Recent guidelines for the management of childhood pneumonia recommend narrow-spectrum antimicrobial agents (eg, ampicillin) for most children; however, few studies have directly compared the effectiveness of narrow-spectrum agents to the broader spectrum third-generation cephalosporins commonly used among children hospitalized with pneumonia.

By using data from 43 children’s hospitals in the United States, we demonstrate equivalent outcomes and costs for children hospitalized with pneumonia and treated empirically with either narrow- (ampicillin/penicillin) or broad-spectrum (ceftriaxone/cefotaxime) antimicrobial therapy. (Read the full article)

Existing data do not demonstrate a need for combination therapy after antimicrobial susceptibility data indicate adequate in vitro activity with β-lactam monotherapy. However, the role of empirical combination therapy for the treatment of Gram-negative bacteremia in children remains unsettled.

We conducted a retrospective, propensity-score matched study demonstrating no improvement in 10-day mortality of children who have Gram-negative bacteremia receiving empirical β-lactam and aminoglycoside combination therapy compared with β-lactam monotherapy, unless the bacteremic episode was attributable to a multidrug-resistant organism. (Read the full article)

Home oxygen has been safely incorporated into emergency department management of bronchiolitis in certain populations. After discharge, a small proportion of patients (2.7%–6%) require subsequent admission. For patients managed successfully as outpatients, pediatricians report variable practice styles and comfort levels.

Our results define the clinical course and outpatient burden associated with discharge on home oxygen. By using an integrated health care system, we captured slightly higher rates (9.4%) of subsequent admission and found fever to be associated with this outcome. (Read the full article)

Chorioamnionitis (CAM) is a major risk factor for early-onset neonatal sepsis. The Committee on the Fetus and Newborn recommends extending the duration of antimicrobial therapy in neonates exposed to CAM and intrapartum antibiotics if laboratory data are abnormal, even if culture results are sterile.

When managed by using a strategy similar to recent Committee on the Fetus and Newborn guidelines, a large number of term and late-preterm infants exposed to CAM who had sterile blood culture findings were treated with prolonged antibiotic therapy, subjected to additional invasive procedures, and had prolonged hospitalization. (Read the full article)

Animal studies document dose-dependent and duration-of-therapy-dependent fluoroquinolone cartilage toxicity in weight-bearing joints. Preliminary pediatric data collected after fluoroquinolone treatment and up to 1 year posttreatment in blinded and unblinded studies suggest the possibility of cartilage toxicity in children.

These are the first prospectively collected data on fluoroquinolone musculoskeletal safety collected posttherapy from randomized, comparative studies of respiratory tract infections and analyzed at 5 years. Long-term musculoskeletal adverse events occurred with equal frequency in both levofloxacin and comparator groups. (Read the full article)

In HIV-infected children, decisions to start antiretroviral therapy must weigh immunologic benefits against potential risks. Current guidelines recommend using CD4 percentage and age when deciding to start treatment. Population-level effects of these factors on immunologic recovery are unknown.

Starting antiretroviral therapy at higher CD4 percentages and younger ages maximizes potential for immunologic recovery. However, not all benefits are sustained, and viral failure may occur. Our results help clinicians better weigh immunologic benefits against viral failure risks. (Read the full article)

Phototherapy decreases bilirubin concentration in skin more rapidly than in blood. During and after phototherapy, transcutaneous bilirubin measurements are considered unreliable and therefore discouraged.

Transcutaneous bilirubin underestimates total serum bilirubin by 2.4 mg/dL (SD, 2.1 mg/dL) during the first 8 hours after phototherapy. This gives a safety margin of ~7 mg/dL below the treatment threshold to omit confirmatory blood sampling. (Read the full article)

Infants with Prader-Willi syndrome suffer from hypotonia, muscle weakness, and motor developmental delay and have increased fat mass combined with decreased muscle mass. Growth hormone improves body composition and motor development.

Ultrasound scans confirmed decreased muscle thickness in infants with Prader-Willi syndrome, which improved as result of growth hormone treatment. Muscle thickness was correlated to muscle strength and motor performance. Catch-up growth in muscle thickness was related to muscle use independent of growth hormone. (Read the full article)

Necrotizing enterocolitis is associated with high mortality and morbidity in premature infants. Anaerobic antimicrobial therapy has been associated with increased risk of intestinal strictures in a small randomized trial. Optimal antimicrobial therapy for necrotizing enterocolitis is unknown.

