General, spinal or regional anaesthesia does not affect strength performance 6 months after ACL reconstruction.

PURPOSE: The recovery of strength is a key element in successfully returning to sports after ACL reconstruction. The type of anaesthesia has been suspected an influential factor in the post-operative recovery of muscle function. METHODS: In this retrospective analysis, n = 442 consecutive patients undergoing primary isolated ACL reconstruction using a hamstring autograft were analysed by pre- and post-operative isokinetic tests in a single orthopaedic centre. These were subdivided into four cohorts: (1) general anaesthesia (n = 47), (2) general anaesthesia with prolonged (48 h) on-demand femoral nerve block (n = 37), (3) spinal anaesthesia (n = 169) and (4) spinal anaesthesia with prolonged (48 h) on-demand femoral nerve block (n = 185). Primary outcome was the change from pre- to post-operative isokinetic strength during knee extension and flexion. RESULTS: Using one-way ANOVA, there was no significant influence of the type of anaesthesia. The main effect of anaesthesia on change in extension forces was not significant, and effect sizes were very small (n.s.). Similarly, the main effect of anaesthesia on change in flexion forces was statistically not significant (n.s.). CONCLUSIONS: The findings of this study support the interpretation that the type of anaesthesia has no significant effect on the ability to recover thigh muscle strength 6 months after isolated hamstring ACL reconstruction. With regard to the recovery of athletic performance and return-to-sports testing criteria, there is no reason to avoid regional anaesthesia. LEVEL OF EVIDENCE: III.

Infection rate and complications after 621 transperineal MRI-TRUS fusion biopsies in local anesthesia without standard antibiotic prophylaxis.

PURPOSE: The aim of this study was to assess the post biopsy infection rate, feasibility and prostate cancer (PCa) detection rate (CDR) by performing transperineal MRI-TRUS fusion biopsy of the prostate (TPBx) under local anesthesia (LA) without antibiotic prophylaxis (AP). METHODS: We prospectively screened 766 men with suspicious lesions on mpMRI, an elevated PSA level or a suspect digital examination undergoing MRI-TRUS-TPBx in LA, from May 2019 to July 2020. Patients with the need for antibiotic prophylaxis or without a PI-RADS target lesion were excluded from final analyses. We reported CDR, perioperative pain (0-10) and postoperative complications. PCa with an ISUP grade ≥ 2 was classified as clinically significant PCa (csPCa). RESULTS: We included 621 patients with a median age of 68 years (IQR 62-74), a PSA of 6.43 ng/mL (IQR 4.72-9.91) and a prostate volume of 45 cc (IQR 32-64). In median, 4 targeted (TB) (IQR 3-4) and 6 (IQR 5-7) systematic biopsies (SB) detected in combination overall 416 (67%) PCa and 324 (52%) csPCa. Overall CDR of TB for PI-RADS 3, 4 and 5 was 26%, 65% and 84%, respectively. Patients reported a median perioperative pain level of 2 (IQR 1-3). Four patients (0.6%) developed a post biopsy infection, one experienced urosepsis. CONCLUSION: Our results demonstrate that transperineal MRI-TRUS fusion-guided prostate biopsy under LA without AP is feasible, safe and well tolerated.

[Surgical treatment of hepatic tumors-liver resection and transplantation]. / Chirurgische Therapie bei Lebertumoren ­ Leberresektion und -transplantation.

The most frequent primary hepatic malignancies are hepatocellular carcinoma (HCC) and intrahepatic cholangiocarcinoma (intrahepatic cholangiocellular adenocarcinoma [iCCA]). For HCC in cirrhosis, liver transplantation offers the advantage of a complete hepatectomy radically removing all tumorous tissue along with the surrounding cirrhotic parenchyma, which is otherwise associated with a very high risk of recurrence. For HCC in non-cirrhotic livers and iCCA, liver resection is the treatment of choice. Nowadays, even extended resections can be performed with low mortality in experienced centers. Surgical therapy is more and more embedded into multimodal treatment concepts and decision making should be interdisciplinary as for other gastrointestinal tumors.

Preoperative endoscopic pyloric balloon dilatation decreases the rate of delayed gastric emptying after Ivor-Lewis esophagectomy.

