PROtocol-based MObilizaTION on intensive care units: stepped-wedge, cluster-randomized pilot study (Pro-Motion).

BACKGROUND: Early mobilization of patients in intensive care units (ICUs) improves patient recovery, but implementation remains challenging. Protocols may enhance the rate of out-of-bed mobilizations. AIM: To evaluate the effect of implementing a protocol for early mobilization on the rate of out-of-bed mobilizations and other outcomes of ICU patients. STUDY DESIGN: Multicentre, stepped-wedge, cluster-randomized pilot study. METHODS: After a control period, five ICUs were allocated to the implementation of an inter-professional protocol for early mobilization in a randomized, monthly order. Mobilization of ICU patients was evaluated by monthly 1-day point prevalence surveys using the ICU Mobility Scale. The primary outcome was the percentage of patients mobilized out of bed, defined as level 3 on the ICU Mobility Scale (sitting on edge of bed) or higher. Secondary outcomes were mechanical ventilation, delirium and ICU- and hospital-days, as well as unwanted safety events. RESULTS: Out-of-bed mobilizations increased non-significantly from 36·2% (n = 55) of 152 patients during the control period to 45·8% (n = 55) of 120 patients during the intervention period (difference 9·6%; 95% confidence interval -2·1 to 21·3%). Of 55 mobilized patients per group, more patients were mobilized once per day during the intervention period (intervention: n = 41 versus control: n = 23 patients). Multiple daily mobilizations decreased (control: n = 32 control versus intervention: n = 14 patients). Secondary outcomes, such as days with mechanical ventilation, delirium and in ICU and hospital, did not significantly differ. Adherence to the protocol was >90%; unwanted safety events were rare. CONCLUSIONS: Implementing a protocol for early mobilization of ICU patients showed a trend towards more patients being mobilized. Without additional staff in participating ICUs, a significant increase in ICU mobilizations was not to be anticipated. More research should address whether more staff would increase the number of frequent mobilizations and if this is relevant to outcomes. RELEVANCE TO CLINICAL PRACTICE: Implementing inter-professional protocols for mobilization is feasible and safe and may contribute to an increase of ICU patients mobilized out of bed.

Delirium in the elderly: Current problems with increasing geriatric age.

Delirium is an acute disorder of attention and cognition seen relatively commonly in people aged 65 yr or older. The prevalence is estimated to be between 11 and 42 per cent for elderly patients on medical wards. The prevalence is also high in nursing homes and long term care (LTC) facilities. The consequences of delirium could be significant such as an increase in mortality in the hospital, long-term cognitive decline, loss of autonomy and increased risk to be institutionalized. Despite being a common condition, it remains under-recognised, poorly understood and not adequately managed. Advanced age and dementia are the most important risk factors. Pain, dehydration, infections, stroke and metabolic disturbances, and surgery are the most common triggering factors. Delirium is preventable in a large proportion of cases and therefore, it is also important from a public health perspective for interventions to reduce further complications and the substantial costs associated with these. Since the aetiology is, in most cases, multifactorial, it is important to consider a multi-component approach to management, both pharmacological and non-pharmacological. Detection and treatment of triggering causes must have high priority in case of delirium. The aim of this review is to highlight the importance of delirium in the elderly population, given the increasing numbers of ageing people as well as increasing geriatric age.

Effect of simulated hearing loss on automatic speech recognition for an android robot-patient.

The importance of simulating patient behavior for medical assessment training has grown in recent decades due to the increasing variety of simulation tools, including standardized/simulated patients, humanoid and android robot-patients. Yet, there is still a need for improvement of current android robot-patients to accurately simulate patient behavior, among which taking into account their hearing loss is of particular importance. This paper is the first to consider hearing loss simulation in an android robot-patient and its results provide valuable insights for future developments. For this purpose, an open-source dataset of audio data and audiograms from human listeners was used to simulate the effect of hearing loss on an automatic speech recognition (ASR) system. The performance of the system was evaluated in terms of both word error rate (WER) and word information preserved (WIP). Comparing different ASR models commonly used in robotics, it appears that the model size alone is insufficient to predict ASR performance in presence of simulated hearing loss. However, though absolute values of WER and WIP do not predict the intelligibility for human listeners, they do highly correlate with it and thus could be used, for example, to compare the performance of hearing aid algorithms.

