Cost-effectiveness of incentives for physical activity in coronary heart disease in Germany: pre-trial health economic model of a complex intervention following the new MRC framework.

Objectives: The German Incentives for Physical Activity in Cardiac Patients trial is a three-arm, randomised controlled trial for secondary prevention of coronary heart disease (CHD). Guidance for developing complex interventions recommends pre-trial health economic modelling. The aim of this study is to model the long-term cost-effectiveness of the incentive-based physical activity interventions in a population with CHD. Methods: A decision-analytical Markov model was developed from a health services provider perspective, following a cohort aged 65 years with a previous myocardial infarction for 25 years. Monetary and social incentives were compared relative to no incentive. Intervention effects associated with physical activity were used to determine the costs, quality-adjusted life-years (QALYs) gained, incremental cost-effectiveness and cost-utility ratios. The probability of cost-effectiveness was calculated through sensitivity analyses. Results: The incremental QALYs gained from the monetary and social incentives, relative to control, were respectively estimated at 0.01 (95% CI 0.00 to 0.01) and 0.04 (95% CI 0.02 to 0.05). Implementation of the monetary and social incentive interventions increased the costs by €874 (95% CI €744 to €1047) and €909 (95% CI €537 to €1625). Incremental cost-utility ratios were €25 912 (95% CI €15 056 to €50 210) and €118 958 (95% CI €82 930 to €196 121) per QALY gained for the social and monetary incentive intervention, respectively. With a willingness-to-pay threshold set at €43 000/QALY, equivalent to the per-capita gross domestic product in Germany, the probability that the social and monetary incentive intervention would be seen as cost-effective was 95% and 0%, respectively. Conclusions: Exercise-based secondary prevention using inventive schemes may offer a cost-effective strategy to reduce the burden of CHD.

Assessment of long-term dietary cadmium exposure in children in Germany: Does consideration of data from total diet studies reduce uncertainties from food monitoring programmes?

Total diet studies (TDS) and food monitoring programmes are different approaches for collecting occurrence data on substances in food. This case study evaluated the practical applicability of TDS data (BfR MEAL Study) and monitoring data for the assessment of long-term cadmium exposure in children in Germany. Cadmium data from both programmes were combined with food consumption data from the KiESEL study. Uncertainties associated with both assessments were systematically described. Using monitoring data resulted in cadmium intakes approximately 3 times higher than the use of BfR MEAL Study data. Incomplete data and neglect of market shares and consumption weights were considered by conservative data adjustments to the monitoring data and mainly explain the higher estimates. Fewer data adjustments were necessary for BfR MEAL Study data, which covered almost the entire diet and considered consumer behaviour during sample collection and sample preparation. In sum, the use of the BfR MEAL Study data resulted in less uncertainty and more reliable exposure estimates for chronic assessments over the entire diet. However, description of variability and upper tails of substance distributions in food remain essential features of monitoring data. The integration of both programmes into a complementary system further improves food safety.

DNA-based assessment of root lesion nematode infections in cereal roots.

Root lesion nematodes (RLN) of the genus Pratylenchus are causing significant damage in cereal production worldwide. Due to climate change and without efficient and environment-friendly treatments, the damages through RLNs are predicted to increase. Microscopic assessments of RLNs in the field and the greenhouses are time-consuming and laborious. As a result, cereal breeders have mostly ignored this pest. We present a method measuring RLN in infected cereal roots using a standardized PCR approach. Publicly available Pratylenchus neglectus primer combinations were evaluated. An optimal primer combination for RT-qPCR assay was identified to detect and quantify P. neglectus within infected cereal roots. Using the RT-qPCR detection assay, P. neglectus could be clearly distinguished from other plant parasitic nematodes. We could identify P. neglectus DNA in barley and wheat roots as low as 0.863 and 0.916 ng/µl of total DNA, respectively. A single P. neglectus individual was detected in water suspension and within barley and wheat roots. The RT-qPCR detection assay provides a robust and accurate alternative to microscopic nematode identification and quantification. It could be of interest for resistance breeding, where large populations must be screened to detect and quantify P. neglectus in farmer's fields.

Direct assessment of microcirculation in shock: a randomized-controlled multicenter study.

