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Choice of antibiotic should be dictated by spectrum of activity, tissue penetration, potency and cost, and local patterns of infection. While advising prescribers to check with their local microbiologist or use their smartphone formulary app, the author describes the most common infectious disease presentations, and the first- and second-line antibiotic therapy based on national guidelines.
OBJECTIVES/GOALS: African-Americans have a 3-fold higher risk of end-stage kidney disease (ESKD) compared to Whites due in part to APOL1 risk alleles. Whether resistant hypertension (RH) magnifies the risk of ESKD among African Americans beyond APOL1 is not known. We examined the interaction between RH and race on ESKD risk and the independent effect of RH beyond APOL1. METHODS/STUDY POPULATION: We designed a retrospective cohort of 240,038 veterans with HTN, enrolled in the Million Veteran Program with an estimated glomerular filtration rate (eGFR) >30 ml/min/1.73m2. The primary exposure was incident RH (time-varying). The primary outcome was incident ESKD during a 13.5 year follow up: 2004-2017. Secondary outcomes were myocardial infarction (MI), stroke, and death. Incident RH was defined as failure to achieve outpatient blood pressure (BP) <140/90 mmHg with 3 antihypertensive drugs, including a thiazide, or use of 4 or more drugs. Poisson models were used to estimate incidence rates and test additive interaction with race and APOL1 genotype. Multivariable Cox models (with Fine-Gray competing-risks models as sensitivity analyses) were used to examine independent effects. RESULTS/ANTICIPATED RESULTS: The cohort comprised 235,046 veterans; median age was 60 years; 21% were African-American and 6% were women, with 23,010 incident RH cases observed over a median follow-up time of 10.2 years [interquartile range, 5.6-12.6]. Patients with RH had higher incidence rates [per 1000 person-years] of ESKD (4.5 vs. 1.3), myocardial infarction (6.5 vs. 3.0), stroke (16.4 vs. 7.6) and death (12.0 vs. 6.9) than non-resistant hypertension (NRH). African-Americans with RH had a 2.6-fold higher risk of ESKD compared to African-Americans with NRH; 3-fold the risk of Whites with RH, and 9.6-fold the risk of Whites with NRH [p-interaction<.001]. Among African-Americans, RH was associated with a 2.2-fold (95%CI, 1.86-2.58) higher risk of incident ESKD in models adjusted for APOL1 genotype and in the subset of African-Americans with no APOL1 risk alleles, RH was associated with an adjusted 2.75-fold (95% CI: 2.00-3.50) higher risk of incident ESKD. DISCUSSION/SIGNIFICANCE OF IMPACT: RH was independently associated with a higher risk of ESKD and cardiovascular outcomes, especially among African-Americans. This elevated risk is independent of APOL1 genotype. Interventions that achieve BP targets among patients with RH could curtail the incidence of ESKD and cardiovascular outcomes in this high-risk population. CONFLICT OF INTEREST DESCRIPTION: None.
Early modern European warfare features prominently in several important discussions of early modern violence, notably the debate on the Military Revolution and its variants, as well as forming part of the standard narrative of state formation and the emergence of an international order based on sovereign states. While the dominant trend was towards establishing the state as a monopoly of legitimate violence, the patterns and practices of European warfare remained diverse, as were the ways in which they interacted with state and ‘international’ structures. The creation of permanent forces was slow and uneven, while their implications varied depending on whether they were navies or armies. This chapter contests conventional conceptual models, such as that of ‘limited war’ waged by allegedly disinterested ‘mercenaries’. It argues that efforts to impose tighter discipline arose from multiple political, cultural, social and religious impulses, and varied in effectiveness. War was certainly not limited in terms of its capacity for violence and destruction, but it nonetheless remained broadly within established Christian concepts of ‘just war’ directed by a ‘proper authority’ for legitimate ends. The risks inherent in military operations were an additional constraining factor, despite this period becoming known as an ‘age of battles’.