Anaerobic antimicrobial therapy was associated with increased risk of stricture formation. Infants with surgical necrotizing enterocolitis treated with anaerobic antimicrobial therapy had lower mortality. For infants with medical necrotizing enterocolitis, there was no added benefit associated with anaerobic antimicrobial therapy. (Read the full article)

Pediatric traumatic brain injury (TBI) contributes to impairments in functioning across multiple settings. Online family problem-solving therapy may be effective in reducing adolescent behavioral morbidity after TBI. However, less is known regarding maintenance of effects over time.

This large randomized clinical trial in adolescents with TBI is the only study to examine maintenance of treatment effects. Findings reveal that brief, online treatment may result in long-term improvements in child functioning, particularly among families of lower socioeconomic status. (Read the full article)

Smoking has been found to increase the risk of some specific congenital anomalies; however, results remain inconsistent. Nicotine replacement therapy (NRT) is increasingly being used as for smoking cessation in pregnancy although little is known about its association with congenital anomalies.

Being prescribed NRT while pregnant was not associated with major congenital anomalies (MCA), except a small increase in respiratory anomalies (3/1000 births). This must be considered in context of the rarity of MCAs and higher morbidities in the NRT group. (Read the full article)

Two prospective studies of children with septic arthritis have shown that the addition of dexamethasone to antibiotic therapy contributes to clinical and laboratory improvement. Nevertheless, the mainstay of treatment remains antibiotics alone.

This study, which was conducted outside a randomized controlled trial, demonstrates that children with septic arthritis treated early with a short course of adjuvant dexamethasone show earlier improvement in clinical and laboratory parameters than children treated with antibiotics alone. (Read the full article)

Since 2012, single low dose of primaquine (SLDPQ, 0.25mg/kg) has been recommended with artemisinin-based combination therapies, as first-line treatment of acute uncomplicated Plasmodium falciparum malaria, to interrupt its transmission, especially in low transmission settings of multidrug, including artemisinin, resistance. Policy makers in Cambodia have been reluctant to implement this recommendation due to primaquine safety concerns and lack of data on its efficacy.

In this randomized controlled trial, 109 Cambodians with acute uncomplicated P. falciparum malaria received dihydroartemisinin-piperaquine (DP) alone or combined with SLDPQ on the first treatment day. Transmission-blocking efficacy of SLDPQ was evaluated on Days 0, 1, 2, 3, 7, 14, 21, 28 and recrudescence by reverse transcriptase polymerase chain reaction (RT-PCR) (gametocyte prevalence) and membrane-feeding assays with Anopheles minimus mosquitoes (gametocyte infectivity). Without the influence of recrudescent infections, DP+SLDPQ reduced gametocyte carriage 3 fold compared to DP. Of 48 patients tested on Day 0, only three patients were infectious to mosquitoes (~6%). Post-treatment, three patients were infectious: on D14 (3.5%, 1/29), and on the first and seventh day of recrudescence (8.3%, 1/12 for each); this overall low infectivity precluded our ability to assess its transmission blocking efficacy.

Our study confirms effective gametocyte clearance of SLDPQ when combined with DP in multidrug resistant P. falciparum and the negative impact of recrudescent infections due to poor DP efficacy. Artesunate-mefloquine (ASMQ) has replaced DP and ASMQ-SLDPQ has been deployed to treat all P. falciparum symptomatic patients to further support the elimination of multidrug resistant P. falciparum in Cambodia.