Delayed gastric emptying (DGE) after Ivor-Lewis esophagectomy occurs postoperatively in up to 50% of the patients. This pyloric dysfunction can lead to severe secondary complications postoperatively such as early aspiration, pneumonia or may even have an impact on anastomotic healing and therefore leakage. Early detection of DGE is essential to prevent further complications. The common treatment postoperatively is endoscopic pyloric balloon dilatation (EPBD) after symptoms already occurred. In our work, we analyzed patients who received a preoperative EPBD during the routine restaging endoscopy and compared those patients to a control group to analyze if preoperative EPBD may prevent postoperative DGE and secondary additional complications. We performed a single-center retrospective analysis of 115 patients who received an Ivor-Lewis esophagectomy by the same surgeon between June 2015 and October 2017. Out of these 115 patients, 91 (79.1%) patients received EPBD preoperatively during the staging/restaging endoscopy (PDG, pyloric dilatation group). In 24 (20.9%) patients, preoperative EPBD was not performed due to stenotic esophageal tumors or logistic reasons (NDG, non-pyloric dilatation group). Data of the PDG and NDG group were compared regarding the rate of postoperative DGE as well as DGE and EPBD related complications. In total, 21 (18.3%) patients developed pyloric dysfunction requiring a total of 27 EPBD during follow-up. There were 12 (13.2%) patients in the PDG and 9 (37.5%) patients in the NDG (p = 0.014), respectively. DGE-related complications such as anastomotic leaks (p = 0.466), pulmonary complications (p = 0.466) and longer median hospital stay (p = 0.685) were more frequent in the NDG group; however this difference did not reach statistical significance. The success rate for postoperative EPBD with 20-mm balloons was lower (58.5%) compared to the usage of 30-mm balloons (93.3%). All pre- and postoperative EPBD were performed without any complications. Preoperative EPBD is feasible, safe and can be combined with restating endoscopy. It seems that preoperative EPBD reduces the incidence of DGE and can prevent the need for early postoperative endoscopic interventions. Our recommendation is therefore to perform an EPBD preoperatively when possible to reduce postoperative complications to a minimum. For postoperative EPBD, we recommend the use of the 30-mm balloon due to lower redilatation rates.

Pregnancy and perinatal conditions and atopic disease prevalence in childhood and adulthood.

BACKGROUND: Previous studies showed controversial results for the influence of pregnancy-related and perinatal factors on subsequent respiratory and atopic diseases in children. The aim of this study was to assess the association between perinatal variables and the prevalence of asthma, bronchial hyperreactivity (BHR), flexural eczema (FE), allergic rhinitis, and sensitization in childhood and early adulthood. METHODS: The studied population was first examined in Munich and Dresden in 1995/1996 at age 9-11 years. Participants were followed until age 19-24 years using questionnaires and clinical examinations. Associations between perinatal data and subsequent atopic diseases were examined using logistic regression analyses adjusting for potential confounders. RESULTS: Cesarean section was statistically significantly associated with BHR in early adulthood (odds ratio 4.8 [95% confidence interval 1.5-15.2]), while assisted birth was associated with presence of asthma symptoms in childhood (2.2 [1.2-3.9]), FE symptoms (2.2 [1.2-4.3]) and doctor's diagnosis of atopic dermatitis (1.9 [1.0-3.4]) in childhood, and sensitization in early adulthood (2.2 [1.1-4.3]). Lower birth length (1.9 [1.1-3.2]), lower birthweight (0.5 [0.3-0.9]), and higher birthweight (0.6 [0.4-1.0]) were predictive of sensitization in early adulthood compared to average birth length and birthweight, respectively. None of the other perinatal factors showed statistically significant associations with the outcomes. CONCLUSIONS: Our results indicate that children who are born by cesarean section and especially by assisted birth, might be at greater risk for developing asthma, FE, and sensitization and should hence be monitored. Prenatal maternal stress might partly explain these associations, which should be further investigated.

Flexible enzymatic activation of artificial polyketide extender units by Streptomyces cinnamonensis into the monensin biosynthetic pathway.

