Corrigendum to "Hydroxychloroquine Use in Lupus Patients during Pregnancy Is Associated with Longer Pregnancy Duration in Preterm Births".

[This corrects the article DOI: 10.1155/2017/2810202.].

The multi-biomarker disease activity test for assessing response to treatment strategies using methotrexate with or without prednisone in the CAMERA-II trial.

OBJECTIVES: The CAMERA-II trial compared two tight-control, treat-to-target strategies, initiating methotrexate with prednisone (MTX+pred) or MTX with placebo (MTX+plac), in early RA-patients. The multi-biomarker disease activity (MBDA) blood test objectively measures RA disease activity with a score of 1-100. In CAMERA-II, response profiles of the MBDA score, its individual biomarkers, and DAS28 were assessed. METHODS: We evaluated 92 patients from CAMERA-II of whom clinical data and serum for MBDA testing at baseline and ≥ 1 time-point from months 1, 2, 3, 4, 5, 6, 9, or 12 were available. Changes (∆) from baseline for DAS28 and MBDA score and comparisons of ∆DAS28 and ∆MBDA score over time within the MTX+pred versus the MTX+plac strategy were tested for significance with t tests. Changes in biomarker concentration from baseline to months 1-5 were tested with Wilcoxon signed rank test and tested for difference between treatment arms by Mann-Whitney U test. RESULTS: MBDA and DAS28 showed similar response profiles, with gradual improvement over the first 6 months in the MTX+plac group, and in the MTX+pred group faster improvement during month 1, followed by gradual improvement. The 12 MBDA biomarkers could be grouped into 4 categories of response profiles, with significant responses for 4 biomarkers during the MTX+plac strategy and 9 biomarkers during the MTX+pred strategy. CONCLUSIONS: MBDA tracked treatment response in CAMERA-II similarly to DAS28. More individual MBDA biomarkers tracked treatment response to MTX+pred than to MTX+plac. Four response profiles could be observed. TRIAL REGISTRATION: CAMERA-II International Standard Randomised Controlled Trial Number: ISRCTN 70365169 . Registered on 29 March 2006, retrospectively registered.

Efficacy and safety of selective glucocorticoid receptor modulators in comparison to glucocorticoids in arthritis, a systematic review.

BACKGROUND: Long-term treatment with glucocorticoids (GCs) plays an important role in the management of arthritis patients, although the efficacy/safety balance is unfavorable. Alternatives with less (severe) adverse effects but with good efficacy are needed. Selective GC receptor modulators (SGRMs) are designed to engage the GC receptor with dissociative characteristics: transactivation of genes, which is mainly responsible for unwanted effects, is less strong while trans-repression of genes, reducing inflammation, is maintained. It is expected that SGRMs thus have a better efficacy/safety balance than GCs. A systematic review providing an overview of the evidence in arthritis is lacking. OBJECTIVE: To systematically review the current literature on efficacy and safety of oral SGRMs in comparison to GCs in arthritis. METHODS: A search was performed in Medline, Embase and the Cochrane Library, from inception dates of databases until May 2017. Experimental studies involving animal arthritis models or human material of arthritis patients, as well as clinical studies in arthritis patients were included, provided they reported original data. All types of arthritis were included. Data was extracted on the SGRM studied and on the GC used as reference standard; the design or setting of the study was extracted as well as the efficacy and safety results. RESULTS: A total of 207 articles was retrieved of which 17 articles were eligible for our analysis. Two studies concerned randomized controlled trials (RCT), five studies were pre-clinical studies using human material, and 10 studies involved pre-clinical animal models (acute and/or chronic arthritis induced in mice or rats). PF-04171327, the only compound investigated in a clinical trial setting, had a better efficacy/safety balance compared to GCs: better clinical anti-inflammatory efficacy and similar safety. CONCLUSION: Studies assessing both efficacy and safety of SGRMs are scarce. There is limited evidence for dissociation of anti-inflammatory and metabolic effects of the SGRMs studied. Development of many SGRMs is haltered in a preclinical phase. One SGRM showed a better clinical efficacy/safety balance.