[Reasons for non-participation in a patient survey in the context of prehospital emergency medical care by community emergency paramedics - A retrospective observational study]. / Gründe für die Nichtteilnahme an einer Patientenbefragung im Kontext der prähospitalen Notfallversorgung durch Gemeindenotfallsanitäter - eine retrospektive Beobachtungsstudie.

BACKGROUND: In order to evaluate whether the new rescue means "community emergency paramedics" (Gemeindenotfallsanitäter [G-NFS]) relieves the emergency medical service (EMS) in the care of low-priority emergencies, the perspective of general practitioners and patients was also surveyed in a written questionnaire as part of an innovation fund project. Recruitment for participation in the study proved to be difficult. The aim of this study is to evaluate why the G-NFS decided against providing information on study participation and what measures would be necessary to include more emergency patients in surveys in the future. METHODS: Retrospective analysis of the assignment protocols from April 1, 2021 to June 30, 2022. In addition to patient characteristics, data on treatments, interventions and recommendations to patients as well as reasons for non-participation in the patient survey were collected. RESULTS: 5,395 G-NFS protocols that contained information on non-participation were included in the analysis. The average age of the patients was 62.4 years (SD 22.7), and 50.2% were female. 57.4% of the cases were categorised as non-urgent, and 35.2% of the cases required an additional ambulance to be alerted. 404 (7.5%) patients used the EMS more than once, 1,120 (20.8%) did not have sufficient language skills, 1,012 (18.8%) patients declined study participation, and 2,975 (55.1%) patients were not able to participate according to the G-NFS assessment. Dementia/neurocognitive impairment (35%), acute/emergency situation (26.5%), mental health impairment (10.3%), and substance abuse (6.5%) were given as reasons for non-participation from the G-NFS perspective. DISCUSSION: The results show that more than half of the patients were unable to take part in a written survey for various reasons, even though there was no need for urgent care. This could be due to a high demand for care and the complex consent procedure. In addition, further resources are required to provide needs-based care for these patients in order to relieve the burden on emergency medical care. Over half of the patients were unable to take part in a written survey for various reasons. Further research is needed to determine what consent procedures are appropriate to facilitate patients' study participation.

Shape of the art: TCR-repertoire after allogeneic hematopoietic cell transplantation.

The human adaptive immune repertoire is characterized by specificity and diversity to provide immunity against past and future tasks. Such tasks are mainly infections but also malignant transformations of cells. With its multiple lines of defense, the human immune system contains both, rapid reaction forces and the potential to capture, disassemble and analyze strange structures in order to teach the adaptive immune system and mount a specific immune response. Prevention and mitigation of autoimmunity is of equal importance. In the context of allogeneic hematopoietic cell transplantation (HCT) specific challenges exist with the transfer of cells from the adapted donor immune system to the immunosuppressed recipient. Those challenges are immunogenetic disparity between donor and host, reconstitution of immunity early after HCT by expansion of mature immune effector cells, and impaired thymic function, if the recipient is an adult (as it is the case in most HCTs). The possibility to characterize the adaptive immune repertoire by massively parallel sequencing of T-cell receptor gene rearrangements allows for a much more detailed characterization of the T-cell repertoire. In addition, high-dimensional characterization of immune effector cells based on their immunophenotype and single cell RNA sequencing allow for much deeper insights in adaptive immune responses. We here review, existing - still incomplete - information on immune reconstitution after allogeneic HCT. Building on the technological advances much deeper insights into immune recovery after HCT and adaptive immune responses and can be expected in the coming years.

[Frequency and characteristics of interventions by community paramedics on people in need of care : Analysis of 2,410 deployment protocols for people aged 65+ years]. / Häufigkeit und Charakteristika von Einsätzen der Gemeindenotfallsanitäter bei Pflegebedürftigen : Analyse von 2410 Einsatzprotokollen bei Personen im Alter von 65+ Jahren.

