biological changes in protein abundance. Surprisingly, the biological variability, protein abundance estimates, and protein fold changes were recorded differently by the software used to quantify the proteins, warranting caution in the comparison of discovery proteomics results. As expected, ∼99% of the proteome was invariant in the isogenic plants in the absence of environmental factors; however, few proteins showed substantial quantitative variability. This naturally occurring variation between individual organisms can have an impact on the causality of reported protein fold changes.

Hemodialysis Hospitalizations and Readmissions: The Effects of Payment Reform.

BACKGROUND: In 2004, the Centers for Medicare & Medicaid Services changed reimbursement for physicians and advanced practitioners caring for patients receiving hemodialysis from a capitated to a tiered fee-for-service system, encouraging increased face-to-face visits. This early version of a pay-for-performance initiative targeted a care process: more frequent provider visits in hemodialysis. Although more frequent provider visits in hemodialysis are associated with fewer hospitalizations and rehospitalizations, it is unknown whether encouraging more frequent visits through reimbursement policy also yielded these benefits. STUDY DESIGN: We used a retrospective cohort interrupted time-series study design to examine whether the 2004 nephrologist reimbursement reform led to reduced hospitalizations and rehospitalizations. We also used published data to estimate a range of annual economic costs associated with more frequent visits. SETTING & PARTICIPANTS: Medicare beneficiaries in the United States receiving hemodialysis in the 2 years prior to and following reimbursement reform. PREDICTOR: The 2 years following nephrologist reimbursement reform. OUTCOMES: Odds of hospitalization and 30-day hospital readmission for all causes and fluid overload; US dollars. RESULTS: We found no significant change in all-cause hospitalization or rehospitalization and slight reductions in fluid overload hospitalization and rehospitalization following reimbursement reform; the estimated economic cost associated with additional visits ranged from $13 to $87 million per year, depending on who (physicians or advanced practitioners) spent additional time visiting patients and how much additional effort was involved. LIMITATIONS: Due to limited information about how much additional time providers spent seeing patients after reimbursement reform, we could only examine a range of potential economic costs associated with the reform. CONCLUSIONS: A Medicare reimbursement policy designed to encourage more frequent visits during outpatient hemodialysis may have been costly. The policy was associated with fewer hospitalizations and rehospitalizations for fluid overload, but had no effect on all-cause hospitalizations or rehospitalizations.

Practice based collaboration to improve the use of immediate intravesical therapy after resection of nonmuscle invasive bladder cancer.

PURPOSE: Perioperative instillation of intravesical chemotherapy after bladder tumor resection is supported by level I evidence showing a 30% decrease in tumor recurrence. However, studies of administrative data sets show poor use in practice. MATERIALS AND METHODS: We prospectively evaluated the use of perioperative intravesical chemotherapy in a multipractice quality improvement collaborative. Cases were categorized as ideal for intravesical chemotherapy (1 or 2 papillary tumors, cTa/cT1 and completely resected) and nonideal. The reasons for not administering intravesical chemotherapy in ideal cases were classified as appropriate or modifiable. Before and after comparative feedback and educational interventions we calculated judicious use of intravesical chemotherapy (nonuse in nonideal cases plus use in ideal cases plus appropriate nonuse in ideal cases) and quality improvement potential (use in nonideal cases plus nonuse in ideal cases attributable to modifiable factors). RESULTS: We accrued a total of 2,794 cases at the 5 sites in 22 months. The rate of use in ideal cases was 38% before and 34.8% after intervention (p=0.36), while use in nonideal cases decreased from 15% to 12% (p=0.08). Overall, intravesical chemotherapy was used judiciously in 83.0% to 85.7% of cases, while the remaining 14.3% to 17.0% represented quality improvement potential. CONCLUSIONS: Judicious use of perioperative intravesical chemotherapy is relatively high in routine practice. Most instances of nonuse represent appropriate clinical judgment. Utilization did not change after quality improvement interventions, suggesting that there may a ceiling effect that makes it difficult to improve care that is high quality at baseline. Moreover, decreasing unnecessary use of an intervention may be easier than encouraging appropriate use of potentially toxic therapy.

The process of identifying major trauma in the older person in a single major trauma centre: A service evaluation.