Hydroxychloroquine Use in Lupus Patients during Pregnancy Is Associated with Longer Pregnancy Duration in Preterm Births.

OBJECTIVE: To investigate the effect of hydroxychloroquine (HCQ) in pregnant women with systemic lupus erythematosus (SLE). METHODS: In SLE pregnancies of a single Dutch center (2000-2015), lupus activity and flares before and during pregnancy and postpartum were assessed using the SLE Disease Activity Index (SLEDAI)/SLEPDAI (SLEDAI adjusted for pregnancy). The association between HCQ use and pregnancy outcomes (early spontaneous abortion, fetal death, and preterm and term live birth) was analyzed using generalized estimating equations (GEE) accounting for the occurrence of multiple pregnancies per patient. Analyses were adjusted for antiphospholipid antibody (aPL) status. RESULTS: 110 pregnancies (63 mostly Caucasian patients) were included, of which, in 30, HCQ was used; overall occurrence of flares was low (non-HCQ group: 5 mild (6.4%) and 2 severe (2.6%); HCQ group: 2 mild (6.7%) and no severe flares). The HCQ group showed a trend towards lower dosage of prednisone (OR 0.2 (95% CI 0.0-1.4); p = 0.10). Pregnancy outcomes were comparable between groups. Among preterm live births, pregnancy duration was significantly longer in HCQ users (2.4 weeks (95% CI 1.0-3.8; p ≤ 0.001)). CONCLUSION: HCQ use was associated with longer pregnancy duration in the vulnerable preterm birth population, underscoring the beneficial effect of HCQ use during pregnancy.

Acute kidney injury following primary hip and knee arthroplasty surgery.

Acute kidney injury (AKI) is a recognised postoperative complication following primary hip/knee arthroplasty surgery. The aim of this study was to determine causative and potentially modifiable risk factors associated with postoperative AKI. Standard data were collected for 413 consecutive arthroplasty patients, both retrospectively and prospectively. Univariate and multivariate analyses were performed to identify any potential causative factors. Eight percent of patients developed postoperative AKI. Univariate analysis found increasing age, history of previous chronic kidney disease and requirement for postoperative intravenous fluids to be risk factors for AKI. The multivariate regression analysis model identified age and volume of postoperative fluid prescription as predictive of postoperative AKI. Antibiotic regime and prescription of non-steroidal anti-inflammatory drugs had no significant effect on the risk of AKI. No patients required dialysis but length of stay increased by 50% in the AKI group. Postoperative AKI may result in significant postoperative morbidity and increased length of stay, and may necessitate invasive therapies such as dialysis. Episodes of AKI could also predispose to future similar episodes and are associated with a long-term decrease in baseline renal function. This study has demonstrated that the identified risk factors are generally non-modifiable. Further work is suggested to determine whether targeted interventions in high risk patients would reduce the incidence of AKI.

Autonomic Dysfunction Precedes Development of Rheumatoid Arthritis: A Prospective Cohort Study.

BACKGROUND: Heart rate variability (HRV) is a validated method to establish autonomic nervous system (ANS) activity. Rheumatoid arthritis (RA) is accompanied by ANS imbalance. We hypothesized that ANS dysfunction may precede the development of RA, which would suggest that it plays a role in its etiopathogenesis. METHODS: First, we assessed HRV parameters in supine (resting) and upright (active) position in healthy subjects (HS, n=20), individuals at risk of developing arthritis (AR subjects, n=50) and RA patients (RA, n=20). Next, we measured resting heart rate (RHR), a parasympathetic HRV parameter, in an independent prospective cohort of AR subjects (n=45). We also evaluated expression levels of the parasympathetic nicotinic acetylcholine receptor type 7 (α7nAChR) on circulating monocytes. FINDINGS: Both AR subjects (68 beats per minute (bpm), interquartile range (IQR) 68-73) and RA patients (68bpm, IQR 62-76) had a significantly higher RHR compared to HS (60bpm, IQR 56-63). RHR was significantly higher at baseline in individuals who subsequently developed arthritis. Expression levels of α7nAChR were lower in AR subjects with RHR ≥70bpm compared to those with RHR <70bpm, consistent with reduced activity of the parasympathetic cholinergic anti-inflammatory pathway. INTERPRETATION: These data support the notion that autonomic dysfunction precedes the development of RA.