Streptomyces cinnamonensis A495 is a variant of the monensin producer which instead of the native polyether antibiotic gives rise to antibiotic and anti-tumour shunt-product premonensin. Through the supplementation of the fermentation medium with suitable precursors, premonensin can be derivatized via the incorporation of new-to-nature extender units into the biosynthetic machinery. Polyketide extender units require activation, typically in form of coenzyme A-thioesters. These are membrane impermeable and thus in the past an artificial mimic was employed. Here, we show the use and preliminary characterization of a highly substrate promiscuous new enzyme for the endogenous thioester formation in a Streptomyces strain. These intracellularly activated alternative extender units are significantly better incorporated into premonensin than the synthetically activated counterparts. SIGNIFICANCE AND IMPACT OF THE STUDY: Polyketide natural products are of enormous relevance in medicine. The hit-rate in finding active compounds for the potential treatment of various diseases among this substance family of microbial origin is high. However, most polyketides require derivatization to render them suitable for the application. Of relevance in this field is the incorporation of artificial substances into the biogenesis of polyketides, hampered by both the microbial metabolism and the complexity of the enzymes involved. This manuscript describes the straightforward and selective biosynthetic incorporation of synthetic substances into a reduced polyketide and showcases a promising new enzyme to aid this purpose.

[Computer-assisted 3D-navigated laparoscopic resection of a vanished colorectal liver metastasis after chemotherapy]. / Die verschwundene Lebermetastase - Neues Einsatzgebiet für die computerassistierte 3D-navigierte laparoskopische Leberesektion?

BACKGROUND: Modern chemotherapy regimen for colorectal cancer results in complete radiologic remission in a substantial number of cases. However, these "vanished liver metastases" (VLM) often contain vital tumor cells, which mandates the resection of such lesions. In these cases, intraoperative identification of VLM can be challenging, in particular in laparoscopic approaches. We describe the first laparoscopic computer-assisted 3D-navigated resection of a VLM. CASE REPORT: A 60-year-old patient with a synchronous liver metastasis (segment IVb) of sigmoid colon cancer (T4 N1 M1) was referred to our center for elective liver resection after laparoscopic sigmoid resection and systemic chemotherapy (FOLFIRI/Panitumumab). The metastasis was not visible anymore on preoperative CT or sonography. Thus, a 3 D reconstruction of the liver was performed. The size of the initial metastasis (before chemotherapy) was transferred into the current CT. A computer-assisted 3D-navigated laparoscopic resection of the metastasis was performed on these fused images. The metastasis was also not clearly visible upon intraoperative ultrasound. Histology of the resected specimen revealed a 0.5 cm metastasis with predominantly vital tumor cells (regression degree 4 of Rubbia-Brandt) and a sufficient resection margin of at least 7 mm. The postoperative course was uneventful. CONCLUSION: Computer-assisted 3D-navigation enabled a safe oncologic resection of a vanished liver metastasis after chemotherapy. This technique was particularly helpful due to the limited haptic feedback of laparoscopic surgery. Further studies are necessary to verify the clinical benefit of computer assisted 3D-navigated liver surgery.

Knowledge management in dementia care networks: a qualitative analysis of successful information and support strategies for people with dementia living at home and their family caregivers.

OBJECTIVES: Stakeholders involved in community dementia support services often work on their own and without coordination with other services. These circumstances can result in a lack of information and support for people with dementia and their family caregivers at home. To increase the coordination between existing support services, so-called 'Dementia Care Networks' (DCNs) have been established. Most of the tasks that are performed in DCNs are based on communication strategies. Therefore, knowledge management (KM) is a key process in these networks. However, few studies have focused on this topic. This study attempted to evaluate KM strategies in DCNs across Germany as part of the DemNet-D study. STUDY DESIGN: A qualitative interview study design was used. METHODS: Qualitative data were collected during single and group interviews with key persons associated with thirteen DCNs. Interviews were audiotaped and transcribed, and a structured content analysis was conducted. The framework for the analysis was derived from a KM model. RESULTS: Information dissemination strategies for people with dementia and their informal caregivers based on actively established contacts appear to be more successful than passive strategies. General practitioners often play a key role as external gatekeepers in initiating contact between a network and a person affected by dementia. In this context, case managers can help integrate external stakeholders, such as general practitioners or pharmacists, into DCNs using different KM strategies. The systematic development of common objectives under an agency-neutral leadership seems to be an important aspect of successful KM within DCNs. CONCLUSIONS: The findings reported here can help DCNs optimize their KM strategies for generating tailored information and support services for people with dementia living at home and their family caregivers. In particular, the identified potential knowledge distribution barriers and facilitators will be of practical use to DCN stakeholders.

