Otorrhea is common in children with tympanostomy tubes: annually, 2 of 3 children develop 1 or more episodes. Antibiotic-glucocorticoid eardrops are the most effective treatment in both the short- and long-term.

Treatment with antibiotic-glucocorticoid eardrops costs less than oral antibiotics and initial observation in children with tympanostomy tubes who develop otorrhea. Non–health care costs constitute a substantial proportion of the total costs of this condition. (Read the full article)

Street youth demonstrate elevated mortality compared with the general adolescent and young adult population. Suicide is a leading cause of death among street youth. Many street youth have experienced childhood maltreatment, including abuse and neglect.

In this prospective cohort of street youth, self-reported attempted suicide and history of childhood maltreatment were common. Individuals who experienced childhood physical abuse, emotional abuse, or emotional neglect were at highest risk of attempting suicide. (Read the full article)

Increasing percentages of youth are living with chronic medical conditions. Although adolescents face peak risks for onset and intensification of alcohol and marijuana use, we know little about these behaviors and their associations with treatment adherence among chronically ill youth.

This study quantifies alcohol and marijuana use behaviors among a heterogeneous sample of chronically ill youth in aggregate and by condition, and measures associations between alcohol use/binge drinking and knowledge about alcohol interactions with medications/laboratory tests and also treatment nonadherence. (Read the full article)

Strictly-defined pediatric bipolar I disorder (BP-I) is a serious condition. Although lithium is a benchmark treatment and has shown effectiveness in adults for decades, no definitive efficacy or long-term safety studies had been performed in pediatric patients with BP-I.

This study provides evidence to support the efficacy of lithium in the acute treatment of youths with BP-I who are currently in a manic or mixed state. Lithium had an adverse effect profile that was acceptable for most patients. (Read the full article)

National guidelines recommend testing and prophylaxis for chlamydia, gonorrhea, and pregnancy for adolescent sexual assault victims. Little is known about rates of testing and prophylaxis in adolescent victims of sexual assault evaluated in pediatric emergency departments.

There is significant variation in testing and prophylaxis practices in the pediatric emergency department evaluation of adolescent victims of sexual assault. Adolescents cared for in emergency departments with clinical pathways are more likely to receive recommended prophylaxis. (Read the full article)

Quantum machine learning, an emerging field that combines machine learning and quantum physics, is the focus of research to discover possible treatments for COVID-19, according to Penn State researchers, who believe that this method could be faster and more economical than the current methods used for drug discovery.

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.

Mucormycosis is a life-threatening infection with high mortality that occurs predominantly in immunocompromised patients. Manogepix (MGX) is a novel antifungal that targets Gwt1, an early step in the conserved glycosylphosphotidyl inositol (GPI) post-translational modification pathway of surface proteins in eukaryotic cells. Inhibition of inositol acylation by MGX results in pleiotropic effects including inhibition of maturation of GPI-anchored proteins necessary for growth and virulence. MGX has been previously shown to have in vitro activity against some strains of Mucorales. Here we assessed the in vivo activity of the prodrug fosmanogepix, currently in clinical development for the treatment of invasive fungal infections, against two Rhizopus arrhizus strains with high (4.0 μg/ml) and low (0.25 μg/ml) minimum effective concentration (MEC) values. In both invasive pulmonary infection models, treatment of mice with 78 mg/kg or 104 mg/kg fosmanogepix, along with 1-aminobenzotriazole to enhance the serum half-live of MGX in mice, significantly increased median survival time and prolonged overall survival by day 21 post infection when compared to placebo. In addition, administration of fosmanogepix resulted in a 1-2 log reduction in both lung and kidney fungal burden. For the 104 mg/kg fosmanogepix dose, tissue clearance and survival were comparable to clinically relevant doses of isavuconazole (ISA), which is FDA approved for the treatment of mucormycosis. These results support continued development of fosmanogepix as a first in class treatment for invasive mucormycosis.

