Levels of Physical Activity, Enjoyment, Self-Efficacy for Exercise, and Social Support Before and After Metabolic and Bariatric Surgery: a Longitudinal Prospective Observational Study.

INTRODUCTION: Physical activity (PA) after metabolic and bariatric surgery (MBS) can influence weight loss, health status, and quality of life. Known mediators to participate in PA are enjoyment, self-efficacy, and social support. Little is known about PA behavior in MBS individuals. The aim of this study was to explore levels of PA and the PA mediators enjoyment, self-efficacy, and social support before and after MBS and to investigate changes over time. METHODS: Adults scheduled to undergo MBS were recruited from a Swedish university hospital. Accelerometer-measured and self-reported PA, body weight, and PA mediators were collected at baseline and at 12 to 18 months post-surgery. RESULTS: Among 90 individuals included, 50 completed the follow-up assessment and had valid accelerometer data. Sedentary time (minutes/day) was unchanged, but sedentary time as percentage of wear time decreased significantly from 67.2% to 64.5% (p<0.05). Time spent in light PA and total PA increased significantly from 259.3 to 288.7 min/day (p < 0.05) and from 270.5 to 303.5 min/day (p < 0.01), respectively. Step counts increased significantly from 6013 to 7460 steps/day (p < 0.01). There was a significant increase in self-reported PA, enjoyment, self-efficacy for exercise, and positive social support from family. The increase in PA mediators did not lead to a significant change in time spent in moderate to vigorous PA. CONCLUSION: The increase in PA-mediators was not associated with an increase in moderate to vigorous PA, but the strengthened PA mediators suggest potential for an increase in moderate to vigorous PA in patients undergoing MBS.

Cost-Effectiveness of Prolonged Physical Activity on Prescription in Previously Non-Complying Patients: Impact of Physical Activity Mediators.

In Sweden, physical activity on prescription (PAP) is used to support patients in increasing their levels of physical activity (PA). The role of healthcare professionals in supporting PA behavior change requires optimization in terms of knowledge, quality and organization. This study aims to evaluate the cost-effectiveness of support from a physiotherapist (PT) compared to continued PAP at a healthcare center (HCC) for patients who remained insufficiently active after 6-month PAP treatment at the HCC. The PT strategy was constituted by a higher follow-up frequency as well as by aerobic physical fitness tests. The analysis was based on an RCT with a three-year time horizon, including 190 patients aged 27-77 with metabolic risk factors. The cost per QALY for the PT strategy compared to the HCC strategy was USD 16,771 with a societal perspective (including individual PA expenses, production loss and time cost for exercise, as well as healthcare resource use) and USD 33,450 with a healthcare perspective (including only costs related to healthcare resource use). Assuming a willingness-to-pay of USD 57,000 for a QALY, the probability of cost-effectiveness for the PT strategy was 0.5 for the societal perspective and 0.6 for the healthcare perspective. Subgroup analyses on cost-effectiveness based on individual characteristics regarding enjoyment, expectations and confidence indicated potential in identifying cost-effective strategies based on mediating factors. However, this needs to be further explored. In conclusion, both PT and HCC interventions are similar from a cost-effectiveness perspective, indicating that both strategies are equally valuable in healthcare's range of treatments.

Digitally distributed Yoga Intervention in Breast Cancer Rehabilitation (DigiYoga CaRe): protocol for a randomised controlled trial.

INTRODUCTION: Breast cancer is the most prevalent cancer among women. The treatment is extensive; in addition to surgery, various combinations of radiation therapy, chemotherapy and antibody and endocrine treatment can be applied. Cancer-related fatigue (CRF) is high in patients with breast cancer, peaking during chemotherapy, but may persist for several years. Physical activity has proven to be effective in reducing CRF in breast cancer rehabilitation, but many patients tend to be less active after the diagnosis. Yoga has a previously demonstrated effect on energy levels and digitally distributed yoga intervention can potentially increase accessibility in pandemic times and facilitate participation for patients susceptible to infection and those living far from organised rehabilitation opportunities. The purpose of this study, Digital Yoga Intervention in Cancer Rehabilitation (DigiYoga CaRe) is to investigate whether a 12-week digitally distributed yoga intervention can reduce CRF and stress, improve health-related quality of life (HRQL) and affect pro-inflammatory and metabolic markers in patients with breast cancer. METHODS AND ANALYSIS: This multicentre study will adopt a randomised controlled design including 240 persons after their breast cancer surgery. They will be randomised to a 12-week digitally distributed yoga intervention or to a control group. The intervention group practice yoga two times a week, one yoga class live-streamed to the patient's computer or mobile device and one prerecorded video class for self-training. The controls receive standardised care, gift cards for flowers and access to yoga video links after the data collection has ended. The primary analysis will be performed following the principle of intention to treat. Data will be collected by questionnaires, blood samples, accelerometers and interviews. ETHICS AND DISSEMINATION: The DigiYoga CaRe study was approved by the Regional Ethical Review Board in Lund. The final results of this study will be disseminated to conference, patient and public involvements and peer-reviewed publications. TRIAL REGISTRATION NUMBER: NCT04812652.

