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.

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.

Duration, frequency, and factors related to lower extremity prosthesis use: systematic review and meta-analysis.

PURPOSE: A systematic review and meta-analysis investigating the duration and frequency of lower extremity prosthesis use and what factors were associated with changes in their use. MATERIALS AND METHODS: A search of PubMed, CINAHL, and Scopus over 20 years revealed 2409 articles. After review, 29 studies remained, representing 4814 participants with lower limb loss. Quality, funding, publication, and quantitative analyses were addressed. RESULTS: The mean prosthesis use was 9.6 (5.3) hours/day and 6.4 (1.9) days/week. Distal amputation sites averaged more hours/day of prostheses use than proximal amputations (13.2 [3.2] vs. 10.8 [5.0], p < .001). After hemipelvectomy or hip dislocations, average prostheses use was less hours/day (6.0 [4.7]) than after transfemoral (12.9 [4.8]) or transtibial amputations (14.0 [4.5]) (p < .05). Pooled effects revealed an association between comorbidities and abandonment (OR 0.35, p = .03). The data supported six empirical evidence statements concerning age, sex, social support, amputation proximity, balance, skin condition, comorbidities, pain, falls, and fitness in association with changes in prosthesis utilization. CONCLUSIONS: The study provided systematic data on lower-extremity prosthesis use, thus helping to inform clinical decision-making and patient education. It also elucidated a path for future studies focused on modifiable factors related to prosthesis use and related outcomes.Implications for rehabilitationLower limb loss can trigger costly and debilitating sequela, which could be mitigated by increased prosthesis use and functionality, but there is no consensus on how often prostheses are being used and what affects changes in their use.When counseling patients on what they can expect after a lower extremity amputation and to set goals, the aggregated means of 9.6 (5.3) hours per day and 6.4 (1.9) days per week can be informative.Individuals who use a lower extremity prosthesis or may have to use one in the future can increase their prosthesis use and mobility by limiting further health deterioration.Rehabilitative care involving the multidisciplinary prioritization of proper socket fit, fitness training, gait training, and social support is associated with increased prosthetic device usage.

Efficacy of a synthetic peptide Chlamydia pecorum major outer membrane protein vaccine in a wild koala (Phascolarctos cinereus) population.

Chlamydiosis is a significant disease affecting Eastern Australian koala (Phascolarctos cinereus) populations, impacting individual animal welfare and fecundity and therefore influencing population dynamics. The aim of this study was to investigate the effect of a synthetic peptide vaccine based on 4 components of the Chlamydia pecorum major outer membrane protein (MOMP), over an 18-month period in a koala population severely impacted by chlamydiosis. Wild koalas were recruited into a vaccination or a placebo treatment group on a random allocation, then followed through a period of 18 months, with recapture at 6 monthly intervals. Vaccination did not alter clinical disease expression or chlamydial shedding from the ocular or urogenital sites. Vaccination did not stimulate a significant plasma anti-MOMP IgG response, when compared to the placebo group. There was no significant effect of vaccination on IFN-γ and IL-17A mRNA expression of peripheral blood lymphocytes when stimulated with rMOMP. We have demonstrated that a synthetic peptide vaccination against chlamydiosis is not an effective management tool in a koala population with a high prevalence of C. pecorum infection and related disease. The lack of antigenic response found in this study suggests that further research utilising a larger, full-length antigen is an avenue worth investigation if we are to consider vaccination as a part of a management strategy in diseased koala populations.

Reduction of Chlamydia pecorum and Koala Retrovirus subtype B expression in wild koalas vaccinated with novel peptide and peptide/recombinant protein formulations.