BACKGROUND: The aim of this study was to obtain a differentiated view of interventions delivered by community paramedics (Gemeindenotfallsanitäter, G­NFS) in older people in need of care living in nursing homes and at home. MATERIALS AND METHODS: A retrospective analysis of G­NFS documentation from 2021 with a focus on patients aged ≥65 years was performed. Data were grouped into callouts to nursing homes or private homes. Interventions, urgency, transport, and further recommendations were analyzed descriptively. RESULTS: Of 5,900 G-NFS protocols, 43.0% (n = 2,410) were related to elderly people (mean age 80.8 years, 49.7% female). A total of 20.6% of these callouts involved nursing home residents, 38.4% (n = 926) were homecare patients, and 41% (n = 988) of callouts were to persons who did not rely on care. No specific interventions except advice were given to 48.4% of nursing home residents, and to even 82.1% of those in homecare and 83.7% of those without care needs. About 60% of the G­NFS interventions were classified as non-urgent. Transport was waived for 63.1% of nursing home residents, for 58.1% in homecare, and for 60.6% of persons without care needs. A visit to the emergency department was recommended to 29.4% of nursing home residents, 37.6% of homecare patients, and 33.6% of persons without need of care. Measures related to urine catheters were documented much more often in nursing homes (38.5%) than in patients in homecare (15.1%) or without need of care (9.3%). CONCLUSION: Community paramedics perform primary care tasks and can contribute to a reduction in unnecessary transport. It should be discussed whether the emergency medical service is responsible for such interventions and how older people in need of care can be cared for according to their needs in the future.

Ventilatory Effects of Isoflurane Sedation via the Sedaconda ACD-S versus ACD-L: A Substudy of a Randomized Trial.

Devices used to deliver inhaled sedation increase dead space ventilation. We therefore compared ventilatory effects among isoflurane sedation via the Sedaconda ACD-S (internal volume: 50 mL), isoflurane sedation via the Sedaconda ACD-L (100 mL), and propofol sedation with standard mechanical ventilation with heat and moisture exchangers (HME). This is a substudy of a randomized trial that compared inhaled isoflurane sedation via the ACD-S or ACD-L to intravenous propofol sedation in 301 intensive care patients. Data from the first 24 h after study inclusion were analyzed using linear mixed models. Primary outcome was minute ventilation. Secondary outcomes were tidal volume, respiratory rate, arterial carbon dioxide pressure, and isoflurane consumption. In total, 151 patients were randomized to propofol and 150 to isoflurane sedation; 64 patients received isoflurane via the ACD-S and 86 patients via the ACD-L. While use of the ACD-L was associated with higher minute ventilation (average difference (95% confidence interval): 1.3 (0.7, 1.8) L/min, p < 0.001), higher tidal volumes (44 (16, 72) mL, p = 0.002), higher respiratory rates (1.2 (0.1, 2.2) breaths/min, p = 0.025), and higher arterial carbon dioxide pressures (3.4 (1.2, 5.6) mmHg, p = 0.002), use of the ACD-S did not significantly affect ventilation compared to standard mechanical ventilation and sedation. Isoflurane consumption was slightly less with the ACD-L compared to the ACD-S (-0.7 (-1.3, 0.1) mL/h, p = 0.022). The Sedaconda ACD-S compared to the ACD-L is associated with reduced minute ventilation and does not significantly affect ventilation compared to a standard mechanical ventilation and sedation setting. The smaller ACD-S is therefore the device of choice to minimize impact on ventilation, especially in patients with a limited ability to compensate (e.g., COPD patients). Volatile anesthetic consumption is slightly higher with the ACD-S compared to the ACD-L.

Effect of High-Dose Selenium on Postoperative Organ Dysfunction and Mortality in Cardiac Surgery Patients: The SUSTAIN CSX Randomized Clinical Trial.

Importance: Selenium contributes to antioxidative, anti-inflammatory, and immunomodulatory pathways, which may improve outcomes in patients at high risk of organ dysfunctions after cardiac surgery. Objective: To assess the ability of high-dose intravenous sodium selenite treatment to reduce postoperative organ dysfunction and mortality in cardiac surgery patients. Design, Setting, and Participants: This multicenter, randomized, double-blind, placebo-controlled trial took place at 23 sites in Germany and Canada from January 2015 to January 2021. Adult cardiac surgery patients with a European System for Cardiac Operative Risk Evaluation II score-predicted mortality of 5% or more or planned combined surgical procedures were randomized. Interventions: Patients were randomly assigned (1:1) by a web-based system to receive either perioperative intravenous high-dose selenium supplementation of 2000 µg/L of sodium selenite prior to cardiopulmonary bypass, 2000 µg/L immediately postoperatively, and 1000 µg/L each day in intensive care for a maximum of 10 days or placebo. Main Outcomes and Measures: The primary end point was a composite of the numbers of days alive and free from organ dysfunction during the first 30 days following cardiac surgery. Results: A total of 1416 adult cardiac surgery patients were analyzed (mean [SD] age, 68.2 [10.4] years; 1043 [74.8%] male). The median (IQR) predicted 30-day mortality by European System for Cardiac Operative Risk Evaluation II score was 8.7% (5.6%-14.9%), and most patients had combined coronary revascularization and valvular procedures. Selenium did not increase the number of persistent organ dysfunction-free and alive days over the first 30 postoperative days (median [IQR], 29 [28-30] vs 29 [28-30]; P = .45). The 30-day mortality rates were 4.2% in the selenium and 5.0% in the placebo group (odds ratio, 0.82; 95% CI, 0.50-1.36; P = .44). Safety outcomes did not differ between the groups. Conclusions and Relevance: In high-risk cardiac surgery patients, perioperative administration of high-dose intravenous sodium selenite did not reduce morbidity or mortality. The present data do not support the routine perioperative use of selenium for patients undergoing cardiac surgery. Trial Registration: ClinicalTrials.gov Identifier: NCT02002247.