Sensory dynamic orthoses in mild to moderate upper limb tremor in multiple sclerosis: a mixed methods feasibility study.

OBJECTIVE: To explore the feasibility of conducting a Phase III randomized controlled trial evaluating sensory dynamic orthoses for upper limb tremor in multiple sclerosis. DESIGN: Mixed methods: double blind randomized placebo controlled pilot study and semi-structured interviews. SETTING: Rehabilitation centre. SUBJECTS: A total of 21 people with multiple sclerosis with upper limb tremor. INTERVENTIONS: Participants received a sensory dynamic orthosis sleeve or a non-compressive sleeve (placebo) that they wore eight hours a day, for nine weeks. MAIN MEASURES: Outcomes were completed at baseline and nine weeks. The primary outcome measure was the Fahn-Tolosa-Marin (FAHN) Tremor Rating Scale. Secondary outcome measures included the: Action Research Arm Test, Canadian Occupational Performance Measure, Psychological Impact of Assistive Device Scale and the Nine-hole Peg Test. RESULTS: Both sleeves were acceptable, although achieving a good fit was an issue. There were no significant between-group differences for the primary outcome measure. The median ± interquartile range change scores were 0.5 ±6.5 and 2 ±8 for the placebo and treatment group, respectively. The median ± interquartile range Canadian Occupational Performance Measure (performance subscale) demonstrated significant improvements ( p = 0.01) for the placebo group (1.1 ±1.65) compared with the treatment group (0 ±1.2). There was no between-group differences in the satisfaction subscale. The primary outcome measure was sensitive to detect change; however the Action Research Arm Test was not responsive in this study population. CONCLUSION: Undertaking an randomized controlled trial would be feasible and a minimum of 200 participants would be needed for a fully powered, definitive randomized controlled trial.

Impact of socioeconomic status and gender on glycaemic control, cardiovascular risk factors and diabetes complications in type 1 and 2 diabetes: a population based analysis from a Scottish region.

AIMS: In this cross-sectional study, the aims were to investigate the association of the socioeconomic status and gender on the prevalence of type 1 and 2 diabetes, glycaemic control, cardiovascular risk factors plus the complications of diabetes in a population-based analysis in the county of Ayrshire and Arran, Scotland. METHODS: Quality Outcome Framework data was obtained from General Practices in Ayrshire and Arran, Scotland (n=15,351 patients). RESULTS: In type 1 diabetes, there was an increasing linear trend in HbA1c across deprivation levels (P<0.01). In type 1 diabetes, obesity in women (P<0.01) and increased non-fasting triglyceride levels in both men and women were associated with deprivation (P<0.05). In type 2 diabetes, there was a significant prevalence trend with deprivation for women (P<0.01) but not with glycaemic control (P=0.12). Smoking, ischaemic heart disease and neuropathy (P<0.01) were all associated with increasing deprivation with gender differences. In type 2 diabetes, reduced HDL cholesterol (P<0.01 both genders), and percentage of people on lipid lowering therapy (men P<0.05; women P<0.01) were associated with deprivation. Smoking, ischaemic heart disease, peripheral vascular disease and neuropathy plus foot ulcers (P<0.05) were all associated with increasing deprivation with gender differences. CONCLUSIONS: Socioeconomic status and gender are associated with changes in glycaemic control and cardiovascular risk factors plus complication development in both type 1 and 2 diabetes. The mechanisms are unclear but follow-up of these patients should allow greater understanding.

Gender differences and patterns of cardiovascular risk factors in Type 1 and Type 2 diabetes: a population-based analysis from a Scottish region.

