Factors Differentiating Nursing Homes With Strong Resident Safety Climate: A Qualitative Study of Leadership and Staff Perspectives.

The current qualitative study assessed leadership and staff perceptions related to resident safety at Department of Veterans Affairs (VA) nursing homes with a range of safety climates. We recruited a purposive sample of six VA nursing homes from geographically diverse regions of the United States and with diverse overall safety climate ratings. We conducted semi-structured phone interviews with 43 senior and middle level nursing home leaders and frontline providers (medical and nursing). We performed a thematic analysis of interview data to assess participant perceptions of factors that influence resident safety at higher and lower safety climate sites. Analyses identified two factors that differentiated VA nursing homes with high safety climate ratings from those with medium or low ratings: (1) communication about resident safety, particularly the important role of accessibility of physicians and managers; and (2) leadership support for and responsiveness to resident safety issues raised by frontline staff. Findings from high safety climate nursing homes underscore the importance of leadership accessibility, communication, support, and follow through regarding resident safety concerns. These results may provide a basis for designing safety climate interventions, such as those designed to improve communication, teamwork, and quality improvement structures and processes. [Journal of Gerontological Nursing, 49(2), 13-17.].

Process design of a fully integrated continuous biopharmaceutical process using economic and ecological impact assessment.

Continuous biomanufacturing is a promising alternative to current batch operation as it offers benefits in terms of improved productivity, product quality, and reduced footprint. This study aims to build a fully integrated continuous platform for monoclonal antibody (mAb) production incorporating novel technologies (like intensified seed expansion and continuous high cell density perfusion operations, single-pass tangential flow filtration, and single-use technologies) as well as media and buffer preparation steps. Economic assessment is performed on the basis of the total cost of goods (COGs), which is $102.2/g in the base-case scenario with a bioreactor scale of 500 L. E-factor is used as an environmental indicator and the result shows that 4865.6kg of process water and 11.1 kg of consumables are required to produce 1 kg mAbs. After the development and analysis of the benchmark process, scenario analysis is performed to assess the impacts of the bioreactor scale (60-2000 L) and upstream titers (1.12-2.08 g/L) on the process economics as well as on the environmental footprint. With the increase of bioreactor scale and mAb titer, the operating COGs per unit product decrease. Moreover, increasing the mAb titer is more favorable in terms of the ecological impacts. To investigate the production capacity, the upstream production is increased and the downstream bottlenecks are determined. It is found that only the multicolumn chromatographic (MCC) operations become the process bottleneck and the order of the MCC unit operation that becomes the process bottleneck depends on capacity utilization for that step. Finally, a new platform is built with the integration of membrane chromatography and the two designed processes are compared in terms of economic and ecological impacts.

Systematic assessment of process analytical technologies for biologics.

The application of process analytical technology (PAT) for biotherapeutic development and manufacturing has been employed owing to technological, economic, and regulatory advantages across the industry. Typically, chromatographic, spectroscopic, and/or mass spectrometric sensors are integrated into upstream and downstream unit operations in in-line, on-line, or at-line fashion to enable real-time monitoring and control of the process. Despite the widespread utility of PAT technologies at various unit operations of the bioprocess, a holistic business value assessment of PAT has not been well addressed in biologics. Thus, in this study, we evaluated PAT technologies based on predefined criteria for their technological attributes such as enablement of better process understanding, control, and high-throughput capabilities; as well as for business attributes such as simplicity of implementation, lead time, and cost reduction. The study involved an industry-wide survey, where input from subject matter industry experts on various PAT tools were collected, assessed, and ranked. The survey results demonstrated on-line liquid Chromatography (LC), in-line Raman, and gas analysis techniques are of high business value especially at the production bioreactor unit operation of upstream processing. In-line variable path-length UV/VIS measurements (VPE), on-line LC, multiangle light scattering (MALS), and automated sampling are of high business value in Protein A purification and polishing steps of the downstream process. We also provide insights, based on our experience in clinical and commercial manufacturing of biologics, into the development and implementation of some of the PAT tools. The results presented in this study are intended to be helpful for the current practitioners of PAT as well as those new to the field to gauge, prioritize and steer their projects for success.

Arbuscular Mycorrhizae Shift Community Composition of N-Cycling Microbes and Suppress Soil N2O Emission.

