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    Blood pressure in dementia, mild cognitive impairment, and subjective cognitive decline related to time of death

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    Objective: It is unknown whether systolic blood pressure (SBP) drop is part of the normal aging process or due to the onset of dementia for some people. SBP drop is referring to the decrease in blood pressure often seen before death. Thus, the aim of this study was to examine whether SBP at time of diagnosis of dementia, mild cognitive impairment, or subjective cognitive decline was associated with years prior to death, and whether these associations were modified by diagnoses, age, and sex. Methods: Participants were 2,236 patients from the Norwegian Registry of Persons Assessed for Cognitive Symptoms (NorCog), who died during follow-up (2009-2017) for whom we had valid blood pressure measurements. Mean age at diagnosis was 77.5 years (SD 8.3), and patients were followed for an average of 3.9 years (SD 2.2, maximum 10.5 years). The patients had subjective cognitive decline (95), mild cognitive impairment (573), dementia (1,401), or no diagnoses related to cognitive deficits (167). SBP as dependent variable was regressed against years prior to death. Results: In men, SBP was 1.8 mmHg lower per year closer to death (p < .01), and this trend was linear without any acceleration. This association between years prior to death and SBP in men was not modified by age, year of diagnosis, or diagnosis. There was no such association in women. Conclusion: SBP was significantly lower for those diagnosed close to death in men, but not in women. This association was not modified by either age or onset of diagnosis. Thus, the lowering of SBP is more related to closeness to death and sex than to dementia or age. The downward trend was linear all 10 years prior to death, with no acceleration closer to death.publishedVersio

    A Randomized Trial of a Transglutaminase 2 Inhibitor for Celiac Disease

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    Background: In celiac disease, small intestinal transglutaminase 2 causes deamidation of glutamine residues in gluten peptides, which enhances stimulation of T cells and leads to mucosal injury. Inhibition of transglutaminase 2 is a potential treatment for celiac disease. Methods: In a proof-of-concept trial, we assessed the efficacy and safety of a 6-week treatment with ZED1227, a selective oral transglutaminase 2 inhibitor, at three dose levels as compared with placebo, in adults with well-controlled celiac disease who underwent a daily gluten challenge. The primary end point was the attenuation of gluten-induced mucosal damage, as measured by the ratio of villus height to crypt depth. Secondary end points included intraepithelial lymphocyte density, the Celiac Symptom Index score, and the Celiac Disease Questionnaire score (for assessment of health-related quality of life). Results: Of the 41 patients assigned to the 10-mg ZED1227 group, the 41 assigned to the 50-mg group, the 41 assigned to the 100-mg group, and the 40 assigned to the placebo group, 35, 39, 38, and 30 patients, respectively, had adequate duodenal-biopsy samples for the assessment of the primary end point. Treatment with ZED1227 at all three dose levels attenuated gluten-induced duodenal mucosal injury. The estimated difference from placebo in the change in the mean ratio of villus height to crypt depth from baseline to week 6 was 0.44 (95% confidence interval [CI], 0.15 to 0.73) in the 10-mg group (P = 0.001), 0.49 (95% CI, 0.20 to 0.77) in the 50-mg group (P<0.001), and 0.48 (95% CI, 0.20 to 0.77) in the 100-mg group (P<0.001). The estimated differences from placebo in the change in intraepithelial lymphocyte density were -2.7 cells per 100 epithelial cells (95% CI, -7.6 to 2.2) in the 10-mg group, -4.2 cells per 100 epithelial cells (95% CI, -8.9 to 0.6) in the 50-mg group, and -9.6 cells per 100 epithelial cells (95% CI, -14.4 to -4.8) in the 100-mg group. Use of the 100-mg dose may have improved symptom and quality-of-life scores. The most common adverse events, the incidences of which were similar across all groups, were headache, nausea, diarrhea, vomiting, and abdominal pain. Rash developed in 3 of 40 patients (8%) in the 100-mg group. Conclusions: In this preliminary trial, treatment with ZED1227 attenuated gluten-induced duodenal mucosal damage in patients with celiac disease. (Funded by Dr. Falk Pharma; CEC-3 EudraCT number, 2017-002241-30.). Copyright © 2021 Massachusetts Medical Society.acceptedVersio

    The Use of Antidepressants, Antipsychotics, and Stimulants in Youth Residential Care

