Tibial fracture associated with use of Arthrex self-tapping screws during tibial plateau leveling osteotomy in dogs and development of transcortical tibial fracture.

OBJECTIVE: Medical records for dogs treated with tibial plateau leveling osteotomy (TPLO) using Arthrex 3.5 mm self-tapping screws (STS) were evaluated to determine the incidence rate of transcortical tibial fractures (TCTF) and development of complications. STUDY DESIGN: Retrospective case report. STUDY POPULATION: A total of 78 dogs. METHODS: Dogs that underwent a TPLO performed from March 2022 to August 2023 were reviewed. Postoperative TPLO radiographs were examined for evidence of a TCTF with Arthrex 3.5 mm STS. Records were reviewed for complications up to 14 weeks after surgery. RESULTS: Evidence of a TCTF was found in 42% of cases (33 of 78) and 14% (36 of 250) of STS screws distal to the osteotomy. TCTFs were only identified distal to the osteotomy. Three dogs had radiographic evidence of more than one TCTF. Of the dogs with radiographic TCTF, 6% of patients (2 of 33) developed a major complication that required surgical stabilization of a tibial fracture associated with screw angulation relative to the plate. CONCLUSION: Use of Arthrex 3.5 mm STS for TPLO is associated with risk of TCTF. TCTF can compromise the structural properties of the tibia and cause complete tibial fracture requiring major revision surgery. CLINICAL SIGNIFICANCE: Development of TCTF after use of STS for TPLO has been recognized, in contrast to use of non-self-tapping screws, and was considered a benign complication. Our findings suggest TCTF associated with Arthrex 3.5 mm STS use in TPLO can contribute to major complications after surgery, including complete tibial fracture, particularly if screws are not placed perpendicular to the plate.

Assessment of online self-testing and self-sampling service providers for sexually transmitted infections against national standards in the UK in 2020.

OBJECTIVES: Online testing for STIs may help overcome barriers of traditional face-to-face testing, such as stigma and inconvenience. However, regulation of these online tests is lacking, and the quality of services is variable, with potential short-term and long-term personal, clinical and public health implications. This study aimed to evaluate online self-testing and self-sampling service providers in the UK against national standards. METHODS: Providers of online STI tests (self-sampling and self-testing) in the UK were identified by an internet search of Google and Amazon (June 2020). Website information on tests and associated services was collected and further information was requested from providers via an online survey, sent twice (July 2020, April 2021). The information obtained was compared with British Association for Sexual Health and HIV and Faculty of Sexual and Reproductive Healthcare guidelines and standards for diagnostics and STI management. RESULTS: 31 providers were identified: 13 self-test, 18 self-sample and 2 laboratories that serviced multiple providers. Seven responded to the online survey. Many conflicts with national guidelines were identified, including: lack of health promotion information, lack of sexual history taking, use of tests licensed for professional-use only marketed for self-testing, inappropriate infections tested for, incorrect specimen type used and lack of advice for postdiagnosis management. CONCLUSIONS: Very few online providers met the national STI management standards assessed, and there is concern that this will also be the case for service provision aspects that were not covered by this study. For-profit providers were the least compliant, with concerning implications for patient care and public health. Regulatory change is urgently needed to ensure that all online providers are compliant with national guidelines to ensure high-quality patient care, and providers are held to account if non-compliant.

Environmental contamination by Chlamydia trachomatis and Neisseria gonorrhoeae: is it time to change our infection control practices? Results of a regional study.