Carbapenems are currently the preferred agents for the treatment of serious Acinetobacter infections. However, whether cefepime/cefpirome can be used to treat Acinetobacter bloodstream infection (BSI) if it is active against the causative pathogens is not clear. This study aimed to compare the efficacy of cefepime/cefpirome and carbapenem monotherapy in patients with Acinetobacter BSI. The population included 360 patients with monomicrobial Acinetobacter BSI receiving appropriate antimicrobial therapy admitted to four medical centres in Taiwan in 2012–2017. The predictors of 30-day mortality were determined by Cox regression analysis. The overall 30-day mortality rate in the appropriate antibiotic treatment group was 25.0% (90/360 patients), respectively. The crude 30-day mortality rates for cefepime/cefpirome and carbapenem therapy were 11.5% (7/61 patients) and 26.3% (21/80 patients), respectively. The patients receiving cefepime/cefpirome/carbapenem therapy were infected by Acinetobacter nosocomialis (51.8%), A. baumannii (18.4%) and A. pittii (12.1%). After adjusting for age, Sequential Organ Failure Assessment (SOFA) score, invasive procedures, and underlying diseases, cefepime/cefpirome therapy was not independently associated with a higher or lower 30-day mortality compared to the carbapenem therapy. SOFA score (hazard ratio [HR], 1.324; 95% confidence interval [CI], 1.137–1.543; P < 0.001) and neutropenia (HR, 7.060; 95% CI, 1.607–31.019; P = 0.010) were independent risk factors for 30-day mortality of patients receiving cefepime/cefpirome or carbapenem monotherapy. The incidence density of 30-day mortality for cefepime/cefpirome versus carbapenem therapy was 0.40% versus 1.04%. The therapeutic response of cefepime/cefpirome therapy was comparable to that of carbapenems among patients with Acinetobacter BSI receiving appropriate antimicrobial therapy.

Ibrexafungerp (formerly SCY-078) is a semisynthetic triterpenoid and potent (1->3)-β-D-glucan synthase inhibitor. We investigated the in vitro activity, pharmacokinetics, and in vivo efficacy of ibrexafungerp (SCY) alone and in combination with anti-mould triazole isavuconazole (ISA) against invasive pulmonary aspergillosis (IPA). The combination of ibrexafungerp and isavuconazole in in vitro studies resulted in an additive and synergistic interactions against Aspergillus spp. Plasma concentration-time curves of ibrexafungerp were compatible with linear dose proportional profile. In vivo efficacy was studied in a well established persistently neutropenic NZW rabbit model of experimental IPA. Treatment groups included untreated rabbits (UC) and rabbits receiving ibrexafungerp at 2.5(SCY2.5) and 7.5(SCY7.5) mg/kg/day, isavuconazole at 40(ISA40) mg/kg/day, or combinations of SCY2.5+ISA40 and SCY7.5+ISA40. The combination of SCY+ISA produced in vitro synergistic interaction. There was significant in vivo reduction of residual fungal burden, lung weights, and pulmonary infarct scores in SCY2.5+ISA40, SCY7.5+ISA40, and ISA40-treatment groups vs that of SCY2.5-treated, SCY7.5-treated and UC (p<0.01). Rabbits treated with SCY2.5+ISA40 and SCY7.5+ISA40 had prolonged survival in comparison to that of SCY2.5-, SCY7.5-, ISA40-treated or UC (p<0.05). Serum GMI and (1->3)-β-D-glucan levels significantly declined in animals treated with the combination of SCY7.5+ISA40 in comparison to those treated with SCY7.5 or ISA40 (p<0.05). Ibrexafungerp and isavuconazole combination demonstrated prolonged survival, decreased pulmonary injury, reduced residual fungal burden, lower GMI and (1->3)-β-D-glucan levels in comparison to those of single therapy for treatment of IPA. These findings provide an experimental foundation for clinical evaluation of the combination of ibrexafungerp and an anti-mould triazole for treatment of IPA.

Chagas disease, caused by the protozoan Trypanosoma cruzi, is one of the main causes of death due to cardiomyopathy and heart failure in Latin American countries. The treatment of Chagas disease is directed at eliminating the parasite, decreasing the probability of cardiomyopathy, and disrupting the disease transmission cycle. Benznidazole (BZ) and nifurtimox (NFX) are recognized as effective drugs for the treatment of Chagas disease by the World Health Organization, but both have high toxicity and limited efficacy, especially in the chronic disease phase. At low doses, aspirin (ASA) has been reported to protect against T. cruzi infection. We evaluated the effectiveness of BZ in combination with ASA at low doses during the acute disease phase and evaluated cardiovascular aspects and cardiac lesions in the chronic phase. ASA treatment prevented the cardiovascular dysfunction (hypertension and tachycardia) and typical cardiac lesions. Moreover, BZ+ASA-treated mice had a smaller cardiac fibrotic area than that in BZ-treated mice. These results were associated with an increase in the number of eosinophils and reticulocytes and level of nitric oxide in the plasma and cardiac tissue of ASA-treated mice relative to respective controls. These effects of ASA and BZ+ASA in chronically infected mice were inhibited by pretreatment with the LXA₄ receptor antagonist, Boc-2, indicating that the protective effects of ASA are mediated by ASA-triggered lipoxin. These results emphasize the importance of exploring new drug combinations for treatments of acute phase of Chagas disease that are beneficial for chronic patients.

