One-year outcome of manualised behavior therapy of chronic tic disorders in children and adolescents.

BACKGROUND: Chronic tic disorders are neurodevelopmental disorders that can be treated with Habit Reversal Training (HRT) and Exposure Response Prevention (ERP). Intermediate and long-term effects have been examined after individual treatment with HRT, whereas evaluation of long-term outcome after an initial treatment with ERP, or a combination of HRT and ERP is lacking. The present study examines the long-term effect after a combined treatment with HRT and ERP delivered in an individual or a group setting METHODS: Fifty-nine children and adolescents diagnosed with a chronic tic disorder were randomised to manualised treatment combining HRT and ERP as individual or group training. Forty-seven were re-examined 1 year after acute outcome. Outcome measures included Total Tic Severity score (TTS) measured by the Yale Global Tic Severity Scale (YGTSS) and Beliefs About Tics Scale (BATS) RESULTS: In a mixed model, it was shown that the initial improvement with both individual and group treatment was maintained throughout the follow-up period. There were no significant differences between the two methods of treatment delivery. Of all participants completing the 12 months evaluation, 74.4% were considered responders. There was a significant positive association between the reduction of TTS and the reduction in BATS. In a latent class post-treatment trajectory analysis, two classes were identified, where high baseline severity increased the likelihood of being in the lesser responder class. Similar, but only as a trend, having ADHD, planning difficulties or hypersensitivity increased the risk of a lesser response. CONCLUSIONS: The present study compares the efficacy in individualised and group treatment of providing manualised therapy for child and adolescent tic disorders using two behavioural methods (combined HRT and ERP) both of which have been shown to have acute benefits but only one of which has been validated for longer term effectiveness. In the present study, both individualised and group treatments showed benefit throughout a 1-year follow-up period with several potential confounds affecting outcomes, while the relative benefits of either HRT and ERP were not addressed. Trial registration NCT04594044, 1-10-72-216-15, registered 19th October 2020, retrospectively registered, https://register.clinicaltrials.gov/prs/app/template/Home.vm?uid=U0005BW2&ts=9&sid=S000ABEY&cx=-wlx7vb The study is approved by the National Ethical Committee (1-10-72-216-15) and the Danish Data Protection Agency (1-16-02-490-15), registered 12 October 2015.

Safety, efficiency and health-related quality of telephone triage conducted by general practitioners, nurses, or physicians in out-of-hours primary care: a quasi-experimental study using the Assessment of Quality in Telephone Triage (AQTT) to assess audio-recorded telephone calls.

BACKGROUND: To explore and compare safety, efficiency, and health-related quality of telephone triage in out-of-hours primary care (OOH-PC) services performed by general practitioners (GPs), nurses using a computerised decision support system (CDSS), or physicians with different medical specialities. METHODS: Natural quasi-experimental cross-sectional study conducted in November and December 2016. We randomly selected 1294 audio-recorded telephone triage calls from two Danish OOH-PC services triaged by GPs (n = 423), nurses using CDSS (n = 430), or physicians with different medical specialities (n = 441). An assessment panel of 24 physicians used a validated assessment tool (Assessment of Quality in Telephone Triage - AQTT) to assess all telephone triage calls and measured health-related quality, safety, and efficiency of triage. RESULTS: The relative risk (RR) of poor quality was significantly lower for nurses compared to GPs in four out of ten items regarding identifying and uncovering of problems. For most items, the quality tended to be lowest for physicians with different medical specialities. Compared to calls triaged by GPs (reference), the risk of clinically relevant undertriage was significantly lower for nurses, while physicians with different medical specialties had a similar risk (GP: 7.3%, nurse: 3.7%, physician: 6.1%). The risk of clinically relevant overtriage was significantly higher for nurses (9.1%) and physicians with different medical specialities (8.2%) compared to GPs (4.3%). GPs had significantly shorter calls (mean: 2 min 57 s, SD: 105 s) than nurses (mean: 4 min 44 s, SD: 168 s). CONCLUSIONS: Our explorative study indicated that nurses using CDSS performed better than GPs in telephone triage on a large number of health-related items, had a lower level of clinically relevant undertriage, but were perceived less efficient. Calls triaged by physicians with different medical specialities were perceived less safe and less efficient compared to GPs. Differences in the organisation of telephone triage may influence the distribution of workload in primary and secondary OOH services. Future research could compare the long-term outcomes following a telephone call to OOH-PC related to safety and efficiency.

