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Louise Moeldrup Nielsen,1,2 Thomas Maribo,3 Hans Kirkegaard,4 Kirsten Schultz Petersen,5 Marianne Lisby,4 Lisa Gregersen Oestergaard2,6 1Department of Occupational Therapy, VIA University College, 2Department of Physiotherapy and Occupational Therapy, Aarhus University Hospital, 3Department of Public Health, Aarhus University, DEFACTUM, 4Department of Clinical Medicine, Research Centre for Emergency Medicine, Aarhus University Hospital, Aarhus, 5Department of Health Science and Technology, Aalborg University, Aalborg, 6Department of Clinical Medicine, Aarhus University and Aarhus University Hospital, Aarhus, Denmark Purpose: To examine the effectiveness of the Elderly Activity Performance Intervention on reducing the risk of readmission in elderly patients discharged from a short-stay unit at the emergency department. Patients and methods: The study was conducted as a nonrandomized, quasi-experimental trial. Three hundred and seventy-five elderly patients were included and allocated to the Elderly Activity Performance Intervention (n=144) or usual practice (n=231). The intervention consisted of 1) assessment of the patients’ performance of daily activities, 2) referral to further rehabilitation, and 3) follow-up visit the day after discharge. Primary outcome was readmission (yes/no) within 26 weeks. The study was registered in ClinicalTrial.gov (NCT02078466). Results: No between-group differences were found in readmission. Overall, 44% of the patients in the intervention group and 42% in the usual practice group were readmitted within 26 weeks (risk difference=0.02, 95% CI: [-0.08; 0.12] and risk ratio=1.05, 95% CI: [0.83; 1.33]). No between-group differences were found in any of the secondary outcomes. Conclusion: The Elderly Activity Performance Intervention showed no effectiveness in reducing the risk of readmission in elderly patients discharged from a short-stay unit at the emergency department. The study revealed that 60% of the elderly patients had a need for further rehabilitation after discharge. Keywords: occupational therapy, rehabilitation, performance of daily activities, activities of daily living, acute care

Previous research has shown that young adult relatives of parents with dementia experience strain through increased responsibility and changed relationships in the family with potential consequences for their emotional, mental and physical well-being. Less is known about how young adult relatives experience their participation in everyday activities typically associated with young adulthood and how their participation is affected by the parent´s dementia. This study explores young adult relatives' experiences of participation in everyday activities and how their participation was affected by having a parent with dementia. The study followed a qualitative, descriptive approach. Semi-structured individual interviews with 11 young adult relatives (aged 21 - 31) of parents with dementia were conducted. The interviews were analysed using Kirsti Malterud's iterative cross case analysis method 'Systematic text condensation'. The analysis identified three categories: Dilemmas of choosing, Not having a choice and Reversal of roles. The young adult relatives experienced dilemmas and constraints regarding participation in everyday activities usually related to young adulthood. They navigated situations where they were to choose between the parent with dementia and their own everyday activities and they often downgraded or cancelled participation in own activities related to leisure time, school, job and career. Moreover, their participation seemed affected by chores and responsibilities resulting in a lack of energy leading them to forego social activities in particular or change their choice of activities. The young adult relatives need help and support in their everyday lives. Health care professionals are encouraged to focus on relieving them from some of the responsibilities and practical tasks enabling them to live their own lives as young adults, while being part of the family and contributing towards the responsibilities and tasks with which they can cope., Competing Interests: Declaration of conflicting interestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Introduction: Pain perception, far from being a pathological mechanism, is a crucial protective stimulus to prevent additional injuries. Any disturbance in this complex system poses significant risks to individuals, affecting their quality of life and even their survival., Objective: This review aims to explore congenital insensitivity to pain, an extremely rare genetic disorder with an autosomal recessive pattern that results in the inability to perceive pain. We will focus on the well-known subtype, congenital insensitivity to pain with anhidrosis (CIPA). Our research seeks to update existing knowledge through a comprehensive literature review., Methodology: The review employs a systematic literature review, analyzing various sources and scientific documents, primarily emphasizing CIPA. The review follows the PROSPERO protocol, registered under CRD42023394489. The literature search was performed on the Scopus, PubMed, and Cinahl databases., Results: Our review reveals secondary complications associated with CIPA, such as recurrent bone fractures, temperature insensitivity, self-mutilation, and, occasionally, intellectual disabilities. The limited available information underscores the need for expanding our knowledge., Conclusions: In summary, CIPA, particularly, presents a significant medical challenge with adverse impacts on quality of life. Early diagnosis, education for families and healthcare professionals, and appropriate nursing care are essential for effective management. This review highlights the necessity of further research and awareness to enhance support for those affected.

Purpose: To assess and identify patients' perceptions about the overall value of physical therapy services for musculoskeletal conditions and how these values were associated with their outcomes., Methods: The association between the perceived value of physical therapy (as a score) and Patient-Reported Outcomes Measurement Information System (PROMIS) pain interference and physical function at 6-weeks was assessed in a prospective cohort. Generalised linear models were used to identify relationships between the value of physical therapy score and PROMIS outcomes. Kendall's tau was used to identify correlations between responses and outcomes., Results: A total of 133 participants met the final inclusion criteria. The majority of participants were female (63.9%) with a mean age of 55.53 (SD 15.36) years. A majority of participants (63.9%) reported a previous positive personal experience with physical therapy. There was no significant relationship between perceived value of physical therapy and pain interference (β -0.32, p = 0.07, 95% CI-0.67, 0.03) or physical function (β 0.19, p = 0.29, 95% CI-0.16, 0.54). Stronger beliefs in agreement with the value of non-invasive treatment were significant, but weakly correlated with lower pain interference (r = -0.18, p = 0.048) and higher physical function scores (r = 0.22, p = 0.03)., Conclusions: Participants had an overall positive perception of the value of physical therapy prior to initiating physical therapy, but this perception was not associated with 6-week pain and function outcomes. A better understanding of the driving factors encouraging patients to seek physical therapy services is needed to provide value-based care., (© 2024 John Wiley & Sons Ltd.)

Purpose: To identify how pre-surgical conservative care is characterized and reported in randomized controlled trials of adults undergoing elective lumbar fusion, including duration and type of treatment., Methods: The study design is a scoping review. Data sources include PubMed, Cumulative Index to Nursing and Allied Health Literature (CINAHL), Ovid Medline, EMBASE, and Cochrane Central Register of Controlled Trials (CENTRAL). All randomized controlled trials published in English between January 1, 2005, and February 15, 2022, assessing lumbar fusion as the intervention were included in this review., Results: Of 166 studies, 62.0% reported a failure in conservative care prior to lumbar fusion, but only 15.1% detailed the type of specific conservative care received. None of the trials provided sufficient details to understand the nature of the pre-surgical conservative treatment, such as frequency, recency/timing, or dosage of conservative interventions., Conclusion: Although roughly two-thirds of trials reported that patients failed conservative care prior to receiving a lumbar fusion, few studies named the conservative intervention provided and no studies provided any details regarding dosing or recency of care. This lack of information creates ambiguity in the surgical decision-making process, setting the assumption that all patients received adequate conservative care prior to surgery. Details about pre-surgical conservative care should be disclosed to allow for appropriate clinical application, decision-making, and interpretation of treatment effects., (© 2023. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Background: A need was identified for an occupational therapy intervention for stroke survivors in a Danish municipal healthcare setting with emphasis on its ability to transfer and generalise what is learned in occupational therapy to everyday life post therapy. Being a possible candidate, the Cognitive Orientation to daily Occupational Performance (CO-OP) approach needed to be adapted to the target group and context, and its feasibility needed examination regarding reach, dose, intervention components, fidelity, perceived value, benefits, harms, and potential outcomes., Aim: To adapt the CO-OP to a Danish healthcare setting and present a protocol for examining its feasibility., Material and Methods: The Adapting interventions to new contexts (ADAPT) guidance was followed to (1) Assess the rationale for intervention and consider intervention-context fit, (2) Plan and undertake adaptations, and (3) Plan a feasibility study., Results: Intervention materials and procedures were translated and adapted for home-based occupational therapy with people in the subacute phase of stroke. A protocol was developed to examine feasibility aspects. Quantitative and qualitative evaluations were planned and measurements chosen., Conclusions and Significance: The planned feasibility study will contribute to further developing and refining the intervention before performing a possible large-scale effectiveness study.

