A clinical trial of nurse practitioner care in residential aged care facilities.

BACKGROUND: Optimising quality of life and reducing hospitalisation for people living in residential aged care facilities (RACF) are important health policy goals. METHODS: A cluster controlled clinical trial of nurse practitioner care in RACF. Six facilities were included: three randomly allocated to intervention where nurse practitioners working with general practitioners and using a best practice guide were responsible for care, and three control. Participants were followed up for a minimum of 12 months unless dead or transferred to another facility. RESULTS: We enrolled two hundred patients (101 intervention and 99 control) with a mean (SD) follow up of 604 (276) days. There were 98 ED visits by intervention participants, resulting in 56 hospitalisations, compared with 121 ED visits and 70 hospitalisations for controls (risk reduction = 8%, 95% CI = -1% -17%, p = 0.10). For the pre-specified secondary outcomes of transfers within the first 12 months of enrolment, the number of residents making at least one visit (46 in each study arm) and rate of ED attendance (0.66 visits per intervention resident versus 0.70 visits per control resident) was not affected by the intervention. After adjusting for dependency and comorbidity, the intervention group had non-significantly lower transfers (OR 0.7, 95% CI 0.3-1.5, p = 0.34). There was a reduction in the rate of decline in the quality of life of intervention compared to control residents. CONCLUSIONS: Nurse practitioner care coordination resulted in no statistically significant change in rates of ED transfer or health care utilisation, but better maintained resident quality of life.

Why It Is Not Always Anxiety: A Tough Diagnosis of Stiff Person Syndrome.

Anxiety disorder is a commonly used diagnosis that may mask underlying conditions. Stiff person syndrome (SPS) is a rare neuroimmunological disorder characterized by progressive rigidity and painful muscle spasms affecting axial and lower extremity musculature. These episodes can be triggered by sudden movement, noise, or emotional stress, which may present as a psychiatric condition. We report the case of a 30-year-old female who presented with recurrent panic attacks with multiple prior hospital admissions for anxiety, rigidity, and difficulty in walking. Previous electroencephalogram (EEG) and brain and cervical spine magnetic resonance imaging (MRI) were unremarkable. She was empirically treated with diazepam and beta-blockers for SPS, which was confirmed by positive glutamic acid decarboxylase (GAD) antibodies. The patient's symptoms became refractory to benzodiazepines and required steroids with intravenous immunoglobulin (IVIG). Her rigidity subsequently responded to plasmapheresis. In SPS, antibodies in the cerebrospinal fluid (CSF) most commonly target the GAD antigen on gamma-aminobutyric acid (GABA) neurons. The goal of treatment is to ameliorate symptoms and improve quality of life. Our case of SPS was masked as generalized anxiety disorder for at least six years since onset of symptoms. The criteria for both diagnoses may overlap as seen in this patient.

TaqMan Low Density Array: MicroRNA Profiling for Biomarker and Oncosuppressor Discovery.

MicroRNAs (miRNAs) have gained a lot of interest as biomarkers and biotherapeutics in recent years. The discovery of miRNAs in circulation as recently as 2008, aided by rapid advances in high-throughput profiling techniques initiated an explosion of investigations dedicated to discovering circulating miRNAs as minimally invasive biomarkers. As miRNAs regulate many cellular processes, investigators are actively exploring their relevance in disease treatment by miRNA restoration. This chapter demonstrates an approach to discover miRNAs of biomarker and therapeutic potential by isolating miRNAs from cell lines, performing global miRNA profiling, investigating miRNA expression in clinical specimens and examining their therapeutic relevance by restoring miRNA expression using Lipofectamine in vitro.

A survey of patient expectations regarding sexual function following radical prostatectomy.

