Influence of marker-selection method in radiostereometric analysis of total knee arthroplasty on tibial baseplate migration patterns: a secondary analysis of a randomized controlled trial with 5-year follow-up.

BACKGROUND AND PURPOSE:  Different marker-selection methods are applied to represent implant and tibial segments in radiostereometric analysis (RSA) studies of total knee arthroplasty (TKA). Either a consistent set of markers throughout subsequent RSA examinations ("consistent-marker method") is used or all available markers at each follow-up ("all-marker method"). The aim of this secondary analysis was to compare marker-selection methods on individual and group level TKA migration results. METHODS:  Data from a randomized RSA study with 72 patients was included. Tibial baseplate migration was evaluated at 3 months, 1, 2, and 5 years postoperatively with both marker-selection methods. Additionally, migration was calculated using 5 fictive points, either plotted based on the consistent set of markers or all available markers. RESULTS:  Migration could be calculated with both marker-selection methods for 248 examinations. The same prosthesis and bone markers (n = 136), different prosthesis markers (n = 71), different bone markers (n = 21), or different prosthesis and bone markers (n = 20) were used. The mean difference in maximum total point motion (MTPM) between all examinations was 0.02 mm, 95% confidence interval -0.26 to 0.31 mm. 5 implants were classified as continuously migrating with the consistent-marker method versus 6 implants (same 5 plus one additional implant) with the all-marker method. Using fictive points, fewer implants were classified as continuously migrating in both marker-selection methods. Differences between TKA groups in mean MTPM were comparable with both marker-selection methods, also when fictive points were used. CONCLUSION:  Estimated group differences in mean MTPM were similar between marker-selection methods, but individual migration results differed. The latter has implications when classifying implants for estimated risk of future loosening.

Stress Hormone Dynamics Are Coupled to Brain Serotonin 4 Receptor Availability in Unmedicated Patients With Major Depressive Disorder: A NeuroPharm Study.

BACKGROUND: A prominent finding in major depressive disorder (MDD) is distorted stress hormone dynamics, which is regulated by serotonergic brain signaling. An interesting feature of the cerebral serotonin system is the serotonin 4 receptor (5-HT4R), which is lower in depressed relative to healthy individuals and also has been highlighted as a promising novel antidepressant target. Here, we test the novel hypothesis that brain 5-HT4R availability in untreated patients with MDD is correlated with cortisol dynamics, indexed by the cortisol awakening response (CAR). Further, we evaluate if CAR changes with antidepressant treatment, including a selective serotonin reuptake inhibitor, and if pretreatment CAR can predict treatment outcome. METHODS: Sixty-six patients (76% women) with a moderate to severe depressive episode underwent positron emission tomography imaging with [11C]SB207145 for quantification of brain 5-HT4R binding using BPND as outcome. Serial home sampling of saliva in the first hour from awakening was performed to assess CAR before and after 8 weeks of antidepressant treatment. Treatment outcome was measured by change in Hamilton Depression Rating Scale 6 items. RESULTS: In the unmedicated depressed state, prefrontal and anterior cingulate cortices 5-HT4R binding was positively associated with CAR. CAR remained unaltered after 8 weeks of antidepressant treatment, and pretreatment CAR did not significantly predict treatment outcome. CONCLUSIONS: Our findings highlight a link between serotonergic disturbances in MDD and cortisol dynamics, which likely is involved in disease and treatment mechanisms. Further, our data support 5-HT4R agonism as a promising precision target in patients with MDD and disturbed stress hormone dynamics.

A randomized controlled trial on virtual reality distraction during venous cannulation in young children.

