Enthesitis in a European registry-based cohort of patients with psoriatic arthritis treated with tumour necrosis factor inhibitors: clinical burden, patient-reported outcomes, and treatment response.

OBJECTIVE: To explore the registration of enthesitis among biologic-naïve patients with psoriatic arthritis (PsA) initiating tumour necrosis factor inhibitor (TNFi) treatment across 12 European registries, compare the disease burden and patient-reported outcomes (PROs) between patients with and without enthesitis, and assess the enthesitis treatment response. METHOD: Demographics, clinical characteristics, and PROs at first TNFi (TNFi-1) initiation (baseline) were assessed in patients with PsA, diagnosed by a rheumatologist, with versus without assessment of entheses and between those with versus without enthesitis. Enthesitis scores and resolution frequency were identified at follow-up. RESULTS: Of 10 547 patients in the European Spondyloarthritis (EuroSpA) Research Collaboration Network initiating TNFi, 1357 underwent evaluation for enthesitis. Eight registries included a validated scoring system for enthesitis. At baseline, 874 patients underwent entheses assessment [Maastricht Ankylosing Spondylitis Enthesitis Score (MASES) 485 patients, Spondyloarthritis Research Consortium of Canada (SPARCC) 389 patients]. Enthesitis was detected by MASES in 170/485 (35%, mean score ± sd 3.1 ± 2.4) and by SPARCC in 236/389 (61%, 4 ± 3.4). Achilles enthesitis was most frequent, by both MASES (unilateral/bilateral 28%/9%) and SPARCC (48%/18%). MASES/SPARCC baseline and follow-up scores for TNFi-1 were available for 100/105 patients. Of these, 63 patients (63%) (MASES) and 46 (43.8%) (SPARCC) achieved resolution of enthesitis. The site-specific enthesitis resolution was overall lower at SPARCC sites (peripheral; 63-80%) than at MASES sites (mainly axial; 82-100%) following TNFi-1. Disease activity and PROs were worse in patients with versus without enthesitis. CONCLUSION: Entheseal assessments are only registered in a minority of patients with PsA in routine care. When assessed, enthesitis was common, and a substantial proportion demonstrated resolution following treatment with TNFi-1.

Levels of C-Reactive Protein and Sodium May Differentiate a Perforated Appendix from a Nonperforated Appendix in Children.

BACKGROUND: Acute appendicitis (AA) might be amenable to conservative antibiotic treatment, whereas a perforated appendix (PA) necessitates surgery. We investigated the value of clinical-laboratory markers in distinguishing AA from a PA. METHODS: Retrospectively obtained preoperative parameters for 306 consecutive patients (<18 years) with histologically confirmed appendicitis (AA (n = 237) vs. PA (n = 69)), treated at our institution between January 2014 and December 2017. RESULTS: A PA was associated with male preponderance, younger age, decreased sodium level and increased white blood cell count, Tzanakis score, C-reactive protein (CRP) level, and CRP-to-lymphocyte ratio (CLR). Upon discrimination analysis, CLR and CRP displayed the highest accuracy in differentiating a PA from AA. Regression analysis identified levels of CRP, sodium, and the Tzanakis score as independent predictors for a PA. CONCLUSION: Levels of CLR, CRP, sodium, and Tzanakis score might support decision-making regarding treatment options for pediatric appendicitis.

Greater trochanteric pain syndrome: predicting who will respond to a local glucocorticoid injection.

