Test and Treat for Prediabetes: A Review of the Health Effects of Prediabetes and the Role of Screening and Prevention.

The term prediabetes describes blood glucose levels above the normal range but below the threshold to diagnose type 2 diabetes. Several population health initiatives encourage a test and treat approach for prediabetes. In this approach, screening and identification of individuals with prediabetes should be followed by prompt referral to structured lifestyle modification programs or pharmacologic interventions that have been shown to prevent or delay the progression to type 2 diabetes in clinical trials. Here we provide a critical review of evidence for this test and treat approach by examining health outcomes associated with prediabetes and the availability and effectiveness of lifestyle modification approaches that target prediabetes. We also describe current limitations to the reach and uptake of evidence-based treatment options for prediabetes. Finally, we highlight lessons learned from identifying and labeling other preconditions to consider challenges and opportunities that may arise with increasing awareness of prediabetes as part of routine preventive care.

Trends in health behaviors of US adults with and without Diabetes: 2007-2018.

AIMS: Understanding health behaviors of people with diabetes can inform strategies to reduce diabetes-related burdens. METHODS: We used serial cross-sectional National Health and Nutrition Examination Surveys over 2007-2018 to characterize self-reported health behaviors among non-pregnant adults, with and without self-reported diabetes. We estimated weighted proportions meeting recommended health behaviors overall and by sociodemographic and glycemic levels. RESULTS: During 2007-2010, proportions of adults with diabetes meeting recommendations were: 61.9 % for added sugar consumption (<10 % of total calories), 17.2 % for physical activity, 68.2 % for weight management, 14.4 % avoided alcohol, 57.5 % avoided tobacco, 34.1 % got adequate sleep, and 97.5 % saw a healthcare provider (compared with 19.2 %, 33.6 %, 68.8 %, 8.5 %, 44.2 %, 33.0 %, and 82.6 % respectively, among those without diabetes). During 2015-2018, adjusted analyses showed more adults with diabetes met sleep (+16.7 percentage-points[pp]; 95 % CI: 10.6,22.8) and physical activity goals (+8.3 pp; 95 % CI: 3.8,12.8), and fewer met added sugar recommendations (-8.8 pp; 95 % CI -14.7, -2.9). Meeting added sugar, physical activity, and weight management varied by age, education, and glycemic level, but not race and ethnicity. CONCLUSIONS: During 2007-2018, there was some improvement in health behaviors. Improving self-management may require targeted interventions for different segments, like age groups or glycemic levels, among those with diabetes.

Benign Colorectal Disorders.

Benign conditions of the colon and rectum are a heterogeneous group of conditions that range from inflammatory to infectious to pelvic floor health conditions that affect large segments of the US population. These conditions include diverticular disease, hemorrhoids, and anorectal lesions. The initial presentation of these very common conditions often occurs in the outpatient primary care setting, and most can be managed by the primary care clinician. This article will provide an overview on the prevalence, diagnosis, and management of some of the most common benign colorectal disorders; these are broadly divided into diverticular disease, hemorrhoids, and anorectal conditions.

Negative Pressure Neurogenesis: A Novel Approach to Accelerate Nerve Regeneration after Complete Peripheral Nerve Transection.

Various modalities to facilitate nerve regeneration have been described in the literature with limited success. We hypothesized that negative pressure applied to a sectioned peripheral nerve would enhance nerve regeneration by promoting angiogenesis and axonal lengthening. METHODS: Wistar rats' sciatic nerves were cut (creating ~7 mm nerve gap) and placed into a silicone T-tube, to which negative pressure was applied. The rats were divided into 4 groups: control (no pressure), group A (low pressure: 10 mm Hg), group B (medium pressure: 20/30 mm Hg) and group C (high pressure: 50/70 mm Hg). The nerve segments were retrieved after 7 days for gross and histological analysis. RESULTS: In total, 22 rats completed the study. The control group showed insignificant nerve growth, whereas the 3 negative pressure groups showed nerve growth and nerve gap reduction. The true nerve growth was highest in group A (median: 3.54 mm) compared to group B, C, and control (medians: 1.19 mm, 1.3 mm, and 0.35 mm); however, only group A was found to be significantly different to the control group (**P < 0.01). Similarly, angiogenesis was observed to be significantly greater in group A (**P < 0.01) in comparison to the control. CONCLUSIONS: Negative pressure stimulated nerve lengthening and angiogenesis within an in vivo rat model. Low negative pressure (10 mm Hg) provided superior results over the higher negative pressure groups and the control, favoring axonal growth. Further studies are required with greater number of rats and longer recovery time to assess the functional outcome.

