Risk of Staphylococcus aureus bacteraemia in patients with rheumatoid arthritis and the effect of orthopaedic implants on the risk: a nationwide observational cohort study.

OBJECTIVE: It remains disputed how much the risk of Staphylococcus aureus bacteraemia (SAB) is increased in patients with rheumatoid arthritis (RA), and the extent to which orthopaedic implants explain the risk. We assessed SAB incidence rates (IRs) and incidence rate ratios (IRRs), comparing RA patients with a general population cohort (GPC) and individuals with versus without orthopaedic implants. METHOD: Danish residents aged ≥ 18 years without prior RA or SAB (=GPC) were followed up for RA and microbiologically verified SAB events (1996-2017). IRRs were calculated by age- and sex-stratified Poisson regression adjusted for age, comorbidities, calendar year, and socioeconomic status. RESULTS: The GPC comprised 5 398 690 individuals. We identified 33 567 incident RA patients (=RA cohort) (median follow-up 7.3 years, IQR 3.6-12.3). We observed 25 023 SAB events (n = 224 in the RA cohort). IRs per 100 000 person-years were 81.0 (RA cohort) and 29.9 (GPC). IRs increased with age. Adjusted IRRs in 18-59-year-old RA patients were 2.6 (95% confidence interval 1.8-3.7) for women and 1.8 (1.1-3.1) for men, compared with same sex and age group GPC. IRRs declined with age. Compared with the GPC without implants, IRRs for RA patients with implants ranged from 1.9 (1.3-2.8) (women ≥ 70 years) to 5.3 (2.2-12.8) (18-59-year-old men). CONCLUSION: In this nationwide registry-based cohort study RA was a risk factor for SAB, and orthopaedic implants further increased the risk. Clinicians should be aware of potential SAB in patients with RA and orthopaedic implants.

Substantial rise in the lifetime risk of primary total knee replacement surgery for osteoarthritis from 2003 to 2013: an international, population-level analysis.

OBJECTIVE: To estimate and compare the lifetime risk of total knee replacement surgery (TKR) for osteoarthritis (OA) between countries, and over time. METHOD: Data on primary TKR procedures performed for OA in 2003 and 2013 were extracted from national arthroplasty registries in Australia, Denmark, Finland, Norway and Sweden. Life tables and population data were also obtained for each country. Lifetime risk of TKR was calculated for 2003 and 2013 using registry, life table and population data. RESULTS: Marked international variation in lifetime risk of TKR was evident, with females consistently demonstrating the greatest risk. In 2013, Finland had the highest lifetime risk for females (22.8%, 95%CI 22.5-23.1%) and Australia had the highest risk for males (15.4%, 95%CI 15.1-15.6%). Norway had the lowest lifetime risk for females (9.7%, 95%CI 9.5-9.9%) and males (5.8%, 95%CI 5.6-5.9%) in 2013. All countries showed a significant rise in lifetime risk of TKR for both sexes over the 10-year study period, with the largest increases observed in Australia (females: from 13.6% to 21.1%; males: from 9.8% to 15.4%). CONCLUSIONS: Using population-based data, this study identified significant increases in the lifetime risk of TKR in all five countries from 2003 to 2013. Lifetime risk of TKR was as high as 1 in 5 women in Finland, and 1 in 7 males in Australia. These risk estimates quantify the healthcare resource burden of knee OA at the population level, providing an important resource for public health policy development and healthcare planning.

Use of antihypertensive drugs and risk of skin cancer.