Quality of out-of-hours telephone triage by general practitioners and nurses: development and testing of the AQTT - an assessment tool measuring communication, patient safety and efficiency.

OBJECTIVE: To develop a valid and reliable assessment tool able to measure quality of communication, patient safety and efficiency in out-of-hours (OOH) telephone triage conducted by both general practitioners (GP) and nurses. DESIGN: The Dutch KERNset tool was translated into Danish and supplemented with items from other existing tools. Face validity, content validity and applicability in OOH telephone triage (OOH-TT) were secured through a two-round Delphi process involving relevant stakeholders. Forty-eight OOH patient contacts were assessed by 24 assessors in test-retest and inter-rater designs. SETTING: OOH-TT services in Denmark conducted by GPs, nurses or doctors with varying medical specialisation. PATIENTS: Audio-recorded OOH patient contacts. MAIN OUTCOME MEASURES: Test-retest and inter-rater reliability were analysed using ICCagreement, Fleiss' kappa and percent agreement. RESULTS: Major adaptations during the Delphi process were made. The 24-item assessment tool (Assessment of Quality in Telephone Triage - AQTT) measured communicative quality, health-related quality and four overall quality aspects. The test-retest ICCagreement reliability was good for the overall quality of communication (0.85), health-related quality (0.83), patient safety (0.81) and efficiency (0.77) and satisfactory when assessing specific aspects. Inter-rater reliability revealed reduced reliability in ICCagreement and in Fleiss' kappa. Percent agreement revealed satisfactory agreements when differentiating between 'poor' and 'sufficient' quality). CONCLUSION: The AQTT demonstrated high face, content and construct validity, satisfactory test-retest reliability, reduced inter-rater reliability, but satisfactory percent agreement when differentiating between 'poor' and 'sufficient' quality. The AQTT was found feasible and clinically relevant for assessing the quality of GP- and nurse-led OOH-TT. KEYPOINTS Comparative knowledge is sparse regarding quality of out-of-hours telephone triage conducted by general practitioners and nurses. The assessment tool (AQTT) enables assessment of quality in OOH telephone triage conducted by nurses and general practitioners AQTT is feasible and clinically relevant for assessment of communication, patient safety and efficiency. AQTT can be used to identify areas for improvement in telephone triage.

Associations of circulating cell-free microRNA with vasculopathy and vascular events in systemic lupus erythematosus patients.

OBJECTIVE: Systemic lupus erythematosus (SLE) is a chronic autoimmune disease with a high risk of atherosclerosis and cardiovascular disease (CVD). MicroRNAs (miRNAs) are small non-coding RNAs that modulate protein translation, and dysregulation is seen in autoimmunity, atherosclerosis, and CVD. We investigate associations between circulating miRNAs and markers of atherosclerosis in SLE patients. METHOD: A group (n = 121) of well-characterized SLE patients were screened for atherosclerosis by cardiac computed tomography and carotid ultrasound. RNA was purified from plasma and 46 specific miRNAs were determined using quantitative real-time polymerase chain reaction. RESULTS: Forty-one miRNAs were consistently detected. Fifty out of 118 available SLE patients had atherosclerosis. A profile consisting of three miRNAs (decreased miR-125b, miR-101, miR-375) was indicative of atherosclerosis. Multivariate logistic regression identified eight clinical manifestations associated with atherosclerotic outcome. The full classification profile showed a specificity of 88% and a sensitivity of 86%. Hierarchical clustering identified an eight-miRNA profile that differentiated a subgroup of SLE patients (n = 16) who had significantly increased venous thrombotic events (p = 0.045), a higher prevalence of ß2-glycoprotein I antibodies (p = 0.029), and an increased prevalence of thrombocytopenia (p = 0.028). CONCLUSION: In this cross-sectional study, the circulating miRNA profile distinguished SLE patients with atherosclerosis from those without. Furthermore, an eight-miRNA signature was associated with thrombocytopenia, venous thrombotic events, and ß2-glycoprotein I antibodies in SLE patients. Prospective studies are needed to confirm the findings and to establish the precise role of circulating miRNA profiling in the evaluation of atherosclerosis in SLE.