Viral Antigen and Inflammatory Biomarkers in Cerebrospinal Fluid in Patients With COVID-19 Infection and Neurologic Symptoms Compared With Control Participants Without Infection or Neurologic Symptoms.

Importance: Neurologic symptoms are common in COVID-19, but the central nervous system (CNS) pathogenesis is unclear, and viral RNA is rarely detected in cerebrospinal fluid (CSF). Objective: To measure viral antigen and inflammatory biomarkers in CSF in relation to neurologic symptoms and disease severity. Design, Setting, and Participants: This cross-sectional study was performed from March 1, 2020, to June 30, 2021, in patients 18 years or older who were admitted to Sahlgrenska University Hospital, Gothenburg, Sweden, with COVID-19. All patients had CSF samples taken because of neurologic symptoms or within a study protocol. Healthy volunteer and prepandemic control groups were included. Exposure: SARS-CoV-2 infection. Main Outcomes and Measures: Outcomes included CSF SARS-CoV-2 nucleocapsid antigen (N-Ag) using an ultrasensitive antigen capture immunoassay platform and CSF biomarkers of immune activation (neopterin, ß2-microglobulin, and cytokines) and neuronal injury (neurofilament light protein [NfL]). Results: Forty-four patients (median [IQR] age, 57 [48-69] years; 30 [68%] male; 26 with moderate COVID-19 and 18 with severe COVID-19 based on the World Health Organization Clinical Progression Scale), 10 healthy controls (median [IQR] age, 58 [54-60] years; 5 [50%] male), and 41 patient controls (COVID negative without evidence of CNS infection) (median [IQR] age, 59 [49-70] years; 19 [46%] male) were included in the study. Twenty-one patients were neuroasymptomatic and 23 were neurosymptomatic (21 with encephalopathy). In 31 of 35 patients for whom data were available (89%), CSF N-Ag was detected; viral RNA test results were negative in all. Nucleocapsid antigen was significantly correlated with CSF neopterin (r = 0.38; P = .03) and interferon γ (r = 0.42; P = .01). No differences in CSF N-Ag concentrations were found between patient groups. Patients had markedly increased CSF neopterin, ß2-microglobulin, interleukin (IL) 2, IL-6, IL-10, and tumor necrosis factor α compared with controls. Neurosymptomatic patients had significantly higher median (IQR) CSF interferon γ (86 [47-172] vs 21 [17-81] fg/mL; P = .03) and had a significantly higher inflammatory biomarker profile using principal component analysis compared with neuroasymptomatic patients (0.54; 95% CI, 0.03-1.05; P = .04). Age-adjusted median (IQR) CSF NfL concentrations were higher in patients compared with controls (960 [673-1307] vs 618 [489-786] ng/L; P = .002). No differences were seen in any CSF biomarkers in moderate compared with severe disease. Conclusions and Relevance: In this study of Swedish adults with COVID-19 infection and neurologic symptoms, compared with control participants, viral antigen was detectable in CSF and correlated with CNS immune activation. Patients with COVID-19 had signs of neuroaxonal injury, and neurosymptomatic patients had a more marked inflammatory profile that could not be attributed to differences in COVID-19 severity. These results highlight the clinical relevance of neurologic symptoms and suggest that viral components can contribute to CNS immune responses without direct viral invasion.

Long-term physical activity on prescription intervention for patients with insufficient physical activity level-a randomized controlled trial.