Telacebec (Q203) is a new anti-tubercular drug with extremely potent activity against Mycobacterium ulcerans. Here, we explored the treatment-shortening potential of Q203 alone or in combination with rifampin (RIF) in a mouse footpad infection model. The first study compared Q203 at 5 and 10 mg/kg doses alone and with rifampin. Q203 alone rendered most mouse footpads culture-negative in 2 weeks. Combining Q203 with rifampin resulted in relapse-free cure 24 weeks after completing 2 weeks of treatment, compared to a 25% relapse rate in mice receiving RIF+clarithromycin, the current standard of care, for 4 weeks.

The second study explored the dose-ranging activity of Q203 alone and with RIF, including the extended activity of Q203 after treatment discontinuation. The bactericidal activity of Q203 persisted for ≥ 4 weeks beyond the last dose. All mice receiving just 1 week of Q203 at 2-10 mg/kg were culture-negative 4 weeks after stopping treatment. Mice receiving 2 weeks of Q203 at 0.5, 2 and 10 mg/kg were culture-negative 4 weeks after treatment. RIF did not increase the efficacy of Q203. A pharmacokinetics sub-study revealed that Q203 doses of 2-10 mg/kg in mice produce plasma concentrations similar to those produced by 100-300 mg doses in humans, with no adverse effect of RIF on Q203 concentrations.

These results indicate the extraordinary potential of Q203 to reduce the duration of treatment necessary for cure to ≤ 1 week (or 5 doses of 2-10 mg/kg) in our mouse footpad infection model and warrant further evaluation of Q203 in clinical trials.

Polymyxins are increasingly used as the critical last-resort therapeutic options for multidrug-resistant gram-negative bacteria. Unfortunately, polymyxin resistance has increased gradually for the last few years. Although studies on mechanisms of polymyxin are expanding, system-wide analyses of the underlying mechanism for polymyxin resistance and stress response are still lacking. To understand how Klebsiella pneumoniae adapt to colistin (polymyxin E) pressure, we carried out proteomic analysis of Klebsiella pneumoniae strain cultured with different concentrations of colistin. Our results showed that the proteomic responses to colistin treatment in Klebsiella pneumoniae involving several pathways, including (i) gluconeogenesis and TCA cycle; (ii) arginine biosynthesis; (iii) porphyrin and chlorophyll metabolism; and (iv) enterobactin biosynthesis. Interestingly, decreased abundance of class A β-lactamases including TEM, SHV-11, SHV-4 were observed in cells treated with colistin. Moreover, we also present comprehensive proteome atlases of paired polymyxin-susceptible and -resistant Klebsiella pneumoniae strains. The polymyxin-resistant strain Ci, a mutant of Klebsiella pneumoniae ATCC BAA 2146, showed missense mutation in crrB. The crrB mutant Ci, which displayed lipid A modification with 4-amino-4-deoxy-L-arabinose (L-Ara4N) and palmitoylation, showed striking increases of CrrAB, PmrAB, PhoPQ, ArnBCADT and PagP. We hypothesize that crrB mutations induce elevated expression of the arnBCADTEF operon and pagP via PmrAB and PhoPQ. Moreover, multidrug efflux pump KexD, which was induced by crrB mutation, also contributed to colistin resistance. Overall, our results demonstrated proteomic responses to colistin treatment and the mechanism of CrrB-mediate colistin resistance, which may further offer valuable information to manage polymyxin resistance.

