Costing pressure ulcer care in an Irish acute care setting: a feasibility study.

OBJECTIVE: To test the feasibility of using a standardised data collection tool to estimate the cost of stage 2-4 pressure ulcer (PU) care within an acute care setting. METHOD: Data on resource use and cost were obtained through a retrospective survey of nursing and medical notes collecting cost data for individual patients who received care for stage 2-4 PUs. RESULTS: Data for 20 patients (12 male/8 female) were analysed. The average patient age was 69 years (range: 37-95 years). Of this sample, seven patients had hospital-acquired PUs (HAPUs) and 14 patients had community-acquired PUs (CAPU) (one patient had both-in different anatomical areas). Over half of the total sample (55%; n=11) had a stage 2 PU. The average length of stay was 31.8 days (range: 5-119 days). Most of the patients (70%; n=14) had a CAPU. The average cost per patient with PU care was €878 (range: €39-2393). The mean cost for patients with a HAPU was €866 (SD: €1313) versus €911 (SD: €567) for patients with a CAPU. The majority of the cost related to equipment and staff time for treatment. CONCLUSION: Overall, the application of the standardised data collection tool to obtain cost data from retrospective inspection of nursing and medical notes is feasible. The cost of PU care in this sample was high, indicating that these wounds may impose a substantial burden on health systems. The costs varied greatly between patients in the sample, reflecting the complexity of PU care. Furthermore, given that costs increased with the higher PU stages, there is a potential to reduce costs by preventing the development of higher stage PUs. Larger-scale studies are required to understand the cost variation and full economic impact of PU care. DECLARATION OF INTEREST: The authors have no conflicts of interest.

Utility of eConsults for COVID-19 vaccine-related concerns in Ontario: a cross-sectional analysis.

BACKGROUND: The Champlain BASE™ and Ontario eConsult services are virtual platforms that serve to facilitate contact between primary care providers and specialists across Ontario, relaying patient-specific questions to relevant specialists via a secure web-based platform. Despite ample evidence regarding the general effectiveness of these platforms, their utility as it pertains to clinical concerns regarding COVID-19 vaccines has not yet been explored. METHODS: We performed a cross-sectional descriptive analysis of COVID-19 vaccine related eConsults on Ontario patients completed by five allergy specialists between February and October of 2021. 4318 COVID-19 vaccine-related eConsults were completed in total during this time; with 1857 completed by the five allergists participating in this analysis. Question types/content were categorized using a taxonomy developed through consensus on a weighted monthly sample of 499 total cases. Data regarding whether external resources were required to answer each eConsult, impact on primary care provider referral decisions, and allergy consultant response times were collected. A 2-question survey was completed by primary care providers following eConsultation and results were collected. RESULTS: 41.08% of eConsults received involved safety concerns regarding COVID-19 vaccine administration in the setting of prior allergic disease and another 36.1% involved a potential reaction the first dose of a COVID-19 vaccine. 72.1% of eConsults were answered by specialist without needing external resources, and only 9.8% of all eConsults received resulted in a recommendation for formal in-person referral to Clinical Immunology & Allergy specialist or another subspecialty. Average time to complete eConsult was 16.4 min, and 79.7% of PCP eConsult queries which would have traditionally resulted in formal consultation were resolved based on advice provided in the eConsult without need for in-person assessment. CONCLUSIONS: Our study demonstrates the utility of the eConsult service as it pertains to COVID-19 vaccine-related concerns. The eConsult platform proved an effective tool in diverting the need for in-person assessment by an Allergist or other medical specialty. This is significant given the large volume of eConsults completed by Allergists, and demonstrates the impact of an effective electronic delivery of care model during a time of strained resources and public health efforts directed at mass vaccination.

Filling the gaps: A community case study in using an interprofessional approach and community-academic partnerships to address COVID-19-related inequities.

