Search

Urinary tract infections (UTIs) are highly recurrent and frequently caused by Uropathogenic Escherichia coli (UPEC) strains that can be found in patient intestines. Seeding of the urinary tract from this intestinal reservoir likely contributes to UTI recurrence (rUTI) rates. Thus, understanding the factors that promote UPEC intestinal colonization is of critical importance to designing therapeutics to reduce rUTI incidence. Although E. coli is found in high abundance in large intestine mucus, little is known about how it is able to maintain residence in this continuously secreted hydrogel. We discovered that the FimH adhesin of type 1 pili (T1P) bound throughout the secreted mucus layers of the colon and to epithelial cells in mouse and human samples. Disruption of T1P led to reduced association with colon mucus. Notably, this mutant up-regulated flagellar production and infiltrated the protective inner mucus layer of the colon. This could explain how UPEC resists being washed off by the continuously secreted mucus layers of the colon.

Millions suffer from urinary tract infections (UTIs) worldwide every year with women accounting for the majority of cases. Uropathogenic Escherichia coli (UPEC) causes most of these primary infections and leads to 25% becoming recurrent or chronic. To repel invading pathogens, the urinary tract mounts a vigorous innate immune response that includes the secretion of antimicrobial peptides (AMPs), rapid recruitment of phagocytes, and exfoliation of superficial umbrella cells. Here, we investigate secretory leukocyte protease inhibitor (SLPI), an AMP with antiprotease, antimicrobial, and immunomodulatory functions, known to play protective roles at other mucosal sites, but not well characterized in UTIs. Using a preclinical model of UPEC-caused UTI, we show that urine SLPI increases in infected mice and that SLPI is localized to bladder epithelial cells. UPEC-infected SLPI-deficient ( Slpi -/- ) mice suffer from higher urine bacterial burdens, prolonged bladder inflammation, and elevated urine neutrophil elastase (NE) levels compared to wild-type ( Slpi +/+ ) controls. Combined with bulk bladder RNA sequencing, our data indicate that Slpi -/- mice have a dysregulated immune and tissue repair response following UTI. We also measure SLPI in urine samples from a small group of female subjects 18-49 years old and find that SLPI tends to be higher in the presence of a uropathogen, except in patients with a history of recent or recurrent UTI, suggesting a dysregulation of SLPI expression in these women. Taken together, our findings show SLPI promotes clearance of UPEC in mice and provides preliminary evidence that SLPI is likewise regulated in response to uropathogen exposure in women.IMPORTANCEAnnually, millions of people suffer from urinary tract infections (UTIs) and more than $3 billion are spent on work absences and treatment of these patients. While the early response to UTI is known to be important in combating urinary pathogens, knowledge of host factors that help curb infection is still limited. Here, we use a preclinical model of UTI to study secretory leukocyte protease inhibitor (SLPI), an antimicrobial protein, to determine how it protects the bladder against infection. We find that SLPI is increased during UTI, accelerates the clearance of bacteriuria, and upregulates genes and pathways needed to fight an infection while preventing prolonged bladder inflammation. In a small clinical study, we show SLPI is readily detectable in human urine and is associated with the presence of a uropathogen in patients without a previous history of UTI, suggesting SLPI may play an important role in protecting from bacterial cystitis., Competing Interests: The authors declare no conflict of interest.

Millions suffer from urinary tract infections (UTIs) worldwide every year with women accounting for the majority of cases. Uropathogenic Escherichia coli (UPEC) causes most of these primary infections and leads to 25% becoming recurrent or chronic. To repel invading pathogens, the urinary tract mounts a vigorous innate immune response that includes the secretion of antimicrobial peptides (AMPs), rapid recruitment of phagocytes and exfoliation of superficial umbrella cells. Here, we investigate secretory leukocyte protease inhibitor (SLPI), an AMP with antiprotease, antimicrobial and immunomodulatory functions, known to play protective roles at other mucosal sites, but not well characterized in UTIs. Using a mouse model of UPEC-caused UTI, we show that urine SLPI increases in infected mice and that SLPI is localized to bladder epithelial cells. UPEC infected SLPI-deficient ( Slpi -/- ) mice suffer from higher urine bacterial burdens, prolonged bladder inflammation, and elevated urine neutrophil elastase (NE) levels compared to wild-type ( Slpi +/+ ) controls. Combined with bulk bladder RNA sequencing, our data indicate that Slpi -/- mice have a dysregulated immune and tissue repair response following UTI. We also measure SLPI in urine samples from a small group of female subjects 18-49 years old and find that SLPI tends to be higher in the presence of a uropathogen, except in patients with history of recent or recurrent UTI (rUTI), suggesting a dysregulation of SLPI expression in these women. Taken together, our findings show SLPI protects against acute UTI in mice and provides preliminary evidence that SLPI is likewise regulated in response to uropathogen exposure in women., Competing Interests: Competing Interests The authors do not have any competing interests to report.

Previous urinary tract infections (UTIs) can predispose one to future infections; however, the underlying mechanisms affecting recurrence are poorly understood. We previously found that UTIs in mice cause differential bladder epithelial (urothelial) remodelling, depending on disease outcome, that impacts susceptibility to recurrent UTI. Here we compared urothelial stem cell (USC) lines isolated from mice with a history of either resolved or chronic uropathogenic Escherichia coli (UPEC) infection, elucidating evidence of molecular imprinting that involved epigenetic changes, including differences in chromatin accessibility, DNA methylation and histone modification. Epigenetic marks in USCs from chronically infected mice enhanced caspase-1-mediated cell death upon UPEC infection, promoting bacterial clearance. Increased Ptgs2os2 expression also occurred, potentially contributing to sustained cyclooxygenase-2 expression, bladder inflammation and mucosal wounding-responses associated with severe recurrent cystitis. Thus, UPEC infection acts as an epi-mutagen reprogramming the urothelial epigenome, leading to urothelial-intrinsic remodelling and training of the innate response to subsequent infection., (© 2023. The Author(s).)

