Two-year results from a randomized clinical trial of revascularization in patients with intermittent claudication.

BACKGROUND: Intermittent claudication is associated with significant impairment of health-related quality of life. The use of revascularization techniques to improve health-related quality of life remains controversial. METHODS: Patients with intermittent claudication due to iliac or femoropopliteal peripheral artery disease were enrolled in the IRONIC trial. They were randomized to either best medical therapy (BMT), including a structured, non-supervised exercise programme, or revascularization with either endovascular or open techniques in addition to BMT. The primary outcome was health-related quality of life at 2 years assessed using the Short Form 36 (SF-36(®) ) questionnaire. Secondary outcomes included VascuQoL questionnaire results, treadmill walking distances and achievement of patient-specified treatment goals. RESULTS: Both randomized groups had improved health-related quality of life and treadmill walking distance at 2-year follow-up. Overall SF-36(®) physical component summary score, three SF-36(®) physical domain scores, overall VascuQoL score, and three of five VascuQoL domain scores showed significantly greater improvement in the group that also received invasive treatment. Intermittent claudication distance on a graded treadmill improved more in the revascularization + BMT group (117 versus 55 m; P = 0·003) whereas maximum walking distance and 6-min walk test distance were similar. Some 44 per cent of patients in the revascularization + BMT group reported they had fully achieved their treatment goal versus 10 per cent in the BMT group. CONCLUSION: A revascularization strategy with unsupervised exercise improved health-related quality of life and intermittent claudication distance more than standard BMT and an unsupervised exercise programme in patients with lifestyle-limiting claudication. REGISTRATION NUMBER: NCT01219842 (http://www.clinicaltrials.gov).

Patient Participation in Rehabilitation Questionnaire (PPRQ)-development and psychometric evaluation.

STUDY DESIGN: A cross-sectional postal questionnaire study. OBJECTIVES: The aim of the study was to evaluate selected psychometric properties of a draft version of the Patient Participation in Rehabilitation Questionnaire (PPRQ) measuring patients' experiences of participation in care and rehabilitation. SETTING: Sweden. METHODS: On the basis of previous qualitative analyses of patient interview data, a 32-item questionnaire covering five domains of participation was developed and sent to 268 persons with spinal cord injury, aged 18-80 years and injured 1-12 years previously. In total, 141 (51%) evaluable questionnaires were returned. Multi-trait analysis was used to assess scaling assumptions by testing item convergent and discriminant validity and internal consistency reliability (Cronbach's α) associated with the hypothesized item-scale structure of the questionnaire. RESULT: Nine items failed to meet scaling assumptions and were omitted. Scaling assumptions were thereafter substantiated for the scales: 'respect and integrity' (6 items); 'planning and decision-making' (4 items); 'information and knowledge' (4 items); 'motivation and encouragement' (5 items); and 'involvement of family' (4 items). Item-scale correlations ranged from 0.67 to 0.85 and most items correlated higher or significantly higher with their hypothesized scale than with other scales. Cronbach's α was 0.89 for all scales. CONCLUSION: The PPRQ appears to adequately assess central aspects of participation in care and rehabilitation from the perspective of patients with spinal cord injury. Further studies using larger samples will be undertaken to confirm the scale structure as well as the sensitivity and responsiveness of the questionnaire.

Patient participation in care and rehabilitation from the perspective of patients with spinal cord injury.

