Immunomodulatory Effects of Modified Bovine Colostrum, Whey, and Their Combination with Other Natural Products: Effects on Human Peripheral Blood Mononuclear Cells.

Background: Many natural products have immunomodulatory properties. However, the mechanism of immunomodulatory activities are poorly understood. Objectives: This study evaluated the influence of bovine colostrum products, a whey product, or their combinations with other natural products on human peripheral blood mononuclear cells' (PBMC) ability to produce cytokines upon activation. Methods: PBMCs were pretreated with ultrafiltered colostrum, nano-filtered bovine colostrum, egg yolk extract, a botanical blend, colostrum + egg yolk extract, colostrum + egg yolk + botanical blend, and fermented whey and then stimulated with lipopolysaccharide or phytohemagglutinin. Cytokine production was measured by the Luminex assay. Results: All study products demonstrated immunomodulatory properties by regulating cytokines production by activated PBMCs. Ultrafiltered colostrum alone displayed the highest immune stimulatory activity. It stimulated proinflammatory cytokine production by lipopolysaccharide-activated PBMCs and suppressed cytokine production by phytohemagglutinin-activated cells. Other study products mainly suppressed cytokine release by both cell types. The immunomodulatory properties depended upon the dose of the products used in the study. Conclusions: All tested products modulated innate and adaptive immune cell activities. Most of the products demonstrated anti-inflammatory properties, except ultrafiltered colostrum, which stimulated the lipopolysaccharide-activated PBMC production of inflammatory cytokines. These products can be potentially used to support overall immune health.

Effects of Chicory (Cichorium intybus L.) Extract on Male Rat Reproductive System, Pregnancy and Offspring Development.

BACKGROUND: We recently reported that extract prepared from the aerial part of Cichorium intybus L. (CE) possesses hepatoprotective, hypolipidemic, and hypoglycemic properties. This paper focuses on the effects of CE on the male rat reproductive system and the effects of this treatment on pregnancy and offspring development. METHODS: The experimental male rats received 100 mg/kg bw/day, 500 mg/kg bw/day, and 1000 mg/kg bw/day of CE orally for 60 consecutive days. Rats that received tap water were used as controls. After treatment, we evaluated the effects of CE on the male reproductive system, fertility, and offspring development. RESULTS: For CE-treated male rats, there was a significant increase in the (1) diameter of seminiferous tubules, (2) spermatogenic index, (3) number of total and motile spermatozoa, and (4) testosterone levels. Additionally, there was a decrease in the pre- and post-implantation death of the embryos in the CE-treated group. All pups born from CE-treated males demonstrated normal development. CONCLUSIONS: CE treatment significantly improved male reproductive functions. No adverse effects on pregnancy and offspring development were observed when males were treated with CE. Further clinical evaluation of CE should lead to the development of a safe and effective phytodrug for treating male infertility.

A role for immature myeloid cells in immune senescence.

The reduced efficiency of the mammalian immune system with aging increases host susceptibility to infectious and autoimmune diseases. However, the mechanisms responsible for these pathologic changes are not well understood. In this study, we demonstrate that the bone marrow, blood, and secondary lymphoid organs of healthy aged mice possess increased numbers of immature myeloid cells that are phenotypically similar to myeloid-derived suppressor cells found in lymphoid organs of mice with progressive tumors and other pathologic conditions associated with chronic inflammation. These cells are characterized by the presence of Gr1 and CD11b markers on their surfaces. Gr1(+)CD11b(+) cells isolated from aged mice possess an ability to suppress T cell proliferation/activation and produce heightened levels of proinflammatory cytokines, both constitutively and upon activation, including IL-12, which promotes an excessive production of IFN-γ. IFN-γ priming is essential for excessive proinflammatory cytokine production and the suppressive activities by Gr1(+)CD11b(+) cells from aged mice. These cells suppress T cell proliferation through an NO-dependent mechanism, as depletion of splenic Gr1(+) cells reduces NO levels and restores T cell proliferation. Insights into mechanisms responsible for the proinflammatory and immune suppressive activities of Gr1(+)CD11b(+) cells from aged mice have uncovered a defective PI3K-Akt signaling pathway, leading to a reduced Akt-dependent inactivation of GSK3ß. Our data demonstrate that abnormal activities of the Gr1(+)CD11b(+) myeloid cell population from aged mice could play a significant role in the mechanisms responsible for immune senescence.

