Footprint evidence of early hominin locomotor diversity at Laetoli, Tanzania.

Bipedal trackways discovered in 1978 at Laetoli site G, Tanzania and dated to 3.66 million years ago are widely accepted as the oldest unequivocal evidence of obligate bipedalism in the human lineage1-3. Another trackway discovered two years earlier at nearby site A was partially excavated and attributed to a hominin, but curious affinities with bears (ursids) marginalized its importance to the paleoanthropological community, and the location of these footprints fell into obscurity3-5. In 2019, we located, excavated and cleaned the site A trackway, producing a digital archive using 3D photogrammetry and laser scanning. Here we compare the footprints at this site with those of American black bears, chimpanzees and humans, and we show that they resemble those of hominins more than ursids. In fact, the narrow step width corroborates the original interpretation of a small, cross-stepping bipedal hominin. However, the inferred foot proportions, gait parameters and 3D morphologies of footprints at site A are readily distinguished from those at site G, indicating that a minimum of two hominin taxa with different feet and gaits coexisted at Laetoli.

Insights into Spt6: a histone chaperone that functions in transcription, DNA replication, and genome stability.

Transcription elongation requires elaborate coordination between the transcriptional machinery and chromatin regulatory factors to successfully produce RNA while preserving the epigenetic landscape. Recent structural and genomic studies have highlighted that suppressor of Ty 6 (Spt6), a conserved histone chaperone and transcription elongation factor, sits at the crux of the transcription elongation process. Other recent studies have revealed that Spt6 also promotes DNA replication and genome integrity. Here, we review recent studies of Spt6 that have provided new insights into the mechanisms by which Spt6 controls transcription and have revealed the breadth of Spt6 functions in eukaryotic cells.

Long-term follow-up of VIALE-A: Venetoclax and azacitidine in chemotherapy-ineligible untreated acute myeloid leukemia.

Venetoclax-azacitidine is approved for treatment of patients with newly diagnosed acute myeloid leukemia (AML) ineligible for intensive chemotherapy based on the interim overall survival (OS) analysis of the VIALE-A study (NCT02993523). Here, long-term follow-up is presented to address survival benefit and long-term outcomes with venetoclax-azacitidine. Patients with newly diagnosed AML who were ineligible for intensive chemotherapy were randomized 2:1 to receive venetoclax-azacitidine or placebo-azacitidine. OS was the primary endpoint; complete remission with/without blood count recovery (CR/CRi) was a key secondary endpoint. This final analysis was conducted when 100% of the predefined 360 OS events occurred. In VIALE-A, 431 patients were enrolled to venetoclax-azacitidine (n = 286) or placebo-azacitidine (n = 145). At 43.2 months median follow-up, median OS was 14.7 months (95% confidence interval [CI], 12.1-18.7) with venetoclax-azacitidine, and 9.6 months (95% CI, 7.4-12.7) with placebo-azacitidine (hazard ratio, 0.58 [95% CI, 0.47-0.72], p < .001); the estimated 24-month OS rate was 37.5% and 16.9%, respectively. Median OS for patients with IDH1/2 mutations and those with measurable residual disease responses was reached in this final analysis. CR/CRi rate was similar to interim analysis. Any-grade hematologic and gastrointestinal adverse events were most common in venetoclax-azacitidine and placebo-azacitidine arms, including thrombocytopenia (47% and 42%) and neutropenia (43% and 29%). No new safety signals were identified. Long-term efficacy and safety confirm venetoclax-azacitidine is an improvement in standard-of-care for patients with AML who are not eligible for intensive chemotherapy because of advanced age or comorbidities.

A review of the distal femur in Australopithecus.

In 1938, the first distal femur of a fossil Australopithecus was discovered at Sterkfontein, South Africa. A decade later, another distal femur was discovered at the same locality. These two fossil femora were the subject of a foundational paper authored by Kingsbury Heiple and Owen Lovejoy in 1971. In this paper, the authors discussed functionally relevant anatomies of these two fossil femora and noted their strong affinity to the modern human condition. Here, we update this work by including eight more fossil Australopithecus distal femora, an expanded comparative dataset, as well as additional linear measurements. Just as Heiple and Lovejoy reported a half-century ago, we find strong overlap between modern humans and cercopithecoids, except for inferiorly flattened condyles and a high bicondylar angle, both of which characterize modern humans and Australopithecus and are directly related to striding bipedalism. All other measured aspects of the femora are by-products of these key morphological traits. Additional fossil material from the early Pliocene will help to inform the evolution of the hominin distal femur and its condition in the Pan-Homo common ancestor that preceded bipedal locomotion.