BACKGROUND: Physical activity (PA) can be used to prevent and treat diseases. In Sweden, licensed healthcare professionals use PA on prescription (PAP) to support patients to increase their PA level. The aim of this randomized controlled trial was to evaluate a 2-year intervention of two different strategies of PAP treatment for patients with insufficient PA level, after a previous 6-month period of ordinary PAP treatment in a primary health care setting. METHODS: We included 190 patients, 27-77 years, physically inactive with metabolic risk factors where the patients were not responding to a previous 6-month PAP treatment with increased PA. The patients were randomized to either enhanced support from a physiotherapist (PT group) or continued ordinary PAP treatment at the health care centre (HCC group). The PAP treatment included an individualized dialogue; an individually dosed PA recommendation, including a written prescription; and a structured follow-up. In addition to PAP, the PT group received aerobic fitness tests and more frequent scheduled follow-ups. The patient PA level, metabolic health, and health-related quality of life (HRQOL) were measured at baseline and at 1- and 2-year follow-ups. RESULTS: At the 2-year follow-up, 62.9% of the PT group and 50.8% of the HCC group had increased their PA level and 31.4% vs. 38.5% achieved ≥ 150 min of moderate-intensity PA/week (difference between groups n.s.). Over 2 years, both groups displayed increased high-density lipoproteins (HDL) (p = 0.004 vs. baseline), increased mental health status (MCS) (p = 0.036), and reduced body mass index (BMI) (p = 0.001), with no difference between groups. CONCLUSION: During long-term PAP interventions, the PA level, metabolic health, and HRQOL increased in patients at metabolic risk without significant differences between groups. The results indicate to be independent of any changes in pharmacological treatment. We demonstrated that the PAP treatment was feasible in ordinary primary care. Both the patients and the healthcare system benefitted from the improvement in metabolic risk factors. Future studies should elucidate effective long-term PAP-treatment strategies. TRIAL REGISTRATION: ClinicalTrials.gov NCT03012516 . Registered on 30 December 2016-retrospectively registered.

Factors associated with blood culture positivity in patients with complicated skin and skin structure infection-a population-based study.

Skin and skin structure infection (SSSI) is classified as complicated (cSSSI) if it involves deep subcutaneous tissue or requires surgery. Factors associated with blood culture sampling and bacteremia have not been established in patients with cSSSI. Moreover, the benefit of information acquired from positive blood culture is unknown. The aim of this study was to address these important issues. In this retrospective population-based study from two Nordic cities, a total of 460 patients with cSSSI were included. Blood cultures were drawn from 258 (56.1%) patients and they were positive in 61 (23.6%) of them. Factors found to be associated with more blood culture sampling in multivariate analysis were diabetes, duration of symptoms shorter than 2 days and higher C-reactive protein (CRP) level. Whereas factors associated with less frequent blood culture sampling were peripheral vascular disease and a surgical wound infection. In patients from whom blood cultures were taken, alcohol abuse was the only factor associated with culture positivity, as CRP level was not. Patients with a positive blood culture had antibiotic streamlining more often than non-bacteremic patients. A high rate of blood culture positivity in patients with cSSSI was observed. Factors related to more frequent blood culture sampling were different from those associated with a positive culture.

Uppsala Longitudinal Adolescent Depression Study (ULADS).

PURPOSE: To present the Uppsala Longitudinal Adolescent Depression Study, initiated in Uppsala, Sweden, in the early 1990s. The initial aim of this epidemiological investigation was to study the prevalence, characteristics and correlates of adolescent depression, and has subsequently expanded to include a broad range of social, economic and health-related long-term outcomes and cost-of-illness analyses. PARTICIPANTS: The source population was first-year students (aged 16-17) in upper-secondary schools in Uppsala during 1991-1992, of which 2300 (93%) were screened for depression. Adolescents with positive screening and sex/age-matched peers were invited to a comprehensive assessment. A total of 631 adolescents (78% females) completed this assessment, and 409 subsequently completed a 15-year follow-up assessment. At both occasions, extensive information was collected on mental disorders, personality and psychosocial situation. Detailed social, economic and health-related data from 1993 onwards have recently been obtained from the Swedish national registries for 576 of the original participants and an age-matched reference population (N≥200 000). FINDINGS TO DATE: The adolescent lifetime prevalence of a major depressive episode was estimated to be 11.4%. Recurrence in young adulthood was reported by the majority, with a particularly poor prognosis for those with a persistent depressive disorder or multiple somatic symptoms. Adolescent depression was also associated with an increased risk of other adversities in adulthood, including additional mental health conditions, low educational attainment and problems related to intimate relationships. FUTURE PLANS: Longitudinal studies of adolescent depression are rare and must be responsibly managed and utilised. We therefore intend to follow the cohort continuously by means of registries. Currently, the participants are approaching mid-adulthood. At this stage, we are focusing on the overall long-term burden of adolescent depression. For this purpose, the research group has incorporated expertise in health economics. We would also welcome extended collaboration with researchers managing similar datasets.

Osteomyelitis Risk in Patients With Transfemoral Amputations Treated With Osseointegration Prostheses.

