Efficacy of Eravacycline Versus Best Previously Available Therapy for Adults With Pneumonia Due to Difficult-to-Treat Resistant (DTR) Acinetobacter baumannii.

BACKGROUND: Multidrug-resistant Acinetobacter baumannii remains challenging to treat. Although eravacycline has in vitro activity against this pathogen, there are no studies evaluating outcomes. OBJECTIVE: To assess the efficacy of eravacycline compared with best previously available therapy in adults with difficult-to-treat resistant (DTR) A. baumannii pneumonia. METHODS: This was a retrospective study of adults hospitalized for pneumonia with DTR A. baumannii. Patients receiving eravacycline were compared with those receiving best previously available therapy. The primary outcome was 30-day in-hospital mortality. Secondary outcomes included clinical cure at Day 14, hospital and intensive care unit (ICU) length of stay, microbiologic cure, and readmission within 90 days with a positive A. baumannii respiratory culture. RESULTS: Ninety-three patients were included, with 27 receiving eravacycline. Eravacycline was associated with higher 30-day mortality (33% vs 15%; P = 0.048), lower microbiologic cure (17% vs 59%; P = 0.004), and longer durations of mechanical ventilation (10.5 vs 6.5 days; P = 0.016). At baseline, eravacycline patients had more A. baumannii bacteremia and coinfection with severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2). Among bacteremic patients, all 4 receiving eravacycline died by Day 30 and both patients receiving best previously available therapy survived. Upon exclusion of patients with bacteremia and SARS-CoV-2, there were no differences between the groups across any outcomes. CONCLUSIONS: Eravacycline-based combination therapy had similar outcomes to best previously available combination therapy for adults with DTR A. baumannii pneumonia. However, eravacycline should be used with caution in the setting of bacteremia as outcomes were poor in this population.

Relationship between pulmonary artery acceleration time and pulmonary artery pressures in infants.

BACKGROUND: Pulmonary artery acceleration time measured by echocardiography inversely correlates with pulmonary artery pressures in adults and children older than 1 year of age. There is a paucity of data investigating this relationship in young children, particularly among preterm infants. OBJECTIVE: To characterize the relationship between pulmonary artery acceleration time (PAAT) and pulmonary artery pressures in infants. DESIGN/METHODS: Patients ≤ 1 year of age at Children's Hospital of Philadelphia between 2011 and 2017 were reviewed. Infants with congenital heart disease were excluded, except those with a patent ductus arteriosus (PDA), atrial septal defect (ASD), or ventricular septal defect (VSD). Linear regression analysis was used to assess the correlation between PAAT measured by echocardiography and systolic pulmonary artery pressure, mean pulmonary artery pressure, and indexed pulmonary vascular resistance from cardiac catheterization. RESULTS: Fifty-seven infants were included, of which 61% were preterm and 49% had a diagnosis of bronchopulmonary dysplasia. The median postmenstrual age and weight at catheterization were 51.1 weeks (IQR 35.8-67.9 weeks) and 4400 g (IQR 3100-6500 g), respectively. Forty-four infants (77%) had a patent ductus arteriosus (PDA). There was a weak inverse correlation between PAAT with mPAP (r = -0.35, P = 0.01), sPAP (r = -0.29, P = 0.03), and PVRi (r = -0.29, P = 0.03). CONCLUSION: There is a weak inverse relationship between PAAT and pulmonary artery pressures. This relationship is less robust in our population of infants with a high incidence of PDAs compared to previous studies in older children. Thus, PAAT may be less clinically meaningful for diagnosing pulmonary arterial hypertension in infants, particularly those with PDAs.

Peripheral Nerve Blocks and Immediate Postoperative Recovery: A Single-Institution Survey of Perianesthesia Nurses' Preferences and Opinions.