Objectives To explore carers' experiences of everyday life impacted by people with dementia who attended a seven-week cognitive stimulation therapy (CST) group intervention. Methods A systematic review of qualitative studies and qualitative mixed method studies was conducted. Eight databases were searched. The selected studies were screened and assessed for methodological quality using the Rayyan Qatar Computing Research Institute (QCRI) and Critical Appraisal Skills Programme Qualitative Checklist (CASP-QC). Three studies were included following an inductive content analysis. Results Two themes were identified: 'Enrichment by enhanced communication' and 'Growth through positive emotional interaction'. Conclusion Qualitative research on the impact of the CST group intervention on carers' everyday life with a person with dementia is scarce. Carers experienced feelings of enrichment due to improvement and equality in communication and a possible source of happiness. There was a sense of togetherness and reconnection through music and singing together as well as a sense of mutual growth, increased positive interaction, increased ability to socialize, and feelings of fondness when experiencing glimpses of the previous personality of the person with dementia. Nevertheless, knowledge about the impact of the CST group intervention on carers' personal everyday life is lacking and requires further research.

Background: Evidence supports the role of occupational therapy (OT) for older adults, and therapeutic use of problem solving may provide a way to improve older adult's occupational performance. Aim: To assess the effectiveness and describe the contents of OT interventions aimed at improving older adults' occupational performance by strengthening their problem-solving skills. Material and Methods: This systematic review followed the phases recommended by the Cochrane Collaboration. The following databases were searched for clinical trials on OT for populations 65+ years: CINAHL, EMBASE, MEDLINE and PsycINFO. The Cochrane risk-of-bias tool (RoB-2) and the GRADE approach were used to assess the quality of the evidence. Results were presented in tables and by narrative syntheses. Results: Five studies were included comprising a total of 685 participants. In four studies, OT with a problem-solving approach outperformed control conditions post intervention. The interventions involved problem identification, analysis, strategy development and implementation. Although no serious risk of bias was detected in the individual studies, the quality of evidence was deemed low due to inconsistent and imprecise results. Conclusions: Low-quality evidence suggests that strengthening older adults' problem-solving skills may improve their occupational performance. Significance: Further investigation is required before firm practice recommendations can be prepared.

Background: Preeclampsia is associated with increased risk of cardiovascular disease later in life, but studies suggest that women with previous preeclampsia are not aware of this. Little is known about how these women perceive the condition and the associated long-term risks. We examined the experiences and perceptions of preeclampsia and the increased risk of cardiovascular disease (CVD) later in life among Danish women with previous preeclampsia and their attitudes towards CVD risk screening., Methods: Ten individual semi-structured interviews were conducted with women with previous preeclampsia. Data were analysed using thematic analysis., Results: We identified six themes: 1) Experiences and perceptions of being diagnosed with preeclampsia, 2) Awareness about increased risk of CVD later in life, 3) Knowledge as a precondition for action, 4) The perception of CVD risk as being modifiable, 5) Motivators for and barriers to a healthy lifestyle, and 6) Screening for CVD. Awareness of the severity of preeclampsia was limited prior to being diagnosed. Particularly among those with few or no symptoms, preeclampsia was perceived as a non-severe condition, which was further reinforced by the experience of having received very little information. Nonetheless, some women were shocked by the diagnosis and feared for the health of the offspring. Many women also experienced physical and psychological consequences of preeclampsia. Awareness of the increased risk of later CVD was lacking; yet, when informed, the women considered this to be essential knowledge to be able to act accordingly. The risk of future CVD was perceived to be partly modifiable with a healthy lifestyle, and the women expressed a need for counselling on appropriate lifestyle changes to reduce CVD risk. Other factors were also mentioned as imperative for lifestyle changes, including social support. The women were generally positive towards potential future screening for CVD because it could provide them with information about their health condition., Conclusions: After preeclampsia, women experienced a lack of knowledge on preeclampsia and the increased risk of CVD later in life. Improved information and follow-up after preeclampsia, including guidance on CVD risk reduction and support from health professionals and family, are warranted., (© 2022. The Author(s).)

Introduction: The World Health Organization Disability Assessment Schedule 2.0 (WHODAS 2.0) is designed to measure functioning and disability in six domains. It is included in the International Classification of Diseases 11th revision (ICD-11). The objective of the study was to examine the construct validity of WHODAS 2.0 and describe its clinical utility for the assessment of functioning and disability among older patients discharged from emergency departments (EDs). Material and Methods: This cross-sectional study is based on data from 129 older patients. Patients completed the 36-item version of WHODAS 2.0 together with the Barthel-20, the Assessment of Motor and Process Skills (AMPS), Timed Up and Go (TUG), and the 30-Second Chair Stand Test (30 s-CST). Construct validity was examined through hypothesis testing by correlating the WHODAS with the other instruments and specifically the mobility domain in WHODAS 2.0 with the TUG and 30 s-CST tests. The clinical utility of WHODAS 2.0 was explored through floor/ceiling effect and missing item responses. Results: WHODAS 2.0 correlated fair with Barthel-20 ( r = -0.49), AMPS process skills ( r = -0.26) and TUG ( r =0.30) and correlated moderate with AMPS motor skills ( r = -0.58) and 30s-CST ( r = -0.52). The WHODAS 2.0 mobility domain correlated fair with TUG ( r = 0.33) and moderate with 30s-CST ( r = -0.60). Four domains demonstrated floor effect: D1 "Cognition," D3 "Self-care," D4 "Getting along," and D5 "Household." Ceiling effect was not identified. The highest proportion of missing item responses were present for Item 3.4 (Staying by yourself for a few days), Item 4.4 (Making new friends), and Item 4.5 (Sexual activities). Conclusion: WHODAS 2.0 had fair-to-moderate correlations with Barthel-20, AMPS, TUG, and 30s-CST and provides additional aspects of disability compared with commonly used instruments. However, the clinical utility of WHODAS 2.0 applied to older patients discharged from EDs poses some challenges due to floor effect and missing item responses. Accordingly, patient and health professional perspectives need further investigation., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Nielsen, Oestergaard, Kirkegaard and Maribo.)

Background: Older adults' occupational performance is challenged due to chronic health conditions, aging processes, and deteriorating functioning. Thus, their occupational performance cannot be expected to remain stable in the long term after an occupational therapy intervention. Older adults may therefore need to strengthen their problem-solving skills during occupational therapy not only to solve current occupational performance issues but also to maintain their improvements and deal with new such issues a later point in time., Aims: This systematic review and meta-analysis aims to identify, analyse and present current scientific knowledge about the effectiveness and contents of occupational therapy interventions aimed at improving older adults' occupational performance by strengthening their problem-solving skills., Methods: MEDLINE, EMBASE, CINAHL and PsycINFO will be searched systematically to identify trials of occupational therapy interventions aimed at improving older adults' occupational performance by strengthening their problem-solving skills. We will include randomized controlled trials and quasi-experimental trials in populations aged 65+. Three reviewers will independently screen and select references, extract data and assess the quality of included studies using the Cochrane Collaboration's risk of bias tool., Significance: The findings can inform and inspire clinical practice and will help to identify the need for further research.