BACKGROUND: Percutaneous anchoring of femoral amputation prostheses using osseointegrating titanium implants has been in use for more than 25 years. The method offers considerable advantages in daily life compared with conventional socket prostheses, however long-term success might be jeopardized by implant-associated infection, especially osteomyelitis, but the long-term risk of this complication is unknown. QUESTIONS/PURPOSES: (1) To quantify the risk of osteomyelitis, (2) to characterize the clinical effect of osteomyelitis (including risk of implant extraction and impairments to function), and (3) to determine whether common patient factors (age, sex, body weight, diabetes, and implant component replacements) are associated with osteomyelitis in patients with transfemoral amputations treated with osseointegrated titanium implants. METHODS: We retrospectively analyzed our first 96 patients receiving femoral implants (102 implants; mean implant time, 95 months) treated at our center between 1990 and 2010 for osteomyelitis. Six patients were lost to followup. The reason for amputation was tumor, trauma, or ischemia in 97 limbs and infection in five. All patients were referred from other orthopaedic centers owing to difficulty with use or to be fitted with socket prostheses. If found ineligible for this implant procedure no other treatment was offered at our center. Osteomyelitis was diagnosed by medical chart review of clinical signs, tissue culture results, and plain radiographic findings. Proportion of daily prosthetic use when osteomyelitis was diagnosed was semiquantitatively graded as 1 to 3. Survivorship free from implant- associated osteomyelitis and extraction attributable to osteomyelitis respectively was calculated using the Kaplan-Meier estimator. Indication for extraction was infection not responsive to conservative treatment with or without minor débridement or loosening of implant. RESULTS: Implant-associated osteomyelitis was diagnosed in 16 patients corresponding to a 10-year cumulative risk of 20% (95% CI 0.12-0.33). Ten implants were extracted owing to osteomyelitis, with a 10-year cumulative risk of 9% (95% CI 0.04-0.20). Prosthetic use was temporarily impaired in four of the six patients with infection who did not undergo implant extraction. With the numbers available, we did not identify any association between age, BMI, or diabetes with osteomyelitis; however, this study was underpowered on this endpoint. CONCLUSION: The increased risk of infection with time calls for numerous measures. First, patients should be made aware of the long-term risks, and the surgical team should have a heightened suspicion in patients with method-specific presentation of possible infection. Second, several research questions have been raised. Will the surgical procedure, rehabilitation, and general care standardization since the start of the program result in lower infection rates? Will improved diagnostics and early treatment resolve infection and prevent subsequent extraction? Although not supported in this study, it is important to know if most infections arise as continuous bacterial invasion from the skin and implant interface and if so, how this can be prevented? LEVEL OF EVIDENCE: Level IV, therapeutic study.

Motivation to uphold physical activity in women with breast cancer during adjuvant chemotherapy treatment.

PURPOSE: Physical activity (PA) is important for recovery after a breast cancer diagnosis; however, women's motivation to engage in PA can be impacted by disease and/or treatment, and can therefore be a challenge. This study explored factors associated with PA levels during chemotherapy among women with breast cancer. METHOD: The study had a cross-sectional descriptive and comparative design using a study-specific questionnaire. One hundred women with breast cancer receiving adjuvant chemotherapy were included. Data were analysed by Pearson's correlation coefficient and linear regression. The open question was subjected to manifest content analysis. RESULTS: Identified factors associated with engaging in PA during chemotherapy treatment were: being physically active before diagnosis, and the information given by the oncology nurse before the treatment start. The physically active women experienced higher psychological wellbeing, less fatigue, and faster recovery after treatment. They also experienced an overall feeling of fitness. CONCLUSION: It seems that PA is associated with less fatigue, better recovery between chemotherapy treatments, and a better mental condition leading to wellbeing. Information given by the oncology nurse may be an important factor for being physically active. Women with breast cancer need to get specific advice about and support in engaging in PA to feel better during chemotherapy treatment. Further research is required to develop guidelines for advice about and support regarding PA during chemotherapy treatment.

No support for premature central nervous system aging in HIV-1 when measured by cerebrospinal fluid phosphorylated tau (p-tau).

BACKGROUND: The prevalence of neurocognitive deficits are reported to be high in HIV-1 positive patients, even with suppressive antiretroviral treatment, and it has been suggested that HIV can cause accelerated aging of the brain. In this study we measured phosphorylated tau (p-tau) in cerebrospinal fluid (CSF) as a potential marker for premature central nervous system (CNS) aging. P-tau increases with normal aging but is not affected by HIV-associated neurocognitive disorders. METHODS: With a cross-sectional retrospective design, p-tau, total tau (t-tau), neopterin and HIV-RNA were measured in CSF together with plasma HIV-RNA and blood CD4+ T-cells of 225 HIV-infected patients <50 y of age, subdivided into 3 groups: untreated neuroasymptomatic (NA) (n = 145), on suppressive antiretroviral treatment (cART) (n = 49), and HIV-associated dementia (HAD) (n = 31). HIV-negative healthy subjects served as controls (n = 79). RESULTS: P-tau was not significantly higher in any HIV-infected group compared to HIV-negative controls. Significant increases in t-tau were found as expected in patients with HAD compared to NA, cART, and control groups (p < 0.001 ). CONCLUSIONS: P-tau was not higher in HIV-infected patients compared to uninfected controls, thus failing to support a role for premature or accelerated brain aging in HIV infection.