Public health challenges rapidly escalated during the COVID-19 pandemic. In response to a severe lack of resources and support in the near western suburbs of Chicago, the COVID Equity Response Collaborative: Loyola (CERCL) was established by an interprofessional team of Loyola University Chicago students, staff, and faculty. CERCL sought to minimize the negative impact of COVID-19 on vulnerable communities, those that are largely Black, Hispanic, or low-income. From April 2020 to the present, the collaborative utilized community-academic partnerships and interdisciplinary collaborations to conduct programming. CERCL's programming included free community-based testing, screening for and assistance with social determinants of health, dissemination of relevant and reliable COVID-related information, provision of personal protective equipment, and facilitation of access to vaccines. With partners, the collaborative conducted 1,500 COVID-19 tests, trained 80 individuals in contact tracing, provided over 100 individuals with specifically tailored resources to address social and legal needs, distributed 5,000 resource bags, held 20 community conversations, canvassed 3,735 homes, and hosted 19 vaccine clinics. Community-academic partnerships with the health system, community and governmental agencies, and the local public health department have been critical to CERCL efforts. The interdisciplinary and interprofessional successes demonstrated in this case study lends the example of a relevant, sustainable, and practical intervention to address nuanced public health issues.

How Should History of Physician Involvement in the Holocaust Inform How Physicians Approach Employers?

In response to a case involving an advertisement for a physician to work in a private detention center housing asylum seekers and immigrants, this commentary considers ethical obligations of physicians responsible for detainees' health care. The commentary also suggests key points a physician should make during a job interview at a detention center and concerns a physician might articulate about caregiving practices for detainees.

Use of a temporary "solubilizing" peptide tag for the Fmoc solid-phase synthesis of human insulin glargine via use of regioselective disulfide bond formation.

Solid-phase peptide synthesis has been refined to a stage where efficient preparation of long and complex peptides is now achievable. However, the postsynthesis handling of poorly soluble peptides often remains a significant hindrance to their purification and further use. Several synthetic schemes have been developed for the preparation of such peptides containing modifications to aid their solubility. However, these require the use of complex chemistry or yield non-native sequences. We describe a simple approach based on the use of penta-lysine "tags" that are linked to the C-terminus of the peptide of interest via a base-labile linker. After ready purification of the now freely solubilized peptide, the "tag" is removed by simple, brief base treatment giving the native sequence in much higher overall yield. The applicability of the method was demonstrated by the novel preparation of insulin glargine via solid-phase synthesis of each of the two chains--including the notoriously poorly soluble A-chain--followed by their combination in solution via regioselective disulfide bond formation. At the conclusion of the chain combination, the solubilizing peptide tag was removed from the A-chain to provide synthetic human glargine in nearly 10% overall yield. This approach should facilitate the development of new insulin analogues as well as be widely applicable to the improved purification and acquisition of otherwise poorly soluble synthetic peptides.

Is (-)-catechin a novel weapon of spotted knapweed (Centaurea stoebe)?

The novel weapons hypothesis states that some invasive weed species owe part of their success as invaders to allelopathy mediated by allelochemicals that are new to the native species. Presumably, no resistance has evolved among the native species to this new allelochemical (i.e., the novel weapon). In their native habitat, however, the plants that co-evolved with these invasive species have theoretically evolved defenses that obviate the allelochemical advantage. Previous studies have claimed that catechin is such a novel weapon of spotted knapweed (Centaurea stoebe = C. maculosa), an invasive species in the non-native habitat of North America. These studies indicated that (-)-catechin is more phytotoxic than (+)-catechin. Other studies have not found sufficient catechin in field soils to support this theory. We report that (-)-catechin and (+)-catechin are essentially equal, but poorly phytotoxic to a variety of plant species in bioassays without soil. In a dose/response experiment with Montana soils, we found the lowest dose for a growth reduction of two native Montana grasses (Koeleria macrantha and Festuca idahoensis) by a racemic mixture of (+/-)-catechin that ranged from about 25 to 50 mM, concentrations, orders of magnitude higher than expected in nature. Autoclaving the soil before adding the catechin did not affect the activity of catechin. We found (-)-catechin to be a potent antioxidant, in contrast to a previous claim that it acts as an allelochemical by causing oxidative stress. Our findings suggest that catechin is not a novel weapon of spotted knapweed and that other allelochemical(s) or alternative mechanisms must be found to explain the success of this species as an invader in North America.