OBJECTIVES: Nucleic acid amplification tests (NAATs) are highly sensitive for the detection of Chlamydia trachomatis (CT) and Neisseria gonorrhoeae (NG) DNA/ribosomal RNA (rRNA). Previous studies have demonstrated contamination of surfaces in sexual health clinics (SHCs) with CT/NG. False positive results can occur if patient samples are contaminated by environmental DNA/rRNA. This can have a dramatic impact on patients' lives and relationships. Previous attempts to reduce contamination, through staff training alone, have been unsuccessful. We aimed to investigate environmental contamination levels in SHCs and to assess a two-armed intervention aimed at reducing surface contamination. METHODS: Questionnaires were sent to 10 SHCs. Six clinics, with differing characteristics, were selected to participate in sample collection. Each clinic followed standardised instructions to sample surfaces using a CT/NG NAAT swab. Clinics were invited to introduce the two-armed intervention. The first arm was cleaning with a chlorine-based cleaning solution once daily. The second arm involved introducing clinic-specific changes to reduce contamination. RESULTS: 7/10 (70%) clinics completed the questionnaire. Overall, 88/263 (33%) swabs were positive for CT/NG. Clinics 1, 3 and 4 had high levels of contamination, with 28/64 (44%), 17/33 (52%) and 30/52 (58%) swabs testing positive, respectively. Clinics 2 and 6 had lower levels of contamination, with 7/46 (15%) and 6/35 (17%), respectively. 0/33 (0%) of swabs were positive at clinic 5 and this was the only clinic already using a chlorine-based solution to clean all surfaces and delivering twice-yearly clinic-specific infection control training. Following both intervention arms at clinic 1, 2/50 (4%, p<0.0001) swabs tested positive for CT/NG. Clinic 4 introduced each arm separately. After the first intervention, 13/52 (25%, p=0.003) swabs tested positive and following the second arm 4/50 (8%, p<0.0001) swabs were positive. CONCLUSIONS: Environmental contamination is a concern in SHCs. We recommend that all SHCs monitor contamination levels and, if necessary, consider using chlorine-based cleaning products and introduce clinic-specific changes to address environmental contamination.

Case of apparent mpox reinfection.

We present an apparent second episode of mpox (monkeypox) genital ulcerative disease in a non-immunosuppressed MSM (man who has sex with men) patient who had completely recovered from a primary mpox infection 4 months previously. The patient had also received a complete two-dose course of smallpox vaccination between the two presentations. This case highlights the importance of continuing to include mpox in the differential diagnoses for individuals presenting with genital or mucosal ulceration, regardless of assumed immunity derived from prior infection or vaccination.

Increased reports of severe myocarditis associated with enterovirus infection in neonates, United Kingdom, 27 June 2022 to 26 April 2023.

Enteroviruses are a common cause of seasonal childhood infections. The vast majority of enterovirus infections are mild and self-limiting, although neonates can sometimes develop severe disease. Myocarditis is a rare complication of enterovirus infection. Between June 2022 and April 2023, twenty cases of severe neonatal enteroviral myocarditis caused by coxsackie B viruses were reported in the United Kingdom. Sixteen required critical care support and two died. Enterovirus PCR on whole blood was the most sensitive diagnostic test. We describe the initial public health investigation into this cluster and aim to raise awareness among paediatricians, laboratories and public health specialists.

No widespread dissemination of Chlamydia trachomatis diagnostic-escape variants and the impact of Neisseria gonorrhoeae positivity on the Aptima Combo 2 assay.

OBJECTIVES: A Finnish Chlamydia trachomatis (CT) new variant was detected in 2019 that escaped detection in the Hologic Aptima Combo 2 (AC2) assay due to a C1515T mutation in the CT 23S rRNA target region. Reflex testing of CT-negative/CT-equivocal specimens as well as those positive for Neisseria gonorrhoeae (NG) with the Hologic Aptima CT (ACT) assay was recommended to identify any CT variants. METHODS: From June to October 2019, specimens with discrepant AC2/ACT CT results were submitted to Public Health England and screened for detectable CT DNA using an inhouse real-time (RT)-PCR. When enough DNA was present, partial CT 23S rRNA gene sequencing was performed. Analysis of available relative light units and interpretative data was performed. RESULTS: A total of 317 discordant AC2/ACT specimens were collected from 315 patients. Three hundred were tested on the RT-PCR; 53.3% (n=160) were negative and 46.7% (n=140) were positive. Due to low DNA load in most specimens, sequencing was successful for only 36 specimens. The CT 23S rRNA wild-type sequence was present in 32 specimens, and two variants with C1514T or G1523A mutation were detected in four specimens from three patients. Of the discordant specimens with NG interpretation, 36.6% of NG-negative/CT-negative AC2 specimens had detectable CT DNA on the inhouse RT-PCR vs 53.3% of NG-positive/CT-negative specimens. CONCLUSIONS: No widespread dissemination of AC2 diagnostic-escape CT variants has occurred in England. We however identified the impact of NG positivity on the discordant AC2/ACT specimens; a proportion appeared due to NG positivity and the associated NG signal, rather than any diagnostic-escape variants or low DNA load. Several patients with gonorrhoea may therefore receive false-negative AC2 CT results. Single diagnostic targets and multiplex diagnostic assays have their limitations such as providing selection pressure for escape mutants and potentially reduced sensitivity, respectively. These limitations must be considered when establishing diagnostic pathways.