OBJECTIVE: To assess the understanding of patients, who had previously undergone radical prostatectomy (RP), about their postoperative sexual function, as clinical experience suggests that some RP patients have unrealistic expectations about their long-term sexual function. PATIENTS AND METHODS: Patients presenting within 3 months of their open RP or robot-assisted laparoscopic prostatectomy (RALP) were questioned about the sexual function information that they had received preoperatively. Patients were questioned about erectile function (EF), postoperative ejaculatory status, orgasm, and postoperative penile morphology changes. Statistical analyses were performed to assess for differences between patients who underwent open RP vs RALP. RESULTS: In all, 336 consecutive patients (from nine surgeons) with a mean (SD) age of 64 (11) years had the survey instrument administered (216 underwent open RP and 120 underwent RALP). There were no significant differences in patient age or comorbidity profiles between the two groups. Only 38% of men had an accurate recollection of their nerve-sparing status. The mean (SD) elapsed time after RP at the time of postoperative assessment was 3 (2) months. RALP patients expected a shorter EF recovery time (6 vs 12 months, P = 0.02), a higher likelihood of recovery back to baseline EF (75% vs 50%, P = 0.01), and a lower potential need for intracavernosal injection therapy (4% vs 20%, P = 0.01). Almost half of all patients were unaware that they were rendered anejaculatory by their surgery. None of the RALP patients and only 10% of open RP patients recalled being informed of the potential for penile length loss (P < 0.01) and none were aware of the association between RP and Peyronie's disease. CONCLUSIONS: Patients who have undergone RP have largely unrealistic expectations about their postoperative sexual function.

miR-134 in extracellular vesicles reduces triple-negative breast cancer aggression and increases drug sensitivity.

Exosomes (EVs) have relevance in cell-to-cell communication carrying pro-tumorigenic factors that participate in oncogenesis and drug resistance and are proposed to have potential as self-delivery systems. Advancing on our studies of EVs in triple-negative breast cancer, here we more comprehensively analysed isogenic cell line variants and their EV populations, tissues cell line variants and their EV populations, as well as breast tumour and normal tissues. Profiling 384 miRNAs showed EV miRNA content to be highly representative of their cells of origin. miRNAs most substantially down-regulated in aggressive cells and their EVs originated from 14q32. Analysis of miR-134, the most substantially down-regulated miRNA, supported its clinical relevance in breast tumours compared to matched normal breast tissue. Functional studies indicated that miR-134 controls STAT5B which, in turn, controls Hsp90. miR-134 delivered by direct transfection into Hs578Ts(i)8 cells (in which it was greatly down-regulated) reduced STAT5B, Hsp90, and Bcl-2 levels, reduced cellular proliferation, and enhanced cisplatin-induced apoptosis. Delivery via miR-134-enriched EVs also reduced STAT5B and Hsp90, reduced cellular migration and invasion, and enhanced sensitivity to anti-Hsp90 drugs. While the differing effects achieved by transfection or EV delivery are likely to be, at least partly, due to specific amounts of miR-134 delivered by these routes, these EV-based studies identified miRNA-134 as a potential biomarker and therapeutic for breast cancer.

Severe Rhabdomyolysis without Systemic Involvement: A Rare Case of Idiopathic Eosinophilic Polymyositis.

Introduction. Eosinophilic polymyositis (EPM) is a rare cause of rhabdomyolysis characterized by eosinophilic infiltrates in the muscle. We describe the case of a young patient with eosinophilic polymyositis causing isolated severe rhabdomyolysis without systemic involvement. Case Presentation. A 22-year-old Haitian female with no past medical history presented with progressive generalized muscle aches without precipitating factors. Examination of the extremities revealed diffuse muscle tenderness. Laboratory findings demonstrated peripheral eosinophilia and high creatinine phosphokinase (CPK) and transaminase levels. Workup for the common causes of rhabdomyolysis were negative. Her CPK continued to rise to greater than 100,000 units/L so a muscle biopsy was performed which showed widespread eosinophilic infiltrate consistent with eosinophilic polymyositis. She was started on high dose systemic corticosteroids with improvement of her symptoms, eosinophilia, and CPK level. Discussion. This case illustrates a systematic workup of rhabdomyolysis in the presence of peripheral eosinophilia. Many differential diagnoses must be considered before establishing a diagnosis of idiopathic eosinophilic polymyositis. To our knowledge, our case of eosinophilic polymyositis is unique as it presented with severe rhabdomyolysis without another organ involvement. Clinicians should maintain a high index of suspicion for this physically debilitating disease to aid in prompt diagnosis.

Nurse led care coordination: trial protocol and development of a best practice resource guide for a cluster controlled clinical trial in Australian aged care facilities.