Future directions for monitoring and human health research for the Arctic Monitoring and Assessment Programme.

For the last two and a half decades, a network of human health experts under the Arctic Monitoring and Assessment Program (AMAP) has produced several human health assessment reports. These reports have provided a base of scientific knowledge regarding environmental contaminants and their impact on human health in the Arctic. These reports provide scientific information and policy-relevant recommendations to Arctic governments. They also support international agreements such as the Stockholm Convention on Persistent Organic Pollutants (POPs) and the Minamata Convention on Mercury. Key topics discussed in this paper regarding future human health research in the circumpolar Arctic are continued contaminant biomonitoring, health effects research and risk communication. The objective of this paper is to describe knowledge gaps and future priorities for these fields.

Circulating microRNA expression pattern separates patients with anti-neutrophil cytoplasmic antibody associated vasculitis from healthy controls.

OBJECTIVES: Antineutrophil cytoplasmic antibody associated vasculitis (AAV) has an unpredictable course and better biomarkers are needed. Micro-RNAs in body fluids are protected from degradation and might be used as biomarkers for diagnosis and prognosis, here we explore the potential in AAV. METHODS: Plasma samples from two AAV cohorts (n=67 and 38) were compared with samples from healthy controls (n=27 and 45) and disease controls (n=20). A panel of 32 miRNAs was measured using a microfluidic quantitative real-time PCR system, and results were compared with clinical data. RESULTS: Seven individual miRNAs were differently expressed compared to controls in both cohorts; miR-29a, -34a, -142-3p and -383 were up-regulated and miR-20a, -92a and -221 were down-regulated. Cluster analysis as well as principal component analysis (PCA) indicated that patterns of miRNA expression differentiate AAV patients from healthy subjects as well as from renal transplant recipients. Loadings plots indicated similar contribution of the same miRNAs in both cohorts to the PCA. Renal engagement was important for miRNA expression but consistent correlations between estimated glomerular filtration rate and miRNA levels were not found. We found no significant correlation between treatment regimens and circulating miRNA levels. CONCLUSIONS: In this first study ever on circulating miRNA profiles in AAV, we find clear indication of their potential as biomarkers for diagnosis and classification, but more studies are needed to identify the best markers as well as the mechanisms responsible for variations.

Changes in circulating microRNA-126 during treatment with chemotherapy and bevacizumab predicts treatment response in patients with metastatic colorectal cancer.

