Azithromycin or Doxycycline for Asymptomatic Rectal Chlamydia trachomatis.

BACKGROUND: Rectal chlamydia is a common bacterial sexually transmissible infection among men who have sex with men. Data from randomized, controlled trials are needed to guide treatment. METHODS: In this double-blind trial conducted at five sexual health clinics in Australia, we randomly assigned men who have sex with men and who had asymptomatic rectal chlamydia to receive doxycycline (100 mg twice daily for 7 days) or azithromycin (1-g single dose). Asymptomatic chlamydia was selected as the trial focus because more than 85% of men with rectal chlamydia infection are asymptomatic, and clinical guidelines recommend a longer treatment course for symptomatic infection. The primary outcome was a negative nucleic acid amplification test for rectal chlamydia (microbiologic cure) at 4 weeks. RESULTS: From August 2016 through August 2019, we enrolled 625 men (314 in the doxycycline group and 311 in the azithromycin group). Primary outcome data were available for 290 men (92.4%) in the doxycycline group and 297 (95.5%) in the azithromycin group. In the modified intention-to-treat population, a microbiologic cure occurred in 281 of 290 men (96.9%; 95% confidence interval [CI], 94.9 to 98.9) in the doxycycline group and in 227 of 297 (76.4%; 95% CI, 73.8 to 79.1) in the azithromycin group, for an adjusted risk difference of 19.9 percentage points (95% CI, 14.6 to 25.3; P<0.001). Adverse events that included nausea, diarrhea, and vomiting were reported in 98 men (33.8%) in the doxycycline group and in 134 (45.1%) in the azithromycin group (risk difference, -11.3 percentage points; 95% CI, -19.5 to -3.2). CONCLUSIONS: A 7-day course of doxycycline was superior to single-dose azithromycin in the treatment of rectal chlamydia infection among men who have sex with men. (Funded by the National Health and Medical Research Council; RTS Australian New Zealand Clinical Trials Registry number, ACTRN12614001125617.).

Performance of Human Papillomavirus Attribution Algorithms to Predict Causative Genotypes in Anal High-Grade Lesions.

BACKGROUND: Gay and bisexual men (GBM) are at increased risk of human papillomavirus (HPV)-associated anal high-grade squamous intraepithelial lesions (HSILs). Understanding the fractions of HSILs attributable to HPV genotypes is important to inform potential impacts of screening and vaccination strategies. However, multiple infections are common, making attribution of causative types difficult. Algorithms developed for predicting HSIL-causative genotype fractions have never been compared with a reference standard in GBM. METHOD: Samples were from the Study of the Prevention of Anal Cancer. Baseline HPV genotypes detected in anal swab samples (160 participants) were compared with HPV genotypes in anal HSILs (222 lesions) determined by laser capture microdissection (LCM). Five algorithms were compared: proportional, hierarchical, maximum, minimum, and maximum likelihood estimation. RESULTS: All algorithms predicted HPV-16 as the most common HSIL-causative genotype, and proportions differed from LCM detection (37.8%) by algorithm (with differences of -6.1%, +20.9%, -20.4%, +2.9%, and +2.2% respectively). Fractions predicted using the proportional method showed a strong positive correlation with LCM, overall (R = 0.73 and P = .002), and by human immunodeficiency virus (HIV) status (HIV positive, R = 0.74 and P = .001; HIV-negative, R = 0.68 and P = .005). CONCLUSIONS: Algorithms produced a range of inaccurate estimates of HSIL attribution, with the proportional algorithm performing best. The high occurrence of multiple HPV infections means that these algorithms may be of limited use in GBM.

Volatile Organic Compounds in the Early Diagnosis of Non-healing Surgical Wounds: A Systematic Review.