BACKGROUND AND OBJECTIVES: Pain management in children is often inadequate, and the single most common painful procedure in children who are hospitalized is needle procedures. Virtual reality (VR) has been shown to decrease anxiety and pain in children undergoing painful procedures primarily in children from the age of 7 years. Our aim for this study is to investigate patient satisfaction and pain reduction by using a three-dimensional VR interactive game as a distraction in 4-7 years old children during venous cannulation. METHODS: In this randomized clinical trial, we enrolled 106 children aged 4-7 years who were scheduled for venous cannulation. Patients assigned to the control group were adherent to standard of care, including topical numbing cream, positioning, and distraction in this group by games of choice on a tablet/smartphone. In the study group, children were adherent to standard of care and were distracted by an interactive VR game. Primary outcomes were patient satisfaction and the procedural pain assessed by using Wong-Baker Faces Pain Rating Scale; secondary outcomes were the procedural time and any adverse events. RESULTS: We found an overall high level of patient satisfaction with our regime of topical numbing cream, positioning, and distraction. The primary outcome of pain during the procedure was median 20 mm (IQR 0-40) and 20 mm (IQR 0-55) (Wong-Baker 0-100 mm) in the VR group and the control group, respectively (difference: 0 mm, 95%CI: 0-20, p = .19). No significant difference was found in procedural times. The number of adverse effects was low, with no significant difference between the two groups. CONCLUSIONS: VR distraction is an acceptable form of distraction for children 4-7 years old when combined with topical numbing cream and positioning during preoperative venous cannulation. No difference was found between VR- and smartphone/tablet distraction.

Late stabilization after initial migration in patients undergoing cemented total knee arthroplasty: a 5-year followup of 2 randomized controlled trials using radiostereometric analysis.

BACKGROUND AND PURPOSE: In total knee arthroplasty (TKA), metal-backed (MBT) and all-polyethylene (APT) designs have shown comparable implant migration up to 2 years postoperatively using radiostereometric analysis (RSA). However, studies comparing mid-term migration of both designs are lacking. Furthermore, continuously migrating TKAs up to 2 years may continue to migrate or stabilize thereafter. Therefore, we compared 5-year migration of MBT and APT using either cruciate-stabilizing (CS) or posteriorstabilizing (PS) designs and specifically assessed migration profiles of continuously migrating TKAs beyond 2 years. PATIENTS AND METHODS: The present study includes results from 2 randomized trials comparing migration of cemented MBT with APT of either CS (CS study, n = 59) or PS (PS study, n = 56) design. 2 surgeons performed all surgeries. We used a linear mixed model for the analyses. RESULTS: The overall migration between MBT and APT TKAs was similar for either the CS or PS design over a 5-year period. In both studies combined, 9 implants showed continuous migration in the second postoperative year, of which 1 (APT-CS) was revised for instability, 4 (2 MBT-CS, MBT-PS, APT-PS) stabilized, and 4 (2 MBT-CS, APT-CS, MBT-PS) lacked 5-year data. INTERPRETATION: Overall migration was similar between MBT and APT TKAs up to 5 years, for both the CS and PS design. 4 initially migrating TKAs stabilized between 2- and 5-year follow-up, stressing the need for longer-term followup to determine whether second-year continuous migration correctly predicts loosening.

Use of sedating medications around nursing home admission in Denmark.

PURPOSE: To examine use of sedating medications around the time of nursing home admission in Denmark. METHODS: We conducted a register-based drug utilization study, describing patterns of commonly used medications with sedative effects leading up to and after nursing home admission using data from 94 Danish nursing homes between 2015 and 2017. RESULTS: We identified 5179 residents (median age 84 years, 63% female) and described monthly incidence and total use of benzodiazepines (BZDs), Z drugs, mirtazapine/mianserin, quetiapine, promethazine, and melatonin. The proportion of unique users of sedating medications was similar before and after admission (42% before vs. 40% after) despite an increase in total use after admission. The overall incidence of sedating medications peaked in the 6 months before and 6 months after admission (peaking at 4.6 per 100 person-months 1 month after admission). The most commonly initiated medications were mirtazapine/mianserin, followed by BZDs and Z drugs. Total use of sedating medications increased leading up to admission (peaking at 1001 defined daily doses per 100 residents per month 1 month after admission) and decreased gradually after admission. CONCLUSIONS: Sedative medication initiation increases sharply leading up to admission in Danish nursing homes. Mirtazapine/mianserin is a commonly used agent in nursing homes, despite limited evidence on benefits and harms. Efforts to promote rational use of these medications in nursing homes remain warranted.

