Developing priorities for quality improvement in acute medicine using a modified Delphi method A consensus process hosted by the Society for Acute Medicine Quality Improvement Committee (SAM-QI).

INTRODUCTION: The SAM Quality Improvement Committee (SAM-QI), set up in 2016, has worked over the last year to determine the priority Acute Medicine QI topics. They have also discussed and put forward proposals to improve QI training for Acute Medicine professionals. METHODS: A modified Delphi process was completed over four rounds to determine priority QI topics. Online meetings were also used to develop proposals for QI training. RESULTS: Same Day Emergency Care (SDEC) was chosen as the priority topic for QI work within Acute Medicine. CONCLUSION: The SAM-QI group settled on SDEC being the priority topic for Acute Medicine QI development. Throughout the Delphi process SAM-QI has also developed proposals for QI training that will help Acute Medicine professionals deliver coordinated meaningful improvements in care.

Disruption of quadriceps tendon after total knee arthroplasty: Case report of four cases.

Quadriceps tendon rupture after total knee arthroplasty (TKA) is a rare but dire complication. It is associated with adverse outcomes and morbidities. Studies on such complications are scarce in the literature. In this study, we share our experience in the management of four patients who sustained quadriceps tendon rupture in the early postoperative period. Efforts should be focused on prevention. Meticulous surgical techniques during the medial parapatellar approach to preserve the integrity of quadriceps can reduce the risk of rupture. The importance of prompt diagnosis is emphasized as delayed treatment may lead to poor outcomes. However, making a diagnosis can be challenging, as worsening of the quadriceps strength after TKA is expected because of the surgical approach that violates the quadriceps muscle. In an event of postoperative trauma with resultant extensor weakness, an ultrasound evaluation to exclude a quadriceps tendon rupture should be promptly performed after a fracture is excluded.

Physician consensus on preventability and predictability of readmissions based on standard case scenarios.

BACKGROUND: Policy makers struggle with unplanned readmissions as a quality indicator since integrating preventability in such indicators is difficult. Most studies on the preventability of readmissions questioned physicians whether they consider a given readmission to be preventable, from which conclusions on factors predicting preventable readmissions were derived. There is no literature on the interobserver agreement of physician judgement. AIM: To assess the degree of agreement among physicians regarding predictability and preventability of medical readmissions. DESIGN: An online survey based on eight real-life case scenarios was distributed to European physicians. METHODS: Physicians were requested to rate from the first four (index admission) scenarios whether they expected these patients to be readmitted within 30 days (the predictability). The remaining four cases, describing a readmission, were used to assess the preventability. The main outcome was the degree of agreement among physicians determined using the intra class correlation coefficient (ICC). RESULTS: 526 European medical physicians completed the survey. Most physicians had internal medicine as primary specialism. The median years of clinical experience was 11. ICC for predictability of readmission was 0.67 (moderate to good) and ICC for preventability of readmission was 0.13 (poor). CONCLUSION: There was moderate to good agreement among physicians on the predictability of readmissions while agreement on preventability was poor. This study indicates that assessing preventability of readmissions based solely on the judgement of physicians is far from perfect. Current literature on the preventability of readmissions and conclusions derived on the basis of physician opinion should be interpreted with caution.

Quantifying the prevalence of frailty in English hospitals.

OBJECTIVES: Population ageing has been associated with an increase in comorbid chronic disease, functional dependence, disability and associated higher health care costs. Frailty Syndromes have been proposed as a way to define this group within older persons. We explore whether frailty syndromes are a reliable methodology to quantify clinically significant frailty within hospital settings, and measure trends and geospatial variation using English secondary care data set Hospital Episode Statistics (HES). SETTING: National English Secondary Care Administrative Data HES. PARTICIPANTS: All 50,540,141 patient spells for patients over 65 years admitted to acute provider hospitals in England (January 2005-March 2013) within HES. PRIMARY AND SECONDARY OUTCOME MEASURES: We explore the prevalence of Frailty Syndromes as coded by International Statistical Classification of Diseases, Injuries and Causes of Death (ICD-10) over time, and their geographic distribution across England. We examine national trends for admission spells, inpatient mortality and 30-day readmission. RESULTS: A rising trend of admission spells was noted from January 2005 to March 2013 (daily average admissions for month rising from over 2000 to over 4000). The overall prevalence of coded frailty is increasing (64,559 spells in January 2005 to 150,085 spells by Jan 2013). The majority of patients had a single frailty syndrome coded (10.2% vs total burden of 13.9%). Cognitive impairment and falls (including significant fracture) are the most common frailty syndromes coded within HES. Geographic variation in frailty burden was in keeping with known distribution of prevalence of the English elderly population and location of National Health Service (NHS) acute provider sites. Overtime, in-hospital mortality has decreased (>65 years) whereas readmission rates have increased (esp.>85 years). CONCLUSIONS: This study provides a novel methodology to reliably quantify clinically significant frailty. Applications include evaluation of health service improvement over time, risk stratification and optimisation of services.