Symptoms in the urogenital organs are common in multiple system atrophy (MSA), also in the years preceding the MSA diagnosis. It is unknown how MSA is triggered and these observations in prodromal MSA led us to hypothesize that synucleinopathy could be triggered by infection of the genitourinary tract causing ɑ-synuclein (ɑSyn) to aggregate in peripheral nerves innervating these organs. As a first proof that peripheral infections could act as a trigger in MSA, this study focused on lower urinary tract infections (UTIs), given the relevance and high frequency of UTIs in prodromal MSA, although other types of infection might also be important triggers of MSA. We performed an epidemiological nested-case control study in the Danish population showing that UTIs are associated with future diagnosis of MSA several years after infection and that it impacts risk in both men and women. Bacterial infection of the urinary bladder triggers synucleinopathy in mice and we propose a novel role of ɑSyn in the innate immune system response to bacteria. Urinary tract infection with uropathogenic E. coli results in the de novo aggregation of ɑSyn during neutrophil infiltration. During the infection, ɑSyn is released extracellularly from neutrophils as part of their extracellular traps. Injection of MSA aggregates into the urinary bladder leads to motor deficits and propagation of ɑSyn pathology to the central nervous system in mice overexpressing oligodendroglial ɑSyn. Repeated UTIs lead to progressive development of synucleinopathy with oligodendroglial involvement in vivo. Our results link bacterial infections with synucleinopathy and show that a host response to environmental triggers can result in ɑSyn pathology that bears semblance to MSA., (© 2023. The Author(s).)

Recurrent urinary tract infections (rUTIs) are a major health burden worldwide, with history of infection being a significant risk factor. While the gut is a known reservoir for uropathogenic bacteria, the role of the microbiota in rUTI remains unclear. We conducted a year-long study of women with (n = 15) and without (n = 16) history of rUTI, from whom we collected urine, blood and monthly faecal samples for metagenomic and transcriptomic interrogation. During the study 24 UTIs were reported, with additional samples collected during and after infection. The gut microbiome of individuals with a history of rUTI was significantly depleted in microbial richness and butyrate-producing bacteria compared with controls, reminiscent of other inflammatory conditions. However, Escherichia coli gut and bladder populations were comparable between cohorts in both relative abundance and phylogroup. Transcriptional analysis of peripheral blood mononuclear cells revealed expression profiles indicative of differential systemic immunity between cohorts. Altogether, these results suggest that rUTI susceptibility is in part mediated through the gut-bladder axis, comprising gut dysbiosis and differential immune response to bacterial bladder colonization, manifesting in symptoms., (© 2022. The Author(s), under exclusive licence to Springer Nature Limited.)

A mucosal infectious disease episode can render the host either more or less susceptible to recurrent infection, but the specific mechanisms that tip the balance remain unclear. We investigated this question in a mouse model of recurrent urinary tract infection and found that a prior bladder infection resulted in an earlier onset of tumor necrosis factor-alpha (TNFɑ)-mediated bladder inflammation upon subsequent bacterial challenge, relative to age-matched naive mice. However, the duration of TNFɑ signaling activation differed according to whether the first infection was chronic (Sensitized) or self-limiting (Resolved). TNFɑ depletion studies revealed that transient early-phase TNFɑ signaling in Resolved mice promoted clearance of bladder-colonizing bacteria via rapid recruitment of neutrophils and subsequent exfoliation of infected bladder cells. In contrast, sustained TNFɑ signaling in Sensitized mice prolonged damaging inflammation, worsening infection. This work reveals how TNFɑ signaling dynamics can be rewired by a prior infection to shape diverse susceptibilities to future mucosal infections., Competing Interests: LY, VO, JL, DD, NB, MC, MC, ER, SH, TH No competing interests declared, (© 2019, Yu et al.)

Urinary tract infections (UTI) are extremely common and can be highly recurrent, with 1-2% of women suffering from six or more recurrent episodes per year. The high incidence of recurrent UTI, including recurrent infections caused by the same bacterial strain that caused the first infection, suggests that at least some women do not mount a protective adaptive immune response to UTI. Here we observed in a mouse model of cystitis (bladder infection) that infection with two different clinical uropathogenic Escherichia coli (UPEC) isolates, UTI89 or CFT073, resulted in different kinetics of bacterial clearance and different susceptibility to same-strain recurrent infection. UTI89 and CFT073 both caused infections that persisted for at least two weeks in similar proportions of mice, but whereas UTI89 infections could persist indefinitely, CFT073 infections began to clear two weeks after inoculation and were uniformly cleared within eight weeks. Mice with a history of CFT073 cystitis lasting four weeks were protected against recurrent CFT073 infection after antibiotic therapy, but were not protected against challenge with UTI89. In contrast, mice with a history of UTI89 cystitis lasting four weeks were highly susceptible to challenge infection with either strain after antibiotic treatment. We found that depletion of CD4+ and CD8+ T cell subsets impaired the ability of the host to clear CFT073 infections and rendered mice with a history of CFT073 cystitis lasting four weeks susceptible to recurrent CFT073 cystitis upon challenge. Our findings demonstrate the complex interplay between the broad genetic diversity of UPEC and the host innate and adaptive immune responses during UTI. A better understanding of these host-pathogen interactions is urgently needed for effective drug and vaccine development in the era of increasing antibiotic resistance., Competing Interests: The authors have declared that no competing interests exist.

Introduction: The bacterial adhesin FimH is a virulence factor and an attractive therapeutic target for urinary tract infection (UTI) and Crohn's Disease (CD). Located on type 1 pili of uropathogenic E. coli (UPEC), the FimH adhesin plays an integral role in the pathogenesis of UPEC. Recent efforts have culminated in the development of small-molecule mannoside FimH antagonists that target the mannose-binding lectin domain of FimH, inhibiting its function and preventing UPEC from binding mannosylated host cells in the bladder, thereby circumventing infection. Areas covered: The authors describe the structure-guided design of mannoside ligands, and review the structural biology of the FimH lectin domain. Additionally, they discuss the lead optimization of mannosides for therapeutic application in UTI and CD, and describe various assays used to measure mannoside potency in vitro and mouse models used to determine efficacy in vivo. Expert opinion: To date, mannoside optimization has led to a diverse set of small-molecule FimH antagonists with oral bioavailability. With clinical trials already initiated in CD and on the horizon for UTI, it is the authors, opinion that mannosides will be a 'first-in-class' treatment strategy for UTI and CD, and will pave the way for treatment of other Gram-negative bacterial infections.