Mental Health and COVID-19: The Psychological Implications of a Pandemic for Nurses.

BACKGROUND: The risk of psychological effects from the COVID-19 pandemic is significant and manifests as stress, anxiety, depression, sleeplessness, and, in some cases, suicide. The need for psychological support services for healthcare providers should be included in all pandemic and disaster planning. OBJECTIVES: The aim of this article is to explore the potential psychological sequelae of nursing during a pandemic and to provide recommendations to support a psychologically healthy work environment. METHODS: Highlights from the literature on psychological sequelae, symptoms, and outcomes related to COVID-19 and prior pandemics is presented, along with insight from the experiences of oncology nurses caring for patients with COVID-19. FINDINGS: Destigmatizing mental health needs for healthcare providers empowers them to seek support. Hospital administrators must develop proactive wellness plans for the triage and management of mental and emotional health needs during a pandemic that prioritize transparent communication, resources for healthcare providers within and beyond the clinical setting, and training.

Ambulatory Oncology: Infrastructure Development in Response to the COVID-19 Pandemic.

BACKGROUND: The COVID-19 pandemic generated challenges to the delivery of safe, efficient, and high-quality cancer care. In ambulatory oncology, where most cancer care is delivered, these challenges required the rapid development of infrastructure. OBJECTIVES: This article describes challenges to the design and implementation of ambulatory oncology infrastructures that support clinical oncology care during a pandemic. METHODS: This article reviews clinical experiences in interprofessional, multicenter, academic, and community settings during the COVID-19 pandemic. Cohesive and efficient services, collaborative processes, and workflows; patient triage and symptom management; technology and equipment; and communication strategies are discussed. National ambulatory care guidelines and practice recommendations are included as applicable and available. FINDINGS: Continued treatment delivery and support for patients with cancer, as well as infrastructure to minimize viral exposure to patients and oncology healthcare workers, are essential when caring for this high-risk population.

PENTOSAN POLYSULFATE AND VISION: Findings from an International Survey of Exposed Individuals.

PURPOSE: To investigate patient-reported visual function among individuals taking pentosan polysulfate (PPS) for interstitial cystitis. METHODS: A 27-item online survey was distributed to an international mailing list of individuals with interstitial cystitis in November 2018. Demographic characteristics, PPS exposure history, subjective visual function, and previous macular diagnoses were queried. The impact of PPS use, grouped by tertile of cumulative exposure, on visual function and macular diagnoses was assessed with multivariate logistic regression. RESULTS: The survey was completed by 912 respondents. Eight hundred and sixty-one (96.4%) were women, and the median age was 55 [interquartile range (IQR), 45-64 years]. Among PPS users, the median exposure was 547.5 g (IQR, 219-1,314 g). Respondents in the highest PPS exposure tertile were more likely to report difficulty with reading small print [adjusted odds ratio 2.29, 95% confidence interval (CI) 1.15-4.57] and to have a diagnosis of macular degeneration and/or pigmentary maculopathy (adjusted odds ratio 2.41, 95% CI 1.44-4.03) than unexposed respondents. CONCLUSION: In this large sample of individuals with interstitial cystitis, those in the highest PPS exposure category were more likely to have difficulties reading small print and to report a previous diagnosis of macular disease. Further study of objective measures of visual function in PPS users is warranted.