In a tertiary-care hospital and affiliated long-term care facility, a stewardship intervention focused on patients with Clostridioides difficile infection (CDI) was associated with a significant reduction in unnecessary non-CDI antibiotic therapy. However, there was no significant reduction in total non-CDI therapy or in the frequency of CDI recurrence.
Approaches to assessing violence in clinical practice have been influenced by developments in the field of risk assessment. As a result, there has been a focus on identifying and describing factors associated with violence. However, a factor-based approach to assessing violence in individual cases has limited clinical utility. In response, the benefits of a formulation-based approach have been promoted. This approach is enhanced by an understanding of the specific mental mechanisms that increase the likelihood of violence in the individual case. Although there is an empirical evidence base for mental mechanisms associated with violence, this literature has not been distilled and synthesised in a way that informs routine clinical practice. In this article the authors present the key mechanisms that are known to be associated with violence in a way that is relevant to the clinical assessment of violence and, in turn, can inform clinical and risk management.
Schmidt-hammer exposure-age dating (SHD) of boulders on cryoplanation terrace treads and associated bedrock cliff faces revealed Holocene ages ranging from 0 ± 825 to 8890 ± 1185 yr. The cliffs were significantly younger than the inner treads, which tended to be younger than the outer treads. Radiocarbon dates from the regolith of 3854 to 4821 cal yr BP (2σ range) indicated maximum rates of cliff recession of ~0.1 mm/yr, which suggests the onset of terrace formation before the last glacial maximum. Age, angularity, and size of clasts, together with planation across bedrock structures and the seepage of groundwater from the cliff foot, all support a process-based conceptual model of cryoplanation terrace development in which frost weathering leads to parallel cliff recession and, hence, terrace extension. The availability of groundwater during autumn freezeback is viewed as critical for frost wedging and/or the growth of segregation ice during prolonged winter frost penetration. Permafrost promotes cryoplanation by providing an impermeable frost table beneath the active layer, focusing groundwater flow, and supplying water for sediment transport by solifluction across the tread. Snow beds are considered an effect rather than a cause of cryoplanation terraces, and cryoplanation is seen as distinct from nivation.
Schmidt-hammer exposure-age dating (SHD) was applied at 15 sites with glacially-transported granite boulders in parts of northern and western Ireland and southwest Scotland that had been exposed by retreat of the last British-Irish Ice Sheet (BIIS) or Younger Dryas (YD) ice masses. Seven of these surfaces had previously been dated using terrestrial cosmogenic nuclide (TCN) exposure-age dating. Application of the granite calibration equation of Tomkins et al. (2018c) indicated a close correspondence between the SHD ages and the TCN ages (within 1σ or 2σ uncertainties). These findings demonstrate that SHD ages can be of comparable accuracy, precision, and reliability to TCN ages and are a strong argument for the more extensive use of SHD in some Quaternary dating projects. However, surface ages obtained by both SHD and TCN dating should not be accepted uncritically; they must be assessed in relation to the wider geological, geomorphological, and geochronological evidence. Evaluation of eight SHD ages, for which corresponding TCN ages are not available, indicate that most are consistent with current theory and field evidence, but some anomalous age estimates occur.
James I's daughter, Elizabeth, married Elector Palatine Frederick V on Valentine's Day 1613. This ‘Palatine match’ was one of the most spectacular events of the Jacobean age, allegedly costing over L93,000 or more than a decade's expenditure on all royal palaces. The expense underscored the wedding's importance in James's ambitions to broker European peace: it was the Protestant counterpart of the attempts to marry Elizabeth's brother Charles to a Catholic Spanish or French princess. The lavish display unfortunately also magnified the subsequent discrepancy between aspirations and achievement. Far from securing peace or advancing Protestantism, Stuart involvement with the Palatinate brought frustration and costly engagement in the Thirty Years’ War, contributing to the monarchy's domestic political difficulties and thus, indirectly, to the Civil Wars.