Engineering the Signal Resolution of a Paper-Based Cell-Free Glutamine Biosensor with Genetic Engineering, Metabolic Engineering, and Process Optimization.

Specialized cancer treatments have the potential to exploit glutamine dependence to increase patient survival rates. Glutamine diagnostics capable of tracking a patient's response to treatment would enable a personalized treatment dosage to optimize the tradeoff between treatment success and dangerous side effects. Current clinical glutamine testing requires sophisticated and expensive lab-based tests, which are not broadly available on a frequent, individualized basis. To address the need for a low-cost, portable glutamine diagnostic, this work engineers a cell-free glutamine biosensor to overcome assay background and signal-to-noise limitations evident in previously reported studies. The findings from this work culminate in the development of a shelf-stable, paper-based, colorimetric glutamine test with a high signal strength and a high signal-to-background ratio for dramatically improved signal resolution. While the engineered glutamine test is important progress towards improving the management of cancer and other health conditions, this work also expands the assay development field of the promising cell-free biosensing platform, which can facilitate the low-cost detection of a broad variety of target molecules with high clinical value.

Adolescent eating disorder treatment outcomes of an in-person partial hospital program versus a virtual intensive outpatient program.

OBJECTIVE: Though virtual outpatient psychotherapy for eating disorders is likely effective, less is known about virtual higher levels of care. The current study examined the clinical outcomes of a family-based virtual intensive outpatient program (vIOP) for youth with eating disorders which was developed in response to the COVID-19 pandemic, compared to the same institution's in-person partial hospital program (PHP). METHODS: Treatment outcomes were assessed via chart review in 102 patients between the ages of 9-23 (M = 15.2, SD = 2.5) who were predominantly cisgender female (84.3%) and primarily diagnosed with anorexia nervosa (64.7%) or atypical anorexia (23.5%). Participants were either treated in the in-person PHP before the pandemic (n = 49) or the vIOP during the pandemic (n = 53). Percent expected body weight (%EBW) was examined at baseline, end of treatment, 3-months post-treatment, and 6-months post-treatment, as well as the frequency of medical, psychiatric, and residential admissions before, during, and after vIOP or PHP participation. RESULTS: Linear mixed models demonstrated no effect of treatment modality (in-person versus virtual) on %EBW over time. The duration of the vIOP was, on average, 12 calendar days longer, though the amount billed for the vIOP was lower. Survival analyses and Cox regression models did not suggest differences in the frequency of hospital and residential treatment admissions during treatment (vIOP: 9.4%, PHP: 10.0%) or post-treatment (vIOP: 15.0%, PHP: 10.2%). DISCUSSION: Findings support virtual family-based programs as suitable alternatives to in-person treatment and underscore the potential cost-effectiveness of a family-based IOP versus PHP. PUBLIC SIGNIFICANCE: This study demonstrates that a virtual, family-based, intensive outpatient program for youth with eating disorders had similar treatment outcomes to an in-person partial hospitalization program. Specifically, the virtual and in-person programs had similar weight restoration outcomes and rates of medical, psychiatric, or residential treatment admissions during or after treatment initiation. Findings support the use of virtual treatment, even for youth requiring a high level of intervention.

Student-led interprofessional global health course: learning impacts during a global crisis.