Urinary tract infections (UTIs) are caused by uropathogenic Escherichia coli (UPEC) strains. In contrast to many enteric E. coli pathogroups, no genetic signature has been identified for UPEC strains. We conducted a high-resolution comparative genomic study using E. coli isolates collected from the urine of women suffering from frequent recurrent UTIs. These isolates were genetically diverse and varied in their urovirulence, that is, their ability to infect the bladder in a mouse model of cystitis. We found no set of genes, including previously defined putative urovirulence factors (PUFs), that were predictive of urovirulence. In addition, in some patients, the E. coli strain causing a recurrent UTI had fewer PUFs than the supplanted strain. In competitive experimental infections in mice, the supplanting strain was more efficient at colonizing the mouse bladder than the supplanted strain. Despite the lack of a clear genomic signature for urovirulence, comparative transcriptomic and phenotypic analyses revealed that the expression of key conserved functions during culture, such as motility and metabolism, could be used to predict subsequent colonization of the mouse bladder. Together, our findings suggest that UTI risk and outcome may be determined by complex interactions between host susceptibility and the urovirulence potential of diverse bacterial strains., (Copyright © 2017, American Association for the Advancement of Science.)

Positive selection in the two-domain type 1 pilus adhesin FimH enhances Escherichia coli fitness in urinary tract infection (UTI). We report a comprehensive atomic-level view of FimH in two-state conformational ensembles in solution, composed of one low-affinity tense (T) and multiple high-affinity relaxed (R) conformations. Positively selected residues allosterically modulate the equilibrium between these two conformational states, each of which engages mannose through distinct binding orientations. A FimH variant that only adopts the R state is severely attenuated early in a mouse model of uncomplicated UTI but is proficient at colonizing catheterized bladders in vivo or bladder transitional-like epithelial cells in vitro. Thus, the bladder habitat has barrier(s) to R state-mediated colonization possibly conferred by the terminally differentiated bladder epithelium and/or decoy receptors in urine. Together, our studies reveal the conformational landscape in solution, binding mechanisms, and adhesive strength of an allosteric two-domain adhesin that evolved "moderate" affinity to optimize persistence in the bladder during UTI.

Recurrent bacterial infections are a significant burden worldwide, and prior history of infection is often a significant risk factor for developing new infections. For urinary tract infection (UTI), a history of two or more episodes is an independent risk factor for acute infection. However, mechanistic knowledge of UTI pathogenesis has come almost exclusively from studies in naive mice. Here we show that, in mice, an initial Escherichia coli UTI, whether chronic or self-limiting, leaves a long-lasting molecular imprint on the bladder tissue that alters the pathophysiology of subsequent infections, affecting host susceptibility and disease outcome. In bladders of previously infected versus non-infected, antibiotic-treated mice, we found (1) an altered transcriptome and defects in cell maturation, (2) a remodelled epithelium that confers resistance to intracellular bacterial colonization, and (3) changes to cyclooxygenase-2-dependent inflammation. Furthermore, in mice with a history of chronic UTI, cyclooxygenase-2-dependent inflammation allowed a variety of clinical E. coli isolates to circumvent intracellular colonization resistance and cause severe recurrent UTI, which could be prevented by cyclooxygenase-2 inhibition or vaccination. This work provides mechanistic insight into how a history of infection can impact the risk for developing recurrent infection and has implications for the development of therapeutics for recurrent UTI.

Urinary tract infections (UTI) are among the most common bacterial infections in humans, affecting millions of people every year. UTI cause significant morbidity in women throughout their lifespan, in infant boys, in older men, in individuals with underlying urinary tract abnormalities, and in those that require long-term urethral catheterization, such as patients with spinal cord injuries or incapacitated individuals living in nursing homes. Serious sequelae include frequent recurrences, pyelonephritis with sepsis, renal damage in young children, pre-term birth, and complications of frequent antimicrobial use including high-level antibiotic resistance and Clostridium difficile colitis. Uropathogenic E. coli (UPEC) cause the vast majority of UTI, but less common pathogens such as Enterococcus faecalis and other enterococci frequently take advantage of an abnormal or catheterized urinary tract to cause opportunistic infections. While antibiotic therapy has historically been very successful in controlling UTI, the high rate of recurrence remains a major problem, and many individuals suffer from chronically recurring UTI, requiring long-term prophylactic antibiotic regimens to prevent recurrent UTI. Furthermore, the global emergence of multi-drug resistant UPEC in the past ten years spotlights the need for alternative therapeutic and preventative strategies to combat UTI, including anti-infective drug therapies and vaccines. In this chapter, we review recent advances in the field of UTI pathogenesis, with an emphasis on the identification of promising drug and vaccine targets. We then discuss the development of new UTI drugs and vaccines, highlighting the challenges these approaches face and the need for a greater understanding of urinary tract mucosal immunity.

Urinary tract infections (UTI) are among the most common bacterial infections of humans. The mouse provides an excellent and tractable model system for cystitis and pyelonephritis caused by Escherichia coli and other uropathogens. Using a well-established model of experimental cystitis in which the bladders of female mice are infected via transurethral catheterization, the molecular details of the pathogenesis of bacterial cystitis have been substantially illuminated in the last decade. Uropathogenic E. coli attach to bladder epithelium (both in human and mouse) via adhesive type 1 pili, establish a replicative niche within epithelial cell cytoplasm, and form intracellular bacterial communities that are protected from antibiotic effects and immune clearance. The use of different inbred and mutant mouse strains offers the opportunity to study outcomes of infection, including resolution, formation of quiescent intracellular bacterial reservoirs, chronic bacterial cystitis, and recurrent infections. Urine, bladder, and kidney tissues can be analyzed by bacterial culture, histology, immunohistochemistry, immunofluorescent and confocal microscopy, electron microscopy, and flow cytometry, while a broad array of soluble markers (e.g., cytokines) can also be profiled in serum, urine, and tissue homogenates by ELISA, Western blotting, multiplex bead array, and other approaches. This model promises to afford continued opportunity for discovery of pathogenic mechanisms and evaluation of therapeutic and preventive strategies for acute, chronic, and recurrent UTI.

Uropathogenic E. coli (UPEC) is the primary cause of urinary tract infections (UTI) affecting approximately 150 million people worldwide. Here, we revealed the importance of transcriptional regulator hypoxia-inducible factor-1 α subunit (HIF-1α) in innate defense against UPEC-mediated UTI. The effects of AKB-4924, a HIF-1α stabilizing agent, were studied using human uroepithelial cells (5637) and a murine UTI model. UPEC adherence and invasion were significantly reduced in 5637 cells when HIF-1α protein was allowed to accumulate. Uroepithelial cells treated with AKB-4924 also experienced reduced cell death and exfoliation upon UPEC challenge. In vivo, fewer UPEC were recovered from the urine, bladders and kidneys of mice treated transurethrally with AKB-4924, whereas increased bacteria were recovered from bladders of mice with a HIF-1α deletion. Bladders and kidneys of AKB-4924 treated mice developed less inflammation as evidenced by decreased pro-inflammatory cytokine release and neutrophil activity. AKB-4924 impairs infection in uroepithelial cells and bladders, and could be correlated with enhanced production of nitric oxide and antimicrobial peptides cathelicidin and β-defensin-2. We conclude that HIF-1α transcriptional regulation plays a key role in defense of the urinary tract against UPEC infection, and that pharmacological HIF-1α boosting could be explored further as an adjunctive therapy strategy for serious or recurrent UTI.