This is well known, but most contemporaries and many historians have generally failed to appreciate the difficulties faced by the Stuarts in shaping a viable policy. My argument is two-fold. First, only by explaining these difficulties can we understand why Stuart policy failed. Second, this explanation lies largely in continental rather than British politics. Defining the Thirty Years’ War is central to our answer. Failure to understand the war (both at the time, and subsequently) is a prime source for confusion. The second section examines the war's roots in the interrelationship between religious and constitutional issues in the Holy Roman Empire. The third part identifies the Palatinate's role in escalating regional problems into full-scale war in 1619. The final section underscores the Stuarts’ dilemma; there was no obvious way they could intervene effectively in continental affairs.
Defining the Thirty Years’ War
To many Britons, the Thirty Years’ War was a struggle between ‘good’ Protestantism and ‘evil’ Catholicism. Subsequent historians have often agreed, though usually without such partisanship, and the conflict has entered popular consciousness as the culmination of an entire age of religious wars beginning with the Reformation. While recent anglophone scholarship stresses religious causes, especially for Britain's Civil Wars, continental European research increasingly questions the appropriateness of the concept of ‘religious war’. The idea of the Thirty Years’ War as a pan-European free-for-all likewise featured in contemporary popular attitudes and shapes many later historical interpretations, notably those related to concepts of a ‘General Crisis of the Seventeenth Century’.
Fomesafen is a protoporphyrinogen oxidase–inhibitor herbicide with an alternative mode of action that provides PRE weed control in strawberry [Fragaria×ananassa (Weston) Duchesne ex Rozier (pro sp.) [chiloensis×virginiana]] produced in a plasticulture setting in Florida. Plasticulture mulch could decrease fomesafen dissipation and increase crop injury in rotational crops. Field experiments were conducted in Balm, FL, to investigate fomesafen persistence and movement in soil in Florida strawberry systems for the 2014/2015 and 2015/2016 production cycles. Treatments included fomesafen preplant at 0, 0.42, and 0.84 kg ai ha−1. Soil samples were taken under the plastic from plots treated with fomesafen at 0.42 kg ha−1 throughout the production cycle. Fomesafen did not injure strawberry or decrease yield. Fomesafen concentration data for the 0.0- to 0.1-m soil depth were described using a three-parameter logistic function. The fomesafen 50% dissipation times were 37 and 47 d for the 2014/2015 and 2015/2016 production cycles, respectively. At the end of the study, fomesafen was last detected in the 0.0- to 0.1-m depth soil at 167 and 194 d after treatment in the 2014/2015 and 2015/2016 production cycles, respectively. Fomesafen concentration was less than 25 ppb on any sampling date for 0.1- to 0.2-m and 0.2- to 0.3-m depths. Fomesafen concentration decreased significantly after strawberry was transplanted and likely leached during overhead and drip irrigation used during the crop establishment.
Antineuronal antibodies are associated with psychosis, although their clinical significance in first episode of psychosis (FEP) is undetermined.
To examine all patients admitted for treatment of FEP for antineuronal antibodies and describe clinical presentations and treatment outcomes in those who were antibody positive.
Individuals admitted for FEP to six mental health units in Queensland, Australia, were prospectively tested for serum antineuronal antibodies. Antibody-positive patients were referred for neurological and immunological assessment and therapy.
Of 113 consenting participants, six had antineuronal antibodies (anti-N-methyl-D-aspartate receptor antibodies [n = 4], voltage-gated potassium channel antibodies [n = 1] and antibodies against uncharacterised antigen [n = 1]). Five received immunotherapy, which prompted resolution of psychosis in four.
A small subgroup of patients admitted to hospital with FEP have antineuronal antibodies detectable in serum and are responsive to immunotherapy. Early diagnosis and treatment is critical to optimise recovery.
There is a growing interest in using cognitive–behavioural therapy (CBT) with people who have Asperger syndrome and comorbid mental health problems.
To examine whether modified group CBT for clinically significant anxiety in an Asperger syndrome population is feasible and likely to be efficacious.
Using a randomised assessor-blind trial, 52 individuals with Asperger syndrome were randomised into a treatment arm or a waiting-list control arm. After 24 weeks, those in the waiting-list control arm received treatment, while those initially randomised to treatment were followed up for 24 weeks.