BACKGROUND: This study assesses the impact of the Interprofessional Global Health Course (IPGHC) on students' fundamental global health knowledge and personal viewpoints on global health domains. It explores the evolution of students' understanding of global health specifically in relation to the COVID-19 pandemic. METHODS: Ninety-nine students were selected from 123 McGill student applicants based on their motivation and commitment to take part in IPGHC's ten-week 2020 curriculum. These IPGHC students were eligible to participate in the study. The study's design is sequential explanatory mixed methods. The cross-sectional survey (quantitative phase) appraises students' global health learning outcomes using pre- and post-course surveys, with the use of 5-point Likert-scale questions. The descriptive qualitative survey (qualitative phase) further explores the impact of IPGHC on student's understanding of global health and the reflections of students on the COVID-19 pandemic after IPGHC. The post-course survey included a course evaluation for quality improvement purposes. RESULTS: Of the 99 students, 81 students across multiple undergraduate and graduate disciplines participated in the study by completing the course surveys. Mean knowledge scores of the following 11 global health topics were increased between pre- and post-course survey: Canadian Indigenous health (P < 0.001), global burden of disease (P < 0.001), global surgery (P < 0.001), infectious diseases and neglected tropical diseases (P < 0.001), refugee and immigrant health (P < 0.001), research and development of drugs (P < 0.001), role of politics and policies in global health (P = 0.02), role of technology in global health (P < 0.001), sexual violence (P < 0.001), systemic racism in healthcare (P = 0.03), and trauma in the global health context (P < 0.001). A positive change in student viewpoints was observed in response to questions regarding their perception of the importance of global health education in their own professional health care programs (P < 0.001), and their understanding of the roles and responsibilities of other healthcare professionals (P < 0.001). In the post-course survey open-ended questions, students exemplified their knowledge gained during the course to create a more informed definition of global health. Several recurring themes were identified in the student reflections on the COVID-19 pandemic, notably policy and politics, followed by access to healthcare and resources. CONCLUSION: This study emphasizes the need for interprofessional global health education at the university level and demonstrates how rapidly global health learners can apply their knowledge to evolving contexts like the COVID-19 pandemic.

The Role of Autopsy in Quality Assurance: Pilot Study of a Method for Prospective Reporting of Diagnostic Errors Discovered at Autopsy.

ABSTRACT: Hospital autopsies frequently reveal errors in diagnosis that could have affected the patient's clinical outcome. The aims of this study were (1) to investigate the ability of autopsy at our institution to elucidate unrecognized antemortem diagnoses and (2) to pilot a method for tabulating diagnostic discrepancies on a prospective basis. The study sample consisted of 296 cases from our hybrid hospital/forensic autopsy service during the period 2016 to 2018. Discrepancies in autopsy and clinical diagnosis were reported by pathologists at the time of autopsy report generation using a standard form. The rates of major discrepancies between autopsy and clinical diagnoses were 37.5% for in-hospital cases and 25% for patients who died outside our hospital (P < 0.05). The most common discrepant category was infection. The overall rates of discrepant causes of death were 14% (in hospital) and 8% (out of hospital) (ns). Overall percentages of cases with major diagnostic discrepancies were higher in our study than have been previously reported. It is possible that the nature of our patient population plays a role in this result. This study describes an important prospective reporting tool that will allow us to track rates of medical errors and improve diagnosis and treatment of the critically ill.

Long-term safety and efficacy of dimethyl fumarate for up to 13 years in patients with relapsing-remitting multiple sclerosis: Final ENDORSE study results.

BACKGROUND: Dimethyl fumarate (DMF) demonstrated favorable benefit-risk in relapsing-remitting multiple sclerosis (RRMS) patients in phase-III DEFINE and CONFIRM trials, and ENDORSE extension. OBJECTIVE: The main aim of this study is assessing DMF safety/efficacy up to 13 years in ENDORSE. METHODS: Randomized patients received DMF 240 mg twice daily or placebo (PBO; Years 0-2), then DMF (Years 3-10; continuous DMF/DMF or PBO/DMF); maximum follow-up (combined studies), 13 years. RESULTS: By January 2020, 1736 patients enrolled/dosed in ENDORSE (median follow-up 8.76 years (ENDORSE range: 0.04-10.98) in DEFINE/CONFIRM and ENDORSE); 52% treated in ENDORSE for ⩾6 years. Overall, 551 (32%) patients experienced serious adverse events (mostly multiple sclerosis (MS) relapse or fall; one progressive multifocal leukoencephalopathy); 243 (14%) discontinued treatment due to adverse events (4% gastrointestinal (GI) disorders). Rare opportunistic infections, malignancies, and serious herpes zoster occurred, irrespective of lymphocyte count. For DMF/DMF (n = 501), overall annualized relapse rate (ARR) remained low (0.143 (95% confidence interval (CI), 0.120-0.169)), while for PBO/DMF (n = 249), ARR decreased after initiating DMF and remained low throughout (ARR 0-2 years, 0.330 (95% CI, 0.266-0.408); overall ARR (ENDORSE, 0.151 (95% CI, 0.118-0.194)). Over 10 years, 72% DMF/DMF and 73% PBO/DMF had no 24-week confirmed disability worsening. CONCLUSION: Sustained DMF safety/efficacy was observed in patients followed up to 13 years, supporting DMF's positive benefit/risk profile for long-term RRMS treatment.

