Improved Time in Range Over 1 Year Is Associated With Reduced Albuminuria in Individuals With Sensor-Augmented Insulin Pump-Treated Type 1 Diabetes.

OBJECTIVE: To investigate the association between treatment-induced change in continuous glucose monitoring (CGM) time in range (TIR) and albuminuria in persons with type 1 diabetes (T1D) treated with sensor-augmented insulin pumps (SAP). RESEARCH DESIGN AND METHODS: Twenty-six out of 55 participants with albuminuria and multiple daily injection therapy (25% females; median 51 [interquartile range 46-63] years of age; glycated hemoglobin A1c (HbA1c) 75 [68-88] mmol/mol [9.0% (8.4-10.4%)]; and urinary albumin-to-creatinine ratio (UACR) 89 [37-250] mg/g) were in a randomized controlled trial assigned to SAP therapy for 1 year. Anthropometrics, CGM data, and blood and urine samples were collected every 3 months. RESULTS: Mean change (95% CI) in percentage of TIR (%TIR) was 13.2% (6.2; 20.2), in HbA1c was -14.4 (-17.4; -10.5) mmol/mol (-1.3% [-1.6; -1.0]), and in UACR was -15% (-38; 17) (all P < 0.05). UACR decreased by 19% (10; 28) per 10% increase in %TIR (P = 0.04), 18% (1; 30) per 10 mmol/mol decrease in HbA1c (P = 0.07), and 31% per 10-mmHg decrease in mean arterial pressure (P < 0.001). CONCLUSIONS: In this longitudinal study, treatment-induced increase in %TIR was significantly associated with decrease in albuminuria in T1D.

Efficacy and safety of oral semaglutide in patients with type 2 diabetes and moderate renal impairment (PIONEER 5): a placebo-controlled, randomised, phase 3a trial.

BACKGROUND: Oral semaglutide is the first oral glucagon-like peptide-1 (GLP-1) receptor agonist for glycaemic control in patients with type 2 diabetes. Type 2 diabetes is commonly associated with renal impairment, restricting treatment options. We aimed to investigate the efficacy and safety of oral semaglutide in patients with type 2 diabetes and moderate renal impairment. METHODS: This randomised, double-blind, phase 3a trial was undertaken at 88 sites in eight countries. Patients aged 18 years and older, with type 2 diabetes, an estimated glomerular filtration rate of 30-59 mL/min per 1·73 m2, and who had been receiving a stable dose of metformin or sulfonylurea, or both, or basal insulin with or without metformin for the past 90 days were eligible. Participants were randomly assigned (1:1) by use of an interactive web-response system, with stratification by glucose-lowering medication and renal function, to receive oral semaglutide (dose escalated to 14 mg once daily) or matching placebo for 26 weeks, in addition to background medication. Participants and site staff were masked to assignment. Two efficacy-related estimands were defined: treatment policy (regardless of treatment discontinuation or rescue medication) and trial product (on treatment without rescue medication) in all participants randomly assigned. Endpoints were change from baseline to week 26 in HbA1c (primary endpoint) and bodyweight (confirmatory secondary endpoint), assessed in all participants with sufficient data. Safety was assessed in all participants who received at least one dose of study drug. This trial is registered on ClinicalTrials.gov, number NCT02827708, and the European Clinical Trials Registry, number EudraCT 2015-005326-19, and is now complete. FINDINGS: Between Sept 20, 2016, and Sept 29, 2017, of 721 patients screened, 324 were eligible and randomly assigned to oral semaglutide (n=163) or placebo (n=161). Mean age at baseline was 70 years (SD 8), and 168 (52%) of participants were female. 133 (82%) participants in the oral semaglutide group and 141 (88%) in the placebo group completed 26 weeks on treatment. At 26 weeks, oral semaglutide was superior to placebo in decreasing HbA1c (estimated mean change of -1·0 percentage point (SE 0·1; -11 mmol/mol [SE 0·8]) vs -0·2 percentage points (SE 0·1; -2 mmol/mol [SE 0·8]); estimated treatment difference [ETD]: -0·8 percentage points, 95% CI -1·0 to -0·6; p<0·0001) and bodyweight (estimated mean change of -3·4 kg [SE 0·3] vs -0·9 kg [SE 0·3]; ETD, -2·5, 95% CI -3·2 to -1·8; p<0·0001) by the treatment policy estimand. Significant differences were seen for the trial product estimand: mean change in HbA1c -1·1 percentage points (SE 0·1; -12 mmol/mol [SE 0·8] versus -0·1 percentage points (SE 0·1; -1 mmol/mol [SE 0·8]; ETD -1·0 percentage points, 95% CI -1·2 to -0·8; p<0·0001); mean change in bodyweight -3·7 kg (SE 0·3) versus -1·1 kg (SE 0·3; ETD -2·7 kg, 95% CI -3·5 to -1·9; p<0·0001). More patients taking oral semaglutide than placebo had adverse events (120 [74%] of 163 vs 105 [65%] of 161), and discontinued treatment as a result (24 [15%] vs eight [5%]). Gastrointestinal events, mainly mild-to-moderate nausea, were more common with oral semaglutide than with placebo. Three deaths occurred during the treatment period that were not condsidered to be treatment related, one in the semaglutide group and two in the placebo group. INTERPRETATION: Oral semaglutide was effective in patients with type 2 diabetes and moderate renal impairment, potentially providing a new treatment option for this population. Safety, including renal safety, was consistent with the GLP-1 receptor agonist class. FUNDING: Novo Nordisk A/S.