Methicillin-resistant Staphylococcus aureus (MRSA) has grown to become a major burden on healthcare systems. The cumulation of limited therapeutic options and worsened patient outcomes with persistent MRSA bacteremia has driven research in optimizing its initial management. The guidelines published by the Infectious Disease of America currently recommend combination therapy for refractory MRSA bacteremia, but the utility of combining antibiotics from the start of therapy is under investigation. The alternative strategy of early use of a β-lactam antibiotics in combination with vancomycin upon initial MRSA bacteremia detection has shown promise. While this concept has gained international attention, providers should give this strategy serious consideration prior to implementation. The objective of this review is to examine retrospective and prospective evidence for early combination with vancomycin and β-lactam antibiotics, as well as explore potential consequences of combination therapy.

OBJECTIVES:

Our first aim was to examine baseline differences in body dissatisfaction, depression, and anxiety symptoms by gender, age, and Tanner (ie, pubertal) stage. Our second aim was to test for changes in youth symptoms over the first year of receiving gender-affirming hormone therapy. Our third aim was to examine potential differences in change over time by demographic and treatment characteristics. Youth experiences of suicidal ideation, suicide attempt, and nonsuicidal self-injury (NSSI) are also reported.

The FDA estimates that between 45 and 50 students at a Massachusetts school for students with autism, emotional disturbances, and intellectual disabilities are subjected to electrical shocks through electrodes attached to their skin.

Alejandro Hoberman
Jul 1, 1999; 104:79-86
ARTICLES

St. Joseph Medical Center has begun using an experimental treatment program called convalescent plasma therapy with a growing number of its COVID-19 positive patients.

Secretary of State Jeffrey Bullock has suspended the Delaware massage therapy license of Christopher D. Dorman in light of allegations of sexual assault made by several female clients.

The therapy involves taking antibodies from the blood of a person who has recovered from COVID-19 and transfusing those antibodies into an active coronavirus patient to help kickstart the immune system.

 The patient from Orai in Uttar Pradesh was admitted to the King George Medical University (KGMU) in Lucknow on April 26.

Therefore, an alternate therapeutic regimen for early deployment is critical, the vaccine-maker said in the statement.

A total of 396 people have recovered from coronavirus infection through early oxygen therapy at Chirayu Hospital in Madhya Pradesh's capital city Bhopal.

This project brings together National Centre for Cell Science (NCCS), Pune; Indian Institute of Technology, Indore, and Gurgaon-based PredOmix Technologies in a collaborative mode for a public health emergency.

The Redford Center, a California-based non-profit co-founded in 2005 by Robert Redford and his son, James, announced that every morning, from April 15-22, 2019, the organization will post an episode a day of "Renewable Therapy for Climate Anxiety," a conversational mini-series featuring Filmmaker, James Redford, and Matthew Nordan, clean energy investor and managing partner at MNL Partners. In each two-minute installment, the pair explores questions that nag environmentalists when it comes to renewable energy. Watch the first episode below.

The Redford Center, a California-based non-profit co-founded in 2005 by Robert Redford and his son, James, announced that every morning, from April 15-22, 2019, the organization will post an episode a day of "Renewable Therapy for Climate Anxiety," a conversational mini-series featuring Filmmaker, James Redford, and Matthew Nordan, clean energy investor and managing partner at MNL Partners. In each two-minute installment, the pair explores questions that nag environmentalists when it comes to renewable energy. Watch the first episode below.

The Redford Center, a California-based non-profit co-founded in 2005 by Robert Redford and his son, James, announced that every morning, from April 15-22, 2019, the organization will post an episode a day of "Renewable Therapy for Climate Anxiety," a conversational mini-series featuring Filmmaker, James Redford, and Matthew Nordan, clean energy investor and managing partner at MNL Partners. In each two-minute installment, the pair explores questions that nag environmentalists when it comes to renewable energy. Watch the first episode below.