Low-Cost Bubble-CPAP Treatment of a Severe Case of Pneumonia in a Low- and Middle-Income Country: A Case Report on the Importance of Optimizing Bubble-CPAP Setup.

A homemade low-cost bubble continuous positive airway pressure (bCPAP) setup can be created using resources available at most secondary healthcare facilities in low- and middle-income countries (LMICs). This setup has the potential of saving millions of children's lives worldwide; however, treatment failure due to bCPAP setup insufficiencies and lack of educated staff remains a significant obstacle. Here, we report a first-hand experience on the use of an established low-cost bCPAP setup to be used in LMICs and how optimization of two parameters was critical to effectively treat a severe case of lower respiratory disease in a 6-month-old infant in Tanzania. We report this case to strengthen that reducing the resistance in the tube system and minimizing air leakage at the nasal interface are crucial for efficient delivery of the CPAP therapy.

This case report describes how it is possible to successfully treat a 6-month-old infant with severe pneumonia in a low resource setting at a district hospital in Tanzania with a homemade low-cost oxygen therapy system called bubble continuous positive airway pressure (bCPAP). The construction was made of an oxygen concentrator, found in most secondary healthcare facilities in Africa, a nasal prong and a sterile water bottle. When optimized, this setup has the potential to mimic the therapeutic effect of an expensive and very effective therapy used in developed countries. The focus of this case report is how two adjustments of the bCPAP setup were necessary to achieve effective and safe treatment; however, we experienced that this homemade setup was very time-demanding and the quality of the treatment critically depended on the clinician to monitor and constantly optimize the equipment. So for this to be an effective and reliable treatment in secondary healthcare facilities in Tanzania, it requires sufficient staff education and nasal prongs that are suited for the purpose.

Use of medication among nursing home residents: a Danish drug utilisation study.

BACKGROUND: Data on drug utilisation patterns in nursing home populations is scarce. We aimed to describe drug use patterns in Danish nursing home residents. METHODS: We established a cohort of 5,179 individuals (63% women; median age of 84 years) admitted into 94 nursing homes across Denmark during 2015-2017. Data on prescription drug use and other census data were obtained from the nationwide Danish health registries. RESULTS: The total number of drug classes filled increased from a median of 6 drugs (interquartile range [IQR] 3-9) at 18-24 months before nursing home admission to a median of 8 drugs (IQR 6-11) just after admission, with the most common drug classes comprising paracetamol (61%), platelet inhibitors (41%), proton pump inhibitors (34%), statins (33%) and potassium supplements (31%). The incidence rate of new drug treatments increased from 21 new treatments/100 residents/month at 12-24 months before admission to a peak of 71 new treatments/100 residents/month in the month prior to admission, while it levelled off to about 34 new treatments/100 residents/month after 6-9 months. The drug classes primarily responsible for this peak were laxatives, antibiotics and analgesics. The largest absolute increases were seen for laxatives (53%), paracetamol (43%) and antidepressants (36%), all showing a marked increase up to and following admission. A high proportion of residents remained on therapy in the 3-year period following admission, with users of antidepressants and antidementia drugs being most persistent. CONCLUSION: Nursing home admission is associated with an increase in use of both predominantly preventive and non-preventive drug classes.

Acute Inhalation Toxicity After Inhalation of ZnO Nanoparticles: Lung Surfactant Function Inhibition In Vitro Correlates With Reduced Tidal Volume in Mice.