Objectives: This study aimed to explore whether certain clinical tests or a rapid improvement in lateral hip pain following periarticular injection are predictive of subsequent efficacy of local glucocorticoid (GC) injection in greater trochanteric pain syndrome (GTPS).Method: This secondary analysis of a randomized controlled trial of an injection of GC and local anaesthetic (LA) versus placebo included 44 patients with GTPS. Two subgroups of patients were defined: (i) 30 min responders, reporting a decrease of ≥ 50% of the initial pain at 30 min post-injection; and (ii) positive triple test, presenting a combination of three positive clinical tests (30-second single-leg stance, FABER, and Lequesne). Median level of numeric rating scale for pain at 1 month was the primary outcome. Interaction analysis of treatment effect in the subgroups was performed using a linear regression adjusting for pain at baseline.Results: Sixteen patients (36%) were 30 min responders. In this group, GC treatment was associated with a significant improvement in pain at 1 month compared to non-responders (p = 0.03). The 30 min response was not associated with the use of LA. Positive triple test (22% of patients) was associated with higher pain scores at baseline (p = 0.03). In this group, patients who received placebo had significantly more pain at 1 month than those with the cortisone injection (p = 0.04).Conclusion: Patients with GTPS who present a rapid decrease in pain after periarticular injection, and those who display a combination of three specific clinical tests, are more likely to benefit from an injection with GC and anaesthetic.

Isolated tracheoesophageal fistula versus esophageal atresia - Early morbidity and short-term outcome. A single institution series.

PURPOSE: We compared the postnatal course, morbidity and early results after repair for cases of isolated or "pure" TEF with those for cases of esophageal atresia (EA) with distal tracheoesophageal fistula (TEF). METHODS: Twenty-four consecutive infants were divided into two groups: isolated TEF [TEF group] (n = 5) and EA with distal TEF [EA group] (n = 19). RESULTS: A high rate of prematurity (29%) and major cardiac and other surgically-relevant malformations (0.8 vs. 0.7 per infant) was found in both groups. The median age at surgery was 8 days for the TEF group vs. 1 day for the EA group (p < 0.01). Most infants of both cohorts had stable acid-base and respiratory parameters at admission. Generally, tracheoscopy provided valuable information regarding the position of the TEF. Surgery for isolated TEF was performed via right cervicotomy in 4 cases and via thoracotomy in one. Postoperative thoracostomy tubes were inserted in 3 cases and one emergency gastrostomy was created for acute gastric overextension (exclusively in patients with EA). The duration of postoperative mechanical ventilation (49 vs. 113 h, p = 0.045) and the median length of stay in the pediatric surgery unit (10 vs. 20.5 days, p = 0.003) were shorter for the isolated TEF group. Four EA patients experienced severe events. Total mortality was 8% (0 out of 5 with TEF vs. 2 out of 19 with EA). CONCLUSION: Developmental delay and a high rate of morbidity were found in both groups. More complex surgery increased perioperative morbidity in cases of EA. With early recognition of isolated TEF, a less complicated course can be expected in comparison with esophageal atresia.

Veterinarian's dilemma: a study of how Danish small animal practitioners handle financially limited clients.

This study examined the extent to which Danish veterinary practices encounter financially limited clients and how different factors relating to the animal, the client and the veterinarian affect decisions to provide treatment for these clients. 300 small animal practices were invited to participate in an online survey. 195 participated, giving a response rate of 65 per cent. The results show that Danish small animal veterinary practices encounter clients with limited finances regularly: 33.8 per cent of them 3-4 times, 24.6 per cent 5-10 times and 19.5 per cent 1-2 times a month. Only around 9 per cent reported having a written practice policy on handling financially limited clients. Factors affecting decisions to treat include the severity and type of the animal's condition, the medical care needed and the client's expressed emotions. The propensity to treat is significantly higher in female veterinarians and in situations involving unborn animals. The overall conclusion is that small animal veterinary practices often provide treatment to clients who are not able to pay-far beyond what is legally required. This can be considered a major economic and psychological challenge for the practising veterinarians.

[Esophageal Atresia Repair - Can We Influence the Schedule?]. / Ösophagusatresie und tracheoösophageale Fistel - ist der Zeitpunkt der Versorgung steuerbar?