Koalas are an endangered species under threat of extinction from several factors, including infections agents. Chlamydia pecorum infection results in morbidity and mortality from ocular and urogenital diseases while Koala Retrovirus (KoRV) infection has been linked to increased rates of cancer and chlamydiosis. Both C. pecorum and KoRV are endemic in many wild Australian koala populations, with limited treatment options available. Fortunately, vaccines for these pathogens are under development and have generated effective immune responses in multiple trials. The current study aimed to improve vaccine formulations by testing a novel peptide version of the Chlamydia vaccine and a combination Chlamydia - KoRV vaccine. Utilising a monitored wild population in Southeast Queensland, this trial followed koalas given either a 'Chlamydia only' vaccine (utilising four peptides from the chlamydial Major Outer Membrane Protein, MOMP), a combination 'Chlamydia and KoRV' vaccine (comprised of the chlamydial peptides plus a KoRV recombinant envelope protein (rEnv)) or no treatment. Clinical observations, C. pecorum and KoRV gene expression, serum IgG, and mucosal immune gene expression were assessed over a 17-month period. Overall, both vaccine formulations resulted in a decrease in chlamydiosis mortality, with decreases in C. pecorum, CD4, CD8ß and IL-17A gene expression observed. In addition, the combination vaccine group also showed an increase in anti-KoRV IgG production that corresponded to a decrease in detected KoRV-B expression. While these results are favourable, the chlamydial peptide vaccine did not appear to outperform the established recombinant chlamydial vaccine and suggests that a combination vaccine formulated with recombinant MOMP plus KoRV rEnv could capitalize on the demonstrated benefits of both for the betterment of koalas into the future.

Long-term survival with IDH wildtype glioblastoma: first results from the ETERNITY Brain Tumor Funders' Collaborative Consortium (EORTC 1419).

BACKGROUND: Median survival with glioblastoma remains in the range of 12 months on population levels. Only few patients survive for more than 5 years. Patient and disease features associated with long-term survival remain poorly defined. METHODS: European Organization for Research and Treatment of Cancer (EORTC) 1419 (ETERNITY) is a registry study supported by the Brain Tumor Funders Collaborative in the US and the EORTC Brain Tumor Group. Patients with glioblastoma surviving at least 5 years from diagnosis were identified at 24 sites in Europe, US, and Australia. In patients with isocitrate dehydrogenase (IDH) wildtype tumours, prognostic factors were analysed using the Kaplan-Meier method and the Cox proportional hazards model. A population-based reference cohort was obtained from the Cantonal cancer registry Zurich. RESULTS: At the database lock of July 2020, 280 patients with histologically centrally confirmed glioblastoma (189 IDH wildtype, 80 IDH mutant, 11 incompletely characterised) had been registered. In the IDH wildtype population, median age was 56 years (range 24-78 years), 96 patients (50.8%) were female, 139 patients (74.3%) had tumours with O6-methylguanine DNA methyltransferase (MGMT) promoter methylation. Median overall survival was 9.9 years (95% confidence interval [95% CI] 7.9-11.9). Patients without recurrence experienced longer median survival (not reached) than patients with one or more recurrences (8.92 years) (p < 0.001) and had a high rate (48.8%) of MGMT promoter-unmethylated tumours. CONCLUSIONS: Freedom from progression is a powerful predictor of overall survival in long-term survivors with glioblastoma. Patients without relapse often have MGMT promoter-unmethylated glioblastoma and may represent a distinct subtype of glioblastoma.

Genome organization and genomics in Chlamydia: whole genome sequencing increases understanding of chlamydial virulence, evolution, and phylogeny.

The genus Chlamydia contains important obligate intracellular bacterial pathogens to humans and animals, including C. trachomatis and C. pneumoniae. Since 1998, when the first Chlamydia genome was published, our understanding of how these microbes interact, evolved and adapted to different intracellular host environments has been transformed due to the expansion of chlamydial genomes. This review explores the current state of knowledge in Chlamydia genomics and how whole genome sequencing has revolutionised our understanding of Chlamydia virulence, evolution, and phylogeny over the past two and a half decades. This review will also highlight developments in multi-omics and other approaches that have complemented whole genome sequencing to advance knowledge of Chlamydia pathogenesis and future directions for chlamydial genomics.

Criteria for Advanced Prosthetic Foot Prescription: Rationale, Design, and Protocol for a Multisite, Randomized Controlled Trial.