BACKGROUND: This study investigated the predictive value of circulating microRNA-126 (cir-miRNA-126) in patients with metastatic colorectal cancer (mCRC) treated with first-line chemotherapy combined with bevacizumab. METHODS: The study included 68 patients. Blood samples (plasma) were collected before the treatment initiation, at the first clinical evaluation after 3 weeks and at progression. Levels of cir-miRNA-126 were determined by qRT-PCR after purification of total RNA from plasma. Primary clinical end points were response rates evaluated according to the Response Evaluation Criteria In Solid Tumours (RECIST) and progression-free survival (PFS). RESULTS: Changes in circulating miRNA-126 during treatment were predictive of tumour response. Non-responding patients had a median increase in cir-miRNA-126 of 0.244 (95% confidence interval (CI), 0.050-0.565) compared with a median decrease of -0.374 (95% CI, -0.472 to -0.111) in the responding patients, P=0.002. A significant positive correlation was demonstrated by comparing the changes in tumour size with the changes in cir-miRNA-126, r=0.48, P=0.0001. Grouping the patients according to the changes in cir-miRNA-126 disclosed a borderline significant separation of the groups in the PFS analysis favouring patients with decreasing miRNA-126 levels, hazard ratio (HR) 0.60 (95% CI, 0.33-1.09), P=0.07. CONCLUSIONS: The present results indicate that changes in cir-miRNA-126 during treatment are related to the response to chemotherapy and bevacizumab in patients with mCRC, thus representing a possible biomarker for the resistance to anti-angiogenic containing treatments.

Variation in prescribing of lipid-lowering medication in primary care is associated with incidence of cardiovascular disease and all-cause mortality in people with screen-detected diabetes: findings from the ADDITION-Denmark trial.

AIMS: To examine variation between general practices in the prescription of lipid-lowering treatment to people with screen-detected Type 2 diabetes, and associations with practice and participant characteristics and risk of cardiovascular events and all-cause mortality. METHODS: Observational cohort analysis of data from 1533 people with screen-detected Type 2 diabetes aged 40-69 years from the ADDITION-Denmark study. One hundred and seventy-four general practices were cluster randomized to receive: (1) routine diabetes care according to national guidelines (623 individuals), or (2) intensive multifactorial target-driven management (910 individuals). Multivariable logistic regression was used to quantify the association between the proportion of individuals in each practice who redeemed prescriptions for lipid-lowering medication in the two years following diabetes diagnosis and a composite cardiovascular disease (CVD) outcome, adjusting for age, sex, prevalent chronic disease, baseline CVD risk factors, smoking and lipid-lowering medication, and follow-up time. RESULTS: The proportion of individuals treated with lipid-lowering medication varied widely between practices (0-100%). There were 118 CVD events over 9431 person-years of follow-up. For the whole trial cohort, the risk of CVD was significantly higher in practices in the lowest compared with the highest quartile for prescribing lipid-lowering medication [adjusted odds ratio (OR) 3.4, 95% confidence interval (CI) 1.6-7.3]. Similar trends were found for all-cause mortality. CONCLUSIONS: More frequent prescription of lipid-lowering treatment was associated with a lower incidence of CVD and all-cause mortality. Improved understanding of factors underlying practice variation in prescribing may enable more frequent use of lipid-lowering treatment. The results highlight the benefits of intensive treatment of people with screen-detected diabetes (Clinical Trials Registry No; NCT 00237549).

Effect of a participant-driven health education programme in primary care for people with hyperglycaemia detected by screening: 3-year results from the Ready to Act randomized controlled trial (nested within the ADDITION-Denmark study).

AIM: To assess whether a 12-week participant-driven health education programme offered to individuals with screening-detected hyperglycaemia in Danish primary care would lead to improvements in cardiovascular risk factors, health behaviour and patient-reported outcomes after 3 years. METHODS: We conducted a randomized controlled trial in 509 patients with screening-detected hyperglycaemia (impaired fasting glucose, impaired glucose tolerance or type 2 diabetes) from 33 general practices in Denmark. Individuals were pre-randomized to receive (i) routine care (n = 187), or (ii) an invitation to participate in the Ready to Act health education programme (n = 322). The programme was delivered over 12 weeks in primary care and focused on motivation, action experience, informed decision-making and social involvement to promote health behaviour change. The primary outcome was 10-year modelled cardiovascular risk. RESULTS: Of 322 individuals, 123 (38%) received the intervention and 436/509 individuals (86%) returned for follow-up assessment. There was no difference between the trial groups in modelled cardiovascular risk at 3 years (relative difference: 1.01; 95% CI: 0.84 to 1.23). Total cholesterol was lower (-0.24mmol/l, 95% CI: -0.45 to -0.03, P = 0.027), and patient activation was higher in the intervention than in the control group (5.3, 95% CI: 0.97 to 9.7). No other between-group differences were observed for any cardiovascular risk factor, health behaviour or patient-reported outcome variables. Subgroup analyses suggested that the intervention was more beneficial in those with impaired fasting glucose/impaired glucose tolerance than in those with type 2 diabetes. CONCLUSION: For patients with screening-detected hyperglycaemia, a participant-driven health education programme was not associated with improvements in most clinical, behavioural and patient-reported outcomes after 3 years of follow-up.