Mycorrhizae are ubiquitous symbiotic associations between arbuscular mycorrhizal fungi (AMF) and terrestrial plants, in which AMF receive photosynthates from and acquire soil nutrients for their host plants. Plant uptake of soil nitrogen (N) reduces N substrate for microbial processes that generate nitrous oxide (N2O), a potent greenhouse gas. However, the underlying microbial mechanisms remain poorly understood, particularly in agroecosystems with high reactive N inputs. We examined how plant roots and AMF affect N2O emissions, N2O-producing (nirK and nirS) and N2O-consuming (nosZ) microbes under normal and high N inputs in conventional (CONV) and organically managed (OM) soils. Here, we show that high N input increased soil N2O emissions and the ratio of nirK to nirS microbes. Roots and AMF did not affect the (nirK + nirS)/nosZ ratio but significantly reduced N2O emissions and the nirK/nirS ratio. They reduced the nirK/nirS ratio by reducing nirK-Rhodobacterales but increasing nirS-Rhodocyclales in the CONV soil while decreasing nirK-Burkholderiales but increasing nirS-Rhizobiales in the OM soil. Our results indicate that plant roots and AMF reduced N2O emission directly by reducing soil N and indirectly through shifting the community composition of N2O-producing microbes in N-enriched agroecosystems, suggesting that harnessing the rhizosphere microbiome through agricultural management might offer additional potential for N2O emission mitigation.

A prospective trial of the THD SphinKeeper® for faecal incontinence.

AIM: THD SphinKeeper® is an emerging surgical technique for faecal incontinence (FI). The safety, indications and efficacy of the procedure are still being investigated. The aim of this study is to present the first experience of SphinKeeper® in Australia. METHOD: This was a prospective single-centre observational study of patients undergoing SphinKeeper® implantation between February 2018 and September 2019. Baseline demographics, intraoperative and postoperative complications, Cleveland Clinic Faecal Incontinence Score, St Mark's Incontinence Score, Faecal Incontinence Quality of Life score (FIQOL), anorectal manometry and endo-anal ultrasound were assessed preoperatively and 3 and 12 months after implantation. RESULTS: Thirteen patients (2 male, 11 female) underwent implantation during the study period. Anal sphincter defects were present in 13 (76.9%) patients [external anal sphincter (EAS) defect, 2 (15.4%); internal anal sphincter (IAS) defect 4 (30.8%); EAS + IAS defect, 4 (30.8%)]. Median follow-up was 32 months (range 18-37 months). There were four complications: one intraoperative (rectal perforation) and three postoperative (one implant extrusion, two implants that required removal due to malposition). At 12 months, an average of 9/10 implants remained ideally placed in each patient. THD SphinKeeper® insertion was associated with an improvement in coping/behaviour as measured using FIQOL (p = 0.047). However, the procedure did not improve FI scores or anorectal manometry parameters. CONCLUSION: In this study, SphinKeeper® marginally improved symptoms of FI but there was no significant impact on anorectal manometric measurements. Larger-scale studies are needed to determine the patient cohort most likely to benefit from this procedure.

The Vertical Rectus Abdominis Myocutaneous Flap to Manage Vaginal Evisceration.

BACKGROUND: Pelvic organ prolapse (POP) is a significant issue requiring surgical correction in 19% of the female population by age 85 years. Complications of POP, especially in women who have undergone hysterectomy, include vaginal evisceration-a serious complication that carries high morbidity and mortality rates. Rarely, vaginal evisceration occurs after colpocleisis. CASE: A 69-year-old female with recurrent vaginal evisceration following colpocleisis underwent surgical repair using a vertical rectus abdominis myocutaneous (VRAM) flap. CONCLUSION: Recurrent cases of POP and vaginal evisceration that are refractory to conventional treatment require consideration of novel management options. To our knowledge, this is the first case using a VRAM flap for the management of vaginal evisceration.

End-to-end collaboration to transform biopharmaceutical development and manufacturing.