People can be exposed to zinc oxide (ZnO) by inhalation of consumer products or during industrial processes. Zinc oxide nanoparticle (NP) exposure can induce acute inhalation toxicity. The toxicological mechanisms underlying the acute effects on the lungs have long focused on the phagolysosomal dissolution of ZnO NPs in macrophages followed by the release of free Zn2+ ions. However, we postulate an alternative mechanism based on the direct interaction of ZnO NPs with the lung surfactant (LS) layer covering the inside of the alveoli. Therefore, we tested the effect of ZnO NPs and Zn2+ ions on the function of LS in vitro using the constrained drop surfactometer. We found that the ZnO NPs inhibited the LS function, whereas Zn2+ ions did not. To examine the role of lung macrophages in the acute toxicity of inhaled ZnO NPs, mice were treated with Clodrosome, a drug that depletes alveolar macrophages, or Encapsome, the empty carrier of the drug. After macrophage depletion, the mice were exposed to an aerosol of ZnO NPs in whole body plethysmographs recording breathing patterns continuously. Mice in both groups developed shallow breathing (reduced tidal volume) shortly after the onset of exposure to ZnO NPs. This suggests a macrophage-independent mechanism of induction. This study shows that acute inhalation toxicity is caused by ZnO NP interaction with LS, independently of NP dissolution in macrophages.

Morbidity and mortality among older people admitted to nursing home.

BACKGROUND: the increasing number of multimorbid older people places high demands on future health care systems. To inform the discussion on how to structure future care strategies, we aimed to describe the temporal relationship between admission, and morbidity and mortality in nursing home residents. METHODS: data on 5,179 older individuals admitted to 94 Danish nursing homes in 12 municipalities during 2015-2017 were linked to the nationwide Danish health registries to retrieve information on the temporal relation between nursing home admission and morbidity and mortality. RESULTS: at the time of nursing home admission, the majority were women (63%). Male residents were younger than women (median 82 vs 85 years) and had a higher prevalence of comorbidities (median Charlson score 2 vs 1 among women). The median survival after nursing home admission was 25.8 months, with the 3-year survival being 37%. Three-year survival was lower among men (29 vs 43% among women) and among the oldest residents (23% among those aged ≥90 years vs 64% among individuals ≤65 years). In addition to age and sex, predictors of mortality included hospitalisations prior to nursing home admission and a high burden of comorbidity. The rate of hospitalisations, primarily for reasons related to frailty, increased substantially during the 9 months prior to nursing home admission. CONCLUSION: we provide detailed information on differences in morbidity and mortality across age span and sex at the time of nursing home admission, thereby contributing to the ongoing discussion of how to structure the future health care system.

Reducing adverse side effects by seasonally lowering nitrate removal in subsurface flow constructed wetlands.

Subsurface flow constructed wetlands with wood chips (SSF-CWs) have proven to effectively reduce the loss of nitrogen (N) from agricultural fields to surface water, however in some cases production of negative side effects such as methane and phosphate occur. We examined if these side effects can be avoided by decreasing the hydraulic retention time (HRT) from on average 82 h to 11 h during summer to autumn in two pilot SSF-CWs. Furthermore, we investigated the potential of the SSF-CWs to reduce phosphorus (P) loss from agricultural drainage systems. The influent and effluent concentration of total N (TN), nitrate-N, total P, phosphate-P, suspended sediment, and sulphate were monitored for five years (2013-2017). Methane concentrations were measured during two periods in 2014 and 2017. Flow was measured continuously by electromagnetic flow-meters. The nitrate-N removal was reduced from 98-100% to 27-32% and the sulphate reduction from 32-53% to 1-2% when decreasing HRT. Concurrently this resulted in a considerable decrease in the difference between the effluent and influent concentration of phosphate-P and methane concentration compared to similar periods in the preceding years. The SSF-CWs retained 67-85% of the annual loading of particulate P, but acted as both a sink and source of phosphate-P, thus further initiatives are therefore required to prevent phosphate-P release from SSF-CWs. Although during the entire monitoring period the SSF-CWs retained 29-33% of the total P loading. In summary, this study stresses how important a holistic approach is when implementing and designing new N mitigation measures.

All-polyethylene versus metal-backed posterior stabilized total knee arthroplasty: similar 2-year results of a randomized radiostereometric analysis study.