BACKGROUND: The normal healing of surgical wounds can be disrupted by infection and/or dehiscence, leading to development of chronic, non-healing wounds (NHW). Diagnosis of NHWs is via clinical acumen and analysis of microbiology wound swabs. Volatile organic compounds (VOCs) are emitted generally by human subjects and specifically as products of bacterial metabolism and are detected in the wound area. This systematic review will assess the potential use of VOCs released by surgical wounds as a non-invasive method for identifying bacterial species and the progression to NHW. METHOD: A systematic search of studies, via PRISMA guidelines, was conducted. Of 220 papers screened, seven studies were included. Outcome data were extracted on methods for VOC analysis and wound/bacterial VOC profiles. RESULTS: The studies have shown that VOC profiles are identified by two methods: gas chromatography-mass spectrometry and electronic nose. There are VOC profiles associated with causative bacterial species, with early indications that they could be anatomically specific or could monitor treatment effects. CONCLUSION: VOC profiling of bacterial species within wounds is possible and could become a point of care test. More research is needed on specific VOC profiles to wound location and whether these profiles may predict progression to NHW.

HIV, Immune Dysfunction, and the Natural History of Anal High-Risk Human Papillomavirus Infection in Gay and Bisexual Men.

BACKGROUND: Incidence of anal cancer is highest in gay and bisexual men (GBM). Better understanding of the natural history of anal high-risk human papillomavirus (hrHPV) infection is needed for anal cancer prevention. METHODS: The Study of the Prevention of Anal Cancer was a 3-year study of Australian GBM, aged 35 years or older. We examined incidence, clearance, and risk factors for 13 hrHPV types at baseline and 3 annual visits. RESULTS: In 525 men with ≥ 2 visits, 348 (66.3%) acquired ≥ 1 incident hrHPV infection. HPV16 incidence rates were similar, but non-16 hrHPV incidence was higher in HIV-positive (51.8/100 person years [PY]) than HIV-negative men (36.5/100 PY, P < .001). Annual clearance rates of HPV16 (13.21/100 PY, 95% confidence interval, 10.53-16.56) were lower than for other hrHPV types. hrHPV clearance rates were not associated with HIV overall but were significantly lower in those with a lower nadir CD4 (<200 cells/µL) for HPV16 (P = .015) and other hrHPV types (P = .007). CONCLUSIONS: Higher incidence of non-16 hrHPV types, coupled with lower clearance of non-16 hrHPV types in those with past impaired immune function, is consistent with the greater role of non-16 hrHPV in anal cancer in HIV-positive people. AUSTRALIA NEW ZEALAND CLINICAL TRIALS REGISTRY: ANZCTR365383.

The Natural History of Anal High-grade Squamous Intraepithelial Lesions in Gay and Bisexual Men.

BACKGROUND: Gay and bisexual men (GBM) are disproportionately affected by anal cancer. Prevention is hindered by incomplete understanding of the natural history of its precursor, anal high-grade squamous intraepithelial lesions (HSIL). METHODS: The Study of the Prevention of Anal Cancer, conducted between 2010 and 2018, enrolled human immunodeficiency virus (HIV)-positive and HIV-negative GBM aged ≥35 years. Anal cytology and high-resolution anoscopy (HRA) were performed at baseline and 3 annual visits. A composite HSIL diagnosis (cytology ± histology) was used. Cytological high-grade squamous intraepithelial lesions (cHSIL) incidence and clearance rates were calculated with 95% confidence intervals (CIs). Predictors were calculated using Cox regression with hazard ratios (HRs) and 95% CIs. RESULTS: Among 617 men, 220 (35.7%) were HIV-positive, median age 49 years. And 124 incident cHSIL cases occurred over 1097.3 person-years (PY) follow-up (11.3, 95% CI 9.5-13.5 per 100 PY). Significant bivariate predictors of higher incidence included age <45 years (HR 1.64, 95% CI 1.11-2.41), HIV positivity (HR 1.43, 95% CI .99-2.06), prior SIL diagnosis (P-trend < .001) and human papillomavirus (HPV)16 (HR 3.39, 2.38-4.84). Over 695.3 PY follow-up, 153 HSIL cleared (clearance 22.0, 95% CI 18.8-25.8 per 100 PY). Predictors were age < 45 years (HR 1.52, 1.08-2.16), anal intraepithelial neoplasia (AIN)2 rather than AIN3 (HR 1.79, 1.29-2.49), smaller lesions (HR 1.62, 1.11-2.36) and no persistent HPV16 (HR 1.72, 1.23-2.41). There was 1 progression to cancer (incidence 0.224, 95% CI .006-1.25 per 100 PY). CONCLUSION: These data strongly suggest that not all anal HSIL detected in screening requires treatment. Men with persistent HPV16 were less likely to clear HSIL and are more likely to benefit from effective HSIL treatments. CLINICAL TRIALS REGISTRATION: Australia New Zealand Clinical Trials Registry (ANZCTR365383).