In this paper we describe (i) the protocol for a cluster controlled clinical trial of nurse led care coordination in residential aged care facilities (RACF); and (ii) the development and content of a best practice resource guide to be implemented as part of this trial. We used published systematic reviews of quantitative studies, existing resources and multidisciplinary expert opinion to develop an intervention for testing in a cluster controlled trial (Australian and New Zealand Clinical Trials Registry Number 12611000933954). The trial will determine whether care coordination of multiple evidenced based strategies can improve quality of life and reduce hospitalization rates amongst people living in RACF. Central to the intervention arm of the trial are two components: (i) experienced nurse practitioners responsible for resident care and (ii) a best practice guide for the care processes being delivered and coordinated by those nurses. In this paper we outline how this practice guide, which is published herein, was refined through consultative processes and practitioner testing.

Exosomes from triple-negative breast cancer cells can transfer phenotypic traits representing their cells of origin to secondary cells.

BACKGROUND: Triple-negative breast cancer (TNBC) accounts for 15-20% of breast cancers but is responsible for a disproportionate number of deaths. We investigated the relevance, in TNBC, of nano-sized exosomes expelled from cells. Specifically, we compared effects of exosomes derived from the claudin-low TNBC cell line Hs578T and its more invasive Hs578Ts(i)8 variant, as well as exosomes from TNBC patient sera compared to normal sera. METHODS: Exosomes were isolated from conditioned media (CM) of Hs578T and Hs578Ts(i)8 cells and from sera by filtration and ultracentrifugation. Successful isolation was confirmed by transmission electron microscopy and immunoblotting. Subsequent analysis, of secondary/recipient cells in response to exosomes, included proliferation; motility/migration; invasion; anoikis assays and endothelial tubule formation assays. RESULTS: Hs578Ts(i)8-exosomes versus Hs578T-exosomes significantly increased the proliferation, migration and invasion capacity of all three recipient cell lines evaluated i.e. SKBR3, MDA-MB-231 and HCC1954. Exosomes from Hs578Ts(i)8 cells also conferred increased invasiveness to parent Hs578T cells. Hs578Ts(i)8-exosomes increased sensitivity of SKBR3, MDA-MB-231 and HCC1954 to anoikis when compared to the effects of Hs578T-exosomes reflecting the fact that Hs578Ts(i)8 cells are themselves innately more sensitive to anoikis. In relation to vasculogenesis and subsequent angiogenesis, Hs578Ts(i)8-exosomes versus Hs578T-exosomes stimulated significantly more endothelial tubules formation. Finally, our pilot translational study showed that exosomes from TNBC patients' sera significantly increased recipient cells' invasion when compared to those derived from age- and gender-matched healthy control sera. CONCLUSION: This study supports the hypothesis that TNBC exosomes may be involved in cancer cell-to-cell communication, conferring phenotypic traits to secondary cells that reflect those of their cells of origin.

Defining the aetiology of erectile dysfunction in men with chronic pelvic pain syndrome.

Men presenting with chronic pelvic pain syndrome (CPPS) frequently report concomitant erectile dysfunction (ED), but the underlying cause of ED in this patient population has not been previously studied. This study prospectively investigated the aetiology of ED in men with CPPS. The study population comprised 46 men with penile pain or dysorgasmia, and concomitant ED. All participants completed the NIH-CPSI and international index of erectile function- erectile function domain (IIEF-EFD) questionnaires, and underwent penile duplex Doppler ultrasonography (DUS), following intracavernosal trimix injection, to evaluate erectile hemodynamic parameters. Pearson's correlation between NIH-CPSI and IIEF-EFD scores, and between NIH-CPSI score and the erectile response to trimix injections was investigated. The prevalence of mild, moderate and severe CPPS symptoms was 26, 48 and 26% respectively. The severity of ED was mild, moderate or severe in 15, 61 and 24% of men respectively. NIH-CPSI and IIEF-EFD scores were negatively correlated (r = -0.32, p = 0.002). Peak systolic velocity (PSV) and end-diastolic velocity (EDV) were normal in 96 and 100% of men respectively. The majority of men (78%) required ≥2 trimix injections to attain an adequate erection for DUS. NIH-CPSI scores and the number of trimix injections needed were positively correlated (r = 0.22, p = 0.035). The aetiology of erectile dysfunction in men who present with CPPS and concomitant ED is almost always psychogenic. Penile DUS in this population of men is fraught with the potential for error, and frequently necessitates more than one dose of a vasoactive agent.