Cerebrospinal fluid markers of central nervous system injury in decompression illness - a case-controlled pilot study.

INTRODUCTION: Decompression sickness (DCS) may cause a wide variety of symptoms, including central nervous system (CNS) manifestations. The main objective of this study was to examine whether DCS is associated with neuronal injury, and whether DCS could result in altered amyloid metabolism. METHODS: Seven, male divers with DCS and seven age-matched controls were included in the study. All the divers were treated by recompression but the controls did not receive hyperbaric oxygen. Cerebrospinal fluid (CSF) samples were collected 7-10 days after the diving injury and at three months follow-up. CSF biomarkers of neuronal injury, astroglial Injury/activation, and a range of markers of amyloid ß (Aß) metabolism, as well as two proinflammatory interleukins, were analysed using immunochemical methods. RESULTS: There were no significant differences in the best-established CSF markers of neuronal injury, total tau (T-tau) and neurofilament light, between DCS patients and controls or between the two sampling time points. Also, there were no significant changes in the astroglial or amyloid (Aß)-related markers between DCS patients and controls. However, the only diver with CNS symptoms had the highest levels of CSF T-tau, Aß38, Aß40 and Aß42. CONCLUSION: The results of our study speak against subclinical CNS injury or induction of inflammation or amyloid build-up in the brain among the six DCS patients without neurological symptoms. Further research, including on divers with CNS DCS, is justified.

Cerebrospinal fluid (CSF) neuronal biomarkers across the spectrum of HIV infection: hierarchy of injury and detection.

The character of central nervous system (CNS) HIV infection and its effects on neuronal integrity vary with evolving systemic infection. Using a cross-sectional design and archived samples, we compared concentrations of cerebrospinal fluid (CSF) neuronal biomarkers in 143 samples from 8 HIV-infected subject groups representing a spectrum of untreated systemic HIV progression and viral suppression: primary infection; four groups of chronic HIV infection neuroasymptomatic (NA) subjects defined by blood CD4+ T cells of >350, 200-349, 50-199, and <50 cells/µL; HAD; treatment-induced viral suppression; and 'elite' controllers. Samples from 20 HIV-uninfected controls were also examined. The neuronal biomarkers included neurofilament light chain protein (NFL), total and phosphorylated tau (t-tau, p-tau), soluble amyloid precursor proteins alpha and beta (sAPPα, sAPPß) and amyloid beta (Aß) fragments 1-42, 1-40 and 1-38. Comparison of the biomarker changes showed a hierarchy of sensitivity in detection and suggested evolving mechanisms with progressive injury. NFL was the most sensitive neuronal biomarker. Its CSF concentration exceeded age-adjusted norms in all HAD patients, 75% of NA CD4<50, 40% of NA CD4 50-199, and 42% of primary infection, indicating common neuronal injury with untreated systemic HIV disease progression as well as transiently during early infection. By contrast, only 75% of HAD subjects had abnormal CSF t-tau levels, and there were no significant differences in t-tau levels among the remaining groups. sAPPα and ß were also abnormal (decreased) in HAD, showed less marked change than NFL with CD4 decline in the absence of HAD, and were not decreased in PHI. The CSF Aß peptides and p-tau concentrations did not differ among the groups, distinguishing the HIV CNS injury profile from Alzheimer's disease. These CSF biomarkers can serve as useful tools in selected research and clinical settings for patient classification, pathogenetic analysis, diagnosis and management.

PXL01 in sodium hyaluronate for improvement of hand recovery after flexor tendon repair surgery: randomized controlled trial.