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    Abstract Objectives: To assess the use of three commonly prescribed psychotropic medications in youth placed in residential care (RC). Methods: Participants were youth aged 0-20 years placed in RC institutions at least once during 2016. Data on filled prescriptions were taken from the Norwegian Prescription Database to compare the use of antidepressants, antipsychotics, and stimulants in RC with the age- and gender-adjusted general child population (GenPop) and how this co-varied with reasons for RC placement, age, and gender. Results: One thousand eight hundred fifty-six children and adolescents were identified in RC, with mean age 14 (range 0-20 years), 46% girls, 81% ≥ 13 years. Among those, 423 or 23% used any of the 3 psychotropics, which was significantly more than the 3.7% in GenPop. The prevalence ratios RC/GenPop were 6.6 for antidepressants, 17.9 for antipsychotics, and 4.4 for stimulants. The median number of days per year for the dispensed defined daily doses varied from 8.3 to 244.0 for the different antipsychotics, indicating short time use for most of the people. Polypharmacy was not frequent in RC, as only 26% used ≥2 classes of medication, but still significantly more frequent than the 10% in GenPop. Youth placed in RC for serious behavior problems had significantly higher use of stimulants than those with other placement reasons. Psychotropics were not used below age 6 years, and although the use of antidepressants and antipsychotics overall increased with age, stimulants were mostly used by 6-16-year olds. The girl/boy ratio for any psychotropic medication use in RC was 1.4 (95% confidence interval [95% CI]: 1.1-1.6), significantly higher than the corresponding ratio in GenPop: 1.0 (95% CI: 0.9-1.0). Conclusion: The present findings do not necessarily suggest an overtreatment with medication in RC. However, the frequent short-term use of antipsychotics, presumably for non-psychotic symptoms, is a concern, as it may reflect that the youth are not provided with the recommended first-line psychological treatments.publishedVersio

    Experiences of older patients with cancer from the radiotherapy pathway – A qualitative study

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    Abstract Purpose To explore and describe experiences of older patients with cancer throughout their radiotherapy treatment, from diagnosis until follow-up after treatment. Methods Individual interviews were conducted to explore different phases of radiotherapy. Interviews were recorded and transcribed verbatim. Inductive content analysis was applied. Each interview was coded separately. Then to the codes were analyzed further, and an overall theme was developed. Results Twelve older patients with cancer, (7 male, 5 female) aged ≥ 65 related their experiences from radiotherapy treatment. A main theme describes the essence of their experiences; Understanding “just enough” . The theme comprises five main categories: Understandable, adapted information is crucial for trusting health services; Previous experiences influence patients' perception and understanding; Involvement of next of kin is crucial to patients' comprehension; Professional treatment decisions and well-organized treatment determines satisfaction and Experiences of cooperation and coordination of services affects dependability. Conclusions Findings from this study describe how understanding “just enough” – not too much nor too little – may assist older patients with cancer in participating in treatment decisions, preventing false beliefs, feeling reassured during treatment and in navigating the complex health care system. Next of kin are important assets for older patients with cancer in understanding “just enough”. Cancer nurses may map comprehension of information, as well as reveal patients' previous experiences. © 2021 The Authors. Published by Elsevier Ltd. This is an open access article under the CC BY-NC-ND licenseThis work was supported by the Innlandet Hospital Trust [grant no.150356].publishedVersio

    Assessment of hospitalization costs and its determinants in infants with clinical severe infection at a public tertiary hospital in Nepal

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    Sepsis, an important and preventable cause of death in the newborn, is associated with high out of pocket hospitalization costs for the parents/guardians. The government of Nepal's Free Newborn Care (FNC) service that covers hospitalization costs has set a maximum limit of Nepalese rupees (NPR) 8000 i.e. USD 73.5, the basis of which is unclear. We aimed to estimate the costs of treatment in neonates and young infants fulfilling clinical criteria for sepsis, defined as clinical severe infection (CSI) to identify determinants of increased cost. This study assessed costs for treatment of 206 infants 3-59 days old, enrolled in a clinical trial, and admitted to the Kanti Children's Hospital in Nepal through June 2017 to December 2018. Total costs were derived as the sum of direct costs for bed charges, investigations, and medicines and indirect costs calculated by using work time loss of parents. We estimated treatment costs for CSI, the proportion exceeding NPR 8000 and performed multivariable linear regression to identify determinants of high cost. Of the 206 infants, 138 (67%) were neonates (3-28 days). The median (IQR) direct costs for treatment of CSI in neonates and young infants (29-59 days) were USD 111.7 (69.8-155.5) and 65.17 (43.4-98.5) respectively. The direct costs exceeded NPR 8000 (USD 73.5) in 69% of neonates with CSI. Age <29 days, moderate malnutrition, presence of any sign of critical illness and documented treatment failure were found to be important determinants of high costs for treatment of CSI. According to this study, the average treatment cost for a newborn with CSI in a public tertiary level hospital is substantial. The maximum limit offered for free newborn care in public hospitals needs to be revised for better acceptance and successful implementation of the FNC service to avert catastrophic health expenditures in developing countries like Nepal. Trial Registration: CTRI/2017/02/007966 (Registered on: 27/02/2017).The work described in the manuscript was supported by a writing grant awarded by the Centre for Intervention Science in Maternal and Child Health (CISMAC; project number 223269), which is funded by the Research Council of Norway through its Centres of Excellence scheme and the University of Bergen (UiB), Norway. Authors SS and RHC were direct recipients of the writing grant. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.publishedVersio