PURPOSE: Shock is a life-threatening condition characterized by substantial alterations in the microcirculation. This study tests the hypothesis that considering sublingual microcirculatory perfusion variables in the therapeutic management reduces 30-day mortality in patients admitted to the intensive care unit (ICU) with shock. METHODS: This randomized, prospective clinical multicenter trial-recruited patients with an arterial lactate value above two mmol/L, requiring vasopressors despite adequate fluid resuscitation, regardless of the cause of shock. All patients received sequential sublingual measurements using a sidestream-dark field (SDF) video microscope at admission to the intensive care unit (± 4 h) and 24 (± 4) hours later that was performed blindly to the treatment team. Patients were randomized to usual routine or to integrating sublingual microcirculatory perfusion variables in the therapy plan. The primary endpoint was 30-day mortality, secondary endpoints were length of stay on the ICU and the hospital, and 6-months mortality. RESULTS: Overall, we included 141 patients with cardiogenic (n = 77), post cardiac surgery (n = 27), or septic shock (n = 22). 69 patients were randomized to the intervention and 72 to routine care. No serious adverse events (SAEs) occurred. In the interventional group, significantly more patients received an adjustment (increase or decrease) in vasoactive drugs or fluids (66.7% vs. 41.8%, p = 0.009) within the next hour. Microcirculatory values 24 h after admission and 30-day mortality did not differ [crude: 32 (47.1%) patients versus 25 (34.7%), relative risk (RR) 1.39 (0.91-1.97); Cox-regression: hazard ratio (HR) 1.54 (95% confidence interval (CI) 0.90-2.66, p = 0.118)]. CONCLUSION: Integrating sublingual microcirculatory perfusion variables in the therapy plan resulted in treatment changes that do not improve survival at all.

The Sequential Organ Failure Assessment (SOFA) Score: has the time come for an update?

The Sequential Organ Failure Assessment (SOFA) score was developed more than 25 years ago to provide a simple method of assessing and monitoring organ dysfunction in critically ill patients. Changes in clinical practice over the last few decades, with new interventions and a greater focus on non-invasive monitoring systems, mean it is time to update the SOFA score. As a first step in this process, we propose some possible new variables that could be included in a SOFA 2.0. By so doing, we hope to stimulate debate and discussion to move toward a new, properly validated score that will be fit for modern practice.

A retrospective cohort study comparing differences in 30-day mortality among critically ill patients aged ≥ 70 years treated in European tax-based healthcare systems (THS) versus social health insurance systems.

In Europe, tax-based healthcare systems (THS) and social health insurance systems (SHI) coexist. We examined differences in 30-day mortality among critically ill patients aged ≥ 70 years treated in intensive care units in a THS or SHI. Retrospective cohort study. 2406 (THS n = 886; SHI n = 1520) critically ill ≥ 70 years patients in 129 ICUs. Generalized estimation equations with robust standard errors were chosen to create population average adjusted odds ratios (aOR). Data were adjusted for patient-specific variables, organ support and health economic data. The primary outcome was 30-day-mortality. Numerical differences between SHI and THS in SOFA scores (6 ± 3 vs. 5 ± 3; p = 0.002) were observed, but clinical frailty scores were similar (> 4; 17% vs. 14%; p = 0.09). Higher rates of renal replacement therapy (18% vs. 11%; p < 0.001) were found in SHI (aOR 0.61 95%CI 0.40-0.92; p = 0.02). No differences regarding intubation rates (68% vs. 70%; p = 0.33), vasopressor use (67% vs. 67%; p = 0.90) and 30-day-mortality rates (47% vs. 50%; p = 0.16) were found. Mortality remained similar between both systems after multivariable adjustment and sensitivity analyses. The retrospective character of this study. Baseline risk and mortality rates were similar between SHI and THS. The type of health care system does not appear to have played a role in the intensive care treatment of critically ill patients ≥ 70 years with COVID-19 in Europe.

Incidence and Risk Assessment of Infolding Using Self-Expandable Devices in TAVR.