Good Sanctuary Doctoring for Undocumented Patients.

Clinicians whose practice includes a significant immigrant population report a climate of fear adversely affecting their current patients. Increased immigration enforcement targeting undocumented immigrants increases these patients' stress and negatively affects their willingness to seek medical care. To address these concerns, this article draws upon the literature and the authors' experience to develop guidance on sanctuary doctoring. These materials provide opportunities for patients to open a dialogue about their immigration concerns and can assist clinicians in connecting patients to networks and resources that can address their needs. The materials are designed to be used in single, brief clinical encounters.

Detection of pepsin and IL-8 in saliva of adult asthmatic patients.

Objective: Asthma and gastric reflux disease are widespread and often coexisting diseases with complex interactions, leading some to suspect that asthma symptoms of patients with reflux may improve with anti-reflux therapy. The objective of this study was to determine whether pepsin in saliva, indicative of airway reflux, could be detected in patients with asthma of varying severity and test the requirement of citric acid as a pepsin preservative. Methods: Saliva samples were collected in the clinic (with/without citric acid) and upon waking the following morning from 25 asthmatic patients. Enzyme-linked immunosorbent assay was performed for pepsin and interleukin-8 (IL-8), an inflammatory cytokine induced by pepsin in other airway epithelia. Pepsin induction of IL-8 was tested in a lung epithelial cell culture model. Results: Pepsin was detected in saliva from 14/25 patients (56%; mean concentration of pepsin in specimens where observed ±SD =80.3±87.5 ng/mL); significant agreement was found between samples collected in the presence/absence of citric acid. No significant associations were found with pepsin and clinical measures of asthma severity. IL-8 was detected in saliva from 22/25 patients (88%; mean IL-8 in all specimens where observed =3.27±3.91 ng/mL). IL-8 was significantly upregulated in human lung epithelial cells exposed to pepsin at pH7 in vitro (P=0.041). Conclusion: In summary, more than half of the asthma patients in this study were found to have pepsin in their saliva, indicative of airway reflux. These data support the use of salivary pepsin as a noninvasive tool for future investigation of airway reflux in a larger cohort. The data further suggest that collection in citric acid as a sample preservative is not warranted and that pooling of multiple saliva samples collected at various timepoints may improve sensitivity of pepsin detection and reduce costs incurred by multiple sample analysis in future studies.

Impaired glucose metabolism and exercise capacity with muscle-specific glycogen synthase 1 (gys1) deletion in adult mice.

OBJECTIVE: Muscle glucose storage and muscle glycogen synthase (gys1) defects have been associated with insulin resistance. As there are multiple mechanisms for insulin resistance, the specific role of glucose storage defects is not clear. The aim of this study was to examine the effects of muscle-specific gys1 deletion on glucose metabolism and exercise capacity. METHODS: Tamoxifen inducible and muscle specific gys-1 KO mice were generated using the Cre/loxP system. Mice were subjected to glucose tolerance tests, euglycemic/hyperinsulinemic clamps and exercise tests. RESULTS: gys1-KO mice showed ≥85% reduction in muscle gys1 mRNA and protein concentrations, 70% reduction in muscle glycogen levels, postprandial hyperglycaemia and hyperinsulinaemia and impaired glucose tolerance. Under insulin-stimulated conditions, gys1-KO mice displayed reduced glucose turnover and muscle glucose uptake, indicative of peripheral insulin resistance, as well as increased plasma and muscle lactate levels and reductions in muscle hexokinase II levels. gys1-KO mice also exhibited markedly reduced exercise and endurance capacity. CONCLUSIONS: Thus, muscle-specific gys1 deletion in adult mice results in glucose intolerance due to insulin resistance and reduced muscle glucose uptake as well as impaired exercise and endurance capacity. IN BRIEF: This study demonstrates why the body prioritises muscle glycogen storage over liver glycogen storage despite the critical role of the liver in supplying glucose to the brain in the fasting state and shows that glycogen deficiency results in impaired glucose metabolism and reduced exercise capacity.