BACKGROUND: The prescription of prosthetic ankle-foot devices is often based on the professional judgment of the limb loss care team or limited evidentiary research. Current prosthetic research efforts have focused on the design and development of prosthetic devices rather than on understanding which devices are the most appropriate to prescribe. This investigation will evaluate biomechanical, functional, and subjective outcome measures to help determine the optimal prescription parameters of prosthetic ankle-foot devices. OBJECTIVE: This study aims to develop evidence-based guidelines for limb loss care teams for the appropriate prescription of commercially available prosthetic ankle-foot devices to improve function and satisfaction. METHODS: This investigation will be a multisite, randomized, crossover clinical trial targeting the enrollment of 100 participants. Participants will use 3 different types of prosthetic devices (energy storing and returning, articulating, and powered) in random order. Participants will be fitted and trained with each device and then separately use each device for a 1-week acclimation period. Following each 1-week acclimation period, participants will be evaluated using several functional measures and subjective surveys. A random subset of participants (30/100, 30%) will also undergo full-body gait analysis, following each 1-week acclimation period, to collect biomechanical data during level ground and incline and decline walking. After all individual device evaluations, participants will be given all 3 prostheses concurrently for 4 weeks of home and community use to capture user preference. Activity monitoring and a guided interview will be used to determine overall user preference. RESULTS: The study was funded in August 2017, and data collection began in 2018. Data collection is expected to be completed before July 2023. Initial dissemination of results is expected to occur in the winter of 2023. CONCLUSIONS: By identifying biomechanical, functional, and subjective outcomes that are sensitive to differences in prosthetic ankle-foot devices, a benchmark of evidence can be developed to guide effective prosthetic prescription. TRIAL REGISTRATION: ClinicalTrials.gov NCT03505983; https://clinicaltrials.gov/ct2/show/NCT03505983. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): DERR1-10.2196/45612.

Staff Low Back Injury Risk During Assisted Falls Virtual Reality Simulations.

BACKGROUND: Assisted falls occur when staff try to minimize the impact of falls by slowing a patient's descent. Assisting a patient fall may decrease patient injury risk, but biomechanical risk of injury to staff has not been evaluated. Assisted falls virtual reality (VR) simulations were conducted to examine staff low back injury risk during common assisted falls scenarios. METHODS: VR simulations of a toilet to wheelchair transfer were developed with a male patient avatar for three assisted falls scenarios: standing up from toilet, sitting down on wheelchair, and ambulation. Patient avatar weight was modified to reflect normal, underweight, and overweight adult patients. The average spinal compression force at L5/S1 was calculated for each participant with five trials per three scenarios while utilizing physical ergonomic techniques and compared to the safe spinal compression limit of 3,400 Newtons (N). FINDINGS: Six staff participants completed 90 VR simulations in total. The average calculated spinal compression force ranged from 7,132 N to 27,901 N. All participant trials exceeded the safe spinal compression limit of 3,400 N for every assisted falls scenario and avatar weight despite application of ergonomic techniques including wide stance, knees bent, and backs straight. CONCLUSIONS/APPLICATION TO PRACTICE: Staff are at risk for low back injury if they assist falls regardless of the adult patient weight and application of ergonomic techniques. Safer alternatives like the implementation of mobility screening tools and safe patient handling and mobility technology are needed to help prevent assisted falls to decrease injury risk to both patients and staff.

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.

Repeat infections with chlamydia in women may be more transcriptionally active with lower responses from some immune genes.

Chlamydia trachomatis, the most common bacterial sexually transmitted infection worldwide, is responsible for considerable health burden due to its significant sequelae. There are growing concerns about chlamydial treatment and management due to widely documented increasing burden of repeat infections. In the current study, a cohort study design of 305 women with urogenital chlamydial infections demonstrated that 11.8% of women experienced repeat infections after treatment with azithromycin. The chlamydial DNA load measured by quantitative PCR was higher in women who experienced a repeat infection (p = 0.0097) and repeat infection was associated with sexual contact. There was no genomic or phenotypic evidence of azithromycin resistance within the chlamydial isolates. During repeat infection, or repeat positive tests during follow up, vaginal chlamydial gene expression (ompA, euo, omcB, htrA, trpAB) was markedly higher compared to baseline, and two of the selected immune genes analyzed had significantly lower expression at the time of repeat infection. Overall, there are two implications of these results. The results could be generalized to all recent infections, or repeat positive events, and indicate that chlamydial infections are have higher transcriptional activity of select genes early in the infection in women. Alternatively, after azithromycin treatment, repeat infections of Chlamydia may be more transcriptionally active at certain genes, and there may be post-treatment immunological alterations that interplay into repeat exposures establishing an active infection. The potential that recent infections may involve a higher level of activity from the organism may have implications for management by more regular testing of the most at risk women to reduce the risk of sequelae.

Comparison of four assays for human papillomavirus detection in the anal canal.

