The effect of regional transmural agreements on the information transfer of frail older patients.

INTRODUCTION: Frail older patients are at risk for many complications when admitted to the hospital. Multidisciplinary regional transmural agreements (RTA) in which guidelines were set concerning the information transfer of frail older patients might improve outcomes. We aim to investigate the effect of implementation of the RTA on the completeness of the information transfer of frail older patients when admitted to and discharged from the hospital. METHODS: This is a retrospective cohort study in which we collected data from 400 randomly selected hospitalized frail older patients (70+) before the implementation of the RTA, January through March 2021, and after, October through December 2021. The cohort was split up into four groups, which determined what correspondence would be checked (referral letter by General Practitioner (GP) and three groups of 'hospital letters': ED letter upon admittance, clinical discharge letter to the elderly care physician and clinical discharge letter to the GP. We assessed for mention of frailty, a medication list and mention of resuscitation orders. RESULTS: In the period before implementation the mean age of patients was 82.6 years (SD 7.4) and 101 were female (50.5%), after implementation mean age was 82.3 (SD 6.9) and 112 were female (56.0%). Frailty was mentioned in hospital letters in 12.7% before and 15.3% after implementation (p = 0.09). More GP referral letters were present after implementation (32.0% vs. 54.0%, p = 0.03), however frailty was mentioned only in 12.5% before and 7.4% after (p = 0.58). There was a good handover of medication lists from the hospital (89.3% before, 94% after, p = 0.20) and even better from the GP (93.8% before, 100% after, p = 0.19). Resuscitation orders were mentioned in 59.3% of letters from the hospital before implementation and 57.3% after (p = 0.77), which is higher than in the referral letters (18.8% before and 22.2% after (p = 0.91). DISCUSSION: The implementation of RTA improved the number of GP referral letters present; however, it did not lead to other significant improvements in communication between the hospital and the GP's. Frailty and resuscitation orders are still frequently not mentioned in the reports. After a successful reimplementation, the improvements of outcomes could be investigated.

Patient experience from a doctor's perspective: A case report concerning treatment, fracture healing and rehabilitation of multiple complex injuries due to a high energy motor vehicle collision.

A 35-year old healthy male trauma surgery chief resident, suffered a high-speed motor vehicle collision. The patient sustained the following injuries: a Gustilo-Anderson grade 2 open comminuted intra-articular fracture of the left distal femur (AO 33C3.3), a Hawkins 1A neck fracture of the right talus (AO 81.2A), an undisplaced Lisfranc injury of the right foot comprising avulsion fractures at the base of the 1st, 2nd and 5th metatarsal as well as the cuboid bone suggesting ligament injury and 2nd to 5th carpometacarpal dislocations of the right (non-dominant) hand with comminuted fractures of the capitate, hamate, trapezoid and the base of the fifth metacarpal bone. A staged-treatment approach ensued. An external fixator (ex-fix) was placed over the left knee, followed by definitive fixation of the distal femoral fracture using a Qwix screw, Non-Contact Bridging (NCB) plate and Locking Compression Plate (LCP). An ex-fix was placed over the right wrist, followed by open reduction and k-wire fixation. The talar fracture of the right foot was treated with a single lag screw and the Lisfranc injury was treated non-operatively with four weeks of non-weight bearing cast immobilization. An intensive clinical rehabilitation program was started, including early use of Continuous Passive Motion (CPM), daily non-weightbearing swimming pool exercises, hand, physical and recreational therapy. One year after the injury the patient was rehabilitated and resumed his surgical residency. Two years after the injury, limited flexion and pain in the left leg remains, possibly related to partial union of the femoral fracture. Range of motion (ROM) of the right ankle and wrist remains limited, not causing significant functional impairment. Lessons learned from a patient experience combined with detailed descriptions of injuries, rehabilitation and long term outcomes can be used as a reference for treating patients with comparable injuries.

Providing care for older adults in the Emergency Department: expert clinical recommendations from the European Task Force on Geriatric Emergency Medicine.