BACKGROUND: Several antihypertensive drugs are photosensitizing and may therefore act as cocarcinogens with ultraviolet radiation. OBJECTIVE: To examine whether antihypertensive drug use is associated with squamous cell carcinoma (SCC), basal cell carcinoma (BCC), and malignant melanoma (MM). METHODS: We used population-based databases to conduct a case-control study including all first-time cases of SCC (n = 2282), BCC (n = 17,242), and MM (n = 3660) in northern Denmark, 1991-2010. We matched approximately 10 controls (n = 231,743) to each case by age, sex and county using risk-set sampling. We used conditional logistic regression to compute odds ratios (ORs) for skin cancer with 95% confidence intervals comparing ever users of antihypertensives (>2 previous prescriptions) with non-users (≤2 previous prescriptions). We adjusted for comorbidity and comedications. We further analysed use by duration (short term: <5 years; long term: ≥5 years) and intensity (low intensity or high intensity: <50% or ≥50% prescription coverage during total duration of use, respectively). RESULTS: Ever users of diuretics were at increased risk of SCC (OR 1.19; 1.06-1.33), driven by potassium-sparing agents alone (OR 1.40; 1.09-1.80) or with low-ceiling diuretics (OR 2.68; 2.24-3.21) and by long-term use (OR 1.41; 1.16-1.72 at low intensity; OR 1.44; 0.98-2.14 at high intensity). Ever users of sulphonamides (OR 1.49; 1.04-2.12) and non-aldosterone antagonist potassium-sparing agents (OR 2.26; 0.85-6.01) were at increased MM risk. The latter was also associated with BCC (OR 1.47; 1.00-2.17), as was low-ceiling diuretics combined with potassium-sparing agents (OR 1.23; 1.12-1.35). Long-term, low-intensity (OR 1.53; 1.05-2.23) and high-intensity (OR 1.44; 0.56-3.69) angiotensin receptor blocker use was associated with MM. Estimates for angiotensin-converting enzyme inhibitors, ß-blockers, and calcium channel blockers were inconsistent or weak (<20% increased). CONCLUSION: Long-term angiotensin receptor blocker use was associated with risk of MM. Moreover, long-term diuretic use was associated with SCC risk, driven by potassium-sparing agents alone or in combination with low-ceiling diuretics.

Association between fixation technique and revision risk in total hip arthroplasty patients younger than 55 years of age. Results from the Nordic Arthroplasty Register Association.

OBJECTIVES: To evaluate implant survival following primary total hip replacement (THR) in younger patients. To describe the diversity in use of cup-stem implant combinations. DESIGN: 29,558 primary THRs osteoarthritis (OA) patients younger than 55 years of age performed from 1995 through 2011 were identified using the Nordic Arthroplasty Registry Association database. We estimated adjusted relative risk (aRR) of revision with 95% confidence interval (CI) using Cox regression. RESULTS: In general, no difference was observed between uncemented and cemented implants in terms of risk of any revision. Hybrid implants were associated with higher risk of any revision (aRR = 1.3, CI: 1.1-1.5). Uncemented implants led to a reduced risk of revision due to aseptic loosening (aRR = 0.5, CI: 0.5-0.6), whereas the risk was similar for hybrid and cemented implants. Compared with cemented implants, both uncemented and hybrid implants led to elevated risk of revision due to other causes, as well as elevated risk of revision due to any reason within 2 years. 183 different uncemented cup-stem implant combinations were registered in Denmark, of these, 172 were used in less than 100 operations which is similar to Norway, Sweden and Finland. CONCLUSIONS: Uncemented implants perform better in relation to long-term risk of aseptic loosening, whereas both uncemented and hybrid rather than cemented implants in patients younger than 55 years had more short-term revisions because problems due to dislocation, periprosthetic fracture and infection has not yet been completely solved. The vast majority of cup-stem combinations were used in very few operations.

Oral bisphosphonates and risk of ischemic stroke: a case-control study.

