How to increase value and reduce waste in research: initial experiences of applying Lean thinking and visual management in research leadership.

Waste in research has been well documented, but initiatives to reduce it are scarce. Here, we share our initial experiences of implementing Lean thinking and visual management into hospital research units in the Region of Southern Denmark. A Transformation Guiding Team (TGT) anchored in the top management was established with participation from leaders, researchers and patient representatives. The role of the TGT was to implement Lean methods, considering patients as primary end-users of the research results. This is in line with an explicit decision on setting patient values first in clinical settings at participating hospitals. The leaders of the research units were instructed in Lean thinking and Lean methods during a five-module course focusing on increasing value and reducing waste in research production. Initial experiences were that Lean tools could create a patient-centred vision that through visual management could identify waste in work processes. Concerns were lack of evidence for using Lean methods in research leadership and that the model itself could be a time consumer. Some lessons learnt were that adding Lean tools in research leadership should not just provide increased research productivity, but also improve other important key performance indicators such as quality of research and patient-relevant results. We intend to evaluate the value of the initiative by follow-up research and publish the outcome of key behavioural and key performance indicators.

Acoustic Emission-Based Condition Monitoring and Remaining Useful Life Prediction of Hydraulic Cylinder Rod Seals.

The foremost reason for unscheduled maintenance of hydraulic cylinders in industry is caused by wear of the hydraulic seals. Therefore, condition monitoring and subsequent estimation of remaining useful life (RUL) methods are highly sought after by the maintenance professionals. This study aimed at investigating the use of acoustic emission (AE) sensors to identify the early stages of external leakage initiation in hydraulic cylinders through run to failure studies (RTF) in a test rig. In this study, the impact of sensor location and rod speeds on the AE signal were investigated using both time- and frequency-based features. Furthermore, a frequency domain analysis was conducted to investigate the power spectral density (PSD) of the AE signal. An accelerated leakage initiation process was performed by creating longitudinal scratches on the piston rod. In addition, the effect on the AE signal from pausing the test rig for a prolonged duration during the RTF tests was investigated. From the extracted features of the AE signal, the root mean square (RMS) feature was observed to be a potent condition indicator (CI) to understand the leakage initiation. In this study, the AE signal showed a large drop in the RMS value caused by the pause in the RTF test operations. However, the RMS value at leakage initiation is seen to be a promising CI because it appears to be linearly scalable to operational conditions such as pressure and speed, with good accuracy, for predicting the leakage threshold.

Injuries can prolong lifespan in Drosophila melanogaster males.

Previous studies have shown that a range of different stresses can increase mean lifespan. Here we investigated the effect of injuries and bacterial inoculation on mean lifespan in lines selected for increased longevity and their controls. The three lines from each selection regime were subjected to one of five treatments ranging from control, over perforating the cuticle with a sterile needle, to inoculating with peptidoglycan or one of two strains of live bacteria. The flies were subjected to the infection stress at two ages and the experiment was conducted on both males and females of replicate lines of each selection regime. The individual lines and sexes differed in response to the treatment. However, overall the sterile injury of young males resulted in prolonged mean lifespan from both selection regimes, whereas inoculating had no additional effect to stabbing with a sterile needle. In middle-aged males only treatment with peptidoglycan had a significant hormetic effect and this was only in longevity-selected flies. In females only one of the tested contrasts was significant and here the effect of the treatment was to reduce average lifespan. As could be expected, the results showed a significant interaction between the effects of sex and infection on survival.

[Waiting time for treatment shall be calculated correctly]. / Ventetid på behandling skal beregnes korrekt.

Every system is perfectly designed to achieve the results it gets and in the Danish health care system there is a significant waiting time for the patients. If we want this result to change, we have to change something in the system, but before we do that, we need to understand the system. With queuing theory as a frame of reference, the anatomy and physiology of waiting time is illuminated in order to bring additional knowledge into the design of systems in health care.