PURPOSE: Despite the rapidly expanding knowledge in the field of Geriatric Emergency Medicine in Europe, widespread implementation of change is still lacking. Many opportunities in everyday clinical care are missed to improve care for this susceptible and growing patient group. The aim was to develop expert clinical recommendations on Geriatric Emergency Medicine to be disseminated across Europe. METHODS: A group of multi-disciplinary experts in the field of Geriatric Emergency Medicine in Europe was assembled. Using a modified Delphi procedure, a prioritized list of topics related to Geriatric Emergency Medicine was created. Next, a multi-disciplinary group of nurses, geriatricians and emergency physicians performed a review of recent guidelines and literature to create recommendations. These recommendations were voted upon by a group of experts and placed on visually attractive posters. The expert group identified the following eight subject areas to develop expert recommendations on: Comprehensive Geriatric Assessment in the Emergency Department (ED), age/frailty adjusted risk stratification, delirium and cognitive impairment, medication reviews in the ED for older adults, family involvement, ED environment, silver trauma, end of life care in the acute setting. RESULTS: Eight posters with expert clinical recommendations on the most important topics in Geriatric Emergency Medicine are now available through https://posters.geriemeurope.eu/ . CONCLUSION: Expert clinical recommendations for Geriatric Emergency Medicine may help to improve care for older patients in the Emergency Department and are ready for dissemination across Europe.

Mortality risk for different presenting complaints amongst older patients assessed with the Manchester triage system.

PURPOSE: Older people often present to the Emergency Department with nonspecific complaints. We aimed (1) to examine characteristics of older patients presenting to the ED triaged with the presentational flowchart 'unwell adult' of the Manchester triage system (MTS) and (2) to assess the different mortality and admission rates among triage categories. METHODS: Retrospective cohort study including all consecutive patients aged 70 years and older who visited the ED of a tertiary care hospital in the Netherlands during a 1-year period. The primary outcome was 30-day mortality. Secondary outcomes were 7-day mortality, hospital admission and ED length of stay. RESULTS: 4255 patients were included in this study. Mean age was 78 years (IQR 73.9-83.4) and 2098 were male (49.3%). The MTS presentational flowchart 'unwell adult' was the most commonly used flowchart (n = 815, 19.3%). After the infrequent flowchart 'major trauma' (n = 9, 13.8%), 'unwell adult' had the highest 30-day mortality (n = 88, 10.8%). When compared to all other flowcharts, patients assigned as 'unwell adult' have significantly higher 30-day mortality rates (OR 1.89 (95%CI 1.46-2.46), p = < 0.001), also when adjusted for age, gender and triage priority (OR 1.75 (95%CI 1.32-2.31), p = < 0.001). Patients from the 'unwell adult' flowchart had the highest hospital admission rate (n = 540, 66.3%), and had among the longest ED length of stay. CONCLUSIONS: Older ED patients are most commonly assigned the presentational flowchart 'unwell adult' when using the MTS. Patients in this category have the highest non-trauma mortality and highest hospital admission rates when compared to other presenting complaints.

Prediction admission in the older population in the Emergency Department: the CLEARED tool.

BACKGROUND: Length of stay (LOS) in the Emergency Department (ED) is correlated with an extended in-hospital LOS and may even increase 30-day mortality. Older patients represent a growing population in the ED and they are especially at risk of adverse outcomes. Screening tools that adequately predict admission could help reduce waiting times in the ED and reduce time to treatment. We aimed to develop and validate a clinical prediction tool for admission, applicable to the aged patient population in the ED. METHODS: Data from 7,606 ED visits of patients aged 70 years and older between 2012 and 2014 were used to develop the CLEARED tool. Model performance was assessed with discrimination using logistic regression and calibration. The model was internally validated by bootstrap resampling in Erasmus Medical Center and externally validated at two other hospitals, Medisch Spectrum Twente (MST) and Leiden University Medical Centre (LUMC). RESULTS: CLEARED contains 10 predictors: body temperature, heart rate, diastolic blood pressure, systolic blood pressure, oxygen saturation, respiratory rate, referral status, the Manchester Triage System category, and the need for laboratory or radiology testing. The internally validated area under the curve (AUC) was 0.766 (95% CI [0.759;0.781]). External validation in MST showed an AUC of 0.797 and in LUMC, an AUC of 0.725. CONCLUSIONS: The developed CLEARED tool reliably predicts admission in elderly patients visiting the ED. It is a promising prompt, although further research is needed to implement the tool and to investigate the benefits in terms of reduction of crowding and LOS in the ED.

The APOP screener and clinical outcomes in older hospitalised internal medicine patients.