Background and purpose - The all-polyethylene tibial (APT) component, introduced in the early 1970s, was surpassed by metal-backed tibial (MBT) trays as the first choice for total knee arthroplasty (TKA). With improved polyethylene, the modern APT components can reduce costs, and have shown equivalent results in survivorship and early migration of the cruciate-retaining and cruciate-stabilizing designs. This study compares the 2-year migration of a similarly designed APT-posterior stabilized (PS) and a MBT-PS TKA, using radiostereometric analysis (RSA).Patients and methods - 60 patients were randomized to receive either an APT Triathlon PS or an MBT Triathlon PS TKA (Stryker, NJ, USA). Migration measured by RSA and clinical scores were evaluated at baseline and at 3, 12, and 24 months postoperatively. Repeated measurements were analyzed with a linear mixed model and generalized estimating equations.Results - The mean maximum total point movement (MTPM) at 3, 12, and 24 months was 0.41 mm (95% CI 0.33-0.50), 0.57 mm (0.44-0.70), and 0.56 mm (0.42-0.69) respectively in the MBT group and 0.46 mm (0.36-0.57), 0.61 mm (0.49-0.73), and 0.64 mm (0.50-0.77) in the APT group. 2 MBT and 1 APT implant were considered unstable at the 2-year follow-up. The KSS Knee score and KSS Function across 3, 12, and 24 months were comparable in both groups.Interpretation - For an APT-PS designed component, MTPM measured with RSA is comparable to the MBT-PS component after 2 years of follow-up. No differences in complications or clinical outcomes were found.

Marker-based versus model-based radiostereometric analysis of total knee arthroplasty migration: a reanalysis with comparable mean outcomes despite distinct types of measurement error.

Background and purpose - Pooling data of studies evaluating total knee arthroplasty migration using radiostereometric analysis (RSA) may be compromised when the RSA method used would influence estimated differences between groups. We therefore reanalyzed a marker-based RSA study with model-based RSA to assess possible limitations of each RSA method, including insert micromotions in modular TKA and their effect on estimated group differences. Patients and methods - All patients had received a cemented Triathlon implant (Stryker, Mahwah, NJ, USA) with either an all-polyethylene (n = 29) or a metal-backed (n = 28) tibial component. The latter group was reanalyzed with model-based RSA. Precision of each RSA method was calculated using double examinations. Bland-Altman plots were constructed to determine the limits of agreement between the 2 RSA methods. Polyethylene insert micromotion was quantified by measuring migration with respect to the metal tray. Finally, analyses of the original study were repeated with the model-based RSA results. Results - Systematic differences were found in translations between marker-based and model-based RSA as a result of different reference origins being used for migration calculations. Micromotions of the polyethylene insert within the metal tray were negligibly small. Mean migration results were comparable between marker-based and model-based RSA when using the same reference origin, even though conclusions on individual patients may differ between RSA methods due to various types of measurement error (e.g., marker occlusion and model-fit inaccuracies). Interpretation - At least for the studied TKA design, pooling mean migration data of different RSA methods appears justified. For translations, however, adjustments should be made to correct for differences in reference origin. Migration patterns of individual patients may differ as a result of distinct types of measurement error.

Nitrogen and Phosphorus Removal from Agricultural Runoff in Integrated Buffer Zones.

Integrated buffer zones (IBZs) represent a novel form of edge-of-field technology in Northwest Europe. Contrary to the common riparian buffer strips, IBZs collect tile drainage water from agricultural fields by combining a ditch-like pond (POND), where soil particles can settle, and a flow-through filter bed (FILTERBED) planted with Alnus glutinosa (L.), a European alder (black alder). The first experimental IBZ facility was constructed and thoroughly tested in Denmark for its capability to retain various nitrogen (N) and phosphorus (P) species within the first three years after construction. We calculated the water and nutrient budget for the total IBZ and for the two compartments, POND and FILTERBED, separately. Furthermore, a tracer experiment using sodium bromide was conducted in order to trace the water flow and estimate the hydraulic residence time in the FILTERBEDs. The monthly average removal efficiency amounted to 10-67% for total N and 31-69% for total P, with performance being highest during the warm season. Accordingly, we suggest that IBZs may be a valuable modification of dry buffer strips in order to mitigate the adverse impacts of high nutrient loading from agricultural fields on the aquatic environment.

