Comorbidity and risk of infection among patients with hip fracture: a Danish population-based cohort study.

Impact of comorbidity on infection risk among hip fracture patients is unclear. We found high incidence of infection. Comorbidity was an important risk factor for infection up to 1 year after surgery. Results indicates a need for additional investment in pre- and postoperative programs that assist patients with high comorbidity. PURPOSE: Comorbidity level and incidence of infection have increased among older patients with hip fracture. The impact of comorbidity on infection risk is unclear. We conducted a cohort study examining the absolute and relative risks of infection in relation to comorbidity level among hip fracture patients. METHODS: Utilizing Danish population-based medical registries, we identified 92,600 patients aged ≥ 65 years undergoing hip fracture surgery between 2004 and 2018. Comorbidity was categorized by Charlson comorbidity index scores (CCI): none (CCI = 0), moderate (CCI = 1-2), or severe (CCI ≥ 3). Primary outcome was any hospital-treated infection. Secondary outcomes were hospital-treated pneumonia, urinary tract infection, sepsis, reoperation due to surgical-site infection (SSI), and a composite of any hospital- or community-treated infection. We calculated cumulative incidence and hazard ratios (aHRs) adjusted for age, sex, and surgery year, including 95% confidence intervals (CIs). RESULTS: Prevalence of moderate and severe comorbidity was 40% and 19%, respectively. Incidence of any hospital-treated infection increased with comorbidity level within 0-30 days (none 13% vs. severe 20%) and 0-365 days (none 22% vs. 37% severe). Patients with moderate and severe comorbidity, compared to no comorbidity, had aHRs of 1.3 (CI: 1.3-1.4) and 1.6 (CI: 1.5-1.7) within 0-30 days, and 1.4 (CI: 1.4-1.5) and 1.9 (CI: 1.9-2.0) within 0-365, respectively. Highest incidence was observed for any hospital- or community-treated infection (severe 72%) within 0-365 days. Highest aHR was observed for sepsis within 0-365 days (severe vs. none: 2.7 (CI: 2.4-2.9)). CONCLUSION: Comorbidity is an important risk factor for infection up to 1 year after hip fracture surgery.

Time trends in use of non-steroidal anti-inflammatory drugs and opioids one year after total hip arthroplasty due to osteoarthritis during 1996-2018: a population-based cohort study of 103,209 patients.

OBJECTIVE: To examine time trends in the use of NSAIDs and opioids for patients with osteoarthritis undergoing total hip arthroplasty (THA) during 1996-2018. METHOD: Using Danish population-based medical databases, we identified 103,209 THA patients. Prevalence rates of NSAID and opioid use among preoperative users and non-users were calculated in four quarters (Q1-Q4) after THA by calendar periods (1996-2000, 2001-2006, 2007-2012 and 2013-2018). Prevalence rate ratios (PRR) were adjusted for age and gender. RESULTS: Among preoperative NSAID users and non-users, NSAID use in Q1 increased from 32.6% in 1996-2000 to 48.0% in 2013-2018 (PRR = 1.49, 95% CI: 1.42-1.55) and from 12.9% to 32.0% (PRR = 2.49 (2.32-2.67)), respectively. Among preoperative opioid users and non-users, opioid use in Q1 increased from 42.7% in 1996-2000 to 76.9% in 2013-2018 (PRR = 1.81 (1.73-1.89)) and from 15.2% to 58.2% (PRR = 3.85 (3.65-4.05)), respectively. NSAID use in Q4 decreased from 24.5% in 1996-2000 to 21.4% in 2013-2018 (PRR = 0.88 (0.83-0.93)) and from 6.9% to 5.6% (PRR = 0.81 (0.73-0.91)) in preoperative NSAIDs users and non-users, respectively. Opioid use in Q4 increased from 26.6% in 1996-2000 to 28.6% (PRR = 1.08 (1.02-1.15)) in 2013-2018 and from 4.1% to 5.0% (PRR = 1.25 (1.11-1.40)) in preoperative opioid users and non-users, respectively. CONCLUSION: We observed up to a 4-fold increase in NSAID and opioid use in Q1 during 1996-2018, while usage in Q4 did not change substantially. However, 5-6% of the preoperative non-users of NSAIDs and opioids were users in Q4, which might relate to inaccurate indication for or timing of THA and the post-surgical phasing out of analgesics use.

