Activity of creatine kinase in sera from healthy women,carriers of Duchenne muscular dystrophy and cord blood,determined by the “European” recommended method with NAC-EDTA activation

Creatine kinase activity has been measured at 37°C in sera from healthy women, carriers of Duchenne muscular dystrophy and cord blood, with activation by N-acetyl cysteine (NAC) and EDTA as recommended by several European committees on standardisation. The upper limit of the reference range for healthy women was found to be 170 U/1. The distributions of creatine kinase activities in healthy and carrier women have been used to calculate probability of carrier status as a function of creatine kinase activity. Although the range of creatine kinase activities in normal cord blood is wide, the data provide a basis for interpretation when Duchenne muscular dystrophy is suspected.     

The accuracy of quantitative parameters in 99mTc‐MAG3 dynamic renography: a national audit based on virtual image data

Assessment of image analysis methods and computer software used in ^99mTc‐MAG3 dynamic renography is important to ensure reliable study results and ultimately the best possible care for patients. In this work, we present a national multicentre study of the quantification accuracy in ^99mTc‐MAG3 renography, utilizing virtual dynamic scintigraphic data obtained by Monte Carlo‐simulated scintillation camera imaging of digital phantoms with time‐varying activity distributions. Three digital phantom studies were distributed to the participating departments, and quantitative evaluation was performed with standard clinical software according to local routines. The differential renal function (DRF) and time to maximum renal activity (T_max) were reported by 21 of the 28 Swedish departments performing ^99mTc‐MAG3 studies as of 2012. The reported DRF estimates showed a significantly lower precision for the phantom with impaired renal uptake than for the phantom with normal uptake. The T_max estimates showed a similar trend, but the difference was only significant for the right kidney. There was a significant bias in the measured DRF for all phantoms caused by different positions of the left and right kidney in the anterior–posterior direction. In conclusion, this study shows that virtual scintigraphic studies are applicable for quality assurance and that there is a considerable uncertainty associated with standard quantitative parameters in dynamic ^99mTc‐MAG3 renography, especially for patients with impaired renal function.     

Measuring integrated care

The positive outcomes of coordination of healthcare services are to an increasing extent becoming clear. However the complexity of the field is an inhibiting factor for vigorously designed trial studies. Conceptual clarity and a consistent theoretical frame-work are thus needed. While researchers respond to these needs, patients and providers face the multiple challenges of today's healthcare environment. Decision makers, planners and managers need evidence based policy options and information on the scope of the integrated care challenges they are facing. The US managed care organization Kaiser Permanente has been put forward as an example for European healthcare systems to follow, although the evidence base is far from conclusive. The thesis has five objectives: 1) To contribute to the understanding of the concept of integration in healthcare systems and to identify measurement methods to capture the multi-dimensional aspects of integrated healthcare delivery. 2) To assess the level of integration of the Danish healthcare system. 3) To assess the use of joint health plans as a tool for coordination between the regional and local level in the Danish healthcare system. 4) To compare the inputs and performance of the Danish healthcare system and the managed care organization Kaiser Permanente, California, US. 5) To compare primary care clinicians' perception of clinical integration in two healthcare systems: Kaiser Permanente, Northern California and the Danish healthcare system. Further to examine the associations between specific organizational factors and clinical integration within each system. The literature was systematically searched to identify methods for measurement of integrated healthcare delivery. A national cross-sectional survey was conducted among major professional stake-holders at five different levels of the Danish healthcare system. The survey data were used to allow for analysis of the level of integration achieved. Data from the survey were additionally used to investigate the use of joint health planning as a tool for coordination of regional-local healthcare delivery. Analysis of secondary data from the Danish healthcare system and Kaiser Permanente, California were used to compare population characteristics, professional staff, delivery structure, utilisation, quality measures and direct costs. A cross-sectional survey among primary care clinicians in Denmark and in Kaiser Permanente, Northern California was completed to allow for comparison of clinical integration in the two systems and system specific associated factors. In this thesis a conceptual framework and a model for assessment of the conditions for integrations as an intermediate healthcare system outcome are presented. Furthermore, the results show that integrated healthcare delivery can be measured: 24 methods are available and some are highly developed. However, the field is still in its early phase and guidelines for how to proceed are devised. It was confirmed on a national level that integration of care is a widespread challenge, and that only half or less than half of patients in need of integrated services receive such care. Options for decision makers and managers are discussed. From a theoretical perspective joint health plans as applied in Denmark do not match the degree of complexity in the healthcare system. It was therefore in agreement with the theoretical findings when major stakeholders agreed that the joint health plans had not been effective as a tool for coordination. Joint health planning processes should actively engage all stakeholders and a high degree of recurrent feedback are warranted. When comparing Kaiser Permanente, California with the Danish healthcare system, our study suggest that Kaiser Permanente has a population with more documented disease and higher operating costs, and performs better than the Danish healthcare system on the observed quality measures. Substantial differences were found in the perception of clinical integration in the two settings. More primary care clinicians in the Northern California region of Kaiser Permanente reported being part of a clinical integrated environment than did Danish general practitioners. By measuring the level of clinical integration in Kaiser Permanente using the Danish healthcare system as a point of reference our findings support the literature that points to the importance of integrated healthcare delivery as a driver for the performance results of Kaiser Permanente. However caution must be advised before making concrete conclusions due to the complexity of the matter and until more studies have been conducted. With this thesis an initial step has been taken into a new research field. Ongoing research will make it possible to deliver the evidence needed by decision makers, planners and managers - ultimately to benefit the patients.     