Unlabelled: The capacity of subinhibitory levels of antibiotics to modulate bacterial virulence in vitro has recently been brought to light, raising concerns over the appropriateness of low-dose therapies, including antibiotic prophylaxis for recurrent urinary tract infection management. However, the mechanisms involved and their relevance in influencing pathogenesis have not been investigated. We characterized the ability of antibiotics to modulate virulence in the uropathogens Staphylococcus saprophyticus and Escherichia coli. Several antibiotics were able to induce the expression of adhesins critical to urothelial colonization, resulting in increased biofilm formation, colonization of murine bladders and kidneys, and promotion of intracellular niche formation. Mice receiving subinhibitory ciprofloxacin treatment were also more susceptible to severe infections and frequent recurrences. A ciprofloxacin prophylaxis model revealed this strategy to be ineffective in reducing recurrences and worsened infection by creating larger intracellular reservoirs at higher frequencies. Our study indicates that certain agents used for antibiotic prophylaxis have the potential to complicate infections., Importance: Antibiotics are the mainstay treatment for bacterial infections; however, evidence is emerging that argues these agents may have off-target effects if sublethal concentrations are present. Most studies have focused on changes occurring in vitro, leaving questions regarding the clinical relevance in vivo. We utilized a murine urinary tract infection model to explore the potential impact of low-dose antibiotics on pathogenesis. Using this model, we showed that subinhibitory antibiotics prime uropathogens for adherence and invasion of murine urothelial tissues. These changes in initial colonization promoted the establishment of chronic infection. Furthermore, treatment of chronically infected mice with subtherapeutic ciprofloxacin served to exacerbate infection. A part of these changes was thought to be due to suppression of mucosal immunity, as demonstrated through reductions in cytokine secretion and migration of leukocytes into the urinary tract. This work identifies novel risk factors associated with antibiotic therapy when dosing strategies fall below subtherapeutic levels., (Copyright © 2015 Goneau et al.)

Urinary tract infections (UTIs) are among the most common bacterial infections, causing considerable morbidity in females. Infection is highly recurrent despite appropriate antibiotic treatment. Uropathogenic Escherichia coli (UPEC), the most common causative agent of UTIs, invades bladder epithelial cells (BECs) and develops into clonal intracellular bacterial communities (IBCs). Upon maturation, IBCs disperse, with bacteria spreading to neighboring BECs to repeat this cycle. This process allows UPEC to gain a foothold in the face of innate defense mechanisms, including micturition, epithelial exfoliation, and the influx of polymorphonuclear leukocytes. Here, we investigated the mechanism and dynamics of urothelial exfoliation in the early acute stages of infection. We show that UPEC α-hemolysin (HlyA) induces Caspase-1/Caspase-4-dependent inflammatory cell death in human urothelial cells, and we demonstrate that the response regulator (CpxR)-sensor kinase (CpxA) two-component system (CpxRA), which regulates virulence gene expression in response to environmental signals, is critical for fine-tuning HlyA cytotoxicity. Deletion of the cpxR transcriptional response regulator derepresses hlyA expression, leading to enhanced Caspase-1/Caspase-4- and NOD-like receptor family, pyrin domain containing 3-dependent inflammatory cell death in human urothelial cells. In vivo, overexpression of HlyA during acute bladder infection induces more rapid and extensive exfoliation and reduced bladder bacterial burdens. Bladder fitness is restored fully by inhibition of Caspase-1 and Caspase-11, the murine homolog of Caspase-4. Thus, we have discovered that fine-tuning of HlyA expression by the CpxRA system is critical for enhancing UPEC fitness in the urinary bladder. These results have significant implications for our understanding of how UPEC establishes persistent colonization.

Purpose of Review: Recurrent urinary tract infection (rUTI) is a serious clinical problem, yet effective therapeutic options are limited, especially against multidrug-resistant uropathogens. In this review, we explore the development of a clinically relevant model of rUTI in previously infected mice and review recent developments in bladder innate immunity that may affect susceptibility to rUTI., Recent Findings: Chronic bladder inflammation during prolonged bacterial cystitis in mice causes bladder mucosal remodelling that sensitizes the host to rUTI. Although constitutive defenses help prevent bacterial colonization of the urinary bladder, once infection occurs, induced cytokine and myeloid cell responses predominate and the balance of immune cell defense and bladder immunopathology is critical for determining disease outcome, in both naïve and experienced mice. In particular, the maintenance of the epithelial barrier appears to be essential for preventing severe infection., Summary: The innate immune response plays a key role in determining susceptibility to rUTI. Future studies should be directed towards understanding how the innate immune response changes as a result of bladder mucosal remodelling in previously infected mice, and validating these findings in human clinical specimens. New therapeutics targeting the immune response should selectively target the induced innate responses that cause bladder immunopathology, while leaving protective defenses intact.

Urinary tract infections (UTIs) afflict over 9 million women in America every year, often necessitating long-term prophylactic antibiotics. One risk factor for UTI is frequent sexual intercourse, which dramatically increases the risk of UTI. The mechanism behind this increased risk is unknown; however, bacteriuria increases immediately after sexual intercourse episodes, suggesting that physical manipulation introduces periurethral flora into the urinary tract. In this paper, we investigated whether superinfection (repeat introduction of bacteria) resulted in increased risk of severe UTI, manifesting as persistent bacteriuria, high titer bladder bacterial burdens and chronic inflammation, an outcome referred to as chronic cystitis. Chronic cystitis represents unchecked luminal bacterial replication and is defined histologically by urothelial hyperplasia and submucosal lymphoid aggregates, a histological pattern similar to that seen in humans suffering chronic UTI. C57BL/6J mice are resistant to chronic cystitis after a single infection; however, they developed persistent bacteriuria and chronic cystitis when superinfected 24 hours apart. Elevated levels of interleukin-6 (IL-6), keratinocyte cytokine (KC/CXCL1), and granulocyte colony-stimulating factor (G-CSF) in the serum of C57BL/6J mice prior to the second infection predicted the development of chronic cystitis. These same cytokines have been found to precede chronic cystitis in singly infected C3H/HeN mice. Furthermore, inoculating C3H/HeN mice twice within a six-hour period doubled the proportion of mice that developed chronic cystitis. Intracellular bacterial replication, regulated hemolysin (HlyA) expression, and caspase 1/11 activation were essential for this increase. Microarrays conducted at four weeks post inoculation in both mouse strains revealed upregulation of IL-1 and antimicrobial peptides during chronic cystitis. These data suggest a mechanism by which caspase-1/11 activation and IL-1 secretion could predispose certain women to recurrent UTI after frequent intercourse, a predisposition predictable by several serum biomarkers in two murine models.