UNLABELLED: The treatment of newborns with esophageal atresia (EA) and tracheoesophageal fistula (TEF) is associated with a great logistic effort. The aim of the presented study was to analyse the possibility to influence the time of surgery. MATERIAL AND METHOD: Data from 30 neonates with EA and TEF regarding the date and mode of birth, biometric data and preoperative acid-base and blood gas values were collected retrospectively. The newborns were divided into two subgroups: birth between Monday and Thursday ("week"), and birth from Friday to Sunday ("weekend"). RESULTS: We observed a seasonal peak of births in November/December. The rate of prenatal ultrasound detection of polyhydramnions was 40%. In 14 of 16 cases with Caesarean section, maternal or foetal problems predicted the date and mode of delivery. In both groups, most newborns had an unimpaired postnatal adaptation. There were no significant differences regarding biometry. Delivery at the weekend was associated with later surgical repair (second vs. first day of life). Repeated estimations of acid-base and blood gas parameters over a median time span of 13 hours revealed a stable situation with a trend to normalisation. DISCUSSION: The time of birth is multifactorial and, in most cases, can neither be predicted nor influenced. Stable respiratory and metabolic parameters in the majority of patients allow a surgical intervention within a limited time frame during the first days of life. CONCLUSION: As it is hardly possible to plan the surgical procedure, an experienced team as well as neonatal intensive care facilities and operation room access must be available throughout the week.

[Greater trochanteric pain syndrome]. / "Périarthrite de la hanche".

Trochanteric bursitis, also known as "greater trochanter pain syndrome", is a frequent and often under-diagnosed cause of pain in the lateral hip region. The diagnosis is essentially based on the clinical examination; however various forms of imaging may be useful to confirm the diagnosis and particularly to ex- clude other aetiologies. The different therapeutic options include non-steroidal anti-inflammatories, physiotherapy, local injections of cortisone and local anaesthetic, and extra-corporeal shock wave therapy. Surgical intervention is only indicated in rare cases.

[Pigmented villonodular synovitis]. / La synovite villonodulaire.

Pigmented villonodular synovitis (PVNS), also known as tenosynovial giant cell tumour is an articular pathology that occurs predominantly in young adults and is caused by an abnormal proliferation of the synovial membrane. The clinical presentation includes pain and joint swelling. MRI represents the best imaging modality to investigate this disease but the histopathology of synovial tissue provides the definitive diagnosis. The management of PVNS is often difficult due to the high risk of relapse after treatment. The objective of this article is to review the literature regarding the diagnosis and therapy of this poorly understood condition.

Potential animal and environmental sources of Q fever infection for humans in Queensland.

Q fever is a vaccine-preventable disease; despite this, high annual notification numbers are still recorded in Australia. We have previously shown seroprevalence in Queensland metropolitan regions is approaching that of rural areas. This study investigated the presence of nucleic acid from Coxiella burnetii, the agent responsible for Q fever, in a number of animal and environmental samples collected throughout Queensland, to identify potential sources of human infection. Samples were collected from 129 geographical locations and included urine, faeces and whole blood from 22 different animal species; 45 ticks were removed from two species, canines and possums; 151 soil samples; 72 atmospheric dust samples collected from two locations and 50 dust swabs collected from domestic vacuum cleaners. PCR testing was performed targeting the IS1111 and COM1 genes for the specific detection of C. burnetii DNA. There were 85 detections from 1318 animal samples, giving a detection rate for each sample type ranging from 2.1 to 6.8%. Equine samples produced a detection rate of 11.9%, whilst feline and canine samples showed detection rates of 7.8% and 5.2%, respectively. Native animals had varying detection rates: pooled urines from flying foxes had 7.8%, whilst koalas had 5.1%, and 6.7% of ticks screened were positive. The soil and dust samples showed the presence of C. burnetii DNA ranging from 2.0 to 6.9%, respectively. These data show that specimens from a variety of animal species and the general environment provide a number of potential sources for C. burnetii infections of humans living in Queensland. These previously unrecognized sources may account for the high seroprevalence rates seen in putative low-risk communities, including Q fever patients with no direct animal contact and those subjects living in a low-risk urban environment.

Advanced paternal age and mortality of offspring under 5 years of age: a register-based cohort study.