STUDY DESIGN: Qualitative method, semi-structured interviews. OBJECTIVES: The aim of the study was to explore the meaning of patient participation in care and rehabilitation from the perspective of patients with spinal cord injury (SCI). SETTING: Post discharge community setting. METHODS: Semi-structured interviews were performed with 10 persons with SCI representing different ages, gender and levels of injury. All interviews were conducted individually and lasted 40-120 min. The interviews were verbally transcribed and the data were analyzed by means of content analysis. RESULTS: All informants stressed the importance of patient participation as a necessary prerequisite for successful care and rehabilitation, but emphasized that participation must be tailored to each patient's own preferences, capacities and needs. They also underscored that the staff should be sensitive and responsive to the fact that desired levels and kinds of participation may vary from patient to patient, as well as for the same patient during the course of the rehabilitation. Five themes reflecting central aspects of participation emerged: respect and integrity, planning and decision-making, information and knowledge, motivation and encouragement, and involvement of family. CONCLUSIONS: Patient participation is a critical component of successful SCI rehabilitation and must be facilitated, promoted and tailored to each patient by the staff. Based on the finding from this study a questionnaire has been developed for assessing patient experiences of five domains of participation in rehabilitation to serve as a tool to help in evaluating provided care and in identifying patients' preferences for participation.

Walking performance and health-related quality of life after surgical or endovascular invasive versus non-invasive treatment for intermittent claudication--a prospective randomised trial.

OBJECTIVES: Despite limited scientific evidence for the effectiveness of invasive treatment for intermittent claudication (IC), revascularisation procedures for IC are increasingly often performed in Sweden. This randomised controlled trial compares the outcome after 2 years of primary invasive (INV) versus primary non-invasive (NON) treatment strategies in unselected IC patients. MATERIALS/METHODS: Based on arterial duplex and clinical examination, IC patients were randomised to INV (endovascular and/or surgical, n = 100) or NON (n = 101). NON patients could request invasive treatment if they deteriorated during follow-up. Primary outcome was maximal walking performance (MWP) on graded treadmill test at 2 years and secondary outcomes included health-related quality of life (HRQL), assessed with Short Form (36) Health Survey (SF-36). RESULTS: MWP was not significantly (p = 0.104) improved in the INV versus the NON group. Two SF-36 physical subscales, Bodily Pain (p < 0.01) and Role Physical (p < 0.05) improved significantly more in the INV versus the NON group. There were 7% crossovers against the study protocol in the INV group. CONCLUSIONS: Although invasive treatment did not show any significant advantage regarding MWP, the HRQL improvements associated with invasive treatment tentatively suggest secondary benefits of this regimen. On the other hand, a primary non-invasive treatment strategy seems to be accepted by most IC patients.

Women's sexual functioning and sex life after spinal cord injury.

STUDY DESIGN: Cross-sectional, mail-back questionnaire study. OBJECTIVES: To describe women's experiences of sexual functioning and sex life after spinal cord injury (SCI). SETTING: Sweden, Denmark, Norway, Finland, and Iceland. METHODS: All community-living SCI women treated at spinal cord centres in Sweden, Denmark, Norway, Finland, and Iceland meeting inclusion criteria (n = 963) were mailed the study-specific SCI Women Questionnaire. Out of the 532 respondents, 392 reported having had sex after injury and were thus included in the study. The included women had a mean age of 42 years (range 18-68) and a mean time since injury of 11 years (range 2-54). RESULTS: The SCI women reported that the injury caused many changes in their sex life and affected many aspects of their sexuality negatively. Some changes were of a physical nature (for example, decreased, lost, or changed sensation; difficulties to achieve orgasm; bladder or bowel problems; and difficulties to move and position oneself) whereas other changes were of a psychological nature (for example, feeling unattractive or less attractive, having less self-confidence, and difficulties to meet or find a partner). CONCLUSION: Successful SCI rehabilitation requires a holistic approach, taking into account the patient's physical, psychological, and interpersonal circumstances. Given that many women with SCI remain sexually active but often experience less satisfaction after injury, it is important that rehabilitation efforts address this aspect of the patient's life. Our results elucidating strategies applied by women with SCI to compensate for loss of genital sensation and cope with physiological impairment during sexual activity may serve to help professionals in developing rehabilitation programmes for women with SCI.

Different origins of green-light photoluminescence emission in structurally ordered and disordered powders of calcium molybdate.