Radiographic cup position following posterior and lateral approach to total hip arthroplasty. An explorative randomized controlled trial.

The two most common surgical approaches to total hip arthroplasty are the posterior approach and lateral approach. The surgical approach may influence cup positioning and restoration of the offset, which may affect the biomechanical properties of the hip joint. The primary aim was to compare cup position between posterior approach and lateral approach. Secondary aims were to compare femoral offset, abductor moment arm and leg length discrepancy between the two approaches. Eighty patients with primary hip osteoarthritis were included in a randomized controlled trial and assigned to total hip arthroplasty using posterior approach or lateral approach. Postoperative radiographs from 38 patients in each group were included in this study for measurement of cup anteversion and inclination. Femoral offset, cup offset, total offset, abductor moment arm and leg length discrepancy were measured on preoperative and postoperative radiographs in 28 patients in each group. We found that mean anteversion was 5° larger in the posterior approach group (95% CI, -8.1 to -1.4; p = 0.006), while mean inclination was 5° less steep (95% CI, 2.7 to 7.2; p<0.001) compared with the lateral approach group. The posterior approach group had a larger mean femoral offset of 4.3mm (95% CI, -7.4 to -1.3, p = 0.006), mean total offset of 6.3mm (95% CI, -9.6 to -3; p<0.001) and mean abductor moment arm of 4.8mm (95% CI, -7.6 to -1.9; p = 0.001) compared with the lateral approach group. We found a larger cup anteversion but less steep cup inclination in the posterior approach group compared with the lateral approach group. Femoral offset and abductor moment arm were restored after total hip arthroplasty using lateral approach but significantly increased when using posterior approach.

Patient-reported outcome after total hip arthroplasty: comparison between lateral and posterior approach.

Background and purpose - Criticism of the lateral approach (LA) for hip arthroplasty is mainly based on the risk of poor patient-reported outcomes compared to the posterior approach (PA). However, there have been no controlled studies comparing patient-reported outcomes between them. In this randomized controlled trial, we tested the hypothesis that patient-reported outcomes are better in patients who have undergone total hip arthroplasty (THA) with PA than in those who have undergone THA with LA, 12 months postoperatively. Patients and methods - 80 patients with hip osteoarthritis (mean age 61 years) were randomized to THA using PA or the modified direct LA. We recorded outcome measures preoperatively and 3, 6, and 12 months postoperatively using the Hip Disability and Osteoarthritis Outcome Score-Physical Function Short Form (HOOS-PS) as the primary outcome. Secondary outcomes were HOOS-Pain, HOOS-Quality-Of-Life, EQ-5D, UCLA Activity Score, and limping. Results - We found no statistically significant difference in the improvements in HOOS-PS between the treatment groups at 12-month follow-up. All secondary outcomes showed similar results except for limping, where PA patients improved significantly more than LA patients. Interpretation - Contrary to our hypothesis, patients treated with PA did not improve more than patients treated with LA regarding physical function, pain, physical activity, and quality of life 12 months postoperatively. However, limping was more pronounced in the LA patients.

