Correction to: Risk factors for readmission among patients receiving outpatient parenteral antimicrobial therapy: a retrospective cohort study

International Journal of Clinical Pharmacy - An amendment to this paper has been published and can be accessed via a link at the top of the paper.     

Spot the red herring: breastfeeding, fruitpurée, and infant autonomic functioning-the generation R study

Several studies have suggested that breastfeeding is related to infant autonomic functioning. The authors investigated whether this is a causal relation. In all, 444 mothers reported breastfeeding practices 2 mo postpartum. Infant autonomic functioning was assessed by heart rate variability at age 14 mo, after discontinuation of breastfeeding. The dose-dependent association between breastfeeding and infant autonomic functioning was tested with linear regression models adjusted for multiple confounders. The authors investigated the relation of fruitpurée consumption with infant autonomic functioning. Fruitpurée consumption has similar socioeconomic epiphenomena but is not related via the same causal mechanism to autonomic regulation as breastfeeding. Nonbreastfed infants had high sympathetic modulation [7.87 log (ms)/SD, 95% CI: 7.71-8.02], partially breastfed infants had intermediate sympathetic modulation [7.75 log (ms)/SD, 95% CI: 7.51-7.82], sympathetic modulation of exclusively breastfed infants was low [7.63 log (ms)/SD, 95% CI: 7.50-7.77]. However, this association could be explained by socioeconomic confounders. Furthermore, fruitpurée consumption was similarly associated with reduced infant sympathetic modulation. The association between breastfeeding practices and infant sympathetic modulation was accounted for by socioeconomic and environmental factors. We found a similar association between fruitpurée consumption and autonomic functioning, further suggesting that the association between breastfeeding and infant autonomic functioning is noncausal.     

Manganese-enhanced magnetic resonance imaging for in vivo assessment of damage and functional improvement following spinal cord injury in mice.

In past decades, much effort has been invested in developing therapies for spinal injuries. Lack of standardization of clinical read-out measures, however, makes direct comparison of experimental therapies difficult. Damage and therapeutic effects in vivo are routinely evaluated using rather subjective behavioral tests. Here we show that manganese-enhanced magnetic resonance imaging (MEMRI) can be used to examine the extent of damage following spinal cord injury (SCI) in mice in vivo. Injection of MnCl2 solution into the cerebrospinal fluid leads to manganese uptake into the spinal cord. Furthermore, after injury MEMRI-derived quantitative measures correlate closely with clinical locomotor scores. Improved locomotion due to treating the detrimental effects of SCI with an established therapy (neutralization of CD95Ligand) is reflected in an increase of manganese uptake into the injured spinal cord. Therefore, we demonstrate that MEMRI is a sensitive and objective tool for in vivo visualization and quantification of damage and functional improvement after SCI. Thus, MEMRI can serve as a reproducible surrogate measure of the clinical status of the spinal cord in mice, potentially becoming a standard approach for evaluating experimental therapies.     

The impact of reading and writing skills on a visuo-motor integration task: a comparison between illiterate and literate subjects.

Previous studies have shown a significant association between reading skills and the performance on visuo-motor tasks. In order to clarify whether reading and writing skills modulate non-linguistic domains, we investigated the performance of two literacy groups on a visuo-motor integration task with non-linguistic stimuli. Twenty-one illiterate participants and twenty matched literate controls were included in the experiment. Subjects were instructed to use the right or the left index finger to point to and touch a randomly presented target on the right or left side of a touch screen. The results showed that the literate subjects were significantly faster in detecting and touching targets on the left compared to the right side of the screen. In contrast, the presentation side did not affect the performance of the illiterate group. These results lend support to the idea that having acquired reading and writing skills, and thus a preferred left-to-right reading direction, influences visual scanning.     