An ambitious 10-year collaborative program is described to invent, design, demonstrate, and support commercialization of integrated biopharmaceutical manufacturing technology intended to transform the industry. Our goal is to enable improved control, robustness, and security of supply, dramatically reduced capital and operating cost, flexibility to supply an extremely diverse and changing portfolio of products in the face of uncertainty and changing demand, and faster product development and supply chain velocity, with sustainable raw materials, components, and energy use. The program is organized into workstreams focused on end-to-end control strategy, equipment flexibility, next generation technology, sustainability, and a physical test bed to evaluate and demonstrate the technologies that are developed. The elements of the program are synergistic. For example, process intensification results in cost reduction as well as increased sustainability. Improved robustness leads to less inventory, which improves costs and supply chain velocity. Flexibility allows more products to be consolidated into fewer factories, reduces the need for new facilities, simplifies the acquisition of additional capacity if needed, and reduces changeover time, which improves cost and velocity. The program incorporates both drug substance and drug product manufacturing, but this paper will focus on the drug substance elements of the program.

A comparison of faecal incontinence scoring systems.

AIM: Questionnaires designed to score the severity of faecal incontinence (FI) are widely used to provide an evaluation of symptoms across settings, studies and time. The Pelvic Floor Disorders Consortium have recommended the use of multiple questionnaires despite some overlap of questions. This study aimed to evaluate whether patient responses to these questionnaires are consistent. METHOD: A retrospective analysis was undertaken of patients with FI who attended a dedicated pelvic floor unit between January 2018 and December 2019 and completed the Fecal Incontinence Severity Index, Cleveland Clinic Florida Incontinence Score and St Mark's Incontinence Score simultaneously. For each questionnaire the frequency of incontinence episodes to solid stool, liquid stool and gas was divided into five categories to allow direct comparison. Answers were deemed equivalent if the allocated response was identical, slightly different if the response was in an adjacent category or very different if the response differed to a greater extent. RESULTS: There were 193 patients who simultaneously completed all three FI questionnaires. There were statistically significant differences between the responses regarding frequency of solid stool, liquid stool and gas incontinence on all three questionnaires (p < 0.005). Across all domains, between 58.0% and 69.9% of responses were equivalent, 14.1%-34.0% of answers were slightly different and 8.0%-18.8% were very different. CONCLUSION: Even when completed at the same time, and by the same person, similar questions are answered differently a significant proportion of the time. The utility of using multiple questionnaires simultaneously in the clinical setting to assess FI symptoms should be questioned.

Rate of anastomotic leak following right hemicolectomy by general surgical trainees.

PURPOSE: Performing a right hemicolectomy (RH) is a core technical competency for general surgical trainees. There is a concern that anastomotic leaks occur more frequently when patients are operated on by trainees rather than by surgeons. This study aims to analyse the quality of care outcomes after RH, stratified by the experience level of the operator. METHODS: Patients were retrospectively recruited from the Bi-National Colorectal Cancer Audit (BCCA) Registry, from 2007 to 2018. All patients who underwent a RH for colorectal cancer were eligible. The primary outcome measure was anastomotic leak rate. RESULTS: A total of 6548 eligible right hemicolectomies were identified, with 74% being performed by consultants, 12% by fellows, and 14% by surgical trainees. The overall incidence of an anastomotic leak was 2.1%, with the highest rate of 3.7% noted among supervised registrars. Positive resection margin rate was the highest among unsupervised trainees at 10.5%, as compared with 4.3% among consultants. Anastomotic leak, anastomotic bleeding, prolonged ileus, and pneumonia occurred significantly less frequently with consultant surgeons, as compared with trainees. Independent risk factors for anastomotic leak were urgent surgery, extended right hemicolectomy, conversion to open surgery, and a lower level of operator seniority. Two independent risk factors were identified for inpatient mortality-a high ASA score (III and above) and urgent surgery. CONCLUSION: RH is a common operative procedure in general surgical training. Data from this study may assist with the structuring of surgical training programmes, aimed at maximising both patient safety and trainee professional development and education.

Results of a Regional Effort to Improve Warfarin Management.