Canine ACL rupture: a spontaneous large animal model of human ACL rupture.

BACKGROUND: Anterior cruciate ligament (ACL) rupture in humans is a common condition associated with knee pain, joint instability, and secondary osteoarthritis (OA). Surgical treatment with an intraarticular graft provides reasonable outcomes at mid and long-term follow-up. Non-modifiable and modifiable factors influence risk of ACL rupture. The etiology, mechanobiology, causal biomechanics, and causal molecular pathways are not fully understood. The dog model has shared features of ACL rupture that make it a valuable spontaneous preclinical animal model. In this article, we review shared and contrasting features of ACL rupture in the two species and present information supporting spontaneous canine ACL rupture as a potentially useful preclinical model of human ACL rupture with a very large subject population. RESULTS: ACL rupture is more common in dogs than in humans and is diagnosed and treated using similar approaches to that of human patients. Development of OA occurs in both species, but progression is more rapid in the dog, and is often present at diagnosis. Use of client-owned dogs for ACL research could reveal impactful molecular pathways, underlying causal genetic variants, biomechanical effects of specific treatments, and opportunities to discover new treatment and prevention targets. Knowledge of the genetic contribution to ACL rupture is more advanced in dogs than in humans. In dogs, ACL rupture has a polygenetic architecture with moderate heritability. Heritability of human ACL rupture has not been estimated. CONCLUSION: This article highlights areas of One Health research that are particularly relevant to future studies using the spontaneous canine ACL rupture model that could fill gaps in current knowledge.

Predictive assessment of single-step BLUP with linear and non-linear similarity RKHS kernels: A case study in chickens.

Single-step GBLUP (ssGBLUP) to obtain genomic prediction was proposed in 2009. Many studies have investigated ssGBLUP in genomic selection in animals and plants using a standard linear kernel (similarity matrix) called genomic relationship matrix (G). More general kernels should allow capturing non-additive effects as well, whereas GBLUP is based on additive gene action. In this study, we generalized ssBLUP to accommodate two non-linear kernels, the averaged Gaussian kernel (AK) and the recently developed arc-cosine deep kernel (DK). We evaluated the methodology using body weight (BW) and hen-housing production (HHP) traits, recorded on a sample of phenotyped and genotyped commercial broiler chickens. There were, thus, different ssGBLUP models corresponding to G, AK and DK. We used random replication of training (TRN) and testing (TST) layouts at different genotyping rates (20%, 40%, 60% and 80% of all birds) in three selective genotyping scenarios. The selections were genotyping the youngest individuals in the pedigree (YS), random genotyping (RS) and genotyping based on parent average (PA). Predictive abilities were measured using rank correlations between the observed and the predictive phenotypic values in TST for each random partition. Prediction accuracy was influenced by the type of kernel when a large proportion of birds was genotyped. An advantage of non-linear kernels (AK and DK) was more apparent when 60 and 80% of birds had been genotyped. For BW, the lowest rank correlations were obtained with G (0.093 ± 0.015 using RS by 20% genotyped individuals) and the highest values with DK (0.320 ± 0.016 in the PA setting with 80% genotyped individuals). For HHP, the lowest and highest rank correlations were obtained by AK with 20% and 80% genotyped individuals, 0.071 ± 0.016 (in RS) and 0.23 ± 0.016 (in PA) respectively. Our results indicated that AK and DK are more effective than G when a large proportion of the target population is genotyped. Our expectation is that ssGBLUP with AK or DK models can perform even better than G when non-additive genetic effects influence the underlying variability of complex traits.