Effects of liraglutide on cardiovascular risk biomarkers in patients with type 2 diabetes and albuminuria: A sub-analysis of a randomized, placebo-controlled, double-blind, crossover trial.

We assessed the effects of liraglutide treatment on five cardiovascular risk biomarkers, reflecting different pathophysiology: tumour necrosis factor (TNF)-α; soluble urokinase plasminogen activator receptor (suPAR); mid-regional pro-adrenomedullin (MR-proADM); mid-regional pro-atrial natriuretic peptide (MR-proANP); and copeptin, in people with type 2 diabetes with albuminuria. In a randomized, double-blind, placebo-controlled, crossover trial we enrolled people with type 2 diabetes and persistent albuminuria (urinary albumin-to-creatinine ratio [UACR] >30 mg/g) and estimated glomerular filtration rate (eGFR) ≥30 mL/min/1.73 m2 . Participants received liraglutide (1.8 mg/d) and matched placebo for 12 weeks, in random order. The primary endpoint was change in albuminuria; this was a prespecified sub-study. A total of 32 participants were randomized, of whom 27 completed the study. TNF-α level was 12% (95% confidence interval [CI] 3; 20) lower after liraglutide treatment compared with placebo (P = .012); MR-proADM level was 4% (95% CI 0; 8) lower after liraglutide treatment compared with placebo (P = .038), and MR-proANP level was 13% (95% CI 4; 21) lower after liraglutide treatment compared with placebo (P = .006). In the present study, we showed anti-inflammatory effects of liraglutide treatment, reflected in reductions in levels of TNF-α and MR-proADM, while the reduction in MR-proANP levels may represent a clinically relevant benefit with regard to heart failure.

The effect of liraglutide on renal function: A randomized clinical trial.

AIMS: Among patients with type 2 diabetes and albuminuria, cardiorenal morbidity and mortality are high despite multifactorial treatment. Short-term reduction in albuminuria is considered suggestive of long-term renoprotective effects. We evaluated the renal effects of the glucagon-like peptide-1 (GLP-1) receptor agonist liraglutide on top of multifactorial care, including renin-angiotensin-system (RAS)-inhibition. MATERIALS AND METHODS: Randomized, double-blind, placebo-controlled, cross-over trial including patients with type 2 diabetes and persistent albuminuria (urinary albumin-to-creatinine ratio >30 mg/g) and estimated glomerular filtration rate (eGFR) ≥30 mL/min/1.73 m2 . Patients received liraglutide (1.8 mg/d) and matched placebo for 12 weeks in a random order. The primary endpoint was change in 24-h urinary albumin excretion rate (UAER). RESULTS: A total of 32 patients were randomized and 27 completed the study. After placebo treatment, geometric mean (IQR) UAER was 199 (81-531) mg/24-h, mean (SD) measured GFR (mGFR) 75 (36) mL/min/1.73 m2 , 24-h blood pressure 145/80 (15/8) mm Hg and HbA1c 61 (11) mmol/mol. Liraglutide reduced HbA1c by 8 (95% CI: 5; 11) mmol/mol (P < .001) and weight by 1.8 (95% CI: 0.2; 3.4) kg (P = .032) compared to placebo. Furthermore, liraglutide reduced UAER by 32 (95% CI: 7; 50)% ( P = .017) compared with placebo. The change in mGFR was -5 (95% CI: -11; 2) mL/min/1.73 m2 ( P = .15), and change in 24-h systolic blood pressure was -5 (95% CI: -10; 0) mm Hg ( P = .07). In multivariate regression models, change in UAER was associated with change in 24-h systolic blood pressure ( P = .025) but not with change in HbA1c, weight or mGFR ( P ≥ .14), overall model R 2 = .39. CONCLUSIONS: Our placebo-controlled randomized trial suggests that liraglutide has renoprotective effects on top of multifactorial treatment, including RAS-inhibition, in patients with type 2 diabetes and albuminuria.