Docetaxel-resistance in prostate cancer: evaluating associated phenotypic changes and potential for resistance transfer via exosomes.

BACKGROUND: Hormone-refractory prostate cancer remains hindered by inevitable progression of resistance to first-line treatment with docetaxel. Recent studies suggest that phenotypic changes associated with cancer may be transferred from cell-to-cell via microvesicles/exosomes. Here we aimed to investigate phenotypic changes associated with docetaxel-resistance in order to help determine the complexity of this problem and to assess the relevance of secreted exosomes in prostate cancer. METHODOLOGY/PRINCIPAL FINDINGS: Docetaxel-resistant variants of DU145 and 22Rv1 were established and characterised in terms of cross-resistance, morphology, proliferation, motility, invasion, anoikis, colony formation, exosomes secretion their and functional relevance. Preliminary analysis of exosomes from relevant serum specimens was also performed. Acquired docetaxel-resistance conferred cross-resistance to doxorubicin and induced alterations in motility, invasion, proliferation and anchorage-independent growth. Exosomes expelled from DU145 and 22Rv1 docetaxel-resistant variants (DU145RD and 22Rv1RD) conferred docetaxel-resistance to DU145, 22Rv1 and LNCap cells, which may be partly due to exosomal MDR-1/P-gp transfer. Exosomes from prostate cancer patients' sera induced increased cell proliferation and invasion, compared to exosomes from age-matched controls. Furthermore, exosomes from sera of patients undergoing a course of docetaxel treatment compared to matched exosomes from the same patients prior to commencing docetaxel treatment, when applied to both DU145 and 22Rv1 cells, showed a correlation between cellular response to docetaxel and patients' response to treatment with docetaxel. CONCLUSIONS/SIGNIFICANCE: Our studies indicate the complex and multifaceted nature of docetaxel-resistance in prostate cancer. Furthermore, our in vitro observations and preliminary clinical studies indicate that exosomes may play an important role in prostate cancer, in cell-cell communication, and thus may offer potential as vehicles containing predictive biomarkers and new therapeutic targets.

Isolation of exosomes for subsequent mRNA, MicroRNA, and protein profiling.

Exosomes are nano-sized, cell membrane surrounded structures that are released from many cell types. These exosomes are believed to transport a range of molecules, including mRNAs, miRNAs, and proteins; the contents depending on their cell of origin. The physiological and pathological relevance of exosomes has yet to be fully elucidated. Exosomes have been implicated in cell-to-cell communication. For example, in relation to the immune system, such exosomes may enable exchange of antigen or major histocompatibility complex-peptide complexes between antigen-bearing cells and antigen-presenting cells; in cancer, they may contain molecules that not only have relevance as biomarkers, but may also be taken up and cause adverse effects on secondary cells. Furthermore, exosomes have been proposed as autologous delivery systems that could be exploited for personalised delivery of therapeutics. In order to explore the contents and functional relevance of exosomes from medium conditioned by culture cells or from other biological fluids, prior to extensive molecular profiling, they must be isolated and purified. Here, we describe differential centrifugation methods suitable for isolating exosomes from conditioned medium and from other biological fluids, including serum, saliva, tumour ascites, and urine. We also detail Western blotting and transmission electron microscopy methods suitable for basic assessment of their presence, size, and purity, prior to progressing to global mRNA, miRNA, or protein profiling.

Outcomes of crural ligation surgery for isolated crural venous leak.