    The impact of surgical site infection—a cost analysis

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    Purpose: Surgical site infection (SSI) occurs in up to 25% of patients after elective laparotomy. We aimed to determine the effect of SSI on healthcare costs and patients' quality of life. Methods: In this post hoc analysis based on the RECIPE trial, we studied a 30-day postoperative outcome of SSI in a single-center, prospective randomized controlled trial comparing subcutaneous wound irrigation with 0.04% polyhexanide to 0.9% saline after elective laparotomy. Total medical costs were analyzed accurately per patient with the tool of our corporate controlling team which is based on diagnosis-related groups in Germany. Results: Between November 2015 and May 2018, 456 patients were recruited. The overall rate of SSI was 28.2%. Overall costs of inpatient treatment were higher in the group with SSI: median 16.685 €; 19.703 USD (IQR 21.638 €; 25.552 USD) vs. median 11.235 €; 13.276 USD (IQR 11.564 €; 13.656 USD); p < 0.001. There was a difference in surgery costs (median 6.664 €; 7.870 USD with SSI vs. median 5.040 €; 5.952 USD without SSI; p = 0.001) and costs on the surgical ward (median 8.404 €; 9.924 USD with SSI vs. median 4.690 €; 5.538 USD without SSI; p < 0.001). Patients with SSI were less satisfied with the cosmetic result (4.3% vs. 16.2%; p < 0.001). Overall costs for patients who were irrigated with saline were median 12.056 €; 14.237 USD vs. median 12.793 €; 15.107 USD in the polyhexanide group (p = 0.52). Conclusion: SSI after elective laparotomy increased hospital costs substantially. This is an additional reason why the prevention of SSI is important. Overall costs for intraoperative wound irrigation with saline were comparable with polyhexanide.Open Access funding enabled and organized by Projekt DEAL.publishedVersio

    Gestational Age, Birth Weight, and Neurocognitive Development in Adolescents in Tanzania

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    Objectives: To investigate the association between gestational age, birthweight, and birthweight adjusted for gestational age, with domains of neurocognitive development and behavioral problems in adolescents in Tanzania. Study design: Data from a long-term follow-up of adolescents aged 11-15 years born to women previously enrolled in a randomized controlled trial of prenatal multiple micronutrient supplementation in Dar es Salaam, Tanzania, were used. A battery of neurodevelopmental tests were administered to measure adolescent general intelligence, executive function, and behavioral problems. The INTERGROWTH-21st newborn anthropometric standards were used to derive birthweight for gestational age z-scores. We assessed the shape of relationships using restricted cubic splines and estimated the associations of gestational age, birthweight, and birthweight for gestational age z-score with adolescent development using multivariable linear regressions. Results: Among adolescents studied (n = 421), higher gestational age (per week), birthweight (per 100 grams), and birthweight for gestational age z-score (per SD) were linearly associated with higher intelligence score (adjusted standardized mean difference, 0.05 SD [95% CI, 0.01-0.09], 0.04 SD [95% CI, 0.02-0.06], and 0.09 SD [95% CI, 0.01-0.17], respectively). Birthweight and birthweight for gestational age z-score, but not gestational age, were also associated with improved executive function. Low birthweight (<2500 g) was associated with lower intelligence and executive function scores. Associations between birthweight and executive function were stronger among adolescents born to women with higher education. Conclusions: The duration of gestation and birthweight were positively associated with adolescent neurodevelopment in Tanzania. These findings suggest that interventions to improve birth outcomes may also benefit adolescent cognitive function.K24 DK104676/DK/NIDDK NIH HHS/United States P30 DK040561/DK/NIDDK NIH HHS/United States R01 HD037701/HD/NICHD NIH HHS/United States R01 HD048969/HD/NICHD NIH HHS/United StatespublishedVersio