Assessing how routes to diagnosis vary by the age of patients with cancer: a nationwide register-based cohort study in Denmark.

BACKGROUND: Older patients with cancer have poorer prognosis compared to younger patients. Moreover, prognosis is related to how cancer is identified, and where in the healthcare system patients present, i.e. routes to diagnosis (RtD). We investigated whether RtD varied by patients' age. METHODS: This population-based national cohort study used Danish registry data. Patients were categorized into age groups and eight mutually exclusive RtD. We employed multinomial logistic regressions adjusted for sex, region, diagnosis year, cohabitation, education, income, immigration status and comorbidities. Screened and non-screened patients were analysed separately. RESULTS: The study included 137,876 patients. Both younger and older patients with cancer were less likely to get diagnosed after a cancer patient pathways referral from primary care physician compared to middle-aged patients. Older patients were more likely to get diagnosed via unplanned admission, death certificate only, and outpatient admission compared to younger patients. The patterns were similar across comorbidity levels. CONCLUSIONS: RtD varied by age groups, and middle-aged patients were the most likely to get diagnosed after cancer patient pathways with referral from primary care. Emphasis should be put on raising clinicians' awareness of cancer being the underlying cause of symptoms in both younger patients and in older patients.

Using multi-event hydrologic and hydraulic signatures from water level sensors to diagnose locations of uncertainty in integrated urban drainage models used in living digital twins.

Digital twins of urban drainage systems require simulation models that can adequately replicate the physical system. All models have their limitations, and it is important to investigate when and where simulation results are acceptable and to communicate the level of performance transparently to end users. This paper first defines a classification of four possible 'locations of uncertainty' in integrated urban drainage models. It then develops a structured framework for identifying and diagnosing various types of errors. This framework compares model outputs with in-sewer water level observations based on hydrologic and hydraulic signatures. The approach is applied on a real case study in Odense, Denmark, with examples from three different system sites: a typical manhole, a small flushing chamber, and an internal overflow structure. This allows diagnosing different model errors ranging from issues in the underlying asset database and missing hydrologic processes to limitations in the model software implementation. Structured use of signatures is promising for continuous, iterative improvements of integrated urban drainage models. It also provides a transparent way to communicate the level of model adequacy to end users.

Validation of the Danish versions of the Bristol Rheumatoid Arthritis Fatigue Multi-Dimensional Questionnaires (BRAFs).

Objective: This study aimed to validate the Danish versions of the Bristol Rheumatoid Arthritis Fatigue Multi-Dimensional Questionnaire (BRAF-MDQ) and BRAF Numerical Rating Scale version 2 (NRSv2).Method: We tested face and content validity, internal consistency, criterion validity, construct validity, and reproducibility for the BRAF-MDQ, and face and criterion validity and reproducibility for the BRAF-NRS.Results: In all, 224/236 patients (95%) completed the questionnaires [70% female, mean ± sd age 59 ± 13.04 years, disease duration 11.2 ± 9.49 years, Health Assessment Questionnaire (HAQ) 0.724 ± 0.70, and 28-joint Disease Activity Score-C-reactive protein 2.55 ± 1.24]. The unidimensionality for the physical and cognitive fatigue subscales was confirmed, whereas the living with fatigue and emotional fatigue subscales were not unidimensional. Cronbach's α was 0.94 for the BRAF-MDQ total and 0.78-0.92 for the four subscales. The correlations between BRAF-MDQ and various measures were: 36-item Short Form Health Survey (SF-36) vitality subscale, 0.75; Hospital Anxiety and Depression Scale (HADS) anxiety subscale, 0.65; HADS depression subscale, 0.62; visual analogue scale (VAS) pain, 0.62; VAS global, 0.73; and HAQ, 0.62. The intraclass correlation coefficient for agreement was 0.995. A Bland-Altman plot showed a mean ± sd difference of -1.9 ± 3.62 for BRAF-MDQ. Correlation coefficients between the BRAF-NRSv2 subscales and other subscales were: BRAF-MDQ subscales, 0.57-0.93; SF-36 vitality subscale, 0.54-0.68; and VAS fatigue, 0.66-0.82.Conclusions: The Danish BRAFs are considered valid and reliable for use among Danish patients with rheumatoid arthritis, despite the subscales living with fatigue and emotional fatigue not being unidimensional, as they are in the original version.

