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Background: Bloodstream infections are associated with substantial morbidity and mortality. Early, appropriate antibiotic therapy is important, but the duration of treatment is uncertain., Methods: In a multicenter, noninferiority trial, we randomly assigned hospitalized patients (including patients in the intensive care unit [ICU]) who had bloodstream infection to receive antibiotic treatment for 7 days or 14 days. Antibiotic selection, dosing, and route were at the discretion of the treating team. We excluded patients with severe immunosuppression, foci requiring prolonged treatment, single cultures with possible contaminants, or cultures yielding Staphylococcus aureus . The primary outcome was death from any cause by 90 days after diagnosis of the bloodstream infection, with a noninferiority margin of 4 percentage points., Results: Across 74 hospitals in seven countries, 3608 patients underwent randomization and were included in the intention-to-treat analysis; 1814 patients were assigned to 7 days of antibiotic treatment, and 1794 to 14 days. At enrollment, 55.0% of patients were in the ICU and 45.0% were on hospital wards. Infections were acquired in the community (75.4%), hospital wards (13.4%) and ICUs (11.2%). Bacteremia most commonly originated from the urinary tract (42.2%), abdomen (18.8%), lung (13.0%), vascular catheters (6.3%), and skin or soft tissue (5.2%). By 90 days, 261 patients (14.5%) receiving antibiotics for 7 days had died and 286 patients (16.1%) receiving antibiotics for 14 days had died (difference, -1.6 percentage points [95.7% confidence interval {CI}, -4.0 to 0.8]), which showed the noninferiority of the shorter treatment duration. Patients were treated for longer than the assigned duration in 23.1% of the patients in the 7-day group and in 10.7% of the patients in the 14-day group. A per-protocol analysis also showed noninferiority (difference, -2.0 percentage points [95% CI, -4.5 to 0.6]). These findings were generally consistent across secondary clinical outcomes and across prespecified subgroups defined according to patient, pathogen, and syndrome characteristics., Conclusions: Among hospitalized patients with bloodstream infection, antibiotic treatment for 7 days was noninferior to treatment for 14 days. (Funded by the Canadian Institutes of Health Research and others; BALANCE ClinicalTrials.gov number, NCT03005145.)., (Copyright © 2024 Massachusetts Medical Society.)

Background: Candidaemia is an invasive infection with high morbidity and mortality. All urology procedures carry risk of post-operative infection. Risk mitigation strategies include preoperative urine culture and treatment of cultured organism(s) regardless of symptoms. After zero cases of candidaemia for two years, there were five cases in elective urology patients within 15 weeks between June - September 2021. This increased incidence of candidaemia amongst these patients prompted multidisciplinary investigation., Methods: Single centre case series, in a 250-bed hospital which annually performs 2000-2500 elective urology surgeries. Affected patients were elderly with multiple comorbidities. Notably, four of five patients had prior indwelling ureteral stents. All five patients had preoperative bacteriuria requiring antibiotics and one patient had pre-operative candiduria., Results: Hypotheses including sterilisation failure, surgical instrument contamination, or surgical technique issues were unfounded. We propose that pre-operative duration of antibacterial therapy, particularly in the setting of ureteral stent biofilm, is a significant factor for candiduria. A new prescribing algorithm for urology patients was devised. Antibiotic treatment duration in asymptomatic patients with indwelling urinary tract foreign material was reduced from 14 to 3 days, and from 14 to 7 days in symptomatic patients. Dedicated pharmacist resources were allocated to support this change and pre-operatively manage these patients. These interventions led to zero candidaemia cases over the subsequent 21 months, along with zero post-operative bacterial bloodstream infections., Conclusions: Prolonged pre-operative antibacterial therapy poses a risk for post-operative candidaemia, especially in patients with ureteral stents. Shortening pre-operative antibiotic courses, coupled with increased pharmacist involvement, effectively reduced candidaemia incidence., (Crown Copyright © 2024. Published by Elsevier B.V. All rights reserved.)