The efficacy of modified direct lateral versus posterior approach on gait function and hip muscle strength after primary total hip arthroplasty at 12months follow-up. An explorative randomised controlled trial.

BACKGROUND: The lateral and the posterior approach are the most commonly used procedures for total hip arthroplasty. Due to the detachment of the hip abductors, lateral approach is claimed to cause reduced hip muscle strength and altered gait pattern. However, this has not been investigated in a randomised controlled trial. The aim was to compare the efficacy of total hip arthroplasty performed by lateral or posterior approach on gait function and hip muscle strength up to 12months post-operatively. We hypothesised that posterior approach would be superior to lateral approach. METHODS: Forty-seven patients with primary hip osteoarthritis were randomised to total hip arthroplasty with either posterior or lateral approach and evaluated pre-operatively, 3 and 12months post-operatively using 3-dimensional gait analyses as objective measures of gait function, including Gait Deviation Index, temporo-spatial parameters and range of motion. Isometric maximal hip muscle strength in abduction, flexion and extension was also tested. FINDINGS: Post-operatively, no between-group difference in gait function was observed. However, both hip abductor and flexor muscle strength improved more in the posterior approach group: -0.20(Nm/kg)[95%CI:-0.4 to 0.0] and -0.20(Nm/kg)[95%CI:-0.4 to 0.0], respectively. INTERPRETATION: Contrary to our first hypothesis, the overall gait function in the posterior approach group did not improve more than in the lateral approach group. However, in agreement with our second hypothesis, patients in the posterior approach group improved more in hip abductor and flexor muscle strength at 12months. Further investigation of the effect of reduced maximal hip muscle strength on functional capacity is needed. ClinicalTrials.gov. No.: NCT01616667.

The Gait Deviation Index Is Associated with Hip Muscle Strength and Patient-Reported Outcome in Patients with Severe Hip Osteoarthritis-A Cross-Sectional Study.

BACKGROUND: The Gait Deviation Index summarizes overall gait 'quality', based on kinematic data from a 3-dimensional gait analysis. However, it is unknown which clinical outcomes may affect the Gait Deviation Index in patients with primary hip osteoarthritis. The aim of this study was to investigate associations between Gait Deviation Index as a measure of gait 'quality' and hip muscle strength and between Gait Deviation Index and patient-reported outcomes in patients with primary hip osteoarthritis. METHOD: Forty-seven patients (34 males), aged 61.1 ± 6.7 years, with BMI 27.3 ± 3.4 (kg/m2) and with severe primary hip osteoarthritis underwent 3-dimensional gait analysis. Mean Gait Deviation Index, pain after walking and maximal isometric hip muscle strength (flexor, extensor, and abductor) were recorded. All patients completed the 'Physical Function Short-form of the Hip disability and Osteoarthritis Outcome Score (HOOS-Physical Function) and the Hip disability and Osteoarthritis Outcome Score subscales for pain (HOOS-Pain) and quality-of-life (HOOS-QOL). RESULTS: Mean Gait Deviation Index was positively associated with hip abduction strength (p<0.01, r = 0.40), hip flexion strength (p = 0.01, r = 0.37), HOOS-Physical Function (p<0.01, r = 0.41) HOOS-QOL (p<0.01, r = 0.41), and negatively associated with HOOS-Pain after walking (p<0.01, r = -0.45). Adjusting the analysis for walking speed did not affect the association. CONCLUSION: Patients with the strongest hip abductor and hip flexor muscles had the best gait 'quality'. Furthermore, patients with higher physical function, quality of life scores and lower pain levels demonstrated better gait 'quality'. These findings indicate that interventions aimed at improving hip muscle strength and pain management may to a moderate degree improve the overall gait 'quality' in patients with primary hip OA.

Effect of Sensor-Augmented Pump Treatment Versus Multiple Daily Injections on Albuminuria: A 1-Year Randomized Study.