Cladribine modifies functional properties of microglia.

Cladribine (CdA), an oral prodrug approved for the treatment of relapsing multiple sclerosis, selectively depletes lymphocytes. CdA passes the blood-brain barrier, suggesting a potential effect on central nervous system (CNS) resident cells. We examined if CdA modifies the phenotype and function of naive and activated primary mouse microglia, when applied in the concentrations 0·1-1 µM that putatively overlap human cerebrospinal fluid (CSF) concentrations. Primary microglia cultures without stimulation or in the presence of proinflammatory lipopolysaccharide (LPS) or anti-inflammatory interleukin (IL)-4 were treated with different concentrations of CdA for 24 h. Viability was assessed by MTT [3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide] assay. Phagocytotic ability and morphology were examined by flow cytometry and random migration using IncuCyte Zoom and TrackMate. Change in gene expression was examined by quantitative polymerase chain reaction (qPCR) and protein secretion by Meso Scale Discovery. We found that LPS and IL-4 up-regulated deoxycytidine kinase (DCK) expression. Only activated microglia were affected by CdA, and this was unrelated to viability. CdA 0·1-1 µM significantly reduced granularity, phagocytotic ability and random migration of activated microglia. CdA 10 µM increased the IL-4-induced gene expression of arginase 1 (Arg1) and LPS-induced expression of IL-1ß, tumor necrosis factor (TNF), inducible nitric oxide synthase (iNOS) and Arg1, but protein secretion remained unaffected. CdA 10 µM potentiated the increased expression of anti-inflammatory TNF receptor 2 (TNF-R2) but not TNF-R1 induced by LPS. This suggests that microglia acquire a less activated phenotype when treated with 0·1-1 µM CdA that putatively overlaps human CSF concentrations. This may be related to the up-regulated gene expression of DCK upon activation, and suggests a potential alternative mechanism of CdA with direct effect on CNS resident cells.

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.

Injection of freshly collected autologous adipose tissue into non-healing wounds after closed incision pilonidal surgery.

BACKGROUND: Chronic non-healing wounds are a major problem after closed incision pilonidal surgery. Freshly collected autologous adipose tissue injected into perianal fistulas in patients with Crohn's disease seems to promote healing. We investigated this technique in patients with non-healing wounds after cleft-lift surgery for pilonidal sinus disease (PSD). METHOD: In a prospective interventional pilot study conducted at our institution autologous adipose tissue from the abdominal wall was harvested, and injected into chronic non-healing PS wounds after surgical revision, healing rate being the primary outcome. The wounds were left open. Patients were followed every 2 to 3 weeks until complete healing (skin coverage, no undermining). RESULTS: 7 male patients were included (mean age 24 ± 0,6 SD years) and complete healing was achieved in 6 patients (86%). Median time to healing was 90 days (range 36-403 days ) and mean follow-up time was 388± 45 days. All patients reported major symptom relief shortly after the procedure. The mean operation time was 80 ± 23 minutes and the mean amount of freshly collected adipose tissue injected was 27.4± 12 ml. There were no complications. CONCLUSIONS: Freshly collected autologous adipose tissue injected into chronic non-healing pilonidal wounds seems safe and efficient.

A comparison of nutrient uptake efficiency and growth rate between different macrophyte growth forms.