Developing and validating a risk prediction model for acute care based on frailty syndromes.

OBJECTIVES: Population ageing may result in increased comorbidity, functional dependence and poor quality of life. Mechanisms and pathophysiology underlying frailty have not been fully elucidated, thus absolute consensus on an operational definition for frailty is lacking. Frailty scores in the acute medical care setting have poor predictive power for clinically relevant outcomes. We explore the utility of frailty syndromes (as recommended by national guidelines) as a risk prediction model for the elderly in the acute care setting. SETTING: English Secondary Care emergency admissions to National Health Service (NHS) acute providers. PARTICIPANTS: There were N=2,099,252 patients over 65 years with emergency admission to NHS acute providers from 01/01/2012 to 31/12/2012 included in the analysis. PRIMARY AND SECONDARY OUTCOME MEASURES: Outcomes investigated include inpatient mortality, 30-day emergency readmission and institutionalisation. We used pseudorandom numbers to split patients into train (60%) and test (40%). Receiver operator characteristic (ROC) curves and ordering the patients by deciles of predicted risk was used to assess model performance. Using English Hospital Episode Statistics (HES) data, we built multivariable logistic regression models with independent variables based on frailty syndromes (10th revision International Statistical Classification of Diseases, Injuries and Causes of Death (ICD-10) coding), demographics and previous hospital utilisation. Patients included were those>65 years with emergency admission to acute provider in England (2012). RESULTS: Frailty syndrome models exhibited ROC scores of 0.624-0.659 for inpatient mortality, 0.63-0.654 for institutionalisation and 0.57-0.63 for 30-day emergency readmission. CONCLUSIONS: Frailty syndromes are a valid predictor of outcomes relevant to acute care. The models predictive power is in keeping with other scores in the literature, but is a simple, clinically relevant and potentially more acceptable measurement for use in the acute care setting. Predictive powers of the score are not sufficient for clinical use.

The neural guidance receptor Plexin C1 delays melanoma progression.

Plexin C1 is a type I transmembrane receptor with intrinsic R-Ras GTPase activity, which regulates cytoskeletal remodeling and adhesion in normal human melanocytes. Melanocytes are pigment-producing cells of the epidermis, precursors for melanoma, and express high levels of Plexin C1, which is lost in melanoma in vitro and in vivo. To determine if Plexin C1 is a tumor suppressor for melanoma, we introduced Plexin C1 into a primary human melanoma cell line, and phenotypes including migration, apoptosis, proliferation and tumor growth in mice were analyzed. Complimentary studies in which Plexin C1 was silenced in human melanocytes were performed. Plexin C1 significantly inhibited migration and proliferation in melanoma, whereas in melanocytes, loss of Plexin C1 increased migration and proliferation. In mouse xenografts, Plexin C1 delayed tumor growth of melanoma at early time points, but tumors eventually escaped the suppressive effects of Plexin C1, due to Plexin C1-dependent activation of the pro-survival protein Akt. R-Ras activation stimulates melanoma migration. Plexin C1 lowered R-Ras activity in melanoma and melanocytes, consistent with inhibitory effects of Plexin C1 on migration of melanocytes and melanoma. To determine if R-Ras is expressed in melanocytic lesions in vivo, staining of tissue microarrays of nevi and melanoma were performed. R-Ras expression was highly limited in melanocytic lesions, being essentially confined to primary melanoma, and almost completely absent in nevi and metastatic melanoma. These data suggest that loss of Plexin C1 in melanoma may promote early steps in melanoma progression through suppression of migration and proliferation, but pro-survival effects of Plexin C1 ultimately abrogate the tumor suppressive effects of Plexin C1. In primary melanoma, loss of Plexin C1 may function in early steps of melanoma progression by releasing inhibition of R-Ras activation, and stimulating migration.

The source of endogenous carbon monoxide formation in human placental chorionic villi.