Best practices for measuring and reporting ground reaction forces in dogs.

Kinetic gait analysis and ground reaction forces (GRFs) have been used in hundreds of scientific manuscripts. Specific methodology, interpretation of results, and translation to clinical veterinary medicine have been inconsistent. This impedes the advance of veterinary medicine and poses a risk to patients. The objective of this report was to address methodological variations and share our consensus on a recommended approach with viable alternatives to data collection methods, analysis, reporting, and interpretation for GRFs in the dog. Investigators with experience performing kinetic gait analysis reviewed the literature and discussed the topics that most influenced GRF data collection, reporting, and interpretation. Methodological variations were reported and a consensus from the group was devised. There are several reasonable alternatives to collect, report, and interpret GRFs in dogs appropriately. Attention to detail is required in several areas to collect and report them. This review and consensus report should assist future investigations and interpretations of studies, optimize comparison between publications, minimize use of animals, and limit the investment in cost and time.

Epidemiology of pleural empyema in English hospitals and the impact of influenza.

Pleural empyema represents a significant healthcare burden due to extended hospital admissions and potential requirement for surgical intervention. This study aimed to assess changes in incidence and management of pleural empyema in England over the past 10 years and the potential impact of influenza on rates.Hospital Episode Statistics data were used to identify patients admitted to English hospitals with pleural empyema between 2008 and 2018. Linear regression was used to analyse the relationship between empyema rates and influenza incidence recorded by Public Health England. The relationship between influenza and empyema was further explored using serological data from a prospective cohort study of patients presenting with pleural empyema.Between April 2008 and March 2018 there were 55 530 patients admitted with pleural empyema. There was male predominance (67% versus 33%), which increased with age. Cases have increased significantly from 4447 in 2008 to 7268 in 2017. Peaks of incidence correlated moderately with rates of laboratory-confirmed influenza in children and young adults (r=0.30). For nine of the 10 years studied, the highest annual point incidence of influenza coincided with the highest admission rate for empyema (with a 2-week lag). In a cohort study of patients presenting to a single UK hospital with pleural empyema/infection, 24% (17 out of 72) had serological evidence of recent influenza infection, compared to 7% in seasonally matched controls with simple parapneumonic or cardiogenic effusions (p<0.001).Rates of empyema admissions in England have increased steadily with a seasonal variation that is temporally related to influenza incidence. Patient-level serological data from a prospective study support the hypothesis that influenza may play a pathogenic role in empyema development.

Evidence of changing sexual behaviours and clinical attendance patterns, alongside increasing diagnoses of STIs in MSM and TPSM.

BACKGROUND: Due to rising numbers of STI diagnosis and increasing prevalence of antimicrobial resistance, we explored trends in STI testing frequency and diagnoses, alongside sexual decision making and attitudes concerning condom use and HIV pre-exposure prophylaxis (PrEP) at a large urban UK sexual health clinic. METHODS: We examined 66 528 electronic patient records covering 40 321 attendees between 2016 and 2019, 3977 of whom were men who have sex with men or trans persons who have sex with men (MSM/TPSM). We also explored responses from MSM/TPSM attendees sent an electronic questionnaire between November 2018 and 2019 (n=1975) examining behaviours/attitudes towards PrEP. We measured trends in STI diagnoses and sexual behaviours including condomless anal intercourse (CAI), using linear and logistic regression analyses. RESULTS: Tests resulting in gonorrhoea, chlamydia or syphilis diagnoses increased among MSM/TPSM from 13.5% to 18.5% between 2016 and 2019 (p<0.001). The average MSM/TPSM STI testing frequency increased from 1.5/person/year to 2.1/person/year (p=0.017). Gay MSM/TPSM had the highest proportions of attendances resulting in diagnoses, increasing from 15.1% to 19.6% between 2016 and 2019 (p<0.001) compared with bisexual/other MSM/TPSM increasing from 6.9% to 14.5% (p<0.001), alongside smaller but significant increases in non-MSM/TPSM from 5.9% to 7.7% (p<0.001).The proportion of MSM/TPSM clinic attendees reporting CAI in the previous 3 months prior to at least one appointment in a given year increased significantly from 40.6% to 45.5% between 2016 and 2019 (p<0.0001) and average number of partners from 3.8 to 4.5 (p=0.002). Of 617 eligible questionnaire responses, 339/578 (58.7%) HIV-negative and 29/39 (74.4%) HIV-positive MSM/TPSM indicated they would be more likely to have CAI with someone on PrEP versus not on PrEP. 358/578 (61.9%) HIV-negative respondents said that PrEP use would make them more likely to have CAI with HIV-negative partners. CONCLUSION: Rising numbers of STI diagnoses among MSM/TPSM are not attributable to increased testing alone. Increased CAI and number of partners may be attributable to evolving sexual decision making among PrEP users and their partners. Proportionally, bisexual/other MSM/TPSM have the steepest increase in STI diagnoses.