[Effectiveness and Cost-Effectiveness of a Multifactorial Fall Prevention Programme in Nursing Homes in a Real-World Setting]. / Effektivität und Kosteneffektivität einer multifaktoriellen Sturzpräventions-maßnahme in Pflegeheimen im Versorgungsalltag.

The purpose of the present study was to analyse the effectiveness and cost-effectiveness of a multifactorial fall prevention programme in nursing home residents in a real-world setting. The adjusted relative risk of a femoral fracture was 0.82 (95% CI 0.72-0.93) in residents exposed to the fall and fracture prevention programme compared to residents from the control group. Given a willingness-to-pay of 50,000 EUR per year free of femoral fractures from a payer perspective the probability that the intervention is cost-effective was 83%.

A brief history of technical developments in intracytoplasmic sperm injection (ICSI). Dedicated to the memory of J.M. Cummins.

Intracytoplasmic sperm injection (ICSI) is an assisted reproductive technology for treatment of severe male infertility introduced into clinical practice in 1992. This review provides a brief history of the development of ICSI by acknowledging major developments in the field. The review addresses key developments in pre-clinical and early studies, how ICSI compares with in vitro fertilisation, long-term consequences, how the mechanistic approach to ICSI has changed in both manual and semi-automated approaches, and how sperm selection procedures are integrated into ICSI. From the beginnings using animal models in the 1960-1970s, the development of ICSI is a remarkable and transformative success story. Indeed, its broad use (70% of cycles globally) exceeds the need required for treating infertile males, and this remains a controversial issue. There remain questions around the long-term health impacts of ICSI. Furthermore, advances in automation of the ICSI procedure are occurring. An estimated 6million children have been born from the ICSI procedure. With further automation of sperm selection technologies, coupled with automation of the injection procedure, it is likely that the proportion of children born from ICSI will further increase.

Brief light stimulation during the mouse nocturnal activity phase simultaneously induces a decline in core temperature and locomotor activity followed by EEG-determined sleep.

Light exerts a variety of effects on mammals. Unexpectedly, one of these effects is the cessation of nocturnal locomotion and the induction of behavioral sleep (photosomnolence). Here, we extend the initial observations in several ways, including the fundamental demonstration that core body temperature (T(c)) drops substantially (about 1.5°C) in response to the light stimulation at CT15 or CT18 in a manner suggesting that the change is a direct response to light rather than simply a result of the locomotor suppression. The results show that 1) the decline of locomotion and T(c) begin soon after nocturnal light stimulation; 2) the variability in the magnitude and onset of light-induced locomotor suppression is very large, whereas the variability in T(c) is very small; 3) T(c) recovers from the light-induced decline in advance of the recovery of locomotion; 4) under entrained and freerunning conditions, the daily late afternoon T(c) increase occurs in advance of the corresponding increase in wheel running; and 5) toward the end of the subjective night, the nocturnally elevated T(c) persists longer than does locomotor activity. Finally, EEG measurements confirm light-induced sleep and, when T(c) or locomotion was measured, show their temporal association with sleep onset. Both EEG- and immobility-based sleep detection methods confirm rapid induction of light-induced sleep. The similarities between light-induced loss of locomotion and drop in T(c) suggest a common cause for parallel responses. The photosomnolence response may be contingent upon both the absence of locomotion and a simultaneous low T(c).

Cost-effectiveness of a multifactorial fall prevention program in nursing homes.