CONTEXT: The effect of glycemic control on persisting albuminuria remains unclear. Insulin delivery and glucose variability may be important. OBJECTIVE: This study aimed to investigate the effect of 1-year treatment with sensor-augmented insulin pump (SAP) or multiple daily injections (MDIs) on albuminuria. DESIGN, PATIENTS, AND METHODS: This was a randomized controlled open-label parallel trial composed of 60 patients with type 1 diabetes with a history of albuminuria and on stable renin-angiotensin system inhibition, were randomly assigned to SAP or MDI. Urine albumin creatinine ratio (UACR) was measured in three urine samples at all visits. Glucose variability and glomerular filtration rate ((51)Cr-EDTA-GFR) were measured at beginning and study end. Using linear mixed model, change in UACR between groups was analyzed as intention to treat. MAIN OUTCOME MEASURE: Change in UACR was measured. RESULTS: Fifty-five patients (SAP, n = 26; MDI, n = 29) completed the study. Diabetes duration (mean ± SD, 33 ± 12 y), UACR (geometric mean, 99 mg/g; interquartile range, 37-233 mg/g), (51)Cr-EDTA-GFR (94 ± 22 mL/min/1.73m(2)), glycosylated hemoglobin (HbA1c) (9.0 ± 1.1%), glucose variability (calculated as SD), 4.0 ± 1.0 mmol/l; no-group differences (P ≥ .06 for all). After 1 year, change in UACR was mean, -13%; 95% confidence interval, -39 to 22 with SAP vs mean, 30%; 95% CI, -12 to 92% on MDI treatment (unadjusted P = .051; adjusted for HbA1c, P = .04). HbA1c decreased 1.3 ± 1.0 vs 0.6 ± 1.0% (P = .013), glucose variability decreased 0.9 ± 1.1 vs 0.3 ± 1.0 mmol/L (P = .04), and (51)Cr-EDTA-GFR declined 5.6 ± 9.6 vs 3.4 ± 13 mL/min/1.73m(2) (P = .50) with SAP vs MDI treatment. There were no changes in blood pressure (P ≥ .27). CONCLUSION: SAP treatment reduced UACR in a randomized controlled trial in type 1 diabetes patients with a history of albuminuria on stable renin-angiotensin system inhibition. Significance was reached after adjustment. SAP treatment reduced HbA1c and glucose variability (calculated as SD).

The use of the Gait Deviation Index for the evaluation of participants following total hip arthroplasty: An explorative randomized trial.

INTRODUCTION: In this paper, the Gait Deviation Index (GDI) was used as a convenient method to evaluate pre-to-postoperative gait pattern changes after total hip arthroplasty and identify factors which might be predictive of outcome. DESIGN: Three-dimensional gait data from a randomized clinical trial was used to determine changes in gait quality in participants walking at self-selected speed. Upon completion of the first assessment, the participants were randomly assigned to either resurfacing hip arthroplasty or conventional hip arthroplasty. The outcome was changes in overall gait 'quality' measured with GDI during the 6-month post-surgery follow-up period. RESULTS: 38 participants with severe unilateral primary hip osteoarthritis took part in the trial. We found no difference in change scores between the two treatment groups; 1.9 [95%CI: -0.3 to 4.0] or between change scores for the non-operated and the operated limbs; 0.3 [95%CI: -2.3 to 1.7]. However, the score for the two groups (pooled data) improved after surgery by 4.4 [95%CI: 1.8-7.0]. The single level regression analysis identified the preoperative GDI score as a strong predictor of outcome (p<0.001). CONCLUSION: Six months after surgery, there was no additional effect of resurfacing hip arthroplasty on GDI scores compared with conventional hip arthroplasty. Participants with the most pathological preoperative gait pattern improved the most. The GDI increased, which indicates an overall improvement in gait pathology after surgery. TRIAL REGISTRATION: NCT01229293.

The effect of posterior and lateral approach on patient-reported outcome measures and physical function in patients with osteoarthritis, undergoing total hip replacement: a randomised controlled trial protocol.

