Health-related quality of life in patients with generalized pustular psoriasis: A systematic literature review.

Generalized pustular psoriasis (GPP) is a rare, chronic, neutrophilic inflammatory skin disease characterized by episodes of widespread eruption of sterile, macroscopic pustules that can be accompanied by systemic inflammation and symptoms. A systematic literature review and narrative synthesis were conducted to determine the impact of GPP on patients' health-related quality of life (HRQoL) and patient-reported severity of symptoms and to compare its impact to patients with plaque psoriasis (plaque PsO). Searches were undertaken in Embase, MEDLINE and the Cochrane Library from 1 January 2002 to 15 September 2022. Screening was carried out by two reviewers independently. Outcome measures included generic (e.g. EQ-5D, SF-36) and dermatology-specific (e.g. DLQI) clinical outcome assessments, and other relevant patient-reported outcome measures (PROMs) (e.g. severity of pain measured by a numerical rating scale). Overall, 20 studies were found to be eligible for inclusion, of which seven also had data for plaque PsO. The DLQI was the most frequently reported outcome measure (16 out of 20 studies). When reported, mean DLQI (SD) scores varied from 5.7 (1.2) to 15.8 (9.6) across the studies, indicating a moderate to very large effect on HRQoL; the wide range of scores and large SDs were explained by the small population sizes (n ≤ 12 for all studies except two). Similar ranges and large SDs were also observed for other measures within individual studies. However, in general, people with GPP reported a greater impact of their skin condition on HRQoL, when compared to people with plaque PsO (i.e. higher DLQI scores) and higher severity for itch, pain and fatigue. This systematic review highlighted the need for studies with a larger population size, a better understanding of the impact of cutaneous and extracutaneous symptoms and comorbidities on HRQoL during and between GPP flares, and outcome measures specifically tailored to the unique symptoms and the natural course/history of GPP.

In silico evaluation of limited sampling strategies for individualized dosing of extended half-life factor IX concentrates in hemophilia B patients.

PURPOSE: Hemophilia B is a bleeding disorder, caused by a factor IX (FIX) deficiency. Recently, FIX concentrates with extended half-life (EHL) have become available. Prophylactic dosing of EHL-FIX concentrates can be optimized by assessment of individual pharmacokinetic (PK) parameters. To determine these parameters, limited sampling strategies (LSSs) may be applied. The study aims to establish adequate LSSs for estimating individual PK parameters of EHL-FIX concentrates using in silico evaluation. METHODS: Monte Carlo simulations were performed to obtain FIX activity versus time profiles using published population PK models for N9-GP (Refixia), rFIXFc (Alprolix), and rIX-FP (Idelvion). Fourteen LSSs, containing three or four samples taken within 8 days after administration, were formulated. Bayesian analysis was applied to obtain estimates for clearance (CL), half-life (t1/2), time to 1% (Time1%), and calculated weekly dose (Dose1%). Bias and precision of these estimates were assessed to determine which LSS was adequate. RESULTS: For all PK parameters of N9-GP, rFIXFc and rIX-FP bias was generally acceptable (range: -5% to 5%). For N9-GP, precision of all parameters for all LSSs was acceptable (< 25%). For rFIXFc, precision was acceptable for CL and Time1%, except for t1/2 (range: 27.1% to 44.7%) and Dose1% (range: 12% to 29.4%). For rIX-FP, all LSSs showed acceptable bias and precision, except for Dose1% using LSS with the last sample taken on day 3 (LSS 6 and 10). CONCLUSION: Best performing LSSs were LSS with samples taken at days 1, 5, 7, and 8 (N9-GP and rFIXFc) and at days 1, 4, 6, and 8 (rIX-FP), respectively.

The 1st year of the COVID-19 epidemic in Estonia: a population-based nationwide sequential/consecutive cross-sectional study.

