Staphylococcus aureus bacteremia is associated with substantial morbidity. Recurrence is common, but incidence and risk factors for recurrence are uncertain. The emergence of methicillin resistance and the ease of administering vancomycin, especially in patients who have renal insufficiency, have led to reliance on this drug with the assumption that it is as effective as beta-lactam antibiotics, an assumption that remains open to debate. We initiated a multicenter, prospective observational study in 6 university hospitals and enrolled 505 consecutive patients with S. aureus bacteremia. All patients were monitored for 6 months and patients with endocarditis were followed for 3 years. Recurrence was defined as return of S. aureus bacteremia after documentation of negative blood cultures and/or clinical improvement after completing a course of antistaphylococcal antibiotic therapy. All blood isolates taken from patients with recurrent bacteremia underwent pulsed-field gel electrophoresis testing. Recurrence was subclassified as reinfection (different pulsed-field gel electrophoresis patterns) or relapse (same pulsed-field gel electrophoresis pattern).Forty-two patients experienced 56 episodes of recurrence (79% were relapses and 21% were reinfection). Relapse occurred earlier than reinfection (median, 36 versus 99 d, p < 0.06). Risk factors for relapse of S. aureus bacteremia included valvular heart disease, cirrhosis of the liver, and deep-seated infection (including endocarditis). Nafcillin was superior to vancomycin in preventing bacteriologic failure (persistent bacteremia or relapse) for methicillin-susceptible S. aureus (MSSA) bacteremia. Failure to remove infected intravascular devices/catheters and vancomycin therapy were common factors in patients experiencing multiple (greater than 2) relapses. However, by multivariate analysis, only endocarditis and therapy with vancomycin (versus nafcillin) were significantly associated with relapse. Recurrences occurred in 9.4% of S. aureus bacteremias following antistaphylococcal therapy, and most were relapses. Duration of antistaphylococcal therapy was not associated with relapse, but type of antibiotic therapy was. Nafcillin was superior to vancomycin in efficacy in patients with MSSA bacteremia.

Our objectives were to determine the incidence of endocarditis in patients whose Staphylococcus aureus bacteremia was community-acquired, related to hemodialysis, or hospital-acquired; to assess clinical factors that would reliably distinguished between S. aureus bacteremia and S. aureus endocarditis; to assess the emergence of methicillin-resistant S. aureus (MRSA) as a cause of endocarditis; and to examine risk factors for mortality in patients with S. aureus endocarditis. We conducted a prospective observational study in 6 university teaching hospitals; we evaluated 505 consecutive patients with Staphylococcus aureus bacteremia. Thirteen percent of patients with S. aureus bacteremia were found to have endocarditis, including 21% with community-acquired S. aureus bacteremia, 5% with hospital-acquired bacteremia, and 12% on hemodialysis. Infection was due to MRSA in 31%. Factors predictive of endocarditis included underlying valvular heart disease, history of prior endocarditis, intravenous drug use, community acquisition of bacteremia, and an unrecognized source. Twelve patients with bacteremia had a prosthetic valve; 17% developed endocarditis. Unexpectedly, nonwhite race proved to be an independent risk factor for endocarditis by both univariate and multivariate analyses. Persistent bacteremia (positive blood cultures at day 3 of appropriate therapy) was identified as an independent risk factor for both endocarditis and mortality, a unique observation not reported in other prospective studies of S. aureus bacteremia. Patients with endocarditis due to MRSA were significantly more likely to have complicating renal insufficiency and to experience persistent bacteremia than those with endocarditis due to MSSA. The 30-day mortality was 31% among patients with endocarditis compared to 21% in patients who had bacteremia without endocarditis (p = 0.055). Risk factors for death due to endocarditis included severity of illness at onset of bacteremia (as measured by Apache III and Pitt bacteremia score), MRSA infection, and presence of atrioventricular block on electrocardiogram. Patients with S. aureus bacteremia who have community acquisition of infection, underlying valvular heart disease, intravenous drug use, unknown portal of entry, history of prior endocarditis, and possibly, nonwhite race should undergo echocardiography to screen for the presence of endocarditis. We recommend that blood cultures be repeated 3 days following initiation of antistaphylococcal antibiotic therapy in all patients with S. aureus bacteremia. Positive blood cultures at 3 days may prove to be a useful marker in promoting more aggressive management, including more potent antibiotic therapy and surgical resection of the valve in endocarditis cases. MRSA as the infecting organism should be added to the list of risk factors for consideration of valvular resection in cases of endocarditis.