A strong greenish-light photoluminescence (PL) emission was measured at room temperature for disordered and ordered powders of CaMoO4 prepared by the polymeric precursor method. The structural evolution from disordered to ordered powders was accompanied by XRD, Raman spectroscopy, and TEM imagery. High-level quantum mechanical calculations in the density functional framework were used to interpret the formation of the structural defects of disorder powders in terms of band diagram and density of states. Complex cluster vacancies [MoO3 x V(O(z))] and [CaO7 x V(O(z))] (where V(O(z)) = V(O(X)), V(O(*)), V(O(**))) were suggested to be responsible to the appearance of new states shallow and deeply inserted in the band gap. These defects give rise to the PL in disordered powders. The natural PL emission of ordered CaMoO4 was attributed to an intrinsic slight distortion of the [MoO4] tetrahedral in the short range.

Pharmacokinetic and pharmacodynamic predictions of novel potential HIV-1 integrase inhibitors.

Virtual screening docking-based approach has been employed in order to select novel HIV-1 integrase (IN) potential inhibitors in large databases. Toxicity, metabolism and drug-like properties have been analyzed for the most promising compounds, using computational chemistry techniques. Results were compared and discussed with that obtained for a known HIV-1 (IN) inhibitor reported in the literature.

Virtual screening, molecular interaction field, molecular dynamics, docking, density functional, and ADMET properties of novel AChE inhibitors in Alzheimer's disease.

Alzheimer's disease (AD) affects approximately 10% of the world's population with 65 years of age, being the most common form of dementia in adults and is characterized by senile plaquets and cholinergic deficits. Many drugs currently used for the treatment of the AD are based on the improvement of cholinergic neurotransmission achieved by Acetylcholinesterase (AChE) inhibition, the enzyme responsible for acetylcholine hydrolysis. We have focused in this work on the usage of computer-aided molecular design by virtual screening, molecular dynamics with implicit and explicit water solvation, density functional, molecular interaction field studies, docking procedures, ADMET predictions in order to propose novel potential AChE inhibitor for the treatment of Alzheimer's disease.

Ten-year trends in health-related quality of life after surgical and conventional treatment for severe obesity: the SOS intervention study.

OBJECTIVE: To examine trends and effects of weight loss treatment on health-related quality of life (HRQL) in the severely obese over 10 years. DESIGN: Swedish obese subjects (SOS) intervention study is a controlled, longitudinal trial of the health effects of weight loss in the severely obese. SUBJECTS: A total of 655 of 851 surgically treated and 621 of 852 conventionally treated obese men (body mass index, BMI>or=34) and women (BMI>or=38) who completed 10 years of the study. MEASUREMENTS: HRQL was assessed before treatment and after 0.5, 1, 2, 3, 4, 6, 8 and 10 years. RESULTS: HRQL change during the 10-year observation period largely followed phases of weight loss, weight regain and weight stability. Improvements and deteriorations in HRQL were associated with the magnitude of weight loss or regain, except regarding anxiety. Peak improvements in the surgical group were observed during the first year of weight loss, whereas the weight regain phase (mainly between 1- and 6-year follow-up) was accompanied by a gradual decline in HRQL. The period from 6- to 10-year follow-up was characterized by relatively stable observations in both weight and HRQL. At 10 years, net gains were noted in all HRQL domains compared to baseline. Comparisons of treatment effects on HRQL in the surgical vs conventional group after 10 years showed significantly better outcome in the surgical group on current health perceptions, social interaction, psychosocial functioning and depression, whereas no significant differences were found for overall mood and anxiety. Long-term results of the study suggest that a maintained weight loss of about 10% is sufficient for positive long-term effects on HRQL, a limit that was reached in about two-thirds of the surgically treated patients who completed 10 years of the study. CONCLUSION: Long-lasting weight reduction in the severely obese has a general long-standing positive outcome on HRQL. Bariatric surgery is a favorable option for the treatment of severe obesity, resulting in long-term weight loss and HRQL improvements in a majority of patients. However, difficulties among some surgical patients to control and maintain weight loss over time should not be ignored. Future research should study if the long-term efficacy of bariatric surgery may be further enhanced by implementing lifestyle modification techniques in the postoperative management of patients.