UNLABELLED: The purpose of this study was to analyze the cost-effectiveness of a multifactorial fall prevention program in nursing home residents. Given a willingness-to-pay (WTP) of 50,000 EUR per year free of femoral fracture, the probability that the intervention is cost-effective is 83%. INTRODUCTION: Despite their increased risk of falls and fractures, nursing home residents have been neglected in economic evaluations of fall prevention programs so far. The purpose of this study was to analyze, for the first time, the cost-effectiveness of a multifactorial fall prevention program in nursing home residents. METHODS: This study is part of a prospective, unblinded, cluster, nonrandomized, controlled study focusing on the transfer of an efficacious fall prevention program into a real-world setting. The analyzed subsample was derived from claims data and consisted of data on intervention (n=256, residents n=10,178) and control homes (n=893, residents n=22,974), representing all insurants of a sickness fund (AOK Bavaria, Germany) who were 65 years or older, residing in a nursing home on the 31st of March 2007 and had a level of care of ≥1 according to the classification of the statutory long-term care insurance. Time free of femoral fracture (ICD-10, S72) was used as measure of health effects. Femoral fracture-related costs and intervention costs were measured from a payer perspective. Multivariate regression models were applied. Sensitivity analyses were performed and cost-effectiveness acceptability curves computed. RESULTS: Within the first year of the intervention, femoral fracture rate was significantly reduced, resulting in a nonsignificant incremental mean time of 1.41 days free of femoral fracture. Incremental mean total direct costs were 29 EUR per resident, which was not significant. The incremental cost-effectiveness ratio (ICER) was 7,481 EUR per year free of femoral fracture. The probability of an ICER<50,000 EUR per year free of femoral fracture was 83%. CONCLUSION: Depending on the amount the decision-maker is willing to pay for the incremental effect, the fall prevention program might be cost-effective within the first year. Future studies should expand the range of costs and effects measured.

Echinococcosis mimicking autoimmune or malignant bile duct disease.

Indeterminate strictures of the bile ducts are common diagnostic dilemmas in gastroenterology, and differential diagnosis includes inflammatory and neoplastic diseases. Alveolar echinococcosis (AE) is rarely considered as a differential diagnosis, although it is endemic in the Northern hemisphere. In this case report on a 50-year-old male patient, the lack of cystic lesions or calcifications on CT, and suggestive ERCP findings made a hilar cholangiocellular carcinoma the most probable differential diagnosis, and only explorative laparotomy provided the definite diagnosis of AE. AE should therefore be included in the differential diagnosis of indeterminate biliary strictures even in the absence of typical stigmata in imaging studies.

Incidences and predictors of difficult laryngoscopy in adult patients undergoing general anesthesia : a single-center analysis of 102,305 cases.

BACKGROUND: Hypoxemia caused by difficulties in airway management presents a major cause for perioperative morbidity and mortality. The ability to predict difficult laryngoscopy more accurately would enable anesthesiologists to take specific precautions to reduce airway risks and prevent patient-threatening events. METHODS: Over a 6-year period of time, all anesthesia records with a documented direct laryngoscopic view were retrieved from the electronic data management system and statistically processed. The Cormack-Lehane four-point scale of grading laryngoscopy was used to assess visibility of the vocal cords. RESULTS: Of 102,306 cases, the overall rate of difficult laryngoscopy was 4.9 %. Male gender (6.5 %), Mallampati score III and IV (17.3 %), obesity with a BMI ≥35 kg/m(2) (6.1 %), as well as physical status ASA III or IV (6.2 %), were identified as risk factors for difficult laryngoscopy. Patients undergoing surgery in the departments of oromaxillofacial (8.9 %), ear nose throat surgery (ENT) (7.4 %), and cardiac surgery (7.0 %) showed the highest rates of difficult laryngoscopy. CONCLUSIONS: The results indicate that the risk for difficult airway situations might substantially differ between surgical patient groups. In hospitals with departmental structures and spatially separated operating rooms, the deduction might be increased awareness and particular structural preparation for difficult airway situations in the respective subspecialties.

Quality of life in nursing homes following the group-living principle: a pilot study measuring the quality of life from the subjective perspective of dependent-living elderly.