BACKGROUND: Acutely hospitalised older patients with indications related to internal medicine have high risks of adverse outcomes. We investigated whether risk stratification using the Acutely Presenting Older Patient (APOP) screening tool associates with clinical outcomes in this patient group. METHODS: Patients aged ≥ 70 years who visited the Emergency Department (ED) and were acutely hospitalised for internal medicine were followed prospectively. The APOP screener assesses demographics, physical and cognitive function at ED presentation, and predicts 3-month mortality and functional decline in the older ED population. Patients with a predicted risk ≥ 45% were considered 'high risk'. Clinical outcome was hospital length of stay (LOS), and adverse outcomes were mortality and functional decline, 3 and 12 months after hospitalisation. RESULTS: We included 319 patients, with a median age of 80 (IQR 74-85) years, of whom 94 (29.5%) were categorised as 'high risk' by the APOP screener. These patients had a longer hospital LOS compared to 'low risk' patients 5 (IQR 3-10) vs. 3 (IQR 1-7) days, respectively; p = 0.006). At 3 months, adverse outcomes were more frequent in 'high risk' patients compared to 'low risk' patients (59.6% vs. 34.7%, respectively; p < 0.001). At 12 months, adverse outcomes (67.0% vs. 46.2%, respectively; p = 0.001) and mortality (48.9% vs. 28.0%, respectively; p < 0.001) were greater in 'high risk' compared to 'low risk' patients. CONCLUSION: The APOP screener identifies acutely hospitalised internal medicine patients at high risk for poor short and long-term outcomes. Early risk stratification at admission could aid in individualised treatment decisions to optimise outcomes for older patients.

Vaccine-Hesitant and Vaccine-Refusing Parents' Reflections on the Way Parenthood Changed Their Attitudes to Vaccination.

Having children compels parents to examine their vaccine beliefs, particularly if they are vaccine-hesitant or refuse all vaccines. Presently, little is known about the specific ways in which having children influences the vaccine beliefs of parents. This research examined how having children changed the attitudes of Australian vaccine-hesitant and vaccine-refusing parents towards childhood vaccination. We asked 904 Australian parents who believed that having children changed their attitudes to vaccination to describe these changes. Parents' responses were inductively, iteratively coded and thematically analysed. Themes were compared between parents who believed all vaccines should be refused, parents with varying degrees of vaccine hesitancy, and parents who were fully vaccine-accepting. Low numbers of responses from fully vaccine-accepting parents meant that this paper focused on mostly vaccine-hesitant and vaccine-refusing vaccine parents. Five themes were identified. Having children prompted all parents to learn about vaccine choices. Hesitant and refusing parents' interpreted vaccine choices through a lens of distrust of pharmaceutical companies and regulatory bodies overseeing vaccine safety. The distrust fuelled parents' fears about vaccination risks, such as side effects. Parents became concerned about the scheduled timing of vaccinations, particularly of the Hepatitis B vaccine. Parents among the three groups that believed some or all vaccines should be refused reported that a vaccine permanently injured their child. This research contributes to understanding how having children affects the vaccine attitudes among vaccine-hesitant and vaccine-refusing parents. Greater support for parents with negative vaccination experiences may prevent hesitant attitudes. The vaccination schedule needs to be communicated to parents better.

The mad leading the blind: Perceptions of the vaccine-refusal movement among Australians who support vaccination.

BACKGROUND: Vaccine refusal is shaped by the social ecology in which it occurs. How people who refuse vaccines are communicated to and treated may affect the nature and strength of their negative vaccine beliefs, and their responsiveness to health promotion messages. Yet little is known about how people who refuse vaccines are perceived by the public. Our research examined perceptions among pro-vaccine Australians of the vaccine-refusal movement. METHODS: Descriptions of the vaccine-refusal movement by 2666 pro-vaccine Australians were analysed using thematic discourse analysis. Descriptive themes were identified via inductive, iterative coding. Discourse analysis techniques were then used to interpret latent beliefs about the vaccine-refusal movement. RESULTS: Participants had negative and stigmatising perceptions of the vaccine-refusal movement. They believed the movement is dangerous, misinformed, and comprised of charlatans and fools who are unintelligent, selfish, overly emotional, conspiratorial and scientifically illiterate. Discursive analysis showed that these perceptions were underpinned by beliefs that people would have to be defective in some way to believe anti-vaccine rhetoric. Furthermore, perceptions were underpinned by beliefs that the movement spreads not only disease, but also dangerous ideas that were seen to attack the social order, institutions, values and reason. Participants' intensely-negative views related to their inability to imagine why someone would refuse vaccines. CONCLUSIONS: This research provides a focused, qualitative account of public perceptions of the vaccine-refusal movement. The findings are concerning: stigma towards vaccine-refusing people may adversely affect their wellbeing and entrench their negative vaccine beliefs. The research suggests that more compassionate, nuanced discussion of vaccine refusal in the public sphere is needed. It also supports the need to systematically examine public attitudes towards vaccine refusal as a determinant of vaccine confidence.