There are limited treatment options for enterococcal urinary tract infections, especially vancomycin-resistant Enterococcus (VRE). Oral fosfomycin is a potential option, although limited data are available guiding dosing and susceptibility. We undertook pharmacodynamic profiling of fosfomycin against E. faecalis and E. faecium isolates using a dynamic in vitro bladder infection model. Eighty-four isolates underwent fosfomycin agar dilution susceptibility testing (E. faecalis MIC_50/90 32/64 μg/mL; E. faecium MIC_50/90 64/128 μg/mL). Sixteen isolates (including E. faecalis ATCC 29212 and E. faecium ATCC 35667) were chosen to reflect the MIC range and tested in the bladder infection model with synthetic human urine (SHU). Under drug-free conditions, E. faecium demonstrated greater growth restriction in SHU compared to E. faecalis (E. faecium maximal growth 5.8 ± 0.6 log₁₀ CFU/mL; E. faecalis 8.0 ± 1.0 log₁₀ CFU/mL). Isolates were exposed to high and low fosfomycin urinary concentrations after a single dose, and two-doses given daily with low urinary exposure. Simulated concentrations closely matched the target (bias 2.3%). E. faecalis isolates required greater fosfomycin exposure for 3 log₁₀ kill from the starting inoculum compared with E. faecium. The fAUC_0-72/MIC and f%T > MIC_0-72 for E. faecalis was 672 and 70%, compared to 216 and 51% for E. faecium, respectively. There was no rise in fosfomycin MIC post-exposure. Two doses of fosfomycin with low urinary concentrations resulted in equivalent growth inhibition to a single dose with high urinary concentrations. With this urinary exposure, fosfomycin was effective in promoting suppression of regrowth (>3 log₁₀ kill) in the majority of isolates.

Clostridioides difficile, the leading cause of nosocomial infections, is an urgent health threat worldwide. The increased incidence and severity of disease, the high recurrence rates, and the dearth of effective anticlostridial drugs have created an urgent need for new therapeutic agents. In an effort to discover new drugs for treatment of Clostridioides difficile infections (CDIs), we investigated a panel of FDA-approved antiparasitic drugs against C. difficile and identified diiodohydroxyquinoline (DIHQ), an FDA-approved oral antiamoebic drug. DIHQ exhibited potent activity against 39 C. difficile isolates, inhibiting growth of 50% and 90% of these isolates at the concentrations of 0.5 μg/mL and 2 μg/mL, respectively. In a time-kill assay, DIHQ was superior to vancomycin and metronidazole, reducing a high bacterial inoculum by 3-log₁₀ within six hours. Furthermore, DIHQ reacted synergistically with vancomycin and metronidazole against C. difficile in vitro. Moreover, at subinhibitory concentrations, DIHQ was superior to vancomycin and metronidazole in inhibiting two key virulence factors of C. difficile, toxin production and spore formation. Additionally, DIHQ did not inhibit growth of key species that compose the host intestinal microbiota, such as Bacteroides, Bifidobacterium and Lactobacillus spp. Collectively, our results indicate that DIHQ is a promising anticlostridial drug that warrants further investigation as a new therapeutic for CDIs.

Tedizolid has demonstrated its efficacy and safety in clinical trials, however, data concerning its tolerability in long-term treatments is scarce. The aim of the study was to assess the indications and to describe the long-term safety profile of tedizolid.

A multicentric, retrospective study of patients who received tedizolid for more than 6-days was conducted. Adverse events (AEs) were identified from patients' medical records and laboratory data. The World Health Organization causality categories were used to discern AEs probably associated with tedizolid.

Eighty-one patients, treated with tedizolid 200mg once-daily for a median (IQR) duration of 28 (14-59) days, were included, 36 (44.4%) had previously received linezolid. Most common reasons for selecting tedizolid were to avoid linezolid potential toxicities or interactions (53.1%) or due to previous linezolid-related toxicities (27.2%). Most common indications were off-label, including prosthetic joint infections, osteomyelitis and respiratory infections (77.8%). Overall, 9/81 patients (11.1%) experienced a probably associated AE. Two patients (2.5%) developed gastrointestinal disorders, 1 (1.2%) anemia and 6 thrombocytopenia (7.4%) after a median (IQR) duration of treatment of 26.5 (17-58.5) days. Four (5%) patients discontinued tedizolid due to AEs. Among 23 patients with chronic renal failure (CRF) the rate of mielotoxicity was 17.4% and only 8.7% had to stop tedizolid and 20 out of 22 with previous linezolid-associated toxicity had no AE.

