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| 2. |
- Stegmayr, Bernd, et al.
(författare)
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Low-dose atorvastatin in severe chronic kidney disease patients : a randomized, controlled endpoint study
- 2005
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Ingår i: Scandinavian Journal of Urology and Nephrology. - 0036-5599 .- 1651-2065. ; 39:6, s. 489-497
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Tidskriftsartikel (refereegranskat)abstract
- Objective. There have been no endpoint studies with statins for patients with severe renal failure. The purpose of this prospective, open, randomized, controlled study was to investigate whether atorvastatin (10 mg/day) would alter cardiovascular endpoints and the overall mortality rate of patients with chronic kidney disease stage 4 or 5 (creatinine clearance < 30 ml/min).Material and methods. The study subjects comprised 143 patients who were randomized either to placebo (controls; n=73; mean age 69.5 years) or to treatment with atorvastatin (n=70; mean age 67.9 years). The patients included were either non-dialysis (n=33), haemodialysis (n=97) or peritoneal dialysis (n=13) patients. Analysis focused on the primary endpoints of all-cause mortality, non-lethal acute myocardial infarction, coronary artery bypass graft surgery and percutaneous transluminal coronary angioplasty. Statistical analysis for endpoint data was mainly by intention-to-treat.Results. Primary endpoints occurred in 74% of the subjects. There was no difference in outcome between the control and atorvastatin groups. The 5-year endpoint-free survival rate from study entry was 20%. Atorvastatin was withdrawn in 20% of patients due to unacceptable side-effects. In the atorvastatin group, low-density lipoprotein (LDL) cholesterol was reduced by 35% at 1 month and then sustained. The controls showed a progressive reduction in LDL cholesterol until 36 months.Conclusions. Although atorvastatin reduced total and LDL cholesterol effectively it was not beneficial regarding the long-term outcomes of cardiovascular endpoints or survival. In contrast to other patient groups, patients with severe chronic kidney disease, especially those on dialysis, seem to derive limited benefit from this lower dose of atorvastatin.
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| 10. |
- Hardy, J, et al.
(författare)
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Transmitter deficits in Alzheimer's disease.
- 1985
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Ingår i: Neurochemistry International. - 0197-0186 .- 1872-9754. ; 7:4, s. 545-63
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Tidskriftsartikel (refereegranskat)abstract
- The pattern of neurotransmitter pathway losses in Alzheimer's disease are reviewed. Deficits of the cholinergic pathway from the nucleus basalis, the noradrenergic pathway from the locus coeruleus and the serotoninergic pathway from the raphe nuclei are established. Cortical somatostatin interneurons are affected and dopaminergic neurons may be affected although these may be late or secondary phenomena in the disease process. Other neuronal systems, particularly in the hippocampus and temporal cortex, are also damaged. However, the disease is not one of generalised neuronal atrophy since some neurons are selectively spared. The established pathway-specific losses are discussed in relation to the clinical symptomatology and the pathology of the disorder. The biochemical and histological findings are compared with similar measurements made on tissues from other dementing disorders in an attempt to trace features common to dementias. Finally, as an addendum, a hypothesis is briefly outlined which attempts to explain the common features of the affected neurons and the pathogenesis of the disorder.
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| 11. |
- Jonasson, S., et al.
(författare)
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Inhalation of chlorine causes long-standing lung inflammation and airway hyperresponsiveness in a murine model of chemical-induced lung injury
- 2013
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Ingår i: Toxicology. - : Elsevier BV. - 0300-483X .- 1879-3185. ; 303, s. 34-42
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Tidskriftsartikel (refereegranskat)abstract
- Chlorine is highly irritating when inhaled, and is a common toxic industrial gas causing tissue damage in the airways followed by an acute inflammatory response. In this study, we investigated mechanisms by which chlorine exposure may cause reactive airways dysfunction syndrome (RADS) and we examined the dose-dependency of the development of symptoms. Mice were exposed to 50 or 200ppm Cl2 during a single 15min exposure in a nose-only container. The experiment terminated 2, 6, 12, 24, 48, 72h and 7, 14, 28 and 90 days post exposure. Inflammatory cell counts in bronchoalveolar lavage (BAL), secretion of inflammatory mediators in BAL, occurrence of lung edema and histopathological changes in lung tissue was analyzed at each time-point. Airway hyperresponsiveness (AHR) was studied after 24 and 48h and 7, 14, 28 and 90 days. The results showed a marked acute response at 6h (50ppm) and 12h (200ppm) post exposure as indicated by induced lung edema, increased airway reactivity in both central and peripheral airways, and an airway inflammation dominated by macrophages and neutrophils. The inflammatory response declined rapidly in airways, being normalized after 48h, but inflammatory cells were sustained in lung tissue for at least seven days. In addition, a sustained AHR was observed for at least 28 days. In summary, this mouse model of chlorine exposure shows delayed symptoms of hyperreactive airways similar to human RADS. We conclude that the model can be used for studies aimed at improved understanding of adverse long-term responses following inhalation of chlorine.