[Care of older patients by community emergency paramedics : Comparison of community-dwellers and nursing home residents]. / Versorgung älterer Patienten durch Gemeindenotfallsanitäter : Vergleich der Einsätze im Pflegeheim und in der Häuslichkeit.

BACKGROUND: Emergency departments and emergency services are increasingly burdened by non-emergency patients. A substantial proportion of these is represented by older people. The project "community emergency paramedic" ("Gemeindenotfallsanitäter" [G-NFS]) was initiated to prevent unnecessary use of emergency services. OBJECTIVE: To identify specific utilizations of the G­NFS services by older people at home and in nursing homes. MATERIAL AND METHODS: Retrospective analysis of the assignment protocols from July 2019 through June 2020. Only data from patients aged ≥ 65 years were included. Data were grouped into whether patients lived on their own or in nursing homes. RESULTS: A total of 2358 protocols of older patients (mean age 80.8 years; 52.9% female) were evaluated and 55% of patients were treated on-site. The most frequently used measures by G­NFS were counselling (79.4%), aid in self-medication (16.7%) and administration of medication (23.2%). Of the G­NFS assignments 329 (14.0%) were carried out for nursing home residents. Measures related to urine catheter complications were more frequently performed in nursing home residents than in patients who lived at home (32.2% vs. 5.7%). Compared to other emergency cases, patients with catheter-related complications were most often treated at the scene (84.3% vs. 52.2%). CONCLUSION: The G­NFS enabled the majority of patients to be treated on-site, thus saving resources of emergency services and hospitals; however, the G­NFS also performed measures that were normally the responsibility of general practitioners. This possibly highlights structural deficits in the medical and nursing care of older people.

[Pitfalls in the diagnosis of delirium]. / Fallstricke in der Diagnostik des Delirs.

BACKGROUND: The diagnosis of delirium is challenging and requires precise definitions in both clinical routine and in studies. AIM: To point out various pitfalls in the clinical diagnosis of delirium and discuss solutions. METHODS: Review. RESULTS: Common problems include (a) clinical judgment of staff vs. the use of valid assessment tools, (b) different lists of criteria for delirium that may consider the symptoms of delirium differently and thus lead to inclusion or exclusion of patients, (c) different assessment tools that test the symptoms of delirium to different extents and thus have different accuracy, (d) patients with limited communication abilities, such as aphasia, where common tests often fail and alternative procedures may be more effective; (e) the decision whether to test delirium once, twice, three times, or more frequently in 24 h has consequences on the incidence and duration of delirium, (f) the end of delirium, often defined retrospectively as a delirium-free interval or prospectively as the time of transfer or occurrence of an exclusion criterion, can lead to considerable measurement inaccuracies. CONCLUSIONS: Although not all problems can be definitively answered, transparent definition, performance, and documentation of diagnostic procedures are recommended.

ILEG - A Case of Recording Patient Journeys.

In 2019 the Gemeindenotfallsanitäter was introduced in the area of Oldenburg, and scientific monitoring starting 2021 with Inanspruchnahme, Leistungen und Effekte des Gemeindenotfallsanitäters. Since then, it is possible to track patient journeys, starting from the emergency call to the subsequent treatment. This short communication provides an overview of the necessary data-acquisition and dataflow from all participating institutions and its possibilities.

(1 → 3)-ß-D-Glucan-guided antifungal therapy in adults with sepsis: the CandiSep randomized clinical trial.

