Carry-over of host nutrients during sampling enhances undesired growth of Staphylococcus aureus in liquid Amies transport medium

Optimal transportation of bacteria is important for accurate clinical interpretation, quantitative assays, and microbiome studies. A transport medium should ideally keep the bacteria alive without supporting growth or altering the relative proportions of the constituent species. We investigated the effect of nasal mucus and mucin on the growth and survival of two Staphylococcus aureus strains in liquid Amies transport medium at room temperature and 4?°C for 14?days. The study showed that the presence of nasal mucus in microbiological samples stimulated undesired S. aureus growth at room temperature in a dose-dependent manner. These findings underscore that microbiological samples from humans and animals should be stored at 4?°C until analysis to avoid undesired S. aureus growth.     

DEVOTE 3: temporal relationships between severe hypoglycaemia,cardiovascular outcomes and mortality

Aims/hypothesis

The double-blind Trial Comparing Cardiovascular Safety of Insulin Degludec vs Insulin Glargine in Patients with Type 2 Diabetes at High Risk of Cardiovascular Events (DEVOTE) assessed the cardiovascular safety of insulin degludec. The incidence and rates of adjudicated severe hypoglycaemia, and all-cause mortality were also determined. This paper reports a secondary analysis investigating associations of severe hypoglycaemia with cardiovascular outcomes and mortality.

Methods

In DEVOTE, patients with type 2 diabetes were randomised to receive either insulin degludec or insulin glargine U100 (100 units/ml) once daily (between dinner and bedtime) in an event-driven, double-blind, treat-to-target cardiovascular outcomes trial. The primary outcome was the first occurrence of an adjudicated major adverse cardiovascular event (MACE; cardiovascular death, non-fatal myocardial infarction or non-fatal stroke). Adjudicated severe hypoglycaemia was the pre-specified secondary outcome. In the present analysis, the associations of severe hypoglycaemia with both MACE and all-cause mortality was evaluated in the pooled trial population using time-to-event analyses, with severe hypoglycaemia as a time-dependent variable and randomised treatment as a fixed factor. An investigation with interaction terms indicated that the effect of severe hypoglycaemia on the risk of MACE and all-cause mortality were the same for both treatment arms, and so the temporal association for severe hypoglycaemia with subsequent MACE and all-cause mortality is reported for the pooled population.

Results

There was a non-significant difference in the risk of MACE for individuals who had vs those who had not experienced severe hypoglycaemia during the trial (HR 1.38, 95% CI 0.96, 1.96; p = 0.080) and therefore there was no temporal relationship between severe hypoglycaemia and MACE. There was a significantly higher risk of all-cause mortality for patients who had vs those who had not experienced severe hypoglycaemia during the trial (HR 2.51, 95% CI 1.79, 3.50; p < 0.001). There was a higher risk of all-cause mortality 15, 30, 60, 90, 180 and 365 days after experiencing severe hypoglycaemia compared with not experiencing severe hypoglycaemia in the same time interval. The association between severe hypoglycaemia and all-cause mortality was maintained after adjustment for the following baseline characteristics: age, sex, HbA_1c, BMI, diabetes duration, insulin regimen, hepatic impairment, renal status and cardiovascular risk group.

Conclusions/interpretation

The results from these analyses demonstrate an association between severe hypoglycaemia and all-cause mortality. Furthermore, they indicate that patients who experienced severe hypoglycaemia were particularly at greater risk of death in the short term after the hypoglycaemic episode. These findings indicate that severe hypoglycaemia is associated with higher subsequent mortality; however, they cannot answer the question as to whether severe hypoglycaemia serves as a risk marker for adverse outcomes or whether there is a direct causal effect.

Trial registration

ClinicalTrials.gov NCT01959529

     

Do patients with chronic rhinosinusitis benefit from consultation with an ENT-doctor?

Conclusion: By consulting an ENT-doctor, patients with chronic rhinosinusitis (CRS), in the general population, receive disease information and adjustment of treatment which can improve disease-specific Quality-of-Life and may improve objective measurements. Objectives: This study aims to follow persons with clinical diagnosed CRS from the general population, to evaluate their benefit from consultation with an ENT-doctor in terms of severity of symptoms and Quality-of-Life. Methods: As part of a trans-European study, selected respondents to a survey questionnaire were invited for a clinical visit. Based on the European Position Paper on Rhinosinusitis and Nasal Polyps, persons were diagnosed with CRS and followed for 2 years. Quality-of-Life was measured using the Sino Nasal Outcome Test 22 and European Quality-of-Life – 5 Dimensions. Clinical examination included rhinoscopy, acoustic rhinometry, peak nasal inspiratory flow, smell test, and skin prick test. Results: Out of 91 persons with CRS, only 42% had previously consulted an ENT-doctor, and 51% were in current treatment for CRS. Most patients were advised medical treatment and 20% underwent surgery. Disease-specific Quality-of-Life, peak nasal inspiratory flow, olfactory function, and the nasal volume significantly increased over the 2-year period.     