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| 12. |
- Jónsson, Pálmi V, et al.
(författare)
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Admission profile is predictive of outcome in acute hospital care.
- 2008
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Ingår i: Aging Clinical and Experimental Research. - 1594-0667 .- 1720-8319. ; 20:6, s. 533-9
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND AND AIMS: The purpose of this study is to describe predictors for discharge and one-year outcomes of acute-care hospital patients, 75 years of age or over, based on admission status information. We carried out a prospective study of a randomly selected patient population, from one urban acute-care hospital in each of the Nordic countries. 763 persons aged 75+ were randomly selected from acute admissions to the participating hospitals. 749 observations at discharge and 655 observations at one year were used in analyses. METHODS: Data were collected with the MDS-AC 1.1 instrument within 24 hours of admission, and at day 7 or discharge, whichever came first. Outcome information was collected either by interviewing the patient or from patient records or registers. Discharge and one-year outcome (home, institution, death) were modeled by multinomial logistic regression, with admission status variables as predictors. RESULTS: At discharge, 84% of subjects returned home, 11% went to an institution and 5.6% had died. At one year, 64% were still living at home, 24% had died, and 12% had moved to an institution. For discharge outcome, those having hospital admission due to a new problem or exacerbation of an old one had a higher risk of dying (OR 3.3) than returning home. Moderate to severe cognitive problems predicted death (OR 2.2) and institutionalization (OR 8.6) compared with discharge home. Problems in instrumental activities of daily living predicted death (OR 3.1) and institutionalization (OR 6.0). At one year, those with exacerbation of an old problem (OR 2.1) or with a new or exacerbated existing problem (OR 2.3) had a higher risk of dying than of institutionalization or discharge home. Having some cognitive problems (OR 2.8) or moderate to severe cognitive problems (OR 6.6) predicted institutionalization, but not dying or discharge home. Those with some problems in activities of daily living had a higher risk of both dying (OR 1.7) and of institutional care (OR 2.7). Those with moderate to severe problems in activities of daily living had also a higher risk of institutional care (OR 4.7) compared with those living at home. CONCLUSIONS: Evidence predictive of discharge and one-year outcomes in older acute hospital medical care patients seems to be visible from the beginning of the hospital stay. In order to increase the efficient use of health care services and quality of care, systematic standardized and streamlined assessment should be performed during the admission process.
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| 13. |
- Jónsson, Pálmi V, et al.
(författare)
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Co-morbidity and functional limitation in older patients underreported in medical records in Nordic Acute Care Hospitals when compared with the MDS-AC instrument
- 2006
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Ingår i: Age and Ageing. - Oxford : Oxford Univ. Press. - 0002-0729 .- 1468-2834. ; 35:4, s. 434-438
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Tidskriftsartikel (refereegranskat)abstract
- SIR—Older persons are characterised by age-related changes, multiple diseases, multiple drug use and functional deficits. For optimal care, a holistic approach is needed; however, the health care systems of today are still essentially organised to provide acute medical care to relatively younger populations with little or no co-morbidity [ 1]. Health systems will have to adapt to this new situation.The value of geriatric assessment has been proven, where targeting is the key to success [ 2]. With shorter hospital stays, it is of importance to do this targeting quickly and effectively. According to a systematic literature review in the older patients, the most important predictors for adverse outcomes of acute care (mortality, frequent readmissions, institutionalisation and long length of stay) are current illness, decline in physical functions and age. In addition, illness severity, co-morbidity, polypharmacy, cognitive decline, poor nutrition and gender are predictive for one or more of the outcomes [ 3].The Minimum Data Set for Acute Care (MDS-AC) instrument was developed to guide care within the hospital and to facilitate the transfer and sharing of information to the next provider of care, thus supporting integrated care. The MDS-AC instrument provides an opportunity to systematically collect information that is reliable on function and co-morbidity and could thus be a valuable addition to the future electronic medical record [ 4].The aim of this study is to investigate to what degree important predictors of adverse outcomes, if present according to the MDS-AC instrument during the first 24 h of care for older patients, were not documented in traditional hospital records in acute care wards in five Nordic countries. Hence, the MDS-AC information is assumed to be a gold standard. A secondary aim is to show that suspected deficient documentation is an international issue.