The management of health care delivery requires the availability of effective 'information management' tools based on e-technologies [eHealth]. In developed economies many of these 'tools' are readily available whereas in Low and Middle Income Countries (LMIC) there is limited access to eHealth technologies and this has been defined as the "digital divide". This paper provides a short introduction to the fundamental understanding of what is meant by information management in health care and how it applies to all social economies. The core of the paper describes the successful implementation of appropriate information management tools in a resource poor environment to manage the HIV/AIDS epidemic and other disease states, in sub-Saharan Africa and how the system has evolved to become the largest open source eHealth project in the world and become the health information infrastructure for several national eHealth economies. The system is known as Open MRS [www.openmrs.org). The continuing successful evolution of the OpenMRS project has permitted its key implementers to define core factors that are the foundations for successful eHealth projects.

The spread of multidrug-resistant microorganisms globally has created an urgent need for novel therapeutic strategies to combat urinary tract infections (UTIs). Immunomodulatory therapy may provide benefit, as treatment of mice with dexamethasone during acute UTI improved outcome by reducing the development of chronic cystitis, which predisposes to recurrent infection. Here we discovered soluble biomarkers engaged in myeloid cell development and chemotaxis that were predictive of future UTI recurrence when elevated in the sera of young women with UTI. Translation of these findings revealed that temperance of the neutrophil response early during UTI, and specifically disruption of bladder epithelial transmigration of neutrophils by inhibition of cyclooxygenase-2, protected mice against chronic and recurrent cystitis. Further, proteomics identified bladder epithelial remodeling consequent to chronic infection that enhances sensitivity to neutrophil damage. Thus, cyclooxygenase-2 expression during acute UTI is a critical molecular trigger determining disease outcome and drugs targeting cyclooxygenase-2 could prevent recurrent UTI.

Progressive evaluations by the Organization for Economic Co-operation and Development (OECD) demonstrate that health care is now or becoming unaffordable. This means nations must change the way they manage health care. The costly nature of health care in most nations, as a percentage of Gross Domestic Product (GDP) seems independent of the national funding models. Increasing evidence is demonstrating that the lack of involvement by clinicians (doctors, nurses, pharmacists, ancillary care and patients) in e-health projects is a major factor for the costly failures of many of these projects. The essential change in focus required to improve healthcare delivery using e-health technologies has to be on clinical care. To achieve this change clinicians must be involved at all stages of e-health implementations. From a clinicians perspective medicine is not a business. Our business is clinical medicine and e-health must be focussed on clinical decision making. This paper views the roles of physicians in e-health structural reforms., (© 2013 The Authors; Internal Medicine Journal © 2013 Royal Australasian College of Physicians.)

Background: Escherichia coli O25b:H4-ST131 represents a predominant clone of multidrug-resistant uropathogens currently circulating worldwide in hospitals and the community. Urinary tract infections (UTIs) caused by E. coli ST131 are typically associated with limited treatment options and are often recurrent., Methods: Using established mouse models of acute and chronic UTI, we mapped the pathogenic trajectory of the reference E. coli ST131 UTI isolate, strain EC958., Results: We demonstrated that E. coli EC958 can invade bladder epithelial cells and form intracellular bacterial communities early during acute UTI. Moreover, E. coli EC958 persisted in the bladder and established chronic UTI. Prophylactic antibiotic administration failed to prevent E. coli EC958-mediated UTI. However, 1 oral dose of a small-molecular-weight compound that inhibits FimH, the type 1 fimbriae adhesin, significantly reduced bacterial colonization of the bladder and prevented acute UTI. Treatment of chronically infected mice with the same FimH inhibitor lowered their bladder bacterial burden by >1000-fold., Conclusions: In this study, we provide novel insight into the pathogenic mechanisms used by the globally disseminated E. coli ST131 clone during acute and chronic UTI and establish the potential of FimH inhibitors as an alternative treatment against multidrug-resistant E. coli.

Estrogen therapy promotes resistance to urinary tract infections in postmenopausal women by altering lower urinary tract mucosal defense mechanisms (Lüthje et al., this issue).

Urinary catheterization elicits major histological and immunological changes that render the bladder susceptible to microbial invasion, colonization, and dissemination. However, it is not understood how catheters induce these changes, how these changes act to promote infection, or whether they may have any protective benefit. In the present study, we examined how catheter-associated inflammation impacts infection by Enterococcus faecalis, a leading cause of catheter-associated urinary tract infection (CAUTI), a source of significant societal and clinical challenges. Using a recently optimized murine model of foreign body-associated UTI, we found that the implanted catheter itself was the primary inducer of inflammation. In the absence of the silicone tubing implant, E. faecalis induced only minimal inflammation and was rapidly cleared from the bladder. The catheter-induced inflammation was only minimally altered by subsequent enterococcal infection and was not suppressed by inhibitors of the neurogenic pathway and only partially by dexamethasone. Despite the robust inflammatory response induced by urinary implantation, E. faecalis produced biofilm and high bladder titers in these animals. Induction of inflammation in the absence of an implanted catheter failed to promote infection, suggesting that the presence of the catheter itself is essential for E. faecalis persistence in the bladder. Immunosuppression prior to urinary catheterization enhanced E. faecalis colonization, suggesting that implant-mediated inflammation contributes to the control of enterococcal infection. Thus, this study underscores the need for novel strategies against CAUTIs that seek to reduce the deleterious effects of implant-mediated inflammation on bladder homeostasis while maintaining an active immune response that effectively limits bacterial invaders.

