Palliative care education and knowledge transfer into practice - a multicenter survey among medical students and resident physicians in Germany using a mixed-methods design.

Objective: In 2009, Palliative care was incorporated into the medical curriculum as Cross-Sectional Subject 13 (QB13) by means of the revision of the Medical Licensing Regulations for Physicians. The aim of this study was to determine the strengths and deficits of QB13 student education for palliative care in clinical practice in a multi-centre setting and to identify potential for improvement. Methods: Online questionnaires filled out by medical students during their Practical Year (PY) and resident physicians from the university hospitals in Aachen, Düsseldorf, and Cologne were descriptively analyzed using SPSS; free-text responses were categorized and quantified. Semi-structured interviews with the resident physicians (using a mixed-methods design) were analyzed through content analysis. Emerging categories were quantified. Results: Analysis of 130 fully completed questionnaires and 23 interviews revealed that participants particularly benefited from patient- and practice-oriented small-group sessions for their clinical work. Despite some university-specific differences, the PY students identified a need for training in end-of-life-care, while resident physicians saw a need for training primarily in dealing with patients and their relatives. They also reported deficits in transferability. Conclusion: QB13 should be organised in cross-university curricula and provide sufficient resources for practical-oriented small-group teaching. Based on the "unit of care", besides caring for palliative patients, dealing with patients' families should also be an education focus. To improve transferability into clinical practice, students should be actively involved in the care of palliative patients.

The last year of life for patients dying from cancer vs. non-cancer causes: a retrospective cross-sectional survey of bereaved relatives.

PURPOSE: To compare health care experiences of patients with cancer or non-cancer diseases in their last year of life. METHODS: A cross-sectional post-bereavement survey was conducted using an adapted German version of the VOICES questionnaire (VOICES-LYOL-Cologne). Differences in the reported experiences were assessed using a two-sided Pearson's chi-square test and Mann-Whitney U test. RESULTS: We collected data from 351 bereaved relatives. More than half of non-cancer patients were not informed that their disease could lead to death (p < 0.001). When this was communicated, in 46.7% of non-cancer and 64.5% of cancer patients, it was reported by the hospital doctor (p = 0.050). In all, 66.9% of non-cancer and 41.6% of cancer patients were not informed about death being imminent (p < 0.001). On average, non-cancer patients had significantly fewer transitions and hospital stays in their last year of life (p = 0.014; p = 0.008, respectively). Non-cancer patients were treated more often by general practitioners, and cancer patients were treated more often by specialists (p = 0.002; p = 0.002, respectively). A substantially lower proportion of non-cancer patients were treated by at least one member of or in the setting of general or specialized palliative care (p < 0.001). CONCLUSIONS: Non-cancer patients experience disadvantages in communication regarding their care and in access to specialized palliative care in their last year of life compared to cancer patients. Regarding the assessment of palliative care needs and the lack of communication of an incurable disease, non-cancer patients are underserved. An early identification of patients requiring palliative care is a major public health concern and should be addressed irrespective of diagnosis. TRIAL REGISTRATION: Prospectively registered by the German Clinical Trials Register (DRKS00011925, data of registration: 13.06.2017).

Oil pulling to relieve medication-induced xerostomia: A randomized, single-blind, crossover trial.