Changes in Endogenous and Exogenous Koala Retrovirus Subtype Expression over Time Reflect Koala Health Outcomes.

Koala retrovirus (KoRV) is unique in that it exists as both an exogenous and actively endogenizing gamma retrovirus of koalas. While nine subtypes of KoRV have been recognized, focused study of these subtypes in koalas over time and with different health outcomes has been lacking. Therefore, in this study, three wild koala cohorts were established and monitored to examine KoRV proviral and expression data from koalas that either remained healthy over time, began healthy before developing chlamydial cystitis, or presented with chlamydial cystitis and were treated with antibiotics. Deep sequencing of the proviral KoRV envelope gene revealed KoRV-A, -B, -D, and -F to be the major subtypes in this population and allowed for subtype-specific assays to be created. Quantification of KoRV transcripts revealed that KoRV-D expression mirrored the total KoRV expression levels (106 copies/ml of plasma), with KoRV-A and KoRV-F expression being ∼10-fold less and KoRV-B expression being ∼100-fold less, when detected. Strikingly, there was significantly higher expression of KoRV-D in healthy koalas than in koalas that developed chlamydial cystitis, with healthy koalas expressing a major KoRV-D/minor KoRV-A profile, whereas koalas that developed cystitis had variable KoRV expression profiles. Total anti-KoRV IgG antibody levels were found not to correlate with the expression of total KoRV or any individual KoRV subtype. Finally, KoRV expression was consistent between systemic and mucosal body sites and during antibiotic treatment. Collectively, this gives a comprehensive picture of KoRV dynamics during several important koala health states.IMPORTANCE The long-term survival of the koala is under serious threat, with this iconic marsupial being declared "vulnerable" by the Australian Government and officially listed as a threatened species. KoRV is clearly contributing to the overall health status of koalas, and research into this virus has been lacking detailed study of the multiple subtypes at both the proviral and expressed viral levels over time. By designing new subtype-specific assays and following well-defined koala cohorts over time, this study has generated a new more complete picture of KoRV and its relationship to koala health outcomes in the wild. Only by building a comprehensive picture of KoRV during both koala health and disease can we bring meaningful koala health interventions into better focus.

Quadrivalent human papillomavirus vaccination successfully reduces the prevalence of vaccine-targeted genotypes in a young, vaccine-eligible-age sample of Australian females.

Background The prevalence of genital tract vaccine-type human papillomavirus (HPV) is on the decline due to high vaccine uptake through the national HPV immunisation program in Australia. The aim of this study was to investigate HPV vaccine coverage and factors associated with HPV in a vaccine-eligible sample of young Australian females. METHODS: Females aged 16-25 years were recruited into the Young Female Health Initiative study, a young women's health study, via Facebook advertising from 2012 to 2017. Sexually active participants were asked to provide a self-collected vaginal swab for the detection of HPV DNA; positive samples were genotyped. Self-reported HPV vaccination status was confirmed by the National HPV Vaccination Program Register. Outcomes of the study were HPV acquisition and genotype, HPV vaccination status and factors associated with HPV. RESULTS: Overall, 22.8% of samples (95% confidence interval (CI) 17.8-27.8%; n = 62/272) were positive for any HPV DNA, of which 19.1% (95% CI 14.4-23.8%; n = 52/272) were oncogenic types. HPV 16 was detected in three samples (1.1%; 95% CI -0.1%, 2.3%; two not HPV vaccinated and one vaccinated after sexual debut). Early sexual debut (<16 years) and multiple sexual partners were independently associated with an increased risk of any HPV. CONCLUSIONS: In a community sample of vaccine-eligible-age females with a high vaccine uptake, the prevalence of vaccine-related HPV genotypes is extremely low. Early sexual debut and multiple sexual partners are positively associated with HPV, underscoring the importance of vaccination at the routinely recommended age of 12-13 years for best vaccine impact.

Contaminated fingers: a potential cause of Chlamydia trachomatis-positive urine specimens.