The recent development of nucleoside analogues with antiviral activity has expanded the small but useful armamentarium for the treatment of certain viral diseases such as the human immunodeficiency virus, cytomegalovirus and others. Their intracellular site of action and need for sequential phosphorylation require that traditional pharmacokinetic parameters be used in conjunction with an understanding of intracellular metabolism when designing dosage regimens. This review summarises the available pharmacokinetic literature for zidovudine, didanosine, zalcitabine, aciclovir, ganciclovir, vidarabine and ribavirin. After oral administration, didanosine, aciclovir and ribavirin are < 50% bioavailable and ganciclovir is < 6% absorbed. In contrast, zidovudine and zalcitabine are > 60% bioavailable, although zidovudine undergoes considerable and variable first-pass hepatic glucuronidation while zalcitabine has no first-pass effect. Zidovudine, zalcitabine and didanosine are absorbed rapidly in the fasted state, with peak plasma concentrations exceeding their respective in vitro antiretroviral inhibitory concentrations. All reviewed agents except ribavirin have a relatively short plasma half-life (approximately 0.5 to 4h), with each agent demonstrating a different intracellular enzymatic activation scheme. For example, the rate-limiting step for formation of zidovudine triphosphate is the conversion of the monophosphate to the diphosphate, while didanosine is ultimately converted to dideoxyadenosine triphosphate which has the longest intracellular half-life (approximately 12 to 24h) among these agents. These drugs are not highly protein bound and they distribute into tissues with an apparent volume of distribution at steady-state ranging from 0.3 to 1.2 L/kg. They vary in the extent to which they enter cerebrospinal fluid, ranging from a low of < 25% for didanosine to a high of > 70% of a concurrent plasma concentration for ribavirin and vidarabine. These agents also vary with regard to degree of renal excretion of the parent drug, with the lowest noted for vidarabine (1 to 3%) and the highest for zalcitabine (approximately 75%) and ganciclovir (> 90%). With the increasing number of clinically useful nucleoside analogues, it is essential for the clinician to appreciate the subtle differences among these agents to ensure that optimal therapeutic outcomes may be attained with minimal toxicity.

Although the majority of patients recover consciousness after a traumatic brain injury (TBI), a minority develop a prolonged disorder of consciousness, which may never fully resolve. For these patients, accurate prognostication is essential to treatment decisions and long-term care planning. In this review, we evaluate the use of resting-state electroencephalography (EEG) as a prognostic measure in disorders of consciousness following TBI. We highlight that routine clinical EEG recordings have prognostic utility in the short to medium term. In particular, measures of alpha power and variability are indicative of relatively better functional outcomes within the first year post-TBI. This is hypothesized to reflect intact thalamocortical loops, and thus the potential for recovery of consciousness even in the apparent absence of current consciousness. However, there is a lack of research into the use of resting-state EEG for predicting longer-term recovery following TBI. We conclude that, given the potential for patients to demonstrate improvements in consciousness and functional capacity even years after TBI, a research focus on EEG-augmented prognostication in very long-term disorders of consciousness is now required.