Effects of Arousal on Habituation of Electarodermal versus Vasomotor Responses

While there is considerable evidence (hat habituation of electrodermal responses is retarded under conditions of heightened arousal, less work has been done on vasomotor responses. A few studies have, however, suggested that arousal has the opposite effect on vasomotor responses, producing an acceleration of habituation In this case. The present study compared skin conductance (SC) and finger pulse volume (PV) responses to a series of tone stimuli under conditions of “high arousal” (HA)-where subjects were standing during testing-and “low arousal” (LA)-where subjects were seated. Tonic measures confirmed that the experimental manipulation was effective in raising SC level and nonspecific activity and lowering PV level in the HA relative to the LA condition. Significant Group (HA vs. LA) X Measure (SC vs. PV) interactions for response frequency and number of trials to habituation were consistent with the prediction that arousal exerts differential effects upon habituation in the two response systems. These data provide further challenges to theories based on unitary models of autonomic response mechanisms.     

Guidelines for the diagnosis and management of critical illness-related corticosteroid insufficiency (CIRCI) in critically ill patients (Part I): Society of Critical Care Medicine (SCCM) and European Society of Intensive Care Medicine (ESICM) 2017

Objective

To update the 2008 consensus statements for the diagnosis and management of critical illness-related corticosteroid insufficiency (CIRCI) in adult and pediatric patients.

Participants

A multispecialty task force of 16 international experts in Critical Care Medicine, endocrinology, and guideline methods, all of them members of the Society of Critical Care Medicine and/or the European Society of Intensive Care Medicine.

Design/methods

The recommendations were based on the summarized evidence from the 2008 document in addition to more recent findings from an updated systematic review of relevant studies from 2008 to 2017 and were formulated using the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) methodology. The strength of each recommendation was classified as strong or conditional, and the quality of evidence was rated from high to very low based on factors including the individual study design, the risk of bias, the consistency of the results, and the directness and precision of the evidence. Recommendation approval required the agreement of at least 80% of the task force members.

Results

The task force was unable to reach agreement on a single test that can reliably diagnose CIRCI, although delta cortisol (change in baseline cortisol at 60 min of <9 µg/dl) after cosyntropin (250 µg) administration and a random plasma cortisol of <10 µg/dl may be used by clinicians. We suggest against using plasma free cortisol or salivary cortisol level over plasma total cortisol (conditional, very low quality of evidence). For treatment of specific conditions, we suggest using intravenous (IV) hydrocortisone <400 mg/day for ≥3 days at full dose in patients with septic shock that is not responsive to fluid and moderate- to high-dose vasopressor therapy (conditional, low quality of evidence). We suggest not using corticosteroids in adult patients with sepsis without shock (conditional recommendation, moderate quality of evidence). We suggest the use of IV methylprednisolone 1 mg/kg/day in patients with early moderate to severe acute respiratory distress syndrome (PaO₂/FiO₂ < 200 and within 14 days of onset) (conditional, moderate quality of evidence). Corticosteroids are not suggested for patients with major trauma (conditional, low quality of evidence).

Conclusions

Evidence-based recommendations for the use of corticosteroids in critically ill patients with sepsis and septic shock, acute respiratory distress syndrome, and major trauma have been developed by a multispecialty task force.

     

Withdrawing versus not offering cardiopulmonary resuscitation: Is there a difference?

Conflict between substitute decision makers (SDMs) and health care providers in the intensive care unit is commonly related to goals of treatment at the end of life. Based on recent court decisions, even medical consensus that ongoing treatment is not clinically indicated cannot justify withdrawal of mechanical ventilation without consent from the SDM. Cardiopulmonary resuscitation (CPR), similar to mechanical ventilation, is a life-sustaining therapy that can result in disagreement between SDMs and clinicians. In contrast to mechanical ventilation, in cases for which CPR is judged by the medical team to not be clinically indicated, there is no explicit or case law in Canada that dictates that withholding/not offering of CPR requires the consent of SDMs. In such cases, physicians can ethically and legally not offer CPR, even against SDM or patient wishes. To ensure that nonclinically indicated CPR is not inappropriately performed, hospitals should consider developing ‘scope of treatment’ forms that make it clear that even if CPR is desired, the individual components of resuscitation to be offered, if any, will be dictated by the medical team’s clinical assessment.     