OBJECTIVES: The detection of an STI agent in a urogenital tract (UGT) specimen from a young child is regarded as being indicative of sexual abuse. However, the probabilities of contamination events that could conceivably lead to STI positive specimens in the absence of sexual contact are unclear. The objective was to estimate the potential for fingers that have come in contact with Chlamydia trachomatis-positive urine to detectably contaminate C. trachomatis-negative urine. METHODS: The study design was based on self-experimentation. Dilutions of C. trachomatis elementary bodies (EBs) were prepared. A participant contacted an EB dilution then a urine surrogate specimen. The experiment was performed by three participants using three C. trachomatis isolates, of genotype E, F and B. Two surrogate urine contact methods were used to mimic contamination of a carer assisting with a child's urine collection. All EB dilutions and urine surrogate specimens were subjected to C. trachomatis assay and quantification in a real-time PCR-based diagnostic system. RESULTS: The amplimer crossing point (Cq) for EB dilutions was 10.0±1.6 less than for corresponding finger contacted urine specimens, which corresponds to ~10 µL of EB suspension transferred. This was largely independent of participant identity, C. trachomatis strain or EB dilution. Hand decontamination led to large reductions in EBs transferred, but transfer remained consistently detectable. Recent Cq data from C. trachomatis-positive clinical urine specimens were collated, and 20% clearly contained sufficient C. trachomatis to detectably contaminate another specimen by finger-mediated transfer, as in this experiment. CONCLUSIONS: This study directly demonstrated the potential for urine contaminated fingers to convert a C. trachomatis-negative urine specimen to C. trachomatis positive as a result of contact. Accordingly, procedures for urine specimen collection, particularly from children, need to be designed to prevent contamination.

Detection of Chlamydia trachomatis mRNA using digital PCR as a more accurate marker of viable organism.

Spontaneous resolution of urogenital Chlamydia trachomatis (CT) without treatment has previously been described, but a limitation of these reports is that DNA or RNA-based amplification tests used do not differentiate between viable infection and non-viable DNA. We modified a previously published CT mRNA detection (omp2) method to differentiate between viable infection and non-viable DNA in a sample of CT DNA PCR positive women. We modified a CT mRNA detection (omp2) method from reverse transcriptase qPCR (RTqPCR) to digital PCR (dPCR) and evaluated it in samples from CT DNA positive women. Firstly, CT infected McCoy B cells treated with azithromycin in vitro identified detectable mRNA levels disappeared <2 days, while DNA persisted up to 6 days. We used 55 self-collected vaginal swabs from a cohort of women diagnosed as DNA positive for chlamydia obtained pre- and 7 days of post-azithromycin treatment. Concordance with DNA results was higher for dPCR than RTqPCR (74.5% versus 65.5%). At visit 1, there was a strong linear relationship between DNA and mRNA (r = 0.9, p < 0.000); 24 samples had both mRNA and DNA detected (82.8%) and 5 had only DNA detected with a potential false positive proportion of 17.2% (95%CI: 5.8, 35.8). At visit 2, there was poor correlation between DNA and mRNA (r = 0.14, p = 0.55); eight specimens had only DNA detected (42.1%; 95%CI: 20.25, 66.50) and one had mRNA detected. DNA detection methods alone may detect non-viable DNA. Consideration should be given to further develop mRNA assays as ancillary tests to improve detection of viable chlamydia.

Looking beyond human papillomavirus (HPV) genotype 16 and 18: Defining HPV genotype distribution in cervical cancers in Australia prior to vaccination.

Australia has implemented a high-coverage HPV vaccination program but has not, to date, established the distribution of HPV types that occur in cervical cancers in Australia. This information is important for determining the potential for cervical cancer prevention with both current and broader spectrum HPV vaccines. We analysed 847 cervical cancers diagnosed 2005 to 2015 in tertiary centres in the three most populous Australian states with resolution of specimens containing multiple HPV types using laser-capture microdissection. Archived FFPE tissue was reviewed by specialist pathologists, sandwich sectioned, and initially whole-tissue sections genotyped for HPV. Samples were first genotyped using SPF10-LiPA25 (version 1). Negative samples were screened with DNA ELISA kit HPV SPF10, followed by genotyping with SPF+ LiPA if ELISA positive. If still negative, samples were tested on a qPCR assay targeting the E6 region of HPV16, 18, 45 and 33. Of the 847 cancers (65.1% squamous, 28.7% adenocarcinoma, 4.3% adenosquamous, 2.0% other), 92.9% had HPV detected. Of the HPV-positive cancers, 607 of 787 (77.1%) contained HPV16 or 18, 125 of 787 (15.9%) contained HPV31/33/45/52 or 58, and 55 (7.0%) another HPV type. There was a strong correlation between HPV type and age, with younger women most likely to have HPV16/18 detected and least likely HPV negative. Our findings indicate that cervical cancers diagnosed in Australia more frequently contain HPV16/18 than in international series. This could be due to cervical screening in Australia increasing the proportion of adenocarcinomas, in which types 18 and 16 more strongly predominate, due to prevention of squamous cancers.

