Background Endoscopic retrograde cholangiopancreatography (ERCP) requires moderate to deep sedation, usually with propofol. Adverse effects of propofol sedation are relatively common, such as respiratory and cardiovascular depression. This study was conducted to determine if doxapram, a respiratory stimulant, could be used to reduce the incidence of respiratory depression. Methods This is a single-center, prospective randomized double-blind study performed in the endoscopy unit of Helsinki University Central Hospital. 56 patients were randomized in a 1:1 ratio to either receive doxapram as an initial 1 mg/kg bolus and an infusion of 1 mg/kg/h (group DOX) or placebo (group P) during propofol sedation for ERCP. Main outcome measures were apneic episodes and hypoxemia (SpO(2) <90%). Mann-Whitney test for continuous variables and Fisher's exact test for discrete variables were used and mixed effects modeling to take into account repeated measurements on the same subject and comparing both changes within a group as a function of time and between the groups. Results There were no statistically significant differences in apneic episodes (p = 0.18) or hypoxemia (p = 0.53) between the groups. There was a statistically significant rise in etCO(2) levels in both groups, but the rise was smaller in group P. There was a statistically significant rise in Bispectral Index (p = 0.002) but not modified Observer's Assessment of Agitation/Sedation (p = 0.21) in group P. There were no statistically significant differences in any other measured parameters. Conclusions Doxapram was not effective in reducing respiratory depression caused by deep propofol sedation during ERCP. Further studies are warranted using different sedation protocols and dosing regimens.

Background Pharmacological interventions for sleep (analgesic, sedative and hypnotic agents) can both disrupt and induce sleep and have many negative side effects within the intensive care population. The use of complementary and alternative medicine therapies to assist with sleep has been studied but given the variety of modalities and methodological limitations no reliable conclusions have been drawn. Objective To synthesise research findings regarding the effectiveness of using complementary and alternative medicine interventions within the domains of mind and body practices (relaxation techniques, acupuncture) and natural biologically based products (herbs, vitamins, minerals, probiotics) on sleep quality and quantity in adult intensive care patients. Review method used Systematic review Data sources Five databases were searched in August 2018 and updated in February 2019 and 2020. Review methods: Searches were limited to peer reviewed randomised controlled trials, published in English involving adult populations in intensive care units. Interventions were related to the complementary and alternative medicine domains of mind and body practices and natural products. Included studies were assessed using Cochrane's risk of bias tool. Results Seventeen studies were included. The interventions used varied: 4 investigated melatonin; 4 music +/- another therapy; 3 acupressure; 2 aromatherapy and 1 each for relaxation and imagery, reflexology, bright light exposure and inspiratory muscle training. Measurement of sleep quantity and quality was also varied: 5 studies used objective measures such as Polysomnography and Bispectral index with the remaining using subjective patient or clinician assessment (for example, Richards-Campbell Sleep Questionnaire, Pittsburgh Sleep Quality Index, observation). Given the different interventions, outcomes and measures used in the studies a meta-analysis was not possible. Generally, the results support the use of complementary and alternative medicine for assisting with sleep with 11 out of 17 trials reporting significant results for the interventions examined. Conclusions Complementary and alternative medicine interventions, in particular, melatonin and music, have shown promise for improving sleep in adults with critically conditions; however, further research that addresses the limitations of small sample sizes and improved techniques for measuring sleep is needed.

Recovery of lower-limb function after spinal cord injury (SCI) is dependent on the extent of remaining neural transmission in the corticospinal pathway. The aim of this proof-of-concept pilot study was to explore the effects of long-term paired associative stimulation (PAS) on leg muscle strength and walking in people with SCI. Five individuals with traumatic incomplete chronic tetraplegia (>34 months post-injury, motor incomplete, 3 females, mean age 60 years) with no contraindications to transcranial magnetic stimulation (TMS) received PAS to one or both legs for 2 months (28 sessions in total, 5 times a week for the first 2 weeks and 3 times a week thereafter). The participants were evaluated with the Manual Muscle Test (MMT), AIS motor and sensory examination, Modified Asworth Scale (MAS), and the Spinal Cord Independence Measure (SCIM) prior to the intervention, after 1 and 2 months of PAS, and after a 1-month follow-up. The study was registered at (NCT03459885). During the intervention, MMT scores and AIS motor scores increased significantly (p = 0.014 and p = 0.033, respectively). Improvements were stable in follow-up. AIS sensory scores, MAS, and SCIM were not modified significantly. MMT score prior to intervention was a good predictor of changes in walking speed (Radj2 = 0.962). The results of this proof-of-concept pilot study justify a larger trial on the effect of long-term PAS on leg muscle strength and walking in people with chronic incomplete SCI.