Objective: To identify trends in stillbirth rates attributed to congenital syphilis in the United States by describing congenital syphilis-related stillbirths and comparing characteristics of pregnant people who had congenital syphilis-related stillbirths with those of people who had preterm and full-term liveborn neonates with congenital syphilis., Methods: Cases of congenital syphilis reported to the Centers for Disease Control and Prevention during 2016-2022 were analyzed and categorized as stillbirth, preterm live birth (before 37 weeks of gestation), or term live birth (37 weeks or later). Cases with unknown vital status or gestational age were excluded. Frequencies were calculated by pregnancy outcome, including pregnant person demographics; receipt of prenatal care; syphilis stage and titer; and timing of prenatal care, testing, and treatment., Results: Overall, 13,393 congenital syphilis cases with vital status and gestational age were reported; of these, 853 (6.4%) were stillbirths. The number of congenital syphilis-related stillbirths increased each year (from 44 to 231); the proportion of congenital syphilis cases resulting in stillbirth ranged from 5.2% to 7.5%. Median gestational age at delivery for stillborn fetuses was 30 weeks (interquartile range 26-33 weeks). People with congenital syphilis-related stillbirths were more likely to have titers at or above 1:32 (78.9% vs 45.5%; P <.001) and to have received no prenatal care (58.4% vs 33.1%; P <.001) than people with liveborn neonates with congenital syphilis. The risk of stillbirth was twice as high in persons with secondary syphilis compared with those with primary syphilis (11.5% vs 5.7%, risk ratio 2.00; 95% CI, 1.27-3.13). Across all congenital syphilis cases, 34.2% of people did not have a syphilis test at their first prenatal visit., Conclusion: Stillbirths occurred in more than 1 in 20 pregnancies complicated by congenital syphilis. Risk factors for stillbirth included high titers, secondary stage, and lack of prenatal care. If the prevalence of congenital syphilis continues to rise, there will be a corresponding increase in the overall stillbirth rate nationally., Competing Interests: Financial Disclosure Lindley Barbee disclosed that while they were at UW, the following occurred: Hologic provided an in-kind donation of test kits for investigator-initiated trials; their institution received funding for an investigator-initiated trial from Nabriva and SpeeDx. The other authors did not report any potential conflicts of interest., (Copyright © 2024 by the American College of Obstetricians and Gynecologists. Published by Wolters Kluwer Health, Inc. All rights reserved.)

Introduction: Blood cultures have low sensitivity for candidemia. Sensitivity can be improved by the culture-independent system T2 Magnetic Resonance (T2). SeptiCyte RAPID is a host response assay quantifying the risk of infection-related inflammation through a scoring system (SeptiScore). We investigate the performance of SeptiScore in detecting persistent candidemia as defined by conventional cultures and T2., Methods: This is a prospective multicentre observational study on patients with candidemia. Blood cultures and blood samples for assessment by T2 and SeptiCyte were collected for 4 consecutive days after the index culture. The performance of SeptiScore was explored to predict persistent candidemia as defined by (1) positive follow-up blood culture (2) either positive follow-up blood culture or T2 sample., Results: 10 patients were enrolled including 34 blood collections assessed with the 3 methods. Overall, 4/34 (12%) follow-up blood cultures and 6/34 (18%) T2 samples were positive. A mixed model showed significantly higher SeptiScores associated with persistent candidemia when this was defined as either a positive follow-up blood culture or T2 sample (0.82, 95%CI 0.06 to 1.58) but not when this was defined as a positive follow-up blood culture only (-0.57, 95%CI -1.28 to 0.14). ROC curve for detection of persistent candidemia by SeptiScore at day 1 follow-up showed an AUC of 0.85 (95%CI 0.52-1.00) when candidemia was defined by positive follow-up blood culture, and an AUC of 1.00 (95%CI 1.00-1.00) when candidemia was defined according to both methods., Conclusion: Integrating transcriptome profiling with culture-independent systems and conventional cultures may increase our ability to diagnose persistent candidemia., (© 2024. The Author(s).)