The bacterial gut microbiome of probiotic-treated very-preterm infants: changes from admission to discharge.

BACKGROUND: Preterm birth is associated with the development of acute and chronic disease, potentially, through the disruption of normal gut microbiome development. Probiotics may correct for microbial imbalances and mitigate disease risk. Here, we used amplicon sequencing to characterise the gut microbiome of probiotic-treated premature infants. We aimed to identify and understand variation in bacterial gut flora from admission to discharge and in association with clinical variables. METHODS: Infants born <32 weeks gestation and <1500 g, and who received probiotic treatment, were recruited in North Queensland Australia. Meconium and faecal samples were collected at admission and discharge. All samples underwent 16S rRNA short amplicon sequencing, and subsequently, a combination of univariate and multivariate analyses. RESULTS: 71 admission and 63 discharge samples were collected. Univariate analyses showed significant changes in the gut flora from admission to discharge. Mixed-effects modelling showed significantly lower alpha diversity in infants diagnosed with either sepsis or retinopathy of prematurity (ROP) and those fed formula. In addition, chorioamnionitis, preeclampsia, sepsis, necrotising enterocolitis and ROP were also all associated with the differential abundance of several taxa. CONCLUSIONS: The lower microbial diversity seen in infants with diagnosed disorders or formula-fed, as well as differing abundances of several taxa across multiple variables, highlights the role of the microbiome in the development of health and disease. This study supports the need for promoting healthy microbiome development in preterm neonates. IMPACT: Low diversity and differing taxonomic abundances in preterm gut microbiota demonstrated in formula-fed infants and those identified with postnatal conditions, as well as differences in taxonomy associated with preeclampsia and chorioamnionitis, reinforcing the association of the microbiome composition changes due to maternal and infant disease. The largest study exploring an association between the preterm infant microbiome and ROP. A novel association between the preterm infant gut microbiome and preeclampsia in a unique cohort of very-premature probiotic-supplemented infants.

Exploring the long-term colonisation and persistence of probiotic-prophylaxis species on the gut microbiome of preterm infants: a pilot study.

Preterm infants suffer from a higher incidence of acute diseases such as necrotising enterocolitis and sepsis. This risk can be mitigated through probiotic prophylaxis during admission. This reduction in risk is likely the result of acute modulation of the gut microbiome induced by probiotic species, which has been observed to occur up until discharge. We aimed to determine if this modulation, and the associated probiotic species, persisted beyond discharge. We conducted both a cross-sectional analysis (n = 18), at ~ 18 months of age, and a longitudinal analysis (n = 6), from admission to 18 months of the gut microbiome of preterm infants using both shotgun metagenomics and 16S rRNA profiling respectively. The 16S amplicon sequencing revealed that the microbial composition of the probiotic-supplemented infants changed dramatically over time, stabilising at discharge. However, species from the probiotic Infloran®, as well as positive modulatory effects previously associated with supplementation, do not appear to persist beyond discharge and once prophylaxis has stopped.    Conclusions: Although differences exist between supplemented and non-supplemented groups, the implications of these differences remain unclear. Additionally, despite a lack of long-term colonisation, the presence of probiotics during early neonatal life may still have modulatory effects on the microbiome assembly and immune system training. What is Known: • Evidence suggests modulation of the microbiome occurs during probiotic prophylaxis, which may support key taxa that exert positive immunological benefits. • Some evidence suggests that this modulation can persist post-prophylaxis. What is New: • We present support for long-term modulation in association with probiotic prophylaxis in a cohort of infants from North Queensland Australia. • We also observed limited persistence of the probiotic species post-discharge.

Dimethyl fumarate treatment shifts the immune environment toward an anti-inflammatory cell profile while maintaining protective humoral immunity.