PURPOSE: To ascertain the preferences of perianesthesia nurses regarding peripheral nerve blocks (PNBs) and their impact on patient recovery after total joint replacement (TJR). DESIGN: Survey of perianesthesia nurses at a single medical center. METHODS: Fifty-nine perianesthesia nurses completed a 23-question survey on PNBs for TJR. FINDINGS: Most agreed PNBs improved patients' pain after knee, hip, and shoulder TJR (35 [92.1%], 35 [92.1%], and 34 [91.9%], respectively). Most felt lower extremity PNBs increased risk of falling (26 [70.3%]), whereas 7 of 35 (20.0%) felt patients fell more after spinal anesthesia than after general anesthesia. Respondents preferred a block to opioid-based analgesia if they were to have lower extremity TJR or total shoulder replacement (100% [30/30 and 33/33]). CONCLUSIONS: The perianesthesia nurses surveyed felt PNBs improved pain control and patient recovery despite a perceived risk of falling for lower extremity TJR, and they preferred PNB when considering TJR surgery for themselves.

The Public Health Responsibility Deal: making the workplace healthier?

Background: The Public Health Responsibility Deal (RD) in England is a public-private partnership which aims to improve public health by addressing issues such as health at work. This paper analyses the RD health at work pledges in terms of their likely effectiveness and added value. Methods: A review of evidence on the effectiveness of the RD 'health at work' pledges to improve health in the workplace; analysis of publically available data on signatory organizations' plans and progress towards achieving the pledges; and assessment of the likelihood that workplace activities pledged by signatories were brought about by participating in the RD. Results: The 'health at work' pledges mostly consist of information sharing activities, and could be more effective if made part of integrated environmental change at the workplace. The evaluation of organizations' plans and progress suggests that very few actions (7%) were motivated by participation in the RD, with most organizations likely (57%) or probably (36%) already engaged in the activities they listed before joining the RD. Conclusions: The RD's 'health at work' pledges are likely to contribute little to improving workplace health as they stand but could contribute more if they were incorporated into broader, coherent workplace health strategies.

No global consensus: a cross-sectional survey of maternal weight policies.

BACKGROUND: Growing evidence suggests that maternal prepregnancy weight and gestational weight gain are risk factors for perinatal complications and subsequent maternal and child health. Postpartum weight retention is also associated with adverse birth outcomes and maternal obesity. Clinical guidelines addressing healthy weight before, during, and after pregnancy have been introduced in some countries, but at present a systematic accounting for these policies has not been conducted. The objective of the present study was to conduct a cross-national comparison of maternal weight guidelines. METHODS: This cross sectional survey administered a questionnaire online to key informants with expertise on the subject of maternal weight to assess the presence and content of preconceptional, pregnancy and postpartum maternal weight guidelines, their rationale and availability. We searched 195 countries, identified potential informants in 80 and received surveys representing 66 countries. We estimated the proportion of countries with guidelines by region, income, and formal or informal policy, and described and compared guideline content, including a rubric to assess presence or absence of 4 guidelines: encourage healthy preconceptional weight, antenatal weighing, encourage appropriate gestational gain, and encourage attainment of healthy postpartum weight. RESULTS: Fifty-three countries reported either a formal or informal policy regarding maternal weight. The majority of these policies included guidelines to assess maternal weight at the first prenatal visit (90%), to monitor gestational weight gain during pregnancy (81%), and to provide recommendations to women about healthy gestational weight gain (62%). Guidelines related to preconceptional (42%) and postpartum (13%) weight were less common. Only 8% of countries reported policies that included all 4 fundamental guidelines. Guideline content and rationale varied considerably between countries, and respondents perceived that within their country, policies were not widely known. CONCLUSIONS: These results suggest that maternal weight is a concern throughout the world. However, we found a lack of international consensus on the content of guidelines. Further research is needed to understand which recommendations or interventions work best with respect to maternal weight in different country settings, and how pregnancy weight policies impact clinical practices and health outcomes for the mother and child.

Management of patients with spontaneous intracranial hypotension causing altered level of consciousness: report of two cases and review of literature.