OBJECTIVES: To determine the subjective effectiveness of oilpulling on medication-induced xerostomia with regard to symptom relief, quality of life, taste, mucosal moisture and oral parameters. MATERIALS AND METHODS: In a randomized, single-blind, crossover trial in participants with medication-induced xerostomia (n = 26; mean age 64.71 (standard deviation (SD) 15.60) years), we investigated oilpulling efficacy (sunflower oil) versus mineral water after one-week use. Xerostomic burden (visual analogue scale, VAS), symptom relief and oral examinations (gingivitis index, plaque index, whole stimulated and unstimulated salivation rates) were investigated at baseline and the end of the follow-up. RESULTS: Oilpulling reduced the xerostomic burden (baseline value 6.46 (SD 1.80), decreasing to 4.93 (SD 2.97)) (p = .003), without difference between oil versus water (p = .067). Baseline values for water were 6.08 (SD 2.17) decreasing to 5.72 (SD 2.17) (p = .124). Compared to water, oil made swallowing easier (p = .031), caused a pleasant mouthfeel (p = .031) and caused less waking up at night (p = .031). Effectiveness (p = .002) and duration (p = .007) of symptom relief showed differences between products in favour of oil. CONCLUSIONS: Oil pulling alleviated the overall xerostomic burden. In the comparison between oil and water, no difference regarding symptom relief could be shown. Patients should be informed of possibilities and limitations of oilpulling as inexpensive and easy-to-obtain alternative to commercially available products for short-term symptom relief.

Immunological Effects of an Add-On Physical Exercise Therapy in Depressed Adolescents and Its Interplay with Depression Severity.

BACKGROUND: Pro-inflammatory cytokines (PICs) have gained attention in the pathophysiology and treatment of depressive disorders. At the same time, the therapeutic effect of physical activity seems to work via immunomodulatory pathways. The interventional study "Mood Vibes" analyzed the influence of exercise on depression severity (primary endpoint) in depressive adolescents; the influence of PICs on the clinical outcome was analyzed as a secondary endpoint. METHODS: Clinically diagnosed depressed adolescents (N = 64; 28.1% male; mean age = 15.9; mean BMI = 24.6) were included and participated either in Whole Body Vibration (WBV) (n = 21) or bicycle ergometer training (n = 20) in addition to treatment-as-usual (TAU). Patients in the control treatment group received TAU only (n = 23). The PICs (interleukin-6-IL-6 and tumor necrosis factor-α-TNF-α) were analyzed before intervention, after 6 weeks of training (t1), and 8 weeks post-intervention (t2). The effects of the treatment on depression severity were rated by self-rating "Depression Inventory for Children and Adolescents" (DIKJ). RESULTS: Basal IL-6 decreased in all groups from t0 to t1, but it increased again in WBV and controls at t2. TNF-α diminished in ergometer and controls from baseline to t1. PIC levels showed no correlation with depression severity at baseline. The influence on DIKJ scores over time was significant for IL-6 in the WBV group (p = 0.008). Sex had an impact on TNF-α (p < 0.001), with higher concentrations in male patients. Higher body mass index was associated with higher IL-6 concentrations over all measurement points (p < 0.001). CONCLUSIONS: The positive effects of an intensive add-on exercise therapy on adolescent depression seem to be partly influenced by immunomodulation. A small sample size and non-randomized controls are limitations of this study.

Improving regional care in the last year of life by setting up a pragmatic evidence-based Plan-Do-Study-Act cycle: results from a cross-sectional survey.

OBJECTIVES: To set up a pragmatic Plan-Do-Study-Act cycle by analysing patient experiences and determinants of satisfaction with care in the last year of life. DESIGN: Cross-sectional postbereavement survey. SETTING: Regional health services research and development structure representing all health and social care providers involved in the last year of life in Cologne, a city with 1 million inhabitants in Germany. PARTICIPANTS: 351 bereaved relatives of adult decedents, representative for age and gender, accidental and suspicious deaths excluded. RESULTS: For the majority (89%) of patients, home was the main place of care during their last year of life. Nevertheless, 91% of patients had at least one hospital admission and 42% died in hospital. Only 60% of informants reported that the decedent had been told that the disease was leading to death. Hospital physicians broke the news most often (58%), with their communication style often (30%) being rated as 'not sensitive'. Informants indicated highly positive experiences with care provided by hospices (89% 'good') and specialist palliative home care teams (87% 'good'). This proportion dropped to 41% for acute care hospitals, this rating being determined by the feeling of not being treated with respect and dignity (OR=23.80, 95% CI 7.503 to 75.498) and the impression that hospitals did not work well together with other services (OR=8.37, 95% CI 2.141 to 32.71). CONCLUSIONS: Following those data, our regional priority for action now is improvement of care in acute hospitals, with two new projects starting, first, how to recognise and communicate a limited life span, and second, how to improve care during the dying phase. Results and further improvement projects will be discussed in a working group with the city of Cologne, and repeating this survey in 2 years will be able to measure regional achievements. TRIAL REGISTRATION NUMBER: DRKS00011925.