A multicentre double-blind randomised controlled trial evaluating the efficacy of daily use of antibacterial mouthwash against oropharyngeal gonorrhoea among men who have sex with men: the OMEGA (Oral Mouthwash use to Eradicate GonorrhoeA) study protocol.

BACKGROUND: Gonorrhoea is one of the most common sexually transmissible infections in men who have sex with men (MSM). Gonorrhoea rates have increased substantially in recent years. There is concern that increasing gonorrhoea prevalence will increase the likelihood of worsening antibiotic resistance in Neisseria gonorrhoeae. A recent randomised controlled trial (RCT) demonstrated that a single-dose of mouthwash has an inhibitory effect against oropharyngeal gonorrhoea. We are conducting the first RCT to evaluate whether daily use of mouthwash could reduce the risk of acquiring oropharyngeal gonorrhoea. METHODS/DESIGN: The OMEGA (Oral Mouthwash use to Eradicate GonorrhoeA) study is a double-blind RCT and will be conducted at several sexual health clinics and high caseload General Practice (GP) clinics in Melbourne and Sydney, Australia. A total of 504 MSM attending the participating sites will be recruited. Participants will be randomised to either using 'Study mouthwash A' or 'Study mouthwash B' for 12 weeks. Study mouthwash A was inhibitory against N. gonorrhoeae in vitro, whereas study mouthwash B was not. Participants will be instructed to rinse and gargle the study mouthwash for 60 seconds every day. The primary outcome is the proportion of participants with oropharyngeal gonorrhoea detected by nucleic acid amplification test by 12 weeks. DISCUSSION: The results from this trial may provide a novel way to reduce gonorrhoea prevalence and transmission without the use of antibiotics that may be associated with development of resistance. If shown to be effective, the widespread use of mouthwash will reduce the prevalence of oropharyngeal gonorrhoea, which plays key role in driving the emergence of gonococcal antimicrobial resistance through DNA exchange with oral commensal bacteria. The anticipated net effect will be interruption of onward transmission of N. gonorrhoeae within high density sexual networks within MSM populations. TRIAL REGISTRATION: Australian New Zealand Clinical Trials Registry ACTRN12616000247471 , registered on 23rd February 2016.

How Are Race, Cultural, and Psychosocial Factors Associated With Outcomes in Veterans With Spinal Cord Injury?

OBJECTIVE: To understand the role of cultural and psychosocial factors in the outcomes of veteran wheelchair users with spinal cord injury (SCI) to help clinicians identify unique factors faced by their patients and help researchers identify target variables for interventions to reduce disparities in outcomes. DESIGN: Cross-sectional cohort study. SETTING: Three urban Veterans Affairs medical centers affiliated with academic medical centers. PARTICIPANTS: Of the patients (N=516) who were eligible to participate, 482 completed the interview and 439 had SCI. Because of small numbers in other race groups, analyses were restricted to white and African American participants, resulting in a final sample of 422. INTERVENTION: Not applicable. MAIN OUTCOME MEASURES: Quality of life (QOL, Veterans RAND 12-Item Health Survey); satisfaction (Client Satisfaction Questionnaire); and participation (Craig Handicap Assessment and Reporting Technique Short Form). RESULTS: African American Veterans reported poorer physical QOL but better mental QOL than did white Veterans. No other significant race differences were found in unadjusted analyses. Multivariable analyses showed that psychosocial factors were predominantly associated with patients' QOL outcomes and satisfaction with service, but demographic and medical factors were predominantly associated with participation outcomes. Interaction analyses showed that there was a stronger negative association between anxiety and mental QOL for African Americans than for whites, and a positive association between higher self-esteem and social integration for whites but not African Americans. CONCLUSIONS: Findings suggest that attempts to improve the outcomes of Veterans with SCI should focus on a tailored approach that emphasizes patients' demographic, medical, and psychosocial assets (eg, building their sense of self-esteem or increasing their feelings of mastery), while providing services targeted to their specific limitations (eg, reducing depression and anxiety).