Zoa took to Instagram and shared photos from the hospital while donating the blood.

In his new book Upheaval, polymath Jared Diamond says nations need a special kind of therapy to solve big problems like climate change, Brexit and nuclear proliferation

A non-profit organization brings dogs to the Buffalo/Niagra airport to help relieve the stress of holiday traveling. Diane Hodges reports.

Many people are turning to virtual therapy and mental health apps to cope with the stress of the coronavirus pandemic, but they may not be as helpful as talking face to face

Title: Two-Drug Therapy Helped Kids With Type 2 Diabetes
Category: Health News
Created: 4/29/2012 6:05:00 PM
Last Editorial Review: 4/30/2012 12:00:00 AM

Title: Study: Gene Therapy for HIV Safe, But Effectiveness Still Unclear
Category: Health News
Created: 5/2/2012 4:05:00 PM
Last Editorial Review: 5/3/2012 12:00:00 AM

Title: Mindfulness Therapy May Help Ease Recurrent Depression
Category: Health News
Created: 4/27/2016 12:00:00 AM
Last Editorial Review: 4/28/2016 12:00:00 AM

Title: Gene Therapy May Help Fight Tough-to-Treat Blood Cancer
Category: Health News
Created: 5/1/2019 12:00:00 AM
Last Editorial Review: 5/2/2019 12:00:00 AM

Adjust oxygen and fluid therapy thresholds for pregnant patients with severe disease, experts advise; early use of a high-flow nasal cannula and prone positioning may help avoid mechanical ventilation.

Title: How Does Cognitive Behavioral Therapy Treat Depression?
Category: Procedures and Tests
Created: 4/29/2020 12:00:00 AM
Last Editorial Review: 4/29/2020 12:00:00 AM

Title: New Study Shakes Up Thinking on Hormone Replacement Therapy
Category: Health News
Created: 12/13/2019 12:00:00 AM
Last Editorial Review: 12/13/2019 12:00:00 AM

Title: AHA News: Estrogen Therapy in Early Menopause May Help Keep Arteries Clear
Category: Health News
Created: 3/3/2020 12:00:00 AM
Last Editorial Review: 3/4/2020 12:00:00 AM

Title: Therapy by Phone Helps Parkinson's Patients Manage Depression
Category: Health News
Created: 4/10/2020 12:00:00 AM
Last Editorial Review: 4/13/2020 12:00:00 AM

Title: Is Electroconvulsive (ECT) Therapy Safe?
Category: Procedures and Tests
Created: 3/6/2020 12:00:00 AM
Last Editorial Review: 3/6/2020 12:00:00 AM

Expression of the DNA/RNA helicase schlafen family member 11 (SLFN11) has been identified as a sensitizer of tumor cells to DNA-damaging agents including platinum chemotherapy. We assessed the impact of SLFN11 expression on response to platinum chemotherapy and outcomes in patients with metastatic castration-resistant prostate cancer (CRPC). Tumor expression of SLFN11 was assessed in 41 patients with CRPC treated with platinum chemotherapy by RNA sequencing (RNA-seq) of metastatic biopsy tissue (n = 27) and/or immunofluorescence in circulating tumor cells (CTC; n = 20). Cox regression and Kaplan–Meier methods were used to evaluate the association of SLFN11 expression with radiographic progression-free survival (rPFS) and overall survival (OS). Multivariate analysis included tumor histology (i.e., adenocarcinoma or neuroendocrine) and the presence or absence of DNA repair aberrations. Patient-derived organoids with SLFN11 expression and after knockout by CRISPR-Cas9 were treated with platinum and assessed for changes in dose response. Patients were treated with platinum combination (N = 38) or platinum monotherapy (N = 3). Median lines of prior therapy for CRPC was two. Median OS was 8.7 months. Overexpression of SLFN11 in metastatic tumors by RNA-seq was associated with longer rPFS compared with those without overexpression (6.9 vs. 2.8 months, HR = 3.72; 95% confidence interval (CI), 1.56–8.87; P < 0.001); similar results were observed for patients with SLFN11-positive versus SLFN11-negative CTCs (rPFS 6.0 vs. 2.2 months, HR = 4.02; 95% CI, 0.77–20.86; P = 0.002). A prostate-specific antigen (PSA) decline of ≥50% was observed in all patients with SLFN11 overexpression. No association was observed between SLFN11 expression and OS. On multivariable analysis, SLFN11 was an independent factor associated with rPFS on platinum therapy. Platinum response of organoids expressing SLFN11 was reduced after SLFN11 knockout. Our data suggest that SLFN11 expression might identify patients with CRPC with a better response to platinum chemotherapy independent of histology or other genomic alterations. Additional studies, also in the context of PARP inhibitors, are warranted.