INTRODUCTION: Venous ligation surgery results for diffuse venous leak have been disappointing, although in isolated crural venous leak (ICVL) cases, efficacy for crural ligation surgery (CLS) has been demonstrated. AIM: The purpose of this study was to present our experience with treatment of ICVL with CLS. METHODS: All patients underwent preoperative cavernosometry. Cavernosography (CG) or perineal compression (PC) was used to define the diagnosis of ICVL. If CG demonstrated ICVL or flow-to-maintain values normalized with PC, the patient was counseled regarding CLS. Baseline and postoperative erectile function (EF) was assessed by the International Index of Erectile Function (IIEF) questionnaire. MAIN OUTCOME MEASURES: EF, using the EF domain (EFD) score of the IIEF, a domain with six questions with a maximum score of 30 and a minimum score of 6 in the sexually active male. All patients completed the questionnaire preoperatively and in a serial fashion after surgery at a time point after 12 months postoperatively. RESULTS: 14 patients underwent CLS. Mean age was 29 ± 7 years. Also, 64% had primary erectile dysfunction. Mean baseline IIEF-EF score was 18 ± 6. Furthermore, 71% of patients had failed phosphodiesterase type 5 (PDE5) inhibitors and 6/10 (60%) failed intracavernosal injections (ICI). Mean postoperative EFD score was 24 ± 3 representing a mean change of 6.5 points per patient. No patient needed ICI after CLS; however, 4/14 patients needed PDE5 inhibitors, all of whom had been using ICI preoperatively. In addition, 71% experienced unassisted sexual intercourse after CLS. CONCLUSIONS: In a highly selected population of young men with ICVL, CLS cures 70% and improves EF in more than 90% of men. Surgical treatment of ICVL by CLS can be performed safely and with sufficient efficacy that larger and longer term studies should be undertaken.

A qualitative exploration of nurse's perception of Critical Outreach Service: a before and after study.

BACKGROUND: Critical Care Outreach Services (CCOS) have been reported to streamline the transfer of patients from the intensive care unit (ICU) to the wards and provide a follow-up service supporting ward staff to provide optimum care for patients discharged from ICU. PURPOSE: The aim of this study was to explore the perceptions of nursing staff before and after the introduction of a CCOS at three adult teaching hospitals in Perth, Western Australia. METHODS: Exploratory focus groups were conducted with registered nurses (RNs) at each of the participating hospitals prior to and 6 months after the introduction of a CCOS. Framework analysis was used to analyse the transcribed data using a thematic approach with themes developed from the narratives of the participants. RESULTS: Inexperienced RNs in particular voiced positive comments about the CCOS. The role was seen as a senior nurse who was an additional resource for less experienced staff as they educated them on complex procedures that were not common on the general wards. The RNs reported that apprehensions about the role that they had pre-implementation were not borne out in practice and that they believed that the CCOS had positive effects on patient outcomes. CONCLUSION: The CCOS improved communication processes between members of the multidisciplinary team and units within the hospital, which subsequently enhanced the ward transition process for critically ill patients and ward nursing staff.

Clinical effectiveness of a critical care nursing outreach service in facilitating discharge from the intensive care unit.

BACKGROUND: Improved discharge planning and extension of care to the general care unit for patients transferring from intensive care may prevent readmission to the intensive care unit and prolonged hospital stays. Morbidity, mortality, and costs increase in readmitted intensive care patients. OBJECTIVES: To evaluate the clinical effectiveness of a critical care nursing outreach service in facilitating discharge from the intensive care unit and providing follow-up in general care areas. METHODS: A before-and-after study design (with historical controls and a 6-month prospective intervention) was used to ascertain differences in clinical outcomes, length of stay, and cost/benefit. Patients admitted to intensive care units in 3 adult teaching hospitals were recruited. The service centered on follow-up visits by specialist intensive care nurses who reviewed and assessed patients who were to be or had been discharged to general care areas from the intensive care unit. Those nurses also provided education and clinical support to staff in general care areas. RESULTS: In total, 1435 patients were discharged during the 6-month prospective period. Length of stay from the time of admission to the intensive care unit to hospital discharge (P = .85), readmissions during the same hospital admission (5.6% vs 5.4%, P = .83), and hospital survival (P = .80) did not differ from before to after the intervention. CONCLUSIONS: Although other studies have shown beneficial outcomes in Australia and the United Kingdom, we found no improvement in length of stay after admission to the intensive care unit, readmission rate, or hospital mortality after a critical care nursing outreach service was implemented.

Discharge delay, room for improvement?