BACKGROUND: Delayed-release dimethyl fumarate (DMF) demonstrates sustained efficacy and safety for relapsing forms of MS. Absolute lymphocyte count (ALC) is reduced initially, then stabilizes on treatment. OBJECTIVE: PROCLAIM, a 96-week, prospective, open-label, phase 3b study, assessed lymphocyte subsets and immunoglobulin (Ig) levels during 48 and 96 weeks (W) of DMF treatment. METHODS: Patients received 240 mg DMF BID. Endpoints: lymphocyte subset count changes (primary); Ig isotypes and ALC changes (secondary); adverse events and relationship between ALC changes and ARR/EDSS (exploratory); and neurofilament assessment (ad hoc). RESULTS: Of 218 patients enrolled, 158 (72%) completed the study. Median ALC decreased 39% from baseline to W96 (BL-W96), stabilizing above the lower limit of normal (baseline: 1.82 × 109/L; W48: 1.06 × 109/L; W96: 1.05 × 109/L). CD4 + and CD8 + T cells correlated highly with ALC from BL-W96 (p < 0.001). Relative to total T cells, naive CD4 + and CD8 + T cells increased, whereas CD4 + and CD8 + central and effector memory T cells decreased. Total IgA, IgG, IgM, and IgG1-4 subclass levels remained stable. Adverse event rates were similar across ALC subgroups. ARR, EDSS, and neurofilament were not correlated with ALCs. CONCLUSION: Lymphocyte decreases with DMF were maintained over treatment, yet immunoglobulins remained stable. No increase in infection incidence was observed in patients with or without lymphopenia. SUPPORT: Biogen.

Dental Implant Placement in Patients With a History of Medications Related to Osteonecrosis of the Jaws: A Systematic Review.

The present systematic review evaluates the safety of placing dental implants in patients with a history of antiresorptive or antiangiogenic drug therapy. The Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) guidelines were followed. PubMed, Cochrane Central Register of Controlled Trials, Scopus, Web of Science, and OpenGrey databases were used to search for clinical studies (English only) to July 16, 2019. Study quality was assessed regarding randomization, allocation sequence concealment, blinding, incomplete outcome data, selective outcome reporting, and other biases using a modified Newcastle-Ottawa scale and the Joanna Briggs Institute critical appraisal checklist for case series. A broad search strategy resulted in the identification of 7542 studies. There were 28 studies reporting on bisphosphonates (5 cohort, 6 case control, and 17 case series) and 1 study reporting on denosumab (case series) that met the inclusion criteria and were included in the qualitative synthesis. The quality assessment revealed an overall moderate quality of evidence among the studies. Results demonstrated that patients with a history of bisphosphonate treatment for osteoporosis are not at increased risk of implant failure in terms of osseointegration. However, all patients with a history of bisphosphonate treatment, whether taken orally for osteoporosis or intravenously for malignancy, appear to be at risk of "implant surgery-triggered" medication-related osteonecrosis of the jaw (MRONJ). In contrast, the risk of MRONJ in patients treated with denosumab for osteoporosis was found to be negligible. In conclusion, general and specialist dentists should exercise caution when planning dental implant therapy in patients with a history of bisphosphonate and denosumab drug therapy. Importantly, all patients with a history of bisphosphonates are at risk of MRONJ, necessitating this to be included in the informed consent obtained before implant placement.

Diroximel fumarate (DRF) in patients with relapsing-remitting multiple sclerosis: Interim safety and efficacy results from the phase 3 EVOLVE-MS-1 study.

BACKGROUND: Diroximel fumarate (DRF) is a novel oral fumarate for patients with relapsing-remitting multiple sclerosis (RRMS). DRF and the approved drug dimethyl fumarate yield bioequivalent exposure to the active metabolite monomethyl fumarate; thus, efficacy/safety profiles are expected to be similar. However, DRF's distinct chemical structure may result in a differentiated gastrointestinal (GI) tolerability profile. OBJECTIVE: To report interim safety/efficacy findings from patients in the ongoing EVOLVE-MS-1 study. METHODS: EVOLVE-MS-1 is an ongoing, open-label, 96-week, phase 3 study assessing DRF safety, tolerability, and efficacy in RRMS patients. Primary endpoint is safety and tolerability; efficacy endpoints are exploratory. RESULTS: As of March 2018, 696 patients were enrolled; median exposure was 59.9 (range: 0.1-98.9) weeks. Adverse events (AEs) occurred in 84.6% (589/696) of patients; the majority were mild (31.2%; 217/696) or moderate (46.8%; 326/696) in severity. Overall treatment discontinuation was 14.9%; 6.3% due to AEs and <1% due to GI AEs. At Week 48, mean number of gadolinium-enhancing lesions was significantly reduced from baseline (77%; p < 0.0001) and adjusted annualized relapse rate was low (0.16; 95% confidence interval: 0.13-0.20). CONCLUSION: Interim data from EVOLVE-MS-1 suggest DRF is a well-tolerated treatment with a favorable safety/efficacy profile for patients with RRMS.