Carbon monoxide (CO) is proposed to play a role in placental vascular control, as the placenta produces and responds to CO. The mechanism by which CO is formed by the placenta is unclear but could be through heme oxygenase (HO) degradation of heme, lipid peroxidation, or both. Human placental cotyledons were perfused with Kreb s solution to remove blood. Chorionic villi segments were prepared for measurements of CO production in the absence/presence of an exogenous supply of heme substrate (methemalbumin), inhibitors of HO, or inhibitors of lipid peroxidation. HO inhibitors used were chromium mesoporphyrin (CrMP) (0.1 mM, 0.3 mM), and azalanstat (0.1 mM, 0.3 mM). The lipid peroxidation inhibitors used were EDTA (0.1 mM, 0.3 mM) and deferoxamine (0.1 mM). Incubation of villi segments with methemalbumin (0.15 mM, 0.3 mM, 0.45 mM) resulted in a concentration-dependent increase in CO formation above the basal, endogenous rate. CrMP and azalanstat inhibited basal endogenous CO production, whereas EDTA and deferoxamine enhanced CO formation above basal level. These results demonstrate that endogenous CO was formed by human chorionic villi from heme, primarily through the action of HO, and are consistent with the hypothesis that HO plays a role in the regulation of placental vasculature by the formation of heme-derived CO.

Geographic distribution and molecular variation of isolates of three whitefly-borne closteroviruses of cucurbits: lettuce infectious yellows virus, cucurbit yellow stunting disorder virus, and beet pseudo-yellows virus.

ABSTRACT The geographic incidence and molecular variation of three whitefly-borne closteroviruses (lettuce infectious yellows virus [LIYV], cucurbit yellow stunting disorder virus [CYSDV], and beet pseudo-yellows virus [BPYV]) were studied in cucurbits collected from several distinct geographic locations. Of 498 samples analyzed, none were found to be infected by LIYV. Sixty-nine samples collected in the Middle East and Mediterranean Europe were found infected by CYSDV, and twelve samples from Crete and Italy were infected by BPYV. Reverse-transcription poly-merase chain reaction of a portion of the heat shock protein 70 homolog coding region, followed by single-strand conformation polymorphism and nucleotide sequence analysis, was used to estimate the intra- and inter-isolate molecular variability. These analyses showed that each BPYV and CYSDV isolate was composed of a population of sequence variants with a nucleotide identity greater than 98%. CYSDV isolates could be divided into two divergent groups. Group I was only composed of isolates from Spain, Jordan, and Turkey, and group II isolates were predominantly found in Saudi Arabia. Nucleotide identity between isolates of the same group was greater than 99%, whereas identity between both groups was less than 92%. All BPYV isolates showed a nucleotide identity greater than 98%.

Autosomal mutations affecting adhesion between wing surfaces in Drosophila melanogaster.

Integrins are evolutionarily conserved transmembrane alpha,beta heterodimeric receptors involved in cell-to-matrix and cell-to-cell adhesions. In Drosophila the position-specific (PS) integrins mediate the formation and maintenance of junctions between muscle and epidermis and between the two epidermal wing surfaces. Besides integrins, other proteins are implicated in integrin-dependent adhesion. In Drosophila, somatic clones of mutations in PS integrin genes disrupt adhesion between wing surfaces to produce wing blisters. To identify other genes whose products function in adhesion between wing surfaces, we conducted a screen for autosomal mutations that produce blisters in somatic wing clones. We isolated 76 independent mutations in 25 complementation groups, 15 of which contain more than one allele. Chromosomal sites were determined by deficiency mapping, and genetic interactions with mutations in the beta PS integrin gene myospheroid were investigated. Mutations in four known genes (blistered, Delta, dumpy and mastermind) were isolated. Mutations were isolated in three new genes (piopio, rhea and steamer duck) that affect myo-epidermal junctions or muscle function in embryos. Mutations in three other genes (kakapo, kiwi and moa) may also affect cell adhesion or muscle function at hatching. These new mutants provide valuable material for the study of integrin-dependent cell-to-cell adhesion.

Disperse versus compact elements for the regulation of runt stripes in Drosophila.

The segmented body pattern of the Drosophila embryo is established through a hierarchical network of interacting genes. At each successive step in this pathway, transcriptional regulation is used to convert coarse positional information into finer patterns of gene expression. Central to this process are the cis-regulatory regions that drive the dynamic spatial expression of the different segmentation genes. Here we describe the cis-regulatory region of the runt gene. As found for both other primary pair-rule genes, hairy and even-skipped, there are stripe-specific elements which mediate the initial regulation of runt stripes by gap genes. We did not find autoregulatory elements as described for even-skipped and fushi tarazu. The regulation of runt by other pair-rule genes is mediated by a large region, extending over 5 kb upstream and downstream of the transcription start site. This "disperse" element cannot be subdivided into functionally independent subelements or minimal elements. Such disperse elements mediating pair-rule gene interactions may have escaped detection in other segmentation genes and may involve molecular mechanisms different from those mediating regulation by gap genes.