BACKGROUND: Decreased level of consciousness is a rare neurological manifestation of spontaneous intracranial hypotension (SIH), which typically presents with orthostatic headache. The optimal management of this uncommon presentation remains uncertain. METHODS: We analyzed the presentation, management and outcome of two patients in our institution and reviewed 22 patients reported in the literature with SIH and decreased level of consciousness, defined as any decrease in the patient's Glasgow Coma Scale score. RESULTS: There were 20 male and four female patients (M:F ratio of 5:1) with an average age of 52 years (range 37 to 68 years). There was a variable time interval of up to many months between the initial presentation of SIH and changes in the level of consciousness. An epidural autologous blood patch was eventually successful in 79% of the patients, although up to three trials were necessary in seven of these patients. Intrathecal saline infusion used as a temporizing measure resulted in excellent response within hours in five out of six patients who received this treatment. Drainage of the subdural collection either did not result in any sustained improvement or resulted in clinical deterioration in 12 out of 12 patients who received this treatment. CONCLUSIONS: In the absence of a clinical trial because of the rarity of this entity, the treatment of SIH complicated by decreased level of consciousness remained controversial in the past. However, current collective experience supports early treatment of patients with SIH and decreased level of consciousness with one or more epidural blood patches. Fibrin glue and surgical duroplasty are the next steps in the management of patients in whom epidural blood patches fail. Drainage of the subdural collections may be detrimental.

The Practice of Fast-Track Liver Transplant Anesthesia.

Prior to the 1990s, prolonged postoperative intubation and admission to the intensive care unit was considered the standard of care following liver transplantation. Advocates of this practice speculated that this time allowed patients to recover from the stress of major surgery and allowed their clinicians to optimize the recipients' hemodynamics. As evidence in the cardiac surgical literature on the feasibility of early extubation grew, clinicians began applying these principles to liver transplant recipients. Further, some centers also began challenging the dogma that patients need to be cared for in the intensive care unit following liver transplantation and instead transferred patients to the floor or stepdown units immediately following surgery, a technique known as "fast-track" liver transplantation. This article aims to provide a history of early extubation for liver transplant recipients and offer practical advice on how to select patients that may be able to bypass the intensive care unit and be recovered in a non-traditional manner.

Preemptive Venoarterial Extracorporeal Membrane Oxygenation for Liver Transplantation-Judicious Candidate Selection.

Portopulmonary hypertension is a relatively common pathologic condition in patients with end-stage liver disease. Traditionally, severe pulmonary hypertension is regarded as a contraindication to liver transplantation (LT) due to a high perioperative mortality rate. Recently, extracorporeal membrane oxygenation (ECMO) has been utilized for intraoperative management of LT. As venoarterial (VA) ECMO may benefit certain high-risk LT patients by reducing the ventricular workload by the equivalent of the programmed flow rate, its usage requires multidisciplinary planning with considerations of the associated complications. We highlighted two cases at our single-center institution as examples of high-risk pulmonary hypertension patients undergoing LT on planned VA ECMO. These patients both survived the intraoperative period; however, they had drastically different postoperative outcomes, generating discussions on the importance of judicious patient selection. Since ECMO has removed the barrier of intraoperative survivability, the patient selection process may need to put weight on the patient's potential for postoperative recovery and rehabilitation. Considerations on LT recipients undergoing preemptive ECMO need to expand from the ability of the patients to withstand the demands of the surgery during the immediate perioperative period to the long-term postoperative recovery course.

A 'strategy of resistance'? How can a place-based empowerment programme influence local media portrayals of neighbourhoods and what are the implications for tackling health inequalities?

Place-based stigma is linked with health and social harms, but few studies have assessed what actions may reduce these. Area-based programmes are one potential strategy but may exacerbate stigma by targeting disadvantaged neighbourhoods. We reviewed newspaper coverage in two stigmatised neighbourhoods to identify whether a programme funded in these localities influenced reporting. While both areas were dominated by negative coverage, the progamme provided an impetus for some positive stories over time and enabled community activists to articulate alternative narratives about where they lived, countering negative external portrayals. The involvement of residents should be central to strategies to tackle place-based stigma.

Structural abnormalities in neurons are sufficient to explain the clinical disease and fatal outcome of experimental rabies in yellow fluorescent protein-expressing transgenic mice.