BACKGROUND: Diagnosis of major trauma in the older person is increasingly recognised as clinically challenging with recent reports finding that older patients sustaining major trauma are commonly under-recognised and subsequently are not receiving gold standard major trauma care. This paper is a service evaluation of the processes of major trauma (ISS > 15) care for patients > 65 years presenting to a UK major trauma centre. AIM: To identify modifiable factors within the patient journey that might inform future service improvement initiatives. METHODS: TARN audit data and retrospective notes review of 190 patients > 65 presenting to UHS ED from 1st January 2018 - 31st December 2018 who did not receive a level 1 trauma call on arrival were used to achieve the dataset. Descriptive statistics were combined with multiple logistic regression to look for associations between specific process factors and a missed or delayed diagnosis. RESULTS: The evaluation found that, of the cohort not receiving a level 1 trauma call, 42 (22.1%) patients received a level 2 trauma call; 87 (45.7%) patients were seen initially by a senior clinician, with only 31 (16.3%) patients meeting best practice tariff for consultant within 5 min; 60 (31.5%) patients were seen directly in the resuscitation room; 48 (25.2%) patients received a trauma CT scan with only 27 (14.2%) meeting BPT for CT head within 1 h; 142 (74.7%) patients were admitted to a trauma specialty after discharge from ED. A total of 76 (40%) patients had a missed diagnosis of major trauma with 80 (42%) having a delayed diagnosis. Logistic regression showed a significant association between being seen in a standard initial assessment area (referred to as pitstop in this article) vs the resuscitation room as a first location (p = 0.007) with a delayed diagnosis; and a significant association between plain film imaging vs CT imaging (p = 0.000) and no trauma call vs trauma call (p = 0.009) with a missed diagnosis of major trauma. CONCLUSION: The findings of this service evaluation suggest that service improvement initiatives should be aimed at the early stages of the patient journey to improve missed or delayed diagnoses of major trauma in this patient group.

The Role of Quality Improvement Projects in a Complex Abdominal Wall Service.

Background Complex abdominal wall hernias have proven challenging to manage, and such patients often require abdominal wall reconstruction (AWR). However, in the context of a socialist healthcare service, which is required to provide equal and fair healthcare access to all, the heavy resource burden and non-life-threatening nature of complex abdominal wall hernias mean that this patient group may not be prioritised. In this paper, we outline the significant quality of life (QoL) burden on patients requiring AWR and the importance of quality improvement projects (QIPs) in establishing and streamlining their care as a robust, transferable model across centres. Methodology We undertook the creation of a regional AWR multidisciplinary team meeting and referral proforma, establishing a joint clinic between the Plastics and General Surgery teams and registering a standard operating procedure for the use of progressive pneumoperitoneum in a subset of AWR patients. We collected qualitative data using questionnaires sent out to clinicians and patients as well as used recognised outcome scales (pre- and post-operative European Hernia Society Quality of Life score, otherwise known as EuraHS-QoL score, and post-operative Carolinas Comfort Scale score) to assess responses to QIPs. Results Both clinicians and patients reported positive feelings towards the implemented changes, and scores following progressive pneumoperitoneum showed significant improvement. Conclusions Therefore, we propose that QIPs have a significant role in the establishment and streamlining of services for patients requiring AWR. Through the repeated use of QIPs, a robust, transferable model could be produced, which could then be shared with other regional specialist centres nationwide. As such, effective care could be offered equally to AWR patients for improved outcomes and reduced strain on healthcare resources.

Safer citalopram use in primary care: Can staff education and prescribing prompts improve adherence to national guidance? A closed loop clinical audit, service evaluation and quality improvement study.