AIM: Patients treated in the intensive care unit (ICU) and identified as suitable for discharge to the ward should have their discharge planned and expedited to improve patient outcomes and manage resources efficiently. We examined the hypothesis that the introduction of a critical care outreach role would decrease the frequency of discharge delay from ICU. METHODS: Discharge delay was compared for two 6-month periods: (1) after introduction of the outreach role in 2008 and (2) in 2000/2001 (from an earlier study). Patients were included if discharged to a ward in the study hospital. Discharge times and reason for delay were collected by Critical Care Outreach Nurses and Critical Care Nurse Specialists. RESULTS: Of the 516 discharges in 2008 (488 patients compared to 607 in 2000/2001), 31% of the discharges were delayed from ICU more than 8h, an increase of 6% from 2000/2001 (p<0.001). Patients in 2008 spent more in hospital from the time of their ICU admission when their discharge was delayed (p<0.001). The most common reasons for delay in 2008 were due to no bed or delay in bed availability (53%) and medical concern (24%). This is in contrast to 2000/2001 when 80% of delays were due to no bed or delay in bed availability and 9% due to medical concern. Many factors impact on patient flow and reducing ICU discharge delays requires a collaborative, multi-factorial approach which adapts to changing organisational policy on patient flow through ICU and the hospital, not just the discharge process in ICU.

Can the International Index of Erectile Function distinguish between organic and psychogenic erectile function?

OBJECTIVE: To define the ability of the International Index of Erectile Function (IIEF) to differentiate between organic and psychogenic erectile dysfunction (ED). PATIENTS AND METHODS: Patients presenting for the evaluation and treatment of ED who had penile duplex Doppler ultrasonography (DUS) completed the IIEF questionnaire. Accepted ranges of the IIEF EF domain were used to grade baseline severity (severe, moderate and mild < or =11, 11-17, 18-25, respectively). Accepted criteria were used to define normality on DUS (peak systolic velocity >30 cm/s and end-diastolic velocity <5 cm/s). Patients with documented Peyronie's disease, hypogonadism and a history of radical prostatectomy were excluded. RESULTS: In all, 112 patients were enrolled, with a mean (sd) age and duration of ED of 56 (16) and 2 (0.6) years, respectively. The vascular risk-factor profile included diabetes in 15%, hypertension in 26% and hyperlipidaemia in 20%. The baseline severity of ED was mild, moderate and severe in 28%, 41% and 32% men, respectively. All patients had normal testosterone levels. Patients also with a normal DUS were diagnosed with psychogenic ED, in 50%, 13% and 17% of men with mild, moderate and severe ED by the IIEF, respectively. No patient with venous leak had mild ED, and 62% of men with venous leak had severe ED. CONCLUSIONS: These results indicate that the IIEF is not completely accurate in differentiating between organic and psychogenic ED, and that almost a fifth of men in this study population with severe ED by the IIEF had normal erectile haemodynamics. These data have potential ramifications for evaluating the baseline severity of ED in trials of erectogenic agents.

Defining the clinical characteristics of Peyronie's disease in young men.

INTRODUCTION: Peyronie's disease (PD) is usually seen in men in their fifth decade of life. AIM: In this study, we investigated the characteristics of the disease in young men. MAIN OUTCOME MEASURES: The demographics, clinical features, and associated comorbidities of the patients with PD were retrospectively reviewed. METHODS: The findings were compared between men with the disease who were under 40 years of age with those over 40 years. Statistical analyses were conducted to define differentiating features between these two groups. RESULTS: Of the 296 patients, 32 were under the age of 40 years and 264 over 40 years. The mean duration of the disease was 2 +/- 4 and 6 +/- 8 months in the respective age groups. Fifty-six percent of the patients under the age of 40 years and 75% of the patients over this age presented with curvature (P < 0.01). Thirty-seven percent under 40 years and 12% men over 40 years had more than one plaque at presentation (P < 0.01). Dupuytren's contracture was seen only in patients over 40 years of age. Pain at presentation was found in 75% under the age of 40 years and in 65% over 40 years (P = 0.03). Trauma history was found in 18% under 40 years and in 5% over this age (P < 0.01). Statistical significant differences were found between the groups under and over the age of 40 years for hypertension (P < 0.01) and dyslipidemia (P < 0.01). Diabetes was noted in 50% of the patients under the age of 40 years and in 18% of the patients over this age (P < 0.001). Multivariate analysis of conditions associated in men with PD under 40 years of age showed statistical significant differences for diabetes (P = 0.015), presentation within 6 months (P = 0.004), and having multiple plaques (P = 0.008). CONCLUSIONS: Young men with PD are more likely to present at an earlier stage of the disease, to have diabetes, and to have more than one plaque at the time of presentation.