PSA and VIM DBS efficiency in essential tremor depends on distance to the dentatorubrothalamic tract.

OBJECTIVE: To investigate the relation between deep brain stimulation (DBS) of the posterior-subthalamic-area (PSA) and the ventral-intermediate-nucleus (VIM) and the distance to the dentatorubrothalamic tract (DRTT) in essential tremor (ET). METHODS: Tremor rating scale (TRS) hemi-scores were analyzed in 13 ET patients, stimulated in both the VIM and the PSA in a randomized, crossover trial. Distances of PSA and VIM contacts to population-based DRTTs were calculated. The relationships between distance to DRTT and stimulation amplitude, as well as DBS efficiency (TRS improvement per amplitude) were investigated. RESULTS: PSA contacts were closer to the DRTT (p = 0.019) and led to a greater improvement in TRS hemi-scores (p = 0.005) than VIM contacts. Proximity to the DRTT was related to lower amplitudes (p < 0.001) and higher DBS efficiency (p = 0.017). CONCLUSIONS: Differences in tremor outcome and stimulation parameters between contacts in the PSA and the VIM can be explained by their different distance to the DRTT.

Higher incidence of perivalvular abscess determines perioperative clinical outcome in patients undergoing surgery for prosthetic valve endocarditis.

BACKGROUND: Cardiac surgery for prosthetic valve endocarditis (PVE) is associated with substantial mortality. We aimed to analyze 30-day and 1-year outcome in patients undergoing surgery for PVE and sought to identify preoperative risk factors for mortality with special regard to perivalvular infection. METHODS: We retrospectively analyzed data of 418 patients undergoing valve surgery for infective endocarditis between January 2009 and July 2018. After 1:1 propensity matching 158 patients (79 PVE/79 NVE) were analyzed with regard to postoperative 30-day and 1-year outcomes. Univariate and multivariable analyses were performed to identify potential risk factors for mortality. RESULTS: 315 patients (75.4%) underwent surgery for NVE and 103 (24.6%) for PVE. After propensity matching groups were comparable with regard to preoperative characteristics, clinical presentation and microbiological findings, except a higher incidence of perivalvular infection in patients with PVE (51.9%) compared to NVE (26.6%) (p = 0.001), longer cardiopulmonary bypass (166 [76-130] vs. 97 [71-125] min; p < 0.001) and crossclamp time (95 [71-125] vs. 68 [55-85] min; p < 0.001). Matched patients with PVE showed a 4-fold increased 30-day mortality (20.3%) in comparison with NVE patients (5.1%) (p = 0.004) and 2-fold increased 1-year mortality (PVE 29.1% vs. NVE 13.9%; p = 0.020). Multivariable analysis revealed perivalvular abscess, sepsis, preoperative AKI and PVE as independent risk factors for mortality. Patients with perivalvular abscess had a significantly higher 30-day mortality (17.7%) compared to patients without perivalvular abscess (8.0%) (p = 0.003) and a higher rate of perioperative complications (need for postoperative pacemaker implantation, postoperative cerebrovascular events, postoperative AKI). However, perivalvular abscess did not influence 1-year mortality (20.9% vs. 22.3%; p = 0.806), or long-term complications such as readmission rate or relapse of IE. CONCLUSIONS: Patients undergoing surgery for PVE had a significantly higher 30-day and 1-year mortality compared to NVE. After propensity-matching 30-day mortality was still 4-fold increased in PVE compared to NVE. Patients with perivalvular abscess showed a significantly higher 30-day mortality and perioperative complications, whereas perivalvular abscess seems to have no relevant impact on 1-year mortality, the rate of readmission or relapse of IE.

