| 1. |
- Munch, Marie W., et al.
(author)
-
Effect of 12 mg vs 6 mg of Dexamethasone on the Number of Days Alive Without Life Support in Adults With COVID-19 and Severe Hypoxemia The COVID STEROID 2 Randomized Trial
- 2021
-
In: Journal of the American Medical Association (JAMA). - : AMER MEDICAL ASSOC. - 0098-7484 .- 1538-3598. ; 326:18, s. 1807-1817
-
Journal article (peer-reviewed)abstract
- Question What is the effect of 12 mg vs 6 mg of dexamethasone on the number of days alive without life support at 28 days in patients with COVID-19 and severe hypoxemia? Findings In this randomized trial that included 1000 patients with COVID-19 and severe hypoxemia, treatment with 12 mg/d of dexamethasone resulted in 22.0 days alive without life support at 28 days compared with 20.5 days in those receiving 6 mg/d of dexamethasone. This difference was not statistically significant. Meaning Compared with 6 mg of dexamethasone, 12 mg of dexamethasone did not statistically significantly reduce the number of days alive without life support at 28 days. This multicenter randomized clinical trial compares the effects of 12 mg/d vs 6 mg/d of dexamethasone in patients with COVID-19 and severe hypoxemia. IMPORTANCE A daily dose with 6 mg of dexamethasone is recommended for up to 10 days in patients with severe and critical COVID-19, but a higher dose may benefit those with more severe disease. OBJECTIVE To assess the effects of 12 mg/d vs 6 mg/d of dexamethasone in patients with COVID-19 and severe hypoxemia. DESIGN, SETTING, AND PARTICIPANTS A multicenter, randomized clinical trial was conducted between August 2020 and May 2021 at 26 hospitals in Europe and India and included 1000 adults with confirmed COVID-19 requiring at least 10 L/min of oxygen or mechanical ventilation. End of 90-day follow-up was on August 19, 2021. INTERVENTIONS Patients were randomized 1:1 to 12 mg/d of intravenous dexamethasone (n = 503) or 6 mg/d of intravenous dexamethasone (n = 497) for up to 10 days. MAIN OUTCOMES AND MEASURES The primary outcome was the number of days alive without life support (invasive mechanical ventilation, circulatory support, or kidney replacement therapy) at 28 days and was adjusted for stratification variables. Of the 8 prespecified secondary outcomes, 5 are included in this analysis (the number of days alive without life support at 90 days, the number of days alive out of the hospital at 90 days, mortality at 28 days and at 90 days, and >= 1 serious adverse reactions at 28 days). RESULTS Of the 1000 randomized patients, 982 were included (median age, 65 [IQR, 55-73] years; 305 [31%] women) and primary outcome data were available for 971 (491 in the 12 mg of dexamethasone group and 480 in the 6 mg of dexamethasone group). The median number of days alive without life support was 22.0 days (IQR, 6.0-28.0 days) in the 12 mg of dexamethasone group and 20.5 days (IQR, 4.0-28.0 days) in the 6 mg of dexamethasone group (adjusted mean difference, 1.3 days [95% CI, 0-2.6 days]; P = .07). Mortality at 28 days was 27.1% in the 12 mg of dexamethasone group vs 32.3% in the 6 mg of dexamethasone group (adjusted relative risk, 0.86 [99% CI, 0.68-1.08]). Mortality at 90 days was 32.0% in the 12 mg of dexamethasone group vs 37.7% in the 6 mg of dexamethasone group (adjusted relative risk, 0.87 [99% CI, 0.70-1.07]). Serious adverse reactions, including septic shock and invasive fungal infections, occurred in 11.3% in the 12 mg of dexamethasone group vs 13.4% in the 6 mg of dexamethasone group (adjusted relative risk, 0.83 [99% CI, 0.54-1.29]). CONCLUSIONS AND RELEVANCE Among patients with COVID-19 and severe hypoxemia, 12 mg/d of dexamethasone compared with 6 mg/d of dexamethasone did not result in statistically significantly more days alive without life support at 28 days. However, the trial may have been underpowered to identify a significant difference.
|
|
| 2. |
- Behrens, Anders, et al.