Patient Falls Prevention: Assessing the Use of an Innovative Color-Coded Flag System in an Outpatient Oncology Infusion Center.

The National Database of Nursing Quality Indicators (NDNQI, 2020) defines a patient fall as an unplanned descent to the floor with or without injury. A fall occurs in 30%-50% of hospitalized patients with cancer in the United States (Jatoi, 2017). According to the Joint Commission (2015), the average cost of each fall with injury in the United States was about $14,000 to the healthcare system, averaging about $50 billion annually (Kartiko et al., 2020). Fall-related injuries to patients can result in additional treatment, hospital admissions, prolonged hospital stays, delays in cancer treatment, immobility, pain, emotional distress, caregiver fatigue, and depression (Joint Commission, 2015). Patients with cancer are highly susceptible to falls because of the neurologic deficits caused by chemotherapy treatments, medications given to prevent side effects, allergic reactions to the chemotherapy medications, increasing age, cognitive status, disease site, and cancer- and treatment-related fatigue (Jatoi, 2017). The high financial costs to patients and healthcare providers, as well as the physical and mental impact on patients, led to this pilot project.

Induction of Complete Transection-Type Spinal Cord Injury in Mice.

Spinal cord injury (SCI) largely leads to irreversible and permanent loss of function, most commonly as a result of trauma. Several treatment options, such as cell transplantation methods, are being researched to overcome the debilitating disabilities arising from SCI. Most pre-clinical animal trials are conducted in rodent models of SCI. While rat models of SCI have been widely used, mouse models have received less attention, even though mouse models can have significant advantages over rat models. The small size of mice equates to lower animal maintenance costs than for rats, and the availability of numerous transgenic mouse models is advantageous for many types of studies. Inducing repeatable and precise injury in the animals is the primary challenge for SCI research, which in small rodents requires high-precision surgery. The transection-type injury model has been a commonly used injury model over the last decade for transplantation-based therapeutic research, however a standardized method for inducing a complete transection-type injury in mice does not exist. We have developed a surgical protocol for inducing a complete transection type injury in C57BL/6 mice at thoracic vertebral level 10 (T10). The procedure uses a small tip drill instead of rongeurs to precisely remove the lamina, after which a thin blade with rounded cutting edge is used to induce the spinal cord transection. This method leads to reproducible transection-type injury in small rodents with minimal collateral muscle and bone damage and therefore minimizes confounding factors, specifically where behavioral functional outcomes are analyzed.

Reliable cell purification and determination of cell purity: crucial aspects of olfactory ensheathing cell transplantation for spinal cord repair.

Transplantation of olfactory ensheathing cells, the glia of the primary olfactory nervous system, has been trialed for spinal cord injury repair with promising but variable outcomes in animals and humans. Olfactory ensheathing cells can be harvested either from the lamina propria beneath the neuroepithelium in the nasal cavity, or from the olfactory bulb in the brain. As these areas contain several other cell types, isolating and purifying olfactory ensheathing cells is a critical part of the process. It is largely unknown how contaminating cells such as fibroblasts, other glial cell types and supporting cells affect olfactory ensheathing cell function post-transplantation; these cells may also cause unwanted side-effects. It is also, however, possible that the presence of some of the contaminant cells can improve outcomes. Here, we reviewed the last decade of olfactory ensheathing cell transplantation studies in rodents, with a focus on olfactory ensheathing cell purity. We analyzed how purification methods and resultant cell purity differed between olfactory mucosa- and olfactory bulb-derived cell preparations. We analyzed how the studies reported on olfactory ensheathing cell purity and which criteria were used to define cells as olfactory ensheathing cells. Finally, we analyzed the correlation between cell purity and transplantation outcomes. We found that olfactory bulb-derived olfactory ensheathing cell preparations are typically purer than mucosa-derived preparations. We concluded that there is an association between high olfactory ensheathing cell purity and favourable outcomes, but the lack of olfactory ensheathing cell-specific markers severely hampers the field.

Reducing Missed Opportunities for Human Papillomavirus Vaccination in School-Based Health Centers: Impact of an Intervention.