Under natural conditions and in some experimental models, rabies virus infection of the central nervous system causes relatively mild histopathological changes, without prominent evidence of neuronal death despite its lethality. In this study, the effects of rabies virus infection on the structure of neurons were investigated with experimentally infected transgenic mice expressing yellow fluorescent protein (YFP) in neuronal subpopulations. Six-week-old mice were inoculated in the hind-limb footpad with the CVS strain of fixed virus or were mock infected with vehicle (phosphate-buffered saline). Brain regions were subsequently examined by light, epifluorescent, and electron microscopy. In moribund CVS-infected mice, histopathological changes were minimal in paraffin-embedded tissue sections, although mild inflammatory changes were present. Terminal deoxynucleotidyltransferase-mediated dUTP-biotin nick end labeling and caspase-3 immunostaining showed only a few apoptotic cells in the cerebral cortex and hippocampus. Silver staining demonstrated the preservation of cytoskeletal integrity in the cerebral cortex. However, fluorescence microscopy revealed marked beading and fragmentation of the dendrites and axons of layer V pyramidal neurons in the cerebral cortex, cerebellar mossy fibers, and axons in brainstem tracts. At an earlier time point, when mice displayed hind-limb paralysis, beading was observed in a few axons in the cerebellar commissure. Toluidine blue-stained resin-embedded sections from moribund YFP-expressing animals revealed vacuoles within the perikarya and proximal dendrites of pyramidal neurons in the cerebral cortex and hippocampus. These vacuoles corresponded with swollen mitochondria under electron microscopy. Vacuolation was also observed ultrastructurally in axons and in presynaptic nerve endings. We conclude that the observed structural changes are sufficient to explain the severe clinical disease with a fatal outcome in this experimental model of rabies.

Symptoms of depression and cognitive impairment in young adults after stroke/transient ischemic attack.

Depression and cognitive complaints are common after stroke; these issues have been studied in older populations, but not in the young. Two hundred and seventy four eligible stroke and TIA patients consented to participate and complete the Center for Epidemiologic Studies Depression Scale, and National Institute of Neurological Disorders and Stroke - Canadian Stroke Network 30-min neuropsychological battery; 57 (21%) were ≤ 50 years of age. Younger patients reported greater symptoms of depression and less executive dysfunction than older patients. This study highlights age differences in post-stroke depression symptoms and cognitive impairment, and emphasizes the need for screening across ages.

Obesity and Weight Gain in Pregnancy and Postpartum: an Evidence Review of Lifestyle Interventions to Inform Maternal and Child Health Policies.

Background: Maternal obesity, excessive gestational weight gain (GWG) and post-partum weight retention (PPWR) constitute new public health challenges, due to the association with negative short- and long-term maternal and neonatal outcomes. The aim of this evidence review was to identify effective lifestyle interventions to manage weight and improve maternal and infant outcomes during pregnancy and postpartum. Methods: A review of systematic reviews and meta-analyses investigating the effects of lifestyle interventions on GWG or PPWR was conducted (Jan 2009-2018) via electronic searches in the databases Medline, Pubmed, Web of Science and Cochrane Library using all keywords related to obesity/weight gain/loss, pregnancy or postpartum and lifestyle interventions;15 relevant reviews were selected. Results: In healthy women from all BMI classes, diet and physical activity interventions can decrease: GWG (mean difference -1.8 to -0.7 kg, high to moderate-quality evidence); the risks of GWG above the IOM guidelines (risk ratio [RR] 0.72 to 0.80, high to low-quality evidence); pregnancy-induced hypertension (RR 0.30 to 0.66, low to very low-quality evidence); cesarean section (RR 0.91 to 0.95; high to moderate-quality evidence) and neonatal respiratory distress syndrome (RR 0.56, high-quality evidence); without any maternal/fetal/neonatal adverse effects. In women with overweight/obesity, multi-component interventions can decrease: GWG (-0.91 to -0.63 kg, moderate to very low-quality evidence); pregnancy-induced hypertension (RR 0.30 to 0.66, low-quality evidence); macrosomia (RR 0.85, 0.73 to 1.0, moderate-quality evidence) and neonatal respiratory distress syndrome (RR 0.47, 0.26 to 0.85, moderate-quality evidence). Diet is associated with greater reduction of the risks of GDM, pregnancy-induced hypertension and preterm birth, compared with any other intervention. After delivery, combined diet and physical activity interventions reduce PPWR in women of any BMI (-2.57 to -2.3 kg, very low quality evidence) or with overweight/obesity (-3.6 to -1.22, moderate to very low-quality-evidence), but no other effects were reported. Conclusions: Multi-component approaches including a balanced diet with low glycaemic load and light to moderate intensity physical activity, 30-60 min per day 3-5 days per week, should be recommended from the first trimester of pregnancy and maintained during the postpartum period. This evidence review should help inform recommendations for health care professionals and women of child-bearing age.