(author)
-
The Computerized General Neuropsychological INPH Test revealed improvement in idiopathic normal pressure hydrocephalus after shunt surgery
- 2020
-
In: Journal of Neurosurgery. - : AMER ASSOC NEUROLOGICAL SURGEONS. - 0022-3085 .- 1933-0693. ; 132:3, s. 733-740
-
Journal article (peer-reviewed)abstract
- OBJECTIVE The Computerized General Neuropsychological INPH Test (CoGNIT) provides the clinician and the researcher with standardized and accessible cognitive assessments in patients with idiopathic normal pressure hydrocephalus (INPH). CoGNIT includes tests of memory, executive functions, attention, manual dexterity, and psychomotor speed. Investigations of the validity and reliability of CoGNIT have been published previously. The aim of this study was to evaluate CoGNIT's sensitivity to cognitive change after shunt surgery in patients with INPH.METHODS Forty-one patients with INPH (median Mini-Mental State Examination score 26) were given CoGNIT preoperatively and at a postoperative follow-up 4 months after shunt surgery. Scores were compared to those of 44 healthy elderly control volunteers. CoGNIT was administered by either a nurse or an occupational therapist.RESULTS Improvement after shunt surgery was seen in all cognitive domains: memory (10-word list test, p < 0.01); executive functions (Stroop incongruent color and word test, p < 0.01); attention (2-choice reaction test, p < 0.01); psychomotor speed (Stroop congruent color and word test, p < 0.01); and manual dexterity (4-finger tapping, p < 0.01). No improvement was seen in the Mini-Mental State Examination score. Preoperative INPH test scores were significantly impaired compared to healthy control subjects (p < 0.001 for all tests).CONCLUSIONS In this study the feasibility for CoGNIT to detect a preoperative impairment and postoperative improvement in INPH was demonstrated. CoGNIT has the potential to become a valuable tool in clinical and research work.
|
|
| 3. |
- Kjölhede, Karin, et al.
(author)
-
Glycemic, maternal and neonatal outcomes in women with type 1 diabetes using continuous glucose monitoring during pregnancy – Pump vs multiple daily injections, a secondary analysis of an observational cohort study
- 2021
-
In: Acta Obstetricia et Gynecologica Scandinavica. - : Wiley. - 0001-6349 .- 1600-0412. ; 100:5, s. 927-933
-
Journal article (peer-reviewed)abstract
- Introduction: Continuous glucose monitoring (CGM) provides detailed information about glucose level fluctuations over time. The method is increasingly being used in pregnant women with type 1 diabetes. However, only one previous study compared CGM results related to pregnancy outcomes in women using insulin pumps with those administering multiple daily injections (MDI). We performed a secondary analysis of CGM metrics from an observational cohort of pregnant women with type 1 diabetes and compared insulin pump and MDI therapies in relation to maternal and neonatal outcomes. Material and methods: The study included 185 pregnant Swedish women with type 1 diabetes undergoing CGM throughout pregnancy. Women were divided according to insulin administration mode, ie MDI (n = 131) or pump (n = 54). A total of 91 women used real-time CGM and 94 women used intermittently viewed CGM. Maternal demographics and maternal and neonatal outcome data were collected from medical records. CGM data were analyzed according to predefined glycemic indices: mean glucose; standard deviation; percentage of time within, below and above glucose target range; mean amplitude of glycemic excursion; high and low glucose indices; and coefficient variation in percent. Associations between insulin administration mode and CGM data, on the one hand, and maternal and neonatal outcomes, on the other, were analyzed with analysis of covariance and logistic regression, respectively, adjusted for confounders. Results: There were no differences in maternal characteristics or glycemic indices between the MDI and pump groups, except for a longer duration of type 1 diabetes and higher frequencies of microangiopathy and real-time CGM among pump users. Despite improvement with each trimester, glucose levels remained suboptimal throughout pregnancy in both groups. There were no differences between the MDI and pump groups concerning the respective associations with any of the outcomes. The frequency of large for gestational age was high in both groups (MDI 49% vs pump 63%) and did not differ significantly. Conclusions: Pregnant women with type 1 diabetes did not differ in glycemic control or pregnancy outcome, related to MDI or pump administration of insulin. Glycemic control remained suboptimal throughout pregnancy, regardless of insulin administration mode.
|
|
| 4. |
|
|
| 5. |
- Konradsson, Elise, et al.
