Resistance and the management of complicated skin and skin structure infections: the role of ceftobiprole

Antimicrobial resistant bacteria are an increasing concern due to the resulting increase in morbidity, mortality, and health-care costs associated with the administration of inadequate or delayed antimicrobial therapy. The implications of inadequate antimicrobial therapy in complicated skin and skin structure infections (cSSSIs) have gained more attention recently, most likely due to the recent emergence of community-acquired methicillin resistant Staphylococcus aureus (MRSA) and the already high prevalence of MRSA in the nosocomial setting. Due to the continuous threat of resistance arising and the limitations of currently available agents for the treatment of cSSSIs, it is necessary to develop new antimicrobials for this indication. Ceftobiprole medocaril, the prodrug of ceftobiprole, is a parental investigational cephalosporin for the treatment of cSSSIs displaying a wide-spectrum of activity against both Gram-positive and Gram-negative species, including MRSA. Ceftobiprole displays noncomplex linear pharmacokinetics, is eliminated primarily by glomerular filtration, and distributes to extracellular fluid. Additionally, it has been shown that the extent of distribution to the site of action with regard to cSSSIs, ie, the extracellular space fluid of subcutaneous adipose tissue and skeletal muscle, is expected to be efficacious, as free concentrations meet efficacy targets for most pathogens. Similar to other beta-lactams, it displays an excellent safety and tolerability profile with the primary adverse events being dysgeusia in healthy volunteers, resulting from the conversion of the prodrug to the active, and nausea in patients. Ceftobiprole has demonstrated noninferiority in two large-scale pivotal studies comparing it to vancomycin, clinical cure rates 93.3% vs 93.5%, respectively, or vancomycin plus ceftazidime, clinical cure rates 90.5% vs 90.2%, respectively. Given the pharmacokinetic and pharmacodynamic properties, ceftobiprole is a promising new agent for the treatment of cSSSIs and has the potential to be used as a single agent for empiric treatment

Retaining interest in caring for underserved patients among future medicine subspecialists: Underserved Medicine and Public Health (UMPH) program.

BACKGROUND: Accessing subspecialty care is hard for underserved patients in the U.S. Published curricula in underserved medicine for Internal Medicine residents target future-primary care physicians, with unknown impact on future medicine subspecialists. METHODS: The aim was to retain interest in caring for underserved patients among Internal Medicine residents who plan for subspecialist careers at an urban university hospital. The two-year Underserved Medicine and Public Health (UMPH) program features community-based clinics, evening seminars, reflection assignments and practicum projects for 3–7 Internal Medicine residents per year. All may apply regardless of anticipated career plans after residency. Seven years of graduates were surveyed. Data were analyzed using descriptive statistics. RESULTS: According to respondents, UMPH provided a meaningful forum to discuss important issues in underserved medicine, fostered interest in treating underserved populations and provided a sense of belonging to a community of providers committed to underserved medicine. After residency, 48% of UMPH graduates pursued subspecialty training and 34% practiced hospitalist medicine. 65% of respondents disagreed that “UMPH made me more likely to practice primary care” and 59% agreed “UMPH should target residents pursuing subpecialty careers.” CONCLUSIONS: A curriculum in underserved medicine can retain interest in caring for underserved patients among future-medicine subspecialists. Lessons learned include [1] building relationships with local community health centers and community-practicing physicians was important for success and [2] thoughtful scheduling promoted high resident attendance at program events and avoided detracting from other activities required during residency for subspecialist career paths. We hope Internal Medicine residency programs consider training in underserved medicine for all trainees. Future work should investigate sustainability, whether training results in improved subspecialty access, and whether subspecialists face unique barriers caring for underserved patients. Future curricula should include advocacy skills to target systemic barriers

Exon-Level Transcriptome Profiling in Murine Breast Cancer Reveals Splicing Changes Specific to Tumors with Different Metastatic Abilities

In breast cancer patients, tumor metastases at distant sites are the main cause of death. However, the molecular mechanisms of metastasis of breast cancer remain unclear. It is thought that changes occurring at the level of RNA processing contribute to cancer. Alternative splicing (AS) of pre-mRNA, a key post-transcriptional mechanism allowing for the production of distinct proteins from a single gene, affects over 90% of human genes. Such splicing events are responsible for generating mRNAs that encode protein isoforms that can have very different biological properties and functions. A well-studied example is the BCL-X gene, whose two major transcript isoforms produce two proteins having antagonistic functions: the short form (BCL-XS) promotes apoptosis while the long form (BCL-XL) is anti-apoptotic. Moreover, overexpression of BCL-XL has been reported to enhance the metastatic potential of breast tumor cells in patients

Effective monitoring of freshwater fish

Freshwater ecosystems constitute only a small fraction of the planet’s water resources, yet support much of its diversity, with freshwater fish accounting for more species than birds, mammals, amphibians, or reptiles. Fresh waters are, however, particularly vulnerable to anthropogenic impacts, including habitat loss, climate and land use change, nutrient enrichment, and biological invasions. This environmental degradation, combined with unprecedented rates of biodiversity change, highlights the importance of robust and replicable programmes to monitor freshwater fish assemblages. Such monitoring programmes can have diverse aims, including confirming the presence of a single species (e.g. early detection of alien species), tracking changes in the abundance of threatened species, or documenting long-term temporal changes in entire communities. Irrespective of their motivation, monitoring programmes are only fit for purpose if they have clearly articulated aims and collect data that can meet those aims. This review, therefore, highlights the importance of identifying the key aims in monitoring programmes, and outlines the different methods of sampling freshwater fish that can be used to meet these aims. We emphasise that investigators must address issues around sampling design, statistical power, species’ detectability, taxonomy, and ethics in their monitoring programmes. Additionally, programmes must ensure that high-quality monitoring data are properly curated and deposited in repositories that will endure. Through fostering improved practice in freshwater fish monitoring, this review aims to help programmes improve understanding of the processes that shape the Earth's freshwater ecosystems, and help protect these systems in face of rapid environmental change