PURPOSE: To investigate whether (1 → 3)-ß-d-Glucan (BDG)-guidance shortens time to antifungal therapy and thereby reduces mortality of sepsis patients with high risk of invasive Candida infection (ICI). METHODS: Multicenter, randomized, controlled trial carried out between September 2016 and September 2019 in 18 intensive care units enrolling adult sepsis patients at high risk for ICI. Patients in the control group received targeted antifungal therapy driven by culture results. In addition to targeted therapy, patients in the BDG group received antifungals if at least one of two consecutive BDG samples taken during the first two study days was ≥ 80 pg/mL. Empirical antifungal therapy was discouraged in both groups. The primary endpoint was 28-day-mortality. RESULTS: 339 patients were enrolled. ICI was diagnosed in 48 patients (14.2%) within the first 96 h after enrollment. In the BDG-group, 48.8% (84/172) patients received antifungals during the first 96 h after enrollment and 6% (10/167) patients in the control group. Death until day 28 occurred in 58 of 172 patients (33.7%) in the BDG group and 51 of 167 patients (30.5%) in the control group (relative risk 1.10; 95% confidence interval, 0.80-1.51; p = 0.53). Median time to antifungal therapy was 1.1 [interquartile range (IQR) 1.0-2.2] days in the BDG group and 4.4 (IQR 2.0-9.1, p < 0.01) days in the control group. CONCLUSIONS: Serum BDG guided antifungal treatment did not improve 28-day mortality among sepsis patients with risk factors for but unexpected low rate of IC. This study cannot comment on the potential benefit of BDG-guidance in a more selected at-risk population.

Veno-venous extracorporeal membrane oxygenation (vv-ECMO) for severe respiratory failure in adult cancer patients: a retrospective multicenter analysis.

PURPOSE: The question of whether cancer patients with severe respiratory failure benefit from veno-venous extracorporeal membrane oxygenation (vv-ECMO) remains unanswered. We, therefore, analyzed clinical characteristics and outcomes of a large cohort of cancer patients treated with vv-ECMO with the aim to identify prognostic factors. METHODS: 297 cancer patients from 19 German and Austrian hospitals who underwent vv-ECMO between 2009 and 2019 were retrospectively analyzed. A multivariable cox proportional hazards analysis for overall survival was performed. In addition, a propensity score-matched analysis and a latent class analysis were conducted. RESULTS: Patients had a median age of 56 (IQR 44-65) years and 214 (72%) were males. 159 (54%) had a solid tumor and 138 (47%) a hematologic malignancy. The 60-day overall survival rate was 26.8% (95% CI 22.1-32.4%). Low platelet count (HR 0.997, 95% CI 0.996-0.999; p = 0.0001 per 1000 platelets/µl), elevated lactate levels (HR 1.048, 95% CI 1.012-1.084; p = 0.0077), and disease status (progressive disease [HR 1.871, 95% CI 1.081-3.238; p = 0.0253], newly diagnosed [HR 1.571, 95% CI 1.044-2.364; p = 0.0304]) were independent adverse prognostic factors for overall survival. A propensity score-matched analysis with patients who did not receive ECMO treatment showed no significant survival advantage for treatment with ECMO. CONCLUSION: The overall survival of cancer patients who require vv-ECMO is poor. This study shows that the value of vv-ECMO in cancer patients with respiratory failure is still unclear and further research is needed. The risk factors identified in the present analysis may help to better select patients who may benefit from vv-ECMO.

[Postoperative delirium and cognitive deficit. Routine delirium monitoring in the intensive care unit]. / Postoperatives Delir und kognitives Defizit. Routinemässiges Delirmonitoring auf der Intensivstation.

Up to 92% of patients in ICU develop delirium, which may be missed without routinely monitoring. Delirium monitoring, though, is often deemed time consuming and dispensable, as mere clinical judgement is considered sufficient. This paper describes the general pitfalls during the introducing of a delirium screening tool and provides tips for daily delirium monitoring.

Electrical impedance tomography compared with thoracic computed tomography during a slow inflation maneuver in experimental models of lung injury.