The clinical effect of an unloader brace on patients with osteoarthritis of the knee, a randomized placebo controlled trial with one year follow up.

BACKGROUND: Treatment of patients with knee osteoarthritis is challenging. Unloader braces have been developed with various success. Unloader One® Knee Brace is light, easily-fitted and shown to be effective by the unloading of the affected compartment. The aim of the study was to assess the clinical outcome of the brace vs. a placebo on patients with knee osteoarthritis. METHODS: Initially 150 patients were randomized to receive either the Unloader brace or a control placebo group look-alike brace where the active strips had been removed. The patients were followed up at 6,12,26 and 52 weeks with Knee Society Score (KSS) and Knee injury and Osteoarthritis Outcome Score (KOOS). The reason for dropout was recorded. RESULTS: A total of 149 patients were included, 74 in the study and 75 in the control group. The mean age was 59.6 vs. 60.2, BMI was 27.5 vs. 26.9, 37% vs. 44% were women in the study vs. control group. Both groups showed improvement in KSS over 52 weeks, with the study group showing higher improvement in mean scores. KSS increased from 64.3 to 84.0 for the study group and from 64.0 to 74.6 for the control group (p = 0.009). The study group improved in KSS function from 67.0 to 78.6 (p < 0.001) and KOOS for knee related symptoms increased/improved from 64.3 to 72.4 (p < 0.001). Activity of daily living increased/improved from 65.3 to 75.2 and Sports/Recreation from 24.6 to 40.2 (p > 0.001) whereas the control group did not show significant improvements in any of the scores. The dropout was higher in the control group, 40 vs. 25. CONCLUSIONS: The brace seems to be more effective and better tolerated than the placebo. TRIAL REGISTRATION: The trial was retrospectively registered with ClinicalTrials.gov ( NCT03454776 ) on March 6th 2018.

Peri-apatite coating decreases uncemented tibial component migration: long-term RSA results of a randomized controlled trial and limitations of short-term results.

Background and purpose - Biological fixation of uncemented knee prostheses can be improved by applying hydroxyapatite coating around the porous surface via a solution deposition technique called Peri-Apatite (PA). The 2-year results of a randomized controlled trial, evaluating the effect of PA, revealed several components with continuous migration in the second postoperative year, particularly in the uncoated group. To evaluate whether absence of early stabilization is diagnostic of loosening, we now present long-term follow-up results. Patients and methods - 60 patients were randomized to PA-coated or uncoated (porous only) total knee arthroplasty of which 58 were evaluated with radiostereometric analysis (RSA) performed at baseline, at 3 months postoperatively and at 1, 2, 5, 7, and 10 years. A linear mixed-effects model was used to analyze the repeated measurements. Results - PA-coated components had a statistically significantly lower mean migration at 10 years of 0.94 mm (95% CI 0.72-1.2) compared with the uncoated group showing a mean migration of 1.72 mm (95% CI 1.4-2.1). Continuous migration in the second postoperative year was seen in 7 uncoated components and in 1 PA-coated component. All of these implants stabilized after 2 years except for 2 uncoated components. Interpretation - Peri-apatite enhances stabilization of uncemented components. The number of components that stabilized after 2 years emphasizes the importance of longer follow-up to determine full stabilization and risk of loosening in uncemented components with biphasic migration profiles.

Migration of all-polyethylene compared with metal-backed tibial components in cemented total knee arthroplasty.