BACKGROUND: The purpose of this study was to analyze the subjective quality of life in elderly people in nursing homes following the group-living principle. METHODS: The Nottingham Health Profile (NHP) was employed. A comparison with the German representative subsample of elderly living independently age-group over 75 was conducted. Psychometric properties and appropriateness were analyzed. RESULTS: The mean NHP scale scores suggest an acceptable perception of residents' quality of life (n = 145). Our findings indicate that with exception of the NHP scale physical mobility, the perceived quality of life of group-living nursing home residents and independently living elderly over 75 years (German reference values) are nearly on the same level. With the exception of the subscale social isolation, the results of the current study show that the NHP is suitable for assessing the subjective quality of life in nursing home environments. CONCLUSION: The results of the first pilot study in the research field of subjective quality of life in group-living nursing homes are presented. The study focused on very old people with age-specific reduced physical and mental abilities. The NHP should also be considered as a reliable, valid and useful alternative to resident satisfaction surveys.

Education Team Time Out in Oncologic Visceral Surgery Optimizes Surgical Resident Training and Team Communication-Results of a Prospective Trial.

BACKGROUND: Surgical education is highly dependent on intraoperative communication. Trainers must know the trainee's training level to ensure high-quality surgical training. A systematic preoperative dialogue (Educational Team Time Out, ETO) was established to discuss the steps of each surgical procedure. METHODS: Over 6 months, ETO was performed within a time limit of 3 minutes. Digital surveys on the utility of ETO and its impact on performance were conducted immediately after surgery and at the end of the study period among the staff of the participating disciplines (trainer, trainee, surgical nursing staff, anaesthesiologists, and medical students). The number of surgical substeps performed was recorded and compared with the equivalent period one year earlier. RESULTS: ETO was performed in 64 of the 103 eligible operations (62%). Liver resection (n = 37) was the most frequent procedure, followed by left-sided colorectal surgery (n = 12), partial pancreaticoduodenectomy (n = 6), right-sided hemicolectomies (n = 5), and thyroidectomies (n = 4). Anaesthesiologists most frequently reported that ETO had a direct impact on their work during surgery (90.9%). The influence scores were 46.8% for trainees, 8.8% for trainers, 53.3% for surgical nursing staff and 66.6% for medical students. During the implementation of ETO, a trend towards more assisted substeps in oncologic visceral surgery was seen compared to the corresponding period one year earlier (51% vs.40%; p = 0.11). CONCLUSION: ETO leads to improved intraoperative communication and more performed substeps during complex procedures, which increases motivation and practical training. This concept can easily be implemented in all surgical specialties to improve surgical education.

Sleep disturbance induces neuroinflammation and impairment of learning and memory.

Hospitalized patients can develop cognitive function decline, the mechanisms of which remain largely to be determined. Sleep disturbance often occurs in hospitalized patients, and neuroinflammation can induce learning and memory impairment. We therefore set out to determine whether sleep disturbance can induce neuroinflammation and impairment of learning and memory in rodents. Five to 6-month-old wild-type C57BL/6J male mice were used in the studies. The mice were placed in rocking cages for 24 h, and two rolling balls were present in each cage. The mice were tested for learning and memory function using the Fear Conditioning Test one and 7 days post-sleep disturbance. Neuroinflammation in the mouse brain tissues was also determined. Of the Fear Conditioning studies at one day and 7 days after sleep disturbance, twenty-four hour sleep disturbance decreased freezing time in the context test, which assesses hippocampus-dependent learning and memory; but not the tone test, which assesses hippocampus-independent learning and memory. Sleep disturbance increased pro-inflammatory cytokine IL-6 levels and induced microglia activation in the mouse hippocampus, but not the cortex. These results suggest that sleep disturbance induces neuroinflammation in the mouse hippocampus, and impairs hippocampus-dependent learning and memory in mice. Pending further studies, these findings suggest that sleep disturbance-induced neuroinflammation and impairment of learning and memory may contribute to the development of cognitive function decline in hospitalized patients.

Involvement of p32 and microtubules in alteration of mitochondrial functions by rubella virus.