Background: A prompt diagnosis of bacteraemia and sepsis is essential. Markers to predict the risk of persistent bacteraemia and metastatic infection are lacking. SeptiCyte RAPID is a host response assay stratifying patients according to the risk of infectious vs sterile inflammation through a scoring system (SeptiScore). In this study we explore the association between SeptiScore and persistent bacteraemia as well as metastatic and persistent infection in the context of a proven bacteraemia episode., Methods: This is a prospective multicentre observational 14-month study on patients with proven bacteraemia caused by Staphylococcus aureus or Gram-negative bacilli. Samples for assessment by SeptiCyte were collected with paired blood cultures for 4 consecutive days after the index blood culture., Results: We included 86 patients in the study, 40 with S. aureus and 46 with Gram-negative bacilli bacteraemia. SeptiScores over the follow-up were higher in patients with Gram-negative compared to S. aureus bacteraemia (median 6.4, IQR 5.5-7.4 vs 5.6 IQR 5.1-6.2, p  = 0.002). Higher SeptiScores were found to be associated with positive blood cultures at follow-up (AUC = 0.86, 95%CI 0.68-1.00) and with a diagnosis of metastatic infection at day 1 and 2 of follow-up (AUC = 0.79, 95%CI 0.57-1.00 and AUC = 0.82, 95%CI 0.63-1.00 respectively) in the context of Gram-negative bacteraemia while no association between SeptiScore and the outcomes of interest was observed in S. aureus bacteraemia. Mixed models confirmed the association of SeptiScore with positive blood cultures at follow-up ( p  = 0.04) and metastatic infection ( p  = 0.03) in the context of Gram-negative bacteraemia but not S. aureus bacteraemia after adjusting for confounders., Conclusions: SeptiScores differ in the follow-up of S. aureus and Gram-negative bacteraemia. In the setting of Gram-negative bacteraemia SeptiScore demonstrated a good negative predictive value for the outcomes of interest and might help rule out the persistence of infection defined as metastatic spread, lack of source control or persistent bacteraemia.

Background: Persistent Staphylococcus aureus bacteremia is associated with metastatic infection and adverse outcomes, whereas gram-negative bacteremia is normally transient and shorter course therapy is increasingly advocated for affected patients. Whether the prolonged detection of pathogen DNA in blood by culture-independent systems could have prognostic value and guide management decisions is unknown., Methods: We performed a multicenter, prospective, observational study on 102 patients with bloodstream infection (BSI) to compare time to bloodstream clearance according to T2 magnetic resonance and blood cultures over a 4-day follow-up. We also explored the association between duration of detectable pathogens according to T2 magnetic resonance (magnetic resonance-DNAemia [MR-DNAemia]) and clinical outcomes., Results: Time to bloodstream clearance according to T2 magnetic resonance was significantly longer than blood culture clearance (HR, .54; 95% CI, .39-.75) and did not differ according to the causative pathogen (P = .5). Each additional day of MR-DNAemia increased the odds of persistent infection (defined as metastatic infection or delayed source control) both in the overall population (OR, 1.98; 95% CI, 1.45-2.70) and in S. aureus (OR, 1.92; 95% CI, 1.12-3.29) and gram-negative bacteremia (OR, 2.21; 95% CI, 1.35-3.60). MR-DNAemia duration was also associated with no improvement in Sequential Organ Failure Assessment score at day 7 from infection onset (OR, 1.76; 95% CI, 1.21-2.56)., Conclusions: T2 magnetic resonance may help diagnose BSI in patients on antimicrobials with negative blood cultures as well as to identify patients with metastatic infection, source control failure, or adverse short-term outcome. Future studies may inform its usefulness within the setting of antimicrobial stewardship programs., Competing Interests: Potential conflicts of interest. D. L. P. has received research funding from Shionogi, Merck, bioMerieux, BioVersys, and Pfizer and has received consulting fees from the AMR Action Fund, CARB-X, Aurobac, Pfizer, Merck, Cepheid, bioMerieux, and Spero and reports a role on the board of the Australasian Society for Infectious Diseases. P. N. A. H. reports research grants from Gilead; has served on advisory boards for OpGen, Merck, and Sandoz; and has received honoraria from OpGen, Sandoz, Pfizer, and bioMerieux. All other authors report no potential conflicts. All authors have submitted the ICMJE Form for Disclosure of Potential Conflicts of Interest. Conflicts that the editors consider relevant to the content of the manuscript have been disclosed., (© The Author(s) 2023. Published by Oxford University Press on behalf of Infectious Diseases Society of America.)