OBJECTIVES: The objective of this study was to assess the population prevalence of SARS-CoV-2 and changes in the prevalence in the adult general population in Estonia during the 1st year of COVID-19 epidemic. STUDY DESIGN: This was a population-based nationwide sequential/consecutive cross-sectional study. METHODS: Using standardised methodology (population-based, random stratified sampling), 11 cross-sectional studies were conducted from April 2020 to February 2021. Data from nasopharyngeal testing and questionnaires were used to estimate the SARS-CoV-2 RNA prevalence and factors associated with test positivity. RESULTS: Between April 23, 2020, and February 2, 2021, results were available from 34,915 individuals and 27,870 samples from 11 consecutive studies. The percentage of people testing positive for SARS-CoV-2 decreased from 0.27% (95% confidence interval [CI] = 0.10%-0.59%) in April to 0.04% (95% CI = 0.00%-0.22%) by the end of May and remained very low (0.01%, 95% CI = 0.00%-0.17%) until the end of August, followed by an increase since November (0.37%, 95% CI = 0.18%-0.68%) that escalated to 2.69% (95% CI = 2.08%-2.69%) in January 2021. In addition to substantial change in time, an increasing number of household members (for one additional odds ratio [OR] = 1.15, 95% CI = 1.02-1.29), reporting current symptoms of COVID-19 (OR = 2.21, 95% CI = 1.59-3.09) and completing questionnaire in the Russian language (OR 1.85, 95% CI 1.15-2.99) were associated with increased odds for SARS-CoV-2 RNA positivity. CONCLUSIONS: SARS-CoV-2 population prevalence needs to be carefully monitored as vaccine programmes are rolled out to inform containment decisions.

Scabies itch: an update on neuroimmune interactions and novel targets.

Frequently described as 'the worst itch' one can ever experience scabies itch is the hallmark of Sarcoptes scabiei mite infestation. Notably, the itchiness often persists for weeks despite scabicides therapy. The mechanism of scabies itch is not yet fully understood, and effective treatment modalities are still missing which can severely affect the quality of life. The aim of this review is to provide an overview of the scope of itch in scabies and highlight candidate mechanisms underlying this itch. We herein discuss scabies itch, with a focus on the nature, candidate underlying mechanisms and treatment options. We also synthesize this information with current understanding of the mechanisms contributing to non-histaminergic itch in other conditions. Itch is a major problem in scabies and can lead to grave consequences. We provide the latest insights on host-mite interaction, secondary microbial infection and neural sensitization with special emphasis on keratinocytes and mast cells to better understand the mechanism of itch in scabies. Also, the most relevant current modalities remaining under investigation that possess promising perspectives for scabies itch (i.e. protease-activated receptor-2 (PAR-2) inhibitor, Mas-related G protein-coupled receptor X2 (MRGPRX2) antagonist) are discussed. Greater understanding of these diverse mechanisms may provide a rational basis for the development of improved and targeted approaches to control itch in individuals with scabies.

Timeline of functional recovery after hip fracture in seniors aged 65 and older: a prospective observational analysis.