Optimization of the APOP screener to predict functional decline or mortality in older emergency department patients: Cross-validation in four prospective cohorts.

INTRODUCTION: Many screening instruments to predict adverse health outcomes in older patients visiting the emergency department (ED) have been developed, but successful implementation has been hampered because they are insufficiently validated or not tailored for the intended use of everyday clinical practice. The present study aims to refine and validate an existing screening instrument (the APOP screener) to predict 90-day functional decline or mortality in older ED patients. METHODS: Consecutive older patients (≥70 years) visiting the EDs of four hospitals were included and prospectively followed. First, an expert panel used predefined criteria to decide which independent predictors (including demographics, illness severity and geriatric parameters) were suitable for refinement of the model predicting functional decline or mortality after 90 days. Second, the model was cross-validated in all four hospitals and predictive performance was assessed. Additionally, a pilot study among triage nurses experiences and clinical usability of the APOP screener was conducted. RESULTS: In total 2629 older patients were included, with a median age of 79 years (IQR 74-84). After 90 days 805 patients (30.6%) experienced functional decline or mortality. The refined prediction model included age, gender, way of arrival, need of regular help, need help in bathing/showering, hospitalization the prior six months and impaired cognition. Calibration was good and cross-validation was successful with a pooled area under the curve of 0.71 (0.69-0.73). In the top 20% patients predicted to be at highest risk in total 58% (95%CI 54%-62%) experienced functional decline or mortality. Triage nurses found the screener well suited for clinical use, with room for improvement. CONCLUSION: In conclusion, optimization of the APOP screener resulted in a short and more simplified screener, which adequately identifies older ED patients at highest risk for functional decline or mortality. The findings of the pilot study were promising for clinical use.

Impaired cognition is associated with adverse outcome in older patients in the Emergency Department; the Acutely Presenting Older Patients (APOP) study.

Objective: to investigate whether cognitive impairment, measured early after Emergency Department (ED) arrival and irrespective of its cause, is independently associated with functional decline or mortality after 3 and 12 months in older ED patients. Design and setting: a prospective multi-centre cohort study in all Acutely Presenting Older Patients visiting the Emergency Department (APOP study) of three hospitals in the Netherlands. Participants: 2,130 patients, ≥70 years. Measurements: data on demographics, disease severity and geriatric characteristics were collected during the first hour of the ED visit. Cognition was measured using the 6-Item-Cognitive-Impairment-Test ('6CIT'). Cognitive impairment was defined as 6CIT ≥11, self-reported dementia or the inability to perform the cognition test. The composite adverse outcome after 3 and 12 months was defined as a 1-point decrease in Katz Activities of Daily Living (ADL), new institutionalisation or mortality. Multivariable regression analysis was used to assess whether cognitive impairment independently associates with adverse outcome. Results: of 2,130 included patients, 588 (27.6%) had cognitive impairment at baseline and 654 patients (30.7%) suffered from adverse outcome after 3 months. Cognitive impairment associated with increased risk for adverse outcome (adjusted odds ratio (OR) 1.72, 95%CI 1.37-2.17). After 12 months, 787 patients (36.9%) suffered from adverse outcome. Again, cognitive impairment independently associated with increased risk for adverse outcome (adjusted OR 1.89, 95%CI 1.46-2.46). ORs were similar for patients who were discharged home versus hospitalised patients. Conclusion: cognitive impairment measured during the early stages of ED visit, irrespective of the cause, is independently associated with adverse outcome after 3 and 12 months in older patients.

Optimising the ISAR-HP to screen efficiently for functional decline in older patients.

INTRODUCTION: The Identification of Seniors At Risk-Hospitalised Patients (ISAR-HP) has recently been included in guidelines as a frailty indicator to identify patients for comprehensive geriatric assessment. Previous studies showed that the conventional cut-off score incorrectly classifies a high percentage of patients as high risk. We aimed to optimise the predictive value of ISAR-HP by using different cut-offs in older acutely hospitalised patients. METHODS: A prospective follow-up study was performed in two Dutch hospitals. Acutely hospitalised patients aged ≥ 70 years were included. Demographics, illness severity parameters, geriatric measurements and the ISAR-HP scores were obtained at baseline. The primary outcome was a combined end point of functional decline or mortality during 90-day follow-up. RESULTS: In total 765 acutely hospitalised older patients were included, with a median age of 79 years, of whom 276 (36.1%) experienced functional decline or mortality. The conventional ISAR-HP cut-off of ≥ 2 assigned 432/765 patients (56.5%) as high risk, with a positive predictive value (PPV) of 0.49 (95%CI 0.45-0.54) and a negative predictive value of 0.81 (95%CI 0.76-0.85). Thus, 51% of those whom the ISAR-HP denoted as high risk did not experience the outcome of interest. Raising the cut-off to ≥ 4 assigned 205/765 patients (26.8%) as high risk, with a marginally increased PPV to 0.55 (95%CI 0.48-0.62). CONCLUSION: The ISAR-HP with the conventional cut-off of ≥ 2 incorrectly identifies a large group of patients at high risk for functional decline or mortality and raising the cut-off to 4 only marginally improved performance. Caution is warranted to ensure efficient screening and follow-up interventions.