BACKGROUND: Improved anticoagulation control with warfarin reduces adverse events and represents a target for quality improvement. No previous study has described an effort to improve anticoagulation control across a health system. OBJECTIVE: To describe the results of an effort to improve anticoagulation control in the New England region of the Veterans Health Administration (VA). METHODS: Our intervention encompassed 8 VA sites managing warfarin for more than 5000 patients in New England (Veterans Integrated Service Network 1 [VISN 1]). We provided sites with a system to measure processes of care, along with targeted audit and feedback. We focused on processes of care associated with site-level anticoagulation control, including prompt follow-up after out-of-range international normalized ratio (INR) values, minimizing loss to follow-up, and use of guideline-concordant INR target ranges. We used a difference-in-differences (DID) model to examine changes in anticoagulation control, measured as percentage time in therapeutic range (TTR), as well as process measures and compared VISN 1 sites with 116 VA sites located outside VISN 1. RESULTS: VISN 1 sites improved on TTR, our main indicator of quality, from 66.4% to 69.2%, whereas sites outside VISN 1 improved from 65.9% to 66.4% (DID 2.3%, P < 0.001). Improvement in TTR correlated strongly with the extent of improvement on process-of-care measures, which varied widely across VISN 1 sites. CONCLUSIONS: A regional quality improvement initiative, using performance measurement with audit and feedback, improved TTR by 2.3% more than control sites, which is a clinically important difference. Improving relevant processes of care can improve outcomes for patients receiving warfarin.

Intermediate soil acidification induces highest nitrous oxide emissions.

Global potent greenhouse gas nitrous oxide (N2O) emissions from soil are accelerating, with increases in the proportion of reactive nitrogen emitted as N2O, i.e., N2O emission factor (EF). Yet, the primary controls and underlying mechanisms of EFs remain unresolved. Based on two independent but complementary global syntheses, and three field studies determining effects of acidity on N2O EFs and soil denitrifying microorganisms, we show that soil pH predominantly controls N2O EFs and emissions by affecting the denitrifier community composition. Analysis of 5438 paired data points of N2O emission fluxes revealed a hump-shaped relationship between soil pH and EFs, with the highest EFs occurring in moderately acidic soils that favored N2O-producing over N2O-consuming microorganisms, and induced high N2O emissions. Our results illustrate that soil pH has a unimodal relationship with soil denitrifiers and EFs, and the net N2O emission depends on both the N2O/(N2O + N2) ratio and overall denitrification rate. These findings can inform strategies to predict and mitigate soil N2O emissions under future nitrogen input scenarios.

The effect of a sexual abuse history on symptoms and anorectal physiology findings in patients presenting to a colorectal pelvic floor service.

BACKGROUND: Studies report that 12%-23% of patients with functional anorectal disorders have a history of sexual abuse (SA). This article aims to assess whether there is a difference in symptom severity, quality of life or anorectal physiology findings in female patients presenting to a colorectal pelvic floor service with and without a history of sexual abuse. METHODS: A retrospective analysis of all female patients attending a single tertiary pelvic floor unit for faecal incontinence or constipation between 2017 and 2019 was performed. Patients were divided into two groups depending on the presence or absence of a volunteered history of sexual abuse. Validated quality of life and symptom severity scores, along with anorectal physiology studies were analysed and compared between the two groups. RESULTS: There were 148 patients included in the study period and 17% reported a history of SA. There was no statistically significant difference in symptom severity, quality of life scores or anorectal physiology studies between those with and without a history of SA. CONCLUSION: In female patients seeking management for defaecatory symptoms, those who have reported a history of SA did not demonstrate any significant difference in symptom severity, quality of life or physiological measures when compared to those without a history of SA.

Perioperative outcomes of emergency and elective colorectal surgery: a bi-institutional study.

BACKGROUND: Emergency colorectal surgery tends to be associated with poorer outcomes compared to elective colorectal surgery. This study assessed the morbidity and mortality in patients undergoing emergency and elective colorectal resection in two metropolitan hospitals. METHODS: Patients were identified retrospectively from two institutions between April 2018 and July 2020. Baseline, operative and postoperative parameters were collected for comparative analysis between emergency and elective surgery groups. A binary logistic regression was performed to identify independent predictors of postoperative complications. RESULTS: During the study period, 454 patients underwent colorectal resection, 135 were emergency cases (29.74%) and 319 were elective cases (70.26%). Compared with elective resections, patients undergoing emergency resections were observed to have a higher American Society of Anesthesiologists (ASA) score of III to IV (53.33% vs. 38.56%) (P = 0.004). The mortality rate was similar between the emergency and elective group (1.48% vs. 0.63%, P = 0.369). The overall complication rate was higher in patients undergoing emergency resections (64.44% vs. 36.68%, P < 0.001), but the major complication rate was similar between groups (12.59% vs. 10.34%, P = 0.484). Independent predictors for postoperative complications included emergency surgery (Odds Ratio (OR) 2.77, 95% Confidence Interval (CI): 1.66 to 4.61) and an ASA Score of III to IV (OR 2.87, 95% CI: 1.84 to 4.47). CONCLUSION: The overall complication rate was higher in patients undergoing emergency colorectal resection, however, rates of major complications and mortality were similar between groups. Higher complication rates reflect advanced disease pathology in patients who are more comorbid.