Long-term tedizolid treatments had good tolerance with rates of gastrointestinal AE and hematological toxicity lower than those reported with linezolid, particularly in patients with CRF and in those with a previous history of linezolid-associated toxicity.

Methicillin-resistant Staphylococcus aureus (MRSA) bloodstream infections (BSI) are associated with substantial morbidity and mortality. Monotherapy with first-line antimicrobials such as vancomycin (VAN; glycopeptide) and daptomycin (DAP; lipopeptide) are inadequate in some cases due to reduced antibiotic susceptibilities or therapeutic failure. In recent years, β-lactam antibiotics have emerged as a potential option for combination therapy with VAN/DAP that may meet an unmet therapeutic need for MRSA BSI. Ceftaroline (CPT), the only commercially available β-lactam in the United States with intrinsic in vitro activity against MRSA, has been increasingly studied in the setting of VAN and DAP failures. Novel combinations of first-line agents (VAN and DAP) with β-lactams have been the subject of many recent investigations due to in vitro findings such as the "see-saw effect", where β-lactam susceptibility may be improved in the presence of decreased glycopeptide and lipopeptide susceptibility. The combination of CPT and DAP, in particular, has become the focus of many scientific evaluations, due to intrinsic anti-MRSA activities and potent in vitro synergistic activity against various MRSA strains. This article reviews the available literature describing these innovative therapeutic approaches for MRSA BSI, focusing on preclinical and clinical studies, and evaluates the potential benefits and limitations of each strategy.

The currently unfolding coronavirus pandemic threatens health systems and economies worldwide....

A case of M. leprae rifampicin resistance after irregular anti-leprosy treatments since 1971 is reported. Whole-genome sequencing from four longitudinal samples indicated relapse due to acquired rifampicin resistance and not to reinfection with another strain. A putative compensatory mutation in rpoC was also detected. Clinical improvement was achieved using an alternative therapy.

Exploring different ways of minimising linezolid toxicity without compromising efficacy is a major quest in the treatment of drug resistant tuberculosis (TB)....

We thank Kim and colleagues for their interest in our study....

Penn State Health has enrolled its first COVID-19 patient into an experimental treatment program called convalescent plasma therapy.

G. C. Liggins
Oct 1, 1972; 50:515-525
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C. Michael Cotten
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Agency: DOT Closing Date: 5/19/2020

Agency: DOC Closing Date: 5/18/2020

Agency: CYF Closing Date: 6/30/2020

NEW CASTLE (July 24, 2018) – Following a 14-month review of Delaware’s opioid use disorder treatment system, a research team from the Johns Hopkins Bloomberg School of Public Health and the Bloomberg American Health Initiative today recommended four major strategies to achieve the state’s goal of a system of care that is accessible, evidence-based, individualized, […]

NEW CASTLE (Oct. 2, 2018) – The Department of Health and Social Services’ Division of Substance Abuse and Mental Health (DSAMH) last week launched its online referral network – Delaware Treatment and Referral Network (DTRN) – allowing Delaware health care providers seeking substance use disorder treatment or mental health services for their patients to make […]

NEW CASTLE (March 13, 2019) – Health and public safety officials are urging people in active use of heroin or other opioids and their families to seek immediate treatment and acquire the overdose-reversing medication naloxone on hand in the wake of three suspected heroin overdose deaths in five days in Sussex County involving the same […]

NEW CASTLE (April 25, 2019) – The Delaware Department of Health and Social Services (DHSS) today announced that Delaware is one of five states selected to partner with the national nonprofit Shatterproof in the development of a new pilot rating system designed to measure quality in addiction treatment programs. Delaware was selected due to the […]