Change in non-alcoholic beverage sales following a 10-pence levy on sugar-sweetened beverages within a national chain of restaurants in the UK: interrupted time series analysis of a natural experiment.

BACKGROUND: This study evaluates changes in sales of non-alcoholic beverages in Jamie's Italian, a national chain of commercial restaurants in the UK, following the introduction of a £0.10 per-beverage levy on sugar-sweetened beverages (SSBs) and supporting activity including beverage menu redesign, new products and establishment of a children's health fund from levy proceeds. METHODS: We used an interrupted time series design to quantify changes in sales of non-alcoholic beverages 12 weeks and 6 months after implementation of the levy, using itemised electronic point of sale data. Main outcomes were number of SSBs and other non-alcoholic beverages sold per customer. Linear regression and multilevel random effects models, adjusting for seasonality and clustering, were used to investigate changes in SSB sales across all restaurants (n=37) and by tertiles of baseline restaurant SSB sales per customer. RESULTS: Compared with the prelevy period, the number of SSBs sold per customer declined by 11.0% (-17.3% to -4.3%) at 12 weeks and 9.3% (-15.2% to -3.2%) at 6 months. For non-levied beverages, sales per customer of children's fruit juice declined by 34.7% (-55.3% to -4.3%) at 12 weeks and 9.9% (-16.8% to -2.4%) at 6 months. At 6 months, sales per customer of fruit juice increased by 21.8% (14.0% to 30.2%) but sales of diet cola (-7.3%; -11.7% to -2.8%) and bottled waters (-6.5%; -11.0% to -1.7%) declined. Changes in sales were only observed in restaurants in the medium and high tertiles of baseline SSB sales per customer. CONCLUSIONS: Introduction of a £0.10 levy on SSBs alongside complementary activities is associated with declines in SSB sales per customer in the short and medium term, particularly in restaurants with higher baseline sales of SSBs.

The Public Health Responsibility deal: has a public-private partnership brought about action on alcohol reduction?

BACKGROUND AND AIMS: The Public Health Responsibility Deal (RD) in England is a public-private partnership involving voluntary pledges between industry, government and other organizations, with the aim of improving public health. This paper aims to evaluate what action resulted from the RD alcohol pledges. METHODS: We analysed publically available data on organizations' plans and progress towards achieving key alcohol pledges of the RD. We assessed the extent to which activities pledged by signatories could have been brought about by the RD, as opposed to having happened anyway (the counterfactual), using a validated coding scheme designed for the purpose. RESULTS: Progress reports were submitted by 92% of signatories in 2013 and 75% of signatories in 2014, and provided mainly descriptive feedback rather than quantifiable performance metrics. Approximately 14% of 2014 progress reports were identical to those presented in 2013. Most organizations (65%) signed pledges that involved actions to which they appear to have been committed already, regardless of the RD. A small but influential group of alcohol producers and retailers reported taking measures to reduce alcohol units available for consumption in the market. However, where reported, these measures appear to involve launching and promoting new lower-alcohol products rather than removing units from existing products. CONCLUSIONS: The RD is unlikely to have contributed significantly to reducing alcohol consumption, as most alcohol pledge signatories appear to have committed to actions that they would have undertaken anyway, regardless of the RD. Irrespective of this, there is considerable scope to improve the clarity of progress reports and reduce the variability of metrics provided by RD pledge signatories.

Nipple Pain in Breastfeeding Mothers: Incidence, Causes and Treatments.