OBJECTIVE: Human papillomavirus (HPV) immunization rates among US adolescents are low. Missed opportunities (MOs) for HPV vaccination are common. School-based health centers (SBHCs) have potential to boost HPV vaccination, but their role in addressing MOs has not been examined. METHODS: We implemented a multicomponent intervention, consisting of 3 immunization process workflow modifications combined with provider performance feedback, in 2 Los Angeles area SBHCs and conducted a pre/post evaluation of MOs. Our primary outcome was SBHC-based MOs for HPV vaccination during all visits, including visits for confidential reproductive health care (ie, confidential visits). Secondary outcomes were MOs for meningococcal (MenACWY) and influenza vaccination during visits for nonconfidential care. RESULTS: MOs for HPV vaccination decreased during all visit types from the baseline to the intervention period (82.3% to 46.1%; adjusted risk ratio [RR] = 0.558, P < .0001). The rate decrease appeared to be greater during physical examination visits than confidential visits (83.4% to 31.6% vs 98.7% to 70.4%, respectively). MOs for MenACWY (74.5% to 35.0%; adjusted RR = 0.47, P < .0001) and influenza (86.7% to 69.3%; adjusted RR = 0.792, P < .0001) vaccination also decreased during nonconfidential visits. Vaccine refusal was the most frequently documented reason for HPV vaccine MOs during both physical examination and confidential visits. CONCLUSIONS: A pragmatic, multicomponent SBHC intervention reduced MOs for HPV vaccination during all visit types. MOs for MenACWY and influenza vaccination also decreased during nonconfidential visits. Findings suggest that practice-level improvements in SBHCs can improve delivery of HPV and other adolescent vaccines.

Prevalence and sociodemographic disparities in ever E-cigarette use among adults in Los Angeles County.

E-cigarette use has increased rapidly among U.S. adults. Few studies have examined the prevalence and risk factors of e-cigarette use among adults in the United States. We conducted descriptive analyses to identify characteristics of ever e-cigarette users among adults (18 years and older) living in Los Angeles (LA) County, the most populous county in the U.S., using data from the 2015 LA County Health Survey. We used logistic regression to examine independent factors associated with ever e-cigarette use. Age-adjusted prevalence of ever e-cigarette use was 8.4%. A significant interaction between conventional cigarette smoking status and gender was found (p < 0.05), and several factors were identified as associated with ever e-cigarette use in models stratified by gender. Various social and demographic factors are associated with ever e-cigarette use and should be incorporated into evidence-based interventions.

Naked Liquid Marbles: A Robust Three-Dimensional Low-Volume Cell-Culturing System.

Three-dimensional (3D) multicellular structures allow cells to behave and interact with each other in a manner that mimics the in vivo environment. In recent years, many 3D cell culture methods have been developed with the goal of producing the most in vivo-like structures possible. Whilst strongly preferable to  conventional cell culture, these approaches are often poorly reproducible, time-consuming, expensive, and labor-intensive and require specialized equipment. Here, we describe a novel 3D culture platform, which we have termed the naked liquid marble (NLM). Cells are cultured in a liquid drop (the NLM) in superhydrophobic-coated plates, which causes the cells to naturally form 3D structures. Inside the NLMs, cells are free to interact with each other, forming multiple 3D spheroids that are uniform in size and shape in less than 24 h. We showed that this system is highly reproducible, suitable for cell coculture, compound screening, and also compatible with laboratory automation systems. The low cost of production, small volume of each NLM, and production via automated liquid handling make this 3D cell-culturing system particularly suitable for high-throughput screening assays such as drug testing as well as numerous other cell-based research applications.

Global landscape of cell envelope protein complexes in Escherichia coli.