We investigated the timeline of functional recovery after hip fracture over 12 months in adults age ≥ 65 years using objective lower extremity function tests and subjective physical functioning. Objective functional recovery was largely complete in the first 6 months, whereas subjective recovery improved up to 9 months after hip fracture. INTRODUCTION: Hip fractures are a major cause of loss of function among seniors. We assessed the timeline of objective and subjective functional recovery after hip fracture. METHODS: We conducted a prospective observational secondary analysis of a 1-year clinical trial on vitamin D and home exercise treatment and complications after hip fracture among 173 patients age ≥ 65 years (mean age 84 years; 79.2% women; 77.4% community-dwelling) conducted from January 2005 through December 2007. Lower extremity function (Timed Up and Go test (TUG), knee extensor and flexor strength) and grip strength was assessed at baseline and at 6 and 12 months follow-up. Subjective physical functioning was assessed using the SF-36 questionnaire also at 3 and 9 months follow-up. Multivariable-adjusted repeated-measures models were used to assess the timeline of functional recovery in the total population and in subgroups of patients. RESULTS: Lower extremity function including TUG (- 61.1%), knee extensor (+ 17.6%), and knee flexor (+ 11.6%) strength improved significantly in the first 6 months (P < 0.001). However, between 6 and 12 months, there was no further significant improvement for any of the functional tests. Grip strength decreased from baseline to 6 months (- 7.9%; P < 0.001) and from 6 to 12 months (- 10.8%; P < 0.001). Subjective physical functioning improved from 3 to 9 months (+ 15.2%, P < 0.001), but no longer thereafter. CONCLUSIONS: Functional recovery after hip fracture may be largely complete in the first 6 months for objective functional tests, whereas may extend up to 9 months for subjective recovery, with oldest-old, female, institutionalized, and cognitively impaired patients recovering most poorly. CLINICAL TRIALS REGISTRY (ORIGINAL TRIAL): NCT00133640.

Effects of a simple home exercise program and vitamin D supplementation on health-related quality of life after a hip fracture: a randomized controlled trial.

PURPOSE: To test the effects of vitamin D intervention and a simple home exercise program (HE) on health-related quality of life (HRQL) in the first 12 months after hip fracture. METHODS: HRQL was reported in 173 acute hip fracture patients (mean age 84 years, 79% females, 77% community dwelling) who were enrolled in the 12-month 2 × 2 factorial Zurich Hip Fracture Trial. Pre-fracture HRQL was assessed at baseline (4.2 ± 2.2 days post-surgery) and then again at 6 and 12 months after hip fracture surgery by the EuroQol EQ-5D-3L index value (EQ-5D-3L questionnaire). The effects of vitamin D intervention (2000 vs. 800 IU vitamin D3) and exercise (HE vs. no HE) or of the combined interventions on HRQL were assessed using multivariable-adjusted repeated-measures linear mixed-effects regression models. RESULTS: The EQ-5D-3L index value significantly worsened from 0.71 pre-fracture to 0.57 over 12 months, but the degree of worsening did not differ between individual or combined interventions. However, regarding only the late recovery between 6 and 12 months, the group receiving neither intervention (800 IU/day and no HE) experienced a significant further decline in the EQ-5D-3L index value (adjusted mean change = 0.08 [95% CI 0.009, 0.15], p = 0.03) while all other groups remained stable. CONCLUSION: Hip fractures have a long-lasting negative effect on HRQL up to 12 months after hip fracture. However, HE and/or 2000 IU vitamin D per day may help prevent a further decline in HRQL after the first 6 months following the acute hip fracture event.

[Differential diagnosis of acute back pain and demarcation to other specialist fields]. / Differenzialdiagnose akuter Rückenschmerz und Abgrenzung zu anderen Fachgebieten.

The treatment of patients with acute back pain is becoming increasingly more important due to the high incidence; however, acute clinical pictures from other disciplines can also primarily be symptomatic with back pain and falsely lead to a consultation with an orthopedist. In order to assure an adequate treatment of potentially critical patients, it is absolutely necessary to exclude life-threatening differential diagnoses by a structured study of the patient history, investigations and diagnostics. Depending on the suspected diagnosis, necessary first aid measures and emergency referral to the appropriate specialist department should be initiated. This article gives an overview of selected clinical pictures and tries to look beyond the field of orthopedics.

[Geriatric patients in orthopedics]. / Der geriatrische Patient in der Orthopädie.

The treatment of geriatric patients in orthopedics is increasing in importance due to the demographic changes. In order to ensure an adequate treatment it is absolutely necessary to address age-specific risk factors. The decision between conservative and surgical treatment has to be made with the patient and the relatives together, taking all comorbidities into consideration and with the objective of preserving the quality of life. This decision also includes the fact that not only the immediate perioperative course but also hospital morbidity and long-term outcome are substantially influenced by typical age-related risk factors. Due to the advancement of interdisciplinary cooperation and an increase in quality and quantity of publications in this field, there are increasingly more unified treatment recommendations for geriatric patients in orthopedics.