A systematic intervention to improve patient information routines and satisfaction in a psychiatric emergency unit

Patients admitted to acute psychiatric hospitalization often report that they are being subject to coercion, irrespective of their official legal status. This experience may be related to a feeling of process exclusion and insufficient information about legal rights. Still, little systematic research has been performed to find effective ways of improving the quality of information presented to the patients and to increase patient satisfaction in a routine clinical setting. The purpose of our study was to systematically record measures of patient satisfaction before, during and after an intervention to improve the information procedures during patient admission. Based on a total of 763 consecutive admissions in an emergency psychiatric ward, 433 completed patient questionnaires were returned, indicating measures of patient satisfaction and factual knowledge in 30 different questions. The patients' general satisfaction scores increased only slightly during and after the intervention, but a robust and sustained improvement of the patients' satisfaction with the information received was recorded. Furthermore, the patients also reported an increased knowledge about specific legal issues related to their hospitalization. As this is an important aspect of patients' rights, we advocate the use of systematic procedures to increase patients' awareness of their legal status and knowledge about procedures in connection with hospitalization.     

Targeted cancer therapy with a novel low-dose rate alpha-emitting radioimmunoconjugate

Alpha-emitting radionuclides are highly cytotoxic and are of considerable interest in the treatment of cancer. A particularly interesting approach is in radioimmunotherapy. However, alpha-emitting antibody conjugates have been difficult to exploit clinically due to the short half-life of the radionuclides, low production capability, or limited source materials. We have developed a novel technology based on the low-dose rate alpha-particle-emitting nuclide (227)Th, exemplified here using the monoclonal antibody rituximab. In vitro, this radioimmunoconjugate killed lymphoma cells at Becquerel per milliliter (Bq/mL) levels. A single injection of (227)Th-rituximab induced complete tumor regression in up to 60% of nude mice bearing macroscopic (32-256 mm(3)) human B-lymphoma xenografts at Becquerel per gram (Bq/g) levels without apparent toxicity. Therapy with (227)Th-rituximab was significantly more effective than the control radioimmunoconjugate (227)Th-trastuzumab and the standard beta-emitting radioimmunoconjugate for CD20(+) lymphoma(90)Y-tiuxetan-ibritumomab. Thorium-227 based constructs may provide a novel approach for targeted therapy against a wide variety of cancers.     

Presence of Insulin-Like Growth Factor Binding Proteins Correlates With Tumor-Promoting Effects of Matrix Metalloproteinase 9 in Breast Cancer