Confocal Raman microscopy of protein adsorbed in chromatographic particles.

Confocal Raman microscopy is a nondestructive analytical technique that combines the chemical information from vibrational spectroscopy with the spatial resolution of confocal microscopy. It was applied, for the first time, to measure conformation and distribution of protein adsorbed in wetted chromatographic particles. Monoclonal antibody was loaded into the Fractogel EMD SO(3) (M) cation exchanger at 2 mS/cm or 10 mS/cm. Amide I and III frequencies in the Raman spectrum of the adsorbed protein suggest that there are no detectable changes of the original ß-sheet conformation in the chromatographic particles. Protein depth profile measurements indicate that, when the conductivity is increased from 2 mS/cm to 10 mS/cm, there is a change in mass transport mechanism for protein adsorption, from the shrinking-core model to the homogeneous-diffusion model. In this study, the use of confocal Raman microscopy to measure protein distribution in chromatographic particles fundamentally agrees with previous confocal laser scanning microscopic investigations, but confocal Raman spectroscopy enjoys additional advantages: use of unlabeled protein to eliminate fluorescent labeling, ability for characterization of protein secondary structure, and ability for spectral normalization to provide a nondestructive experimental approach to correct light attenuation effects caused by refractive index (RI) mismatching in semiopaque chromatographic particles.

A rare case of colo-salpingeal fistula complicating acute sigmoid diverticulitis.

Colo-salpingeal fistulae due to acute diverticulitis are rare entities. A 65-year-old female with a 5-day history of left iliac fossa pain, fevers and diarrhoea was seen in a metropolitan hospital. Initial computed tomography of the abdomen and pelvis characterized a left tubular adnexal structure with an air fluid level and normal-appearing colon and was reported as pyosalpingitis. Worsening sepsis despite antibiotics prompted further imaging where thickening of the sigmoid colon was noted, and the provisional diagnosis was revised to complicated acute diverticulitis with perforation into the left fallopian tube/ovary. This was managed with a laparoscopic anterior resection and en bloc left salpingo-oopherectomy, and was followed by an uneventful recovery. The presence of a gas-containing collection remains a sensitive imaging sign for the presence of an enteric fistula and a high index of suspicion should be maintained when this is encountered.

De-implementing and sustaining an intervention to eliminate nursing home resident bed and chair alarms: interviews on leadership and staff perspectives.

BACKGROUND: Improving nursing home quality of care relies partly on reducing or stopping ineffective or harmful practices, a process known as de-implementation. We know little about de-implementation in this setting. Relatively recent policy changes reclassified resident position-change (bed and chair) alarms, which monitor resident movement, as restraints. This created an optimal environment in which to study impressions of an alarm de-implementation and sustainment intervention. METHODS: This cross-sectional interview study focused on understanding participants' experience of a quality improvement program in the Department of Veterans Affairs Community Living Centers (nursing homes). The program's goal was to improve resident outcomes and staff communication and teamwork through, among other foci, eliminating resident position-change alarms. The Community Living Centers were located in geographically dispersed areas of the continental United States. Interview participants were leadership and staff members from seven Community Living Centers. We conducted in-depth, semi-structured qualitative interviews using a convenience sample and used a thematic analytic approach. RESULTS: We conducted seventeen interviews. We identified five main themes: Initiating De-implementation (compelling participants with evidence, engaging local leadership, and site-level education and training), Changing Expectations (educating staff and family members), Using Contrasting Approaches (gradual or abrupt elimination of alarms), Witnessing Positive Effects of De-implementation (reduction in resident falls, improved resident sleep, reduction in distressing behaviors, and increased resident engagement), and Staying the Course (sustainment of the initiative). CONCLUSIONS: Findings highlight how participants overcame barriers and successfully eliminated resident position-change alarms and sustained the de-implementation through using convincing evidence for the initiative, local leadership involvement and support, and staff and family member education and engagement. These findings and the resulting three-phase process to support nursing homes' de-implementation efforts expand the de-implementation science knowledge base and provide a promising framework for other nursing home-based de-implementation initiatives.