BACKGROUND: Postoperative adhesions constitute a substantial clinical problem in hand surgery. Fexor tendon injury and repair result in adhesion formation around the tendon, which restricts the gliding function of the tendon, leading to decreased digit mobility and impaired hand recovery. This study evaluated the efficacy and safety of the peptide PXL01 in preventing adhesions, and correspondingly improving hand function, in flexor tendon repair surgery. METHODS: This prospective, randomised, double-blind trial included 138 patients admitted for flexor tendon repair surgery. PXL01 in carrier sodium hyaluronate or placebo was administered around the repaired tendon. Efficacy was assessed by total active motion of the injured finger, tip-to-crease distance, sensory function, tenolysis rate and grip strength, and safety parameters were followed, for 12 months post-surgery. RESULTS: The most pronounced difference between the treatment groups was observed at 6 months post-surgery. At this timepoint, the total active motion of the distal finger joint was improved in the PXL01 group (60 vs. 41 degrees for PXL01 vs. placebo group, p = 0.016 in PPAS). The proportion of patients with excellent/good digit mobility was higher in the PXL01 group (61% vs. 38%, p = 0.0499 in PPAS). Consistently, the PXL01 group presented improved tip-to-crease distance (5.0 vs. 15.5 mm for PXL01 vs. placebo group, p = 0.048 in PPAS). Sensory evaluation showed that more patients in the PXL01 group felt the thinnest monofilaments (FAS: 74% vs. 35%, p = 0.021; PPAS: 76% vs. 35%, p = 0.016). At 12 months post-surgery, more patients in the placebo group were considered to benefit from tenolysis (30% vs. 12%, p = 0.086 in PPAS). The treatment was safe, well tolerated, and did not increase the rate of tendon rupture. CONCLUSIONS: Treatment with PXL01 in sodium hyaluronate improves hand recovery after flexor tendon repair surgery. Further clinical trials are warranted to determine the most efficient dose and health economic benefits. TRIAL REGISTRATION: ClinicalTrials.gov NCT01022242; EU Clinical Trials 2009-012703-25.

Neurochemical evidence of potential neurotoxicity after prophylactic cranial irradiation.

PURPOSE: To examine whether cerebrospinal fluid biomarkers for neuroaxonal damage, neuroglial activation, and amyloid ß-related processes could characterize the neurochemical response to cranial radiation. METHODS AND MATERIALS: Before prophylactic cranial irradiation (PCI) of patients with small cell lung cancer, each patient underwent magnetic resonance imaging of the brain, lumbar puncture, and Mini-Mental State Examination of cognitive function. These examinations were repeated at approximately 3 and 12 months after radiation. RESULTS: The major findings were as follows. (1) Cerebrospinal fluid markers for neuronal and neuroglial injury were elevated during the subacute phase after PCI. Neurofilament and T-tau increased 120% and 50%, respectively, after PCI (P<.05). The same was seen for the neuroglial markers YKL-40 and glial fibrillary acidic protein, which increased 144% and 106%, respectively, after PCI (P<.05). (2) The levels of secreted amyloid precursor protein-α and -ß were reduced 44% and 46%, respectively, 3 months after PCI, and the levels continued to decrease as long as 1 year after treatment (P<.05). (3) Mini-Mental State Examination did not reveal any cognitive decline, indicating that a more sensitive test should be used in future studies. CONCLUSION: In conclusion, we were able to detect radiation therapy-induced changes in several markers reflecting neuronal injury, inflammatory/astroglial activation, and altered amyloid precursor protein/amyloid ß metabolism, despite the low number of patients and quite moderate radiation doses (20-30 Gy). These changes are hypothesis generating and could potentially be used to assess the individual risk of developing long-term symptoms of chronic encephalopathy after PCI. This has to be evaluated in large studies with extended clinical follow-up and more detailed neurocognitive assessments.

Distinct inflammatory mediator patterns characterize infectious and sterile systemic inflammation in febrile neutropenic hematology patients.

BACKGROUND: Invasive infections and sterile tissue damage can both give rise to systemic inflammation with fever and production of inflammatory mediators. This makes it difficult to diagnose infections in patients who are already inflamed, e.g. due to cell and tissue damage. For example, fever in patients with hematological malignancies may depend on infection, lysis of malignant cells, and/or chemotherapy-induced mucosal damage. We hypothesized that it would be possible to distinguish patterns of inflammatory mediators characterizing infectious and non-infectious causes of inflammation, respectively. Analysis of a broad range of parameters using a multivariate method of pattern recognition was done for this purpose. METHODS: In this prospective study, febrile (>38°C) neutropenic patients (n = 42) with hematologic malignancies were classified as having or not having a microbiologically defined infection by an infectious disease specialist. In parallel, blood was analyzed for 116 biomarkers, and 23 clinical variables were recorded for each patient. Using O-PLS (orthogonal projection to latent structures), a model was constructed based on these 139 variables that could separate the infected from the non-infected patients. Non-discriminatory variables were discarded until a final model was reached. Finally, the capacity of this model to accurately classify a validation set of febrile neutropenic patients (n = 10) as infected or non-infected was tested. RESULTS: A model that could segregate infected from non-infected patients was achieved based on discrete differences in the levels of 40 variables. These variables included acute phase proteins, cytokines, measures of coagulation, metabolism, organ stress and iron turn-over. The model correctly identified the infectious status of nine out of ten subsequently recruited febrile neutropenic hematology patients. CONCLUSIONS: It is possible to separate patients with infectious inflammation from those with sterile inflammation based on inflammatory mediator patterns. This strategy could be developed into a decision-making tool for diverse clinical applications.