Background: Citalopram is a drug with many important safety considerations in prescribing including dosage adjustments, pre-prescription testing and multiple interactions. Because of this, the UK government issued advice regarding the prescription of citalopram and escitalopram in its Drug Safety Update Vol 5 Issue 5, Dec 2011,[1] and the expectation is that all prescribers adhere to this. Purpose/Aim: To establish the adherence to prescribing guidance of citalopram at the practice level, implement change to address the lack of adherence and then evaluate the effectiveness of the change using re-audit techniques. Methods: Patients were identified using data searching techniques on EMIS for February-April 2020. Parameters searched for included age, hepatic impairment, cardiac disease, known QT prolongation and concomitant use with other QT-prolonging medication. Following the first cycle teaching on the safer use of citalopram was delivered to all prescribers and an EMIS prompt was also set up. A second audit cycle was then carried out. Data was analysed using Statistical Package for Social Sciences software to assess the significance of the results. Results: Following the presentation of the first cycle findings and the introduction of the EMIS safety prompt, there was a statistically significant reduction in incorrect citalopram dose prescription in the over 65s (8 vs 1), a statistically significant reduction in the incidence of dangerous drug interactions involving citalopram (44 vs 8) and a significant reduction in the incidence of unsafe prescribing of citalopram overall (47 vs 9). Conclusion: The introduction of an EMIS prompt and one-off prescriber teaching resulted in a statistically significant reduction in incorrect prescriptions of citalopram when re-audited a year later. These interventions resulted in improved patient safety and more effective use of resources and could easily be replicated at other practices throughout the country both for citalopram and other drugs with multiple safety considerations.

Optimizing Door-to-Groin Puncture Time: The Mayo Clinic Experience.

Objectives: To provide a better understanding of methods that can be used to improve patient outcomes by reducing the door-to-groin puncture (DTP) time and present the results of a stroke quality improvement project (QIP) conducted by Mayo Clinic Arizona's stroke center. Methods: We conducted a systematic literature search of Ovid MEDLINE(R), Ovid EMBASE, Scopus, and Web of Science for studies that evaluated DTP time reduction strategies. Those determined eligible for the purpose of this analysis were assessed for quality. The strategies for DTP time reduction were categorized on the basis of modified Target: Stroke Phase III recommendations and analyzed using a meta-analysis. The Mayo Clinic QIP implemented a single-call activation system to reduce DTP times by decreasing the time from neurosurgery notification to case start. Results: Fourteen studies were selected for the analysis, consisting of 2277 patients with acute ischemic stroke secondary to large-vessel occlusions. After intervention, all the studies showed a reduction in the DTP time, with the pooled DTP improvement being the standardized mean difference (1.37; 95% confidence interval, 1.20-1.93; τ2=1.09; P<.001). The Mayo Clinic QIP similarly displayed a DTP time reduction, with the DTP time dropping from 125.1 to 82.5 minutes after strategy implementation. Conclusion: Computed tomography flow modifications produced the largest and most consistent reduction in the DTP time. However, the reduction in the DTP time across all the studies suggests that any systematic protocol aimed at reducing the DTP time can produce a beneficial effect. The relative novelty of mechanical thrombectomy and the consequential lack of research call for future investigation into the efficacy of varying DTP time reduction strategies.

Managing opioid consumption after caesarean delivery: a quality improvement initiative.

INTRODUCTION: Caesarean delivery is the most common major surgical procedure performed worldwide and pain management after caesarean delivery remains challenging. Finding a balance between sufficient postoperative pain relief and excess sedation secondary to opioids is often difficult in this patient population. This quality improvement project aimed to manage the amount of opioid consumption after caesarean delivery using a new postoperative analgesic regimen. METHODS: The current practice was analysed in 52 patients before introducing the new regimen. Oxycodone consumption, pain scores and quality of recovery were recorded. Following this pre-implementation audit, a new postoperative analgesic protocol was introduced. All patients received standard doses of intrathecal morphine, paracetamol and diclofenac. Regular oxycodone sustained-release (SR) was replaced with oxycodone immediate-release (IR) as needed. These changes also coincided with education to improve midwifery assessment of pain and the delivery of analgesia. RESULTS: The outcome measures were re-audited in 178 patients which showed that oxycodone consumption had reduced median (IQR) 30 mg (20-40) vs 10 mg (5-15) (p < 0.001). There was no significant difference in the pain scores between the before and after groups at rest median (IQR) 2.0 (0-4.8) vs 2.0 (0.8-4.0) or at movement 5.0 (3.0-6.0) vs 5.0 (3.0-6.3) (p = 0.292, p = 0.482 respectively). The quality of recovery scores were also equivalent mean (SD) 78.6 (20.6) vs 77.8 (19.0) (p = 0.792). CONCLUSION: The results of this study suggest that postoperative opioid consumption can be reduced with specific analgesic protocols and allow us to improve patient's quality of recovery.

Low Quality of International Classification of Diseases, 10th Revision, Procedural Coding System Data Undermines the Validity of the Standardized Transfusion Ratio: Time to Chart a New Course?