Urinary tract infections (UTI), primarily caused by uropathogenic Escherichia coli (UPEC), are one of the leading bacterial infections due to their high frequency and rate of recurrence. Both type 1 pilus adhesive organelles (fim) and the QseC sensor kinase have been implicated in UPEC virulence during UTI and have been individually reported to be promising drug targets. Deletion of qseC leads to pleiotropic effects due to unregulated activation of the cognate response regulator QseB, influencing conserved metabolic processes and diminishing expression of virulence genes, including type 1 pili. Here, we discern the type 1 pilus-dependent and -independent effects that contribute to the virulence attenuation of a UPEC qseC deletion mutant in a murine model of experimental UTI. We show that although a ΔqseC mutant restored for type 1 pilus expression regains the ability to colonize the host and initiate acute infection up to 16 h postinfection, it is rapidly outcompeted during acute infection when coinoculated with a wild-type strain. As a result, this strain has a diminished capacity to establish chronic infection. A prophylactic oral dose of a FimH small-molecular-weight antagonist (ZFH-02056) further reduced the ability of the qseC mutant to establish chronic infection. Thus, loss of QseC significantly enhances the efficacy of ZFH-02056. Collectively, our work indicates that type 1 pili and QseC become critical in different infection stages, and that dual targeting of these factors has an additive effect on ablating UPEC virulence.

Bladder infections affect millions of people yearly, and recurrent symptomatic infections (cystitis) are very common. The rapid increase in infections caused by multidrug-resistant uropathogens threatens to make recurrent cystitis an increasingly troubling public health concern. Uropathogenic Escherichia coli (UPEC) cause the vast majority of bladder infections. Upon entry into the lower urinary tract, UPEC face obstacles to colonization that constitute population bottlenecks, reducing diversity, and selecting for fit clones. A critical mucosal barrier to bladder infection is the epithelium (urothelium). UPEC bypass this barrier when they invade urothelial cells and form intracellular bacterial communities (IBCs), a process which requires type 1 pili. IBCs are transient in nature, occurring primarily during acute infection. Chronic bladder infection is common and can be either latent, in the form of the quiescent intracellular reservoir (QIR), or active, in the form of asymptomatic bacteriuria (ASB/ABU) or chronic cystitis. In mice, the fate of bladder infection, QIR, ASB, or chronic cystitis, is determined within the first 24 h of infection and constitutes a putative host-pathogen mucosal checkpoint that contributes to susceptibility to recurrent cystitis. Knowledge of these checkpoints and bottlenecks is critical for our understanding of bladder infection and efforts to devise novel therapeutic strategies., (© 2012 Federation of European Microbiological Societies. Published by Blackwell Publishing Ltd. All rights reserved.)

Chronic infections are an increasing problem due to the aging population and the increase in antibiotic resistant organisms. Therefore, understanding the host-pathogen interactions that result in chronic infection is of great importance. Here, we investigate the molecular basis of chronic bacterial cystitis. We establish that introduction of uropathogenic E. coli (UPEC) into the bladders of C3H mice results in two distinct disease outcomes: resolution of acute infection or development of chronic cystitis lasting months. The incidence of chronic cystitis is both host strain and infectious dose-dependent. Further, development of chronic cystitis is preceded by biomarkers of local and systemic acute inflammation at 24 hours post-infection, including severe pyuria and bladder inflammation with mucosal injury, and a distinct serum cytokine signature consisting of elevated IL-5, IL-6, G-CSF, and the IL-8 analog KC. Mice deficient in TLR4 signaling or lymphocytes lack these innate responses and are resistant, to varying degrees, to developing chronic cystitis. Treatment of C3H mice with the glucocorticoid anti-inflammatory drug dexamethasone prior to UPEC infection also suppresses the development of chronic cystitis. Finally, individuals with a history of chronic cystitis, lasting at least 14 days, are significantly more susceptible to redeveloping severe, chronic cystitis upon bacterial challenge. Thus, we have discovered that the development of chronic cystitis in C3H mice by UPEC is facilitated by severe acute inflammatory responses early in infection, which subsequently are predisposing to recurrent cystitis, an insidious problem in women. Overall, these results have significant implications for our understanding of how early host-pathogen interactions at the mucosal surface determines the fate of disease.

Background: The Medical Morning Handover Report is a form of clinical handover and is considered to be an essential mechanism for continuity of care and adverse event minimisation within a hospital environment. It is considered a significant Quality of Care activity recommended in Australian Medical Association clinical handover guidelines. The sustainability of such activities has not been reported., Aim: We aimed to assess the sustainability of Medical Morning Handover Reporting (MMHR) in the Department of Medicine at the Launceston General Hospital since its implementation in 2001., Methods: We conducted a quality improvement survey amongst the medical staff (pre-graduate and post graduate medical faculties) to assess its sustainability since implementation in 2001., Results: There were 30 respondents of whom 19 attended MMHR daily, four attended weekly, and only five attended less than weekly. Attendance rates at MMHR were maintained from 2001 to 2009 based on comparisons with previously conducted surveys., Conclusions: This study shows MMHR is sustainable and has evolved in format to incorporate advances in Health Information Technology. We believe adherence is dependent on providing leadership and structure to MMHR.

Uropathogenic Escherichia coli (UPEC) contain multiple horizontally acquired pathogenicity-associated islands (PAI) implicated in the pathogenesis of urinary tract infection. In a murine model of cystitis, type 1 pili-mediated bladder epithelial invasion and intracellular proliferation are key events associated with UPEC virulence. In this study, we examined the mechanisms by which a conserved PAI contributes to UPEC pathogenesis in acute cystitis. In the human UPEC strain UTI89, spontaneous excision of PAI II(UTI89) disrupts the adjacent leuX tRNA locus. Loss of wild-type leuX-encoded tRNA(5)(Leu) significantly delayed, but did not eliminate, FimB recombinase-mediated phase variation of type 1 pili. FimX, an additional FimB-like, leuX-independent recombinase, was also found to mediate type 1 pili phase variation. However, whereas FimX activity is relatively slow in vitro, it is rapid in vivo as a non-piliated strain lacking the other fim recombinases rapidly expressed type 1 pili upon experimental infection. Finally, we found that disruption of leuX, but not loss of PAI II(UTI89) genes, reduced bladder epithelial invasion and intracellular proliferation, independent of type 1 piliation. These findings indicate that the predominant mechanism for preservation of PAI II(UTI89) during the establishment of acute cystitis is maintenance of wild-type leuX, and not PAI II(UTI89) gene content.