Intermittent versus indwelling urinary catheterisation in hip surgery patients: a randomised controlled trial with cost-effectiveness analysis.

BACKGROUND: Hip surgery is associated with the risk of postoperative urinary retention. To avoid urinary retention hip surgery patients undergo urinary catheterisation. Urinary catheterisation, however, is associated with increased risk for urinary tract infection (UTI). At present, there is limited evidence for whether intermittent or indwelling urinary catheterisation is the preferred choice for short-term bladder drainage in patients undergoing hip surgery. OBJECTIVES: The aim of the study was to investigate differences between intermittent and indwelling urinary catheterisation in hip surgery patients in relation to nosocomial UTI and cost-effectiveness. DESIGN: Randomised controlled trial with cost-effectiveness analysis. SETTING: The study was carried out at an orthopaedic department at a Swedish University Hospital. METHODS: One hundred and seventy hip surgery patients (patients with fractures or with osteoarthritis) were randomly allocated to either intermittent or indwelling urinary catheterisation. Data collection took place at four time points: during stay in hospital, at discharge and at 4 weeks and 4 months after discharge. RESULTS: Eighteen patients contracted nosocomial UTIs, 8 in the intermittent catheterisation group and 10 in the indwelling catheterisation group (absolute difference 2.4%, 95% CI -6.9-11.6%) The patients in the intermittent catheterisation group were more often catheterised (p<0.001) and required more bladder scans (p<0.001) but regained normal bladder function sooner than the patients in the indwelling catheterisation group (p<0.001). Fourteen percent of the patients in the intermittent group did not need any catheterisation. Cost-effectiveness was similar between the indwelling and intermittent urinary catheterisation methods. CONCLUSIONS: Both indwelling and intermittent methods could be appropriate in clinical practice. Both methods have advantages and disadvantages but by not using routine indwelling catheterisation, unnecessary catheterisations might be avoided in this patient group.

Quality of life and cost-effectiveness of a 3-year trial of lifestyle intervention in primary health care.

BACKGROUND: Lifestyle interventions reduce cardiovascular risk and risk of diabetes mellitus, but reports on long-term effects on quality of life (QOL) and health care utilization are rare. We investigated the impact of a primary health care-based lifestyle intervention program on QOL and cost-effectiveness over 3 years. METHODS: A total of 151 men and women, aged 18 to 65 years, at moderate to high risk for cardiovascular disease, were randomly assigned to either lifestyle intervention with standard care or standard care alone. Intervention consisted of supervised exercise sessions and diet counseling for 3 months, followed by regular group meetings over a 3-year period. Change in QOL was measured with EuroQol (5-dimensional EuroQol-5D [EQ-5D] and EuroQol-VAS [EQ-VAS]), the 36-Item Short-Form Health Survey (SF-36), and the 6-dimensional Short-Form 6D (SF-6D). The health economic evaluation was performed from a societal view and a treatment perspective. In a cost-utility analysis, the costs, gained quality-adjusted life-years (QALYs), and savings in health care were considered. Cost-effectiveness was also described using the net monetary benefit method. RESULTS: Significant differences between the groups over the 3-year period were shown in the EQ-VAS (P = .002), SF-6D (P = .01), and SF-36 (P = .04) physical component summary but not in the EQ-5D (P = .24) or SF-36 (P = .37) mental component summary. The net savings were $47 per participant. Costs per gained QALY, savings not counted, were $1668 to $4813. Probabilities of cost-effectiveness were 89% to 100% when the amount of $50,000 was used as stakeholder's threshold of willingness to pay for a gained QALY. CONCLUSION: Lifestyle intervention in primary care improves QOL and is highly cost-effective in relation to standard care. Trial Registration clinicaltrials.gov Identifier: NCT00486941.

Osseointegrated titanium implants for limb prostheses attachments: infectious complications.

BACKGROUND: The concept of osseointegration involves direct contact between titanium implant and bone. This transcutaneous prosthetic system for amputees is intended to assure stable long-term fixation. Most metal transcutaneous implants have failed, primarily owing to infection. QUESTIONS/PURPOSES: We determined the frequency and describe the presentation of infectious complications with this novel method. We also evaluated the bacterial flora at the skin-penetration area and its relation to the development of local and implant-related infection. PATIENTS AND METHODS: We prospectively followed 39 patients with arm and leg amputations fitted with transcutaneous osseointegrated titanium implants a mean of 56 months earlier (range, 132-133 months). There were 33 femoral, one tibial, four ulnar, four radial, and three humeral implants. Patients were selected during a 6-month period in 2005 and identically reevaluated after 3 years. Implant infection was defined as definite, probable, or possible based on clinical, radiologic, and microbiologic evidence. RESULTS: The frequency of implant infection was 5% at inclusion and 18% at followup. One patient with infection recovered owing to antibiotic treatment and another patient had the implant removed. Most implant infections had low infectious activity, and in five of the seven patients with infections, prosthetic use was not affected. The most common bacteria in superficial and deep cultures were Staphylococcus aureus and coagulase-negative staphylococci. CONCLUSIONS: Despite frequent colonization around the skin-implant interface by potentially virulent bacteria such as Staphylococcus aureus and bacteria associated with biomedical device infections such as coagulase-negative staphylococci, this titanium implant system for bone-anchored prostheses caused few infections leading to disability or implant removal. LEVEL OF EVIDENCE: Level IV, therapeutic study. See the Guidelines for Authors for a complete description of levels of evidence.