OBJECTIVE: Anal cancer is preceded by high-risk human papillomavirus (HRHPV) infection, predominantly HPV16. No HPV assay is licenced for use in anal screening. We aimed to determine the sensitivity and specificity of four anal canal swab HPV assays to predict high-grade squamous epithelial lesions (HSIL). METHODS: In a cohort of Australian HIV-positive and negative gay and bisexual men, we compared the sensitivity and specificity of detection of 13 anal HRHPV genotypes by Linear Array (LA), Cobas 4800, EuroArray, and Anyplex II HPV28 (+ and ++ cut offs), compared their ability to predict prevalent anal HSIL, and compared anal canal HRHPV detection with HRHPV isolated from HSIL using laser capture microdissection (LCM). RESULTS: A total of 475 participants had baseline results available for all four assays (166, 35.0% HIV positive), and 169 participants had a diagnosis of cytological and/or histological HSIL. The HPV16 and any HRHPV detection were highest with Anyplex II HPV28 (+) (156, 32.8% 95% CI 28.6-37.2 and 359, 75.6%, 95% CI 71.5-79.4, respectively). For detection of concurrent HSIL and HPV16, the assay sensitivity was similar, ranging from 49.1%, 95% CI 41.4-56.9 (Anyplex II HPV28 ++) to 55.0%, 95% CI 47.2-62.7 (Anyplex II HPV28 +). For concurrent HSIL and any HRHPV detection, EuroArray was more specific than Anyplex II HPV28 (+) (45.9% 95% CI 40.2-51.7 vs 36.7%, 95% CI 31.3-42.4, p = 0.021) and had comparable specificity with Anyplex II HPV28 (++) (45.9% vs 47.2%, 95% CI 41.5-53.0, p = 0.75). All assays had high sensitivities for predicting HPV16 detected on LCM (92.5-97.5%). Anyplex II HPV28 and EuroArray were significantly more sensitive than LA for lesions caused by non-HPV16 HRHPV types on LCM. DISCUSSION: Anyplex II HPV28 and EuroArray detected more non-16 HRHPV genotypes than LA. Increasing the Anyplex II HPV28 cutoff improved specificity without compromising sensitivity for detection of concurrent HSIL.

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.

Gene methylation of CADM1 and MAL identified as a biomarker of high grade anal intraepithelial neoplasia.

Human papillomavirus (HPV) is detected in up to 96% of anal squamous cell cancers, where screening programs needed. However, the best methodology is still undetermined. Host DNA methylation markers CADM1, MAL and miR124 have been identified in cervical disease, but not anal disease. Anal swabs varying by disease grade were assessed for DNA methylation of CADM1, MAL and miR124-2. Each marker was compared across disease grades, stratified by HPV and HIV status. Receiver operating characteristic curves identified the predictive value of significant gene candidates. CADM1 methylation was significantly higher in high-grade squamous intraepithelial lesions (HSIL) compared with low-grade (LSIL) (p = 0.005) or normal (p < 0.001) samples with 67.2% correctly identified as HSIL. MAL methylation was significantly (p = 0.002) increased in HSIL compared with LSIL in HIV positive participants with 79.8% correctly indicated as HSIL. Gene miR124-2, showed no difference between disease grades. Biomarkers with established diagnostic value in cervical disease have limited utility in the prediction of anal disease, with CADM1 identified as a marker with screening potential in a gay and bisexual men (GBM) population and MAL in HIV positive GBM population. New markers specific to the anal mucosa are required to improve triage of high-risk individuals.

Dexterity, activity performance, disability, quality of life, and independence in upper limb Veteran prosthesis users: a normative study.

PURPOSE: To present population data on standardized measures of dexterity, activity performance, disability, health-related quality of life (HRQoL) and community integration for persons with upper limb amputation (ULA), compare outcomes to normative values, and examine differences by prosthesis type and laterality (unilateral vs. bilateral amputation). MATERIALS AND METHODS: Multi-site, cross-sectional design, with in-person evaluations, functional performance, and self-report measures. Descriptive and comparative analyses were performed by amputation level and prosthesis type, data were compared for unilateral and bilateral amputation. RESULTS: One hundred and twenty-seven individuals participated; mean age 57 years, 59% percent body-powered prostheses users. All measures of dexterity differed (p < 0.05) by amputation level and by laterality. All measures of activity differed by amputation level with the best scores in transradial (TR) amputation groups. Comparisons of body-powered users with TR amputation found that dexterity was better for those with bilateral compared to unilateral amputation. CONCLUSIONS: Dexterity is markedly impaired in persons with ULA. Individuals with more proximal ULA levels are most impacted. HRQoL and community participation are less impacted and more equivalent to unimpaired persons. Further research is needed to examine differences by terminal device type and determine how best to match persons with ULA to the optimal prosthesis type and componentry, based on individual characteristics.Implications for RehabilitationThis study provides population-based, comparative data on dexterity, activity performance, disability, quality of life, and independence in upper limb prosthesis users.The study provides preliminary analyses comparing the effectiveness of body-powered devices, myoelectric devices with single degree of freedom and multi-degree of freedom terminal devices.The data presented in this study can be used to benchmark outcomes in patients who are upper limb prosthesis users.The data will also be useful to inform comparative evaluations of existing and emerging prosthetic technology.