Hybridization and invasion: an experimental test with diffuse knapweed (Centaurea diffusa Lam.).

A number of studies have suggested a link between hybridization and invasion. In this study, we experimentally test the potential for hybridization to influence invasion through a greenhouse common garden study. Diffuse knapweed (DK) (Centaurea diffusa Lam.) was introduced to North America with admixture from spotted knapweed (SK) (Centaurea stoebe subsp. stoebe L.). Comparisons between North American DK (including hybrid phenotypes) and native (European) DK in a common garden did not reveal enhanced performance or increased phenotypic variance, suggesting that pre-introduction hybridization or, more generally, post-introduction evolutionary change has not significantly contributed to the invasion of DK. In contrast, early generation hybrids [artificially created Backcross 1 (BC1) plants] exhibited increased variance for eight of the examined traits, and greater leaf and reproductive shoot production when compared to North American DK. Individual BC1 lines differed for several traits, suggesting the importance of the cross for drawing conclusions from such comparisons. When compared to the parental species (DK and SK), the BC1 plants were not transgressive for any of the measured traits. Overall, these findings suggest that if diploid SK is introduced to North America, interspecific hybridization has the potential to result in even more aggressive invaders.

The New Zealand obese mouse model of obesity insulin resistance and poor breeding performance: evaluation of ovarian structure and function.

Infertility, associated with oligo/anovulation, increased ovarian volume, numerous follicular cysts, and metabolic disturbances such as obesity and insulin resistance (IR) are characteristics common to polycystic ovary syndrome (PCOS), the most common endocrine disorder in women of reproductive age. Here, we show that New Zealand obese (NZO) mice display similar metabolic characteristics such as obesity, leptin insensitivity, glucose intolerance, and IR. Importantly, NZO mice are poor breeders; however, the mechanism for this has not been investigated. The aim of this study was to assess the ovarian structure/morphology and sex hormone levels in female NZO and lean C57BL/6J control mice. Twenty-five NZO and twenty female control mice were studied at three different ages (young, adult, and aged). The animals were weighed, an insulin tolerance test was carried out, and blood was collected for measurement of hormone levels. The ovaries were removed for histological analysis. As expected, NZO mice presented higher body weights (P=0.001), increased basal plasma glucose (P=0.007), and insulin levels (P=0.001) as well as IR, compared with control mice. NZO mice showed an increased ovarian volume, reduced numbers of corpora lutea, and higher total follicle numbers (P=0.0001). The number of primordial follicles increased (P=0.02) at the young stage, as well as the amount of atretic follicles (P=0.03), in NZO compared with control mice. NZO mice also displayed reduced plasma LH and increased estradiol levels. In conclusion, NZO mice show a poor breeding performance due to decreased ovulation, increased number of primordial and atretic follicles, and ovarian size. Given that NZO mice are obese, hyperinsulinemic and insulin resistant, they are suitable for investigating pathophysiological mechanisms linking metabolic alterations with reproductive defects.

Hybridization and invasion: one of North America's most devastating invasive plants shows evidence for a history of interspecific hybridization.

Hybridization has been hypothesized to influence invasion through the generation of novel phenotypes and/or increased levels of genetic variance. Based on morphology, hybrids between diffuse knapweed and spotted knapweed, two invasive plants in North America, are present in the invaded range. Some individuals within most diffuse knapweed sites in North America exhibit intermediate diffuse × spotted floral morphology. We examined hybridization at the molecular level, using amplified fragment length polymorphisms. Approximately a quarter of the assayed North American diffuse knapweed individuals exhibited evidence of introgression from spotted knapweed. However, plants with intermediate morphology did not show evidence of mixed ancestry more often than the plants with typical diffuse knapweed morphology. The high proportion of hybrid individuals in North American diffuse knapweed sites found here, combined with evidence from recent studies, suggests that diffuse knapweed was likely introduced with admixed individuals, and the hybrids are not newly created postintroduction. A century of backcrossing with diffuse knapweed has likely decoupled the relationship between morphology and admixture at the molecular level. In contrast to the scenario encountered in North America, in the native range where diploid diffuse and spotted knapweed overlap, hybrid swarms are common. In such sites, the floral phenotype aligns more closely with the genotype.