Background: Research to date suggests that physical activity (PA) can buffer menopausal symptoms and support well-being, but there is limited evidence on the link between PA and menopausal symptoms in the United Kingdom, and no study has assessed how PA affects well-being through menopausal symptoms and three psychosomatic factors (i.e. depression, anxiety and stress)., Objectives: This study investigated whether PA affects well-being through menopausal symptoms and psychosomatic factors. This study focuses on how PA influences working women with menopause., Design: A cross-sectional design based on the STROBE (i.e. Strengthening the Reporting of Observational Studies in Epidemiology) checklist was adopted., Methods: The participants were 324 working women in England. An online self-reported questionnaire was utilised to gather data through Qualtrics. The data were analysed with path analysis through structural equation modelling, and sensitivity analyses were performed to avoid or reduce statistical bias., Results: PA had a negative effect on menopausal symptoms (β = -0.21; p  < 0.001) but a positive effect on well-being (β = 0.19; p  < 0.001). Menopausal symptoms had a negative indirect effect on well-being, but PA had a positive indirect effect on well-being through menopausal symptoms and the three psychosomatic factors., Conclusion: PA was positively associated with well-being but negatively associated with menopausal symptoms. Menopausal symptoms may lower well-being through anxiety, depression and stress, but PA can be associated with better well-being through depression, anxiety and stress.

Introduction: Congenital syphilis cases in the United States increased 755% during 2012-2021. Syphilis during pregnancy can lead to stillbirth, miscarriage, infant death, and maternal and infant morbidity; these outcomes can be prevented through appropriate screening and treatment., Methods: A cascading framework was used to identify and classify missed opportunities to prevent congenital syphilis among cases reported to CDC in 2022 through the National Notifiable Diseases Surveillance System. Data on testing and treatment during pregnancy and clinical manifestations present in the newborn were used to identify missed opportunities to prevent congenital syphilis., Results: In 2022, a total of 3,761 cases of congenital syphilis in the United States were reported to CDC, including 231 (6%) stillbirths and 51 (1%) infant deaths. Lack of timely testing and adequate treatment during pregnancy contributed to 88% of cases of congenital syphilis. Testing and treatment gaps were present in the majority of cases across all races, ethnicities, and U.S. Census Bureau regions., Conclusions and Implications for Public Health Practice: Addressing missed opportunities for prevention, primarily timely testing and appropriate treatment of syphilis during pregnancy, is important for reversing congenital syphilis trends in the United States. Implementing tailored strategies addressing missed opportunities at the local and national levels could substantially reduce congenital syphilis., Competing Interests: All authors have completed and submitted the International Committee of Medical Journal Editors form for disclosure of potential conflicts of interest. No potential conflicts of interest were disclosed.

Introduction: The reemergence of syphilis, especially congenital syphilis, presents a significant public health threat. Accurate diagnosis of syphilis depends on recognition of a constellation of symptoms, review of medical and sexual history, and multiple laboratory tests. While reliable, current tests for syphilis can be difficult to interpret, which can lead to delays in treatment., Area Covered: This review summarizes the major advantages and limitations of available diagnostic laboratory methods for syphilis, provides an update on recent advances in laboratory tools, and highlights the urgent need for coordinated efforts to create new tools to halt the resurgence of syphilis., Expert Opinion: In syphilis, the wide variety of short-lived signs and symptoms followed by periods of latency create diagnostic challenges. Currently available laboratory tests, when positive, require additional information to interpret (prior testing, treatment, and sexual history). Point-of-care tests that can rapidly and accurately detect both treponemal and non-treponemal antibodies would be a huge step toward reducing test turnaround time and time to treatment. Incorporating biological insights and technology innovations to advance the development of direct detection assays is urgently needed. A comprehensive coordinated effort is critical to stem the tide of rising syphilis in the United States and globally.