The Hin dimer interface is critical for Fis-mediated activation of the catalytic steps of site-specific DNA inversion.

BACKGROUND: Hin is a member of an extended family of site-specific recombinases--the DNA invertase/resolvase family--that catalyze inversion or deletion of DNA. DNA inversion by Hin occurs between two recombination sites and requires the regulatory protein Fis, which associates with a cis-acting recombinational enhancer sequence. Hin recombinase dimers bind to the two recombination sites and assemble onto the Fis-bound enhancer to generate an invertasome structure, at which time they become competent to catalyze DNA cleavage and strand exchange. In this report, we investigate the role of the Hin dimer interface in the activation of its catalytic functions. RESULTS: We show that the Hin dimer is formed at an interface that contains putative amphipathic alpha-helices in a manner that is very similar to gamma delta resolvase. Certain detergents weakened cooperative interactions between the subunits of the Hin dimer and dramatically increased the rate of the first chemical step of the reaction--double-strand cleavage events at the center of the recombination sites. Amino-acid substitutions within the dimer interface led to profound changes in the catalytic properties of the recombinase. Nearly all mutations strongly affected the ability of the dimer to cleave DNA and most abolished DNA strand exchange in vitro. Some amino-acid substitutions altered the concerted nature of the DNA cleavage events within both recombination sites, and two mutations resulted in cleavage activity that was independent of Fis activation in vitro. Disulfide-linked Hin dimers were catalytically inactive; however, subsequent to the addition of the Fis-bound enhancer sequence, catalytic activity was no longer affected by the presence of oxidizing agents. CONCLUSIONS: The combined results demonstrate that the Hin dimer interface is of critical importance for the activation of catalysis and imply that interactions with the Fis-bound enhancer may trigger a conformational adjustment within the region that is important for concerted DNA cleavage within both recombination sites, and possibly for the subsequent exchange of DNA strands.

Outcome of pregnancy in patients with organic heart disease in Taiwan.

A total of 122 pregnancies in 101 women with organic heart disease were reviewed. The incidence of organic heart disease in pregnant women was 0.25%. The ratio of rheumatic to congenital heart disease was 1.0 to 1.5. In the congenital heart disease group, IUGR was more frequent in the cyanotic group as were preterm births. Patients with cyanotic lesions had a significantly higher maternal mortality rate than those with acyanotic lesions. The cyanotic group without surgical correction had a significantly higher maternal mortality rate and more IUGR than those with correction. Congestive heart failure was the most common maternal complication, with a rate of 38.1%. The patients with good cardiac status control during pregnancy developed less IUGR, had fewer preterm births, less maternal morbidity and less maternal mortality than those in poor condition. Patients in functional classes I and II before pregnancy carried less risk of maternal morbidity than those in classes III and IV.

Extracranial head and neck: PET imaging with 2-[F-18]fluoro-2-deoxy-D-glucose and MR imaging correlation.

The aim of this study was to define and quantitate the normal anatomy of the extracranial head and neck with 2-[fluorine-18]fluoro-2-deoxy-D-glucose (FDG) positron emission tomography (PET). This information was used to study 12 patients with primary squamous cell carcinomas. In all cases, the lymphoid tissue of the Waldeyer ring and the palatine and lingual tonsils could be differentiated from the airway, striated muscle, osseous structures, and salivary glands. Striated muscle had markedly less activity than lymphoid or salivary gland tissue. In the 12 patients with primary tumors, FDG PET depicted the tumor as an area of increased activity significantly higher than that of normal tissue. In one instance, FDG PET allowed detection of a tumor not seen at magnetic resonance (MR) imaging or computed tomography. Of the 34 lymph nodes positive for carcinoma, 24 were positive according to MR size criteria and 25 were detected with FDG PET. FDG PET allowed detection of three nonenlarged metastatic nodes that were negative at MR imaging.

The Drosophila segmentation gene runt has an extended cis-regulatory region that is required for vital expression at other stages of development.