Understanding Implications of Residual Limb Length, Strength, and Range-of-Motion Impairments of Veterans With Upper Limb Amputation.

OBJECTIVE: The aim of the study was to describe and quantify the relationship between limb impairment variables to key functional outcomes. DESIGN: This was an observational study of 107 participants with unilateral above/at-elbow or below-elbow/wrist amputation. Demographics, prosthesis characteristics, residual limb length, and prevalence of passive range-of-motion restrictions, and strength impairments were described. Correlations between impairment variables were estimated. Linear regressions examined associations between impairment variables and activity performance, health-related quality of life, disability, and prosthesis satisfaction. RESULTS: Prevalence of short/very short below- and above-elbow residua was 25.7% and 12.5%, respectively. Shorter below-elbow/wrist residual limb length was correlated with elbow flexion weakness (r = 0.30) and prevalence of passive range of motion (r = 0.25). Shoulder prevalence of passive range-of-motion restrictions were correlated with shoulder (r = 0.27-0.51) and elbow weakness (r = 0.25-0.46). In regressions, activity performance was worse for those with shoulder flexion prevalence of passive range-of-motion restrictions (B = -5.0, P = 0.03) and better for those with flexion restrictions (B = 3.3, P = 0.04) compared with normal prevalence of passive range of motion. Prosthetic satisfaction was lower for those with limited elbow prevalence of passive range of motion. CONCLUSIONS: Short below-elbow residual limb length was correlated with impairment of elbow flexion strength and prevalence of passive range of motion. Prevalence of passive range-of-motion restrictions were most prevalent at the shoulder and were strongly correlated with weakness in the same planes of motion. Few significant associations were found between impairment variables and outcomes.

Is Chlamydia to Blame for Koala Reproductive Cysts?

A significant threat to koala populations is infection from Chlamydia, which results in disease and death. Wild koalas with Chlamydia infections are admitted to wildlife hospitals and treated with antibiotics; however, up to 50% of koalas that present to wildlife hospitals do not survive. A major contributor to high mortality is the development of reproductive cysts, resulting in female infertility and euthanasia. However, the diagnosis of reproductive disease is limited to ultrasound with no further investigations. This communication highlights reports of histological and microbiological findings, the accuracy of ultrasound to necropsy reports and other possible causes for reproductive cyst development previously reported in other hosts. Our conclusions identify a significant knowledge gap in the aetiology of koala reproductive cysts and highlight the urgent need for future investigations.

Chlamydial clinical isolates show subtle differences in persistence phenotypes and growth in vitro.

Urogenital Chlamydia trachomatis infection is the most common sexually transmitted bacterial infection throughout the world. While progress has been made to better understand how type strains develop and respond to environmental stress in vitro, very few studies have examined how clinical isolates behave under similar conditions. Here, we examined the development and persistence phenotypes of several clinical isolates, to determine how similar they are to each other, and the type strain C. trachomatis D/UW-3/Cx. The type strain was shown to produce infectious progeny at a higher magnitude than each of the clinical isolates, in each of the six tested cell lines. All chlamydial strains produced the highest number of infectious progeny at 44 h post-infection in the McCoy B murine fibroblast cell line, yet showed higher levels of infectivity in the MCF-7 human epithelial cell line. The clinical isolates were shown to be more susceptible than the type strain to the effects of penicillin and iron deprivation persistence models in the MCF-7 cell line. While subtle differences between clinical isolates were observed throughout the experiments conducted, no significant differences were identified. This study reinforces the importance of examining clinical isolates when trying to relate in vitro data to clinical outcomes, as well as the importance of considering the adaptations many type strains have to being cultured in vitro.

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.).