Novel multi-virus rapid respiratory microbiological point-of-care testing in primary care: a mixed-methods feasibility evaluation.

BACKGROUND AND OBJECTIVES: Rapid multi-viral respiratory microbiological point-of-care tests (POCTs) have not been evaluated in UK primary care. The aim of this study was to evaluate the use of a multi-viral microbiological POCT for suspected respiratory tract infections (RTIs). METHODS: In this observational, mixed-methods feasibility study practices were provided with a POCT machine for any patient aged ≥3 months with suspected RTI. Dual throat/nose swabs tested for 17 respiratory viruses and three atypical bacteria, 65 minutes per sample. RESULTS: Twenty clinicians recruited 93 patients (estimated 1:3 of all RTI cases). Patient's median age was 29, 57% female, and 44% with co-morbidities. Pre-test diagnoses: upper RTI (48%); lower RTI (30%); viral/influenza-like illness (18%); other (4%). Median set-up time was 2.72 minutes, with 72% swabs processed <4 hours, 90% <24 hours. Tests detected ≥1 virus in 58%, no pathogen 37% and atypical bacteria 2% (3% inconclusive). Antibiotics were prescribed pre-test to 35% of patients with no pathogen detected and 25% with a virus. Post-test diagnoses changed in 20%, and diagnostic certainty increased (P = 0.02), more so when the test was positive rather than negative (P < 0.001). Clinicians predicted decreased antibiotic benefit post-test (P = 0.02). Interviews revealed the POCT has clear potential, was easy to use and well-liked, but limited by time-to-result and the absence of testing for typical respiratory bacteria. CONCLUSIONS: This POCT was acceptable and appeared to influence clinical reasoning. Clinicians wanted faster time-to-results and more information about bacteria. Randomized trials are needed to understand the safety, efficacy and patient perceptions of these POCTs.

The UK government has called for the introduction of rapid diagnostics to curb overuse of antibiotics for common infections. Multi-viral respiratory 'point-of-care' tests (POCTs) are available but have not been used in UK primary care before. These POCTs use samples from the nose or back of the throat and give results quickly, to see if viruses or bacteria are there. In this study, four GP practices were given POCT machines for 6 weeks to see how they were used. Of the 93 patient samples tested, 3% were inconclusive, 37% tested negative, 58% had at least one virus and only 2% had a bacterial infection. Clinicians were more certain of patient diagnoses after testing especially when a virus or bacterium was detected and they were also less likely to predict the patient would benefit from antibiotics. Clinical diagnoses changed in 20% of patients after testing but less than 10% were contacted to change their treatment plan. During interviews, clinicians revealed they liked the test finding it easy-to-use but wanted faster time-to-results and testing for more bacteria. Clinical trials are needed to see if these POCTs can safely and cost-effectively reduce antibiotic prescribing in primary care.

Relationship between microbiology of throat swab and clinical course among primary care patients with acute cough: a prospective cohort study.