UNLABELLED: Bisphosphonates have been associated with an increased risk of atrial fibrillation and may thus be associated with an increased risk of ischemic stroke. This would have substantial clinical and public health implications. We found no evidence of an association between bisphosphonate use and risk of ischemic stroke. INTRODUCTION: Bisphosphonates have been associated with an increased risk of atrial fibrillation in some studies and may be associated with an increased risk of ischemic stroke. However, data regarding these possibilities are limited. METHODS: We conducted a population-based case-control study of 6,257 female cases of ischemic stroke and 31,285 age- and gender-matched population controls. Data on bisphosphonate use, other medication use, comorbidity, and ischemic stroke were obtained from medical databases. Current bisphosphonate use was defined as at least one redeemed prescription within 90 days before diagnosis/index date. We estimated the odds ratio (OR) of ischemic stroke among users and nonusers of bisphosphonates using conditional logistic regression, controlling for potential confounding factors. RESULTS: One hundred eighty-two (2.9%) cases and 901 (2.9%) controls were current users of bisphosphonates. Etidronate and alendronate were prescribed with similar frequency among cases and controls. The adjusted OR of ischemic stroke for bisphosphonate users compared with nonusers was 0.97 (95% confidence interval [CI], 0.82-1.15). New and continuing bisphosphonate users had adjusted ORs for ischemic stroke of 1.16 (95% CI, 0.69-1.96) and 0.97 (95% CI, 0.81-1.16), respectively. Excluding patients with known atrial fibrillation/flutter yielded an OR of 1.00 (95% CI, 0.85-1.19). The OR for ischemic stroke was 0.59 (95% CI, 0.32-1.09) among patients with a history of previous hospitalization for cardiovascular disease and 1.07 (95% CI, 0.88-1.18) among those without (P < 0.001). The OR for former users was 1.23 (95% CI, 1.01-1.49). CONCLUSION: We found no evidence of an association of oral bisphosphonate use with the risk of ischemic stroke.

Generation, characterization and ELISA of monospecific antibodies against the subunits of a Ca2+-dependent protein kinase and a Ca2+-transport ATPase from rabbit skeletal muscle.

Monospecific precipitating sheep antibodies were generated for the first time against the purified, homogeneous alpha-, beta- and gamma-subunits of the Ca2+-dependent protein kinase, phosphorylase kinase, from rabbit muscle. As reference, antibodies against the holoenzyme and the CA2+-transport ATPase of sarcoplasmic reticulum were induced. In all cases antibody titers could be quantitated (standard error 5-10%) by enzyme-linked immunosorbent assay. Differentiation of antibody binding was achieved by quantitative precipitation and complement fixation assays. In general maximal antibody titers were reached 56 days after primary immunization and high titers (approximately 5000) were maintained for several weeks. Anti-alpha, anti-beta and anti-gamma avidly precipitate the denatured subunits employed as immunogens as well as the native enzyme. No cross-reactivity between antibodies against a specific subunit and any of the other heterologous subunits was demonstrable in double immunodiffusion assays providing no evidence for immunologically identical sites on the alpha-, beta- and gamma-subunits. Since anti-alpha, anti-beta and anti-gamma strongly inhibit enzyme activity, it is likely that they do so primarily by sterically interfering with the binding of the large substrate phosphorylase b (Mr 2.0 X 10(5)) to phosphorylase kinase (Mr 1.3 X 10(6)). It cannot be excluded, however, that anti-beta and anti-gamma bind to the active sites on these 2 subunits.

[High resolution multislice CT of the lung: comparison with sequential HRCT slices]. / Hochauflösende Mehrschicht-CT der Lunge: Vergleich mit HRCT-Einzelschichten.