The validity of the standardized transfusion ratio, a quality measure for dialysis facilities, may have been affected by the transition from International Classification of Diseases, Ninth Revision (ICD-9) to International Classification of Diseases, Tenth Revision (ICD-10) procedure coding in October 2015. We analyzed Medicare Part A claims for inpatient care among dialysis patients in 2014-2017 and investigated billing patterns for blood transfusion during the last year of ICD-9 coding and the first and second years of ICD-10 coding. We identified 2205 hospitals with a steady volume of dialysis patient admissions. In nearly one-third (31.7%) of hospitals, the apparent incidence of blood transfusion during hospitalization fell >50% between the last year of ICD-9 coding and the first year of ICD-10 coding. Between the first and second years of ICD-10 coding, the apparent incidence of blood transfusion during hospitalization fell >20% in 24.5% of hospitals and rose >25% in 14.8% of hospitals. Furthermore, hospital-specific changes in the apparent incidence of blood transfusion among dialysis patients and all Medicare beneficiaries were highly correlated. These findings suggest that the standardized transfusion ratio reflects differential misclassification of transfusions among hospitals. Alternative measures to judge the quality of anemia management, such as attainment of hemoglobin within a target range, may be more appropriate.

Neopeptide Analyser: A software tool for neopeptide discovery in proteomics data.

Experiments involving mass spectrometry (MS)-based proteomics are widely used for analyses of connective tissues. Common examples include the use of relative quantification to identify differentially expressed peptides and proteins in cartilage and tendon. We are working on characterising so-called 'neopeptides', i.e. peptides formed due to native cleavage of proteins, for example under pathological conditions. Unlike peptides typically quantified in MS workflows due to the in vitro use of an enzyme such as trypsin, a neopeptide has at least one terminus that was not due to the use of trypsin in the workflow. The identification of neopeptides within these datasets is important in understanding disease pathology, and the development of antibodies that could be utilised as diagnostic biomarkers for diseases, such as osteoarthritis, and targets for novel treatments. Our previously described neopeptide data analysis workflow was laborious and was not amenable to robust statistical analysis, which reduced confidence in the neopeptides identified. To overcome this, we developed 'Neopeptide Analyser', a user friendly neopeptide analysis tool used in conjunction with label-free MS quantification tool Progenesis QIP for proteomics. Neopeptide Analyser filters data sourced from Progenesis QIP output to identify neopeptide sequences, as well as give the residues that are adjacent to the peptide in its corresponding protein sequence. It also produces normalised values for the neopeptide quantification values and uses these to perform statistical tests, which are also included in the output. Neopeptide Analyser is available as a Java application for Mac, Windows and Linux. The analysis features and ease of use encourages data exploration, which could aid the discovery of novel pathways in extracellular matrix degradation, the identification of potential biomarkers and as a tool to investigate matrix turnover. Neopeptide Analyser is available from https://github.com/PGB-LIV/neo-pep-tool/releases/.

How to conduct a clinical audit and quality improvement project.

Audits and quality improvement projects are vital aspects of clinical governance and continual service improvement in medicine. In this article we describe the process of clinical audit and quality improvement project. Guidance is also provided on how to design an effective audit and bypass barriers encountered during the process.

The medical director and quality requirements in the dialysis facility.

Four decades after the successful implementation of the ESRD program currently providing life-saving dialysis therapy to >430,000 patients, the definitions of and demands for a high-quality program have evolved and increased at the same time. Through substantial technological advances ESRD care improved, with a predominant focus on the technical aspects of care and the introduction of medications such as erythropoiesis-stimulating agents and active vitamin D for anemia and bone disease management. Despite many advances, the size of the program and the increasingly older and multimorbid patient population have contributed to continuing challenges for providing consistently high-quality care. Medicare's Final Rule of the Conditions for Coverage (April 2008) define the medical director of the dialysis center as the leader of the interdisciplinary team and the person ultimately accountable for quality, safety, and care provided in the center. Knowledge and active leadership with a hands-on approach in the quality assessment and performance improvement process (QAPI) is essential for the achievement of high-quality outcomes in dialysis centers. A collaborative approach between the dialysis provider and medical director is required to optimize outcomes and deliver evidence-based quality care. In 2011 the Centers for Medicare & Medicaid Services introduced a pay-for-performance program-the ESRD quality incentive program (QIP)- with yearly varying quality metrics that result in payment reductions in subsequent years when targets are not achieved during the performance period. Success with the QIP requires a clear understanding of the structure, metrics, and scoring methods. Information on achievement and nonachievement is publicly available, both in facilities (through the facility performance score card) and on public websites (including Medicare's Dialysis Facility Compare). By assuming the leadership role in the quality program of dialysis facilities, the medical director is given an important opportunity to improve patients' lives and effect true change in a patient population dealing with a very challenging chronic disease. This article in the series on the role of the medical director summarizes the medical director's specific role in the quality improvement process in the dialysis facility and the associated requirements and programs, including QAPI and QIP.