Quality and Equity in Wheelchairs Used by Veterans.

OBJECTIVES: To assess in Veterans with spinal cord injury (SCI) or amputated limb (AL) the following: (1) patient demographics, medical factors, cultural and psychosocial characteristic by race; (2) wheelchair quality by race; and (3) the independent associations of patient race and the other factors with wheelchair quality. DESIGN: Cross-sectional cohort study. SETTING: Three Department of Veterans Affairs (VA) medical centers affiliated with academic medical centers. PARTICIPANTS: Eligible participants were Veterans with SCI or ALs (N=516); 482 of them completed the interview. Analyses were restricted to white and African American participants. Because there was no variation in wheelchair quality among AL patients (n=42), they were excluded from all but descriptive analyses, leading to a final sample size of 421. INTERVENTIONS: Not applicable. MAIN OUTCOME MEASURE: Wheelchair quality as defined by the Medicare Healthcare Common Procedure Coding System. RESULTS: We found race differences in many of our variables, but not in quality for manual (odds ratio [OR]=.67; 95% confidence interval [CI], .33-1.36) or power (OR=.82; 95% CI, .51-1.34) wheelchairs. Several factors including age (OR=.96; 95% CI, .93-.99) and income (OR=3.78; 95% CI, 1.43-9.97) were associated with wheelchair quality. There were no significant associations of cultural or psychosocial factors with wheelchair quality. CONCLUSIONS: Although there were no racial differences in wheelchair quality, we found a significant association of older age and lower income with poorer wheelchair quality among Veterans. Efforts are needed to raise awareness of such disparities among VA wheelchair providers and to take steps to eliminate these disparities in prescription practice across VA sites.

Neisseria gonorrhoeae Bacterial DNA Load in the Pharynges and Saliva of Men Who Have Sex with Men.

Neisseria gonorrhoeae can be cultured in the saliva of individuals with pharyngeal gonorrhea. The aim of this study was to quantify the gonococcal bacterial DNA loads in the pharynges and saliva among men who have sex with men (MSM) with untreated pharyngeal gonorrhea. Untreated MSM who tested positive for pharyngeal gonorrhea by culture and returned for antibiotic treatment within 14 days at the Melbourne Sexual Health Centre between October 2014 and March 2015 were eligible for this study. The gonococcal bacterial DNA load was measured using real-time quantitative PCR. The median gonococcal bacterial DNA loads in the pharynges and saliva were calculated and compared to culture positivity using the Mann-Whitney U test. A total of 33 men were included in this study. The median gonococcal bacterial DNA load did not differ between the pharynges in men who were culture positive (2.5 × 10(5) copies/swab) and culture negative (2.9 × 10(4) copies/swab) (P = 0.166) and the saliva (culture positive, 2.2 × 10(5) copies/ml; culture negative, 2.7 × 10(5) copies/ml) (P = 0.499). The bacterial DNA load in the pharynges (P = 0.695) and saliva (P = 0.969) did not differ between who men returned for treatment within 7 days and those who returned 8 to 14 days later. Substantial gonococcal bacterial DNA loads were detected in both saliva and pharynges among MSM with pharyngeal gonorrhea. These findings suggest that gonorrhea can be transmitted via sexual practices involving exposure to saliva, such as oroanal practices (rimming) and saliva use as a lubricant for anal sex.

Detection of Neisseria gonorrhoeae in the pharynx and saliva: implications for gonorrhoea transmission.