A considerable proportion of shift workers have work schedule-related insomnia and/or excessive sleepiness, a phenomenon described as shift work disorder (SWD). There is yet a lack of evidence on whether or not employees recover from symptoms of SWD between work shifts. We studied whether SWD and its subtypes are associated with insomnia and excessive sleepiness during weekly non-work days and with 24-h sleep time. Hospital employees answered a survey on SWD, insomnia and excessive sleepiness on weekly non-work day s, and 24-h sleep. To identify shift workers with night shifts (n=2,900, 18% with SWD) and SWD, we linked survey responses to employers' register on NI orking hours. SWD included three subtypes: insomnia only (SWD-I, 4%, n=102), excessive sleepiness only (SWD-Es, 8%, n=244), and both insomnia and excessive sleepiness (SWD-IEs, 6%, n=183). Based on regression analy ses, SWD was associated with excessive sleepiness on non-work days (OR: 1.42, 95% CI: 1.07-1.88) and with insomnia on non-work days (0.53, 0.31-0.91). SWD-I was associated with excessive sleepiness on non-work days (2.25, 1.31-3.87) and with shorter sleep (7-7.5 h: 1.96, 1.06-3.63; = 8 h). The results suggest that especially employees with SWD-I may need longer time to overcome excessive sleepiness than allowed by their roster.

BackgroundTechnical applications can promote home-based exercise and physical activity of community-dwelling stroke survivors. Caregivers are often able and willing to assist with home-based exercise and physical activity but lack the knowledge and resources to do so. ActivABLES was established to promote home-based exercise and physical activity among community-dwelling stroke survivors, with support from their caregivers. The aim of our study is to investigate the feasibility of ActivABLES in terms of acceptability, demand, implementation and practicality.MethodsA convergent design of mixed methods research in which quantitative results were combined with personal experiences of a four-week use of ActivABLES by community-dwelling stroke survivors with support from their caregivers. Data collection before, during and after the four-week period included the Berg Balance Scale (BBS), Activities-Specific Balance Confidence Scale (ABC), Timed-Up-and-Go (TUG) and Five Times Sit to Stand Test (5xSST) and data from motion detectors. Semi-structured interviews were conducted with stroke survivors and caregivers after the four-week period. Descriptive statistics were used for quantitative data. Qualitative data was analysed with direct content analysis. Themes were identified related to the domains of feasibility: acceptability, demand, implementation and practicality. Data was integrated by examining any (dis)congruence in the quantitative and qualitative findings.ResultsTen stroke survivors aged 55-79years participated with their informal caregivers. Functional improvements were shown in BBS (+2.5), ABC (+0.9), TUG (-4.2) and 5xSST (-2.7). More physical activity was detected with motion detectors (stand up/sit down +2, number of steps +227, standing +0.3h, hours sitting/lying -0.3h). The qualitative interviews identified themes for each feasibility domain: (i) acceptability: appreciation, functional improvements, self-initiated activities and expressed potential for future stroke survivors; (2) demand: reported use, interest in further use and need for follow-up; (3) implementation: importance of feedback, variety of exercises and progression of exercises and (4) practicality: need for support and technical problems. The quantitative and qualitative findings converged well with each other and supported the feasibility of ActivABLES.ConclusionsActivABLES is feasible and can be a good asset for stroke survivors with slight or moderate disability to use in their homes. Further studies are needed with larger samples.

We developed numerical simulations of potential future ecological states of the Baltic Sea ecosystem at the end of century under five scenarios. We used a spatial food web (Ecospace) model, forced by a physical-biogeochemical model. The scenarios are built on consistent storylines that describe plausible developments of climatic and socioeconomic factors in the Baltic Sea region. Modelled species diversity and fish catches are driven by climate- and nutrient load-related changes in habitat quality and by fisheries management strategies. Our results suggest that a scenario including low greenhouse gas concentrations and nutrient pollution and ecologically focused fisheries management results in high biodiversity and catch value. On the other hand, scenarios envisioning increasing societal inequality or economic growth based on fossil fuels, high greenhouse gas emissions and high nutrient loads result in decreased habitat quality and diminished biodiversity. Under the latter scenarios catches are high but they predominantly consist of lower-valued fish.