Convalescent plasma in patients admitted to hospital with COVID-19 (RECOVERY): a randomised controlled, open-label, platform trial

SummaryBackground Azithromycin has been proposed as a treatment for COVID-19 on the basis of its immunomodulatoryactions. We aimed to evaluate the safety and efficacy of azithromycin in patients admitted to hospital with COVID-19.Methods In this randomised, controlled, open-label, adaptive platform trial (Randomised Evaluation of COVID-19Therapy [RECOVERY]), several possible treatments were compared with usual care in patients admitted to hospitalwith COVID-19 in the UK. The trial is underway at 176 hospitals in the UK. Eligible and consenting patients wererandomly allocated to either usual standard of care alone or usual standard of care plus azithromycin 500 mg once perday by mouth or intravenously for 10 days or until discharge (or allocation to one of the other RECOVERY treatmentgroups). Patients were assigned via web-based simple (unstratified) randomisation with allocation concealment andwere twice as likely to be randomly assigned to usual care than to any of the active treatment groups. Participants andlocal study staff were not masked to the allocated treatment, but all others involved in the trial were masked to theoutcome data during the trial. The primary outcome was 28-day all-cause mortality, assessed in the intention-to-treatpopulation. The trial is registered with ISRCTN, 50189673, and ClinicalTrials.gov, NCT04381936.Findings Between April 7 and Nov 27, 2020, of 16 442 patients enrolled in the RECOVERY trial, 9433 (57%) wereeligible and 7763 were included in the assessment of azithromycin. The mean age of these study participants was65·3 years (SD 15·7) and approximately a third were women (2944 [38%] of 7763). 2582 patients were randomlyallocated to receive azithromycin and 5181 patients were randomly allocated to usual care alone. Overall,561 (22%) patients allocated to azithromycin and 1162 (22%) patients allocated to usual care died within 28 days(rate ratio 0·97, 95% CI 0·87–1·07; p=0·50). No significant difference was seen in duration of hospital stay (median10 days [IQR 5 to >28] vs 11 days [5 to >28]) or the proportion of patients discharged from hospital alive within 28 days(rate ratio 1·04, 95% CI 0·98–1·10; p=0·19). Among those not on invasive mechanical ventilation at baseline, nosignificant difference was seen in the proportion meeting the composite endpoint of invasive mechanical ventilationor death (risk ratio 0·95, 95% CI 0·87–1·03; p=0·24).Interpretation In patients admitted to hospital with COVID-19, azithromycin did not improve survival or otherprespecified clinical outcomes. Azithromycin use in patients admitted to hospital with COVID-19 should be restrictedto patients in whom there is a clear antimicrobial indication

Diabetes Flowsheet Quality Improvement Project

Outpatient management of diabetes involves targeted interventions and investigations aimed at improving diabetes-related complications. In the fast-paced environment of the modern primary care clinic, providers often fall short of meeting the numerous requirements of comprehensive diabetes care. To that end, we have developed a diabetes “flowsheet” for incorporation into the electronic medical record. This flowsheet is comprised of key clinical investigations (e.g. proteinuria) and outcomes (e.g. HbA1C) and may help primary care providers meet diabetes management goals and ultimately improve outcomes. Our goal was to introduce the flowsheet to medical residents and achieve a usership rate of 50% (i.e. 50% of residents would use the flowsheet in their diabetic patients\u27 progress notes). However, our first several PDSA cycles instead focused on addressing two major challenges: creating a flowsheet that balances usability with ease-of-use, and overcoming technical obstacles to incorporation of the flowsheet into a medical note. Moving forward, we will focus our efforts on promoting use of the flowsheet and ultimately evaluate its impact on quality measures and clinical outcomes

Improving Lung Cancer Screening in Primary Care

The most common cause of mortality from malignancy is lung cancer. Unfortunately the overwhelming majority of lung cancers is detected in advanced stages, which is likely the driving factor for poor survival rates. There is evidence that early detection of lung cancer by screening high risk patients with annual low-dose CT scans can improve the survival rate by 20%. However, low dose CTs are not ordered by primary care physicians as routinely as other screening tests such as mammography. In the resident clinic at the Medical Faculty Associates at George Washington University Hospital, only 4.3% of physicians documented whether or not a patient met criteria for lung cancer screening. Documentation remained low despite both residents receiving information on lung cancer screening as well as forms distributed in clinic highlighting those meeting screening criteria. The initial thought was residents were not coached by attending physicians to screen for lung cancer in comparison to other screening tests during health maintenance exams. Preliminary surveys in January 2017 with attending physicians in primary care clinic indicated reasons for low screening rate may include lack of knowledge of guidelines, lack of habitual practice of new guidelines, obtaining insufficient smoking history to assess risk, overlooking high risk of former smokers, and concerns about insurance coverage. No physicians surveyed stated disagreement with lung cancer screening guidelines. Therefore, the major barrier to appropriate documentation may be increasing knowledge and emphasizing importance of lung cancer screening in primary care clinic. Our aim is to increase the rate of evidence-based documentation of candidacy for lung cancer screening by twofold over a six month period among Internal Medicine residents in the outpatient setting during the annual physical. Future strategies to reach this goal include education on appropriate screening steps and documentation, including lung cancer screening into health maintenance exam note macros, and reinforcement of guidelines by attending physicians