STUDY QUESTION: Do children born to fathers of advanced age have an increased risk of dying before the age of 5 years? SUMMARY ANSWER: Children born to fathers aged 40 years or more have an increased risk of dying in early childhood due to an excess risk of fatal congenital anomalies, malignancies and external causes. WHAT IS KNOWN ALREADY: Advanced paternal age has previously been associated with adverse reproductive outcomes and some long-term health problems in the offspring. This is possibly due to specific point mutations, a condition known to increase in the sperm with increasing paternal age. STUDY DESIGN, SIZE, DURATION: A Danish population-based register study, designed as a prospective cohort study, of 1 575 521 live born children born from 1978 to 2004. The age of the child (in days) was used as the underlying time and the children entered the cohort the day they were born and were followed until 31 December 2009. The children were censored on date of turning 5 years, date of death or date of emigration, whichever occurred first. PARTICIPANTS/MATERIALS, SETTING, METHODS: Data from population-covering registers from Statistics Denmark including the Integrated Database for Labour Market Research, the Medical Birth Registry and the Registry of Causes of Death was linked using the unique civil registry number. Hazard ratios (HR) with 95% confidence intervals (CI) were used to estimate the risk of under-five mortality. The effect of paternal age was examined using restricted cubic splines and paternal age groups. MAIN RESULTS AND THE ROLE OF CHANCE: Compared with children born to fathers aged 30-34 years, a statistically significant excess risk was found for children born to fathers aged 40-44 years [HR: 1.10 (95% CI: 1.00-1.21)] and children born to fathers aged 45+ years [HR: 1.16 (95% CI: 1.02-1.32)]. When only looking at 1-5 year olds, the relative risk (HR) among children born to fathers aged 40-44 years increased to 1.24 (95% CI: 1.00-1.53) and the risk in the oldest paternal age group (45+ years) rose to 1.65 (95% CI: 1.24-2.18). The results suggest that the elevated risk for children of fathers aged 40 years or more was primarily attributed to an elevated risk of dying from congenital malformations, malignancies and external causes. LIMITATIONS, REASONS FOR CAUTION: Specific causes of death might be misclassified; however, this is not likely to be dependent on paternal age. In some cases, the biological father may differ from the father registered. This misclassification is most likely non-differential. WIDER IMPLICATIONS OF THE FINDINGS: The excess risk of mortality among children born to older fathers is in accordance with the literature. The association needs further attention as it can provide valuable knowledge of the etiology of genetic diseases. Also, the association could become of greater importance in the future if the proportion of fathers aged 40+ years keeps growing. STUDY FUNDING/COMPETING INTEREST (S): None.

Polymerase chain reaction-based screening for the ceftriaxone-resistant Neisseria gonorrhoeae F89 strain.

Emergence and spread of Neisseria gonorrhoeae resistant to extended spectrum cephalosporins is a major problem threatening treatment of gonorrhoea and is further highlighted by the recent report of a second ceftriaxone-resistant N. gonorrhoeae strain (F89) in Europe, initially observed in France and subsequently identified in Spain. N. gonorrhoeae antimicrobial resistance (AMR) surveillance has acquired new importance and molecular tools have the potential to enhance bacterial culture-based methods. In this study, we established a polymerase chain reaction (PCR) protocol for direct detection of the F89 strain. A key component of this screening protocol was the development of a hybridisation probe-based melting curve analysis assay (mosaic501-hybPCR) to detect the presence of an A501P substitution on the N. gonorrhoeae mosaic penicillin binding protein 2 (PBP2) sequence, an important characteristic of the F89 strain. The mosaic501-hybPCR was evaluated using plasmid-derived positive controls (n=3) and characterised gonococcal (n=33) and non-gonococcal (n=58) isolates. The protocol was then applied to 159 clinical specimens from Sydney, Australia, collected during the first half of the year 2012 that were N. gonorrhoeae PCR-positive. Overall, the results indicate that the PCR-based protocol is suitable for direct detection of the N. gonorrhoeae F89 strain in non-cultured clinical samples. It therefore provides an additional tool to aid investigations into the potential spread of F89 strain throughout Europe and elsewhere.