The deletion variant of nicotinamide nucleotide transhydrogenase (Nnt) does not affect insulin secretion or glucose tolerance.

The C57BL/6J (B6J) strain is the most widely used mouse strain in metabolic research. B6J mice produce a truncated form of nicotinamide nucleotide transhydrogenase (NNT), an enzyme that pumps protons across the inner mitochondrial membrane. It has been proposed that this results in B6J mice having reduced insulin secretion and glucose intolerance compared with other strains of mice (e.g. C3H/HeH and DBA/2) that have a full-length NNT. The aim of this study was to determine whether truncated NNT was associated with reduced insulin secretion and glucose intolerance, comparing B6 substrains that differ in having a truncated NNT. C57BL/6N (B6N) mice have wild-type Nnt. We compared Nnt expression and activity levels as well as in vivo insulin secretion and glucose tolerance between these mice and B6J. Body weights and specific fat-pad depot masses were alike and Nnt expression and activity levels were similar between B6N and B6J mice. Glucose-mediated insulin secretion and insulin sensitivity were comparable between the two groups of mice, as were plasma glucose and insulin levels during the oral glucose tolerance test. The presence of a truncated Nnt did not affect insulin secretion or glucose tolerance on the C57BL/6 background. We suggest that low or normal levels of NNT (regardless of truncation) have little effect on insulin secretion. Rather, it is the increase in expression of Nnt that regulates and enhances insulin secretion. Our data confirm that B6J is a reasonable control strain for diabetes research; this is especially important considering that it is the strain commonly used to generate genetically modified animals.

Gynecologic cancers.

Office visits centering on preventive and gynecologic concerns compose a significant proportion of any primary care practice. The detection and prevention of gynecologic cancers are topics that often predominate such visits. The trend of increasing obesity in the general population and the exploding public awareness of the prevalence of human papillomavirus are examples of topics that affect the primary care physician's approach toward gynecologic cancer screening for women. Changing incidence rates in endometrial cancer and cervical cancer challenge the traditional approach to screening, guiding the primary care physician to consider individual risk factors during the routine health maintenance examination. In this article, the epidemiology, screening guidelines, and a review of management are presented for vulvar, cervical, ovarian, and endometrial cancer.

The case against (-)-catechin involvement in allelopathy of Centaurea stoebe (spotted knapweed).

Proving allelopathic chemical interference is a daunting endeavor, in that production and movement of a phytotoxin from a donor plant to a receiving plant must be demonstrated in the substrate in which the plants grow, which is usually a complex soil matrix. The soil levels or soil flux levels of the compound generated by the donor must be proven to be sufficient to adversely affect the receiving plant. Reports of (-)-catechin to be the novel weapon used by Centaurea stoebe (spotted knapweed) to invade new territories are not supported by the paper featured in this Addendum, nor by papers produced by two other laboratories. These papers find that (-)-catechin levels in soil in which C. stoebe grows are orders of magnitude below levels that cause only minor growth effects on reported sensitive species. Furthermore, the claim that (-)-catechin acts as a phytotoxin through causing oxidative damage is refuted by the fact that the molecule is a strong antioxidant and is quickly degraded by extracellular root enzymes.

Evaluating the glucose tolerance test in mice.