Background: The endonasal transsphenoidal approach (TSA) has emerged as the preferred approach in order to treat pituitary adenoma and related sellar pathologies. The recently adopted expanded endonasal approach (EEA) has improved access to the ventral skull base whilst retaining the principles of minimally invasive surgery. Despite the advantages these approaches offer, cerebrospinal fluid (CSF) rhinorrhoea remains a common complication. There is currently a lack of comparative evidence to guide the best choice of skull base reconstruction, resulting in considerable heterogeneity of current practice. This study aims to determine: (1) the scope of the methods of skull base repair; and (2) the corresponding rates of postoperative CSF rhinorrhoea in contemporary neurosurgical practice in the UK and Ireland. Methods: We will adopt a multicentre, prospective, observational cohort design. All neurosurgical units in the UK and Ireland performing the relevant surgeries (TSA and EEA) will be eligible to participate. Eligible cases will be prospectively recruited over 6 months with 6 months of postoperative follow-up. Data points collected will include: demographics, tumour characteristics, operative data), and postoperative outcomes. Primary outcomes include skull base repair technique and CSF rhinorrhoea (biochemically confirmed and/ or requiring intervention) rates. Pooled data will be analysed using descriptive statistics. All skull base repair methods used and CSF leak rates for TSA and EEA will be compared against rates listed in the literature. Ethics and dissemination: Formal institutional ethical board review was not required owing to the nature of the studythis was confirmed with the Health Research Authority, UK. Conclusions: The need for this multicentre, prospective, observational study is highlighted by the relative paucity of literature and the resultant lack of consensus on the topic. It is hoped that the results will give insight into contemporary practice in the UK and Ireland and will inform future studies.

Didanosine has demonstrated preliminary efficacy in the treatment of late-stage HIV infection; however, its effect on patient survival, its efficacy relative to ZDV, and its utility in combination with other agents are still under evaluation.

Accurate early prognostication is vital for appropriate long-term care decisions after traumatic brain injury. While measures of resting-state EEG oscillations and their network properties, derived from graph theory, have been shown to provide clinically useful information regarding diagnosis and recovery in patients with chronic disorders of consciousness, little is known about the value of these network measures when calculated from a standard clinical low-density EEG in the acute phase post-injury. To investigate this link, we first validated a set of measures of oscillatory network features between high-density and low-density resting state EEG in healthy individuals, thus ensuring accurate estimation of underlying cortical function in clinical recordings from patients. Next, we investigated the relationship between these features and the clinical picture and outcome of a group of 18-patients in acute post-traumatic unresponsive states who were not following commands 2-days+ after sedation hold. While the complexity of the alpha network, as indexed by the standard deviation of the participation coefficients, was significantly related to the patients’ clinical picture at the time of EEG, no network features were significantly related to outcome at 3- or 6-months post-injury. Rather, mean relative alpha power across all electrodes improved the accuracy of outcome prediction at 3-months relative to clinical features alone. These results highlight the link between the alpha rhythm and clinical signs of consciousness and suggest the potential for simple measures of resting-state EEG band-power to provide a coarse snapshot of brain health for stratification of patients for rehabilitation, therapy, and assessments of both covert and overt cognition.

Background During the coronavirus disease 2019 (COVID-19) pandemic, concerns have been raised regarding the increased risk of perioperative mortality for patients with COVID-19, and the transmission risk to healthcare workers, especially during endonasal neurosurgical operations. The Pituitary Society has produced recommendations to guide management during this era. We sought to assess contemporary neurosurgical practice and the effects of COVID-19. Methods A multicenter prospective observational cohort study was conducted at 12 tertiary neurosurgical units (United Kingdom and Ireland). Data were collected from March 23 to July 31, 2020, inclusive. The data points collected included patient demographics, preoperative COVID-19 test results, operative modifications, and 30-day COVID-19 infection rates. Results A total of 124 patients were included. Of the 124 patients, 116 (94%) had undergone COVID-19 testing preoperatively (transsphenoidal approach, 97 of 105 [92%]; expanded endoscopic endonasal approach, 19 of 19 [100%]). One patient (1 of 116 [0.9%]) had tested positive for COVID-19 preoperatively, requiring a delay in surgery until the infection had been confirmed as resolved. Other than transient diabetes insipidus, no other complications were reported for this patient. All operating room staff had worn at least level 2 personal protective equipment. Adaptations to surgical techniques included minimizing drilling, draping modifications, and the use of a nasal iodine wash. At 30 days postoperatively, no evidence of COVID-19 infection (symptoms or positive formal testing results) were found in our cohort and no mortality had occurred. Conclusions Preoperative screening protocols and operative modifications have facilitated endonasal neurosurgery during the COVID-19 pandemic, with the Pituitary Society guidelines followed for most of these operations. We found no evidence of COVID-19 infection in our cohort and no mortality, supporting the use of risk mitigation strategies to continue endonasal neurosurgery in subsequent pandemic waves.