(author)
-
Establishment and Initial Experience of Clinical FLASH Radiotherapy in Canine Cancer Patients
- 2021
-
In: Frontiers in Oncology. - : Frontiers Media SA. - 2234-943X. ; 11
-
Journal article (peer-reviewed)abstract
- FLASH radiotherapy has emerged as a treatment technique with great potential to increase the differential effect between normal tissue toxicity and tumor response compared to conventional radiotherapy. To evaluate the feasibility of FLASH radiotherapy in a relevant clinical setting, we have commenced a feasibility and safety study of FLASH radiotherapy in canine cancer patients with spontaneous superficial solid tumors or microscopic residual disease, using the electron beam of our modified clinical linear accelerator. The setup for FLASH radiotherapy was established using a short electron applicator with a nominal source-to-surface distance of 70 cm and custom-made Cerrobend blocks for collimation. The beam was characterized by measuring dose profiles and depth dose curves for various field sizes. Ten canine cancer patients were included in this initial study; seven patients with nine solid superficial tumors and three patients with microscopic disease. The administered dose ranged from 15 to 35 Gy. To ensure correct delivery of the prescribed dose, film measurements were performed prior to and during treatment, and a Farmer-type ion-chamber was used for monitoring. Treatments were found to be feasible, with partial response, complete response or stable disease recorded in 11/13 irradiated tumors. Adverse events observed at follow-up ranging from 3-6 months were mild and consisted of local alopecia, leukotricia, dry desquamation, mild erythema or swelling. One patient receiving a 35 Gy dose to the nasal planum, had a grade 3 skin adverse event. Dosimetric procedures, safety and an efficient clincal workflow for FLASH radiotherapy was established. The experience from this initial study will be used as a basis for a veterinary phase I/II clinical trial with more specific patient inclusion selection, and subsequently for human trials.
|
|
| 6. |
- Kristensen, Jeppe A., et al.
(author)
-
Background insect herbivory increases with local elevation but makes minor contribution to element cycling along natural gradients in the Subarctic
- 2020
-
In: Ecology and Evolution. - : John Wiley & Sons. - 2045-7758. ; 10:20, s. 11684-11698
-
Journal article (peer-reviewed)abstract
- Herbivores can exert major controls over biogeochemical cycling. As invertebrates are highly sensitive to temperature shifts (ectothermal), the abundances of insects in high-latitude systems, where climate warming is rapid, is expected to increase. In subarctic mountain birch forests, research has focussed on geometrid moth outbreaks, while the contribution of background insect herbivory (BIH) to elemental cycling is poorly constrained. In northern Sweden, we estimated BIH along 9 elevational gradients distributed across a gradient in regional elevation, temperature, and precipitation to allow evaluation of consistency in local versus regional variation. We converted foliar loss via BIH to fluxes of C, nitrogen (N), and phosphorus (P) from the birch canopy to the soil to compare with other relevant soil inputs of the same elements and assessed different abiotic and biotic drivers of the observed variability. We found that leaf area loss due to BIH was similar to 1.6% on average. This is comparable to estimates from tundra, but considerably lower than ecosystems at lower latitudes. The C, N, and P fluxes from canopy to soil associated with BIH were 1-2 orders of magnitude lower than the soil input from senesced litter and external nutrient sources such as biological N fixation, atmospheric deposition of N, and P weathering estimated from the literature. Despite the minor contribution to overall elemental cycling in subarctic birch forests, the higher quality and earlier timing of the input of herbivore deposits to soils compared to senesced litter may make this contribution disproportionally important for various ecosystem functions. BIH increased significantly with leaf N content as well as local elevation along each transect, yet showed no significant relationship with temperature or humidity, nor the commonly used temperature proxy, absolute elevation. The lack of consistency between the local and regional elevational trends calls for caution when using elevation gradients as climate proxies.
|
|
| 7. |
- Kvale, Gerd, et al.