Bacterial cell envelope protein (CEP) complexes mediate a range of processes, including membrane assembly, antibiotic resistance and metabolic coordination. However, only limited characterization of relevant macromolecules has been reported to date. Here we present a proteomic survey of 1,347 CEPs encompassing 90% inner- and outer-membrane and periplasmic proteins of Escherichia coli. After extraction with non-denaturing detergents, we affinity-purified 785 endogenously tagged CEPs and identified stably associated polypeptides by precision mass spectrometry. The resulting high-quality physical interaction network, comprising 77% of targeted CEPs, revealed many previously uncharacterized heteromeric complexes. We found that the secretion of autotransporters requires translocation and the assembly module TamB to nucleate proper folding from periplasm to cell surface through a cooperative mechanism involving the ß-barrel assembly machinery. We also establish that an ABC transporter of unknown function, YadH, together with the Mla system preserves outer membrane lipid asymmetry. This E. coli CEP 'interactome' provides insights into the functional landscape governing CE systems essential to bacterial growth, metabolism and drug resistance.

Cefepime-induced neurotoxicity in a patient with coronary artery bypass.

We present here a case of 58-year-old male operated for coronary artery bypass graft surgery with four grafts. He developed neurologic symptoms with injection cefepime which recovered after withdrawal of the drug.

PilN Binding Modulates the Structure and Binding Partners of the Pseudomonas aeruginosa Type IVa Pilus Protein PilM.

Pseudomonas aeruginosa is an opportunistic bacterial pathogen that expresses type IVa pili. The pilus assembly system, which promotes surface-associated twitching motility and virulence, is composed of inner and outer membrane subcomplexes, connected by an alignment subcomplex composed of PilMNOP. PilM binds to the N terminus of PilN, and we hypothesize that this interaction causes functionally significant structural changes in PilM. To characterize this interaction, we determined the crystal structures of PilM and a PilM chimera where PilM was fused to the first 12 residues of PilN (PilM·PilN(1-12)). Structural analysis, multiangle light scattering coupled with size exclusion chromatography, and bacterial two-hybrid data revealed that PilM forms dimers mediated by the binding of a novel conserved motif in the N terminus of PilM, and binding PilN abrogates this binding interface, resulting in PilM monomerization. Structural comparison of PilM with PilM·PilN(1-12) revealed that upon PilN binding, there is a large domain closure in PilM that alters its ATP binding site. Using biolayer interferometry, we found that the association rate of PilN with PilM is higher in the presence of ATP compared with ADP. Bacterial two-hybrid data suggested the connectivity of the cytoplasmic and inner membrane components of the type IVa pilus machinery in P. aeruginosa, with PilM binding to PilB, PilT, and PilC in addition to PilN. Pull-down experiments demonstrated direct interactions of PilM with PilB and PilT. We propose a working model in which dynamic binding of PilN facilitates functionally relevant structural changes in PilM.

Optimal post-treatment surveillance in cancer survivors: is more really better?

A substantial rise in the number of cancer survivors has led to management questions regarding effective post-treatment surveillance strategies. Although a number of professional societies have proposed surveillance guidelines, clinical practice varies; the general trend is toward more intensive strategies. The evidence supporting intensive surveillance is relatively lacking, with most studies showing that more intense surveillance regimens have minimal, if any, impact on outcomes in terms of survival, quality of life, or overall cost-effectiveness. This has been demonstrated in breast cancer, and data supporting a similar conclusion may be evolving in colorectal cancer, where large prospective studies call into question the utility of intensive surveillance; in prostate cancer, retrospective data suggest a similar trend. In this review, we discuss the established guidelines and current evidence regarding post-treatment surveillance, and we propose general management strategies in prostate, colorectal, and breast cancers.

Mediators and Moderators of the Effectiveness of a Community Health Worker Intervention That Improved Dietary Outcomes in Pregnant Latino Women.