BACKGROUND: Persistent nipple pain is one of the most common reasons given by mothers for ceasing exclusive breastfeeding. We aimed to determine the frequency of nipple pain as a reason for consultation, the most common attributed aetiologies, and the effectiveness of the advice and treatment given. METHODS: All consultations at the Breast Feeding Centre of Western Australia (WA) were audited over two six-month periods in 2011 (n = 469) and 2014 (n = 708). Attributed cause(s) of nipple pain, microbiology results, treatment(s) advised, and resolution of pain were recorded. RESULTS: Nipple pain was one of the reasons for consultation in 36% of cases. The most common attributed cause of nipple pain was incorrect positioning and attachment, followed by tongue tie, infection, palatal anomaly, flat or inverted nipples, mastitis, and vasospasm. Advice included correction of positioning and attachment, use of a nipple shield, resting the nipples and expressing breastmilk, frenotomy, oral antibiotics, topical treatments, and cold or warm compresses. Pain was resolving or resolved in 57% of cases after 18 days (range 2-110). CONCLUSION: The multiple attributed causes of nipple pain, possibly as a result of a cascade of events, suggests that effective early lactation management for prevention of nipple pain and early diagnosis and effective treatment are crucial to avoid early weaning.

Therapy with minocycline aggravates experimental rabies in mice.

Minocycline is a tetracycline derivative with antiapoptotic and anti-inflammatory properties, and the drug has been shown to have beneficial effects in a variety of models of neurological disorders. The potentially neuroprotective role of minocycline was assessed in experimental in vitro and in vivo models of rabies virus infection. In this study, 5 nM minocycline did not improve the viability of embryonic mouse cortical and hippocampal neurons infected in vitro with the attenuated SAD-D29 strain of rabies virus, based on assessments using trypan blue exclusion. Two-day-old ICR mice were inoculated in the right hind limb thigh muscle with SAD-D29, and they received daily subcutaneous injections of either 50 mg/kg minocycline or vehicle (phosphate-buffered saline). Infected minocycline-treated mice experienced an earlier onset of neurologic signs and greater mortality (83% versus 50%) than those receiving vehicle (log rank test, P=0.002 and P=0.003, respectively). Immunohistochemical analysis of rabies virus antigen distribution was performed at early time points and in moribund mice. There were greater numbers of infected neurons in the regional brain areas of minocycline-treated mice than in vehicle-treated mice, which was significant in the CA1 region of the hippocampus. There was less apoptosis (P=0.01) and caspase 3 immunostaining (P=0.0008) in the midbrains of mice treated with minocycline than in mice treated with vehicle, consistent with a neuroprotective role of neuronal apoptosis that may have had a mild effect of inhibiting viral spread. Reduced infiltration of CD3+ T cells was observed in the pons/medulla of moribund mice that received minocycline therapy (P=0.008), suggesting that the anti-inflammatory actions of minocycline may intensify the neurologic disease. These findings indicate that minocycline has important detrimental effects in the therapy of experimental rabies. Empirical therapy with minocycline should therefore be approached with caution in cases of human rabies and possibly other viral encephalitides until more experimental data become available.

Rabies virus infection of primary neuronal cultures and adult mice: failure to demonstrate evidence of excitotoxicity.

Cultures derived from the cerebral cortices and hippocampi of 17-day-old mouse fetuses infected with the CVS strain of rabies virus showed loss of trypan blue exclusion, morphological apoptotic features, and activated caspase 3 expression, indicating apoptosis. The NMDA (N-methyl-D-aspartate acid) antagonists ketamine (125 microM) and MK-801 (60 microM) were found to have no significant neuroprotective effect on CVS-infected neurons, while the caspase inhibitor Ac-Asp-Glu-Val aspartic acid aldehyde (25 microM) exerted a marked neuroprotective effect. Glutamate-stimulated increases in levels of intracellular calcium were reduced in CVS-infected hippocampal neurons. Ketamine (120 mg/kg of body weight/day intraperitoneally) given to CVS-infected adult mice produced no beneficial effects. We have found no supportive evidence that excitotoxicity plays an important role in rabies virus infection.