Background: Transcatheter aortic valve replacement is an evolving interventional therapy for patients with symptomatic severe aortic stenosis. Infolding (INF) as wrinkling along the valve frame is only seen in self-expandable transcatheter valves or surgical sutureless prostheses and is known to be a very rare event during delivery but probably underreported. Therefore, we aimed to (1) determine the frequency of events, (2) identify potential predictors of INF, and (3) evaluate the potential clinical impact of this adverse event. Methods: INF cases of 2 centers were retrospectively analyzed in an all-comer cohort of 1416 patients with older- and newer-generation self-expandable (SEV) devices. The underlying functional, anatomical, and procedural conditions were evaluated by univariate analysis. Results: INF+ was observed in 14 patients (1.0%) with the following valve size distribution: SEV-26: 14.3%, SEV-29: 28.6%, and SEV-34: 57.4%. Several dependent predictors of INF were pointed out, such as severe peripheral kinking, severe aortic calcification, resheathing maneuvers, valve-in-valve procedures, and the use of the largest valve size. INF+ patients showed a higher incidence of acute kidney injury (INF- vs. INF+: 12.3% vs. 35.7%; p = 0.008), of a new atrioventricular block (INF- vs. INF+: 14.8% vs. 42.9%; p = 0.003), and a higher need of permanent pacemaker implantation (INF- vs. INF+: 14.9% vs. 35.7%; p = 0.031). Conclusions: Identifying potential predictors of INF can probably influence the implantation strategy and improve safety algorithms and clinical outcomes. Even being a rare but potentially life-threatening and underreported event, safety rules must be established when expanding transcatheter aortic valve replacement treatment to younger patients.

The management of multi-morbidity in elderly patients: Ready yet for precision medicine in intensive care?

There is ongoing demographic ageing and increasing longevity of the population, with previously devastating and often-fatal diseases now transformed into chronic conditions. This is turning multi-morbidity into a major challenge in the world of critical care. After many years of research and innovation, mainly in geriatric care, the concept of multi-morbidity now requires fine-tuning to support decision-making for patients along their whole trajectory in healthcare, including in the intensive care unit (ICU). This article will discuss current challenges and present approaches to adapt critical care services to the needs of these patients.

Sex-specific outcome disparities in very old patients admitted to intensive care medicine: a propensity matched analysis.

Female and male very elderly intensive patients (VIPs) might differ in characteristics and outcomes. We aimed to compare female versus male VIPs in a large, multinational collective of VIPs with regards to outcome and predictors of mortality. In total, 7555 patients were included in this analysis, 3973 (53%) male and 3582 (47%) female patients. The primary endpoint was 30-day-mortality. Baseline characteristics, data on management and geriatric scores including frailty assessed by Clinical Frailty Scale (CFS) were documented. Two propensity scores (for being male) were obtained for consecutive matching, score 1 for baseline characteristics and score 2 for baseline characteristics and ICU management. Male VIPs were younger (83 ± 5 vs. 84 ± 5; p < 0.001), less often frail (CFS > 4; 38% versus 49%; p < 0.001) but evidenced higher SOFA (7 ± 6 versus 6 ± 6 points; p < 0.001) scores. After propensity score matching, no differences in baseline characteristics could be observed. In the paired analysis, the mortality in male VIPs was higher (mean difference 3.34% 95%CI 0.92-5.76%; p = 0.007) compared to females. In both multivariable logistic regression models correcting for propensity score 1 (aOR 1.15 95%CI 1.03-1.27; p = 0.007) and propensity score 2 (aOR 1.15 95%CI 1.04-1.27; p = 0.007) male sex was independently associated with higher odds for 30-day-mortality. Of note, male gender was not associated with ICU mortality (OR 1.08 95%CI 0.98-1.19; p = 0.14). Outcomes of elderly intensive care patients evidenced independent sex differences. Male sex was associated with adverse 30-day-mortality but not ICU-mortality. Further research to identify potential sex-specific risk factors after ICU discharge is warranted.Trial registration: NCT03134807 and NCT03370692; Registered on May 1, 2017 https://clinicaltrials.gov/ct2/show/NCT03370692 .

Aggregated aluminium exposure: risk assessment for the general population.