Mode of coreceptor use by R5 HIV type 1 correlates with disease stage: a study of paired plasma and cerebrospinal fluid isolates.

Through the use of chimeric CXCR4/CCR5 receptors we have previously shown that CCR5-tropic (R5) HIV-1 isolates acquire a more flexible receptor use over time, and that this links to a reduced viral susceptibility to inhibition by the CCR5 ligand RANTES. These findings may have relevance with regards to the efficacy of antiretroviral compounds that target CCR5/virus interactions. Compartmentalized discrepancies in coreceptor use may occur, which could also affect the efficacy of these compounds at specific anatomical sites, such as within the CNS. In this cross-sectional study we have used wild-type CCR5 and CXCR4 as well as chimeric CXCR4/CCR5 receptors to characterize coreceptor use by paired plasma and cerebrospinal fluid (CSF) isolates from 28 HIV-1-infected individuals. Furthermore, selected R5 isolates, with varying chimeric receptor use, were tested for sensitivity to inhibition by the CCR5 antagonist TAK-779. Discordant CSF/plasma virus coreceptor use was found in 10/28 patients. Low CD4+ T cell counts correlated strongly with a more flexible mode of R5 virus CCR5 usage, as disclosed by an increased ability to utilize chimeric CXCR4/CCR5 receptors, specifically receptor FC-2. Importantly, an elevated ability to utilize chimeric receptors correlated with a reduced susceptibility to inhibition by TAK-779. Our findings show that a discordant CSF and plasma virus coreceptor use is not uncommon. Furthermore, we provide support for an emerging paradigm, where the acquisition of a more flexible mode of CCR5 usage is a key event in R5 virus pathogenesis. This may, in turn, negatively impact the efficacy of CCR5 antagonist treatment in late stage HIV-1 disease.

CSF neurofilament protein (NFL) -- a marker of active HIV-related neurodegeneration.

BACKGROUND AND METHODS: The light subunit of the neurofilament protein (NFL), a major structural component of myelinated axons, is a sensitive indicator of axonal injury in the central nervous system (CNS) in a variety of neurodegenerative disorders. Cerebrospinal fluid (CSF) NFL concentrations were measured by ELISA (normal < 250 ng/l) in archived samples from 210 HIV-infected patients not taking antiretroviral treatment: 55 with AIDS dementia complex (ADC), 44 with various CNS opportunistic infections/tumours (CNS OIs), 95 without neurological symptoms or signs, and 16 with primary HIV infection (PHI). The effect of highly active antiretroviral treatment (HAART) was studied by repeated CSF sampling in four of the ADC patients initiating treatment. RESULTS: CSF NFL concentrations were significantly higher in patients with ADC (median 2590 ng/l, IQR 780-7360) and CNS OIs (2315 ng/l, 985-7390 ng/l) than in neuroasymptomatic patients (<250 ng/l, <250-300) or PHI (<250 ng/l, <250-280), p < 0.001. Among patients with ADC, those with more severe disease (stage 2-4) had higher levels than those with milder disease (stage 0.5-1), p < 0.01. CSF NFL declined during HAART to the limit of detection in parallel with virological response and neurological improvement in ADC.CSF NFL concentrations were higher in neuroasymptomatic patients with lower CD4-cell strata than higher, p < 0.001. This increase was less marked than in the ADC patients and noted in 26/58 neuroasymptomatic patients with CD4 counts <200/microl compared to 1/37 with CD4-cells > or =200/microl. CONCLUSIONS: The findings of this study support the value of CSF NFL as a useful marker of ongoing CNS damage in HIV infection. Markedly elevated CSF NFL concentrations in patients without CNS OIs are associated with ADC, follow the grade of severity, and decrease after initiation of effective antiretroviral treatment. Nearly all previously suggested CSF markers of ADC relate to immune activation or HIV viral load that do not directly indicate brain injury. By contrast NFL is a sensitive marker of such injury, and should prove useful in evaluating the presence and activity of ongoing CNS injury in HIV infection.