Association between subclinical thyroid dysfunction and change in bone mineral density in prospective cohorts.

BACKGROUND: Subclinical hyperthyroidism (SHyper) has been associated with increased risk of hip and other fractures, but the linking mechanisms remain unclear. OBJECTIVE: To investigate the association between subclinical thyroid dysfunction and bone loss. METHODS: Individual participant data analysis was performed after a systematic literature search in MEDLINE/EMBASE (1946-2016). Two reviewers independently screened and selected prospective cohorts providing baseline thyroid status and serial bone mineral density (BMD) measurements. We classified thyroid status as euthyroidism (thyroid-stimulating hormone [TSH] 0.45-4.49 mIU/L), SHyper (TSH < 0.45 mIU/L) and subclinical hypothyroidism (SHypo, TSH ≥ 4.50-19.99 mIU/L) both with normal free thyroxine levels. Our primary outcome was annualized percentage BMD change (%ΔBMD) from serial dual X-ray absorptiometry scans of the femoral neck, total hip and lumbar spine, obtained from multivariable regression in a random-effects two-step approach. RESULTS: Amongst 5458 individuals (median age 72 years, 49.1% women) from six prospective cohorts, 451 (8.3%) had SHypo and 284 (5.2%) had SHyper. During 36 569 person-years of follow-up, those with SHyper had a greater annual bone loss at the femoral neck versus euthyroidism: %ΔBMD = -0.18 (95% CI: -0.34, -0.02; I2 = 0%), with a nonstatistically significant pattern at the total hip: %ΔBMD = -0.14 (95% CI: -0.38, 0.10; I2 = 53%), but not at the lumbar spine: %ΔBMD = 0.03 (95% CI: -0.30, 0.36; I2 = 25%); especially participants with TSH < 0.10 mIU/L showed an increased bone loss in the femoral neck (%Δ BMD = -0.59; [95% CI: -0.99, -0.19]) and total hip region (%ΔBMD = -0.46 [95% CI: -1.05, -0.13]). In contrast, SHypo was not associated with bone loss at any site. CONCLUSION: Amongst adults, SHyper was associated with increased femoral neck bone loss, potentially contributing to the increased fracture risk.

Diagnostic accuracy of point-of-care ultrasound for evaluation of early blood-induced joint changes: Comparison with MRI.

INTRODUCTION: Recurrent joint bleeding is the hallmark of haemophilia. Synovial hypertrophy observed with Magnetic Resonance Imaging (MRI) is associated with an increased risk of future joint bleeding. AIM: The aim of this study was to investigate whether point-of-care ultrasound (POC-US) is an accurate alternative for MRI for the detection of early joint changes. METHODS: In this single centre diagnostic accuracy study, bilateral knees and ankles of haemophilia patients with no or minimal arthropathy on X-rays were scanned using POC-US and 3 Tesla MRI. POC-US was performed by 1 medical doctor, blinded for MRI, according to the "Haemophilia Early Arthropathy Detection with Ultrasound" (HEAD-US) protocol. MRIs were independently scored by 2 radiologists, blinded for clinical data and ultrasound results. Diagnostic accuracy parameters were calculated with 95% confidence intervals (CI). RESULTS: Knees and ankles of 24 haemophilia patients (96 joints), aged 18-34, were studied. Synovial hypertrophy on MRI was observed in 20% of joints. POC-US for synovial tissue was correct (overall accuracy) in 97% (CI: 91-99) with a positive predictive value of 94% (CI: 73-100) and a negative predictive value of 97% (CI: 91-100). The overall accuracy of POC-US for cartilage abnormalities was 91% (CI: 83-96) and for bone surface irregularities 97% (CI: 91-99). CONCLUSION: POC-US could accurately assess synovial hypertrophy, bone surface irregularities and cartilage abnormalities in haemophilia patients with limited joint disease. As POC-US is an accurate and available alternative for MRI, it can be used for routine evaluation of early joint changes.