Effect of early palliative care for patients with glioblastoma (EPCOG): a randomised phase III clinical trial protocol.

​INTRODUCTION: Randomised controlled trials (RCTs) have shown a positive effect of early integration of palliative care (EIPC) in various advanced cancer entities regarding patients' quality of life (QoL), survival, mood, caregiver burden and reduction of aggressiveness of treatment near the end of life. However, RCTs investigating the positive effect of EIPC for patients suffering from glioblastoma multiforme (GBM) are lacking. After modelling work identifying the specific needs of GBM patients and their caregivers, the aim of this study is to investigate the impact of EIPC in this particular patient group. ​METHODS AND ANALYSIS: The recruitment period of this multicenter RCT started in May 2019. GBM patients (n=214) and their caregivers will be randomly assigned to either the intervention group (receiving proactive EIPC on a monthly basis) or the control group (receiving treatment according to international standards and additional, regular assessment of QoL ('optimised' standard care)).The primary outcome is QoL assessed by subscales of the Functional Assessment of Cancer Therapy for brain tumour (FACT-Br) from baseline to 6 months of treatment. Secondary outcomes are changes in QoL after 12 (end of intervention), 18 and 24 months (end of follow-up), the full FACT-Br scale, patients' palliative care needs, depression/anxiety, cognitive impairment, caregiver burden, healthcare use, cost-effectiveness and overall survival. ​ETHICS AND DISSEMINATION: The study will be conducted in accordance with the Declaration of Helsinki and has been approved by the local ethics committees of the University Clinics of Cologne, Aachen, Bonn, Freiburg and Munich (LMU). Results of the trial will be submitted for publication in a peer-reviewed, open access journal and disseminated through presentations at conferences. TRIAL REGISTRATION NUMBER: German Register for Clinical Studies (DRKS) (DRKS00016066); Pre-results.

The Role of Previous Therapies and Sites of Metastasis as Influencing Factors on Discordance of ER, PR and HER2 Status Between Primary and Metastasized Breast Cancer.

BACKGROUND/AIM: The aim of the present study was to analyze metastasized breast cancer (BC) patients with regard to the discordance of estrogen receptor (ER), progesterone receptor (PR) and human epidermal growth factor receptor 2 (HER2). We especially aimed to analyze the association between the change of tumor biology and previous treatment or metastatic sites. PATIENTS AND METHODS: Patients with metastasized BC who were treated at the Department of Gynecology/Breast Center of the University Hospital of Cologne were analyzed. RESULTS: Loss of HER2 occurred more frequently in lymph node metastases that were not in the axillary region (p=0.026). Letrozole showed a significant correlation with loss of ER and/or PR (p=0.041). Improved overall survival and post-metastasis survival were noticed with a gain of HER2 (p=0.044 and p=0.009, respectively) and concordant positive ER and PR status (p=0.002 and p=0.001, respectively). CONCLUSION: The discordance of receptors and the dependence of BC on therapies as well as metastatic sites stresses the necessity of early sample taking to offer patients suitable therapy options.

Clinical impact of PD-L1 and PD-1 expression in squamous cell cancer of the vulva.