Qip gene in Fusarium oxysporum is required for normal hyphae morphology and virulence.

Ribonucleic acid (RNA)-silencing mechanisms exist in many eukaryotes to regulate a variety of biological processes. The known molecular components are related to Dicers, Argonautes and RNA-dependent RNA polymerases. Previous biochemical studies have also suggested that Qip, with an exonuclease domain, facilitates the conversion of duplex small interfering RNAs into single strands. In our study, the Qip gene in Fusarium oxysporum was disrupted using homologous recombination technology. The deletion of the Qip gene resulted in a decrease in colony growth rates but increased the number of branches. Additionally, the ΔQip mutant had a reduced pathogenicity in cabbage. Our results show Qip gene in F. oxysporum is required for normal hyphae morphology and virulence. The mutant will be useful for elucidating the relationship between the RNA-silencing mechanism and hyphal growth and development in F. oxysporum.

Identification and characterization of multiple conserved nuclear localization signals within adenovirus E1A.

The human adenovirus 5 (HAdV-5) E1A protein has a well defined canonical nuclear localization signal (NLS) located at its C-terminus. We used a genetic assay in the yeast Saccharomyces cerevisiae to demonstrate that the canonical NLS is present and functional in the E1A proteins of each of the six HAdV species. This assay also detects a previously described non-canonical NLS within conserved region 3 and a novel active NLS within the N-terminal/conserved region 1 portion of HAdV-5 E1A. These activities were also present in the E1A proteins of each of the other five HAdV species. These results demonstrate that, despite substantial differences in primary sequence, HAdV E1A proteins are remarkably consistent in that they contain one canonical and two non-canonical NLSs. By utilizing independent mechanisms, these multiple NLSs ensure nuclear localization of E1A in the infected cell.

Nuclear Respiratory Factor 2ß (NRF-2ß) recruits NRF-2α to the nucleus by binding to importin-α:ß via an unusual monopartite-type nuclear localization signal.

Nuclear respiratory factor 2 (NRF-2) is a mammalian transcription factor composed of two distinct and unrelated proteins: NRF-2α, which binds to DNA through its Ets domain, and NRF-2ß, which contains the transcription activation domain. The activity of NRF-2 in neurons is regulated by nuclear localization; however, the mechanism by which NRF-2 is imported into the nucleus remains unknown. By using in vitro nuclear import assays and immuno-cytofluorescence, we dissect the nuclear import pathways of NRF-2. We show that both NRF-2α and NRF-2ß contain intrinsic nuclear localization signals (NLSs): the Ets domain within NRF-2α and the NLS within NRF-2ß (amino acids 311/321: EEPPAKRQCIE) that is recognized by importin-α:ß. When NRF-2α and NRF-2ß form a complex, the nuclear import of NRF-2αß becomes strictly dependent on the NLS within NRF-2ß. Therefore, the nuclear import mechanism of NRF-2 is unique among Ets factors. The NRF-2ß NLS contains only two lysine/arginine residues, unlike other known importin-α:ß-dependent NLSs. Using ELISA-based binding assays, we show that it is bound by importin-α in almost the same manner and with similar affinity to that of the classical monopartite NLSs, such as c-myc and SV40 T-antigen NLSs. However, the part of the tryptophan array of importin-α that is essential for the recognition of classical monopartite NLSs by generating apolar pockets for the P3 and the P5 lysine/arginine side chains is not required for the recognition of the NRF-2ß NLS. We conclude that the NRF-2ß NLS is an unusual but is, nevertheless, a bona fide monopartite-type NLS.