OBJECTIVE: To determine the validity of functional electric impedance tomography to monitor regional ventilation distribution in experimental acute lung injury, and to develop a simple electric impedance tomography index detecting alveolar recruitment. DESIGN: Randomized prospective experimental study. SETTING: Academic research laboratory. SUBJECTS: Sixteen anesthetized, tracheotomized, and mechanically ventilated pigs. INTERVENTIONS: Acute lung injury was induced either by acid aspiration (direct acute lung injury) or by abdominal hypertension plus oleic acid injection (indirect acute lung injury) in ten pigs. Six pigs with normal lungs were studied as a control group and with endotracheal suction-related atelectasis. After 4 hrs of mechanical ventilation, a slow inflation was performed. MEASUREMENTS AND MAIN RESULTS: During slow inflation, simultaneous measurements of regional ventilation by electric impedance tomography and dynamic computed tomography were highly correlated in quadrants of a transversal thoracic plane (r2 = .63-.88, p < .0001, bias <5%) in both direct and indirect acute lung injury. Variability between methods was lower in direct than indirect acute lung injury (11 +/- 2% vs. 18 +/- 3%, respectively, p < .05). Electric impedance tomography indexes to detect alveolar recruitment were determined by mathematical curve analysis of regional impedance time curves. Empirical tests of different methods revealed that regional ventilation delay, that is, time delay of regional impedance time curve to reach a threshold, correlated well with recruited volume as measured by CT (r2 = .63). Correlation coefficients in subgroups were r2 = .71 and r2 = .48 in pigs with normal lungs with and without closed suction related atelectasis and r2 = .79 in pigs subject to indirect acute lung injury, respectively, whereas no significant correlation was found in pigs undergoing direct acute lung injury. CONCLUSIONS: Electric impedance tomography allows assessment of regional ventilation distribution and recruitment in experimental models of direct and indirect acute lung injury as well as normal lungs. Except for pigs with direct acute lung injury, regional ventilation delay determined during a slow inflation from impedance time curves appears to be a simple index for clinical monitoring of alveolar recruitment.

Delirium in the elderly: current problems with increasing geriatric age.

Delirium is an acute disorder of attention and cognition seen relatively commonly in people aged 65 yr or older. The prevalence is estimated to be between 11 and 42 per cent for elderly patients on medical wards. The prevalence is also high in nursing homes and long term care (LTC) facilities. The consequences of delirium could be significant such as an increase in mortality in the hospital, long-term cognitive decline, loss of autonomy and increased risk to be institutionalized. Despite being a common condition, it remains under-recognised, poorly understood and not adequately managed. Advanced age and dementia are the most important risk factors. Pain, dehydration, infections, stroke and metabolic disturbances, and surgery are the most common triggering factors. Delirium is preventable in a large proportion of cases and therefore, it is also important from a public health perspective for interventions to reduce further complications and the substantial costs associated with these. Since the aetiology is, in most cases, multfactorial, it is important to consider a multi-component approach to management, both pharmacological and non-pharmacological. Detection and treatment of triggering causes must have high priority in case of delirium. The aim of this review is to highlight the importance of delirium in the elderly population, given the increasing numbers of ageing people as well as increasing geriatric age.

Haplotypes and SNPs in 13 lipid-relevant genes explain most of the genetic variance in high-density lipoprotein and low-density lipoprotein cholesterol.

Single nucleotide polymorphisms (SNPs) and derived haplotypes within multiple genes may explain genetic variance in complex traits; however, this hypothesis has not been rigorously tested. In an earlier study we analyzed six genes and have now expanded this investigation to include 13. We studied 250 families including 1054 individuals and measured lipid phenotypes. We focused on low-density cholesterol (LDL), high-density cholesterol (HDL) and their ratio (LDL/HDL). A component analysis of the phenotypic variance relying on a standard genetic model' showed that the genetic variance on LDL explained 26%, on HDL explained 38% and on LDL/HDL explained 28% of the total variance, respectively. Genotyping of 93 SNPs in 13 lipid-relevant genes generated 230 haplotypes. The association of haplotypes in all the genes tested explained a major fraction of the genetic phenotypic variance component. For LDL, the association with haplotypes explained 67% and for HDL 58% of the genetic variance relative to the polygenic background. We conclude that these haplotypes explain most of the genetic variance in LDL, HDL and LDL/HDL in these representative German families. An analysis of the contribution to the genetic variance at each locus showed that APOE (50%), CETP (28%), LIPC (9%), APOB (8%) and LDLR (5%) influenced variation in LDL. LIPC (53%), CETP (25%), ABCA1 (10%), LPL (6%) and LDLR (6%) influenced the HDL variance. The LDL/HDL ratio was primarily influenced by APOE (36%), CETP (27%) and LIPC (31%). This expanded analysis substantially increases the explanation of genetic variance on these complex traits.