AIM: To explore the gender differences, along with the relationships between BMI, glycaemic control, cardiovascular risk factors and the prevalence of diabetes complications, in a representative population-based group of people with Type 1 and Type 2 diabetes. METHODS: Data were obtained from general practices in Ayrshire and Arran, Scotland for 15 351 patients. RESULTS: In the cohort with Type 1 diabetes, after adjustment for age, men had a significantly lower BMI (P = 0.007) and significantly lower total cholesterol (P = 0.005), HDL-cholesterol (P = 2.5*10(-17)) and HbA1c levels (P = 0.003) than women. By contrast, men had higher blood pressure, both systolic (P = 0.034) and diastolic (P = 0.0003), and higher non-fasting triglyceride levels (P = 0.001). Men with Type 1 diabetes had a higher prevalence of neuropathy (P = 0.021). Among people with Type 2 diabetes, men had a significantly lower BMI (P = 4.26*10(-37)), and significantly lower total cholesterol (P = 2.96*10(-62)) and HDL-cholesterol levels (P = 8.25*10(-141)) but higher non-fasting triglyceride levels (P = 0.0002). In Type 2 diabetes, men had a higher prevalence of ischaemic heart disease (P = 1.66*10(-25)), stroke (P = 0.002) and peripheral vascular disease (P = 1.68*10(-12)), while women were older (P = 4.83*10(-23)), heavier and had a higher prevalence of hypertension (P = 5.32*10(-12)). More people with Type 2 diabetes were on lipid-lowering treatment (84.7 vs 52.4%; P = 5.51*10(-8)) than were those with Type 1 diabetes. The prevalence of retinopathy was higher among non-smokers thank smokers in people with both Type 1 and Type 2 diabetes (Type 1, P = 0.016; Type 2, P = 0.001). CONCLUSIONS: The study shows gender differences between Type 1 and 2 diabetes that are of clinical significance and require further investigation. Follow-up of the patients included in the present study should give us much greater understanding of the importance of gender in the development of metabolic abnormalities and diabetes complications.

Features of the synovium of individuals at risk of developing rheumatoid arthritis: implications for understanding preclinical rheumatoid arthritis.

OBJECTIVE: Findings from previous studies have suggested that subclinical inflammation of the synovium does not coincide with the appearance of rheumatoid arthritis (RA)-specific autoantibodies. This study was undertaken to examine the relationship between the presence of autoantibodies, changes in the synovium, and development of arthritis over time in a markedly larger, prospective study. METHODS: Fifty-five individuals who were IgM rheumatoid factor positive and/or anti-citrullinated protein antibody (ACPA) positive (detected by the anti-cyclic citrullinated peptide antibody test) and who were without any evidence of arthritis upon physical examination were included in the study. ACPAs were subsequently also detected using a multiplex chip-based assay. All individuals underwent magnetic resonance imaging and mini-arthroscopic synovial biopsy sampling of a knee joint at inclusion and were prospectively followed up. Proportional hazards regression analysis was performed to investigate whether changes in the synovium were associated with the onset of arthritis. RESULTS: Fifteen individuals (27%) developed arthritis after a median followup time of 13 months (interquartile range 6-27 months; range 1-47 months). No overt synovial inflammation was observed, but CD3+ T cell numbers in the biopsy tissue showed a borderline association with subsequent development of clinically manifest arthritis (hazard ratio 2.8, 95% confidence interval [95% CI] 0.9-9.1; P = 0.088). In addition, the presence of CD8+ T cells was associated with ACPA positivity (odds ratio [OR] 16.0, 95% CI 1.7-151.1) and with the total number of ACPAs present (OR 1.4, 95% CI 1.0-1.8). CONCLUSION: These findings confirm and extend previous results showing the absence of clearcut synovial inflammation in individuals having systemic autoimmunity associated with RA. However, subtle infiltration by synovial T cells may precede the signs and symptoms of arthritis in preclinical RA.

Rheumatoid arthritis synovial tissue harbours dominant B-cell and plasma-cell clones associated with autoreactivity.