Background: Readmission is a serious and adverse event for elderly patients. Despite efforts, predicting the risk of readmission remains imprecise. The objective of this study is to examine if performance-based tests of daily activities can identify elderly patients at risk of readmission within 26 weeks after discharge from a short-stay unit in the emergency department., Methods: The current study is an observational study based on data from 144 elderly patients included in a previous non-randomised controlled trial. Before discharge, patients were assessed for limitations in performing daily activities using three performance-based tests with predetermined cut-off values: the Assessment of Motor and Process Skills, Timed Up and Go and the 30s-Chair Stand Test. Outcome was risk of readmission within 26 weeks after discharge., Results: Limitations in performing daily activities were associated with risk of readmission as measured by the Assessment of Motor and Process Skills motor scale (Crude OR = 4.38 [1.36; 14.12]), (Adjusted OR = 4.17 [1.18; 14.75]) and the 30s-Chair Stand Test (Adjusted OR = 3.36 [1.42; 7.93]). No significant associations were found in regards to other measures., Conclusion: The Assessment of Motor and Process Skills motor scale and the age, gender and comorbidity adjusted 30s-Chair Stand Test can identify elderly patients at increased risk of readmission after discharge from the emergency department. The results were limited by one-third of the patients did not perform the Assessment of Motor and Process Skills and the association between 30s-Chair Stand Test and risk of readmission were only positive when adjusted for age, gender and comorbidity.

Introduction: Elderly patients often receive care and rehabilitation from different providers across healthcare settings. Collaboration between hospital and primary care providers is therefore essential to ensure that the discharge and transition of rehabilitation is coherent. However, research that focuses on elderly patients' experiences of the discharge, and their everyday lives after, has attracted little attention., Purpose: This study explores elderly patients' experiences of being discharged and returning to everyday lives after discharge from a short-stay unit at the Emergency Department., Methods: Eleven qualitative interviews with elderly patients were conducted two weeks after their discharge. The transcribed interviews were analysed using systematic text condensation., Results: The study identified four themes related to the participants experiences. In the participants perspective it was difficult, due to fatigue and pain, to perform daily activities after discharge. Participants who experienced not being prepared and clarified in relation to their discharge continued to have concerns for the future. They also experienced some challenges related to lack of being involved and lack of receiving the information needed., Conclusion: The findings contribute with impotant knowledge about elderly patients' experiences and concerns which should be taken into consideration in the discharge planning process .

Background: Limitations in performing daily activities and a incoherent discharge are risk factors for readmission of elderly patients after discharge from the emergency department. This paper describes the development and design of a complex intervention whose aim was to reduce the risk of readmission of elderly patients discharged from the emergency department., Methods: The intervention was described using the Intervention Mapping approach. In step 1, a needs assessment was conducted to analyse causes of readmission. In steps 2 and 3, expected improvements in terms of intervention outcomes, performance objectives and change objectives were specified and linked to selected theory- and evidence-based methods. In step 4, the specific intervention components were developed; and in step 5, an implementation plan was described. Finally, in step 6, a plan for evaluating the effectiveness of the intervention was described. The intervention was informed by input from a literature search, informal interviews and an expert steering group., Results: A three-phased theory- and evidence-based intervention was developed. The intervention consisted of 1) assessment of performance of daily activities, 2) defining a rehabilitation plan and 3) a follow-up home visit the day after discharge with focus on enhancing the patients' performance of daily activities., Conclusion: The intervention mapping protocol was found to be a useful method to describe and systemize this theory- and evidence-based intervention.

Background: Factors such as age, gender, and genetic polymorphisms may explain individual differences in pain phenotype. Genetic associations with pain sensitivity have previously been investigated in osteoarthritis patients, with a focus on the P2X7, TRPV1, and TACR1 genes. However, other genes may play a role as well. Osteoarthritis is a common joint disease, and many patients suffering from this disease are thought to have increased sensitivity to noxious stimuli resulting from sensitization in the nociceptive system. The aim of this study was to investigate if genetic variants of mu, kappa, and delta opioid receptor genes (OPRM1, OPRK1, and OPRD1) and the catechol-O-methyltransferase gene (COMT) influenced the pain phenotype in patients with osteoarthritis., Methods: The frequencies of 17 polymorphisms were examined. Pain sensitivity was assessed preoperatively by (1) hip rotation, (2) contact heat stimulation, (3) conditioned pain modulation effect, and (4) pressure stimulation at the tibia in both the affected and the unaffected leg., Results: Ninety-two patients (mean age 66 years) with unilateral hip osteoarthritis were included in the study. Carriage of the OPRM1 rs589046T allele was found to be associated with increased pain ratings during hip rotation (P = 0.04) and increased conditioned pain modulation (P = 0.049). Carriage of the OPRD1 rs2234918C allele was found to be associated with an increased pain detection threshold to contact heat stimulation (P = 0.001). No other associations were found (all P > 0.05)., Conclusion: Results from the present study suggest that, in patients with hip osteoarthritis, genetic variants in OPRM1 and OPRD1 may contribute to the pain phenotype., (© 2017 World Institute of Pain.)

Gamma-hydroxybutyrate (GHB) is a drug of abuse, for which physical addiction develops quickly. GHB withdrawal can develop into a life-threatening condition and has previously been treated mainly with benzodiazepines. These have not always proven effective, leading to long hospitalizations in intensive care units. Based on successful Dutch treatment results for using GHB to treat GHB withdrawal symptoms, we propose to implement a similar method in Denmark. The method requires an interdisciplinary effort for which The Danish Poison Information Centre should be consulted for expertise.

Human studies on experimentally induced pain are of value to elucidate the genetic influence on morphine analgesia under controlled conditions. The aim of this study was to investigate whether genetic variants of mu-, kappa- and delta-opioid receptor genes (OPRM1, OPRK1 and OPRD1) and catechol-O-methyltransferase gene (COMT) are associated with the morphine analgesia. The study was a randomized, double-blind, two-way, crossover, single-dose study conducted in 40 healthy participants, where morphine was compared with placebo. Pain was induced by contact heat, muscle pressure, bone pressure, rectal stimulations (mechanical, electrical and thermal) and cold pressor test (immersion of the hand into ice water). Sixteen genetic polymorphisms of four candidate genes were explored. Variability in morphine analgesia to contact heat stimulation was associated with COMT rs4680 (p = 0.04), and rectal thermal stimulation was associated with OPRM1 rs9479757 (p = 0.03). Moreover, in males, variability in morphine analgesia to rectal thermal stimulation was associated with OPRD1 polymorphisms: rs2234918 (p = 0.01) and rs533123 (p = 0.046). The study was explorative and hypothesis-generating due to the relatively small study size. However, results suggest that genetic variants in the COMT and OPRM1 irrespective of gender, and OPRD1 in males may contribute to the variability in morphine analgesia in experimental pain models., (© 2017 Nordic Association for the Publication of BCPT (former Nordic Pharmacological Society).)