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| 24. |
- Svartbo, B, et al.
(författare)
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Inpatient care quality: analyzing Swedish hospitals with stroke as a tracer
- 2000
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Ingår i: International journal of health care quality assurance incorporating Leadership in health services. - : Emerald. - 1366-0756. ; 13:4-5, s. 218-22
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Tidskriftsartikel (refereegranskat)abstract
- Mortality statistics are an important source of information concerning variations in time and place, identification of risk factors and the evaluation of treatment programs. In this study, a new death certificate was completed “blind” on the basis of hospital records from the last episode of care, across a random sample of 1,376 cases. The results showed that the overlap between the official register’s underlying cause of death and that of a panel was 72 per cent at the three‐digit level. The official underlying cause of death from cerebrovascular diseases (CVD) was 72 cases in this sample, while 93 were deemed to have CVD by a panel. Additionally, of the 1,233 cases originally reported as non‐CVD, the panel deemed non‐CVD to be the true underlying cause in 1,176 cases. The paper concludes that CVD was most often correctly reported as the underlying cause of death in the investigated ages up to 75 years but plain differences were found between specialities and in different hospital size.
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| 25. |
- Thors, L., et al.
(författare)
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Comparison of skin decontamination efficacy of commercial decontamination products following exposure to VX on human skin
- 2017
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Ingår i: Chemico-Biological Interactions. - : Elsevier BV. - 0009-2797 .- 1872-7786. ; 273, s. 82-89
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Tidskriftsartikel (refereegranskat)abstract
- The decontamination efficacy of four commercially available skin decontamination products following exposure to the nerve agent VX was evaluated in vitro utilizing a diffusion cell and dermatomed human skin. The products included were Reactive Skin Decontamination Lotion (RSDL), the Swedish decontamination powder 104 (PS104), the absorbent Fuller's Earth and the aqueous solution alldecontMED. In addition, various decontamination procedures were assessed to further investigate important mechanisms involved in the specific products, e.g. decontamination removal from skin, physical removal by sponge swabbing and activation of degradation mechanisms. The efficacy of each decontamination product was evaluated 5 or 30 min after dermal application of VX (neat or diluted to 20% in water).The RSDL-lotion was superior in reducing the penetration of VX through human skin, both when exposed as neat agent and when diluted to 20% in water. Swabbing with the RSDL-sponge during 2 min revealed decreased efficacy compared to applying the RSDL-lotion directly on the skin for 30 min. Decontamination with Fuller's Earth and alldecontMED significantly reduced the penetration of neat concentration of VX through human skin. PS104-powder was insufficient for decontamination of VX at both time-points, independently of the skin contact time of PS104. The PS104-slurry (a mixture of PS104-powder and water), slightly improved the decontamination efficacy. Comparing the time-points for initiated decontamination revealed less penetrated VX for RSDL and Fuller's Earth when decontamination was initiated after 5 min compared to 30 min post-exposure, while alldecontMED displayed similar efficacy at both time-points. Decontamination by washing with water only resulted in a significant reduction of penetrated VX when washing was performed 5 min after exposure, but not when decontamination was delayed to 30 min post-exposure of neat VX.In conclusion, early initiated decontamination with the RSDL-lotion, containing both absorption and degrading properties, allowed to act on skin for 30 min was superior in preventing VX from penetrating human skin. Adding water during decontamination resulted in increased penetration of neat VX, however, water in the decontaminant removal process did not influence the decontamination efficacy. From our study on commercially available decontaminants, it is recommended that future product developments should include both strong absorbents and efficient nerve agent degrading components.