Early in the coronavirus disease 2019 (COVID-19) pandemic, the CDC recommended collection of a lower respiratory tract (LRT) specimen for severe acute respiratory coronavirus virus 2 (SARS-CoV-2) testing in addition to the routinely recommended upper respiratory tract (URT) testing in mechanically ventilated patients. Significant operational challenges were noted at our institution using this approach. In this report, we describe our experience with routine collection of paired URT and LRT sample testing. Our results revealed a high concordance between the 2 sources, and that all children tested for SARS-CoV-2 were appropriately diagnosed with URT testing alone. There was no added benefit to LRT testing. Based on these findings, our institutional approach was therefore adjusted to sample the URT alone for most patients, with LRT sampling reserved for patients with ongoing clinical suspicion for SARS-CoV-2 after a negative URT test.

Background: COVID-19 is known to cause an acute respiratory illness, although clinical manifestations outside of the respiratory tract may occur. Early reports have identified SARS-CoV-2 as a cause of subacute thyroiditis (SAT)., Methods: A systematic review was conducted in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. MEDLINE, Web of Science and PubMed databases were queried in February 2021 for studies from December 2019 to February 2021. MeSH search terms 'COVID-19', 'SARS-CoV-2' and 'coronavirus' along with search terms 'thyroiditis', 'thyrotoxicosis' and 'thyroid' were used. Descriptive statistics for continuous variables and proportions for categorical variables were calculated., Results: Fifteen publications reporting on 17 individual cases of COVID-19-induced SAT were identified. Age ranged from 18 to 69 years. The majority (14 of 17; 82%) of cases were female. The delay between onset of respiratory symptoms and diagnosis of SAT ranged from 5 to 49 days (mean, 26.5). Systemic inflammatory response syndrome related to viral infection was uncommonly reported at the time of SAT diagnosis. Thyroid ultrasonography frequently reported an enlarged hypoechoic thyroid with decreased vascularity and heterogenous echotexture. Elevated C-reactive protein (CRP) was common at the time of SAT diagnosis, with results ranging from 4.5 to 176 mg/L (mean, 41 mg/L). Antithyroid antibodies were frequently negative. SAT-specific treatment included corticosteroids for 12 of 17 (70.5%) patients. Most returned to normal thyroid status., Conclusion: COVID-19-associated SAT may be difficult to identify in a timely manner due to potential absence of classic symptoms, as well as cross-over of common clinical features between COVID-19 and thyrotoxicosis., (© 2021 Royal Australasian College of Physicians.)

Vancomycin and piperacillin-tazobactam are commonly used antibiotics. There is increasing evidence to indicate that these therapies in combination predispose patients to acute kidney injury (AKI). However, studies of intensive care unit (ICU) patients with these antibiotics have produced conflicting results. In this single-centre, retrospective cohort study, data was collected on ICU patients prescribed combination vancomycin and piperacillin-tazobactam (VPT) for at least 48 h, compared with patients prescribed vancomycin with either cefepime or meropenem (VMC) for the same time period. Primary outcome was incidence of AKI; secondary outcomes included a desirability of outcome ranking (DOOR) scale, and association between antibiotic duration and kidney injury. A total of 260 patients were included. AKI was observed in 27% of cases overall. Incidence of AKI was higher with VPT compared with VMC on bivariate (relative risk reduction [RRR] 1.9, 95% confidence interval [CI] 0.9-4.1, P = 0.08) and multivariate (RRR 2.2, 95% CI 1.0-4.9, P = 0.05) analyses. Longer duration of antibiotic therapy was associated with increased rates of AKI independent of which antibiotics were prescribed: RRR 4.9, 95% CI 2.1-11.1, P = <0.001 for 5-6 days compared with <5 days, and RRR 2.3, 95% CI 1.0-5.5, P = 0.05 for >7 days compared with <5 days. This study demonstrated an association between increased risk of nephrotoxicity and combination VPT therapy in ICU patients. The concept remains controversial, with recent suggestions that VPT does not truly cause nephrotoxicity. Given our findings and the weight of previous studies, there is a strong mandate to undertake prospective trials to resolve the issue., (Copyright © 2020 Elsevier Ltd. All rights reserved.)