    The effect of active learning methods to increase theoretical skills in goal-directed interventions within bachelor degree therapists

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    The purpose of this study was to see if active learning methods increased bachelor degree therapists’ theoretical skills in goal-directed interventions in accordance with the checklist by Løkke and Salthe (2012) which is defined by 1) observation and assessment prior to selection of goals and intervention, 2) goal and intervention, and 3) evaluation and reporting. Teaching methods were interteaching, self-study with tasks, lectures, videos, and practical tasks, and a Facebook group where the participants could discuss, and share subject matter related goal-directed interventions. The course lasted ten months and 22 participants, which were employed by municipalities in Innlandet County, Norway, completed pre- and posttest. 19 showed increased skills on posttest. Seven of the 13 participants who completed a follow-up test showed further increase. The participants also evaluated the course days, largely positively. We discuss validity threats to the results, as well as possible improvements of similar courses. Keywords: active learning methods, goal-directed interventions, social educators, multiple component staff training.publishedVersio

    The Damaging Outcome of the POLAR Phase III Trials Was Due to Avoidable Time-Dependent Redox Interaction between Oxaliplatin and PledOx

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    On 2 July 2021, highly negative results were reported from the POLAR A and M phase III trials in patients with colorectal cancer, treated with an oxaliplatin-based regimen and co-treated with calmangafodipir (CaM; PledOx®; PledPharma AB/Egetis Therapeutics AB) or placebo. The results revealed persistent chemotherapy-induced peripheral neuropathy (CIPN) in 54.8% of the patients treated with PledOx, compared with 40.0% of the patients treated with the placebo (p < 0.05), i.e., a 37% increase in incidence of the side effect that the trial was aimed to prevent. The damaging outcome of the trials differed diametrically from an in-parallel conducted mice study and from a clinical trial with mangafodipir, the active ingredient of CaM. According to the authors of the POLAR report, the etiology of the profound increase in CIPN in the PledOx arm is unclear. However, these devastating effects are presumably explained by intravenous administrations of PledOx and oxaliplatin being too close in time and, thereby, causing unfavorable redox interactions between Mn2+ and Pt2-. In the mice study as well as in the preceding phase II clinical trial (PLIANT), PledOx was administered 10 min before the start of the oxaliplatin infusion; this was clearly an administration procedure, where the devastating interactions between PledOx and oxaliplatin could be avoided. However, when it comes to the POLAR trials, PledOx was administered, for incomprehensible reasons, "on Top of Modified FOLFOX6" at day one, i.e., after the two-hour oxaliplatin infusion instead of before oxaliplatin. This is a time point when the plasma concentration of oxaliplatin and Pt2+-metabolites is at its highest, and where the risk of devastating redox interactions between PledOx and oxaliplatin, in turn, is at its highest. Keywords: calmangafodipir; chemotherapy-induced peripheral neuropathy; colorectal cancer; drug interactions; mangafodipir; oxaliplatin.publishedVersio

    Hair Lead, Aluminum, and Other Toxic Metals in Normal-Weight and Obese Patients with Coronary Heart Disease

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    Abstract The objective of the present study was to evaluate hair toxic metal levels in patients with obesity and/or coronary heart disease (CHD). Following a 2 × 2 factorial design, subjects without CHD were grouped into normal weight control (n = 123) and obese groups (n = 140). Patients suffering from CHD were divided into normal weight (n = 180) and obese CHD subjects (n = 240). Hair Al, As, Cd, Hg, Ni, and Pb levels were evaluated using inductively-coupled plasma mass-spectrometry. The data demonstrate that hair Al and Hg levels were higher in obese subjects as compared to normal weight controls. Normal weight CHD patients were characterized by significantly higher hair Al, As, Cd, and Pb levels when compared to healthy subjects. The highest hair Al, As, and Pb levels were observed in obese CHD patients, significantly exceeding the respective values in other groups. Factorial analysis revealed significant influence of factorial interaction (CHD*obesity) only for hair Pb content. Given the role of obesity as a risk factor for CHD, it is proposed that increased toxic metal accumulation in obesity may promote further development of cardiovascular diseases. Keywords: coronary heart disease; ischemic heart disease; lead; obesity; toxicity.publishedVersio

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