BACKGROUND: Pregnancy is an opportune time to initiate diabetes prevention strategies for minority and underserved women, using culturally tailored interventions delivered by community health workers. A community-partnered randomized controlled trial (RCT) with pregnant Latino women resulted in significantly improved vegetable, fiber, added sugar, and total fat consumption compared to a minimal intervention group. However, studying RCT intervention effects alone does not explain the mechanisms by which the intervention was successful or help identify which participants may have benefitted most. PURPOSE: To improve the development and targeting of future community health worker interventions for high-risk pregnant women, we examined baseline characteristics (moderators) and potential mechanisms (mediators) associated with these dietary changes. METHOD: Secondary analysis of data for 220 Latina RCT participants was conducted. A linear regression with effects for intervention group, moderator, and interaction between intervention group and moderator was used to test each hypothesized moderator of dietary changes. Sobel-Goodman mediation test was used to assess mediating effects on dietary outcomes. RESULTS: Results varied by dietary outcome. Improvements in vegetable consumption were greatest for women who reported high spousal support at baseline. Women younger than age 30 were more likely to reduce added sugar consumption than older women. Participants who reported higher baseline perceived control were more likely to reduce fat consumption. No examined mediators were significantly associated with intervention effects. CONCLUSION: Future interventions with pregnant Latinas may benefit from tailoring dietary goals to consider age, level of spousal support, and perceived control to eat healthy.

Antineutrophil cytoplasmic antibody vasculitis associated with influenza vaccination.

BACKGROUND: Administration of influenza vaccines has been associated with the development of autoantibodies and autoimmune rheumatic disease. PATIENTS: We discuss 2 patients who developed antineutrophil cytoplasmic antibody-associated vasculitis (AAV) in temporal association with influenza immunization. AAV was diagnosed 2 and 4 weeks after immunization in these patients. Both patients had renal involvement with one requiring dialysis. Both patients were treated with cyclophosphamide and corticosteroids, and plasmapheresis was added to the immunosuppressive regimen in one patient with dialysis-dependent renal failure. Both patients achieved disease remission. The patient with initial dialysis-dependent renal failure reached end-stage renal disease. There are 6 previous cases of AAV in the literature described in temporal association with administration of influenza vaccines. CONCLUSION: A causal role of vaccines in AAV cannot be confirmed with these case reports. The temporality suggests that the influenza vaccine may be a triggering factor for induction of vasculitis in predisposed individuals. We review the literature on reported cases of AAV following influenza vaccine administration and discuss possible mechanisms for influenza vaccine-associated AAV.

Effect of disease-modifying therapies on brain volume in relapsing-remitting multiple sclerosis: results of a five-year brain MRI study.

OBJECTIVE: To compare the long-term effect of disease-modifying therapies (DMT) on brain volume loss in relapsing-remitting MS (RRMS) patients. METHODS: We conducted a study to examine the effect of daily glatiramer acetate (GA), weekly low dose interferon beta (LD-IFNB), and high-dose high-frequency interferon beta disease (HD-IFNB) on brain volume loss over 5 years in RRMS patients. All patients were previously treatment naïve, had disease duration ≤5 years at the time of initiating DMT, and subsequently received the same DMT for 5 years continuously. The percentage change in brain volume (PCBV) was measured using fully automated software. MRI analysis was performed blinded to treatment allocation. RESULTS: The adjusted PCBV from baseline to year 5 was -2.27% in GA, -2.62% in LD-IFNB, and -3.21% in the HD-IFNB groups (-2.27 vs -2.62, p=0.0036; -2.27 vs -3.21, p<0.0001; -2.62 vs -3.21, p<0.0001). These data remained unchanged from year 1 to year 5, after adjusting for pseudoatrophy in the first year. A group of RRMS patients that remained untreated for a period ranging from 8 to 24 months, served as controls. All treatment groups were significantly better than the rate of projected brain volume loss in the untreated group over 5 years (p<0.0001). CONCLUSIONS: Global brain volume loss is a dynamic process even in relatively early RRMS patients that occurs despite intervention with therapy. However, all DMT significantly reduced the loss of brain volume compared to no treatment. The GA-treated group experienced the least reduction in brain volume over 5 years, compared to the LD-IFNB and HD-IFNB treated groups. These differences could be partly related to the immunologic consequences of GA therapy in RRMS.