The diagnostic accuracy of multiparametric magnetic resonance imaging before biopsy in the detection of prostate cancer.

OBJECTIVES: To determine the extent to which clinically significant prostate cancer (csPCa) can be detected in a routine National Health Service setting in men with no previous biopsy, when multiparametric magnetic resonance imaging (mpMRI) is introduced into the diagnostic pathway. PATIENTS AND METHODS: In all, 1 090 mpMRIs were performed between July 2013 and April 2016 in biopsy-naïve men with an abnormal prostate-specific antigen level and/or digital rectal examination. Data were collected from patient records at the Royal Devon and Exeter NHS Foundation Trust. mpMRI Prostate Imaging Reporting and Data System (PI-RADS) scores were compared to transperineal or transrectal ultrasonography (TRUS)-guided biopsy findings as the reference standard. csPCa was defined as Gleason score of ≥3+4. The diagnostic accuracy of mpMRI was also assessed. RESULTS: The mpMRI was interpretable in 1 023 men and 792 underwent biopsy, of which 106 were transperineal. The median number of cores taken in transperineal and TRUS-guided biopsy were 10 and 6, respectively. The detection rate of csPCa was 37%; csPCa rose from 15% of PI-RADS 1 and 2 to 86% of PI-RADS 5. The sensitivity, negative predictive value, specificity, and positive predictive value were 82%, 85%, 59% and 54%, respectively. The study is limited by its retrospective nature and lack of reporting of follow-up for 'missed cancers'. Men with low mpMRI PI-RADS were also less likely to undergo biopsy. Whilst this selection bias may overestimate the detection rate of csPCa, this reflects the shared decisions patients and clinicians make in day-to-day practice outside of research centres. CONCLUSION: In a routine clinical setting, the higher the mpMRI PI-RADS, the greater the detection rate of csPCa in biopsy-naïve men. A normal mpMRI does not exclude csPCa; however, mpMRI may have utility in informing shared-decision making on whether to proceed to biopsy and subsequent treatment.

A novel technique for awake, minimally invasive transforaminal lumbar interbody fusion: technical note.

Minimally invasive transforaminal lumbar interbody fusion (MI-TLIF) is associated with improved patient-reported outcomes in well-selected patients. Recently, some neurosurgeons have aimed to further improve outcomes by utilizing multimodal methods to avoid the use of general anesthesia. Here, the authors report on the use of a novel awake technique for MI-TLIF in two patients. They describe the successful use of liposomal bupivacaine in combination with a spinal anesthetic to allow for operative analgesia.

Comparison of the Alere i Strep A Test and the BD Veritor System in the Detection of Group A Streptococcus and the Hypothetical Impact of Results on Antibiotic Utilization.

Rapid detection of group A Streptococcus (GAS) is an integral component of treatment decisions in the clinic, especially in the pediatric population. We prospectively collected 216 specimens from symptomatic, predominantly pediatric patients and evaluated the performance of the Alere i Strep A test (Alere i; Alere Inc., Scarborough, ME) and the BD Veritor system (BD Veritor; Becton, Dickinson and Company, Sparks, MD), with culture results being used as a comparator. Real-time PCR (RT-PCR) was performed as an arbiter in discordant cases. Comprehensive chart review was also done to determine the hypothetical impact of the results on antibiotic use. Alere i had a sensitivity and a specificity of 100% and 91.3%, respectively, and BD Veritor had a sensitivity and a specificity of 76.2% and 93.6%, respectively, when the results were compared to those of GAS culture. Further analysis of discordant results using RT-PCR revealed that while BD Veritor missed 13 confirmed positive cases, Alere i detected 100% (n = 13) of the same cases. Analysis of assay agreement showed that Alere i and BD Veritor had only moderate agreement (agreement = 0.888 [95% confidence interval {CI}, 0.838 to 0.927]; kappa index = 0.689 [95% CI, 0.91 to 0.974]). We also found both the underutilization and the overutilization of antibiotics based on the results of molecular testing. Overall, Alere i showed superior performance over BD Veritor in the detection of GAS pharyngitis and could potentially assist in better antibiotic utilization.

The British Association of Urological Surgeons (BAUS) radical prostatectomy audit 2014/2015 - an update on current practice and outcomes by centre and surgeon case-volume.