BACKGROUND: Acute lower respiratory tract infections (ALRTIs) account for most antibiotics prescribed in primary care despite lack of efficacy, partly due to clinician uncertainty about aetiology and patient concerns about illness course. Nucleic acid amplification tests could assist antibiotic targeting. METHODS: In this prospective cohort study, 645 patients presenting to primary care with acute cough and suspected ALRTI, provided throat swabs at baseline. These were tested for respiratory pathogens by real-time polymerase chain reaction and classified as having a respiratory virus, bacteria, both or neither. Three hundred fifty-four participants scored the symptoms severity daily for 1 week in a diary (0 = absent to 4 = severe problem). RESULTS: Organisms were identified in 346/645 (53.6%) participants. There were differences in the prevalence of seven symptoms between the organism groups at baseline. Those with a virus alone, and those with both virus and bacteria, had higher average severity scores of all symptoms combined during the week of follow-up than those in whom no organisms were detected [adjusted mean differences 0.204 (95% confidence interval 0.010 to 0.398) and 0.348 (0.098 to 0.598), respectively]. There were no differences in the duration of symptoms rated as moderate or severe between organism groups. CONCLUSIONS: Differences in presenting symptoms and symptoms severity can be identified between patients with viruses and bacteria identified on throat swabs. The magnitude of these differences is unlikely to influence management. Most patients had mild symptoms at 7 days regardless of aetiology, which could inform patients about likely symptom duration.

Management of chlamydia and gonorrhoea infections diagnosed in primary care using a centralised nurse-led telephone-based service: mixed methods evaluation.

BACKGROUND: Up to 18% of genital Chlamydia infections and 9% of Gonorrhoea infections in England are diagnosed in Primary Care. Evidence suggests that a substantial proportion of these cases are not managed appropriately in line with national guidelines. With the increase in sexually transmitted infections and the emergence of antimicrobial resistance, their timely and appropriate treatment is a priority. We investigated feasibility and acceptability of extending the National Chlamydia Screening Programme's centralised, nurse-led, telephone management (NLTM) as an option for management of all cases of chlamydia and gonorrhoea diagnosed in Primary Care. METHODS: Randomised feasibility trial in 11 practices in Bristol with nested qualitative study. In intervention practices patients and health care providers (HCPs) had the option of choosing NLTM or usual care for all patients tested for Chlamydia and Gonorrhoea. In control practices patients received usual care. RESULTS: One thousand one hundred fifty-four Chlamydia/gonorrhoea tests took place during the 6-month study, with a chlamydia positivity rate of 2.6% and gonorrhoea positivity rate of 0.8%. The NLTM managed 335 patients. Interviews were conducted with sixteen HCPs (11 GPs, 5 nurses) and 12 patients (8 female). HCPs were positive about the NLTM, welcomed the partner notification service, though requested more timely feedback on the management of their patients. Explaining the NLTM to patients didn't negatively impact on consultations. Patients found the NLTM acceptable, more convenient and provided greater anonymity than usual care. Patients appreciated getting a text message regarding a negative result and valued talking to a sexual health specialist about positive results. CONCLUSION: Extension of this established NLTM intervention to a greater proportion of patients was both feasible and acceptable to both patients and HCP, could provide a better service for patients, whilst decreasing primacy care workload. The study provides evidence to support the wider implementation of this NLTM approach to managing chlamydia and gonorrhoea diagnosed in primary care.

Prevalence of new variants of Chlamydia trachomatis escaping detection by the Aptima Combo 2 assay, England, June to August 2019.

We identified two new Chlamydia trachomatis (CT) variants escaping Aptima Combo 2 (AC2) assay detection, in clinical specimens of two patients. One had a C1514T mutation the other a G1523A mutation, both within the AC2 23S rRNA target region. The prevalence of such variants among persons tested for CT in England was estimated to be fewer than 0.003%.

Proinflammatory polarization of stifle synovial macrophages in dogs with cruciate ligament rupture.