ADMET properties, database screening, molecular dynamics, density functional, and docking studies of novel potential anti-cancer compounds.

Database screening was performed in a large database (hundreds of thousands of molecules which we optimized at the AM1 level) yielding a set of potential bioactive ligands. One new ligand was selected among the top solutions and optimized at the B3LYP/6-31G* level, yielding also NBO (Natural Bond Order) charges. A flexible docking program was used to investigate the interactions between the receptor and the new ligand. The stability as well as the main protein-ligand contacts of our proposed novel ligand as well as the crystallographic RAR ligand was investigated by molecular dynamics. The ADMET (Absorption, Distribution, Metabolism, Excretion and Toxicity) properties as well as the parameters of the Rule of Five were investigated. The result of this work is compared with a crystallographic ligand of RAR. Our novel proposed anti-cancer ligand indicates hydrophobic interactions and strong polar interactions with the receptor.

Homology modeling and molecular interaction field studies of alpha-glucosidases as a guide to structure-based design of novel proposed anti-HIV inhibitors.

For AIDS therapy, there are currently a number of compounds available for multiple targets already approved by the FDA and in clinic, e.g. protease inhibitors, reverse transcriptase inhibitors (NRTI, NNRTI), fusion inhibitors, CCR4, CCR5 among others. Some pharmaceuticals act against the virus before the entrance of HIV into the host cells. One of these targets is the glucosidase protein. This novel fusion target has been recently explored because the synthesis of viral glycoproteins depends on the activity of enzymes, such as glucosidase and transferase, for the elaboration of the polysaccharides. In this work we have built an homology model of Saccharomyces cerevisiae glucosidase and superimposed all relevant glucosidase-like enzymes in complex with carbohydrates, and calculated as well molecular interaction fields in our S. cerevisiae active site model. Our results suggest that there are two saccharide binding sites which are the most important for the binding of inhibitors with this family of enzymes which supports the possibility of inhibitors containing only two sugar units. Based on these results, we have proposed a novel pseudo-dissacharide which is a potential pharmaceutical for AIDS treatment.

Performance of the SF-36 health survey in screening for depressive and anxiety disorders in an elderly female Swedish population.

OBJECTIVE: To assess the sensitivity, specificity and predictive validity of suggested cut-off scores in the SF-36 mental health (MH) and mental component summary (MCS) in screening for depressive and anxiety disorders in a population sample of older Swedish women. METHOD: The sample comprised 586 randomly selected females aged 70-84 years who took part in an in-depth psychiatric examination. This provided the 'gold standard' against which the usefulness of SF-36 recommended thresholds for screening for depressive and anxiety disorders in older Swedish women was examined. RESULTS: Based on DSM-III-R criteria, 69 women (12%) were diagnosed with depression (major depression, dysthymia and/or depression NOS) and 49 (8%) with generalised anxiety and panic disorders. The previously recommended MH and MCS cut-offs (i.e. 52 and 42) gave a specificity for diagnosis of depression of 92 and 82% and sensitivity of 58 and 71%, respectively. Both the MH and MCS were good predictors of depressive disorders but poor predictors of anxiety disorders. CONCLUSION: The study supports the predictive validity of suggested SF-36 MH and MCS cut-off scores in screening for depressive disorder but not for anxiety disorder in older women in Sweden.

Molecular dynamics, database screening, density functional and docking studies of novel RAR ligands in cancer chemotherapy.