Aquatic macrophytes grow abundantly in many lowland streams and play a key role in ecosystem functioning, such as nutrient retention. In this study, we performed a microcosm experiment to quantify and compare the contribution of two freshwater macrophyte growth forms to nutrient cycling. We measured and compared inorganic nitrogen (NH4-N and NO3-N) and phosphorus (PO4-P) uptake kinetic parameters (Vmax and Cmin) in 12 submerged and seven amphibious plant species. We tested whether relative growth rate (RGR) was related to high Vmax and low Cmin, and quantified changes in nutrient uptake kinetic in a subset of six out of 19 plants species during the growth season. Uptake rates of NH4-N were higher in submerged compared to amphibious plants, whereas uptake rates of NO3-N were significantly higher in amphibious species; PO4-P uptake kinetics were not significantly different between the two growth forms. There were also significant seasonal differences in Vmax NH4-N rate among both submerged and amphibious species and in Vmax NO3-N among amphibious species. Highest uptake rates were observed in summer for both submerged and amphibious species. Overall, we found that nutrient uptake kinetics differed between the two growth forms within and between seasons. Consequently, the presence of both growth forms should extend the period of nutrient uptake across the year and enhance nutrient uptake within seasons. We conclude that higher functional diversity enhances annual nutrient uptake in streams and that stream restoration efforts should consider increasing the niche space available for both submerged and amphibious species.

Loss of B Cells in Patients with Heterozygous Mutations in IKAROS.

BACKGROUND: Common variable immunodeficiency (CVID) is characterized by late-onset hypogammaglobulinemia in the absence of predisposing factors. The genetic cause is unknown in the majority of cases, and less than 10% of patients have a family history of the disease. Most patients have normal numbers of B cells but lack plasma cells. METHODS: We used whole-exome sequencing and array-based comparative genomic hybridization to evaluate a subset of patients with CVID and low B-cell numbers. Mutant proteins were analyzed for DNA binding with the use of an electrophoretic mobility-shift assay (EMSA) and confocal microscopy. Flow cytometry was used to analyze peripheral-blood lymphocytes and bone marrow aspirates. RESULTS: Six different heterozygous mutations in IKZF1, the gene encoding the transcription factor IKAROS, were identified in 29 persons from six families. In two families, the mutation was a de novo event in the proband. All the mutations, four amino acid substitutions, an intragenic deletion, and a 4.7-Mb multigene deletion involved the DNA-binding domain of IKAROS. The proteins bearing missense mutations failed to bind target DNA sequences on EMSA and confocal microscopy; however, they did not inhibit the binding of wild-type IKAROS. Studies in family members showed progressive loss of B cells and serum immunoglobulins. Bone marrow aspirates in two patients had markedly decreased early B-cell precursors, but plasma cells were present. Acute lymphoblastic leukemia developed in 2 of the 29 patients. CONCLUSIONS: Heterozygous mutations in the transcription factor IKAROS caused an autosomal dominant form of CVID that is associated with a striking decrease in B-cell numbers. (Funded by the National Institutes of Health and others.).

Preoperative antithrombotic therapy and risk of blood transfusion and mortality following hip fracture surgery: a Danish nationwide cohort study.

Hip fracture surgery is associated with high risk of bleeding and mortality. The patients often have cardiovascular comorbidity, which requires antithrombotic treatment. This study found that preoperative use of oral anticoagulants was not associated with transfusion or mortality following hip fracture surgery, whereas increased risk may exist for antiplatelet drugs. INTRODUCTION: Hip fracture surgery is associated with high bleeding risk and mortality; however, data on operative outcomes of hip fracture patients admitted while on antithrombotic therapy is sparse. We examined if preoperative antithrombotic treatment was associated with increased use of blood transfusion and 30-day mortality following hip fracture surgery. METHODS: Using data from the Danish Multidisciplinary Hip Fracture Registry, we identified 74,791 hip fracture surgery patients aged ≥ 65 years during 2005-2016. Exposure was treatment with non-vitamin K antagonist oral anticoagulant (NOAC), vitamin K antagonists (VKA), or antiplatelet drugs at admission for hip fracture. Outcome was blood transfusion within 7 days postsurgery and death within 30 days. RESULTS: A 45.3% of patients received blood transfusion and 10.6% died. Current NOAC use was associated with slightly increased risk of transfusion (adjusted relative risk (aRR) 1.07, 95% confidence interval (CI) 1.01-1.14), but similar mortality risk (adjusted hazard ratio (aHR) 0.88, 95% CI 0.75-1.03) compared with non-users. The pattern remained when restricting to patients with short surgical delay (< 24 h). VKA users did not have increased risk of transfusion or mortality. The risks of transfusion (aRR 1.15 95% CI 1.12-1.18) and 30-day mortality (aHR 1.18 95% CI 1.14-1.23) were increased among antiplatelet users compared with non-users. CONCLUSIONS: In an observational setting, neither preoperative NOAC nor VKA treatments were associated with increased risk of 30-day postoperative mortality among hip fracture patients. NOAC was associated with slightly increased risk of transfusion. Preoperative use of antiplatelet drugs was associated with increased risk of transfusion and mortality.