A shape-level flanker facilitation effect in contour integration and the role of shape complexity.

The detection of an object in the visual field requires the visual system to integrate a variety of local features into a single object. How these local processes and their global integration is influenced by the presence of other shapes in the visual field is poorly understood. The detectability (contour integration) of a central target object in the form of a two dimensional Gaborized contour was compared in the presence or absence of nearby surrounding objects. A 2-AFC staircase procedure added orientation jitter to the constituent Gabor patches to determine the detectability of the target contour. The set of contours was generated using shape profiles of everyday objects and geometric forms. Experiment 1 examined the effect of three types of congruencies between the target and two flanking contours (contour shape, symmetry and familiarity). Experiment 2 investigated the effect of varying the number and spatial positions of the flankers. In addition, a measure of shape complexity (reciprocal of shape compactness) was used to assess the effects of contour complexity on detection. Across both experiments the detectability of the target contour increased when the target and flanker had the same shape and this was related to both the number of flankers and the complexity of the target shapes. Another factor that modulated this shape-level flanker facilitation effect was the presence of symmetry. The overall results are consistent with a contour integration process in which the visual system incorporates contextual information to extract the most likely smooth contour within a noise field.

Polishing approach with fully connected flow-through purification for therapeutic monoclonal antibody.

The biopharmaceutical industry is evolving toward process intensification that can offer increased productivity and improved economics without sacrificing process robustness. A semi-continuous downstream process linking purification/polishing unit operations in series can reduce or eliminate intermediate holding tanks and reduce overall processing time. Accordingly, we have developed a therapeutic monoclonal antibody polishing template comprised of a connected flow-through polishing technologies that include activated carbon, cation exchange, and anion-exchange chromatography. In this report, we evaluated fully-connected pool-less polishing with three flow-through technologies, operating as a single skid to streamline and improve an mAb purification platform. Laboratory-scale pool-less processing was achieved without utilizing in-line pH adjustment and conductivity dilution based on the previously optimized single process parameter. Two connected flow-through configurations of polishing steps were evaluated: a two-step process using anion exchange and cation exchange and a three step process using activated carbon, anion exchange and cation exchange chromatography. Laboratory-scale proof of concept studies showed comparable performance between the batch purification process and the pool-less process configuration. Three step polishing highly intensified the processes and provided higher process loading and achieved bulk drug specification with higher impurity clearance (>95%) and high overall mAb yield (>95%).

Botulinum-toxin-A Injection Following Conservative Management in Patients with Dyssynergic Defaecation Only Improves Symptoms in the Short Term: A Retrospective Study

Abstract Objective Dyssynergic defaecation (DD) is an important cause of chronic constipation. In patients where conservative treatments fail, injections of botulinum toxin A (BTX-A) into the puborectalis and anal sphincter muscles can be effective. Complications of this procedure are reported to be rare and generally mild. This study aimed to identify the complication rates and short- to medium-term success rates of BTX-A injections as a treatment for DD. Methods A retrospective review was conducted on patients diagnosed with DD who had undergone BTX-A injections at a functional colorectal unit. Patient demographics, manometric assessment, conservative management, and injection technique were collected through a chart review. Subjective patient reports and comparison of pre- and postprocedure symptom scores were used to determine efficacy. Results The 21 patients included (24 procedures, with 3 patients receiving BTX-A on two separate occasions) all received stool modification and dietary advice, and 20 patients underwent pelvic floor physiotherapy, averaging 8 sessions. The injections were universally applied under general anesthetic, primarily targeting the anal sphincter and/or puborectalis muscles. There were 6 reports of faecal urge/incontinence, with all but one being resolved within weeks. The BTX-A injection was subjectively reported as beneficial in 19 cases, averaging 4.7 months (range 1-32) of improvement. Only 2 were sustained beyond 12 months. Despite overall improvements in symptom scores from pre- to postprocedure, none were statistically significant. Conclusion Following a course of conservative management, the BTX-A injection appears to be a safe treatment for DD, but only has short term efficacy.