Due to the major challenge which cancer treatment and cure still imposes after many decades to the international scientific community, there is actually considerable interest in new ligands with increased bioactivity. We have focused on the retinoid acid receptor, which is considered an interesting target for drug design. In this work, we have carried out density functional geometry optimizations and different docking procedures. We have performed screening in a large database (hundreds of thousands of molecules which we optimized at the AM1 level) yielding a set of potential bioactive ligands. Two new ligands were selected and optimized at B3LYP/6-31G* level. A flexible docking program was used to investigate the interactions between the receptor and the new ligands. Molecular dynamics were performed in order to investigate the stability of the two ligands as well as the crystallographic RAR ligand inside the RAR active site. We also investigated the stability of all the main protein-ligand contacts. The parameters of the Rule of Five were investigated. The result of this work is compared with a crystallographic ligand of RAR. One of our theoretically bioactive new ligands indicates stronger and more polar and hydrophobic interactions with the receptor.

Child and family safety device affordability by country income level: an 18 country comparison.

OBJECTIVE: To compare availability, urban price, and affordability of child/family safety devices between 18 economically diverse countries. DESIGN: Descriptive: urban price surveys by local safety organisations or shoppers. SETTING: Retail stores and internet vendors. MAIN OUTCOME MEASURES: Prices expressed in US dollars, and affordability measured by hours of factory work needed to buy a child safety seat, a belt-positioning booster seat, a child bicycle helmet, and a smoke alarm. RESULTS: Prices of child and family safety devices varied widely between countries but the variation for child safety seats and bicycle helmets did not relate strongly to country income. Safety devices were expensive, often prohibitively so, in lower income countries. Far more hours of factory work were required to earn a child safety device in lower income than middle income, and middle income than higher income, countries. A bicycle helmet, for example, cost 10 hours of factory work in lower income countries but less than an hour in higher income countries. Smoke alarms and booster seats were not available in many lower income countries. CONCLUSIONS: Bicycles and two-axle motor vehicles were numerous in lower and middle income countries, but corresponding child safety devices were often unaffordable and sometimes not readily available. The apparent market distortions and their causes merit investigation. Advocacy, social marketing, local device production, lowering of tariffs, and mandatory use legislation might stimulate market growth. Arguably, a moral obligation exists to offer subsidies that give all children a fair chance of surviving to adulthood.

A comparative controlled study of personality in severe obesity: a 2-y follow-up after intervention.

OBJECTIVE: The primary purpose was to examine 2-y effects of weight change on personality traits in severely obese subjects treated conventionally or surgically. We also assessed differences between the severely obese patients and a primarily normal-weight reference group. METHOD: Personality traits were assessed using 7 of 15 scales from the Karolinska Scales of Personality (KSP): Somatic Anxiety, Muscular Tension, Psychasthenia, Psychic Anxiety, Monotony Avoidance, Impulsiveness, and Irritability. A total of 1380 surgical candidates, 1241 conventionally treated patients and 1135 subjects from the SOS (Swedish Obese Subjects) reference study, representing the general population, completed the KSP. Data presented in this study were gathered twice from the patients (prior to treatment and after 2 y) and once from the reference subjects. Significance tests and effect sizes (ES) were calculated. RESULTS: At baseline, the obese were characterised as more anxiety prone, impulsive, irritable and less monotony avoiding than the reference group; surgery patients more so than the conventionally treated. At follow-up, it was found that anxiety proneness decreased and Monotony Avoidance increased with increasing weight loss. The conventionally treated were, on average, weight stable and, hence, only a small decrease was noted regarding Somatic Anxiety. The surgery group lost on average 28 kg, and differences between surgically treated and the reference group decreased on all scales except Impulsiveness, which remained unchanged. The largest improvement was in relation to Psychasthenia. CONCLUSIONS: Weight reduction maintained for 2 y was associated with changes on practically all personality traits in proportion to the magnitude of weight loss. In particular, Psychasthenia seemed to be alleviated, while Impulsiveness was unaffected.

Computer-aided molecular design of novel glucosidase inhibitors for AIDS treatment.