PURPOSE: Squamous cell carcinoma of the vulva (SQCV) is the fifth most common cancer in women and accounts for about 5% of all genital cancers in women. The PD-L1 signaling pathway is activated in many malignant neoplasms and its blockade enhances anti-cancer immunity. The aim of our study was to examine the protein expression of PD-L1 and PD-1 in squamous cell cancer of the vulva, its correlations with clinicopathologic features and prognostic value. METHODS: Patients with SQCV treated in one institution were used for the analyses. PD-L1 immunohistochemistry was performed on 4 µm-thick section of the respective FFPE tissue blocks using the 28-8 antibody. PD-L1 scoring was performed separately for tumour cells (TC) and tumour associated immune cells. DNA was extracted to determine HPV status. Kaplan-Meier estimates for disease-free-survival and overall-survival were calculated and compared by log-rank test. RESULTS: PD-L1 expression in tumour cells could be observed in 32.9% of the patients. The expression of PD-L1 in peritumoural immune cells was confirmed in 91.4% of the patients. A significant correlation between PD-L1 expression in tumour cells and tumour stage was detected (p = 0.007). PD-L1 expression was independent from HPV status. Using the log-rank test we could not prove any significant differences in disease-free survival (p = 0.434) and overall survival (p = 0.858). Regression analysis showed that nodal status is a predictive factor of survival (p < 0.001). CONCLUSION: The present study showed that a relevant amount of patients with squamous cell cancer of the vulva express PD-L1 in both, tumour cells and tumour-associated immune cells. Furthermore, the significant correlation of PD-L1 expression in TCs with tumour stage indicated the clinical impact of PD-L1 expression during tumour development. These data indicate that SQCV might be amenable to immune checkpoint-inhibition and constitute a rational for the future clinical trials.

Severity of Presentation, Not Sex, Increases Risk of Surgery for Infective Endocarditis.

BACKGROUND: Cardiac surgery for infective endocarditis (IE) is associated with substantial short- and long-term mortality, and female sex seems to be associated with even worse outcomes. The aim of our study was to analyze the impact of sex on 30-day and long-term mortality and to identify sex-related risk factors in IE patients requiring cardiac surgery. METHODS: Relevant clinical data of all consecutive 305 patients undergoing cardiac surgery for IE between 2009 and 2016 were extracted from our institutional database and retrospectively analyzed. Infective endocarditis was defined according to the recent modified Duke criteria and surgery indicated in compliance with current European Society of Cardiology guidelines. Sex-related postoperative outcomes including 30-day and 1-year mortality were recorded. Univariate and multivariable analysis was performed to identify potential sex-dependent risk factors. RESULTS: In all, 229 male patients (75.1%) and 76 female patients (24.9%) underwent surgery for IE. Female patients showed significantly more mitral valve infection (52.6% versus 33.6%, p = 0.003), and Staphylococcus aureus as causative microorganisms was diagnosed in 44.7% of female patients compared with 24.5% of male patients (p = 0.001). Female sex was associated with a higher 30-day mortality (18.4% versus 8.3%, p = 0.014) and 1-year mortality (46.1% versus 27.1%, p = 0.002). Multivariable analysis revealed not female sex, but European System for Cardiac Operative Risk Evaluation II score, reexploration for bleeding, and postoperative acute kidney injury as independent risk factors for 30-day mortality and preoperative dialysis for 1-year mortality, respectively. CONCLUSIONS: In this study, female sex was associated with more severe manifestations of IE and significantly higher 30-day and 1-year mortality. After multivariable analysis, not female sex, but the underlying comorbidities seem to determine clinical outcomes.

DBS of the PSA and the VIM in essential tremor: A randomized, double-blind, crossover trial.

OBJECTIVE: To evaluate deep brain stimulation (DBS) of the posterior subthalamic area (PSA) in essential tremor (ET) and compare it to the ventral intermediate nucleus of the thalamus (VIM) in terms of stimulation efficacy, efficiency, and side effects. METHODS: DBS leads were implanted such that contacts were placed in the VIM, on the intercommissural line, and in the PSA. Thirteen patients with ET entered a randomized, double-blind crossover phase and completed a 1-year follow-up. RESULTS: PSA-DBS significantly reduced tremor severity and improved quality of life. There were no relevant differences in quality and frequency of stimulation side effects between VIM and PSA, with a tendency toward greater tremor improvement with PSA stimulation. Clinical benefit was achieved at significantly lower stimulation amplitudes in the PSA. The majority of patients remained with PSA-DBS after 1 year. CONCLUSION: In accordance with previous retrospective investigations, our prospective data suggest that PSA-DBS is at least equally effective as but possibly more efficient than VIM-DBS. CLASSIFICATION OF EVIDENCE: This study provides Class I evidence that for patients with essential tremor, PSA-DBS is not significantly different from VIM-DBS in suppressing tremor, but clinical benefit from PSA-DBS is attained at lower stimulation amplitudes.