Aluminium is one of the most abundant elements in earth's crust and its manifold uses result in an exposure of the population from many sources. Developmental toxicity, effects on the urinary tract and neurotoxicity are known effects of aluminium and its compounds. Here, we assessed the health risks resulting from total consumer exposure towards aluminium and various aluminium compounds, including contributions from foodstuffs, food additives, food contact materials (FCM), and cosmetic products. For the estimation of aluminium contents in foodstuff, data from the German "Pilot-Total-Diet-Study" were used, which was conducted as part of the European TDS-Exposure project. These were combined with consumption data from the German National Consumption Survey II to yield aluminium exposure via food for adults. It was found that the average weekly aluminium exposure resulting from food intake amounts to approx. 50% of the tolerable weekly intake (TWI) of 1 mg/kg body weight (bw)/week, derived by the European Food Safety Authority (EFSA). For children, data from the French "Infant Total Diet Study" and the "Second French Total Diet Study" were used to estimate aluminium exposure via food. As a result, the TWI can be exhausted or slightly exceeded-particularly for infants who are not exclusively breastfed and young children relying on specially adapted diets (e.g. soy-based, lactose free, hypoallergenic). When taking into account the overall aluminium exposure from foods, cosmetic products (cosmetics), pharmaceuticals and FCM from uncoated aluminium, a significant exceedance of the EFSA-derived TWI and even the PTWI of 2 mg/kg bw/week, derived by the Joint FAO/WHO Expert Committee on Food Additives, may occur. Specifically, high exposure levels were found for adolescents aged 11-14 years. Although exposure data were collected with special regard to the German population, it is also representative for European and comparable to international consumers. From a toxicological point of view, regular exceedance of the lifetime tolerable aluminium intake (TWI/PTWI) is undesirable, since this results in an increased risk for health impairments. Consequently, recommendations on how to reduce overall aluminium exposure are given.

Easy prognostic assessment of concomitant organ failure in critically ill patients undergoing mechanical ventilation.

BACKGROUND: Acute respiratory distress syndrome (ARDS) is a life-threatening disease. We evaluated the prognostic utility of Model for End-stage Liver Disease excluding INR (MELD-XI) score for predicting mortality in a cohort of critically ill patients on mechanical ventilation. METHODS: In total, 11,091 mechanically ventilated patients were included in our post-hoc retrospective analysis, a subgroup of the VENTILA study (NCT02731898). Evaluation of associations with mortality was done by logistic and Cox regression analysis, an optimal cut-off was calculated using the Youden Index. We divided the cohort in two sub-groups based on their MELD-XI score at the optimal cut-off (12 score points). RESULTS: Peak-, plateau- and positive end-expiratory pressure were higher in patients with MELD-XI>12. Patients with MELD-XI>12 had higher driving pressures (14 ±â€¯6 cmH2O versus 13 ±â€¯6; p < 0.001). MELD-XI was associated with 28-day mortality after correction for relevant cofounders including SAPS II and ventilation pressures (HR 1.04 95%CI 1.03-1.05; p < 0.001. Patients with MELD-XI>12 evidenced both increased hospital (46% versus 27%; p < 0.001) and 28-day mortality (39% versus 22%). CONCLUSIONS: MELD-XI is independently associated with mortality and constitutes a useful and easily applicable tool for risk stratification in critically ill patients receiving mechanical ventilation. TRIAL REGISTRATION: NCT02731898, registered 4 April 2016.

Assessment of microcirculation in cardiogenic shock.

PURPOSE OF REVIEW: Adequate tissue perfusion is of utmost importance to avoid organ failure in patients with cardiogenic shock. Within the recent years, the microcirculation, defined as the perfusion of the smallest vessels, has been identified to play a crucial role. Microcirculatory changes may include capillary flow disturbances as well as changes in the density of perfused vessels. Due to the availability of new technologies to assess the microcirculation, interesting new data came up and it is the purpose of this review to summarize recent studies in the field. RECENT FINDINGS: Nowadays, an increasing number of studies confirm parameters of the microcirculation, derived by intravital microscopy, to represent strong outcome predictors in cardiogenic shock. In addition, microcirculation as read-out parameter in innovative clinical studies has meanwhile been accepted as serious endpoint. Treatment strategies such as mechanical assist devices, blood pressure regulating agents or fluids use tissue perfusion and microcirculatory network density as targets in addition to clinical perfusion evaluation and decreasing serum lactate levels. SUMMARY: The parameter most frequently used to detect tissue malperfusion is serum lactate. Novel, noninvasive methods to quantify microvascular perfusion have the potential to guide treatment in terms of optimizing organ perfusion and oxygenation probably paving the way for an individualized therapy.