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| 26. |
- Thors, L., et al.
(författare)
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In vitro human skin penetration model for organophosphorus compounds with different physicochemical properties
- 2016
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Ingår i: Toxicology in Vitro. - : Elsevier. - 0887-2333 .- 1879-3177. ; 32, s. 198-204
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Tidskriftsartikel (refereegranskat)abstract
- A flow-through diffusion cell was validated for in vitro human epidermal penetration studies of organophosphorus compounds (OPCs) applied by infinite dosing. By testing OPCs with similar molecular weight but different physicochemical properties, it was shown that hydrophilic and lipophilic properties are major determinants for the penetration rate. Lipophilic OPCs displayed maximum cumulative penetration in the 20-75% agent concentration range whereas the hydrophilic OPCs displayed maximum cumulative penetration at 10 or 20% agent concentration. Low penetration was observed for all agents at 1% agent concentration or when applied as neat agents. The impact of the receptor solution composition was evaluated by comparing the penetration using receptor solutions of different ratios of ethanol and water. For diluted OPCs, a high concentration of ethanol in the receptor solution significantly increased the penetration compared to lower concentrations. When OPCs were applied as neat agents, the composition of the receptor solution only affected the penetration for one of four tested compounds. In conclusion, the flow-through diffusion cell was useful for examining the penetration of OPCs through the epidermal membrane. It was also demonstrated that the penetration rates of OPCs are strongly influenced by dilution in water and the receptor fluid composition.
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| 27. |
- Thors, L., et al.
(författare)
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RSDL decontamination of human skin contaminated with the nerve agent VX
- 2017
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Ingår i: Toxicology Letters. - : Elsevier BV. - 0378-4274 .- 1879-3169. ; 269, s. 47-54
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Tidskriftsartikel (refereegranskat)abstract
- Dermal exposure to low volatile organophosphorus compounds (OPC) may lead to penetration through the skin and uptake in the blood circulation. Skin decontamination of toxic OPCs, such as pesticides and chemical warfare nerve agents, might therefore be crucial for mitigating the systemic toxicity following dermal exposure. Reactive skin decontamination lotion (RSDL) has been shown to reduce toxic effects in animals dermally exposed to the nerve agent VX. In the present study, an in vitro flow-through diffusion cell was utilized to evaluate the efficacy of RSDL for decontamination of VX exposed to human epidermis. In particular, the impact of timing in the initiation of decontamination and agent dilution in water was studied. The impact of the lipophilic properties of VX in the RSDL decontamination was additionally addressed by comparing chemical degradation in RSDL and decontamination efficacy between the VX and the hydrophilic OPC triethyl phosphonoacetate (TEPA). The epidermal membrane was exposed to 20, 75 or 90% OPC diluted in deionized water and the decontamination was initiated 5,10, 30, 60 or 120 min post exposure. Early decontamination of VXwith RSDL, initiated 5-10 min after skin exposure, was very effective. Delayed decontamination initiated 30-60 min post-exposure was less effective but still the amount of penetrated agent was significantly reduced, while further delayed start of decontamination to 120 min resulted in very low efficacy. Comparing.RSDL decontamination of VX with that of TEPA showed that the decontamination efficacy at high agent concentrations was higher for VX. The degradation mechanism of VX and TEPA during decontamination was dissected by P-31 NMR spectroscopy of the OPCs following reactions with RSDL and its three nucleophile components. The degradation rate was clearly associated with the high pH of the specific solution investigated; i.e. increased pH resulted in a more rapid degradation. In addition, the solubility of the OPC in RSDL also influenced the degradation rate since the degradation of VX was significantly faster when the NMR analysis was performed in the organic solvent acetonitrile compared to water. In conclusion, we have applied the in vitro flow-through diffusion cell for evaluation of skin decontamination procedures of human epidermis exposed to OPCs. It was demonstrated that early decontamination is crucial for efficient mitigation of epidermal penetration of VX and that almost complete removal of the nerve agent from the skin surface is possible. Our data also indicate that the pH of RSDL together with the solubility of OPC in RSDL are of primary importance for the decontamination efficacy.
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