Use of anti-osteoporosis medication dispensing by patients with hip fracture: could we do better?

Although Scandinavian countries have the highest incidence of hip fracture in the world, trends in anti-osteoporosis medication use have not been studied. We found less than one-third of Danish hip fracture patients had dispensing of anti-osteoporosis medication over a 10-year period using routinely collected data from population-based registries. INTRODUCTION: To examine trend in dispensing of anti-osteoporosis medication before and after hip fracture surgery in Denmark over a 10-year period using routinely collected data from population-based registries. METHODS: From the Danish Multidisciplinary Hip Fracture Registry, we included 65,011 patients aged 65 years or older with an incident hip fracture in 2005-2015. We calculated, for each calendar year of hip fracture diagnosis, the prevalence of use of anti-osteoporosis medication (at least one dispensing of bisphosphonates, strontium ranelate, denosumab, selective estrogen receptor modulators, or teriparatide) in the year before and in the year following hip fracture diagnosis. Among those without a dispensing in the year before hip fracture, we computed 1-year cumulative incidence of use following hip fracture. We treated death as a competing risk and stratified the analysis on sex, age, and comorbidity. RESULTS: The prevalence of use before hip fracture varied between 7 and 12%, increasing slightly from 2005 to 2015. The cumulative incidence of use following hip fracture decreased from 16% in 2005 to 13% in 2010, whereupon it increased to 20%. A similar pattern was seen with each stratum of sex, age groups, and comorbidity. The overall prevalence of use after hip fracture was below 22% in all calendar years. CONCLUSIONS: Less than one-third of hip fracture patients had dispensing of anti-osteoporosis medication up to 1 year after hip fracture. We observed only a slight increase in dispensing after hip fracture over the study period, irrespective of patient sex, age, and comorbidity at the time of hip fracture.

Helicobacter pylori infection is not associated with rheumatoid arthritis.

OBJECTIVE: Rheumatoid arthritis (RA) is an autoinflammatory disease caused by genetic susceptibility and environmental triggers, which include infectious agents. Helicobacter pylori, a bacterium that frequently colonizes the stomach, is associated with the development of certain autoinflammatory disorders. This study examined a possible association between H. pylori infection and RA. METHOD: This cohort study was performed in the Central Denmark Region. Patients were enrolled from primary healthcare centres after a urea breath test (UBT) for H. pylori and followed for a median of 8 years. Nationwide administrative registries provided information about the patients' diagnoses, country of birth, and gender. Comorbidity was determined using the Charlson Comorbidity Index. We compared the prevalence of RA via odds ratios (ORs) and incidences using Cox regression to calculate the hazard ratios (HRs) by comparing H. pylori-positive and H. pylori-negative individuals and adjusting for confounding variables. RESULTS: A total of 56 000 people diagnosed as H. pylori positive or negative had similar rates of comorbidity. No link was found between H. pylori and RA. There was no difference in RA prevalence until time of UBT [OR = 0.91, 95% confidence interval (CI) 0.70-1.19)] or incidence of new RA cases after UBT (HR = 0.80, 95% CI 0.56-1.13) between H. pylori-positive and -negative subjects. Validation via four other RA definitions provided similar results. CONCLUSION: This study found no association between H. pylori infection and RA. This result does not support the involvement of H. pylori in a gut-joint axis of importance for RA development.

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.

Concomitant sensitization to legumin, Fag e 2 and Fag e 5 predicts buckwheat allergy.