BAY 94-9027, a PEGylated recombinant factor VIII, exhibits a prolonged half-life and higher area under the curve in patients with severe haemophilia A: Comprehensive pharmacokinetic assessment from clinical studies.

INTRODUCTION: Recombinant factor VIII (rFVIII) products with extended half-lives, such as BAY 94-9027, can potentially maintain higher FVIII levels for longer periods of time, thus providing improved bleeding protection vs standard-acting FVIII products. AIM: To characterize the pharmacokinetic (PK) profile of BAY 94-9027 from phase 1, phase 2/3 (PROTECT VIII) and phase 3 (PROTECT VIII Kids) clinical trials in adults, adolescents and children with severe haemophilia A METHODS: Patients with severe haemophilia A (FVIII <1%) with >50 FVIII exposure days (EDs) and no history of inhibitors were included in the phase 1 (18-65 years, ≥150 EDs), PROTECT VIII (12-65 years, ≥150 EDs) and PROTECT VIII Kids (<12 years, >50 EDs) trials. PK parameters were assessed following a 25-IU/kg or 60-IU/kg BAY 94-9027 dose in the phase 1 study after the first and repeated infusion, in PROTECT VIII after the first and repeated 60-IU/kg infusion and in PROTECT VIII Kids after a single 60-IU/kg infusion. The chromogenic assay was used to assess FVIII activity. RESULTS: Compared with sucrose-formulated rFVIII, BAY 94-9027 had reduced clearance that resulted in a ~1.4-fold increase in half-life and dose-normalized area under the curve (AUC). The BAY 94-9027 PK profile was comparable after single- and repeated-dose administrations. Dose-proportional increases were observed between 25- and 60-IU/kg administrations. BAY 94-9027 PK characteristics were age dependent, consistent with other FVIII products. CONCLUSIONS: BAY 94-9027 shows an extended half-life and increased AUC vs standard-acting FVIII products. These PK characteristics will result in higher FVIII levels for longer duration.

Vaccinations are not associated with inhibitor development in boys with severe haemophilia A.

BACKGROUND: Inhibitor development in previously untreated patients (PUPs) with severe haemophilia A is a multifactorial event. It is unknown whether paediatric vaccinations given in close proximity to factor VIII (FVIII) are associated with inhibitor development. OBJECTIVE: To assess whether paediatric vaccinations in close proximity to FVIII within the first 75 exposure days (EDs) are associated with inhibitor development in PUPs with severe haemophilia A. METHODS: We included 375 PUPs with severe haemophilia A (<0.01 IU/mL) from the PedNet Registry who had received vaccinations between the first and 75th ED or inhibitor development. Inhibitor risk was compared between patients who did and who did not receive vaccinations within 24, 72 or 120 hours of FVIII infusion. Unadjusted and adjusted hazard ratios were calculated for any or repeated vaccinations in close proximity to FVIII, using Cox regression. RESULTS: Inhibitor development occurred in 77 of 375 patients (20.5%). Overall inhibitor development appeared similar or lower in patients receiving vaccinations in close proximity to FVIII as compared to patients receiving vaccinations without FVIII: for 24 hours, this was 19.2% and 21.4% (P = .186), for 72 hours, 16.4% and 27.3% (P = .023) and for 120 hours, 18.3% and 25.0% (P = .085), respectively. CONCLUSION: We found no association between vaccinations given in close proximity to FVIII exposure within the first 75 EDs and inhibitor development. Our data do not support avoiding administration of FVIII at time of routine vaccinations.