Effects of Kyusho Jitsu on Physical Activity-levels and Quality of Life in Breast Cancer Patients.

BACKGROUND/AIM: Breast cancer survivors often report a decrease in physical activity levels and quality of life. The aim of this study was to explore whether a "Kyusho Jitsu" martial arts intervention is feasible and can improve general well-being and physical activity levels in breast cancer survivors. MATERIALS AND METHODS: Breast cancer survivors (N=51) were randomly assigned to the intervention or control group. The intervention group participated in a 24-week Kyusho Jitsu intervention. Both groups were assessed at baseline, 3, and 6 months. RESULTS: Analysis of original data showed several significant improvements in favor of the intervention group, but also some of the control group. Sensitivity analysis supports these findings. No adverse events were observed. CONCLUSION: To our knowledge this is the first study showing that a holistic Kyusho Jitsu martial arts intervention can be feasible and effective for breast cancer survivors.

The DEsire to DIe in Palliative care: Optimization of Management (DEDIPOM) - a study protocol.

BACKGROUND: A desire to die (DD) is frequent in palliative care (PC). However, uncertainty remains as to the appropriate therapeutic response. (Proactive) discussion of DD is not usually part of standard care. To support health practitioners' (HPs) reactions to a patient's DD, a training program has been developed, piloted and evaluated. Within this framework, a first draft of a semi-structured clinical interview schedule with prompts (CISP) has been developed, including recommendations for action to support HPs' self-confidence. The aim of this study is the further development of the CISP to support routine exploration of death and dying distress and proactive addressing of a DD. METHODS: This observatory, prospective health services study comprises a three step study design: 1. Revision of the CISP and consensus finding based on semi-structured interviews with patients and a Delphi process with (inter-)national experts, patient representatives and relatives; 2. Increasing confidence in HPs through a 2 day-training program using the consented CISP; 3. A formative quantitative evaluation of conversations between HPs and patients (300 palliative patients at three time points) and a qualitative evaluation based on interview triads of patients, relatives and HPs. The evaluation of conversations will include patient-oriented outcomes, including perceived relationships with HPs and death and dying distress. We will also consider aspects of social inequality and gender. DISCUSSION: The intervention can provide a framework for open discussion of DD and a basis for enhancing a trustful HP-patient relationship in which such difficult topics can be addressed. The benefits of this study will include (a) the creation of the first consented semi-structured approach to identify and address DD and to respond therapeutically, (b) the multi-professional enhancement of confidence in dealing with patients' DD and an intervention that can flexibly be integrated into other training and education programs and (c) an evaluation of effects of this intervention on patients, relatives and HPs, with attention to social inequality and gender. TRIAL REGISTRATION: The study is registered in the German Clinical Trials Register ( DRKS00012988 ; registration date: 27.9.2017) and in the Health Services Research Database ( VfD_DEDIPOM_17_003889 ; registration date: 14.9.2017).

A Retrospective Analysis of Ki-67 Index and its Prognostic Significance in Over 800 Primary Breast Cancer Cases.