Use of antiretroviral treatment among people living with HIV in Australia between 1997 and 2012.

Current international targets aim for 90% of people diagnosed with HIV to be on antiretroviral treatment (ART). This paper aims to identify sociodemographic and attitudinal factors associated with ART non-use over time in three samples of Australian people living with HIV (PLHIV). Data for this paper were derived from an Australian cross-sectional survey of PLHIV that was repeated at three different time points: 1997, 2003, and 2012. There were approximately 1000 respondents to each survey (n = 3042 in total). The survey included approximately 250 items related broadly to health and well-being, ART use, and attitudes towards ART use. Univariate and multivariate logistic regression analyses were used. While the proportion of participants using ART increased between 1997 and 2012 (78.8-87.6%, p < .001), there was a decrease between 1997 and 2003 to 70.6% (p < .001). Factors linked to ART non-use remained steady over those 15 years. In all cohorts, people less likely to be using ART were younger and had a more recent diagnosis of HIV. In 2003 and 2012, people in full-time employment were less likely to be using ART, while those whose main source of income was a pension or social security were more likely to be using ART. Multivariate models showed that, at each time point, a belief in the health benefits of delayed ART uptake was associated with non-use. These findings suggest that there may be barriers to ART uptake that have persisted over time despite changes to clinical guidelines that now encourage early uptake.

Predicting adverse health outcomes in older emergency department patients: the APOP study.

BACKGROUND: Older patients experience high rates of adverse outcomes after an emergency department (ED) visit. Early identification of those at high risk could guide preventive interventions and tailored treatment decisions, but available models perform poorly in discriminating those at highest risk. The present study aims to develop and validate a prediction model for functional decline and mortality in older patients presenting to the ED. METHODS: A prospective follow-up study in patients aged ≥ 70, attending the EDs of the LUMC, the Netherlands (derivation) and Alrijne Hospital, the Netherlands (validation) was conducted. A baseline assessment was performed and the main outcome, a composite of functional decline and mortality, was obtained after 90 days of follow-up. RESULTS: In total 751 patients were enrolled in the Leiden University Medical Center of whom 230 patients (30.6%) experienced the composite outcome and 71 patients (9.5%) died. The final model for the composite outcome resulted in an area under the curve (AUC) of 0.73 (95% CI 0.67-0.77) and was experienced in 69% of the patients at highest risk. For mortality the AUC was 0.79 (95% CI 0.73-0.85) and 36% of the patients at highest risk died. External validation in 881 patients of Alrijne Hospital showed an AUC of 0.71 (95% CI 0.67-0.75) for the composite outcome and 0.67 (95% CI 0.60-0.73) for mortality. CONCLUSION: We successfully developed and validated prediction models for 90-day composite outcome and 90-day mortality in older emergency patients. The benefits for patient management by implementing these models with preventive interventions have to be investigated.

Young women's psychological distress after a diagnosis of polycystic ovary syndrome or endometriosis.