OBJECTIVES: This study aimed to determine the proportion of untreated pharyngeal swabs or saliva samples positive by culture or nucleic acid amplification tests (NAATs) for Neisseria gonorrhoeae up to 14 days after an initial culture-positive pharyngeal swab. METHODS: Men who have sex with men who tested positive for pharyngeal gonorrhoea at Melbourne Sexual Health Centre (MSHC) and returned to MSHC for treatment within 14 days between 13 October 2014 and 25 March 2015 were included in this study. Pharyngeal swabs and saliva samples were collected for culture and NAAT. RESULTS: Of 33 initially culture-positive pharyngeal swabs, 32 saliva samples and 31 pharyngeal swabs were positive by NAAT and 14 pharyngeal and 6 saliva samples were positive by culture within 14 days. There was a significant decline in the proportion of repeated pharyngeal culture samples positive by culture over time (p<0.001). CONCLUSIONS: The rapid decline suggests pharyngeal gonorrhoea is short-lived, and the finding of gonorrhoea commonly in the saliva implicates this body fluid in its transmission without direct throat inoculation.

Can Routine Histopathology Distinguish Between Vulvar Cutaneous Candidosis and Dermatophytosis?

OBJECTIVES: This study aimed to determine if vulvar cutaneous candidosis and dermatophytosis can be distinguished by routine histopathology. MATERIALS AND METHODS: Twenty-four cases of periodic acid-Schiff-stained vulvar biopsies with a diagnosis of cutaneous mycosis were reviewed and histopathological characteristics on both periodic acid-Schiff and hematoxylin and eosin were recorded. Data were collected on age, clinical impression, microbiological results, and treatment, and all specimens underwent multiplex polymerase chain reaction analysis. RESULTS: The mean age was 60 years, and all but 3 women had at least 1 risk factor for mycosis including 15 (62.5%) with lichen sclerosus and/or planus managed with topical corticosteroids. A clinical suspicion of tinea or candidosis was documented in 12 (50%) of the cases. Vulvovaginal swabs showed Candida species in 9 women; one skin scraping was positive for Trichophyton rubrum. Microbiology was not obtained in 8 patients, 5 had a negative swab, and 1 had negative skin scrapings. No histopathological or morphological features distinguished Candida species from dermatophytes. Organisms appeared as basophilic structures in the stratum corneum in 15 (62.5%) hematoxylin and eosin-stained slides. Polymerase chain reaction results were positive for Candida species in 5 (21%) and for dermatophytes in 3 (13%), negative in 13, and unassessable in 3 cases. CONCLUSIONS: Vulvar cutaneous candidosis and dermatophytosis cannot be reliably distinguished by routine histopathology or specific polymerase chain reaction. A high index of suspicion combined with adequate microbiological testing remains the best approach to differentiating between the 2, which impacts on counseling, treatment, and prognosis.

Plant characterization of Roundup Ready 2 Yield ® soybean, MON 89788, for use in ecological risk assessment.

During the development of a genetically modified (GM) crop product, extensive phenotypic and agronomic data are collected to characterize the plant in comparison to a conventional control with a similar genetic background. The data are evaluated for potential differences resulting from the genetic modification process or the GM trait, and the differences--if any--are subsequently considered in the context of contributing to the pest potential of the GM crop. Ultimately, these study results and those of other studies are used in an ecological risk assessment of the GM crop. In the studies reported here, seed germination, vegetative and reproductive growth, and pollen morphology of Roundup Ready 2 Yield(®) soybean, MON 89788, were compared to those of A3244, a conventional control soybean variety with the same genetic background. Any statistically significant differences were considered in the context of the genetic variation known to occur in soybean and were evaluated as indicators of an effect of the genetic modification process and assessed for impact on plant pest (weed) characteristics and adverse ecological impact (ecological risk). The results of these studies revealed no effects attributable to the genetic modification process or to the GM trait in the plant that would result in increased pest potential or adverse ecological impact of MON 89788 compared with A3244. These results and the associated risk assessments obtained from diverse geographic and environmental conditions in the United States and Argentina can be used by regulators in other countries to inform various assessments of ecological risk.

Evaluation of Seegene Anyplex II Performance for Detection of Human Papillomavirus Genotypes in Formalin-Fixed, Paraffin-Embedded Cervical Cancer Specimens.