(author)
-
Effect of D-Cycloserine on the Effect of Concentrated Exposure and Response Prevention in Difficult-to-Treat Obsessive-Compulsive Disorder : A Randomized Clinical Trial
- 2020
-
In: JAMA Network Open. - : American Medical Association (AMA). - 2574-3805. ; 3:8
-
Journal article (peer-reviewed)abstract
- IMPORTANCE: Evidence is lacking for viable treatment options for patients with difficult-to-treat obsessive-compulsive disorder (OCD). It has been suggested that D-cycloserine (DCS) could potentiate the effect of exposure and response prevention (ERP) treatment, but the hypothesis has not been tested among patients with difficult-to-treat OCD.OBJECTIVE: To evaluate whether DCS potentiates the effect of concentrated ERP among patients with difficult-to-treat OCD.DESIGN, SETTING, AND PARTICIPANTS: The study was a randomized placebo-controlled triple-masked study with a 12-month follow-up. Participants were adult outpatients with difficult-to-treat OCD. A total of 220 potential participants were referred, of whom 36 did not meet inclusion criteria and 21 declined to participate. Patients had either relapsed after (n = 100) or not responded to (n = 63) previous ERP treatment. A total of 9 specialized OCD teams within the public health care system in Norway participated, giving national coverage. An expert team of therapists from the coordinating site delivered treatment. Inclusion of patients started in January 2016 and ended in August 2017. Data analysis was conducted February to September 2019.INTERVENTIONS: All patients received individual, concentrated ERP treatment delivered during 4 consecutive days in a group setting (the Bergen 4-day treatment format) combined with 100 mg DCS, 250 mg DCS, or placebo.MAIN OUTCOMES AND MEASURES: Change in symptoms of OCD and change in diagnostic status. Secondary outcomes measures included self-reported symptoms of OCD, anxiety, depression, and quality of life.RESULTS: The total sample of 163 patients had a mean (SD) age of 34.5 (10.9) years, and most were women (117 [71.8%]). They had experienced OCD for a mean (SD) of 16.2 (10.2) years. A total of 65 patients (39.9%) were randomized to receive 100 mg DCS, 67 (41.1%) to 250 mg of DCS, and 31 (19.0%) to placebo. Overall, 91 (56.5%) achieved remission at posttreatment, while 70 (47.9%) did so at the 12-month follow-up. There was no significant difference in remission rates among groups. There was a significant reduction in symptoms at 12 months, and within-group effect sizes ranged from 3.01 (95% CI, 2.38-3.63) for the group receiving 250 mg DCS to 3.49 (95% CI, 2.78-4.18) for the group receiving 100 mg DCS (all P < .001). However, there was no significant effect of treatment group compared with placebo in obsessive-compulsive symptoms (250 mg group at posttreatment: d = 0.33; 95% CI, -0.10 to 0.76; 100 mg group at posttreatment: d = 0.36; 95% CI, -0.08 to 0.79), symptoms of depression and anxiety (eg, Patient Health Questionnaire-9 score among 250 mg group at 12-month follow-up: d = 0.30; 95% CI, -0.17 to 0.76; Generalized Anxiety Disorder-7 score among 100 mg group at 12-month follow-up: d = 0.27; 95% CI, -0.19 to 0.73), and well-being (250 mg group: d = 0.10; 95% CI, -0.42 to 0.63; 100 mg group: d = 0.34; 95% CI, -0.19 to 0.86). No serious adverse effects were reported.CONCLUSIONS AND RELEVANCE: In this study, DCS did not potentiate ERP treatment effect, but concentrated ERP treatment was associated with improvement. This randomized clinical trial evaluates whether D-cycloserine potentiates the effect of concentrated exposure and response prevention among patients with difficult-to-treat obsessive-compulsive disorder.
|
|
| 8. |
- Overgaard, Anders, et al.
(author)
-
The implications of an aging population and increased obesity for knee arthroplasty rates in Sweden : a register-based study
- 2020
-
In: Acta Orthopaedica. - : Medical Journals Sweden AB. - 1745-3674 .- 1745-3682. ; 91:6, s. 738-742
-
Journal article (peer-reviewed)abstract
- Background and purpose — Total knee arthroplasty (TKA) has increased substantially in Sweden. We quantified the relative risk for TKA in the Swedish population for different BMI categories and age groups to investigate whether the continued increase in TKA is attributable to increased prevalence of obesity and elderly people in the population, and to put forward model predictions for coming needs for TKA. Patients and methods — We used the Swedish Nationwide Health Survey (SNHS) and the Swedish Knee Arthroplasty Register (SKAR) 2009–2015 to calculate the relative risk (RR) of TKA by age (middle-aged 45–64 years and elderly 65–84 years) and BMI (BMI 18.5–24.9 normal weight; BMI 25.0–29.9 overweight; BMI > 30 obese). The RR for TKA was applied to the demographic forecasts for the Swedish population as a forecasting model. Results — Population size increased 5.2% from 2009 to 2015 to 40,000 middle-aged and 250,000 elderly, and the prevalence of obesity increased from 16% to 18% in these 2 age categories. Compared with those of normal weight, the RR for TKA was 2.7 (95% CI 2.5–3.0) higher for the overweight and 7.3 (6.7–8.0) higher for the obese, aged 45–64. The corresponding figures for individuals aged 65–84 were 2.1 (2.0–2.2) and 4.0 (3.8–4.3) higher, respectively. The changes in the prevalence of obesity and an increase in the elderly population accounted for an estimated increase of 1,700 TKAs over the 7 years. Interpretation — The increase in obesity frequency and the rise in the population of middle-aged and elderly may, to some extent, explain the rise in TKA utilization in Sweden.