The conversion rate for this trial was high (1.6:1), while attrition was 13%. After 24 weeks, there was no significant difference between those randomised to the treatment arm compared with those randomised to the waiting-list control arm on the primary outcome measure, the Hamilton Rating Scale for Anxiety.
Trials of psychological therapies with this population are feasible. Larger definitive trials are now needed.
To identify, using a novel enhanced method of recovery, environmental sites where spores of Clostridium difficile persist despite cleaning and hydrogen peroxide aerial decontamination.
Tertiary referral center teaching hospital.
In total, 16 sites representing high-frequency contact or difficult-to-clean surfaces in a single-isolation room or bed area in patient bed bays were sampled before and after terminal or hydrogen peroxide disinfection using a sponge swab. In some rooms, individual sites were not present (eg, there were no en-suite rooms in the ICU). Swab contents were homogenized, concentrated by membrane-filtration, and plated onto selective media. Results of C. difficile sampling were used to focus cleaning.
Over 1 year, 2,529 sites from 146 rooms and 44 bays were sampled. Clostridium difficile was found on 131 of 572 surfaces (22.9%) before terminal cleaning, on 105 of 959 surfaces (10.6%) after terminal cleaning, and on 43 of 967 surfaces (4.4%) after hydrogen peroxide disinfection. Clostridium difficile persisted most frequently on floor corners (97 of 334; 29.0%) after disinfection. Between the first and third quarters, we observed a significant decrease in the number of positive sites (25 of 390 vs 6 of 256). However, no similar change in the number of isolates before terminal cleaning was observed.
Persistence of C. difficile in the clinical environment was widespread. Although feedback of results did not improve the efficacy of manual disinfection, numbers of C. difficile following hydrogen peroxide gradually declined.
Fomesafen is a protoporphyrinogen oxidase (PROTOX) inhibitor that has the potential to be used as an alternative mechanism of action for PRE nutsedge and broadleaf weed control in Florida production of small fruit and vegetables. Fumigation in the raised-bed plasticulture system may increase herbicide persistence. Fomesafen persistence could dissuade Florida growers from using the herbicide for fear of injury to subsequent susceptible crops. Field experiments were conducted in Balm, FL, in 2015 and 2016 to investigate the effect of fumigation on fomesafen dissipation, eggplant tolerance, and purple nutsedge control. Treatments included fomesafen at 0.42 kg ai ha−1, S-metolachlor at 1.06 kg ai ha−1, and a nontreated control in either a fumigated bed injected with a combination of 39% 1,3-dichloropropene and 59.6% chloropicrin at 336 kg ha−1 or no fumigant. Fomesafen concentration in the soil decreased by 83% and 96% from application to harvest in 2015 and 2016, respectively. Fumigation did not affect fomesafen dissipation in either year. At 2 wk after transplant (WATr), fomesafen caused 14% eggplant injury. Injury decreased to less than 5% at 6 WATr. Fomesafen and S-metolachlor treatments did not reduce eggplant height or yields compared with the nontreated control. Fumigation and fomesafen did not decrease purple nutsedge density; however, S-metolachlor applications resulted in a 48% reduction. Further research is needed to assess efficacy on broadleaf and grass weeds.
Mulches used in plasticulture systems could decrease dissipation of fomesafen, a protoporphyrinogen oxidase inhibitor, and dissuade producers from using the herbicide for fear of crop injury in subsequent growing seasons. Field experiments were conducted in Balm, FL, in 2015 and 2016 to investigate the effect of different plastic mulches on fomesafen dissipation, squash tolerance, and efficacy on purple nutsedge. Squash was injured less than 5% from fomesafen applications. The use of plastic mulches reduced purple nutsedge density at transplant by 60% compared with the no-mulch treatment. At transplant, treatments with low-density polyethylene mulch (LDPE), virtually impermeable film (VIF), and totally impermeable film (TIF) mulch had greater than 2-fold the fomesafen concentrations than treatments with clear or no mulch. At harvest in 2015, LDPE, VIF, and TIF treatments had greater fomesafen concentrations than clear and no-mulch treatments; however, concentrations in 2016 were similar for all treatments. Fomesafen can persist at high concentrations throughout the growing season in Florida plasticulture possibly limiting producer options for crop rotation and the use of cover crops.