Textural Properties of Beta-lactoglobulin - Sodium Alginate Mixed Gels at Large Scale Deformation.

The denaturation and gelling properties of mixed systems of ß-lactoglobulin and sodium-alginate have been investigated as a function of alginate molecular weight, chemical composition, concentration, pH and ionic strength. Differential scanning calorimetry and small strain oscillatory measurements showed that denaturation temperature were lower than the gelling temperatures under the conditions examined. The denaturation temperatures were dependent on both pH and ionic strength, but unaffected by alginate concentration and type. The mechanical and textural properties of mixed gels of ß-lactoglobulin and sodium alginate were dependent on several factors; the gel strength increased as a function of alginate concentration under ambient conditions, and decreased as the pH and/or the ionic strength were changed. High molecular weight alginate gave the most pronounced effects, probably due to the accessibility of the alginate for protein binding. The chemical composition of the alginate had negligible effect on the mechanical properties of the gels. PRACTICAL APPLICATIONS: As both proteins and polysaccharides are widely used in the food industry, it is important to understand the interactions between these two biopolymers in order to envisage final product properties. The present article gives an overview of several important parameters when mixing ß-lactoglobulin and sodium alginate. ß-Lactoglobulin is the main protein in whey and one of the major food protein ingredients. Alginate is a polysaccharide that is often used in the food industry because of its functional properties. This study shows that if the conditions and the alginate type are adequately chosen, the textural properties of food products can be controlled and tailored.

Photonic crystal fiber based evanescent-wave sensor for detection of biomolecules in aqueous solutions.

We demonstrate highly efficient evanescent-wave detection of fluorophore-labeled biomolecules in aqueous solutions positioned in the air holes of the microstructured part of a photonic crystal fiber. The air-suspended silica structures located between three neighboring air holes in the cladding crystal guide light with a large fraction of the optical field penetrating into the sample even at wavelengths in the visible range. An effective interaction length of several centimeters is obtained when a sample volume of less than 1 microL is used.

When is an anesthesiologist needed in a helicopter emergency medical service in northern Norway?

BACKGROUND: A national air ambulance service, including helicopters and airplanes, was implemented in Norway in 1988. The main intention was to offer advanced medical services when needed. All helicopters are manned by anesthesiologists. Catchment areas for the 11 helicopters span from cities to scarcely populated areas, particularly in the north. Our aim was to assess what proportion of ambulance missions carried out by the rescue helicopter in Bodø, northern Norway, delivered advanced medical treatment needing the skills of an anesthesiologist. METHODS: Flight and ambulance records (n = 2078) from 1988 and 1990-98 (10 years) were analyzed retrospectively. Inter-hospital transfers (n = 147) and search- and rescue missions (n = 332) were not included. According to the level of medical treatment given missions were categorized into three groups (A, B and C). Treatment in groups A and B would not require an anesthesiologist. RESULTS: Two thousand and seventy-eight ambulance missions carried 2166 patients (114 per 100 000 per year). Median take-off and on-scene times were 29 and 55 min, respectively. Seven hundred and fifty-five patients (35%) suffered from cardiovascular disease, 495 (23%) were injured and 250 (12%) were parturients. One hundred and seven patients (5.0%) received advanced prehospital emergency treatment requiring an anesthesiologist. Forty-five of the 107 patients survived to discharge from hospital, amongst whom 28 had received intravenous nitroglycerin for angina or suspected myocardial infarction. CONCLUSION: In our rural area, with a widely scattered population, 95% of patients received medical treatment not requiring an anesthesiologist. A selective use of the anesthesiologist seems indicated.