Transurethral resection of non-muscle-invasive bladder transitional cell cancers with or without 5-aminolevulinic Acid under visible and fluorescent light: results of a prospective, randomised, multicentre study.

BACKGROUND: Fluorescent light (FL)-guided cystoscopy induced by 5-aminolevulinic acid (5-ALA) has been reported to detect more tumours compared with standard white-light (WL) cystoscopy. Most reports are from single centres with relatively few patients. OBJECTIVE: To evaluate whether 5-ALA-induced FL and WL cystoscopy at transurethral resection (TUR) is superior compared with standard procedures under WL only with respect to tumour recurrence and progression in patients with non-muscle-invasive bladder cancer. DESIGN, SETTING, AND PARTICIPANTS: This randomised, multicentre, observer- and pathologist-blinded, prospective phase 3 clinical trial enrolled 300 patients, and of those patients, 153 were randomised to FL cystoscopy and 147 were randomised to standard WL cystoscopy. INTERVENTION: All patients were first inspected under WL and all lesions were recorded. Patients randomised to FL underwent a second inspection. TUR was carried out in both groups. MEASUREMENTS: Control cystoscopy under WL was performed in all patients every 3 mo during the first year after randomisation and biannually thereafter. RESULTS AND LIMITATIONS: At the first TUR, the mean number of resection specimens per patient was 2.5 (FL: 2.5; WL: 2.4; p=0.37) and the resulting mean number of resected tumours was 1.7 with FL and 1.8 with WL (p=0.85). More patients were diagnosed with carcinoma in situ (CIS) in the WL group (13%) than in the FL group (4.2%). Within-patient comparison of FL patients only showed that FL detected more lesions than WL. Tumour lesions solely detected by FL cystoscopy that would not otherwise be detected by WL cystoscopy included 52% dysplasia, 33% CIS, 18% papillary neoplasms, 13% pT1, and 7% pTa. Outcome at 12 mo did not show any difference between groups with regard to recurrence-free and progression-free survival rates. CONCLUSIONS: In this prospective, randomised, multi-institutional study, we found no clinical advantage of FL cystoscopy compared with WL cystoscopy and TUR.

Fibrin clot structure in patients with end-stage renal disease.

Fibrin clots with reduced permeability, increased clot stiffness and reduced fibrinolysis susceptibility may predispose to cardiovascular disease (CVD). Little is known, however, about the structure of fibrin clots in patients with end-stage renal disease (ESRD). These patients suffer from a high risk of CVD in addition to their chronic low-grade inflammation. Using permeability, compaction and turbidity studies in 22 ESRD patients and 24 healthy controls, fibrin clots made from patient plasma were found to be less permeable (p < 0.001), less compactable (p < 0.001), and less susceptible to fibrinolysis (p < 0.001) than clots from controls. The maximum rate of turbidity increase was also higher for the patients than controls (p < 0.001), and scanning electron microscopy revealed higher clot density of fibrin fibers in clots from patients than clots from controls (p < 0.001). Patients had higher plasma concentrations of fibrinogen, C-reactive protein and interleukin 6 than controls. These plasma markers of inflammation correlated significantly with most of the fibrin structure characteristics observed in the patients. In contrast, plasma markers of azothemia showed no such correlations. The results suggest that in ESRD patients fibrin clots are significantly different from healthy controls, and that the fibrin structure characteristics in the patients are associated primarily with the inflammatory plasma milieu rather than with level of azothemia.

Phase-II study on stereotactic radiotherapy of locally advanced pancreatic carcinoma.