CONTEXT.­: Detection of human papillomavirus (HPV) in formalin-fixed, paraffin-embedded (FFPE) tissues may identify the cause of lesions and has value for the development of new diagnostic assays and epidemiologic studies. Seegene Anyplex II assays are widely used for HPV screening, but their performance using FFPE samples has not been fully explored. OBJECTIVE.­: To validate Anyplex II HPV HR Detection (Anyplex II, Seegene) using FFPE samples. DESIGN.­: We used 248 stored DNA extracts from cervical cancer FFPE samples collected during 2005-2015 that tested HPV positive using the RHA kit HPV SPF10-LiPA25, v1 (SPF10, Labo Biomedical Products) HPV genotyping assay, manufacturer-validated for FFPE samples. RESULTS.­: Of the selected 248 samples, 243 were used in our analysis. Consistent with SPF10 genotyping results, Anyplex II detected all 12 oncogenic types and had an overall HPV detection rate of 86.4% (210 of 243 samples). Anyplex II and SPF10 showed very high agreement for the detection of the 2 most important oncogenic genotypes: HPV 16 (219 of 226; 96.9%; 95% CI, 93.7-98.75) and HPV 18 (221 of 226; 97.8%; 95% CI, 94.9-99.3). CONCLUSIONS.­: Overall results showed that both platforms produced comparable HPV genotyping results, indicating the suitability of Anyplex II for FFPE samples. The Anyplex II assay has the added convenience of being an efficient, single-well semiquantitative polymerase chain reaction assay. Further optimization of Anyplex II may enhance its performance using FFPE samples by improving the detection limit.

Effects of a Powered Ankle-Foot Prosthesis and Physical Therapy on Function for Individuals With Transfemoral Limb Loss: Rationale, Design, and Protocol for a Multisite Clinical Trial.

BACKGROUND: Powered ankle-foot prosthetic devices can generate net positive mechanical work during gait, which mimics the physiological ankle. However, gait deviations can persist in individuals with transfemoral limb loss because of habit or lack of rehabilitation. Prosthetic research efforts favor the design or evaluation of prosthetic componentry and rarely incorporate any type of rehabilitation, despite evidence suggesting that it is critical for minimizing gait imbalances. Given the accelerated rate of innovation in prosthetics, there is a fundamental knowledge gap concerning how individuals with transfemoral limb loss should learn to correctly use powered ankle-foot devices for maximum functional benefit. Because of the recent advances in prosthetic technology, there is also a critical unmet need to develop guidelines for the prescription of advanced prosthetic devices that incorporate both physical and psychological components to identify appropriate candidates for advanced technology. OBJECTIVE: The primary goal of this investigation is to examine the roles of advanced prosthetic technology and a device-specific rehabilitative intervention on gait biomechanics, functional efficacy, and pain in individuals with transfemoral limb loss. The secondary goal is to develop preliminary rehabilitation guidelines for advanced lower limb prosthetic devices to minimize gait imbalances and maximize function and to establish preliminary guidelines for powered ankle-foot prosthetic prescription. METHODS: This prospective, multisite study will enroll 30 individuals with unilateral transfemoral limb loss. At baseline, participants will undergo a full gait analysis and assessment of function, neurocognition, cognitive load, subjective preferences, and pain using their current passive prosthesis. The participants will then be fitted with a powered ankle-foot device and randomized into 2 equal groups: a powered device with a device-specific rehabilitation intervention (group A) or a powered device with the current standard of practice (group B). Group A will undergo 4 weeks of device-specific rehabilitation. Group B will receive the current standard of practice, which includes basic device education but no further device-specific rehabilitation. Data collection procedures will then be repeated after 4 weeks and 8 weeks of powered ankle use. RESULTS: This study was funded in September 2017. Enrollment began in September 2018. Data collection will conclude by March 2024. The initial dissemination of results is expected in August 2024. CONCLUSIONS: The projected trends indicate that the number of individuals with limb loss will dramatically increase in the United States. The absence of effective, evidence-based interventions may make individuals with transfemoral limb loss more susceptible to increased secondary physical conditions and degenerative changes. With this expected growth, considerable resources will be required for prosthetic and rehabilitation services. Identifying potential mechanisms for correcting gait asymmetries, either through advanced prosthetic technology or rehabilitative interventions, can provide a benchmark for understanding the optimal treatment strategies for individuals with transfemoral limb loss. TRIAL REGISTRATION: ClinicalTrials.gov NCT03625921; https://clinicaltrials.gov/study/NCT03625921. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): DERR1-10.2196/53412.