OBJECTIVES: To describe contemporary radical prostatectomy (RP) practice using the British Association of Urological Surgeons (BAUS) data and audit project and to observe differences in practice in relation to surgeon or centre case-volume. PATIENTS AND METHODS: Data on 13 920 RP procedures performed by 179 surgeons across 86 centres were recorded on the BAUS data and audit platform between 1 January 2014 and 31 December 2015. This equates to ~95% of total RPs performed over this period when compared to Hospital Episode Statistics (HES) data. Centre case-volumes were categorised as 'high' (>200), 'medium' (100-200) and 'low' (<100); surgeon case-volumes were categorised as 'high' (>100) and 'low' (<100). Differences in surgical practice and selected outcome measures were observed between groups. All data and volume categories were for the combined 2-year period. RESULTS: The median number of RPs performed over the 2-year period was 63.5 per surgeon and 164 per centre. Overall, surgical approach was robot-assisted laparoscopic RP (RALP) in 65%, laparoscopic RP (LRP) in 23%, and open RP (ORP) in 12%. The dominant approach in high-case-volume centres and by high-case-volume surgeons was RALP (74.3% and 69.2%, respectively). There was a greater percentage of ORPs reported by low-volume surgeons and centres when compared to higher volume equivalents. In all, 51.6% of all patients in this series underwent RP in high-case-volume centres using robot-assisted surgery (RAS). High-case-volume surgeons performed nerve-sparing (NS) procedures on 57.3% of their cases; low-volume surgeons performing NS on 48.2%. Overall, lymph node dissection (LND) rates were very similar across the groups. An 'extended' LND was more commonly performed in high-volume centres (22.1%). The median length of stay (LOS) was lowest in patients undergoing RALP at high-volume centres (1 day) and highest in ORP across all volume categories (3-4 days). Reported pT2 positive surgical margin (PSM) rate varied by technique, centre volume, and surgeon volume. In general, observed PSM rates were lower when RALP was the surgical approach (14.4%) and when high-volume surgeons were compared to low-volume surgeons (13.6% vs 17.7%). Transfusion rates were highest in ORP across all centres and surgeons (2.96-4.49%) compared to techniques using a minimally-invasive approach (0.25-2.41%). Training cases ranged from 0.5% in low-volume centres to 6.0% in high-volume centres. CONCLUSIONS: Compliance with data registration for centres and surgeons performing RP is high in the present series. Most RPs were performed in high-case-volume centres and by high-case-volume surgeons, with the most common approaches being minimally invasive and specifically RAS. High-case-volume centres and surgeons reported higher rates of extended LND and training cases. Higher-case-volume surgeons reported lower pT2 PSM rates, whilst the most marked differences in transfusion rates and LOS were seen when ORP was compared to minimally invasive approaches. Caution must be applied when interpreting these differences on the basis of this being registry data - causality cannot be assumed.

Open radical cystectomy in England: the current standard of care - an analysis of the British Association of Urological Surgeons (BAUS) cystectomy audit and Hospital Episodes Statistics (HES) data.

OBJECTIVE: To establish the current standard for open radical cystectomy (ORC) in England, as data entry by surgeons performing RC to the British Association of Urological Surgeons (BAUS) database was mandated in 2013 and combining this with Hospital Episodes Statistics (HES) data has allowed comprehensive outcome analysis for the first time. PATIENTS AND METHODS: All patients were included in this analysis if they were uploaded to the BAUS data registry and reported to have been performed in the 2 years between 1 January 2014 and 31 December 2015 in England (from mandate onwards) and had been documented as being performed in an open fashion (not laparoscopic, robot assisted or the technique field left blank). The HES data were accessed via the HES website. Office of Population Censuses and Surveys Classification of Surgical Operations and Procedures version 4 (OPCS-4) Code M34 was searched during the same 2-year time frame (not including M34.4 for simple cystectomy or with additional minimal access codes Y75.1-9 documenting a laparoscopic or robotic approach was used) to assess data capture. RESULTS: A total of 2 537 ORCs were recorded in the BAUS registry and 3 043 in the HES data. This indicates a capture rate of 83.4% of all cases. The median operative time was 5 h, harvesting a median of 11-20 lymph nodes, with a median blood loss of 500-1 000 mL, and a transfusion rate of 21.8%. The median length of stay was 11 days, with a 30-day mortality rate of 1.58%. CONCLUSIONS: This is the largest, contemporary cohort of ORCs in England, encompassing >80% of all performed operations. We now know the current standard for ORC in England. This provides the basis for individual surgeons and units to compare their outcomes and a standard with which future techniques and modifications can be compared.