The stroma of breast cancer can promote the disease’s progression, but whether its composition and functions are shared among different subtypes is poorly explored. We compared stromal components of a luminal [mouse mammary tumor virus (MMTV)–Neu] and a triple-negative/basal-like [C3(1)–Simian virus 40 large T antigen (Tag)] genetically engineered breast cancer mouse model. The types of cytokines and their expression levels were very different in the two models, as was the extent of innate immune cell infiltration; however, both models showed infiltration of innate immune cells that expressed matrix metalloproteinase 9 (MMP9), an extracellular protease linked to the progression of many types of cancer. By intercrossing with Mmp9 null mice, we found that the absence of MMP9 delayed tumor onset in the C3(1)-Tag model but had no effect on tumor onset in the MMTV-Neu model. We discovered that protein levels of insulin-like growth factor binding protein-1 (IGFBP-1), an MMP9 substrate, were increased in C3(1)-Tag;Mmp9^−/− compared to C3(1)-Tag;Mmp9^+/+ tumors. In contrast, IGFBP-1 protein expression was low in MMTV-Neu tumors regardless of Mmp9 status. IGFBP-1 binds and antagonizes IGFs, preventing them from activating their receptors to promote cell proliferation and survival. Tumors from C3(1)-Tag;Mmp9^−/− mice had reduced IGF-1 receptor phosphorylation, consistent with slower tumor onset. Finally, gene expression analysis of human breast tumors showed that high expression of IGFBP mRNA was strongly correlated with good prognosis but not when MMP9 mRNA was also highly expressed. In conclusion, MMP9 has different effects on breast cancer progression depending on whether IGFBPs are expressed.Abbreviations: αSMA, α smooth muscle actin, C3(1)-Tag, transgene mouse expressing Simian virus 40 large T antigen under a C3(1) promoter, HER2, human epidermal growth factor receptor 2, IGF, insulin-like growth factor, IGFBP, insulin-like growth factor binding protein, IL, interleukin, MMP, matrix metalloproteinase, MMTV, mouse mammary tumor virus, NF-κB, nuclear factor κB, PyMT, polyoma middle T antigen     

Assessment of quality in psychiatric nursing documentation – a clinical audit

Background

Quality in nursing documentation facilitates continuity of care and patient safety. Lack of communication between healthcare providers is associated with errors and adverse events. Shortcomings are identified in nursing documentation in several clinical specialties, but very little is known about the quality of how nurses document in the field of psychiatry. Therefore, the aim of this study was to assess the quality of the written nursing documentation in a psychiatric hospital.

Method

A cross-sectional, retrospective patient record review was conducted using the N-Catch audit instrument. In 2011 the nursing documentation from 21 persons admitted to a psychiatric department from September to December 2010 was assessed. The N-Catch instrument was used to audit the record structure, admission notes, nursing care plans, progress and outcome reports, discharge notes and information about the patients’ personal details. The items of N-Catch were scored for quantity and/or quality (0–3 points).

Results

The item ‘quantity of progress and evaluation notes’ had the lowest score: in 86% of the records progress and outcome were evaluated only sporadically. The items ‘the patients’ personal details’ and ‘quantity of record structure’ had the highest scores: respectively 100% and 71% of the records achieved the highest score of these items.

Conclusions

Deficiencies in nursing documentation identified in other clinical specialties also apply to the clinical field of psychiatry. The quality of electronic written nursing documentation in psychiatric nursing needs improvements to ensure continuity and patient safety. This study shows the importance of the existence of a validated tool, readily available to assess local levels of nursing documentation quality.

     

Perceived stress and risk of colorectal cancer in men and women: a prospective cohort study

Objective. We aim to assess the relationship between stress and risk of primary colorectal cancer in men and women. Design. A prospective cohort study Setting. The Copenhagen City Heart Study, Denmark Subjects. A total of 6488 women and 5426 men were included in the study. The participants were asked about intensity and frequency of stress at baseline in 1981–1983 and were followed until the end of 2000 in the Danish Cancer Registry. Less than 0.1% was lost to follow‐up. Main outcome measures. First time incidence of primary colorectal cancer. Results. During follow‐up 162 women and 166 men were diagnosed with colorectal cancer. Women with moderate and high stress intensity had a hazard ratio of 0.60 (95% CI: 0.37–0.98) and 0.52 (0.23–1.14) for colorectal cancer, respectively, compared to women with no stress. For colon cancer, a one‐unit increase on a seven‐point stress‐score was associated with an 11% lower incidence of the disease (HR = 0.89, 95% CI: 0.81–0.99) amongst women. There was no consistent evidence of an association between stress and colorectal cancer in men. Conclusion. Perceived stress was associated with lower risk of particularly colon cancer in women, whilst there was no clear relationship between stress and colorectal cancer in men.