Measuring activities and participation in persons with haemophilia: A systematic review of commonly used instruments.

INTRODUCTION: Monitoring clinical outcome in persons with haemophilia (PWH) is essential in order to provide optimal treatment for individual patients and compare effectiveness of treatment strategies. Experience with measurement of activities and participation in haemophilia is limited and consensus on preferred tools is lacking. AIM: The aim of this study was to give a comprehensive overview of the measurement properties of a selection of commonly used tools developed to assess activities and participation in PWH. METHODS: Electronic databases were searched for articles that reported on reliability, validity or responsiveness of predetermined measurement tools (5 self-reported and 4 performance based measurement tools). Methodological quality of the studies was assessed according to the COSMIN checklist. Best evidence synthesis was used to summarize evidence on the measurement properties. RESULTS: The search resulted in 3453 unique hits. Forty-two articles were included. The self-reported Haemophilia Acitivity List (HAL), Pediatric HAL (PedHAL) and the performance based Functional Independence Score in Haemophilia (FISH) were studied most extensively. Methodological quality of the studies was limited. Measurement error, cross-cultural validity and responsiveness have been insufficiently evaluated. CONCLUSION: Albeit based on limited evidence, the measurement properties of the PedHAL, HAL and FISH are currently considered most satisfactory. Further research needs to focus on measurement error, responsiveness, interpretability and cross-cultural validity of the self-reported tools and validity of performance based tools which are able to assess limitations in sports and leisure activities.

Does chemical preconditioning contribute to the effectiveness of scaling and root planing? An in vitro pilot investigation.

OBJECTIVES: A solution based on hypochlorite and amino acids was introduced to improve cleaning efficacy on the root surfaces. The purpose of this in vitro pilot study was to evaluate the time reduction and number of strokes required to clean untreated root surfaces in vitro. METHODS: Sixty extracted human teeth displaying areas with subgingival calculus were assigned equally to one of three treatment groups (n = 20) according to the size of occupied areas, estimated by the number of pixels. The groups were assigned to either 30 s penetration time (I) or 300 s (II) or no pretreatment application (III). The weight for instrumentation was calibrated for a M25A curette (Deppeler/Switzerland) with 500 g. A new set of tools was used for each group, and each instrument was sharpened after single use by an EasySharp Device (Deppeler/Switzerland). RESULTS: The time (in seconds) for instrumentation was recorded as follows: Group I: 32/23.5/50 (median/first quartile/third quartile); group II: 33/20/52.5; group III: 46.5/35.5/52.3. The results for the numbers of strokes were: Group I: 18/14.3/28; group II: 18.5/13/30.5; group III: 17.5/15/25. No statistically significant differences (P < 0.05) were found between the three groups for the variables 'time' and 'number of strokes'. CONCLUSIONS: Within the limits of this in vitro pilot study, preconditioning of the calculus on root surfaces with an alkaline solution failed to reduce the number of strokes and time of instrumentation significantly.

Testing the Efficacy of Contrast-Enhanced Ultrasound in Detecting Transplant Rejection Using a Murine Model of Heart Transplantation.

One of the key unmet needs to improve long-term outcomes of heart transplantation is to develop accurate, noninvasive, and practical diagnostic tools to detect transplant rejection. Early intragraft inflammation and endothelial cell injuries occur prior to advanced transplant rejection. We developed a novel diagnostic imaging platform to detect early declines in microvascular perfusion (MP) of cardiac transplants using contrast-enhanced ultrasonography (CEUS). The efficacy of CEUS in detecting transplant rejection was tested in a murine model of heart transplants, a standard preclinical model of solid organ transplant. As compared to the syngeneic groups, a progressive decline in MP was demonstrated in the allografts undergoing acute transplant rejection (40%, 64%, and 92% on days 4, 6, and 8 posttransplantation, respectively) and chronic rejection (33%, 33%, and 92% on days 5, 14, and 30 posttransplantation, respectively). Our perfusion studies showed restoration of MP following antirejection therapy, highlighting its potential to help monitor efficacy of antirejection therapy. Our data suggest that early endothelial cell injury and platelet aggregation contributed to the early MP decline observed in the allografts. High-resolution MP mapping may allow for noninvasive detection of heart transplant rejection. The data presented have the potential to help in the development of next-generation imaging approaches to diagnose transplant rejection.