Background and purpose - With a rapidly increasing population in need of total knee arthroplasty (TKA), there is renewed interest in cost-saving all-polyethylene designs. Differences between metal-backed and all-polyethylene designs in initial component migration assessed by radiostereometric analysis (RSA), a proven predictor for late aseptic loosening, have been scantily reported. The purpose of this study was to compare implant migration and clinical outcomes of all-polyethylene tibial components versus metal-backed trays of similar geometrical shape. Patients and methods - In this randomized controlled trial, 59 patients received a cemented Triathlon condylar-stabilizing implant (Stryker, Mahwah, NJ, USA) with either an all-polyethylene (n = 29) or a metal-backed tibial component (n = 30). RSA measurements and clinical scores (the Knee Society Score, Forgotten Joint Score, and Knee Osteoarthritis and Injury Outcome Score) were evaluated at baseline and postoperatively at 3, 12, and 24 months. A linear mixed-effects model was used to analyze the repeated measurements. Results - A statistically significant difference in mean migration after 2 years was found in favor of the all-polyethylene group, with a mean maximum total point motion of 0.61 mm (95% CI 0.49-0.74) versus 0.81 mm (95% CI 0.68-0.96) for the cemented group (p = 0.03). However, this difference was smaller and not statistically significant after post hoc adjustment for surgeon effect. Both groups showed comparable improvements on all clinical outcome scores over time. Interpretation - The Triathlon all-polyethylene tibial component showed less migration, suggesting a lower risk of late loosening as compared with its metal-backed counterpart. However, the found surgeon effect warrants further investigation.

Re-evaluation of the WHO (2010) formaldehyde indoor air quality guideline for cancer risk assessment.

In 2010, the World Health Organization (WHO) established an indoor air quality guideline for short- and long-term exposures to formaldehyde (FA) of 0.1 mg/m3 (0.08 ppm) for all 30-min periods at lifelong exposure. This guideline was supported by studies from 2010 to 2013. Since 2013, new key studies have been published and key cancer cohorts have been updated, which we have evaluated and compared with the WHO guideline. FA is genotoxic, causing DNA adduct formation, and has a clastogenic effect; exposure-response relationships were nonlinear. Relevant genetic polymorphisms were not identified. Normal indoor air FA concentrations do not pass beyond the respiratory epithelium, and therefore FA's direct effects are limited to portal-of-entry effects. However, systemic effects have been observed in rats and mice, which may be due to secondary effects as airway inflammation and (sensory) irritation of eyes and the upper airways, which inter alia decreases respiratory ventilation. Both secondary effects are prevented at the guideline level. Nasopharyngeal cancer and leukaemia were observed inconsistently among studies; new updates of the US National Cancer Institute (NCI) cohort confirmed that the relative risk was not increased with mean FA exposures below 1 ppm and peak exposures below 4 ppm. Hodgkin's lymphoma, not observed in the other studies reviewed and not considered FA dependent, was increased in the NCI cohort at a mean concentration ≥0.6 mg/m3 and at peak exposures ≥2.5 mg/m3; both levels are above the WHO guideline. Overall, the credibility of the WHO guideline has not been challenged by new studies.

Ten-year results of physical activity after high tibial osteotomy in patients with knee osteoarthritis.