BACKGROUND AND PURPOSE: The majority of patients with pancreatic cancer have advanced disease at the time of diagnosis and are not amenable for surgery. Stereotactic radiotherapy (SRT) may be an alternative treatment for patients with locally advanced disease. The effect of SRT was investigated in the present phase-II trial. PATIENTS AND METHODS: Twenty-two patients with locally advanced and surgically non-resectable, histological proven pancreatic carcinoma were included into the trial. The patients were immobilized by the Elekta stereotactic body frame (SBF) or a custom made body frame. SRT was given on standard LINAC with standard multi-leaf collimator. Central dose was 15 Gyx3 within 5-10 days. RESULTS: Evaluation of response was found to be very difficult due to radiation and tumour related tissue reaction. Only two patients (9%) were found to have a partial response (PR), the remaining had no change (NC) or progression (PD) after treatment. Six patients had local tumour progression, but only one patient had an isolated local failure without simultaneous distant metastasis. Median time to local or distant progression was 4.8 months. Median survival time was 5.7 months and only 5% were alive 1 year after treatment. Acute toxicity reported 14 days after treatment was pronounced. There was a significant deterioration of performance status (P=0.008), more nausea (P=0.001) and more pain (P=0.008) after 14 days compared with base-line. However, 8 of 12 patients (66%) improved in performance status, scored less nausea, pain, or needed less analgesic drugs at 3 months after treatment. Four patients suffered from severe mucositis or ulceration of the stomach or duodenum and one of the patients had a non-fatal ulcer perforation of the stomach. CONCLUSIONS: SRT was associated with poor outcome, unacceptable toxicity and questionable palliative effect and cannot be recommended for patients with advanced pancreatic carcinoma.

Microbial flora in ileal and colonic neobladders.

OBJECTIVE: To describe bacterial colonization in patients with ileal and colonic neobladders. METHODS: Twenty-three patients with right colon neobladders, 30 with ileal neobladders, 11 who had undergone radical prostatectomy, and 6 healthy controls were included. Culture of clean-catch, midstream urine specimens was done weekly for 3 weeks, and this was repeated after 6 months. Residual urine was measured, and the patients were interviewed about leakage. All patients and controls were antibiotic free during the study except for 13 of the ileal neobladder patients, who were treated with trimethoprim 100mg daily. RESULTS: Urine cultures from controls and prostatectomy patients were negative for bacteria, whereas 67% of the specimens from patients with neobladders, not on antibiotic therapy, were culture positive, and half of these contained uropathogenic species, such as Escherichia coli, Klebsiella pneumoniae, Pseudomonas aeruginosa, and Enterococcus faecalis. Bacterial colonization (including uropathogenic strains) was strongly correlated with residual urine (p<0.005), but not with leakage. Anaerobic strains were found more frequently (p=0.04) in urine from ileal neobladders than in urine from colonic neobladders. The 13 patients with ileal neobladders and on prophylactic antibiotic therapy carried bacteriuria in 80% of the samples, the majority being anaerobic strains. Uropathogenic strains, mainly Enterecoccus faecalis was revealed in 30% of the samples. CONCLUSIONS: The lower urinary tract of patients with ileal or colonic neobladders is heavily colonized with potentially uropathogenic and anaerobic bacteria. Complete bladder emptying reduces the bacterial burden. Anaerobic colonization is increased in neobladders reconstructed from ileum. Prophylactic antibiotic therapy does not seem to reduce the bacterial burden, but interferes with the bacterial composition.

Soxhlet extraction of acrylamide from potato chips.

The problem of complete extraction of acrylamide from potato chips was investigated. A method was developed based on the Soxhlet extraction technique. A defatted sample was extracted continuously with methanol, for 10 days, in a Soxhlet extractor. After about 7 days, a constant concentration of acrylamide was reached. This indicates that all the acrylamide that could be removed from the sample had been extracted. Acrylamide was identified in the extract using GC-MS and scan mode. Total concentration was 14500 microg kg(-1) using GC-FID and standard additions. Complementary determinations, using an external standard (GC-FID and GC-MS) and an internal standard (GC-FID), showed results within +/- 5%. A previously published study, using a static extraction method and GC-MS and LC-MS-MS, showed concentrations of 2287 and 1993 microg kg(-1), respectively. The results are discussed in relation to a recent model and analogous experiments. The extracted amount of acrylamide is affected by several parameters: solvent properties, solvent volume, extraction time, temperature, particle size, and the microstructure of the sample.

Relative importance of sources of symptom-induced distress in urinary bladder cancer survivors.