OBJECTIVE: To identify potential autoreactive B-cell and plasma-cell clones by quantitatively analysing the complete human B-cell receptor (BCR) repertoire in synovium and peripheral blood in early and established rheumatoid arthritis (RA). METHODS: The BCR repertoire was screened in synovium and blood of six patients with early RA (ERA) (<6 months) and six with established RA (ESRA) (>20 months). In two patients, the repertoires in different joints were compared. Repertoires were analysed by next-generation sequencing from mRNA, generating >10 000 BCR heavy-chain sequence reads per sample. For each clone, the degree of expansion was calculated as the percentage of the total number of reads encoding the specific clonal sequence. Clones with a frequency ≥ 0.5% were considered dominant. RESULTS: Multiple dominant clones were found in inflamed synovium but hardly any in blood. Within an individual patient, the same dominant clones were detected in different joints. The majority of the synovial clones were class-switched; however, the fraction of clones that expressed IgM was higher in ESRA than ERA patients. Dominant synovial clones showed autoreactive features: in ERA in particular the clones were enriched for immunoglobulin heavy chain gene segment V4-34 (IGHV4-34) and showed longer CDR3 lengths. Dominant synovial clones that did not encode IGHV4-34 also had longer CDR3s than peripheral blood. CONCLUSIONS: In RA, the synovium forms a niche where expanded--potentially autoreactive--B cells and plasma cells reside. The inflamed target tissue, especially in the earliest phase of disease, seems to be the most promising compartment for studying autoreactive cells.

The cellular composition of lymph nodes in the earliest phase of inflammatory arthritis.

OBJECTIVES: Rheumatoid arthritis (RA) is an immune-mediated inflammatory disease of unknown aetiology. Recent work has shown that systemic autoimmunity precedes synovial inflammation, and animal models have suggested that changes in the lymph nodes may precede those in the synovial tissue. Therefore, we investigated the cellular composition of the lymph node in the earliest phases of inflammatory arthritis. METHODS: Thirteen individuals positive for immunoglobulin M (IgM) rheumatoid factor and/or anticitrullinated protein antibodies without arthritis were included. Additionally, we studied 14 early arthritis patients (arthritis duration ≤6 months, naïve for disease-modifying antirheumatic drugs), and eight healthy controls. All subjects underwent ultrasound-guided inguinal lymph node biopsy. Different T- and B-lymphocyte subsets were analysed by multicolour flow cytometry. RESULTS: There was an increase in activated CD69 CD8 T cells and CD19 B cells in early arthritis patients compared with healthy controls. We also observed a trend towards increased CD19 B cells in autoantibody-positive individuals without arthritis compared with healthy controls. CONCLUSIONS: This exploratory study suggests that there is increased immune cell activation within lymph nodes of early arthritis patients as well as in autoantibody-positive individuals at risk of developing RA. This method provides a unique tool to investigate immunological changes in the lymph node compartment in the earliest phases of inflammatory arthritis.

Comparison of Maddrey Discriminant Function, Child-Pugh Score and Glasgow Alcoholic Hepatitis Score in predicting 28-day mortality on admission in patients with acute hepatitis.

BACKGROUND: Acute hepatitis (AH) in patients with chronic alcoholic liver disease is associated with high mortality. It is therefore vital to identify patients at greatest risk of mortality who may benefit from aggressive intervention. The scoring systems used to assess the severity of AH [Maddrey Discriminant Function (mDF), Child-Pugh Score (CPS) and Glasgow Alcoholic Hepatitis Score (GAHS)] have shown to be useful in determining severity and predicting mortality in these patients. AIM: The aim of this study was to compare three scoring systems in predicting 28-day mortality in AH on admission. METHOD AND RESULTS: Case notes of 82 patients with AH were reviewed on admission; mDF, CPS, GAHS were calculated and their outcome recorded on day 28. Thirty-six patients (44%) died within 28 days of admission. There was no difference in the age of patients who survived (51.2 ± 11 years) and those who died (52.6 ± 10 years). However, mDF, CPS and GAHS were significantly higher in dead patients (68.7 ± 56.4, 11.8 ± 1.3, 8.6 ± 1.6, respectively) compared to those who survived (36.2 ± 25.9, 10 ± 1.6, 7.6 ± 1.5, respectively) (p < 0.01). Similarly, prothrombin time (PT) was significantly higher in patients who died (23 ± 2 s) compared to those who survived (17.6 ± 0.7 s) (p = 0.007). CONCLUSION: There was no difference among three scoring systems in predicting 28-day mortality at the time of admission in patients with AH. In addition, increased PT, gastro-intestinal bleeding and advanced encephalopathy at presentation were associated with high mortality. Furthermore, rise in creatinine from admission increased risk of mortality.