Effectiveness of the Incredible Years Parenting Program for Families with Socioeconomically Disadvantaged and Ethnic Minority Backgrounds

Families with socioeconomically disadvantaged and ethnic minority backgrounds are often hard to reach for the prevention and treatment of disruptive child behavior problems. We examined whether the Incredible Years parenting intervention can successfully reach and benefit families with socioeconomic disadvantaged and ethnic minority backgrounds in the Netherlands. One hundred fifty-four families from a wide range of socioeconomic and ethnic backgrounds were recruited in an outpatient clinic for child and adolescent psychiatry and in elementary schools serving deprived neighborhoods. Families were randomly assigned to the BASIC Incredible Years parenting intervention or a waiting list control condition. Children were 3–8 years old (M = 5.59, SD = 1.35; 62% boys, 66% ethnic minorities) and 65% of the children met Diagnostic and Statistical Manual of Mental Disorders (4th ed., text rev.) criteria for oppositional defiant disorder, conduct disorder, and/or attention-deficit hyperactivity disorder. Incredible Years reduced parent-reported disruptive child behavior and teacher-reported hyperactive and inattentive child behavior and increased parent-reported use of praise and incentives and reduced harsh and inconsistent discipline. Incredible Years did not affect parent-reported hyperactive and inattentive child behavior; teacher-reported child conduct problems; and parent-reported use of appropriate discipline techniques, clear expectations, physical punishment, and parenting stress. Of importance, the effectiveness of Incredible Years did not differ across families with different socioeconomic and ethnic backgrounds. Effects were maintained at 3-month follow-up. This study shows that socioeconomically disadvantaged and ethnic minority families in disadvantaged neighborhoods can be engaged in and benefit from parenting interventions to reduce disruptive child behavior.     

Uncovering the genomic heterogeneity of multifocal breast cancer

Multifocal breast cancer (MFBC), defined as multiple synchronous unilateral lesions of invasive breast cancer, is relatively frequent and has been associated with more aggressive features than unifocal cancer. Here, we aimed to investigate the genomic heterogeneity between MFBC lesions sharing similar histopathological parameters. Characterization of different lesions from 36 patients with ductal MFBC involved the identification of non‐silent coding mutations in 360 protein‐coding genes (171 tumour and 36 matched normal samples). We selected only patients with lesions presenting the same grade, ER, and HER2 status. Mutations were classified as ‘oncogenic’ in the case of recurrent substitutions reported in COSMIC or truncating mutations affecting tumour suppressor genes. All mutations identified in a given patient were further interrogated in all samples from that patient through deep resequencing using an orthogonal platform. Whole‐genome rearrangement screen was further conducted in 8/36 patients. Twenty‐four patients (67%) had substitutions/indels shared by all their lesions, of which 11 carried the same mutations in all lesions, and 13 had lesions with both common and private mutations. Three‐quarters of those 24 patients shared oncogenic variants. The remaining 12 patients (33%) did not share any substitution/indels, with inter‐lesion heterogeneity observed for oncogenic mutation(s) in genes such as PIK3CA, TP53, GATA3, and PTEN. Genomically heterogeneous lesions tended to be further apart in the mammary gland than homogeneous lesions. Genome‐wide analyses of a limited number of patients identified a common somatic background in all studied MFBCs, including those with no mutation in common between the lesions. To conclude, as the number of molecular targeted therapies increases and trials driven by genomic screening are ongoing, our findings highlight the presence of genomic inter‐lesion heterogeneity in one‐third, despite similar pathological features. This implies that deeper molecular characterization of all MFBC lesions is warranted for the adequate management of those cancers. © 2015 The Authors. Pathological Society of Great Britain and Ireland.