The dimethoxyphenyl-N-((2-methoxyphenyl)methyl)ethanamine (NBOMe) compounds are potent serotonin 5-HT2A receptor agonists and have recently been subject to recreational use due to their hallucinogenic effects. Use of NBOMe compounds has been known since 2011, and several non-fatal and fatal intoxication cases have been reported in the scientific literature. The aim of this study was to determine the importance of the different cytochrome P450 enzymes (CYP) involved in the metabolism of 2-(4-iodo-2,5-dimethoxyphenyl)-N-(2methoxybenzyl)ethanamine (25I-NBOMe) and 2-[[2-(4-iodo-2,5dimethoxyphenyl)ethylamino]methyl]phenol (25I-NBOH) and to characterize the metabolites. The following approaches were used to identify the main enzymes involved in primary metabolism: incubation with a panel of CYP and monoamine oxidase (MAO) enzymes and incubation in pooled human liver microsomes (HLM) with and without specific CYP chemical inhibitors. The study was further substantiated by an evaluation of 25I-NBOMe and 25I-NBOH metabolism in single donor HLM. The metabolism pathways of 25I-NBOMe and 25I-NBOH were NADPHdependent with intrinsic clearance values of (CLint) of 70.1 and 118.7 mL/min/kg, respectively. The biotransformations included hydroxylation, O-demethylation, N-dealkylation, dehydrogenation, and combinations thereof. The most abundant metabolites were all identified by retention time and spectrum matching with synthesized reference standards. The major CYP enzymes involved in the metabolism of 25I-NBOMe and 25INBOH were identified as CYP3A4 and CYP2D6, respectively. The compound 25I-NBOH was also liable to direct glucuronidation, which may diminish the impact of CYP2D6 genetic polymorphism. Users of 25I-NBOMe may be subject to drug-drug interactions (DDI) if 25I-NBOMe is taken with a strong CYP3A4 inhibitor. Copyright © 2016 John Wiley & Sons, Ltd., (Copyright © 2016 John Wiley & Sons, Ltd.)

Background: Assessment of functional ability in elderly patients is often based on self-reported rather than performance-based measures. This study aims to compare self-reported and performance-based measures of functional ability in a population of elderly patients at an emergency department (ED)., Methods: Participants were 61 patients aged 65 years and above admitted to an ED. The self-reported measure used was the Barthel-20; the performance-based measures were Timed Up and Go (TUG); 30s-Chair Stand Test (30s-CST) and Assessment of Motor and Process Skills (AMPS) with the two scales; motor and process. Correlation analyses were conducted to examine the relationships between the self-reported and performance-based measures of functional ability., Results: The correlation between the Barthel-20 and the TUG was moderate (r = -0.64). The correlation between the Barthel-20 and the AMPS motor was also moderate (r = 0.53). The correlation between the Barthel-20 and the 30s-CST was fair (r = 0.45). The correlation between Barthel-20 and the AMPS process was non-significant. The results were affected by high ceiling effect (Barthel-20)., Conclusion: Self-reported and performance-based measures seem to assess different aspects of functional ability. Thus, the two methods provide different information, and this highlight the importance of supplementing self-reported measures with performance-based measures when assessing functional ability in elderly patients.

The genetic influence on sensitivity to noxious stimuli (pain sensitivity) remains controversial and needs further investigation. In the present study, the possible influence of polymorphisms in three opioid receptor (OPRM, OPRD and OPRK) genes and the catechol-O-methyltransferase (COMT) gene on pain sensitivity in healthy participants was investigated. Catechol-O-methyltransferase has an indirect effect on the mu opioid receptor by changing its activity through an altered endogenous ligand effect. Blood samples for genetic analysis were withdrawn in a multi-modal and multi-tissue experimental pain model in 40 healthy participants aged 20-65. Seventeen different single nucleotide polymorphisms in different genes (OPRM, OPRK, OPRD and COMT) were included in the analysis. Experimental pain tests included thermal skin stimulation, mechanical muscle and bone stimulation and mechanical, electrical and thermal visceral stimulations. A cold pressor test was also conducted. DNA was available from 38 of 40 participants. Compared to non-carriers of the COMT rs4680A allele, carriers reported higher bone pressure pain tolerance threshold (i.e. less pain) by up to 23.8% (p < 0.015). Additionally, carriers of the C allele (CC/CT) of OPRK rs6473799 reported a 30.4% higher mechanical visceral pain tolerance threshold than non-carriers (TT; p < 0.019). For the other polymorphisms and stimulations, no associations were found (all p > 0.05). In conclusion, COMT rs4680 and OPRK rs6473799 polymorphisms seem to be associated with pain sensitivity. Thus, the findings support a possible genetic influence on pain sensitivity., (© 2016 Nordic Association for the Publication of BCPT (former Nordic Pharmacological Society).)

Background: Gastro-oesophageal reflux disease (GORD) is a major health problem that is frequently accompanied by debilitating oesophageal pain symptoms., Objectives: The first objective of the study was to examine the association between catastrophizing and oesophageal pain sensitivity. The second objective was to examine whether catastrophizing was associated with the magnitude of acid-induced oesophageal sensitization., Methods: Twenty-five healthy volunteers (median age: 24.0 years; range: 22-31) were recruited and were asked to complete the Pain Catastrophizing Scale (PCS). During two subsequent study visits, mechanical, thermal, and electrical pain sensitivity in the oesophagus was assessed before and after inducing oesophageal sensitization using a 30-min intraluminal oesophageal acid perfusion procedure., Results: Analyses were conducted based on data averaged across the two study visits. At baseline, catastrophizing was significantly associated with mechanical (r = -0.42, p < 0.05) and electrical (r = -0.60, p < 0.01) pain thresholds. After acid perfusion, catastrophizing was also significantly associated with mechanical (r = -0.58, p < 0.01) and electrical (r = -0.50, p < 0.05) pain thresholds. Catastrophizing was not significantly associated with thermal pain thresholds. Subsequent analyses revealed that catastrophizing was not significantly associated with the magnitude of acid-induced oesophageal sensitization., Conclusion: Taken together, findings from the present study suggest that catastrophic thinking exerts an influence on oesophageal pain sensitivity, but not necessarily on the magnitude of acid-induced oesophageal sensitization. WHAT DOES THIS STUDY ADD?: Catastrophizing is associated with heightened pain sensitivity in the oesophagus. This was substantiated by assessing responses to noxious stimulation of the oesophagus using an experimental paradigm mimicking features and symptoms experienced by patients with gastro-oesophageal reflux disease (GORD)., (© 2016 European Pain Federation - EFIC®)

In recent years, synthetic cannabinoids have emerged in the illicit drug market, in particular via the Internet, leading to abuse of these drugs. There is currently limited knowledge about the specific enzymes involved in the metabolism of these drugs. In this study, we investigated the cytochrome P450 (CYP) enzymes involved in the metabolism of the two synthetic cannabinoids (1-pentyl-1H-indol-3-yl)-(2,2,3,3-tetramethylcyclopropyl)methanone (UR-144) and [1-(5-fluoropentyl)-1H-indol-3-yl)](2,2,3,3-tetramethylcyclopropyl)methanone (XLR-11). This study extends previous studies by identifying the specific CYP enzymes involved in the metabolism of UR-144 and XLR-11 utilizing a panel of nine recombinant enzymes (CYP1A2, 2B6, 2C8, 2C9, 2C18, 2C19, 2D6, 3A4, and 2E1). This is followed by an investigation of the effect of specific inhibitors targeted against CYP1A2, 2B6, 2C9, 2C19, 2D6 and 3A4 in human liver microsomes (HLM). Incubations of UR-144 and XLR-11 with recombinant CYP enzymes revealed that UR-144 and XLR-11 are extensively metabolized by CYP3A4 at the tetramethylcyclopropyl (TMCP) moiety, but also CYP1A2 and CYP2C19 showed activity. Inhibition of CYP3A4 in HLM attenuated the metabolism of UR-144 and XLR-11, while inhibition of the other CYP enzymes in HLM had only minor effects. Thus, CYP3A4 is the major contributor to the CYP mediated metabolism of UR-144 and XLR-11 with minor contributions from CYP1A2. Users of UR-144 and XLR-11 are thus subject to the influence of potential drug-drug interactions, if they are concomitantly medicated with CYP3A4 inducers (e.g. some antiepileptics) or inhibitors (e.g. some antifungal drugs). Copyright © 2015 John Wiley & Sons, Ltd., (Copyright © 2015 John Wiley & Sons, Ltd.)