STUDY QUESTION: Do young women with polycystic ovary syndrome (PCOS) or endometriosis report more psychological distress than their peers without a history of these conditions? SUMMARY ANSWER: Young women (aged 18-23 years) with PCOS or endometriosis had a greater risk of moderate to severe psychological distress than women without a history of these conditions. WHAT IS KNOWN ALREADY: Psychological distress appears common among women with PCOS and endometriosis. However, population-based studies that examine the psychological outcomes for adolescents and young women are generally absent from the literature. STUDY DESIGN, SIZE, DURATION: This is a secondary analysis of data collected from 17 015 young, Australian women participating in a national, longitudinal cohort study. Women were first surveyed in 2012-2013 when they were aged 18-23 years. In 2014, women completed the second survey when they were aged 19-24 years and 11324 (67%) women responded. PARTICIPANTS/MATERIALS, SETTING, METHODS: We analysed data from 11 238 women who participated in both Surveys 1 and 2 and who responded to questions about PCOS and endometriosis. Using logistic regression, we compared the odds of moderate to severe psychological distress at Surveys 1 and 2 for women reporting a recent diagnosis (within the last 12 months) of PCOS or endometriosis and women with a pre-existing diagnosis, with that for women without a history of these conditions. MAIN RESULTS AND THE ROLE OF CHANCE: At Survey 2, around 60% of women reporting a diagnosis of PCOS or endometriosis had moderate to severe levels of psychological distress. Compared to women without a history of these conditions, the odds of moderate to severe psychological distress at Survey 2 were significantly higher for women recently diagnosed with PCOS [Adjusted Odds Ratio (AOR) = 1.62, 95% CI = 1.21-2.18] or endometriosis (AOR= 1.77; 95% CI = 1.20-2.63) and for women with a pre-existing diagnosis of PCOS (AOR = 1.57, 95% CI = 1.30-1.89) or endometriosis (AOR = 1.61; 95% CI = 1.26-2.06). Women recently diagnosed with PCOS or endometriosis also had a greater likelihood of moderate to severe distress in the year prior to their diagnosis. The association between PCOS and psychological distress was attenuated when adjusting for BMI, but hormonal contraceptive use did not attenuate the risk of distress among the women with PCOS or endometriosis. LIMITATIONS, REASONS FOR CAUTION: All data were self-reported and, therefore, the diagnoses of PCOS or endometriosis were not confirmed by a medical practitioner. WIDER IMPLICATIONS OF THE FINDINGS: Health professionals should be aware of the potential psychosocial and healthcare needs among young women with these conditions, particularly women with PCOS who are obese. While hormonal contraceptives may help to regulate the hormonal aspects of these conditions, they do not appear to reduce women's psychological distress. Because psychological distress among the young women in this study remained elevated even after diagnosis, this supports the need for multidisciplinary health care to help women adjust to their diagnosis and treatment regimens and facilitate positive, long-term mental health outcomes. Future research that examines medical and psychosocial sources of distress for young women with PCOS and endometriosis is needed. STUDY FUNDING/COMPETING INTERESTS: I.J.R. was supported by an Australian National Health and Medical Research Council Centre for Research Excellence (grant number: APP1000986). G.D.M. is funded by the Australian Research Council Future Fellowship (FT120100812). The Australian Longitudinal Study on Women's Health is funded by the Australian Government Department of Health. H.T. is supported by an Australian National Health and Medical Research Council Practitioner Fellowship. The authors declare that no competing interests exist. TRIAL REGISTRATION NUMBER: N/A.

Mesenchymal Stromal Cells Prevent Allostimulation In Vivo and Control Checkpoints of Th1 Priming: Migration of Human DC to Lymph Nodes and NK Cell Activation.

Although the immunomodulatory potency of mesenchymal stromal cells (MSC) is well established, the mechanisms behind are still not clear. The crosstalk between myeloid dendritic cells (mDC) and natural killer (NK) cells and especially NK cell-derived interferon-gamma (IFN-γ) play a pivotal role in the development of type 1 helper (Th1) cell immune responses. While many studies explored the isolated impact of MSC on either in vitro generated DC, NK, or T cells, there are only few data available on the complex interplay between these cells. Here, we investigated the impact of MSC on the functionality of human mDC and the consequences for NK cell and Th1 priming in vitro and in vivo. In critical limb ischemia patients, who have been treated with allogeneic placenta-derived mesenchymal-like stromal cells (PLX-PAD), no in vivo priming of Th1 responses toward the major histocompatibility complex (MHC) mismatches could be detected. Further in vitro studies revealed that mDC reprogramming could play a central role for these effects. Following crosstalk with MSC, activated mDC acquired a tolerogenic phenotype characterized by reduced migration toward CCR7 ligand and impaired ability to stimulate NK cell-derived IFN-γ production. These effects, which were strongly related to an altered interleukin (IL)-12/IL-10 production by mDC, were accompanied by an effective prevention of Th1 priming in vivo. Our findings provide novel evidence for the regulation of Th1 priming by MSC via modulation of mDC and NK cell crosstalk and show that off-the-shelf produced MHC-mismatched PLX-PAD can be used in patients without any sign of immunogenicity.

Circulating interleukin-6 concentration and cognitive decline in old age: the PROSPER study.