A bivalent Neisseria meningitidis recombinant lipidated factor H binding protein vaccine in young adults: results of a randomised, controlled, dose-escalation phase 1 trial.

Neisseria meningitidis is a leading cause of meningitis and septicaemia, but a broadly-protective vaccine against endemic serogroup B disease is not licensed and available. The conserved, outer-membrane lipoprotein factor H binding protein (fHBP, also known as LP2086) is expressed as one of two subfamily variants in virtually all meningococci. This study investigated the safety, tolerability, and immunogenicity of a recombinant-expressed bivalent fHBP (r-fHBP) vaccine in healthy adults. Participants (N=103) aged 18-25 years were recruited into three ascending dose level cohorts of 20, 60, and 200µg of a bivalent r-fHBP vaccine formulation and randomised to receive vaccine or placebo at 0, 1, and 6 months. The vaccine was well tolerated. Geometric mean titres (GMTs) for r-fHBP subfamily-specific IgG antibodies increased 19-168-fold from pre-vaccination to post-dose 2 in a dose level-dependent manner. In addition, robust serum bactericidal assay using human complement (hSBA) responses for strains expressing both homologous and heterologous fHBP variants were observed. After three vaccinations, 16-52% of the placebo group and 47-90%, 75-100%, and 88-100%, of the 20, 60, and 200µg dose levels, respectively, had seroprotective (≥ 1:4) hSBA titres against six serogroup B strains. The bivalent r-fHBP vaccine was well tolerated and induced robust bactericidal activity against six diverse serogroup B strains in young adults at the 60 and 200µg dose levels.

False-negative results using Neisseria gonorrhoeae porA pseudogene PCR - a clinical gonococcal isolate with an N. meningitidis porA sequence, Australia, March 2011.

The gonococcal porA pseudogene is a popular target for in-house Neisseria gonorrhoeae PCR methods. With this study we present two novel findings: the first case of an N. gonorrhoeae porA pseudogene PCR false-negative result caused by sequence variation, and in the same organism, the first description of a clinical N. gonorrhoeae strain harbouring an N. meningitidis porA sequence.

Comparison of a multiplexed MassARRAY system with real-time allele-specific PCR technology for genotyping of methicillin-resistant Staphylococcus aureus.

The Sequenom MassARRAY iPLEX single-nucleotide polymorphism (SNP) typing platform uses matrix-assisted laser desorption ionization time-of-flight mass spectrometry (MALDI-TOF MS) coupled with single-base extension PCR for high-throughput multiplex SNP detection. In this study, we investigated the use of iPLEX MassARRAY technology for methicillin-resistant Staphylococcus aureus (MRSA) genotyping. A 16-plex MassARRAY iPLEX GOLD assay (MRSA-iPLEX) was developed that targets a set of informative SNPs and binary genes for MRSA characterization. The method was evaluated with 147 MRSA isolates, and the results were compared with those of an established SYBR Green-based real-time PCR system utilizing the same SNP-binary markers. A total of 2352 markers belonging to 44 SNP-binary profiles were analysed by both real-time PCR and MRSA-iPLEX. With real-time PCR as the reference standard, MRSA-iPLEX correctly assigned 2298 of the 2352 (97.7%) markers. Sequence variation in the MRSA-iPLEX primer targets accounted for the majority of MRSA-iPLEX erroneous results, highlighting the importance of primer target selection. MRSA-iPLEX provided optimal throughput for MRSA genotyping, and was, on a reagent basis, more cost-effective than the real-time PCR methods. The 16-plex MRSA-iPLEX is a suitable alternative to SYBR Green-based real-time PCR typing of major sequence types and clonal complexes of MRSA.

Evaluation of a clinical scoring system and directed laboratory testing for respiratory virus infection in hematopoietic stem cell transplant recipients.