Background: Rotator cuff rupture is associated with dysfunction, pain and muscular weakness related to the upper extremity. Some evidence exists to support the beneficial effect of exercises but there is lack of evidence of which exercises imply the best effect and how physiotherapy should be administered. Therefore, the purpose of this study was to examine the effect of a neuromuscular exercise program for patients with irreparable rotator cuff rupture., Methods: Based on sample-size calculations thirty patients with chronic irreparable rotator cuff tears (of at least m. supraspinatus and m. infraspinatus) was consecutively included. Twenty-four patients completed the five months training to restore function with focus on centering the humeral head in the glenoid cavity trough strengthening m. deltoideus anterior and m. teres minor. The primary outcome measure was Oxford Shoulder Score which was completed at baseline, 3 and 5 months follow-up. One-way, repeated-measure ANOVA was used if data was normally distributed. Secondary outcome measures included EQ-5D, range of motion, strength and muscle activity. Paired t-test and Wilcoxon Signed Ranks Test was used to the appropriate outcomes., Results: Improvements was seen for both primary and secondary outcomes from baseline to follow-up. Oxford Shoulder Score improved from 25.6 (SD 8.1) at baseline to 33.8 (SD 8.7) at 3 months (p = 0.004) and 37.2 (SD 8.2) at five months (p < 0.001). Range of motion in abduction significantly increased by 34.4° (95 % CI: 11.6-57.2). Strength measured in flexion 45, flexion 90 and abduction also significantly increased at 5 months by 10.2 (95 % CI: 0.8-19.6), 7.0 (95 % CI: 0.0-14.0) and 12.3 (95 % CI: 3.4-21.3) respectively. The remaining outcomes for range of motion and strengths only showed small and non-significant changes. Furthermore patients reported higher levels of quality of life and reduced level of pain after five months., Conclusion: Following a five months exercise protocol patients with irreparable rotator cuff tears showed increased function in their symptomatic shoulder, reduced pain and increased quality of life. This study therefore supports the use of exercise therapy in patients with irreparable rotator cuff rupture., Trial Registration: This study is approved by The National Committee on Health Research Ethics (N-20120040) and registered retrospectively at ClinicalTrials.gov in April 2016 ( NCT02740946 ).

Synthetic cannabinoid designer drugs have emerged as drugs of abuse during the last decade, and acute intoxication cases are documented in the scientific literature. Synthetic cannabinoids are extensively metabolized, but our knowledge of the involved enzymes is limited. Here, we investigated the metabolism of N-(1-adamantyl)-1-pentyl-1H-indazole-3-carboxamide (AKB-48), a compound identified in herbal blends from 2012 and onwards. We screened for metabolite formation using a panel of nine recombinant cytochrome P450 (CYP) enzymes (CYP1A2, 2B6, 2C8, 2C9, 2C18, 2C19, 2D6, 2E1, and 3A4) and compared the formed metabolites to human liver microsomal (HLM) incubations with specific inhibitors against CYP2D6, 2C19, and 3A4, respectively. The data reported here demonstrate CYP3A4 to be the major CYP enzyme responsible for the oxidative metabolism of AKB-48, preferentially performing the oxidation on the adamantyl moiety. Genetic polymorphisms are likely not important with regard to toxicity given the major involvement of CYP3A4. Adverse drug-drug interactions (DDIs) could potentially occur in cases with co-intake of strong CYP3A4 inhibitors, e.g., HIV antivirals and azole antifungal agents.

Human experimental pain studies are of value to study basic pain mechanisms under controlled conditions. The aim of this study was to investigate whether genetic variation across selected mu-, kappa- and delta-opioid receptor genes (OPRM1, OPRK1and OPRD1, respectively) influenced analgesic response to oxycodone in healthy volunteers. Experimental multimodal, multitissue pain data from previously published studies carried out in Caucasian volunteers were used. Data on thermal skin pain tolerance threshold (PTT) (n = 37), muscle pressure PTT (n = 31), mechanical visceral PTT (n = 43) and thermal visceral PTT (n = 41) were included. Genetic associations with pain outcomes were explored. Nineteen opioid receptor genetic polymorphisms were included in this study. Variability in oxycodone response to skin heat was associated with OPRM1 single-nucleotide polymorphisms (SNPs) rs589046 (P < 0.0001) and rs563649 (P < 0.0001). Variability in oxycodone response to visceral pressure was associated with four OPRM1 SNPs: rs589046 (P = 0.015), rs1799971 (P = 0.045), rs9479757 (P = 0.009) and rs533586 (P = 0.046). OPRM1 SNPs were not associated with oxycodone visceral heat threshold, however, one OPRD1 rs419335 reached significance (P = 0.015). Another OPRD1 SNP rs2234918 (P = 0.041) was associated with muscle pressure. There were no associations with OPRK1 SNPs and oxycodone response for any of the pain modalities. Associations were found between analgesic effects of oxycodone and OPRM1 and OPRD1 SNPs; therefore, variation in opioid receptor genes may partly explain responder characteristics to oxycodone., (© 2015 Société Française de Pharmacologie et de Thérapeutique.)

On an individual level, there is a difference in the analgesic response to a given opioid. Various factors such as gender, age, and genetic variation can affect the analgesic response. The genetic variation can influence pharmacokinetics (eg drug transporters and drug-metabolizing enzymes) and/or pharmacodynamics (eg opioid receptor and catechol-O-methyltransferase enzymes). We present recent experimentally induced pain, postoperative pain, and cancer pain and chronic non-malignant pain conditions studies in humans, focusing on the association between genetic variation and analgesic response assessed as opioid consumption or changes in pain scores. Studies have shown promising results regarding pharmacogenetics as a diagnostic tool for predicting the individual response to a given opioid in the experimental settings; however, in the clinic, it is a more complicated task to accomplish., (© 2014 World Institute of Pain.)

Synthetic cannabimimetic agents are a large group of diverse compounds which act as agonists at cannabinoid receptors. Since 2004, synthetic cannabinoids have been used recreationally, although several of the compounds have been shown to cause severe toxicity in humans. In this study, the metabolism of two indazole carboxamide derivatives, AB-PINACA and AB-FUBINACA, was investigated by using human liver microsomes (HLM). For both compounds, a major metabolic pathway was the enzymatic hydrolysis of the primary amide, resulting in the major metabolites AB-PINACA-COOH and AB-FUBINACA-COOH. Other major metabolic pathways were mono-hydroxylation of the N-pentyl chain in AB-PINACA and mono-hydroxylation of the 1-amino-3-methyl-1-oxobutane moiety in AB-FUBINACA. To identify the enzyme(s) responsible for the amide hydrolysis, incubations with recombinant carboxylesterases and human serum, as well as inhibition studies in HLM and human pulmonary microsomes (HPM) were performed. Carboxylesterase 1 (CES1) was identified as the major human hepatic and pulmonary enzyme responsible for the amide hydrolysis.We employed similar studies to identify the esterase(s) involved in the previously described hydrolytic metabolism of two quinolineindole synthetic cannabinoids, PB-22 and 5F-PB-22, as well as the closely related compound, BB-22. Our investigations again revealed CES1 to be the key enzyme catalyzing these reactions. The identified major metabolites of AB-PINACA and AB-FUBINACA are likely to be useful in documenting drug usage in forensic and clinical screening. Additionally, the identification of CES1 as the main enzyme hydrolyzing these compounds improves our knowledge in the emerging field of xenobiotic metabolism by esterases., (Copyright © 2014 John Wiley & Sons, Ltd.)