BACKGROUND: Inflammation is involved in the pathogenesis of cardiovascular disease and cognitive decline. Interleukin-6 (IL-6) has a role in cardiovascular disease, but the association of IL-6 concentration and the functional IL-6 -174 polymorphism with cognitive decline has not been demonstrated unequivocally. The objective of this study was to investigate the associations between both high concentration of IL-6 and the -174 promoter polymorphism, and increased cognitive decline in old age. METHODS: Over 5000 participants of the Prospective Study of Pravastatin in the Elderly at Risk (PROSPER) with a mean age of 75 years and a history of cardiovascular disease or its risk factors were included in this study. We determined baseline concentrations of IL-6 and genotype of the IL-6 -174 polymorphism, of which the C allele was previously shown to be associated with higher circulating concentrations of IL-6. A cognitive test battery was administered at baseline and repeatedly during follow-up (mean 39 months). RESULTS: In the cross-sectional analysis of 5653 participants, higher IL-6 concentration was associated with worse executive cognitive function (P < 0.001), independent of cardiovascular disease status and risk factors. No association was found between IL-6 concentration and memory function (P > 0.14). In the prospective analysis, higher IL-6 concentration was associated with an increased rate of cognitive decline in both executive function (P = 0.002) and memory function (P = 0.002), again independent of cardiovascular disease status and risk factors. Although not associated with IL-6 concentrations, the IL-6 -174 CC genotype was associated with worse performance on the Stroop test (P = 0.045). CONCLUSIONS: Higher circulating levels of IL-6 were associated with worse cognitive function and steeper cognitive decline and provide preliminary genetic evidence for a potential causal association. The findings support the importance of the need for further investigation of the IL-6 pathway in cognitive decline.

A longitudinal study of the bi-directional relationship between tobacco smoking and psychological distress in a community sample of young Australian women.

BACKGROUND: Tobacco smoking and poor mental health are both prevalent and detrimental health problems in young women. The temporal relationship between the two variables is unclear. We investigated the prospective bi-directional relationship between smoking and mental health over 13 years. METHOD: Participants were a randomly selected community sample of 10 012 young women with no experience of pregnancy, aged 18-23 years at baseline (1996) from the Australian Longitudinal Study on Women's Health. Follow-up surveys over 13 years were completed in 2000, 2003, 2006 and 2009, allowing for five waves of data. Measures included self-reported smoking and mental health measured by the Mental Health Index from the 36-item short-form health questionnaire and the 10-item Center for Epidemiologic Studies Depression Scale. Sociodemographic control variables included marital status, education level and employment status. RESULTS: A strong cross-sectional dose-response relationship between smoking and poor mental health was found at each wave [odds ratio (OR) 1.41, 95% confidence intervals (CI) 1.17-1.70 to OR 2.27, 95% CI 1.82-2.81]. Longitudinal results showed that women who smoked had 1.21 (95% CI 1.06-1.39) to 1.62 (95% CI 1.24-2.11) times higher odds of having poor mental health at subsequent waves. Women with poor mental health had 1.12 (95% CI 1.17-1.20) to 2.11 (95% CI 1.68-2.65) times higher odds of smoking at subsequent waves. These results held after adjusting for mental health history and smoking history and sociodemographic factors. Correlation analysis and structural equation modelling results were consistent in showing that both directions of the relationship were statistically significant. CONCLUSIONS: The association between poor mental health and smoking in young women appeared to be bi-directional.

The impact of a tele-ICU on provider attitudes about teamwork and safety climate.

OBJECTIVE: To measure teamwork and safety climate in three intensive care units (ICUs) before and after remote monitoring by intensivists using telemedicine technology (tele-ICU). DESIGN: Controlled pre tele-ICU and post tele-ICU cross-sectional survey. SETTING: ICUs in two non-teaching community hospitals and one tertiary care teaching hospital. Subjects ICU physicians and nurses. INTERVENTIONS: Remote monitoring of ICU patients by intensivists. OUTCOME MEASUREMENTS: Teamwork Climate Scale (TWS), a Safety Climate Score (SCS) and survey items related to tele-ICU. MAIN RESULTS: The mean (SD) teamwork climate score was 69.7 (25.3) and 78.8 (17.2), pre and post tele-ICU (p = 0.009). The mean SCS score was 66.4 (24.6) and 73.4 (18.5), pre and post tele-ICU (p = 0.045). While SCS scores within the ICUs improved, the overall SCS scores for these hospitals decreased from 69.0 to 65.4. Three of the non-scaled items were significantly different pre and post tele-ICU at p<0.001. The item means (SD) pre and post tele-ICU were: "others interrupt my work to tell me something about my patient that I already know" 2.5 (1.2) and 1.6 (1.3); "I am confident that my patients are adequately covered when I am off the unit" 3.2 (1.3) and 4.2 (1.1); and "I can reach a physician in an urgent situation in a timely manner" 3.8 (1.2) and 4.6 (0.6). CONCLUSIONS: Implementation of a tele-ICU was associated with improved teamwork climate and safety climate in some ICUs, especially among nurses. Providers were also more confident about patient coverage and physician accessibility, and did not report unnecessary interruptions.