BACKGROUND: Total hip replacement provides pain relief and improves physical function and quality of life in patients with end-stage hip osteoarthritis. The incidence of hip replacement operations is expected to increase due to the growing elderly population. Overall, the posterior approach and lateral approach are the two most commonly used approaches for hip replacement operations. The posterior approach is associated with an increased risk of revision due to dislocations, and some studies have shown that the lateral approach is associated with reduced patient-reported outcomes, including physical function and pain; however, this has not been investigated in a randomised controlled trial with a twelve-month follow-up. We hypothesized that the lateral approach has an inferior outcome in patient-reported outcome compared with the posterior approach after one year. METHODS/DESIGN: The trial is a prospective, double blinded, parallel-group controlled trial with balanced randomisation [1: 1]. Patients with hip osteoarthritis scheduled for hip replacement surgery, aged 45-70 years, will be consecutively recruited and randomised into two groups. Group A will receive hip replacement using the posterior approach, and Group B will receive hip replacement using the lateral approach. The primary end-point for assessing the outcome of the two interventions will be twelve months after surgery. Follow-up will also be performed after three and six months. The primary outcome is Hip Disability and Osteoarthritis Outcome Score, subscale of "Physical function Short form" (HOOS-PS) Secondary outcome measures include two other subscales of HOOS ("Pain" and "Hip related Quality of Life"), physical activity level (UCLA activity score), limping (HHS) and general health status (EQ-5D-3L). Explorative outcomes include physical function test, 3D-gait-analysis and muscle strength. DISCUSSION: To our knowledge, this is the first randomised controlled trial comparing the posterior approach with the lateral approach with patient reported outcome as the primary outcome and with a twelve-month follow-up. TRIAL REGISTRATION: Clinicaltrial.gov: NCT01616667.

Treatment with continuous subcutaneous insulin infusion is associated with lower arterial stiffness.

AIMS: To investigate the relationship between arterial stiffness and insulin treatment mode [continuous subcutaneous insulin infusion (CSII) versus multiple daily injections (MDI)] in type 1 diabetes patients. METHODS: Cross-sectional study, from 2009 to 2011, including 601 Caucasian type 1 diabetes patients, 58 and 543 treated with CSII and MDI, respectively. Arterial stiffness was measured as pulse wave velocity (PWV) (SphygmoCor, AtCor Medical). Adjustment included gender, age, diabetes duration, HbA1c, heart rate, mean arterial pressure, P-creatinine, urinary albumin excretion rate (UAER), smoking, total daily insulin dose, antihypertensive treatment, previous cardiovascular disease (CVD), total cholesterol and statin treatment. Albuminuria was UAER ≥30 mg/24-h, and CVD included myocardial infarction, revascularization, peripheral arterial disease and stroke. RESULTS: CSII- versus MDI-treated patients were 48 versus 57 % men, 51 ± 11 versus 54 ± 13 years old (mean ± SD), had 33 ± 12 versus 32 ± 16 years diabetes duration and HbA1c 7.8 ± 0.9 % (62 ± 10 mmol/mol) versus 8.0 ± 1.2 % (64 ± 13 mmol/mol) (P ≥ 0.08 for all). PWV was lower in CSII- versus MDI-treated patients (9.3 ± 2.8 vs. 10.4 ± 3.4 m/s; P = 0.016). In fully adjusted analysis, CSII treatment was significantly (P = 0.038) associated with lower PWV, whereas HbA1c-level was not (P = 0.93). CONCLUSIONS: In type 1 diabetes patients, CSII treatment was associated with lower arterial stiffness independent of other risk factors, while HbA1c was not. Although glucose variability was not assessed, our results suggest that glucose variability and not HbA1c-level affect arterial stiffness. This needs confirmation in randomised prospective studies.

Total knee arthroplasty in younger patients evaluated by alternative outcome measures.

In this prospective multicenter study we included subjects younger than 60 years of age and scheduled for primary total knee arthroplasty (TKA). The study assessed patients' overall satisfaction, fulfillment of preoperative expectations, the effect on socioeconomic parameters, and quality of sexual life. Questionnaires including Oxford Knee Score (OKS) and SF-36 were evaluated preoperatively and 3, 6, and 12 months postoperatively. OKS and SF-36 showed significant improvements. However, patient satisfaction and fulfillment of personal expectations did not reflect these scores. Overall, TKA did not affect the patients' socioeconomic status, and overall, patients did not experience impairment of sexual life, but decreased frequency and negative affection of sexual practice should be anticipated. Alternative outcome measurements of TKA surgery not focusing on implants and surgical techniques shed new light on important consequences of arthroplasty surgery.