OBJECTIVE: The influence of specific symptoms on emotions and social activities in the individual patient varies. Little is known about this variation in urinary bladder cancer survivors (in other words, about the relative importance of sources of symptom-induced distress). METHODS: We attempted to enroll 404 surgical patients treated with cystectomy and a conduit or reservoir in four Swedish towns (Stockholm, Orebro, Jönköping, Linköping), 101 surgical patients treated with cystectomy and orthotopic neobladder at the Herlev Hospital in Copenhagen, Denmark, and 71 patients treated with radical radiotherapy for bladder cancer, as well as 581 men and women controls in Stockholm and Copenhagen. An anonymous postal questionnaire was used to collect the information. RESULTS: A total of 503 out of 576 (87%) treated patients and 422 out of 581 (73%) controls participated but 59 patients were excluded. The primary source of self-assessed distress among cystectomised patients was compromised sexual function; reduced intercourse frequency caused great distress in 19% of the conduit patients, 20% of the reservoir patients and 19% of the bladder substitute patients. The primary source of self-assessed distress in patients treated with radical radiotherapy was symptoms from the bowel; 17% reported great distress due to diarrhoea, 16% due to abdominal pain, 14% due to defecation urgency and 14% due to faecal leakage. The highest proportion of subjects being distressed was 93% (substantial: 43%, moderate: 29% and little: 21%) for treated upper or lower urinary retention (indwelling catheter or nephrostomy). CONCLUSION: The distress caused by a specific symptom varies considerably and the prevalence of symptoms causing great distress differs between treatments in bladder cancer survivors. It is possible that patient care and clinical research can be made more effective by focusing on important sources of symptom-induced distress.

Complex segregation analysis of hypospadias.

Hypospadias, when the urethra opens on the ventral side of the penis, is a common malformation seen in about 3 per 1000 male births. It is considered a complex disorder with both genetic and environmental factors involved in the pathogenesis. Low birth weight is known to be an important risk factor for hypospadias, but several observations speak in favour of genetic factors as well. In order to delineate the relative contribution of the genetic factors behind hypospadias, we performed a complex segregation analysis of 2005 pedigrees in Sweden. The probands were ascertained through the departments of paediatric surgery and departments of plastic surgery and urology in Sweden where boys with hypospadias undergo surgery. In 7% of the ascertained families one or more additional cases of hypospadias were present. The complex segregation analysis showed a heritability of 0.99 and evidence for multifactorial inheritance. The results suggest that hypospadias might be due to monogenic effects in a small proportion of the families, but that there is a multifactorial cause for the majority of the cases.

Heredity of hypospadias and the significance of low birth weight.

PURPOSE: We analyzed a large group of patients with hypospadias regarding familial aggregation, phenotype, twin rate and ethnic origin and assessed the correlation of low birth weight with hypospadias. MATERIALS AND METHODS: We mailed questionnaires to 2,503 boys operated on for hypospadias in Sweden asking for additional cases of hypospadias in the family, the number of brothers in the nuclear family, and birth weight of the boys with hypospadias and their brothers. RESULTS: Of the boys 7% reported 1 or more additional family members with hypospadias. The birth weight of the boys with hypospadias was significantly lower (p = 5 x 10-13) than the birth weight of their unaffected brothers. Phenotyping of 676 individuals revealed glandular hypospadias in 53%, penile forms in 39%, penoscrotal or perineal variants in 6% and cleaved prepuce as the only manifestation in 2%. There were 50% more twins than expected compared to the general population and established zygosity in 83% (67% monozygotic, 33% dizygotic). Non-Swedish ethnicity was noted in 22% of the subjects, a third of whom were from Middle Eastern countries. CONCLUSIONS: We present data on heredity, birth weight, phenotype and ethnic origin in a large group of patients with hypospadias. The finding of additional members with hypospadias in 7% of the families supports the concept that genetic factors are involved in the pathogenesis. The strong association with low birth weight may be explained by genetic and environmental factors.