A main challenge in food safety research is to demonstrate that processing of foodstuffs does not lead to the formation of substances for which the safety upon consumption might be questioned. This is especially so since food is a complex matrix in which the analytical detection of substances, and consequent risk assessment thereof, is difficult to determine. Here, a pragmatic novel safety assessment strategy is applied to the production of non-selective extracts (NSEs), used for different purposes in food such as for colouring purposes, which are complex food mixtures prepared from reference juices. The Complex Mixture Safety Assessment Strategy (CoMSAS) is an exposure driven approach enabling to efficiently assess the safety of the NSE by focussing on newly formed substances or substances that may increase in exposure during the processing of the NSE. CoMSAS enables to distinguish toxicologically relevant from toxicologically less relevant substances, when related to their respective levels of exposure. This will reduce the amount of work needed for identification, characterisation and safety assessment of unknown substances detected at low concentration, without the need for toxicity testing using animal studies. In this paper, the CoMSAS approach has been applied for elderberry and pumpkin NSEs used for food colouring purposes., (Copyright © 2015 Elsevier Ltd. All rights reserved.)

PPC-5650 is a new pharmacological agent that can modulate acid-sensing ion channel activity, leading to a reduction in the pain signal under up-regulated conditions. The non-clinical programme for PPC-5650 supported a role for this novel agent in the treatment of pain in patients with irritable bowel syndrome (IBS). In patients with IBS, the aims of the study were: (1) to assess the efficacy of a single bolus of PPC-5650 locally applied in the rectum using multi-modal stimulations of the recto sigmoid and (2) to assess the safety profile of PPC-5650. The study was a randomized, double-blind, placebo-controlled, cross-over trial in patients with IBS, excluding females of child-bearing potential. The study consisted of a training visit, study visit 1 and 2 and a follow-up visit. Rectosigmoid electrical, thermal and mechanical stimulations were performed, pain perception was rated on a pain intensity scale and referred pain areas were assessed. All adverse events were registered. Twenty-five patients with IBS were enrolled and completed the study (9 women and 16 men; mean age 50.4 ± 12.7 years). No effects of the study drug were found on any of the rectal stimulations or for referred pain areas (all p > 0.05). No significant or clinically relevant treatment-related differences were seen for the laboratory safety variables or any other reported adverse event. In conclusion, in patients with IBS on rectal sensitivity to multi-modal stimulations, PPC-5650 did not produce efficacy relative to placebo. The overall safety and tolerability of PPC-5650 was acceptable., (© 2014 Nordic Association for the Publication of BCPT (former Nordic Pharmacological Society).)

Objective: Gastroesophageal reflux disease (GERD) is a common condition associated with symptoms as heart burn, regurgitation, chest pain, and gastrointestinal discomfort. PPC-5650 is a new pharmacological agent that can modulate acid-sensing ion channel activity, potentially leading to reduction in the pain signal. In healthy volunteers the esophagus was sensitized with acid to mimic GERD with the aims: 1) to assess the efficacy of a single bolus of PPC-5650 locally applied to the esophagus using multimodal pain stimulations, and 2) to assess the safety profile of PPC-5650., Materials and Methods: The study was a randomized, double-blinded, placebo-controlled, crossover trial in healthy males. Esophageal electrical, thermal, mechanical, and chemical stimulations were performed, pain perception was rated, and referred pain areas were drawn. Sensitization was induced by intraluminal esophageal acid perfusions. Adverse events were registered., Results: Twenty-five healthy males completed the study (mean age 23.4 ± 2.0 years). About 90 min after drug administration, PPC-5650 increased the volume tolerated at moderate pain during mechanical stimulation compared to placebo (difference 13.5, 95% CI: 0.58-26.47, p = 0.04), but there was no effects on thermal-, electrical-, and chemical-induced pain (all p > 0.05). PPC-5650 did not affect referred pain areas to any stimulation (all p > 0.05). Ten participants reported adverse events during the placebo treatment period, and nine participants reported adverse events during the PPC-5650 treatment period (p = 0.8)., Conclusion: Sensitization to mechanical stimulation of the esophagus was reduced by PPC-5650 compared to placebo. The overall safety and tolerability of PPC-5650 was acceptable. Thus, PPC-5650 may play a role in the future treatment of patients with GERD.

The analysis of designer drugs in human plasma is highly complex, as most of these drugs are metabolized quickly, and often into multiple products. For novel designer drugs, it is common that reference compounds for these metabolites are unavailable at the time of analysis. Hence, the usage of in silico procedures to accurately predict the chemical structures of these metabolites would be very useful. In this study, the differences between several methods for prediction of site of metabolism for cytochrome P450 mediated drug metabolism are described, and their prediction accuracies are analyzed on a set of designer drugs. It is found that ligand-based methods, which are simpler and faster, are better than or at least as good as much more complex structure-based methods.

Chronic pancreatitis (CP) is an inflammatory disease of the pancreas characterized by progressive fibrotic destruction of the pancreatic secretory parenchyma. Despite the heterogeneity in pathogenesis and involved risk factors, processes such as necrosis/apoptosis, inflammation or duct obstruction are involved. This fibrosing process ultimately leads to progressive loss of the lobular morphology and structure of the pancreas, deformation of the large ducts and severe changes in the arrangement and composition of the islets. These conditions lead to irreversible morphological and structural changes resulting in impairment of both exocrine and endocrine functions. The prevalence of the disease is largely dependent on culture and geography. The etiological risk-factors associated with CP are multiple and involve both genetic and environmental factors. Throughout this review the M-ANNHEIM classification system will be used, comprising a detailed description of risk factors such as: alcohol-consumption, nicotine-consumption, nutritional factors, hereditary factors, efferent duct factors, immunological factors and miscellaneous and rare metabolic factors. Increased knowledge of the different etiological factors may encourage the use of further advanced diagnostic tools, which potentially will help clinicians to diagnose CP at an earlier stage. However, in view of the multi factorial disease and the complex clinical picture, it is not surprising that treatment of patients with CP is challenging and often unsuccessful.

In biology the interplay between multiple light-absorbers gives rise to complex quantum effects such as superposition states that are of extreme importance for life, both for harvesting solar energy and likely protecting nucleic acids from radiation damage. Still the characteristics of these states and their quantum dynamics are a much debated issue. While the electronic properties of single bases are fairly well understood, the situation for strands is complicated by the fact that stacked bases electronically couple when photoexcited. These newly arising states are denoted as exciton states and are simply linear combinations of localised wavefunctions that involve N - 1 ground-state bases and one base in its excited state (cf. the Frenkel exciton model). There is disagreement over the number of bases, N, that coherently couple, i.e., the spatial extent of the exciton, and how electronic deexcitation back to the ground state occurs. The importance of dark charge-transfer states has been inferred both from time-resolved fluorescence and transient absorption experiments. These states were suggested to be responsible for long deexcitation times but it is unclear whether 'long' is tens of picoseconds or nanoseconds. In this review paper, we focus on the bright states initially populated and discuss their nature based on information obtained from systematic absorption and circular dichroism experiments on single strands of different lengths. Our results from the last five years are compared with those from other groups, and are discussed in the context of successive deexcitation schemes. Pieces to the puzzle have come from different experiments and theory but a complete description has yet to emerge. As such the story about DNA/RNA photophysical decay mechanisms resembles the tale about the blind men and the elephant where all see the beast in different, correct but incomplete ways.