PURPOSE: To compare the image quality of high-resolution (HR) spiral CT scans from a multislice CT scanner with sequential HRCT scans from a singleslice CT scanner. MATERIALS AND METHODS: 20 patients with diffuse lung disease received a high-resolution spiral CT on a multislice scanner (4 slices) and 5 HRCT single slices (1 mm) on a singleslice scanner. Scan parameters of the multislice scanner were: Collimation 4 x 1 mm, pitch 6, slice thickness 1 mm. 5 HRCT slices were compared to the corresponding HR spiral CT slices using a 5-point scale by 5 radiologists with regard to the image quality and the number of artifacts. The evaluation was performed with a multivariate analysis (MANOVA test). RESULTS: Overall impression of image quality, noise, central vessels and bronchi, and all pathological changes were not significantly different between the two CT methods. Sequential HRCT scans were considered to be significantly better than HR spiral CT scans for spatial resolution (p = 0.02), depiction of peripheral vessels (p = 0.02), and of small bronchi (p = 0.05), and significantly worse for depiction of interlobar septa (p < 0.001). Diagnostically relevant differences were found in only 2.2%. Breathing and heartbeat artifacts each were 3 times higher in the sequential HRCT technique than in the multislice-spiral technique (p < 0.0001). CONCLUSION: HR spiral CT scans performed on a multislice CT scanner provide significantly less artifacts and an equal diagnostic image quality compared to sequential HRCT scans performed on a singleslice CT scanner. Multislice spiral CT in HR technique may replace the common scanning technique with conventional spiral CT and additional HRCT scans for diffuse lung diseases.

[Imaging diagnosis of solitary pulmonary nodules on an open low-field MRI system--comparison of two MR sequences with spiral CT]. / Bildgebende Diagnostik solitärer Lungenrundherde am offenen Niederfeld-MRT--Ein Vergleich zweier MR-Sequenzen mit der Spiral-CT.

OBJECTIVE: To evaluate and compare two fast gradient-echo sequences (GRE) concerning the visualization of solitary pulmonary nodules with an open low-field MRI system in comparison to computed tomography. MATERIALS AND METHODS: Fourteen patients with solitary pulmonary nodules detected by spiral CT ranging in size from 6 mm to 42 mm (mean 20 mm) underwent MRI on an open 0.2 T scanner using a spoiled 2D GRE (2D FLASH; TR/ TE/Flip = 100 ms/7.5 ms/30 degrees ) and a totally refocused 2D steady-state GRE (True-FISP; TR/TE/FA = 7.3 ms/3.5 ms/80 degrees ). The image quality concerning artifacts (by flow, breathing and susceptibility) and the morphologic characteristics of the nodules were scored and compared with CT by two independent radiologists. The diameters of the nodules measured by MRI were compared with CT measurements. The sequences were also evaluated with regard to the signal-to-noise ratio (SNR) of the lesion. RESULTS: All lesions were detected with the 2D FLASH sequence. True-FISP failed to find a granuloma with a size of 6 mm. The 2D FLASH was rated significantly superior to true FISP concerning image quality artifacts by susceptibility as well as concerning to CT the presentation of nodule characteristics. In MR images, the size of lesions was significantly smaller than in CT images for both sequences: for 2D FLASH the mean difference was 0.9 mm and for true FISP 2.6 mm. The SNR of the nodules was significantly higher for the 2D FLASH than for the true FISP. CONCLUSION: In low field MRI, the 2D FLASH sequence is superior to the 2D true FISP sequence in imaging of pulmonary nodules. With the 2D FLASH sequence nodules of 6 mm or larger in size can be visualized.

The risk of venous thromboembolism, myocardial infarction, stroke, major bleeding and death in patients undergoing total hip and knee replacement: a 15-year retrospective cohort study of routine clinical practice.

We examined the risk of thrombotic and major bleeding events in patients undergoing total hip and knee replacement (THR and TKR) treated with thromboprophylaxis, using nationwide population-based databases. We identified 83 756 primary procedures performed between 1997 and 2011. The outcomes were symptomatic venous thromboembolism (VTE), myocardial infarction (MI), stroke, death and major bleeding requiring hospitalisation within 90 days of surgery. A total of 1114 (1.3%) and 483 (0.6%) patients experienced VTE and bleeding, respectively. The annual risk of VTE varied between 0.9% and 1.6%, and of bleeding between 0.4% and 0.8%. The risk of VTE and bleeding was unchanged over a 15-year period. A total of 0.7% of patients died within 90 days, with a decrease from 1% in 1997 to 0.6% in 2011 (p < 0.001). A high level of comorbidity and general anaesthesia were strong risk factors for both VTE and bleeding, with no difference between THR and TKR patients. The risk of both MI and stroke was 0.5%, which remained unchanged during the study period. In this cohort study of patients undergoing THR and TKR patients in routine clinical practice, approximately 3% experienced VTE, MI, stroke or bleeding. These risks did not decline during the 15-year study period, but the risk of dying fell substantially.