[Acrodermatitis chronica atrophicans can be difficult to diagnose]. / Acrodermatitis chronica atrophicans kan være vanskelig at diagnosticere.

A healthy 29 year-old man developed over four years a slowly increasing swelling and violet discolouring of the third toe on his left foot. He was examined by several specialists and an amputation was recommended since the condition was unknown and aggravating. On suspicion of Borrelia infection the patient was prescribed penicillin treatment for 28 days with convincing effect. Serologic tests showed increased Borrelia titer. Biopsy showed chronic inflammation without any suspicion of malignity. Denmark is endemic for borreliosis and per year approximately 50 cases develop acrodermatitis chronic atrophicans.

Outcome and clinical characteristics in pleural empyema: a retrospective study.

BACKGROUND: Pleural empyema is a serious condition with a considerable mortality rate and morbidity. This study evaluated the correlations between several potential prognostic factors (age, predisposing diseases, early drainage, insufficient initial antimicrobial therapy, thoracic surgical treatment, intrapleural fibrinolysis, and nosocomial status) and outcome. METHODS: Danish patients with positive pleural cultures attending 3 hospitals over a 9-y period, were identified in the laboratory databases. Clinical details and outcome were evaluated retrospectively by audit of the medical records. RESULTS: We included 158 patients in this study. The overall mortality was 27% and the median length of stay was 29 days. Mortality correlated independently with several factors: nosocomial infection (odds ratio (OR) 2.62, 95% confidence interval (CI) 1.71-4.16), predisposing conditions (OR 2.17, 95% CI 1.50-3.14), and also with the possibly interventional factors of sufficient initial antimicrobial therapy (OR 0.45, 95% CI 0.31-0.65), thoracic surgery treatment (OR 0.27, 95% CI 0.14-0.52) and local fibrinolytic therapy (OR 0.13, 95% CI 0.06-0.28). Delay in chest tube drainage more than 2 days was not independently correlated with mortality. The initial biochemical diagnostics of non-purulent pleural effusions (63%) did not follow the current international guidelines. CONCLUSION: Factors correlating independently with survival included the possible interventional parameters of fibrinolytic therapy, insufficient initial antimicrobial therapy, and having thoracic surgery treatment.

Bacteriological aetiology and antimicrobial treatment of pleural empyema.

BACKGROUND: Our aims were to describe the aetiologies of culture-positive pleural infections and to evaluate the choice of empiric antimicrobial treatment regimens according to antimicrobial sensitivity, and to evaluate the possible influence of this on outcome. METHODS: All cases over a 9-y period were identified from 3 hospitals using the laboratory databases of the clinical microbiology departments, and were verified by evaluating the medical records. RESULTS: We identified 291 isolates in pleural fluid cultures from 158 patients. These included viridans streptococci (25%), Staphylococcus aureus (18%), anaerobic bacteria (17%), Enterobacteriaceae (12%), Staphylococcus epidermidis (10%), and Streptococcus pneumoniae (7%), with differences between nosocomial and community-acquired infections. The mortality (overall 27%) was highest among the patients with Enterobacteriaceae (50%) and S. aureus (36%) infections, and in patients with mixed infections (34%). The actual empiric treatment or the recommended penicillin plus metronidazole had low antimicrobial coverage (49%) compared to the proposed cefuroxime plus metronidazole (78%). Thoracentesis was often delayed (median 2 days). The adequacy of empiric antimicrobial therapy was independently correlated with mortality (odds ratio 0.43, 95% confidence interval 0.30-0.62). CONCLUSIONS: The early diagnosis of pleural infection could be optimized. In this North-European patient population, we suggest that the recommended empiric antimicrobial treatment be changed to cefuroxime plus metronidazole for community-acquired and nosocomial infections.