|
|
| 9. |
- Sinkeviciute, Dovile, et al.
(author)
-
A novel biomarker of MMP-cleaved prolargin is elevated in patients with psoriatic arthritis
- 2020
-
In: Scientific Reports. - : Springer Science and Business Media LLC. - 2045-2322. ; 10:1
-
Journal article (peer-reviewed)abstract
- Psoriatic arthritis (PsA) is a chronic musculoskeletal inflammatory disease found in up to 30% of psoriasis patients. Prolargin—an extracellular matrix (ECM) protein present in cartilage and tendon—has been previously shown elevated in serum of patients with psoriasis. ECM protein fragments can reflect tissue turnover and pathological changes; thus, this study aimed to develop, validate and characterize a novel biomarker PROM targeting a matrix metalloproteinase (MMP)-cleaved prolargin neo-epitope, and to evaluate it as a biomarker for PsA. A competitive ELISA was developed with a monoclonal mouse antibody; dilution- and spiking-recovery, inter- and intra-variation, and accuracy were evaluated. Serum levels were evaluated in 55 healthy individuals and 111 patients diagnosed with PsA by the CASPAR criteria. Results indicated that the PROM assay was specific for the neo-epitope. Inter- and intra- assay variations were 11% and 4%, respectively. PROM was elevated (p = 0.0003) in patients with PsA (median: 0.24, IQR: 0.19–0.31) compared to healthy controls (0.18; 0.14–0.23) at baseline. AUROC for separation of healthy controls from PsA patients was 0.674 (95% CI 0.597–0.744, P < 0.001). In conclusion, MMP-cleaved prolargin can be quantified in serum by the PROM assay and has the potential to separate patients with PsA from healthy controls.
|
|
| 10. |
- van Mourik, Maaike S. M., et al.
(author)
-
PRAISE : providing a roadmap for automated infection surveillance in Europe
- 2021
-
In: Clinical Microbiology and Infection. - : Elsevier. - 1198-743X .- 1469-0691. ; 27, s. S3-S19
-
Journal article (peer-reviewed)abstract
- Introduction: Healthcare-associated infections (HAI) are among the most common adverse events of medical care. Surveillance of HAI is a key component of successful infection prevention programmes. Conventional surveillance - manual chart review - is resource intensive and limited by concerns regarding interrater reliability. This has led to the development and use of automated surveillance (AS). Many AS systems are the product of in-house development efforts and heterogeneous in their design and methods. With this roadmap, the PRAISE network aims to provide guidance on how to move AS from the research setting to large-scale implementation, and how to ensure the delivery of surveillance data that are uniform and useful for improvement of quality of care. Methods: The PRAISE network brings together 30 experts from ten European countries. This roadmap is based on the outcome of two workshops, teleconference meetings and review by an independent panel of international experts. Results: This roadmap focuses on the surveillance of HAI within networks of healthcare facilities for the purpose of comparison, prevention and quality improvement initiatives. The roadmap does the following: discusses the selection of surveillance targets, different organizational and methodologic approaches and their advantages, disadvantages and risks; defines key performance requirements of AS systems and suggestions for their design; provides guidance on successful implementation and maintenance; and discusses areas of future research and training requirements for the infection prevention and related disciplines. The roadmap is supported by accompanying documents regarding the governance and information technology aspects of implementing AS. Conclusions: Large-scale implementation of AS requires guidance and coordination within and across surveillance networks. Transitions to large-scale AS entail redevelopment of surveillance methods and their interpretation, intensive dialogue with stakeholders and the investment of considerable resources. This roadmap can be used to guide future steps towards implementation, including designing solutions for AS and practical guidance checklists. (C) 2021 Published by Elsevier Ltd on behalf of European Society of Clinical Microbiology and Infectious Diseases.
|
|