2019 Recovery MonthEvent includes recovery walk, treatment information, live performances and recovery stories WILMINGTON (Sept. 19, 2019) –The Treatment Access Center (TASC), the primary liaison between the Department of Health and Social Services’ Division of Substance Abuse and Mental Health (DSAMH) and the criminal justice system, will host its first event celebrating Recovery Month. Celebrating […]

NEW CASTLE (Sept. 26, 2019) – The Centers for Medicare and Medicaid Services (CMS) recently awarded the Delaware Department of Health and Social Services a $3.58 million planning grant to increase the treatment capacity of Medicaid providers to deliver substance use disorder treatment and recovery services to Delawareans in need. Delaware was one of 15 […]

Terming this as one of the first known antibodies to neutralize SARS-CoV-2, Jason McLellan, associate professor of molecular biosciences at UT Austin and co-senior author, made a reference to the virus that causes COVID-19.

Australian authorities have reported a spike in drug smuggling – but not the kind they usually deal with. Aussies are importing hydroxychloroquine, an anti-malarial medication used as a controversial antidote to Covid-19.
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•An in silico clinical trial is underway with the 3DEXPERIENCE platform to evaluate the Living Heart simulated 3D heart for transforming how new devices can be tested •Five-year extension of their collaborative research agreement aims to spur medical device innovation by enabling innovative, new product designs •Both Dassault Systèmes and the FDA recognize the transformative impact of modeling and simulation on public health and patient safety

When the world’s largest working advanced digestion plant opened last month, it showed the power- hungry process of treating waste in the $360 billion water industry can be self-sufficient in terms of energy use.

Extracting energy from “processed poo” to help power homes in the Birmingham area is what Severn Trent Plc, Britain’s second-largest publicly traded water company, is now doing to generate a cost-saving renewable gas.

In Woods Building Services v Milton Keynes Council [2015] EWHC 2011 (TCC), the High Court upheld a challenge by an unsuccessful bidder (“Woods”) of a tender process undertaken by Milton Keynes Council (the “Council”) on the g...

Introduction In a recent judgment on an application to vary consent orders relating to the establishment of a confidentiality ring (Bombardier Transportation UK Limited v Merseytravel [2017] EWHC 726 (TCC)), the court decided that despite some conce...

This week, an Advocate General gave a landmark opinion that the VAT exemption for the management of certain special investment funds can apply to property management, as well as to other fund management services. The opinion represents a completely ...

Following the publication by the European Commission of the conclusions on best available techniques (BAT) in the waste sector on 17th August 2018, the operators are required to submit a reconsideration file (“dossier de réexamen”...

The UK government announced at the March Budget that they intend to introduce a requirement for large businesses to notify HMRC where they adopt an “uncertain tax treatment”.  The proposal is designed to improve HMRC’s ability...

In line with the Federal Ministry of Finance's press release dated 3 April 2020, Germany and Austria have concluded a mutual agreement for Covid 19-related home office activities on 15 April 2020, which relates to the application of the Double Tax ...

Six critically ill coronavirus patients in Israel who were considered high-risk for mortality were treated with Pluristem and survived.

Chinese scientists say they have identified two antibodies that could be candidates for a cocktail treatment for patients with different strains of the coronavirus.The antibodies were found to work together as a team to prevent the virus from latching onto a host cell, in a study led by Chinese Centre for Disease Control and Prevention director George Fu Gao with collaborators from across the country.They said that even a mutant strain was likely to be neutralised because the antibodies…

The Indonesian government said on Thursday it was seeking clarification and investigation from the Chinese and South Korean governments over the deaths of four Indonesian seamen working on a Chinese longliner.The request follows South Korean media reports quoting Indonesian crew members of Chinese-flagged Long Xing 629 tuna longliner as saying their crewmates were denied medical treatment and subjected to physical abuse.Foreign Minister Retno Marsudi told a press conference that she spoke with…

Bomet Governor, Isaac Ruto who was being treated for injuries at Nairobi Hospital after clashes with police will be transferred a hospital in South Africa, a report says..