BACKGROUND: Buckwheat (Fagopyrum esculentum) has become increasingly popular as a healthy food in Europe. However, for sensitized individuals, consumption can cause anaphylactic reactions. The aim of this study was to identify individual well-characterized buckwheat allergens for component-resolved diagnosis. METHODS: Patients were selected by positive skin prick test to buckwheat and divided into two groups: (1) sensitized to buckwheat without clinical symptoms and (2) buckwheat allergy. Buckwheat proteins were extracted from raw buckwheat seeds, purified applying a combination of protein precipitation and chromatographic methods, and analyzed by IgE immunoblotting and ELISA. RESULTS: Buckwheat-allergic patients had a significantly larger median skin prick test weal diameter for buckwheat than the sensitized group and the positive control. Also, IgE immunoblotting clearly showed a distinct pattern in sera from allergic patients when compared to sensitized individuals. Several IgE-reactive proteins were purified from crude buckwheat extract, namely legumin (Fag e 1 plus its large subunit), Fag e 2 (2S albumin), and newly identified Fag e 5 (vicilin-like) as well as hevein-like antimicrobial peptides, designated Fag e 4. All four allergens showed superior diagnostic precision compared to extract-based ImmunoCAP with high sensitivity as well as high specificity. CONCLUSIONS: Patients with clinical symptoms clearly show a distinct allergen recognition pattern. We characterized a buckwheat vicilin-like protein as a new relevant marker allergen, designated Fag e 5. Additionally, another new allergen, Fag e 4, potentially important for cross-reactivity to latex was added to the allergen panel of buckwheat. Further, our data show that the full-length legumin comprising both, large and small subunit should be applied for component-resolved diagnosis. Our data indicate that concomitant sensitization to legumin, Fag e 2 and Fag e 5, predicts buckwheat allergy.

Submerged freshwater plant communities do not show species complementarity effect in wetland mesocosms.

It is a generally accepted theory that ecological functions are enhanced with increased diversity in plant communities due to species complementarity effects. We tested this theory in a mesocosm study using freshwater submerged plant beds to determine if increasing species number caused overyielding and species complementarity. We applied a maximum of four species in the plant beds corresponding to the typical species number in natural freshwater plant beds. We found no clear effects of species number (1-4) on biomass production and thus no conclusive overyielding and complementarity effect. This may be explained by low species differentiation among the four species in plant traits relevant for resource acquisition in freshwater, or that other species interactions, e.g. allelopathy, were inhibiting overyielding. The existing knowledge on species complementarity in aquatic plant communities is sparse and inconclusive and calls for more research.

Return to work predictors after traumatic brain injury in a welfare state.

OBJECTIVE: To identify predictors of return to work (RTW) and stable labour market attachment (LMA) after severe traumatic brain injury (TBI) in Denmark. MATERIALS & METHODS: Patients aged 18-64 years, admitted to highly specialized neurorehabilitation after severe TBI 2004-2012 were included and followed up for ≤6 years. Weekly LMA data were retrieved from a national register of public assistance benefits. Weeks without or with supplemental public assistance benefits were defined as LMA weeks. Time of RTW was defined as first week with LMA. Stable LMA was defined as weeks with LMA ≥75% first year after RTW. Multivariable regressions were used to identify predictors of RTW and stable LMA among preinjury characteristics, injury severity, functional ability and rehabilitation trajectories. RESULTS: For the analyses of RTW and stable LMA, 651 and 336 patients were included, respectively. RTW was significantly associated with age (adjusted subhazard ratio 0.98, 95% CI 0.97-0.99), education (1.83, 95% CI 1.16-2.89), supplemental benefits (3.97, 95% CI 2.04-7.71), no benefits (4.86, 95% CI 2.90-8.17), length of stay in acute care (0.77, 95% CI 0.60-0.99) and time period of injury (1.56, 95% CI 1.15-2.10). The only significant predictor of stable LMA was age (adjusted odds ratio 0.97, 95% CI 0.95-0.99). CONCLUSION: RTW after severe TBI was associated with several socio-economic factors, whereas maintaining LMA depended on age only. We suggest that RTW rates could be improved by extensive rehabilitation targeting people that are older and low-educated, as these were less likely to RTW.

Homocarnosinosis: A historical update and findings in the SPG11 gene.