Prenatal exposure to acid-suppressive drugs and the risk of childhood asthma: a population-based Danish cohort study.

BACKGROUND: Proton pump inhibitors (PPIs) may activate the immune system and cause asthma. AIM: To investigate the association of prenatal exposure to PPIs and histamine 2-receptor antagonists (H2RAs) with risk of asthma. METHODS: In this cohort study, 197,060 singletons born between 1996 and 2008 in northern Denmark were followed until the end of 2009. Data were obtained through Danish medical registries. Asthma in offspring was defined as at least two prescriptions of both a ß-agonist and an inhaled glucocorticoid and/or a hospital diagnosis of asthma during the follow-up. Cox proportional-hazard regression was used to compute incidence rate ratios, adjusting for covariates. RESULTS: A total of 2238 (1.1%) children were prenatally exposed to PPIs and 24,506 (12.4%) children developed asthma during follow-up (median follow-up = 6.8 years). The adjusted IRR (aIRR) of asthma associated with prenatal exposure to PPIs was 1.41 (95% confidence interval (CI): 1.27-1.56), compared with those unexposed. The association did not vary by trimester of exposure, and prenatal exposure to H2RAs was associated with similar increase in risk. The aIRR for maternal PPI and H2RA use in the year after, but not during pregnancy was 1.32 (95% CI: 1.20-1.46) and 1.13 (0.93-1.36), respectively, compared with non-use during and in the year after pregnancy. CONCLUSIONS: Prenatal exposure to both PPIs and H2RAs was associated with an increased risk of asthma in our study. Because the observed association is not drug specific and also observed for maternal postnatal use it may be explained by a 'class effect' or maternal underlying condition.

Risk of revision of a total hip replacement in patients with diabetes mellitus: a population-based follow up study.

We have evaluated the extent to which diabetes affects the revision rate following total hip replacement (THR). Through the Danish Hip Arthroplasty Registry we identified all patients undergoing a primary THR (n = 57 575) between 1 January 1996 and 31 December 2005, of whom 3278 had diabetes. The presence of diabetes among these patients was identified through the Danish National Registry of Patients and the Danish National Drug Prescription Database. We estimated the relative risk for revision and the 95% confidence intervals for patients with diabetes compared to those without, adjusting for the confounding factors. Diabetes is associated with an increased risk of revision due to deep infection (relative risk = 1.45 (95% confidence interval 1.00 to 2.09), particularly in those with type 2 diabetes (relative risk = 1.49 (95% confidence interval 1.02 to 2.18)), those with diabetes for less than five years prior to THR (relative risk = 1.69 (95% confidence interval 1.24 to 2.32)), those with complications due to diabetes (relative risk = 2.11 (95% confidence interval 1.41 to 3.17)), and those with cardiovascular comorbidities prior to surgery (relative risk = 2.35 (95% confidence interval 1.39 to 3.98)). Patients and surgeons should be aware of the relatively elevated risk of revision due to deep infection following THR in diabetes particularly in those with insufficient control of their glucose level.

Risk factors for venous thromboembolism in patients undergoing total hip replacement and receiving routine thromboprophylaxis.