Physical and chemical DNA-damaging agents are used widely in the treatment of cancer. Double-strand break (DSB) lesions in DNA are the most deleterious form of damage and, if left unrepaired, can effectively kill cancer cells. DNA-dependent protein kinase (DNA-PK) is a critical component of nonhomologous end joining (NHEJ), one of the two major pathways for DSB repair. Although DNA-PK has been considered an attractive target for cancer therapy, the development of pharmacologic DNA-PK inhibitors for clinical use has been lagging. Here, we report the discovery and characterization of a potent, selective, and orally bioavailable DNA-PK inhibitor, M3814 (peposertib), and provide in vivo proof of principle for DNA-PK inhibition as a novel approach to combination radiotherapy. M3814 potently inhibits DNA-PK catalytic activity and sensitizes multiple cancer cell lines to ionizing radiation (IR) and DSB-inducing agents. Inhibition of DNA-PK autophosphorylation in cancer cells or xenograft tumors led to an increased number of persistent DSBs. Oral administration of M3814 to two xenograft models of human cancer, using a clinically established 6-week fractionated radiation schedule, strongly potentiated the antitumor activity of IR and led to complete tumor regression at nontoxic doses. Our results strongly support DNA-PK inhibition as a novel approach for the combination radiotherapy of cancer. M3814 is currently under investigation in combination with radiotherapy in clinical trials.

Cholesterol/sphingolipid-rich membrane domains, known as lipid rafts or membrane rafts, play a critical role in the compartmentalization of signaling pathways. Physical segregation of proteins in lipid rafts may modulate the accessibility of proteins to regulatory or effector molecules. Thus, lipid rafts serve as sorting platforms and hubs for signal transduction proteins. Cancer cells contain higher levels of intracellular cholesterol and lipid rafts than their normal non-tumorigenic counterparts. Many signal transduction processes involved in cancer development (insulin-like growth factor system and phosphatidylinositol 3-kinase-AKT) and metastasis [cluster of differentiation (CD)44] are dependent on or modulated by lipid rafts. Additional proteins playing an important role in several malignant cancers (e.g., transmembrane glycoprotein mucin 1) are also being detected in association with lipid rafts, suggesting a major role of lipid rafts in tumor progression. Conversely, lipid rafts also serve as scaffolds for the recruitment and clustering of Fas/CD95 death receptors and downstream signaling molecules leading to cell death-promoting raft platforms. The partition of death receptors and downstream signaling molecules in aggregated lipid rafts has led to the formation of the so-called cluster of apoptotic signaling molecule-enriched rafts, or CASMER, which leads to apoptosis amplification and can be pharmacologically modulated. These death-promoting rafts can be viewed as a linchpin from which apoptotic signals are launched. In this review, we discuss the involvement of lipid rafts in major signaling processes in cancer cells, including cell survival, cell death, and metastasis, and we consider the potential of lipid raft modulation as a promising target in cancer therapy.

For decades inhaled corticosteroids have been central to the management of asthma and are proven to be effective in maintaining symptom control, reducing exacerbations and preserving quality of life through mediation of airway inflammation. However, a small minority of patients have disease which is refractory to high dose inhaled corticosteroid (ICS) therapy and require additional oral corticosteroids to achieve acceptable control of symptoms and exacerbations. Severe asthma represents less than 10% of the total asthma population [1] but is the most serious, life-affecting and costly form of the condition [2].

Introduction

Inhaled corticosteroids (ICS) achieve disease control in the majority of asthmatic patients, although adherence to prescribed ICS is often poor. Patients with severe eosinophilic asthma may require treatment with oral corticosteroids (OCS) and/or biologic agents such as mepolizumab. It is unknown if ICS adherence changes on, or alters clinical response to, biologic therapy.