PURPOSE: The purpose was to describe physical activity with respect to leisure and working activity in patients operated on by high tibial osteotomy using the hemicallotasis technique for knee osteoarthritis (OA), preoperatively and 10 years postoperatively. METHODS: Seventy-nine patients, median age 55 (range 35-66), operated on by high tibial osteotomy using the hemicallotasis technique for knee OA 2001-2003 were included. Questionnaires for evaluation of physical and working activity, satisfaction as well as the Knee injury and Osteoarthritis Outcome Score (KOOS) were filled in preoperatively and 2 and 10 years postoperatively. Conversion to knee arthroplasty was obtained through the Swedish Knee Arthroplasty Register. Changes between two postoperative measurements were assessed by Wilcoxon's rank test. RESULTS: Twenty-five patients were converted to a total knee arthroplasty, and nine patients were lost to follow-up during the 10 years, resulted in 45 patients available for follow-up. Preoperatively, 33/45 patients were physically active mainly in heavy yard/household work, and 43/45 patients were working active. Ten years after the HCO, 23/45 patients were still active with golf, dancing, hiking, etc., and 23/45 were retired. At 10 years postoperatively compared to 2 years postoperatively, the patients experienced more problems with pain (89 compared to 69, p = <0.0001). Of 45 patients, 36 were satisfied with the high tibial osteotomy surgery in general 10 years postoperatively, while 13/45 were satisfied with their sport and recreational function. CONCLUSIONS: The 10-year results indicate that high tibial osteotomy using the hemicallotasis technique for knee OA is an option for selected patients that improves the level of physical activity, with mild deterioration over time, and gives the majority of the patients the possibility to be working active until retirement. LEVEL OF EVIDENCE: Level IV.

A Proposed In Vitro Method to Assess Effects of Inhaled Particles on Lung Surfactant Function.

The lung surfactant (LS) lining is a thin liquid film covering the air-liquid interface of the respiratory tract. LS reduces surface tension, enabling lung surface expansion and contraction with minimal work during respiration. Disruption of surface tension is believed to play a key role in severe lung conditions. Inhalation of aerosols that interfere with the LS may induce a toxic response and, as a part of the safety assessment of chemicals and inhaled medicines, it may be relevant to study their impact on LS function. Here, we present a novel in vitro method, based on the constrained drop surfactometer, to study LS functionality after aerosol exposure. The applicability of the method was investigated using three inhaled asthma medicines, micronized lactose, a pharmaceutical excipient used in inhaled medication, and micronized albumin, a known inhibitor of surfactant function. The surfactometer was modified to allow particles mixed in air to flow through the chamber holding the surfactant drop. The deposited dose was measured with a custom-built quartz crystal microbalance. The alterations allowed the study of continuously increasing quantified doses of particles, allowing determination of the dose of particles that affects the LS function. The tested pharmaceuticals did not inhibit the function of a model LS even at extreme doses--neither did lactose. Micronized albumin, however, impaired surfactant function. The method can discriminate between safe inhaled aerosols--as exemplified by the approved inhaled medicines and the pharmaceutical excipient lactose--and albumin known to impair lung functionality by inhibiting LS function.

Generation and Characterization of Indoor Fungal Aerosols for Inhalation Studies.

In the indoor environment, people are exposed to several fungal species. Evident dampness is associated with increased respiratory symptoms. To examine the immune responses associated with fungal exposure, mice are often exposed to a single species grown on an agar medium. The aim of this study was to develop an inhalation exposure system to be able to examine responses in mice exposed to mixed fungal species aerosolized from fungus-infested building materials. Indoor airborne fungi were sampled and cultivated on gypsum boards. Aerosols were characterized and compared with aerosols in homes. Aerosols containing 10(7)CFU of fungi/m(3)air were generated repeatedly from fungus-infested gypsum boards in a mouse exposure chamber. Aerosols contained Aspergillus nidulans,Aspergillus niger, Aspergillus ustus, Aspergillus versicolor,Chaetomium globosum,Cladosporium herbarum,Penicillium brevicompactum,Penicillium camemberti,Penicillium chrysogenum,Penicillium commune,Penicillium glabrum,Penicillium olsonii,Penicillium rugulosum,Stachybotrys chartarum, and Wallemia sebi They were all among the most abundant airborne species identified in 28 homes. Nine species from gypsum boards and 11 species in the homes are associated with water damage. Most fungi were present as single spores, but chains and clusters of different species and fragments were also present. The variation in exposure level during the 60 min of aerosol generation was similar to the variation measured in homes. Through aerosolization of fungi from the indoor environment, cultured on gypsum boards, it was possible to generate realistic aerosols in terms of species composition, concentration, and particle sizes. The inhalation-exposure system can be used to study responses to indoor fungi associated with water damage and the importance of fungal species composition.