Objective To discover common genetic variants associated with poststroke outcomes using a genome-wide association (GWA) study. Methods The study comprised 6,165 patients with ischemic stroke from 12 studies in Europe, the United States, and Australia included in the GISCOME (Genetics of Ischaemic Stroke Functional Outcome) network. The primary outcome was modified Rankin Scale score after 60 to 190 days, evaluated as 2 dichotomous variables (0-2 vs 3-6 and 0-1 vs 2-6) and subsequently as an ordinal variable. GWA analyses were performed in each study independently and results were meta-analyzed. Analyses were adjusted for age, sex, stroke severity (baseline NIH Stroke Scale score), and ancestry. The significance level was p <5 x 10(-8). Results We identified one genetic variant associated with functional outcome with genome-wide significance (modified Rankin Scale scores 0-2 vs 3-6, p = 5.3 x 10(-9)). This intronic variant (rs1842681) in the LOC105372028 gene is a previously reported trans-expression quantitative trait locus for PPP1R21, which encodes a regulatory subunit of protein phosphatase 1. This ubiquitous phosphatase is implicated in brain functions such as brain plasticity. Several variants detected in this study demonstrated suggestive association with outcome (p <10(-5)), some of which are within or near genes with experimental evidence of influence on ischemic stroke volume and/or brain recovery (e.g., NTN4, TEK, and PTCH1). Conclusions In this large GWA study on functional outcome after ischemic stroke, we report one significant variant and several variants with suggestive association to outcome 3 months after stroke onset with plausible mechanistic links to poststroke recovery. Future replication studies and exploration of potential functional mechanisms for identified genetic variants are warranted.

The influence of lake restoration efforts on lake bottom-water conditions and varve preservation is not well known. We studied varved sediments deposited during the last 80 years along a water-depth transect in the Enonsaari Deep, a deep-water area of the southernmost Enonselka Basin, Lake Vesijarvi, southern Finland. For the last few decades, the Enonselka Basin has been subject to ongoing restoration efforts. Varve, elemental, and diatom analyses were undertaken to explore how these actions and other human activities affected varve preservation in the Enonsaari Deep. In contrast to most varved Finnish lakes, whose water columns have a natural tendency to stratify, and possess varve records that span thousands of years, varve formation and preservation in Lake Vesijarvi was triggered by relatively recent anthropogenic stressors. The multi-core varve analysis revealed that sediment in the Enonsaari Deep was initially non-varved, but became fully varved in the late 1930s, a time of increasing anthropogenic influence on the lake. The largest spatial extent of varves occurred in the 1970s, which was followed by a period of less distinguishable varves, which coincided with diversion of sewage from the lake. Varve preservation weakened during subsequent decades and was terminated completely by lake aeration in the 2010s. Despite improvements in water quality, hypolimnetic oxygen depletion and varve preservation persisted beyond the reduction in sewage loading, initial aeration, and biomanipulation. These restoration efforts, however, along with other human actions such as harbor construction and dredging, did influence varve characteristics. Varves were also influenced by diatom responses to anthropogenic forcing, because diatoms form a substantial part of the varve structure. Of all the restoration efforts, a second episode of aeration seems to have had the single most dramatic impact on profundal conditions in the basin, resulting in replacement of a sediment accumulation zone by a transport or erosional zone in the Enonsaari Deep. We conclude that human activities in a lake and its catchment can alter lake hypolimnetic conditions, leading to shifts in lake bottom dynamics and changes in varve preservation.

Purpose: Interleukin 6 (IL-6) and the acute phase C-reactive protein (CRP) blood concentrations after lumbar spine fusion may be affected by age. The purpose of this prospective observational study was to assess postoperative serum levels of pro-inflammatory IL-6 and CRP after instrumented lumbar spine fusion surgery. We hypothesized that older patients would have increased levels of IL-6 and CRP after surgery. Methods: IL-6 and high-sensitive CRP biochemical marker levels were measured before instrumented spinal fusion, and postoperatively at 1 and 3 days, 6 weeks, and 3 months. The 49 patients in this sample were divided into two groups: age 60 years (n = 26). Results: Acute changes in IL-6 high-sensitivity and CRP from preoperative levels to postoperative day (POD) 1 increased with age. Mean (95% CI) difference between the age-groups in changes of IL-6 at PODs 1 and 3 was 45 pg/ml (10-83, p = 0.014) and 20 pg/ml (5-36, p = 0.021), respectively. Mean (95% CI) difference between groups in changes of CRP at PODs 1 and 3 was 9.6 mg/l (-3.5 to 22.7, p = 0.47) and 24.8 mg/l (-17 to 67, p = 0.33), respectively. Both groups had decreased IL-6 and CRP levels at 6 weeks after surgery compared to the preoperative level. Conclusions: Elevation of IL-6 and CRP is stronger in patients over 60 years old after instrumented lumbar spinal fusion. The CRP and IL-6 are sensitive markers for acute postoperative inflammation. Even high acute CRP values do not necessarily indicate postoperative infection.