A simple clinical screening (CS) tool for respiratory virus (RV) infection was introduced and evaluated in a single hematology ward, as part of a strategy to reduce nosocomial RV infection. Up to 6 clinical symptoms or signs were scored and a predefined threshold score of ≥ 2 prompted paired nose/throat swab (NTS) collection for RV testing. The criterion standard for RV infection was positive immunofluorescence (IF) or polymerase chain reaction (PCR) for 7 and 15 viruses, respectively. The tool was shown to be most beneficial at excluding infection at a threshold score of 1 (negative predictive value [NPV] 89%, [95% confidence interval 78-96%], sensitivity 85% [70-94%], specificity 35% [27-43%]), compared with a score of 2 (NPV 85% [76-91%], sensitivity 63% [46-77%], specificity 57% [48-65%]) at a prevalence of 22%. The tool's ability to diagnose infection was limited (positive predictive value 27% and 29% at thresholds 1 and 2). The sensitivity of IF compared with PCR was 45% for the 7 viruses common to both, and 23% for the extended virus panel detected by PCR. An algorithm incorporating CS, paired NTS collection at a threshold of 1 symptom or sign, and sensitive testing including PCR can guide infection control measures in hospitalized hematopoietic stem cell transplant recipients.

Q fever seroprevalence in metropolitan samples is similar to rural/remote samples in Queensland, Australia.

Q fever is a vaccine preventable disease; however, despite this, high notification numbers are still recorded annually in Australia. We investigated the seroprevalence of Coxiella burnetii, the Q fever agent, in a Queensland sample population. Notification data (N = 6425) from 1984-2008 were collated, identifying high risk areas of Q fever exposure. Of these 177 were recorded in children. Serum samples were collected from Queensland and screened using both an immunoflourescence assay at 1:10 dilution and a commercially available ELISA kit. Results were collated based on age, geographical location and sex. From 1988 Queensland samples screened, 103 were identified as Q fever IgG-positive, giving a seroprevalence of 5.2% (95% CI 4.3-6.2%). Seroprevalence in the rural/remote population was 5.3% (95% CI 4.6-6.6%), and the metropolitan Brisbane population, which is considered not at risk, was 5.0% (95% CI 3.7-6.7%). Sixty-three seropositive males and 40 females were identified, along with an increase in seropositivity with increasing age. The seropositivity of children was 1.3% (95% CI 0.7-2.3%) from 844 samples. We have shown that both metropolitan and paediatric populations which are considered low risk of Coxiella exposure have surprisingly high seropositivity. These emerging groups require further investigation and consideration for the introduction of preventive measures.

Rapid single-nucleotide polymorphism-based identification of clonal Pseudomonas aeruginosa isolates from patients with cystic fibrosis by the use of real-time PCR and high-resolution melting curve analysis.

Pseudomonas aeruginosa genotyping relies mainly upon DNA fingerprinting methods, which can be subjective, expensive and time-consuming. The detection of at least three different clonal P. aeruginosa strains in patients attending two cystic fibrosis (CF) centres in a single Australian city prompted the design of a non-gel-based PCR method to enable clinical microbiology laboratories to readily identify these clonal strains. We designed a detection method utilizing heat-denatured P. aeruginosa isolates and a ten-single-nucleotide polymorphism (SNP) profile. Strain differences were detected by SYBR Green-based real-time PCR and high-resolution melting curve analysis (HRM10SNP assay). Overall, 106 P. aeruginosa sputum isolates collected from 74 patients with CF, as well as five reference strains, were analysed with the HRM10SNP assay, and the results were compared with those obtained by pulsed-field gel electrophoresis (PFGE). The HRM10SNP assay accurately identified all 45 isolates as members of one of the three major clonal strains characterized by PFGE in two Brisbane CF centres (Australian epidemic strain-1, Australian epidemic strain-2 and P42) from 61 other P. aeruginosa strains from Australian CF patients and two representative overseas epidemic strain isolates. The HRM10SNP method is simple, is relatively inexpensive and can be completed in <3 h. In our setting, it could be made easily available for clinical microbiology laboratories to screen for local P. aeruginosa strains and to guide infection control policies. Further studies are needed to determine whether the HRM10SNP assay can also be modified to detect additional clonal strains that are prevalent in other CF centres.