The objective of this study was to determine the optimal conditions under which to assess glucose tolerance in chow- and high-fat-fed C57BL/6J mice. Mice were fed either chow or high-fat diet for 8 wk. Variables tested were fasting duration (0-, 3-, 6-, and 24-h and overnight fasting), route of administration (intraperitoneal vs. oral) load of glucose given (2, 1, or 0.5 g/kg and fixed 50-mg dose), and state of consciousness. Basal glucose concentrations were increased in high-fat- compared with chow-fed mice following 6 h of fasting (9.1 +/- 0.3 vs. 7.9 +/- 0.4 mmol/l P = 0.01). Glucose tolerance was most different and therefore significant (P = 0.001) in high-fat-fed mice after 6 h of fasting (1,973 +/- 96 vs. 1,248 +/- 83 mmol.l(-1).120 min(-1)). The difference in glucose tolerance was greater following an OGTT (142%), in contrast to an IPGTT, with a 127% difference between high fat and chow. We also found that administering 2 g/kg of glucose resulted in a greater level of significance (P = 0.0008) in glucose intolerance in high-fat- compared with chow-fed mice. A fixed dose of 50 mg glucose regardless of body weight was enough to show glucose intolerance in high-fat- vs. chow-fed mice. Finally, high-fat-fed mice showed glucose intolerance compared with their chow-fed counterparts whether they were tested under conscious or anesthetized conditions. We conclude that 2 g/kg glucose administered orally following 6 h of fasting is best to assess glucose tolerance in mice under these conditions.

Increased glucose production in mice overexpressing human fructose-1,6-bisphosphatase in the liver.

Increased endogenous glucose production (EGP) predominantly from the liver is a characteristic feature of type 2 diabetes, which positively correlates with fasting hyperglycemia. Gluconeogenesis is the biochemical pathway shown to significantly contribute to increased EGP in diabetes. Fructose-1,6-bisphosphatase (FBPase) is a regulated enzyme in gluconeogenesis that is increased in animal models of obesity and insulin resistance. However, whether a specific increase in liver FBPase can result in increased EGP has not been shown. The objective of this study was to determine the role of upregulated liver FBPase in glucose homeostasis. To achieve this goal, we generated human liver FBPase transgenic mice under the control of the transthyretin promoter, using insulator sequences to flank the transgene and protect it from site-of-integration effects. This resulted in a liver-specific model, as transgene expression was not detected in other tissues. Mice were studied under the following conditions: 1) at two ages (24 wk and 1 yr old), 2) after a 60% high-fat diet, and 3) when bred to homozygosity. Hemizygous transgenic mice had an approximately threefold increase in total liver FBPase mRNA with concomitant increases in FBPase protein and enzyme activity levels. After high-fat feeding, hemizygous transgenics were glucose intolerant compared with negative littermates (P < 0.02). Furthermore, when bred to homozygosity, chow-fed transgenic mice showed a 5.5-fold increase in liver FBPase levels and were glucose intolerant compared with negative littermates, with a significantly higher rate of EGP (P < 0.006). This is the first study to show that FBPase regulates EGP and whole body glucose homeostasis in a liver-specific transgenic model. Our homozygous transgenic model may be useful for testing human FBPase inhibitor compounds with the potential to treat patients with type 2 diabetes.

A lack of evidence for an ecological role of the putative allelochemical (+/-)-catechin in spotted knapweed invasion success.

Allelopathy is a notoriously difficult mechanism to demonstrate. There has been a recent resurgence of interest in allelopathy because of the work done on the invasive weed spotted knapweed and its putative allelochemical, (+/-)-catechin. In this study we collected and analyzed soil samples taken from three, long-term knapweed infested sites in Montana, USA during the summer and fall of 2005. We only detected catechin in all the soil cores at one time point (August, 2005) at two of the sites. Field levels from these two sites were nearly three orders of magnitude lower than what has previously been reported to cause reduced growth in a sensitive native species. Fourteen percent of the remaining soil cores contained low but detectable levels (<0.11 ppm) of (+/-)-catechin. Additional experiments indicated that soil moisture appears to play a significant role in whether or not catechin degrades rapidly or remains in the soil. Adding to previous work, this paper sheds doubt on the importance of this chemical in spotted knapweed invasion success.