BACKGROUND/AIM: The Ki-67 index is chiefly important for distinguishing between luminal A and luminal B human epidermal growth factor receptor 2 (HER2neu)-negative breast cancer subtypes. However, its ability to predict response to chemotherapy is uncertain. PATIENTS AND METHODS: Patients treated for primary breast cancer at the University Hospital of Cologne were identified. Immunohistochemistry for Ki-67 detection was performed according to standard protocols. Kaplan-Meier survival curves were calculated and compared using the log-rank test. RESULTS: Patients with low Ki-67 index had a significantly better disease-free-survival (DFS) than patients with high Ki-67 index (hazard ratio=2.85; 95% confidence interval=1.45-5.59; p=0.002). A significant influence on DFS was demonstrated (hazard ratio(HR)=1.02; confidence interval(CI)=1.00-1.04; p=0.048) within the subgroup of hormone receptor-positive and HER2neu-negative patients, but not within the subgroup of those with luminal B/HER2neu-negative tumors (DFS: p=0.801; overall-survival: p=0.379). CONCLUSION: The Ki-67 index has a prognostic impact on DFS in patients with hormone receptor-positive and HER2neu-negative tumors. The strict cut-off value was not suitable for distinguishing between high- and low-risk patients and their response to adjuvant chemotherapy.

Interprofessional Medication Management in Patients With Multiple Morbidities.

BACKGROUND: Medication reviews and medication management are being used more and more around the world to improve medication safety. Both of these tools were originally conceived as pharmaceutical care activities and have recently been developed into interdisciplinary approaches. We studied the efficacy of interprofessional medication management for multimorbid patients that takes their medical conditions, but also their general living situation into account. METHODS: A comprehensive medication management was performed, which involved the collection of information on the drugs each patient took, the way they were stored, the patient's drug intake and handling, and any problems that arose with pharmacotherapy. The interventional approach was evaluated over a period of 15 months in a cluster-randomized controlled trial with a stepped wedge design. The primary endpoint was the quality of pharmacotherapy, as assessed with the Medication Appropriateness Index (MAI). A mixed model was used to analyze efficacy. RESULTS: 162 patients were enrolled in the study; 142 were included in the intention-to-treat analysis (53.3% women, mean age 76.8 ± 6.3 years). The mean total MAI score decreased significantly (p ≤ 0.001) from the control phase (29.21, 95% CI [26.09; 32.33]) to the intervention phase (22.27 [19.00; 25.54]), with an effect strength (Cohen's d) of -0.24 [-0.36; -0.13]. The number of drug-related problems declined as well. CONCLUSION: In this study, interprofessional collaboration increased medication safety. Working across disciplinary boundaries allowed for a decrease in drugrelated problems and brought up aspects outside the purview of the primary care physician.

Predictors of sentinel lymph node metastases in breast cancer-radioactivity and Ki-67.

OBJECTIVES: Since the introduction of the sentinel node technique for breast cancer in the 1990s patient's morbidity was reduced. Tracer uptake is known to be dependent from lymph node integrity and activity of macrophages. The aim of this study was to assess whether radioactivity of the tracer can predict sentinel lymph node metastases. Furthermore, a potential association with Ki-67 index was examined. Non-invasive prediction of lymph node metastases could lead to a further decrease of morbidity. METHODS: We retrospectively analyzed patients with primary breast cancer who underwent surgery at the Department of Obstetrics and Gynecology in the University Hospital of Cologne between 2012 and 2013. Injection of radioactive tracer was done a day before surgery in the department of Nuclear Medicine. Clinical data and radioactivity of the sentinel node measured the day before and intraoperatively were abstracted from patient's files. RESULTS: Of 246 patients, 64 patients had at least one, five patients had two and one patient had three positive sentinel lymph nodes. Occurrence of sentinel lymph node metastases was not associated with preoperative tracer activity (p = 0,319), intraoperative tracer activity of first sentinel node (p = 0,086) or with loss of tracer activity until operation (p = 0,909). There was no correlation between preoperative Ki-67 index and occurrence of lymph node metastases (p = 0,403). CONCLUSION: In our cohort, there was no correlation between radioactivity and sentinel node metastases. Tracer uptake might not only be influenced by lymph node metastases and does not predict metastatic lymph node involvement.