The effect of training in an interactive dynamic stander on ankle dorsiflexion and gross motor function in children with cerebral palsy

Objective: To study the effect of active stretching of ankle plantarflexors using an interactive dynamic stander in children with cerebral palsy (CP).

Methods: Six children in Gross Motor Function Classification System classes I–III, aged 4–10 years, trained intensive active dorsiflexion in an interactive dynamic stander using ankle movement to play custom computer games following a 10-week control period. Gross Motor Function Measure Item Set, gait performance and passive and active dorsiflexion with extended and flexed knee were chosen as outcome parameters.

Results: Median active and passive ankle dorsiflexion increased significantly (5 and 10 degrees, respectively) with extended knee. There was a small but clinically significant increase in gross motor function. The intervention had no effect on temporospatial gait parameters.

Conclusion: In spite of the low number of participants, these results may indicate that intensive active stretching in an interactive dynamic stander could be an effective new conservative clinical treatment of ankle plantarflexor contracture in children with CP.     

Synthesis and Structure–Activity Relationships of N-Benzyl Phenethylamines as 5-HT2A/2C Agonists

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Deoxygenation of the Baltic Sea during the last century

Deoxygenation is a global problem in coastal and open regions of the ocean, and has led to expanding areas of oxygen minimum zones and coastal hypoxia. The recent expansion of hypoxia in coastal ecosystems has been primarily attributed to global warming and enhanced nutrient input from land and atmosphere. The largest anthropogenically induced hypoxic area in the world is the Baltic Sea, where the relative importance of physical forcing versus eutrophication is still debated. We have analyzed water column oxygen and salinity profiles to reconstruct oxygen and stratification conditions over the last 115 y and compare the influence of both climate and anthropogenic forcing on hypoxia. We report a 10-fold increase of hypoxia in the Baltic Sea and show that this is primarily linked to increased inputs of nutrients from land, although increased respiration from higher temperatures during the last two decades has contributed to worsening oxygen conditions. Although shifts in climate and physical circulation are important factors modulating the extent of hypoxia, further nutrient reductions in the Baltic Sea will be necessary to reduce the ecosystems impacts of deoxygenation.Dead zones are hypoxic (low-oxygen) areas unable to support most marine life, and over the past 50 y they have spread rapidly in the open ocean (1) as well as in coastal ecosystems (2). Global warming is thought to be a major driver for these changes (3), although biogeochemical factors have also been recognized, especially in coastal marine ecosystems (4, 5). In the Baltic Sea, the present spread of hypoxia is the combined result of climate changes influencing deepwater oxygenation (6) and increased eutrophication (7, 8), resulting in a hypoxic area ranging between 12,000 and 70,000 km² with an average of 49,000 km² over the time period 1961–2000 (7). Here, we separate the effects of the two factors on oxygen conditions.Physical factors are an important consideration in whether an ecosystem will experience hypoxia. The Baltic Sea is naturally prone to hypoxia due to a restricted water exchange with the ocean and a long residence time above 30 y (9, 10). Saltier, denser water from the North Atlantic flows over a series of shallow sills in the Danish Straits to ventilate waters below the permanent halocline and are governed by meteorological-induced variations in sea levels (11), displaying variations at decadal scales (12, 13). The dense saltwater inflows bring new supplies of oxygen to bottom waters, but at the same time enhance stratification, creating larger bottom areas that experience hypoxia (14). In particular, the ventilation of the deeper waters is attributed to events of larger inflows of high-saline water (>17), termed Major Baltic Inflows (MBIs), that have been less frequent in the last three decades (6).Climate warming decreases oxygen solubility due to higher water temperature, increases stratification, and enhances respiration processes (15). Climate warming is likely to be accompanied by increased precipitation and inflows of freshwater and nutrients to coastal waters in many areas of the globe. Increasing nutrient inputs from land stimulates primary production and export of organic material to the deep waters, thereby disrupting the subtle natural balance between oxygen supply from physical processes and oxygen demand from consumption of organic material. However, the importance of decreasing oxygenation versus increasing nutrient inputs for explaining the recent spread of hypoxia is not known (6, 7).Water column measurements of dissolved oxygen concentrations began around 1900 with more regularly spaced measurements commencing in the 1960s (Fig. S1), allowing a more consistent assessment of the spatial extent of hypoxia (7, 14). The sparse temporal and spatial resolution of oxygen data before 1960 allowed only assessing hypoxia at specific locations (16) or specific years (17). To our knowledge, our study is the first to report basin-wide trends of stratification and oxygen conditions from 1898 to present, and here we will focus on the two basins that have perennial hypoxia—the Bornholm Basin and the Gotland Basin (Fig. S2). These two basins are connected via a channel with a sill depth of 60 m.