OBJECTIVE: To determine polarization of synovial macrophages during development of cruciate ligament rupture (CR) and determine whether differences in synovial macrophage polarization in CR, osteoarthritis (OA), and healthy joints exist. STUDY DESIGN: Prospective case-controlled study. ANIMALS: Client-owned dogs with unstable stifles with CR (n = 22), paired stable contralateral stifles with partial CR (pCR; n = 7), joints with OA not related to CR (n = 6), and clinically normal (Normal; n = 7) joints. METHODS: Synovial fluid samples were collected. Smears were made for differential cytology counts and estimated total nucleated cell counts. Cytospin preparations were made, and immunocytochemical staining was performed with the pan-macrophage marker CD68, M1 macrophage markers inducible nitric oxide synthase (iNOS) and chemokine (C-C motif) receptor 7 (CCR7), and M2 macrophage markers arginase 1 and CD163. Positively stained cells were counted. RESULTS: Numbers of lymphocytes were increased in the CR group compared with the OA and Normal groups (P < .05). Numbers of CD68+ , CCR7+ , and iNOS+ cells in the CR and OA groups were increased compared with the Normal group (P < .05). Globally, the ratio of positively stained M1 polarized CD68+ cells to M2 polarized CD68+ cells was highest for the OA group (2.49), followed by the pCR (2.1), CR (1.63), and Normal (0.7) groups. CONCLUSION: Polarization of synovial macrophages toward an M1 proinflammatory phenotype is an early event in the development of canine CR. CLINICAL SIGNIFICANCE: M1 polarization in pCR stifles provides evidence of a possible role for macrophages in progressive development of cruciate ligament fiber damage. Lymphocytes may play a role in the synovitis found in CR joints. Our findings provide evidence that these cells are therapeutic targets.

Which azithromycin regimen should be used for treating Mycoplasma genitalium? A meta-analysis.

BACKGROUND: There is increasing evidence that azithromycin 1 g is driving the emergence of macrolide resistance in Mycoplasma genitalium worldwide. We undertook a meta-analysis of M. genitalium treatment studies using azithromycin 1 g single dose and azithromycin 500 mg on day 1 then 250 mg daily for 4 days (5-day regimen) to determine rates of treatment failure and resistance in both regimens. METHODS: The online databases PubMed and Medline were searched using terms "Mycoplasma genitalium", "macrolide" or "azithromycin" and "resistance" up to April 2016. Studies were eligible if they: used azithromycin 1 g or 5 days, assessed patients for macrolide resistant genetic mutations prior to treatment and patients who failed were again resistance genotyped. Random effects meta-analysis was used to estimate failure and resistance rates. RESULTS: Eight studies were identified totalling 435 patients of whom 82 (18.9%) had received the 5-day regimen. The random effects pooled rate of treatment failure and development of macrolide antimicrobial resistance mutations with azithromycin 1 g was 13.9% (95% CI 7.7% to 20.1%) and 12.0% (7.1% to 16.9%), respectively. Of individuals treated with the 5-day regimen, with no prior doxycycline treatment, fewer (3.7%; 95% CI 0.8% to 10.3%, p=0.012) failed treatment, all of whom developed resistance (p=0.027). CONCLUSION: Azithromycin 1 g is associated with high rates of treatment failure and development of macrolide resistance in M. genitalium infection with no pre-existing macrolide mutations. There is moderate but conflicting evidence that the 5-day regimen may be more effective and less likely to cause resistance.

Cross-sectional study to evaluate Trichomonas vaginalis positivity in women tested for Neisseria gonorrhoeae and Chlamydia trachomatis, attending genitourinary medicine and primary care clinics in Bristol, South West England.

BACKGROUND: Highly sensitive, commercial nucleic acid amplification tests (NAAT) for Trichomonas vaginalis have only recently been recommended for use in the UK. While testing for T. vaginalis is routine in symptomatic women attending genitourinary medicine (GUM) clinics, it is rare in asymptomatic women or those attending primary care. The aim of this study was to evaluate the positivity of T. vaginalis using a commercial NAAT, in symptomatic and asymptomatic women undergoing testing for chlamydia and gonorrhoea in GUM and primary care settings. METHODS: Samples from 9186 women undergoing chlamydia and gonorrhoea testing in South West England between May 2013 and Jan 2015 were also tested for T. vaginalis by NAAT alongside existing tests. RESULTS: T. vaginalis positivity using NAAT was as follows: in GUM 4.5% (24/530, symptomatic) and 1.7% (27/1584, asymptomatic); in primary care 2.7% (94/3499, symptomatic) and 1.2% (41/3573, asymptomatic). Multivariable regression found that in GUM older age, black ethnicity and deprivation were independent risk factors for T. vaginalis infection. Older age and deprivation were also risk factors in primary care. Testing women presenting with symptoms in GUM and primary care using TV NAATs is estimated to cost £260 per positive case diagnosed compared with £716 using current microbiological tests. CONCLUSIONS: Aptima TV outperforms existing testing methods used to identify T. vaginalis infection in this population. An NAAT should be used when testing for T. vaginalis in women who present for testing with symptoms in primary care and GUM, based on test performance and cost.