Objective: To investigate the prevalence and format of medical morning handover report (MMHR) in Australian hospitals., Design, Setting and Participants: Questionnaire survey faxed to 76 Australian hospitals accredited for basic physician training by the Royal Australasian College of Physicians (RACP). The survey was conducted in 2005., Main Outcome Measures: Use of MMHR; structure and format of meetings., Results: 53 of 76 (70%) hospitals responded. However, some data (1.7% of possible responses) were missing or illegible. Prevalence of the use of MMHR in respondent hospitals was 58% (31/53). Analysing the data by RACP accreditation level, 18/24 Level 3 hospitals (75%) conducted MMHR compared with 5/9 Level 2 hospitals (56%) and 7/18 Level 1 hospitals (39%) (odds ratio [OR] for trend, 2.17; 95% CI, 1.12-4.23; P = 0.023). 44 of 53 respondents reported their Rural, Remote and Metropolitan Areas (RRMA) classification. MMHR is less likely to be held in hospitals in regions classified as RRMA 2-4 (8/21 [38%]) than those in capital cities (RRMA 1) (16/23 [70%]) (OR, 0.27; 95% CI, 0.08-0.95; P = 0.042). In 62% of hospitals, MMHR was chaired by a consultant, and at most hospitals (23/31 [74%]), meetings were 15-30 minutes long., Conclusions: In spite of RACP accreditation requirements, the use of MMHR in Australian hospitals accredited for basic physician training is low.

Providing high-quality HIV/AIDS care requires high-quality, accessible data on individual patients and visits. These data can also drive strategic decision-making by health systems, national programs, and funding agencies. One major obstacle to HIV/AIDS care in developing countries is lack of electronic medical record systems (EMRs) to collect, manage, and report clinical data. In 2001, we implemented a simple primary care EMR at a rural health centre in western Kenya. This EMR evolved into a comprehensive, scalable system serving 19 urban and rural health centres. To date, the AMPATH Medical Record System contains 10 million observations from 400,000 visit records on 45,000 patients. Critical components include paper encounter forms for adults and children, technicians entering/managing data, and modules for patient registration, scheduling, encounters, clinical observations, setting user privileges, and a concept dictionary. Key outputs include patient summaries, care reminders, and reports for program management, operating ancillary services (e.g., tracing patients who fail to return for appointments), strategic planning (e.g., hiring health care providers and staff), reports to national AIDS programs and funding agencies, and research.

Gram-negative pathogens commonly use the chaperone-usher pathway to assemble adhesive multisubunit fibers on their surface. In the periplasm, subunits are stabilized by a chaperone that donates a beta strand to complement the subunits' truncated immunoglobulin-like fold. Pilus assembly proceeds through a "donor-strand exchange" (DSE) mechanism whereby this complementary beta strand is replaced by the N-terminal extension (Nte) of an incoming pilus subunit. Using X-ray crystallography and real-time electrospray ionization mass spectrometry (ESI-MS), we demonstrate that DSE requires the formation of a transient ternary complex between the chaperone-subunit complex and the Nte of the next subunit to be assembled. The process is crucially dependent on an initiation site (the P5 pocket) needed to recruit the incoming Nte. The data also suggest a capping reaction displacing DSE toward product formation. These results support a zip-in-zip-out mechanism for DSE and a catalytic role for the usher, the molecular platform at which pili are assembled.

Administering and monitoring therapy is crucial to the battle against HIV/AIDS in sub-Saharan Africa. Electronic medical records (EMRs) can aid in documenting care, monitoring drug adherence and response to therapy, and providing data for quality improvement and research. Faculty at Moi University in Kenya and Indiana and University in the USA opened adult and pediatric HIV clinics in a national referral hospital, a district hospital, and six rural health centers in western Kenya using a newly developed EMR to support comprehensive outpatient HIV/AIDS care. Demographic, clinical, and HIV risk data, diagnostic test results, and treatment information are recorded on paper encounter forms and hand-entered into a central database that prints summary flowsheets and reminders for appropriate testing and treatment. There are separate modules for monitoring the Antenatal Clinic and Pharmacy. The EMR was designed with input from clinicians who understand the local community and constraints of providing care in resource poor settings. To date, the EMR contains more than 30,000 visit records for more than 4000 patients, almost half taking antiretroviral drugs. We describe the development and structure of this EMR and plans for future development that include wireless connections, tablet computers, and migration to a Web-based platform.

Millions of people are either living with or dying from HIV/AIDS; most of this living and dying is taking place in developing countries. There is an immediate need for electronic medical record systems to help scale up HIV/AIDS prevention and treatment programs, reduce critical human errors, and support the research necessary to guide future efforts. Several groups are working on this problem, but most of this work is occurring within silos. To be more effective, we must find ways to collaborate.

Background: It is now recognized that post-traumatic stress disorder (PTSD) can occur following road traffic accidents, but controversy exists about the possibility of PTSD in people sustaining traumatic brain injury (TBI). The present investigation examined the frequency, course and comorbidity of PTSD in children with and without mild TBI after traffic accidents., Method: Interviews were conducted with 43 children and their parents 6 weeks after a traffic accident,assessing PTSD and associated symptomatology. Fourteen children sustained mild TBI and 29 had no TBI. A sub-set (n=32) was re-interviewed 7 weeks later., Results: Children both with and without TBI reported PTSD symptomatology, but no significant group differences were found. At initial assessment, 74% of children were classified as having clinically significant PTSD symptomatology (86% and 69% in groups with and without TBI, respectively), which was strongly associated with report of general anxiety. At follow-up, PTSD symptomatology decreased, but 44% remained symptomatic (38% and 46% for those with and without TBI, respectively). Child and parental report of PTSD symptomatology were not significantly correlated., Conclusions: Presence of mild TBI did not influence the likelihood of experiencing PTSD symptomatology following a traffic accident. Given that PTSD symptomatology is a common consequence of traffic accidents in children, there is a clear need for provision of systematic assessment and, where appropriate, the implementation of intervention strategies to treat children.

The authors implemented an electronic medical record system in a rural Kenyan health center. Visit data are recorded on a paper encounter form, eliminating duplicate documentation in multiple clinic logbooks. Data are entered into an MS-Access database supported by redundant power systems. The system was initiated in February 2001, and 10,000 visit records were entered for 6,190 patients in six months. The authors present a summary of the clinics visited, diagnoses made, drugs prescribed, and tests performed. After system implementation, patient visits were 22% shorter. They spent 58% less time with providers (p < 0.001) and 38% less time waiting (p = 0.06). Clinic personnel spent 50% less time interacting with patients, two thirds less time interacting with each other, and more time in personal activities. This simple electronic medical record system has bridged the "digital divide." Financial and technical sustainability by Kenyans will be key to its future use and development.