The Psychiatric Emergency Service in Copenhagen is unique as the only psychiatric outgoing service in Denmark with medical doctor expertise. The service has been active since 1997 and is serving 1.28 million inhabitants. The target group of the service are psychiatric patients, who are not able to attend the psychiatric emergency rooms, for example because of severe affect, psychosis or substance abuse. A quantitative and qualitative evaluation of the journals from all 1,653 contacts to the service in 2010 and 2011 clearly shows the efficacy and necessity of such a service.

A complete understanding of the physics underlying the varied colors of firefly bioluminescence remains elusive because it is difficult to disentangle different enzyme-lumophore interactions. Experiments on isolated ions are useful to establish a proper reference when there are no microenvironmental perturbations. Here, we use action spectroscopy to compare the absorption by the firefly oxyluciferin lumophore isolated in vacuo and complexed with a single water molecule. While the process relevant to bioluminescence within the luciferase cavity is light emission, the absorption data presented here provide a unique insight into how the electronic states of oxyluciferin are altered by microenvironmental perturbations. For the bare ion we observe broad absorption with a maximum at 548 ± 10 nm, and addition of a water molecule is found to blue-shift the absorption by approximately 50 nm (0.23 eV). Test calculations at various levels of theory uniformly predict a blue-shift in absorption caused by a single water molecule, but are only qualitatively in agreement with experiment highlighting limitations in what can be expected from methods commonly used in studies on oxyluciferin. Combined molecular dynamics simulations and time-dependent density functional theory calculations closely reproduce the broad experimental peaks and also indicate that the preferred binding site for the water molecule is the phenolate oxygen of the anion. Predicting the effects of microenvironmental interactions on the electronic structure of the oxyluciferin anion with high accuracy is a nontrivial task for theory, and our experimental results therefore serve as important benchmarks for future calculations.

Clinical studies comparing the response and side effects of various opioids have not been able to show robust differences between drugs. Hence, recommendations of the regulatory authorities have been driven by costs with a general tendency in many countries to restrict physician's use of opioids to morphine. Although this approach is recognized as cost-effective in most cases there is solid evidence that, on an individual patient basis, opioids are not all equal. Therefore it is important to have an armamentarium of strong analgesics in clinical practice to ensure a personalized approach in patients who do not respond to standard treatment. In this review we highlight differences between opioids in human studies from a pharmacological, experimental, clinical and health economics point of view. We provide evidence that individuals respond differently to opioids, and that general differences between classes of opioids exist. We recommend that this recognition is used to individualize treatment in difficult cases allowing physicians to have a wide range of treatment options. In the end this will reduce pain and side effects, leading to improved quality of life for the patient and reduce the exploding pain related costs., (© 2012 The Authors. British Journal of Clinical Pharmacology © 2012 The British Pharmacological Society.)

Absorbance spectroscopy is used extensively to tell when two DNA single strands come together and form a double strand. Here we show that circular dichroism in the vacuum ultraviolet region provides an even stronger indication for duplex formation in the case of short strands of adenine and thymine (4 to 16 bases in each strand). Indeed, our results show that a strong positive CD band appears at 179 nm when double strands are formed. Melting experiments were done in aqueous solution with and without added Na(+) counter ions. With additional salt present a huge increase in the 179 nm CD band was observed when lowering the temperature. A 179 nm CD marker band for duplex formation can be used to measure the kinetics for the association of two single strands. Such experiments rely on large changes at one particular wavelength since it is too time-consuming to record a full-wavelength spectrum.

Circular dichroism spectra (176-330 nm) of RNA adenine oligomers, (rA)(n) (n = 1-10, 12, 15, and 20), reveal electronic coupling between two bases in short strands. The number of interacting bases in long strands is more and larger than that reported previously for the corresponding DNA strands.

The degree of electronic coupling between DNA bases is a topic being up for much debate. Here we report on the intrinsic electronic properties of isolated DNA strands in vacuo free of solvent, which is a good starting point for high-level excited states calculations. Action spectra of DNA single strands of adenine reveal sign of exciton coupling between stacked bases from blueshifted absorption bands (~3 nm) relative to that of the dAMP mononucleotide (one adenine base). The bands are blueshifted by about 10 nm compared to those of solvated strands, which is a shift similar to that for the adenine molecule and the dAMP mononucleotide. Desolvation has little effect on the bandwidth, which implies that inhomogenous broadening of the absorption bands in aqueous solution is of minor importance compared to, e.g., conformational disorder. Finally, at high photon energies, internal conversion competes with electron detachment since dissociation of the bare photoexcited ions on the microsecond time scale is measured., (© 2012 American Institute of Physics)

Objective: To compare the effects of physical rehabilitation with (PRT) and without (CON) progressive resistance training following treatment of spastic plantarflexors with botulinum toxin type A (BoNT) in children with cerebral palsy (CP)., Methods: Fourteen children with CP performed supervised PRT (n=7) or CON (n=7) two times per week for 12 weeks, following the BoNT-treatment. Outcome measurements were performed at baseline (pre BoNT), and 4 and 12 weeks post BoNT. They consisted of: ankle muscle function (maximal torque and submaximal torque steadiness of isometric ankle dorsi- and plantarflexion and associated ankle muscle [EMG] activity), gait function (3-dimensional gait analysis), balance function (sway analysis), gross motor function (GMFM-66), and spasticity (modified Ashworth)., Results: Submaximal torque control (torque steadiness) of isometric dorsiflexion improved similarly in the two groups, and the improvement was related to the reduction in antagonist (soleus) co-activity (P< 0.05). Maximal plantarflexion torque increased after PRT, whereas a reduction was seen after CON (P< 0.05). No changes in function were observed., Conclusions: Both types of physical rehabilitation in combination with BoNT-treatment improved antagonist (ankle dorsiflexion) torque-control to the same extent - which was related to the reduction in antagonist co-activity - but only rehabilitation with PRT increased maximal plantarflexion torque.

Circular dichroism (CD) is a powerful technique to obtain information on electronic transitions and has been used extensively for studies on DNA. Most experiments are done in the UV region but new information is often revealed from extending the wavelength region down into the vacuum ultraviolet (VUV) region. Such experiments are most easily carried out with synchrotron radiation (SR) light sources that provide large photon fluxes. Here we provide a summary of the SRCD data taken on different DNA strands with emphasis on results from our own laboratory within the last five years.(1-3) Signal intensities in the VUV are often significantly larger than those in the UV, and the electronic coupling between bases may increase with excitation energy. CD spectroscopy is particularly useful for investigating the extent of electronic coupling within a strand, i.e., the degree of delocalisation of the excited-state electronic wavefunction. The spatial extent of the wavefunction may be limited to just one base or it extends over two or more bases in a stack or between bases on different strands.(4,5) The actual character of the electronically excited state is linked to base composition and sequence as well as DNA folding motif (A-, B-, Z-DNA, triplexes, quadruplexes, etc.). The latter depends on experimental conditions such as solution acidity, temperature, ionic strength, and solvent.