Since the onset of the AIDS epidemic, some 20 million people have died and the estimate is that today close to 40 million are living with type 1 human immunodeficiency virus (HIV)/AIDS. About 14 thousands people are infected worldwide daily with this disease. Still, only a few pharmaceuticals are available for AIDS chemotheraphy. Some pharmaceuticals act against the virus before the entrance of the HIV into the host cells. One of these targets is the glucosidase protein. This class of enzymes has been recently explored because the synthesis of viral glycoproteins depends on the activity of enzymes, such as glucosidase and transferase, for the elaboration of the polysaccharides. In this work we study several glucosidase inhibitors. The DFT method is used to compute atomic charges and the ligand/receptor interaction was simulated with docking software. Analysis of the interactions of the proposed pharmaceutical, a pseudodisaccharide, with the Thermotoga maritima 4-alpha-glucanotransferase in complex with modified acarbose, the scores from docking as well as the graphical superposition of all the ligands, suggest that our molecular designed pseudo-disaccharide may be a potent glucosidase inhibitor.

Predictors of treatment outcome in intermittent claudication.

OBJECTIVE: To derive formulae to predict the likely 12-month health-related quality of life outcome following different treatments for intermittent claudication (IC). DESIGN: A prospective, randomized, controlled study. MATERIALS: One hundred and seventy-one unselected patients with stable IC were sequentially randomized to invasive therapy, supervised physical training or observation. Hierarchical analysis was used to identify significant predictors of outcome. RESULTS: The strongest outcome predictors were baseline values of the respective outcome variables in all groups. No more than two significant secondary predictors were identified for each outcome variable and no outcome variable was a predictor of any other outcome variable. Resulting prediction equations achieved between 61 and 90% concordance with improvement (75% considered adequate), with best prediction for invasive therapy and poorest for observation. Suggested cutpoints for the various endpoints in the three groups had sensitivities ranging between 65 and 100% and false positive rates between 5 and 50%. CONCLUSIONS: The derived equations adequately predicted improvement on the various outcome variables in invasive therapy and supervised physical training, and may serve as aids in selecting patients likely to benefit most from a particular treatment strategy. The uniqueness of the outcome variables underscores the importance of implementing a comprehensive set of endpoints relevant to the impacts of the condition.

Severe obesity and personality: a comparative controlled study of personality traits.

OBJECTIVE: The primary purpose was to assess personality trait differences between the severely obese seeking treatment and a mainly non-obese reference group. We also investigated gender differences and differences between obese patients and obese not seeking treatment. METHOD: Personality traits were assessed using 7 of 15 scales from the Karolinska Scales of Personality (KSP): Somatic Anxiety, Muscular Tension, Psychastenia, Psychic Anxiety, Monotony Avoidance, Impulsiveness, and Irritability. Patients from the Swedish Obese Subjects (SOS) intervention study (n=3270, ages 37-57, 71% women) and the SOS reference study (n=1135, 54% women) completed the survey. Data presented in this study were gathered prior to treatment. Significance tests and effects sizes were calculated. RESULTS: Although statistically significant differences were found between obese patients and reference subjects on nearly all personality traits, effect sizes were at most moderate. Of the three scales with moderate effects sizes, differences on Somatic Anxiety and Psychastenia could be traced to items tapping condition-specific symptoms, e.g., problems with sweating and breathing as indicators of Somatic Anxiety. Moderate differences on the Impulsiveness scale (men alone) could not be explained by item composition. Further, the obese patients differed from obese in the reference group, and both obese and reference women reported significantly higher levels on Somatic Anxiety, Muscular Tension and Psychic Anxiety compared to men (effect size: small). CONCLUSIONS: Our results provided no evidence of a general obese personality profile, instead considerable heterogeneity in personality traits was observed across our obese samples (treatment seekers vs non-seekers, men vs women) and generally only small differences were noted compared to a reference study population. Further research is needed to investigate if the somewhat elevated levels of Impulsiveness, particularly among male obese patients, is affected by weight loss. When assessing personality traits in diseased groups consideration should be given to possible confounding from, e.g., somatic symptoms.