OBJECTIVES: A family with homocarnosinosis was reported in the literature in 1976. Three affected siblings had spastic paraplegia, retinitis pigmentosa, mental retardation, and cerebrospinal fluid (CSF) homocarnosine concentrations 20 times higher than in controls. Based on the clinical findings and new genetic techniques, we have been able to establish a precise genetic diagnosis. METHOD: The medical records were re-evaluated, and genetic analyses were performed post-mortem in this original family. SNP array-based whole genome homozygosity mapping and Sanger sequencing of the SPG11 gene were performed. Seven additional Norwegian SPG11 patients and their disease-causing variants and clinical findings were evaluated. Homocarnosine levels in CSF were measured in four of these seven patients. RESULTS: A homozygous pathogenic splice-site variant in the SPG11 gene, c.2316 + 1G>A, was found. The clinical findings in the original family correlate with the heterogeneous SPG11 phenotype. The same variant was found in seven other Norwegian SPG11 patients, unrelated to the original family, either as homozygous or compound heterozygous constellation. Normal homocarnosine levels were found in the CSF of all unrelated SPG11 patients. CONCLUSIONS: A re-evaluation of the clinical symptoms and findings in the original family correlates with the SPG11 phenotype. The increased levels of homocarnosine do not seem to be a biomarker for SPG11 in our patients. Homocarnosinosis is still a biochemical aberration with unknown clinical significance.

Salivary secretion in health and disease.

Saliva is a complex fluid produced by 3 pairs of major salivary glands and by hundreds of minor salivary glands. It comprises a large variety of constituents and physicochemical properties, which are important for the maintenance of oral health. Saliva not only protects the teeth and the oropharyngeal mucosa, it also facilitates articulation of speech, and is imperative for mastication and swallowing. Furthermore, saliva plays an important role in maintaining a balanced microbiota. Thus, the multiple functions provided by saliva are essential for proper protection and functioning of the body as a whole and for the general health. A large number of diseases and medications can affect salivary secretion through different mechanisms, leading to salivary gland dysfunction and associated oral problems, including xerostomia, dental caries and fungal infections. The first part of this review article provides an updated insight into our understanding of salivary gland structure, the neural regulation of salivary gland secretion, the mechanisms underlying the formation of saliva, the various functions of saliva and factors that influence salivary secretion under normal physiological conditions. The second part focuses on how various diseases and medical treatment including commonly prescribed medications and cancer therapies can affect salivary gland structure and function. We also provide a brief insight into how to diagnose salivary gland dysfunction.

A comparison of attitudes to laryngeal cancer treatment outcomes: A time trade-off study.

DESIGN: Time trade-off choice experiment. SETTING: Two large head and neck cancer centres. PARTICIPANTS: Patients who have received treatment for head and neck cancer and members of the head and neck cancer multidisciplinary team. MAIN OUTCOME MEASURES: Participants were asked to rank the outcome scenarios, assign utility values using time trade-off and rate the importance of survival on treatment choice. RESULTS: A total of 49 patients with head and neck cancer and 73 staff members were recruited. Chemoradiotherapy (CRT) optimal outcome was the most preferred health state (34 of 49, 69% patients, and 50 of 73, 68% staff), and CRT with complications was least preferred (27 of 49, 55% patients, and 51 of 73, 70% staff). Using time trade-off, mean utility values were calculated for CRT optimal outcome (0.73 for patients, 0.77 for staff), total laryngectomy (TL) optimal outcome (0.67 for patients, 0.69 for staff), TL outcome with complications (0.46 for patients, 0.51 for staff) and CRT with complications (0.36 for patients, 0.49 for staff). The average survival advantage required for a participant to change their preferred choice was 2.6 years. CONCLUSIONS: We have demonstrated that a significant proportion of patients with head and neck cancer and staff members would not choose CRT to manage locally advanced laryngeal cancer. Staff members rated the health states associated with laryngeal cancer treatment higher than patients who have experienced them, and this is particularly evident when considering the poorer outcomes. The head and neck cancer community should develop methods of practice and decision-making which incorporate elicitation and reporting of patient values as a central principle.