[Autologous bone-marrow stem-cell transplantation for induction of arteriogenesis for limb salvage in critical limb ischaemia]. / Extremitätenerhalt durch autologe Knochenmarksstammzelltransplantation zur Induktion der Arteriogenese bei kritischer, nicht-revaskularisierbarer Extremitätenischämie.

BACKGROUND: Bone marrow cell transplantation has been shown to induce angiogenesis and thus improve ischaemic artery disease. This study evaluates the effects of intramuscular bone marrow cell transplantation in patients with limb-threatening critical limb ischaemia with a very high risk for major amputation. METHODS AND RESULTS: After failed or impossible operative and / or interventional revascularisation and after unsuccessful maximum conservative therapy, 51 patients with impending major amputation due to severe critical limb ischaemia had autologous bone marrow cells (BMC) transplant-ed into the ischaemic leg. Patients 1-12 received Ficoll-isolated bone marrow mononuclear cells (total cell number 1.1 +/- 1.1 x 10(9)), patients 13-51 received point of care isolated bone marrow total nucleated cells (3.0 +/- 1.7 x 10(9)). Limb salvage was 59 % at 6 months and 53 % at last follow-up (mean: 411 +/- 261 days, range: 175-1186 days). Perfusion measured with the ankle-brachial-index (ABI) and transcutaneous oxygen tension (tcpO2) at baseline and after 6 months increased in -patients with consecutive limb salvage (ABI 0.33 +/- 0.18 to 0.46 +/- 0.15, tcpO2 12 +/- 12 to 25 +/- 15 mmHg) and did not change in patients eventually undergoing major amputation. No differences in clinical outcome between the isolation methods were seen. Clinically most important, patients with limb salvage improved from a mean Rutherford category of 4.9 at baseline to 3.3 at 6 months (p = 0.0001). Analgesics consumption was reduced by 62 %. -Total walking distance improved in non-amputees from zero to 40 metres. Three severe peri-procedural adverse events resolved without sequelae, and no unexpected long-term adverse events occurred. CONCLUSIONS: In no-option patients with end-stage critical limb ischaemia due to peripheral -artery disease, bone marrow cell transplantation is a safe procedure which can improve leg perfusion sufficiently to reduce major amputations and permit durable limb salvage.

Autologous bone marrow cell transplantation increases leg perfusion and reduces amputations in patients with advanced critical limb ischemia due to peripheral artery disease.

Bone marrow cell transplantation has been shown to induce angiogenesis and thus improve ischemic artery disease. This study evaluates the effects of intramuscular bone marrow cell transplantation in patients with limb-threatening critical limb ischemia with a very high risk for major amputation. After failed or impossible operative and/or interventional revascularization and after unsuccessful maximum conservative therapy, 51 patients with impending major amputation due to severe critical limb ischemia had autologous bone marrow cells (BMC) transplanted into the ischemic leg. Patients 1-12 received Ficoll-isolated bone marrow mononuclear cells (total cell number 1.1 +/- 1.1 x 10(9)), patients 13-51 received point of care isolated bone marrow total nucleated cells (3.0 +/- 1.7 x 10(9)). Limb salvage was 59% at 6 months and 53% at last follow-up (mean 411 +/- 261 days, range 175-1186). Perfusion measured with ankle-brachial index (ABI) and transcutaneous oxygen tension (tcpO(2)) at baseline and after 6 months increased in patients with consecutive limb salvage (ABI 0.33 +/- 0.18 to 0.46 +/- 0.15, tcpO(2) 12 +/- 12 to 25 +/- 15 mmHg) and did not change in patients eventually undergoing major amputation. No difference in clinical outcome between the isolation methods were seen. Clinically most important, patients with limb salvage improved from a mean Rutherford category of 4.9 at baseline to 3.3 at 6 months (p = 0.0001). Analgesics consumption was reduced by 62%. Total walking distance improved in nonamputees from zero to 40 m. Three severe periprocedural adverse events resolved without sequelae, and no unexpected long-term adverse events occurred. In no-option patients with end-stage critical limb ischemia due to peripheral artery disease, bone marrow cell transplantation is a safe procedure that can improve leg perfusion sufficiently to reduce major amputations and permit durable limb salvage.