Gender-specific association between dietary acid load and total lean body mass and its dependency on protein intake in seniors.

Diet-related mild metabolic acidosis may play a role in the development of sarcopenia. We investigated the relationship between dietary acid load and total lean body mass in male and female seniors age ≥ 60 years. We found that a more alkaline diet was associated with a higher %TLM only among senior women. INTRODUCTION: The aim of this study was to determine if dietary acid load is associated with total lean body mass in male and female seniors age ≥ 60 years. METHODS: We investigated 243 seniors (mean age 70.3 ± 6.3; 53% women) age ≥ 60 years who participated in the baseline assessment of a clinical trial on vitamin D treatment and rehabilitation after unilateral knee replacement due to severe knee osteoarthritis. The potential renal acid load (PRAL) was assessed based on individual nutrient intakes derived from a food frequency questionnaire. Body composition including percentage of total lean body mass (%TLM) was determined using dual-energy X-ray absorptiometry. Cross-sectional analyses were performed for men and women separately using multivariable regression models controlling for age, physical activity, smoking status, protein intake (g/kg BW per day), energy intake (kcal), and serum 25-hydroxyvitamin D concentration. We included a pre-defined subgroup analysis by protein intake (< 1 g/kg BW day, > 1 g/kg BW day) and by age group (< 70 years, ≥ 70 years). RESULTS: Adjusted %TLM decreased significantly across PRAL quartiles only among women (P trend = 0.004). Moreover, in subgroup analysis, the negative association between the PRAL and %TLM was most pronounced among women with low protein intake (< 1 g/kg BW per day) and age below 70 years (P = 0.002). Among men, there was no association between the PRAL and %TLM. CONCLUSION: The association between dietary acid load and %TLM seems to be gender-specific, with a negative impact on total lean mass only among senior women. Therefore, an alkaline diet may be beneficial for preserving total lean mass in senior women, especially in those with low protein intake.

Observation of Mollow Triplets with Tunable Interactions in Double Lambda Systems of Individual Hole Spins.

Although individual spins in quantum dots have been studied extensively as qubits, their investigation under strong resonant driving in the scope of accessing Mollow physics is still an open question. Here, we have grown high quality positively charged quantum dots embedded in a planar microcavity that enable enhanced light-matter interactions. Under a strong magnetic field in the Voigt configuration, individual positively charged quantum dots provide a double lambda level structure. Using a combination of above-band and resonant excitation, we observe the formation of Mollow triplets on all optical transitions. We find that when the strong resonant drive power is used to tune the Mollow-triplet lines through each other, we observe anticrossings. We also demonstrate that the interaction that gives rise to the anticrossings can be controlled in strength by tuning the polarization of the resonant laser drive. Quantum-optical modeling of our system fully captures the experimentally observed spectra and provides insight on the complicated level structure that results from the strong driving of the double lambda system.

Moraxella catarrhalis induces CEACAM3-Syk-CARD9-dependent activation of human granulocytes.