Campylobacter jejuni strains from patients with Guillain-Barré syndrome.

Guillain-Barré syndrome (GBS), an acute demyelinating peripheral neuropathy, may be triggered by an acute infectious illness; infection with Campylobacter jejuni is the most frequently reported antecedent event. In Japan, O:19 is the most common serotype among GBS-associated C. jejuni strains. To determine whether serotype O:19 occurs among GBS-associated strains in the United States and Europe, we serotyped seven such strains and found that two (29%) of seven GBS-associated strains from patients in the United States and Germany were serotype O:19. To determine whether GBS-associated strains may be resistant to killing by normal human serum (NHS), we studied the serum susceptibility of 17 GBS- and 27 enteritis-associated strains (including many O:19 and non-O:19 strains) using C. jejuni antibody positive (pool 1) or negative (pool 2) human serum. Using pool 1 serum we found that one (6%) of 18 serotype O:19 strains compared with 11 (42%) of 26 non-O:19 strains were killed; results using pool 2 serum were nearly identical. Finally, 8 O:19 and 8 non-O:19 strains were not significantly different in their ability to bind complement component C3. Serotype O:19 C. jejuni strains were overrepresented among GBS-associated strains in the United States and Germany and were significantly more serum-resistant than non-O:19 strains. The mechanism of this resistance appears unrelated to C3 binding.

Outcome of infected total knee arthroplasty.

The results of 44 cases of deep infection after total knee arthroplasty were reviewed. The average age of the patients was 62 years (range, 31-81 years), and all had positive bacterial cultures from deep aspiration or tissue biopsy. Osteitis was revealed in 22 cases. One case was initially treated with antibiotics only, 27 cases were treated with surgical debridement and antibiotics, and 16 cases had immediate removal of the prosthesis. In 21 cases, failed debridement was followed by removal of the prosthesis. Revision arthroplasty was attempted in 15 of the 37 cases in which the prosthesis was removed; the infection was cured in 11 cases. A total of 25 cases that underwent removal of the prosthesis had an arthrodesis performed, and 4 ultimately underwent amputation. In no case of osteitis was the infection cured merely by debridement and antibiotics, and the index prostheses were retained mainly in cases in which osteitis did not develop.

[Quality assurance of patient information--knee and hip alloplasty]. / Kvalitetssikring af patientinformation--før knae- og hoftealloplastik.

In order to estimate the efficiency of given information we asked 245 patients to fill in a questionnaire. The questions were based on written information given three to 36 months earlier in relation to joint replacement surgery of the knee or hip. One hundred and ninety-seven questionnaires were returned. Eighty-six percent of the patients were satisfied with the received information. Among patients, who had not kept the written information the knowledge about the operation, possible complications and safety rules after discharge from the hospital was poor. Several patients wanted further information about anaesthesia and rehabilitation. Like other investigations, this study demonstrates that information is to a great extent forgotten by the patients. This could be the result of patients' poor knowledge about the body and its functions together with a poor motivation for receiving "unpleasant" information. Better time for verbal information and a more professional lay-out of written information could improve the effectiveness of information.

Surveying medical groups in an aging America.

The Zitter Group also used an educational grant from Syntex Laboratories to survey medical groups on how the aging of the population is affecting them and how they are responding. The results are featured in this article by Connie Mahoney, Ph.D., and Amy Carlesen.

'Practice makes perfect'.

Several group practices around the country are offering innovative services to meet the needs of their older patients. The Zitter Group, in conjunction with MGMA/CRAHCA and Syntex Laboratories, conducted a nationwide contest to find the most outstanding of these programs and the winners are featured in this article.