Inflamed target tissue provides a specific niche for highly expanded T-cell clones in early human autoimmune disease.

OBJECTIVE: To profile quantitatively the T-cell repertoire in multiple joints and peripheral blood of patients with recent onset (early) or established rheumatoid arthritis (RA) using a novel next-generation sequencing protocol to identify potential autoreactive clones. METHODS: Synovium of patients with recent onset (early) RA (<6 months) (n=6) or established RA (>18 months) (n=6) was screened for T-cell clones by sequencing over 10 000 T-cell receptors (TCR) per sample. T cells from paired blood samples were analysed for comparison. From two patients synovial T cells were obtained from multiple inflamed joints. The degree of expansion of each individual clone was based on its unique CDR3 sequence frequency within a sample. Clones with a frequency of over 0.5% were considered to be highly expanded clones (HEC). RESULTS: In early RA synovium, the T-cell repertoire was dominated by 35 HEC (median, range 2-70) accounting for 56% of the TCR sequenced. The clonal dominance in the synovium was patient specific and significantly greater than in established RA (median of 11 HEC (range 5-24) in established RA synovium accounting for 9.8% of T cells; p<0.01). 34% (range 28-40%) of the most expanded T-cell clones were shared between different joints in the same patients, compared with only 4% (range 0-8%) between synovium and blood (p=0.01). CONCLUSIONS: In RA, a systemic autoimmune disease, the inflamed synovium forms a niche for specific expanded T-cell clones, especially in early disease. This suggests that, at least in RA, autoreactive T cells should be addressed specifically in the inflamed tissue, preferably in the early phase of the disease.

The clinical picture of rheumatoid arthritis according to the 2010 American College of Rheumatology/European League Against Rheumatism criteria: is this still the same disease?

OBJECTIVE: To examine the implications of using the new classification criteria for rheumatoid arthritis (RA) in clinical practice in a cohort of patients with very early arthritis. METHODS: The study group comprised 301 disease-modifying antirheumatic drug-naive patients with early arthritis. The baseline diagnosis was assessed by applying the 1987 American College of Rheumatology (ACR) and 2010 ACR/European League Against Rheumatism (EULAR) criteria for RA as well as established diagnostic criteria for other rheumatic diseases. Diagnostic and prognostic data were collected after 2 years of followup. Fulfillment of the 2010 ACR/EULAR criteria was evaluated in the subset of patients in whom undifferentiated arthritis (UA) was diagnosed when the 1987 ACR criteria were applied, and fulfillment of RA criteria over time was tested by applying the 2 different criteria sets. RESULTS: The median arthritis duration at baseline was 4 months (range 0-12 months). At baseline, 28% of the patients fulfilled the 1987 ACR criteria, and 45% fulfilled the 2010 ACR/EULAR criteria for RA. Among the patients classified as having UA at baseline according to the 1987 ACR criteria, 36% had fulfilled the 2010 ACR/EULAR criteria already at baseline. Among the patients classified as having UA at baseline but who fulfilled the 1987 ACR criteria after 2 years of followup, 85% had fulfilled the 2010 ACR/EULAR criteria at baseline. Patients with early disease who fulfilled the 2010 ACR/EULAR criteria were less likely to be autoantibody positive and more likely to have monarthritis at presentation than those fulfilling the 1987 ACR criteria. CONCLUSION: Use of the 2010 ACR/EULAR criteria clearly allows earlier diagnosis of RA, although the clinical picture is slightly different on the group level, and RA may be falsely diagnosed in some patients with self-limiting disease.

Pregnancy-specific reference ranges for haematological variables in a Scottish population.