The human restricted pathogen Moraxella catarrhalis is an important causal agent for exacerbations in chronic obstructive lung disease in adults. In such patients, increased numbers of granulocytes are present in the airways, which correlate with bacteria-induced exacerbations and severity of the disease. Our study investigated whether the interaction of M. catarrhalis with the human granulocyte-specific carcinoembryonic antigen-related cell adhesion molecule (CEACAM)-3 is linked to NF-κB activation, resulting in chemokine production. Granulocytes from healthy donors and NB4 cells were infected with M. catarrhalis in the presence of different inhibitors, blocking antibodies and siRNA. The supernatants were analysed by enzyme-linked immunosorbent assay for chemokines. NF-κB activation was determined using a luciferase reporter gene assay and chromatin-immunoprecipitation. We found evidence that the specific engagement of CEACAM3 by M. catarrhalis ubiquitous surface protein A1 (UspA1) results in the activation of pro-inflammatory events, such as degranulation of neutrophils, ROS production and chemokine secretion. The interaction of UspA1 with CEACAM3 induced the activation of the NF-κB pathway via Syk and the CARD9 pathway and was dependent on the phosphorylation of the CEACAM3 ITAM-like motif. These findings suggest that the CEACAM3 signalling in neutrophils is able to specifically modulate airway inflammation caused by infection with M. catarrhalis.

Monitoring joint health in haemophilia: Factors associated with deterioration.

INTRODUCTION: Joint bleeds in patients with haemophilia may result in haemophilic arthropathy. Monitoring joint health is essential for identifying early signs of deterioration and allows timely adjustment of treatment. AIM: The aim was to describe changes in joint health over 5-10 years follow-up and identify factors associated with joint health deterioration in patients with haemophilia. METHODS: A post hoc analysis was performed from previous cohort studies in patients with moderate/severe haemophilia, ≥16 years. Joint health of ankles, knees and elbows was measured with the Haemophilia Joint Health Score (HJHS) from 2006-2008 (T0) to 2011-2016 (T1). Analyses were performed on patient level (ΔHJHS-total) and joint level (ΔHJHS-joint). Deterioration was defined as ΔHJHS-total ≥4 and ΔHJHS-joint ≥2. RESULTS: Sixty-two patients (median age 25, 73% severe haemophilia, median [interquartile range] 0.0 [0.0;2.0] joint bleeds between T0 to T1) were included. After median 8 years, HJHS-total deteriorated in 37% and HJHS-joint in 17%. Ankle joints (31%) showed deterioration more often than elbows (19%) and knees (3%). Deterioration of HJHS-total was only associated with severe haemophilia. Deterioration of HJHS-joint was weakly associated with a lower HJHS at baseline and more self-reported limitations in activities, and strongly with more joint bleeds between T0 and T1 and presence of synovitis. CONCLUSION: In 37% of patients with moderate/severe haemophilia and low joint bleeding rates, joint health deteriorated over 5-10 years. Ankle and elbow joints showed deterioration most frequently. Factors found in this study help to identify which joints need frequent monitoring in patients with haemophilia with access to early prophylaxis.

Choosing outcome assessment tools in haemophilia care and research: a multidisciplinary perspective.

INTRODUCTION: The implementation of early long-term, regular clotting factor concentrate (CFC) replacement therapy ('prophylaxis') has made it possible to offer boys with haemophilia a near normal life. Many different regimens have reported favourable results, but the optimum treatment regimens have not been established and the cost of prophylaxis is very high. Both for optimizing treatment and reimbursement issues, there is a need to provide objective evidence of both short- and long-term results and benefits of prophylactic regimens. AIMS: This report presents a critical review of outcome measures for use in the assessment of musculoskeletal health in persons with haemophilia according to the International Classification of Functioning, Disability and Health (ICF). This framework considers structural and functional changes, activities and participation in a context of both personal and environmental factors. METHODS: Results were generated by a combination of a critical review of available literature plus expert opinion derived from a two day consensus conference between 48 health care experts from different disciplines involved in haemophilia assessment and care. Outcome tools used in haemophilia were reviewed for reliability and validity in different patient groups and for resources required. RESULTS AND CONCLUSION: Recommendations for choice of outcome tools were made according to the ICF domains, economic setting, and reason for use (clinical or research). The next step will be to identify a 'core' set of outcome measures for use in clinical care or studies evaluating treatment.