The role that tobacco consumption plays in the etiology of oral cancer carcinogenesis, and of alcohol consumption acting as a co-factor, have been well established. However, in recent years, the contribution of alcohol consumption alone to oral cancer has been proposed. In fact, a high percentage of patients who develop oral cancer have both habits (tobacco and alcohol consumption), and other small patient groups only consume alcohol or do not have any other identifiable bad habits. In the present study we demonstrate, using a combination of dynamic molecular modelling and Raman spectroscopy, that ethanol has a significant effect on oral cells in vitro, mainly interacting with the lipids of the cell membrane, changing their conformation. Thus, it is possible to conclude that ethanol can affect the cell permeability, and by consequence serve as a possible trigger in oral carcinogenesis., Competing Interests: Declaration of Competing Interest None declared., (Copyright © 2020 Elsevier B.V. All rights reserved.)

Background: Influenza-like illness is often caused by respiratory viral infections, and is a frequent cause of presentation to hospital. Rapid diagnostics for respiratory viruses, with turnaround times of less than sixty minutes, are increasingly available. Early physician knowledge of positive respiratory virus tests has previously been shown to impact patient care in a paediatric population but hasn't been evaluated in adults., Methods: Rapid testing for the respiratory viruses Influenza A, Influenza B and respiratory syncytial virus (RSV) was introduced in our institution in 2018. This reduced turnaround time for tests from more than 24 h, to 1-10 h depending on time of day. A retrospective cohort study was performed on patients presenting with influenza-like illness, in whom a nasopharyngeal swab for respiratory viruses was requested. Data was collected before and after the introduction of the rapid assay. Outcomes included antibiotic use (less or more than 24 h) and length of hospital stay (less or more than 24 h)., Results: In all patients who tested positive for a respiratory virus, there was an association between rapid testing and less antibiotic use. This was largely driven by paediatric cases; there was no change in prescribing for adult patients. There was no impact on timing of patient discharge., Conclusions: Rapid testing for respiratory viruses has a potentially useful role in antimicrobial stewardship. It is unclear why earlier knowledge of positive viral test didn't lead to less antibiotics in adults. This study showed no impact of rapid testing on time to patient discharge., (Copyright © 2019 Australasian College for Infection Prevention and Control. All rights reserved.)

People who inject drugs (PWID) are susceptible to endovascular and deep-seated infections which require prolonged antibiotic therapy. There are concerns regarding this cohort's suitability for outpatient parenteral antimicrobial therapy (OPAT), but relatively little published data. Our aim is to publish our outcomes in this setting, to inform other clinicians' decisions regarding PWID in OPAT. We reviewed case records of all PWID in our OPAT service from July 2015 to December 2017. Successful completion of OPAT care was defined as completing the duration of parenteral therapy as planned at the outset, with expected clinical improvement. Data was collected on complications including hospital re-admission, new blood stream infections, patient non-compliance including ongoing non-prescribed intravenous drug use, and staff safety compromise. Twenty-eight of 38 (76.2%) episodes of OPAT care for PWID were completed successfully, with 724 bed days of care provided. The cohort was labour intensive to manage with high rates of re-admission, non-attendance and line-associated infections. There were no adverse events for staff safety, and no patient deaths on the programme. OPAT can be a viable option for PWID provided there is careful patient selection, good patient engagement and sufficient resources allocated for patient management.