Using laboratory reference ranges, B12 deficiency is inappropriately diagnosed and treated in pregnancy. We aim to define reference ranges for ferritin, folate, haemoglobin and B12 in a pregnant population with advancing gestation. A total of 190 women participated in a cross-sectional study, 113 in the 1st and 77 in the 3rd trimester. All variables studied except red cell folate, decreased significantly from the 1st to the 3rd trimester. A total of 34% (64/190) of women were found to have 'low' B12 as defined by traditional ranges. In women with anaemia and apparent B12 deficiency, co-existing ferritin deficiency was demonstrated. All women with 'low' B12 levels were invited to attend postnatally for re-testing. A total of 28% (18/64) attended, in whom all B12 levels spontaneously increased. The use of gestation specific reference ranges for haematological variables may reduce inappropriate diagnosis of B12 deficiency. In most women with apparent low B12 levels and anaemia, ferritin deficiency was demonstrated. Therefore iron should be the initial management therapy.

Stratifying risk in chronic kidney disease: an observational study of UK guidelines for measuring total proteinuria and albuminuria.

BACKGROUND: Proteinuria predicts poor renal and cardiovascular outcomes. Some guidelines recommend measuring proteinuria using albumin:creatinine ratio (ACR), while others recommend total protein:creatinine ratio (TPCR). AIM: To compare renal outcomes and mortality in the populations identified by these different recommendations. DESIGN: Retrospective longitudinal cohort study. METHODS: Baseline ACR and TPCR measurements were obtained from 5586 patients with chronic kidney disease (CKD) attending a Scottish hospital nephrology clinic. The cohort was divided into three groups with concordant results by ACR and TPCR (no proteinuria; low proteinuria; significant proteinuria) and one group with discordant results (significant proteinuria with TPCR, but not ACR). Outcomes were assessed using Kaplan-Meier plots and Cox proportional hazards models. RESULTS: Median follow-up was 3.5 years [interquartile range (IQR) 2.1-6.0]; 844 (15%) died at 3.0 years (IQR 1.8-4.7) and 468 (8%) started renal replacement therapy (RRT) at 1.7 years (IQR 0.6-3.4). Proteinuria was associated with a substantially increased risk of RRT and death. Patients with significant proteinuria by TPCR, but not ACR (n = 231) had high renal risk, and the highest all-cause mortality (log-rank P < 0.001). With multivariate analysis the risk fell below those with significant proteinuria with concordant results by ACR and TPCR but remained considerably higher than those without significant proteinuria. CONCLUSION: Proteinuria screening with TPCR identifies an additional 16% of patients with significant proteinuria, not identified using ACR. This subgroup has high renal risk, and high risk of all-cause mortality and therefore warrant identification. Guideline recommendations on proteinuria screening in CKD should be reconsidered.

Do wind and brass players snore less? A cross-sectional study of snoring and daytime fatigue in professional orchestral musicians.

OBJECTIVES: To determine whether playing a wind or brass musical instrument is associated with reduced snoring or daytime fatigue. DESIGN: Cross-sectional, controlled, anonymous, questionnaire-based observational study. SETTING: Rehearsal and performance halls. PARTICIPANTS: Three hundred and forty musicians from Scotland's five professional orchestras. MAIN OUTCOME MEASURES: Snore Outcomes Survey questionnaire and the Epworth Sleepiness Score. STATISTICAL METHOD: Hierarchical linear regression analysis. RESULTS: No significant difference was found between the snoring severity (Snore Outcomes Survey score) or daytime sleepiness (Epworth score) of wind/brass and other professional musicians. A regression model with snoring severity (Snore Outcomes Survey score) as the dependent variable and the three covariates of gender, age and body mass index as independent variables was significant [F(3, 206) = 28.77, P < 0.01, adjusted r(2) = 0.285]. Increasing age, body mass index and male gender were all significantly associated with lower Snore Outcomes Survey scores (i.e. worse snoring).The addition of instrument type did not significantly increase the fit of the model, and the regression coefficient for instrument type was not significant. There were similar results when the Epworth Sleepiness Score was used as the dependent variable. CONCLUSIONS: This study demonstrated no significant difference between the snoring severity or daytime sleepiness of brass/wind players and other professional orchestral musicians. This result may have been attributed to comparatively low levels of snoring/daytime sleepiness in the population studied. The findings contrast with previous studies examining the effects of singing and didgeridoo playing but concur with a recent similar study of orchestral musicians. A prospective interventional study would be required to determine whether playing a wind or brass instrument improves these variables in patients complaining of disruptive snoring.