Multivariate genome-wide association analysis identifies novel and relevant variants associated with anterior cruciate ligament rupture risk in the dog model.

BACKGROUND: Anterior cruciate ligament rupture (ACLR) is a debilitating and potentially life-changing condition in humans, as there is a high prevalence of early-onset osteoarthritis after injury. Identification of high-risk individuals before they become patients is important, as post-treatment lifetime burden of ACLR in the USA ranges from $7.6 to $17.7 billion annually. ACLR is a complex disease with multiple risk factors including genetic predisposition. Naturally occurring ACLR in the dog is an excellent model for human ACLR, as risk factors and disease characteristics in humans and dogs are similar. In a univariate genome-wide association study (GWAS) of 237 Labrador Retrievers, we identified 99 ACLR candidate loci. It is likely that additional variants remain to be identified. Joint analysis of multiple correlated phenotypes is an underutilized technique that increases statistical power, even when only one phenotype is associated with the trait. Proximal tibial morphology has been shown to affect ACLR risk in both humans and dogs. In the present study, tibial plateau angle (TPA) and relative tibial tuberosity width (rTTW) were measured on bilateral radiographs from purebred Labrador Retrievers that were recruited to our initial GWAS. We performed a multivariate genome wide association analysis of ACLR status, TPA, and rTTW. RESULTS: Our analysis identified 3 loci with moderate evidence of association that were not previously associated with ACLR. A locus on Chr1 associated with both ACLR and rTTW is located within ROR2, a gene important for cartilage and bone development. A locus on Chr4 associated with both ACLR and TPA resides within DOCK2, a gene that has been shown to promote immune cell migration and invasion in synovitis, an important predictor of ACLR. A third locus on Chr23 associated with only ACLR is located near a long non-coding RNA (lncRNA). LncRNA's are important for regulation of gene transcription and translation. CONCLUSIONS: These results did not overlap with our previous GWAS, which is reflective of the different methods used, and supports the need for further work. The results of the present study are highly relevant to ACLR pathogenesis, and identify potential drug targets for medical treatment.

Assessment of overall thoracic limb axial alignment in dogs with antebrachial deformity.

OBJECTIVE: To assess overall thoracic limb axial alignment in dogs with and without angular limb deformity (ALD). STUDY DESIGN: Ex vivo and retrospective observational clinical study. ANIMALS: Forty canine thoracic limbs from bilateral normal specimens (10 pairs) and unilateral antebrachial ALD (10 uniapical and 10 biapical deformities). METHODS: Computed tomography images of the entire thoracic limb were collected for multiplanar reconstruction. Baseline limb axis was defined by the humeral anatomic axis. Axial alignment of the distal humerus, proximal and distal radius, and metacarpal bones were obtained and compared among levels and groups. RESULTS: The mean overall thoracic limb rotation of normal dogs was 35.4 ° (95% CI, 27.2 °, 43.6 °). Mean overall limb rotation in uniapical and biapical deformity was 41.6 ° (95% CI, 33.0 °, 50.1 °) and 54.4 ° (95% CI, 45.8 °, 62.9 °), respectively, but was not statistically different (P = .096). Only overall limb rotation in limbs with biapical ALD was different from normal limbs (P = .008). Rotation at the level of the elbow was 77% and 85% of overall limb rotation in normal and deformity limbs, respectively, and was increased from normal in limbs with ALD (both P < .05). Radial torsion did not differ among groups but was moderately correlated with overall limb rotation. CONCLUSION: Rotation arising in the elbow of limbs with ALD was higher than in normal limbs and accounted for the greatest contribution of overall limb rotation. CLINICAL SIGNIFICANCE: Assessment of radial torsion alone is insufficient to understand overall limb axial alignment in dogs with antebrachial bone deformity.