Naturally acquired immunity to malaria is robust and protective against all strains of the same species of Plasmodium This develops as a result of repeated natural infection, taking several years to develop. Evidence suggests that apoptosis of immune lymphocytes due to uncontrolled parasite growth contributes to the slow acquisition of immunity. To hasten and augment the development of natural immunity, we studied controlled infection immunization (CII) using low-dose exposure to different parasite species ( Plasmodium chabaudi , P. yoelii , or P. falciparum ) in two rodent systems (BALB/c and C57BL/6 mice) and in human volunteers, with drug therapy commencing at the time of initiation of infection. CIIs with infected erythrocytes and in conjunction with doxycycline or azithromycin, which are delayed death drugs targeting the parasite's apicoplast, allowed extended exposure to parasites at low levels. In turn, this induced strong protection against homologous challenge in all immunized mice. We show that P. chabaudi / P. yoelii infection initiated at the commencement of doxycycline therapy leads to cellular or antibody-mediated protective immune responses in mice, with a broad Th1 cytokine response providing the best correlate of protection against homologous and heterologous species of Plasmodium P. falciparum CII with doxycycline was additionally tested in a pilot clinical study ( n = 4) and was found to be well tolerated and immunogenic, with immunological studies primarily detecting increased cell-associated immune responses. Furthermore, we report that a single dose of the longer-acting drug, azithromycin, given to mice ( n = 5) as a single subcutaneous treatment at the initiation of infection controlled P. yoelii infection and protected all mice against subsequent challenge., (Copyright © 2018 Low et al.)

Plastic litter is encountered in aquatic ecosystems across the globe, including polar environments and the deep sea. To mitigate the adverse societal and ecological impacts of this waste, there has been debate on whether 'biodegradable' materials should be granted exemptions from plastic bag bans and levies. However, great care must be exercised when attempting to define this term, due to the broad and complex range of physical and chemical conditions encountered within natural ecosystems. Here, we review existing international industry standards and regional test methods for evaluating the biodegradability of plastics within aquatic environments (wastewater, unmanaged freshwater and marine habitats). We argue that current standards and test methods are insufficient in their ability to realistically predict the biodegradability of carrier bags in these environments, due to several shortcomings in experimental procedures and a paucity of information in the scientific literature. Moreover, existing biodegradability standards and test methods for aquatic environments do not involve toxicity testing or account for the potentially adverse ecological impacts of carrier bags, plastic additives, polymer degradation products or small (microscopic) plastic particles that can arise via fragmentation. Successfully addressing these knowledge gaps is a key requirement for developing new biodegradability standard(s) for lightweight carrier bags., Competing Interests: We declare we have no competing interests.

Transcatheter aortic valve replacement (TAVR) is a safe and effective therapy for aortic valve replacement in patients ineligible for or at high risk for surgery. However, outcomes after TAVR based on an individual's sex remain to be fully elucidated. We searched PUBMED and EMBASE using the keywords: "transcatheter aortic valve replacement," "transcatheter aortic valve implantation," "sex differences," "gender," "sex characteristics" and collected information on baseline features, procedural characteristics, and postprocedural outcomes in women. Inclusion/exclusion resulted in 23 publications. Women had less preexisting comorbidities than men. Most studies reported better survival in women (range of hazard ratio [95% CI] = 0.27 [0.09-0.84] to 0.91 [0.75-1.10]). At 30 days, women also had more vascular complications (6-20% vs 2-14%) and higher bleeding rates (10-44% vs 8-25%). Stroke rates were similar at 30 days (women, 1-7%; men, 1-5%). This literature review showed better survival in women than men after TAVR. However, women had more vascular complications and bleeding; stroke rates were similar. These findings may partly be explained by fewer baseline comorbidities in women. These results should be interpreted with caution as most measures only include unadjusted percentages.