In this work we have recorded synchrotron radiation circular dichroism (SRCD) spectra from 180 nm to 360 nm of cytosine strands [(dC)(n), n = 1, 2, ..., 10] in aqueous solution at different pH values to reveal electronic coupling between bases in different ionisation states. The geometry of the strands is determined by the pH value and the strand length and the local organisation of the cytosines will determine the base-to-base interaction that impacts on the CD signal. At low pH where all bases are protonated, there is no signature of electronic coupling between the bases, and the SRCD spectrum is simply n times that of the n = 1 spectrum. At higher pH where all bases are neutral, the spectra for n > 1 differ from the monomer spectrum, which implies electronic coupling between bases. The correlation between the CD signal and n is linear, and the spatial extent of the excited state wavefunction is therefore over just two stacked bases both in the UV and VUV. At intermediate pH, the low-n spectra are different from the high-n spectra, and a transition is seen to occur at n = 6-8. We ascribe this behavior to the formation of i-motif structures between four (dC)(n) strands for high n.

We investigated whether the quality of management of COPD in general practice could be improved by the participation of general practitioners and their staff in a COPD-specific educational programme. One-hundred and fifty-four doctors participated in the study, and 2549 patient record forms were included in the first audit and 2394 in the second audit. We observed a significantly increased utilisation of spirometry from the first (52.7%) to the second audit (71.4%) (p < 0,001) and improvement in other parameters describing the quality of management. We conclude that participation in an educational programme can improve the quality of COPD care in general practice.

Aim: We studied the quality of care for COPD patients in a large sample of general practices in Denmark. We focussed on whether participation by general practitioners (GPs) in an educational programme could enhance the use of spirometry in the diagnosis and staging of the disease and improve adherence to COPD guidelines., Methods: We performed two audit surveys of GPs' patients' notes, one year apart, before and after an educational programme for participating GPs and their staff. A total of 154 GPs participated in the study. 2549 patient records were included in the first survey and 2394 in the second., Results: Based on analysis of all patient records, we observed a substantial improvement in the quality of care: recording of FEV1 improved from 52.7% of cases in the first survey to 71.4% in the second (p< 0.001). There was a significant improvement in the recording of body mass index and provision of smoking cessation advice, recommendation of physical activity, checking of inhalation technique, dietary instruction, and referral to pulmonary rehabilitation. We also found a decline in the use of inhaled corticosteroids in patients with mild COPD, from 60.2% in the first survey to 48.8% in the second. When analysing the results focussing on the performance of single GPs there was an improvement in quality, but this was less than the improvement for patients overall - suggesting that improvement in quality of care was not equally distributed throughout the GPs' practices., Conclusion: We conclude that it is possible to improve the quality of COPD care by educating GPs and their staff.

Aims: To compare health effects and risk reduction in two different strategies of nutritional counselling in primary health care for patients at high risk of ischaemic heart disease., Methods: In a cluster-randomized trial 60 general practitioners (GPs) in the Copenhagen County were randomized to give nutritional counselling or to refer patients to a dietician. Patients were included after opportunistically screening (n=503 patients), and received nutritional counselling by GP or dietician over 12 months. Health effects were measured by changes in weight, waist circumference and blood lipids. Risk of cardiovascular disease was calculated by The Copenhagen Risk Score. Data on use of medicine and primary health care was obtained from central registers., Results: Altogether 339 (67%) patients completed the intervention. Weight loss was larger in the dietician group (mean 4.5 kg vs. 2.4 kg), and increase of HDL-cholesterol was larger in the GP group (mean 0.13 mmol/l vs. 0.03 mmol/l). The reduction of the cardiovascular risk score was significantly larger in the GP group (P=0.0005). Other health outcomes were not significantly different., Conclusions: GPs were aware of substantial risk factors of cardiovascular disease and addressed these when counselling. The guidance from a GP was of significant importance for risk reduction in relation to IHD. However, a long-term lifestyle intervention by GP was difficult to implement. In the case of obesity it was effective to refer to long-term nutritional counselling by a dietician.

Introduction: The aim of the study was to describe the course of respiratory syncytial virus (RSV) infections in children under two years of age seen in general practice., Material and Methods: Children under two years of age presenting acute respiratory infection during the registration period on 59 GPs' lists participated in the study. The GPs recorded data on a registration chart and a questionnaire was sent to the parents of the children in question one month after the date of inclusion. The children were tested in general practice for the presence of RSV. The GPs' objective findings and choice of treatment as well as the parents' account of the course of disease were compared in children with and without the presence of RSV. A total of 221 children participated in the study., Results: Fifty-seven children were found RSV positive (25.8%). Among the RSV positive children there were significantly more with wheezing audibly detected with examination by stethoscope than among the RSV negative. The remaining parameters (the GP's objective examination, treatment and course of the disease) were distributed independently of the result of the RSV analysis., Discussion: The results showed that RSV infections in children under two years in general practice are frequent and that the clinical picture most often is uncomplicated.

Adverse effects of perioperative blood transfusion appear to be storage-time-dependent and may be related to extracellular accumulation of bioactive substances in blood products. In this study the clinical effects of leukofiltered and non-filtered blood products in patients undergoing surgery for burn trauma are investigated. 24 consecutive patients were randomly selected to receive transfusion with non-filtered blood components (group A, n = 12) or similar products, which were prestorage leukofiltered (group B, n = 12). The burn injury was scored using the Bull and Fischer index of age and burn surface area. Histamine, interleukin-6 (IL-6), plasminogen activator inhibitor-1 (PAI-1), eosinophil cationic protein (ECP) and myeloperoxidase (MPO) were analysed in plasma or serum collected from all patients 30 min before skin incision, at skin incision and 5, 10 and 30 min and thereafter every 30 min after skin incision until the grafts were secured by wrapping. Samples were also taken 8 h after skin incision and in the morning of postoperative days 1-5. The amount of blood products transfused from admission until day 5 postoperatively was recorded. All patients were followed until discharge or death. The Bull and Fischer index was comparable in the two groups. Prestorage leukofiltration reduced the amount of blood products required for transfusion significantly (p < 0.05) compared with non-filtered products. The levels of the various bioactive substances changed during and after the operation. In particular, ECP and MPO levels increased significantly (p < 0.05) in group A patients compared with unchanged (ECP) or decreased (MPO) levels in group B patients. IL-6 analyses showed, that the trauma had more severe impact on group B patients than on group A patients. Nevertheless, 4 patients died in group A and 2 in group B; all with a Bull and Fischer index between 1.0 and 2.0. Prestorage leukocyte filtration may reduce transfusion related accumulation of various bioactive substances and the requirement for blood in burn trauma patients.

Even though the clinical efficacy is not well established, theophylline is commonly prescribed as a second or third line drug after inhaled beta 2-agonists and corticosteroids for patients with chronic obstructive pulmonary disease (COPD). The therapeutic index is narrow, and therefore theophylline is often given in a "safe standard dose", e.g. 300 mg b.i.d. We studied the long-term effect of sustained-release theophylline 300 mg b.i.d. over four weeks in 48 patients with severe irreversible COPD (FEV1: 0.99 +/- 0.45 l, FVC: 2.21 +/- 0.68 l) in a randomized, double-blind crossover study. During theophylline treatment there was significant improvements in dyspnoea score (p < 0.001) and morning peak-flow (p < 0.05). In spite of this, there was no significant change in the patients' "sense of well-being" or their daily use of inhaled beta-agonist. Spirometric tests or arterial blood gas values did not change significantly either. It is concluded that addition of theophylline in a "safe standard dose" (i.e. 300 mg b.i.d.) has only limited value in these patients.