Removal of Soluble Fms-Like Tyrosine Kinase-1 by Dextran Sulfate Apheresis in Preeclampsia.

Preeclampsia is a devastating complication of pregnancy. Soluble Fms-like tyrosine kinase-1 (sFlt-1) is an antiangiogenic protein believed to mediate the signs and symptoms of preeclampsia. We conducted an open pilot study to evaluate the safety and potential efficacy of therapeutic apheresis with a plasma-specific dextran sulfate column to remove circulating sFlt-1 in 11 pregnant women (20-38 years of age) with very preterm preeclampsia (23-32 weeks of gestation, systolic BP ≥140 mmHg or diastolic BP ≥90 mmHg, new onset protein/creatinine ratio >0.30 g/g, and sFlt-1/placental growth factor ratio >85). We evaluated the extent of sFlt-1 removal, proteinuria reduction, pregnancy continuation, and neonatal and fetal safety of apheresis after one (n=6), two (n=4), or three (n=1) apheresis treatments. Mean sFlt-1 levels were reduced by 18% (range 7%-28%) with concomitant reductions of 44% in protein/creatinine ratios. Pregnancy continued for 8 days (range 2-11) and 15 days (range 11-21) in women treated once and multiple times, respectively, compared with 3 days (range 0-14) in untreated contemporaneous preeclampsia controls (n=22). Transient maternal BP reduction during apheresis was managed by withholding pre-apheresis antihypertensive therapy, saline prehydration, and reducing blood flow through the apheresis column. Compared with infants born prematurely to untreated women with and without preeclampsia (n=22 per group), no adverse effects of apheresis were observed. In conclusion, therapeutic apheresis reduced circulating sFlt-1 and proteinuria in women with very preterm preeclampsia and appeared to prolong pregnancy without major adverse maternal or fetal consequences. A controlled trial is warranted to confirm these findings.

Effect evaluation of an interprofessional medication therapy management approach for multimorbid patients in primary care: a cluster-randomized controlled trial in community care (WestGem study protocol).

BACKGROUND: Pharmaceutical practice worldwide is developing towards patient care. Medication Review (MR) and Medication Therapy Management (MTM) are evolving as the most prominent services in pharmaceutical care and have a strong potential to provide a large benefit for patients and society. MTMs can only be performed in an interprofessional, collaborative setting. Several international studies have explored the effects of a MTM on the quality of therapy and costs. For Germany the data is still deficient. This study aims to provide data on the effects of an interprofessional MTM regarding quality of therapy, quality of life, costs and cost-effectiveness. METHOD/DESIGN: The study is designed as a cluster-randomized controlled trial in primary care, involving 12 outpatient clinics (clusters) and 165 patients. Primary care units are allocated to interventions using a Stepped Wedge Design. All units are initially assigned to the control group. After a 6 month observation period, general practitioners (GP) are randomly allocated to one of three groups and the interprofessional medication therapy management approach is implemented sequentially per each group with a lag of 3 months between. The primary outcome is the change in the quality of therapy measured by the MAI (Medication Appropriateness Index). Secondary outcomes include changes in the number of drug related problems, medication complexity, changes in drug-adherence, changes in health-status and function, quality of life, direct costs and the incremental cost-effectiveness ratio. The acceptance of the interprofessional Medication Therapy Management approach is assessed by qualitative methods. DISCUSSION: The patient interview and brown bag review are activities, typically provided by the pharmacist. In this trial the patient is blinded to the pharmacist. The strength of having the patient blinded to the pharmacists is to exclude skepticism of the patient toward unknown pharmacies, which might be a major confounder in a regional and community setting. A weakness is that some patient related data might reach the pharmacists in a way, which might differ from self-acquired data. TRIAL REGISTRATION: Current controlled trials ISRCTN41595373 .