The Drosophila runt gene functions in several developmental pathways during embryogenesis. This gene was initially characterized due to the pivotal role that it plays in the genetic regulatory network that establishes the segmented body pattern. Recently it was found that this X-chromosome-linked gene is one of several dosage-sensitive, X-linked components that is involved in activating the Sex-lethal gene in blastoderm stage female embryos. Finally, this gene is also extensively re-expressed in later stages of embryogenesis in the developing nervous system where it plays an important role in the development of specific neural lineages. We have initiated an analysis of the runt cis-regulatory region in order to investigate runt's roles in these (and other) developmental pathways. Analysis of both the function and the expression patterns of runt genes with truncated cis-regulatory regions indicates that there are multiple elements that make quantitative contributions to runt regulation during segmentation. We find that sequences that are more than 8.5 kb upstream of the runt promoter are necessary for normal expression during the post-blastoderm stages of embryogenesis. Genetic experiments indicate that the post-blastoderm expression of runt is vital to the organism.

The expression of C-jun and junB mRNA in renal cell cancer and in vitro regulation by transforming growth factor beta 1 and tumor necrosis factor alpha 1.

The proto-oncogene C-jun acts as a transcriptional activator or repressor for numerous cellular genes, and the overexpression of these genes may cause malignant transformation. JunB inhibits c-jun's transforming activities. We investigated the expression of jun genes in renal cell cancer (RCC) and their regulation by cytokines and transforming growth factor beta 1 (TGF-b1). The constitutive expression of c-jun was detected in 39 of 43 fresh frozen RCC, 5 of 10 normal kidneys, and the expression of junB detected in 28 of 34 RCC, 5 of 6 normal kidneys. C-jun was also found expressed in all 10 RCC tumor lines examined and junB was expressed at low levels in 6 of 10 renal tumor lines. TGF-b1 and tumor necrosis factor alpha (TNF-a) have been shown to alter the expression of jun genes in other tissue types. Additionally, TGF-b1, TNF-a, and gamma interferon (g-IFN) were shown to inhibit the growth of RCC. We found that TGF-b1 highly augmented the expression of junB (mean of 34 folds, p less than .05), but did not significantly alter the expression of c-jun, the transforming gene. In contrast, TNF-a significantly enhanced the expression of both c-jun (mean fold enhancement of 2.1, p less than .05) and junB (2.2 folds, p less than .05). Interleukin-2 (IL-2), interleukin-4 (IL-4) and g-IFN did not significantly alter jun expression. The findings presented suggest that c-jun may have a role in inducing malignant transformation in RCC and a novel mechanism by which TGF-b1 may exert its anti-tumor effects, via the activation of junB. Additionally, although TGF-b1, TNF-a, and g-IFN all have anti-proliferative actions on RCC in vitro, they were found to have different effects in altering jun expressions.

Meconium peritonitis-antenatal diagnosis by ultrasound.

Meconium peritonitis is usually the result of prenatal bowel obstruction with subsequent perforation, then the contents spread into the peritoneal cavity, which results in a sterile inflammatory reaction. The incidence ranges from 1/1500 to 1/2000, if without prenatal diagnosis and planned postnatal treatment, the mortality rate is as high as 62%. We describe three children, two with surgically, one with autoptically confirmed meconium peritonitis. All had abnormally prenatal ultrasonographic examinations. The first fetus showed a large 10 x 11 cm intra-abdominal mass with floating echogenic substances inside and with an echogenic rim. The second showed increased echogenicity with dilated bowel in abdominal cavity in one of the twin, and the third had an intra-abdominal cyst with several echogenic bands inside, fetal ascites was also noted. It is remarkable that the ultrasonographic findings were different in the three children. Two of the three children survived postoperation, one died 3 hours later after induction out at 31 weeks of gestational age due to multiple congenital anomalies.

Enhanced stimulatory effect of high density lipoproteins (HDL) and other agonists on vascular prostacyclin production in rats fed alcohol-containing diets.

Chronic administration of liquid diets containing 36% of energy as ethanol to rats increased the serum level of high density lipoproteins (HDL) by 40% and potentiated 2 to 3-fold the stimulatory effect of these lipoproteins on the production of prostacyclin by aortic rings, as compared to pair-fed controls given isocaloric carbohydrate instead of ethanol. Cross-incubations between aortic rings and HDL from either alcohol-fed or pair-fed control rats revealed two factors operating in opposite directions. On the one hand, the predominant mechanism for the potentiation was increased reactivity of the vessel to these lipoproteins. This increased reactivity was also apparent with other agonists of prostacyclin formation. On the other hand, for equal amounts of either cholesterol or protein, the HDL from alcohol-fed rats were less stimulatory than those from controls. This was associated with a smaller content of arachidonate in the HDL of alcohol-fed rats. These ethanol effects on prostacyclin, a potent vasodilator and platelet antiaggregator, may contribute to the decreased incidence of ischemic heart disease observed in moderate alcohol drinkers.