The interaction of the rubella virus (RV) capsid (C) protein and the mitochondrial p32 protein is believed to participate in virus replication. In this study, the physiological significance of the association of RV with mitochondria was investigated by silencing p32 through RNA interference. It was demonstrated that downregulation of p32 interferes with microtubule-directed redistribution of mitochondria in RV-infected cells. However, the association of the viral C protein with mitochondria was not affected. When cell lines either pretreated with respiratory chain inhibitors or cultivated under (mild) hypoxic conditions were infected with RV, viral replication was reduced in a time-dependent fashion. Additionally, RV infection induces increased activity of mitochondrial electron transport chain complex III, which was associated with an increase in the mitochondrial membrane potential. These effects are outstanding among the examples of mitochondrial alterations caused by viruses. In contrast to the preferential localization of p32 to the mitochondrial matrix in most cell lines, RV-permissive cell lines were characterized by an almost exclusive membrane association of p32. Conceivably, this contributes to p32 function(s) during RV replication. The data presented suggest that p32 fulfills an essential function for RV replication in directing trafficking of mitochondria near sites of viral replication to meet the energy demands of the virus.

[Fall and fracture prevention based on the National Expert Standard. Implementation and costs in a real world setting in nursing homes]. / Sturz- und Frakturprävention auf der Grundlage des Nationalen Expertenstandards Sturzprophylaxe. Umsetzung und Kosten im Versorgungsalltag im Setting Pflegeheim.

BACKGROUND: A National Expert Standard for Fall and Fracture Prevention ("Expertenstandard Sturzprophylaxe") was established a few years ago in Germany. The purpose of this study was to determine for the first time the implementation and costs of fall and fracture prevention measures based on this National Expert Standard in German nursing homes in a real world setting. MATERIAL AND METHODS: This before/after study is based on an un-blinded, controlled translational study focussing on the primary prevention of fall-related hip fractures in nursing homes in Bavaria. 274 nursing homes were included in this study in 2008. The intervention aimed at implementing fall and fracture prevention measures based on the National Expert Standard. A random sample of 79 nursing homes was assessed via telephone at baseline and two follow ups. Costs were determined from a societal perspective, based on a questionnaire covering use and costs of fall and fracture prevention measures. Costs were analysed using paired t-tests and non-parametric bootstrapping techniques. RESULTS: The implementation of this program led to an increase in fall and fracture prevention activities and to additional mean costs of 6,248 EUR (± SD 7,340 EUR; pricing year 2008) per nursing home over 18 months. Costs varied widely between nursing homes. The majority of additional costs occurred for the implementation of strength and balance training. Depending on type and costs of staff conducting the training, total costs varied between 4,347 EUR (± SD 7,167 EUR) and 7,024 EUR (± SD 7,439 EUR). CONCLUSION: The implementation of fall and fracture prevention measures based on the National Expert Standard led to additional costs. Cost figures can be used by decision-makers with respect to decisions on resource allocation for different prevention programs (e.g., different National Expert Standards), to determine the main cost components, and finally for model-based cost-effectiveness analyses of fall-prevention programs in nursing homes.

Two novel mouse models of slow-wave-sleep enhancement in aging and Alzheimer's disease.

Aging and Alzheimer's disease (AD) are both associated with reduced quantity and quality of the deepest stage of sleep, called slow-wave-sleep (SWS). Slow-wave-sleep deficits have been shown to worsen AD symptoms and prevent healthy aging. However, the mechanism remains poorly understood due to the lack of animal models in which SWS can be specifically manipulated. Notably, a mouse model of SWS enhancement has been recently developed in adult mice. As a prelude to studies assessing the impact of SWS enhancement on aging and neurodegeneration, we first asked whether SWS can be enhanced in animal models of aging and AD. The chemogenetic receptor hM3Dq was conditionally expressed in GABAergic neurons of the parafacial zone of aged mice and AD (APP/PS1) mouse model. Sleep-wake phenotypes were analyzed in baseline condition and following clozapine-N-oxide (CNO) and vehicle injections. Both aged and AD mice display deficits in sleep quality, characterized by decreased slow wave activity. Both aged and AD mice show SWS enhancement following CNO injection, characterized by a shorter SWS latency, increased SWS amount and consolidation, and enhanced slow wave activity, compared with vehicle injection. Importantly, the SWS enhancement phenotypes in aged and APP/PS1 model mice are comparable to those seen in adult and littermate wild-type mice, respectively. These mouse models will allow investigation of the role of SWS in aging and AD, using, for the first time, gain-of SWS experiments.