BACKGROUND: Data on the risk factors for venous thromboembolism among patients undergoing total hip replacement and receiving pharmacological thromboprophylaxis are limited. The purpose of this study was to examine potential patient-related risk factors for venous thromboembolism following total hip replacement in a nationwide follow-up study. METHODS: Using medical databases, we identified all patients who underwent primary total hip replacement and received pharmacological thromboprophylaxis in Denmark from 1995 to 2006. The outcome measure was hospitalization with venous thromboembolism within ninety days of surgery. We considered age, sex, indication for primary total hip replacement, calendar year of surgery, and comorbidity history as potential risk factors. RESULTS: The overall rate of hospitalization for venous thromboembolism within ninety days following a primary total hip replacement was 1.02% (686 hospitalizations after 67,469 procedures) at a median of twenty-two days. The incidence of symptomatic deep venous thrombosis and of nonfatal pulmonary embolism was 0.7% (499 of 67,469) and 0.3% (205 of 67,469), respectively. The incidence of death due to venous thromboembolism or from all causes was 0.05% (thirty-eight patients) and 1.0% (678 patients), respectively. Patients with rheumatoid arthritis had a reduced relative risk for venous thromboembolism compared with patients with primary osteoarthritis (adjusted relative risk = 0.47; 95% confidence interval, 0.25 to 0.90). Patients with a high score on the Charlson comorbidity index had an increased relative risk for venous thromboembolism compared with patients with a low score (adjusted relative risk = 1.45; 95% confidence interval, 1.02 to 2.05). Patients with a history of cardiovascular disease (relative risk = 1.40; 95% confidence interval, 1.15 to 1.70) or prior venous thromboembolism (relative risk = 8.09; 95% confidence interval, 6.07 to 10.77) had an increased risk for venous thromboembolism compared with patients without that history. CONCLUSIONS: The cumulative incidence of a venous thromboembolism within ninety days of surgery among patients with total hip replacement receiving pharmacological thromboprophylaxis was 1%. This information on the associated risk factors could be used to better anticipate the risk of venous thromboembolism for an individual patient.

[Complications of percutaneous endoscopic gastrostomy (PEG)]. / Komplikationen der perkutanen endoskopischen Gastrostomie (PEG).

Percutaneous endoscopic gastrostomy (PEG) is a simple technique for the endoscopic placement of a permanent feeding access. The procedure is relatively safe and the technique well established. PEG can, however, be associated with serious complications and death. Following the rare PEG-related complication of an abdominal dislocation we review technique, indications and complications of this sixteen year old method.

[Contributions to the mechanism of the Witebsky-test (author's transl)]. / Zum Mechanismus des Witebsky-Tests

The assumption that immune and normal alloantibodies of the ABO system could be distinguished by partial neutralization with soluble specific blood group substance (Witebsky test) has been reexamined. The following results were presented: 1. ABO alloantibodies in both normal and immune sera as well as their IgG and IgM preparations were inhibited by their homologous soluble specific blood group substances. 2. Anti-A and anti-B immune antibodies as well as normal antibodies of the IgG class were found to be strong hemagglutinins in a saline medium; therefore they have to be called "complete" hemagglutinins as have anti-A and anti-B antibodies of the class IgM too. 3. ABO alloantibodies in both IgG and IgM preparations were able to form precipitation pellets with their homologous soluble specific blood group substances. IgM revealed a stronger precipitation power as IgG. 4. Agglutination reaction in saline was inhibited by the 50-200-fold group substance concentration needed for a optimal precipitation reaction, whereas agglutination of enzyme treated erythrocytes or red cells tested with antiglobulin (Coombs) sera was inhibited by a 20,000-80,000-fold concentration of the blood group substances. 5. Soluble antigen-antibody complexes, prepared from solubilized precipitates or from Witebsky test mixtures using chromatography, ultracentrifuge or ultrafiltration for separation were able to agglutinate erythrocytes in the antiglobulin or papain test. Following conclusions were drawn: A. Soluble antigen-antibody complexes are the main component leading to a positive Witebsky test. B. The mechanism of the Witebsky test as it has to be assumed in respect to our findings do not allow the distinguish immune and normal alloantibodies resp. IgG and IgM alloagglutinins in the ABO system.