Infants and young children are frequently colonized with C. difficile but rarely have symptomatic disease. However, C. difficile testing remains prevalent in this age group.
To design a computerized provider order entry (CPOE) alert to decrease testing for C. difficile in young children and infants.
An interventional age-targeted before-after trial with comparison group
Monroe Carell Jr. Children’s Hospital at Vanderbilt University, Nashville, Tennessee.
All children seen in the inpatient or emergency room settings from July 2012 through July 2013 (pre-CPOE alert) and September 2013 through September 2014 (post-CPOE alert)
In August of 2013, we implemented a CPOE alert advising against testing in infants and young children based on the American Academy of Pediatrics recommendations with an optional override. We further offered healthcare providers educational seminars regarding recommended C. difficile testing.
The average monthly testing rate significantly decreased after the CPOE alert for children 0–11 months old (11.5 pre-alert vs 0 post-alert per 10,000 patient days; P<.001) and 12–35 months old (61.6 pre-alert vs 30.1 post-alert per 10,000 patients days; P<.001), but not for those children ≥36 months old (50.9 pre-alert vs 46.4 post-alert per 10,000 patient days; P=.3) who were not targeted with a CPOE alert. There were no complications in those children who testing positive for C. difficile.
The average monthly testing rate for C. difficile for children <35 months old decreased without complication after the use of a CPOE alert in those who tested positive for C. difficile.
Transcatheter device closure has become the established standard of care for suitable atrial septal defects. Device erosion has been a recent focus and has prompted changes in the Instructions for Users documentation released by device companies. We reviewed our entire local experience with atrial septal defect device closure, focussing on the evolution of this procedure in our centre and particularly on complications.
We carried out a retrospective review of 581 consecutive patients undergoing attempted transcatheter device closure of an atrial septal defect in Auckland from December 1997 to June 2014. We reviewed all complications recorded and compared our outcomes with the current literature. We sought to understand the impact of the evolution in recommendations and clinical practice on patient outcomes in our programme.
There were a total of 24 complications (4.1%), including 10 device embolisations (1.7%), nine arrhythmias (1.5%), two significant vascular access-related complications (0.3%), one device erosion (0.2%), one malposed device (0.2%), and one probable wire perforation of the left atrial appendage (0.2%). There was one mortality related to device embolisation. All device embolisations occurred following the change in Instructions for Users after publication of the first device erosion report in 2004. This increase in embolisation rate was statistically significant (p-value 0.015).
In our series, the incidence of device embolisation was higher than that anticipated, with a significant increase following changes to the Instructions for Users. This highlights the need for ongoing data collection on complication incidence and for ongoing review of the impact of changes in clinical practice on complication rates.
The success of scaling out depends on a clear understanding of the factors that affect adoption of grain legumes and account for the dynamism of those factors across heterogeneous contexts of sub-Saharan Africa. We reviewed literature on adoption of grain legumes and other technologies in sub-Saharan Africa and other developing countries. Our review enabled us to define broad factors affecting different components of the scaling out programme of N2Africa and the scales at which those factors were important. We identified three strategies for managing those factors in the N2Africa scaling out programme: (i) testing different technologies and practices; (ii) evaluating the performance of different technologies in different contexts; and (iii) monitoring factors that are difficult to predict. We incorporated the review lessons in a design to appropriately target and evaluate technologies in multiple contexts across scales from that of the farm to whole countries. Our implementation of this design has only been partially successful because of competing reasons for selecting activity sites. Nevertheless, we observe that grain legume species have been successfully targeted for multiple biophysical environments across sub-Saharan Africa, and to social and economic contexts within countries. Rhizobium inoculant and legume specific fertiliser blends have also been targeted to specific contexts, although not in all countries. Relatively fewer input and output marketing models have been tested due to public–private partnerships, which are a key mechanism for dissemination in the N2Africa project.