To improve care, one must measure it. In the US, electronic medical record systems have been installed in many institutions to support health care management, quality improvement, and research. Developing countries lack such systems and thus have difficulties managing scarce resources and investigating means of improving health care delivery and outcomes. We describe the implementation and use of the first documented electronic medical record system in ambulatory care in sub-Saharan Africa. After one year, it has captured data for more than 13,000 patients making more than 26,000 visits. We present lessons learned and modifications made to this system to improve its capture of data and ability to support a comprehensive clinical care and research agenda.

The authors of this paper describe the second phase of the implementation of the Mosoriot Medical Record System (MMRS) in a remote health care facility on the outskirts of Eldoret, Kenya, located in sub-Saharan Africa. We describe of the collaboration between Indiana University (IU) and the Moi University (MU), and the process that led to the development of the computer-based Mosoriot Medical Record System (MMRS) is provided. We then provide the conceptualization and initial implementation of this basic electronic medical record system. We also describe the different processes for assessing the MMRS' effects on health care, including time-motion studies and a strict implementation plan that is necessary for the successful implementation of the system. The MMRS project has many features that make it significant in the domain of CBPR systems. It may serve as a model for establishing similar, basic electronic record systems in the developed and developing world. In developing countries there are few (if any) projects that have attempted to implement such a system. This paper describes the planning, end-user education to new technologies, and time-motion studies necessary for the successful implementation of the MMRS. The system will be used to improve the quality of health data collection and subsequently patient care. It will also be used to link data from ongoing public health surveys and this can be used in public health research programs of the Moi University.

Mosoriot Health Center is a rural primary care facility situated on the outskirts of Eldoret, Kenya in sub-Saharan Africa. The region is characterised by widespread poverty and a very poor technology infrastructure. Many houses do not have electricity, telephones or tap water. The health center does have electricity and tap water. In a collaborative project between Indiana University and the Moi University Faculty of Health Sciences (MUFHS), we designed a core electronic medical record system within the Mosoriot Health Center, with the intention of improving the quality of health data collection and, subsequently, patient care. The electronic medical record system will also be used to link clinical data from the health center to information collected from the public health surveys performed by medical students participating in the public health research programs of Moi University. This paper describes the processes involved in the development of the computer-based Mosoriot medical record system (MMRS) up to the point of implementation. It particularly focuses on the decisions and trade-offs that must be made when introducing this technology into an established health care system in a developing country.

Objective: To measure functional outcome in the 2 years after traumatic brain injury (TBI) in 2 groups of children and to determine the usefulness of a TBI severity classification system for resource allocation., Design: Prospective inception cohort study with 3 assessment points during the 2 years after trauma., Setting: Tertiary pediatric trauma center in Sydney, Australia., Participants: Eighty-one consecutive admissions aged 0 to 14 years. Fifty-one were allocated to the Mild (n = 26) or Severe (n = 25) TBI groups, according to preset determinants of severity; 30 admissions with non-TBI trauma constituted the control group., Main Outcome Measures: Standardized psychometric and clinical assessments of cognition, communication and feeding ability, motor performance (ambulation, fine and gross motor), neurologic status, self-care independence, and school/academic performance., Results: Those with Mild TBI severity had no significant deficits at the 2-year data point. In contrast, those in the Severe TBI group demonstrated continued problems with fine motor performance, neurologic status, self care, and school/academic performance., Conclusions: A classification system has been developed that may be useful in the allocation of children with a TBI, age younger than 15 years, to 1 of 2 severity groups early in their rehabilitation. This classification system may be useful in determining areas of high and low resource prioritization.

Adverse drug reactions and inappropriate administration of medications account for poor outcomes for patients. They place patients in life-threatening situations, lead to increased health care costs, extend length of stay in hospitals, as well as increasing litigation. This paper will highlight the incidence of adverse drug events (ADE) in health care and show the low rate of detection within conventional medical records. I will also show how electronic medical records (EMR) improve detection of ADE, enhance clinician compliance to their management, improve patient outcomes, and reduce health care costs.

Variation in the use of clinical resources, outcomes, costs, access to health care and quality is a well recognized, ever present feature of health care. It is a phenomenon that affects all sectors of the health care delivery process and is important to clinicians, administrators and patients. As a phenomenon variation can be appropriate or inappropriate and the elimination of inappropriate variation is a fundamental principal behind continuous quality improvement in health care. The primary tools for the management of variation exists within the electronic medical record (EMR). The EMR utilizes the existing and evolving information storage technologies (data repositories) and information management tools (applications), to integrate the elements within this long-term data storage. Through this integration the EMR systems are able to provide knowledge representation in differing formats to the decision-makers and this will facilitate more accurate and appropriate decision-making with subsequent improvements in health care delivery.

Hospices were founded to alleviate suffering at the end of life. Quality improvement in hospices should, therefore, target patients' subjective assessments of their care and its outcomes. However, little is known about the relationships among subjective measures of care among hospice patients. The aim was to assess the relationships between hospice patients' physical and psychological symptoms, quality of life, and satisfaction with inpatient care. This was achieved with a prospective cohort study of 42 patients admitted to an Australian hospice's inpatient service during a two-month study period. The Edmonton symptom assessment system, McGill quality of life questionnaire, and a new measure of patients satisfaction with hospice inpatient care were used. It was shown that while there were marked variations in symptoms and quality of life scores, most patients were satisfied with their care. Satisfaction on the day after admission was lower among patients with worse quality of life scores (r = -0.40, P = 0.008), but there was no correlation with symptoms (r = -0.12, P = 0.43). Among the 26 patients (62%) with at least one subsequent inpatient interview, satisfaction was correlated with both worse quality of life (r = -0.51, P = 0.01) and symptoms (r = -0.41, P = 0.05). The symptom, quality of life, and satisfaction scales all had sufficient precision to identify patients with significant changes between the two interviews. It can be concluded that satisfaction with hospice care was associated with quality of life more than symptoms, although symptoms became important later during inpatient stays. Patients can assess their care and can provide valuable information for improving palliative care.

This paper will outline the tasks involved, completed and not achieved over an eight year period involving the implementation of the Johns Hopkins Oncology Center Information System (OCIS) in an oncology department of a secondary/tertiary care hospital in Australia.