Probiotics and Their Bioproducts: A Promising Approach for Targeting Methicillin-Resistant Staphylococcus aureus and Vancomycin-Resistant Enterococcus.

Antibiotic resistance is a serious global health problem that poses a threat to the successful treatment of various bacterial infections, especially those caused by methicillin-resistant Staphylococcus aureus (MRSA) and vancomycin-resistant Enterococcus (VRE). Conventional treatment of MRSA and VRE infections is challenging and often requires alternative or combination therapies that may have limited efficacy, higher costs, and/or more adverse effects. Therefore, there is an urgent need to find new strategies to combat antibiotic-resistant bacteria. Probiotics and antimicrobial peptides (AMPs) are two promising approaches that have shown potential benefits in various diseases. Probiotics are live microorganisms that confer health benefits to the host when administered in adequate amounts. AMPs, usually produced with probiotic bacteria, are short amino acid sequences that have broad-spectrum activity against bacteria, fungi, viruses, and parasites. Both probiotics and AMPs can modulate the host immune system, inhibit the growth and adhesion of pathogens, disrupt biofilms, and enhance intestinal barrier function. In this paper, we review the current knowledge on the role of probiotics and AMPs in targeting multi-drug-resistant bacteria, with a focus on MRSA and VRE. In addition, we discuss future directions for the clinical use of probiotics.

Current use of complementary and conventional medicine for treatment of pediatric patients with gastrointestinal disorders.

Infants, children, and adolescents are at risk of experiencing a multitude of gastrointestinal disorders (GID). These disorders can adversely affect the quality of life or be life-threatening. Various interventions that span the conventional and complementary therapeutic categories have been developed. Nowadays, parents increasingly seek complementary options for their children to use concurrently with conventional therapies. Due to the high prevalence and morbidity of diarrhea, constipation, and irritable bowel syndrome (IBS) in children, in this review, we decided to focus on the current state of the evidence for conventional and complementary therapies used for the treatment of these diseases in children. Diarrhea treatment focuses on the identification of the cause and fluid management. Oral rehydration with supplementation of deficient micronutrients, especially zinc, is well established and recommended. Some probiotic strains have shown promise in reducing the duration of diarrhea. For the management of constipation, available clinical trials are insufficient for conclusive recommendations of dietary modifications, including increased use of fruit juice, fiber, and fluid. However, the role of laxatives as conventional treatment is becoming more established. Polyethylene glycol is the most studied, with lactulose, milk of magnesia, mineral oil, bisacodyl, and senna presenting as viable alternatives. Conventional treatments of the abdominal pain associated with IBS are poorly studied in children. Available studies investigating the effectiveness of antidepressants on abdominal pain in children with IBS were inconclusive. At the same time, probiotics and peppermint oil have a fair record of benefits and safety. The overall body of evidence indicates that a careful balance of conventional and complementary treatment strategies may be required to manage gastrointestinal conditions in children.

Drug exposure during pregnancy: Current understanding and approaches to measure maternal-fetal drug exposure.

Prescription drug use is prevalent during pregnancy, yet there is limited knowledge about maternal-fetal safety and efficacy of this drug use because pregnant individuals have historically been excluded from clinical trials. Underrepresentation has resulted in a lack of data available to estimate or predict fetal drug exposure. Approaches to study fetal drug pharmacology are limited and must be evaluated for feasibility and accuracy. Anatomic and physiological changes throughout pregnancy fluctuate based on gestational age and can affect drug pharmacokinetics (PK) for both mother and fetus. Drug concentrations have been studied throughout different stages of gestation and at or following delivery in tissue and fluid biospecimens. Sampling amniotic fluid, umbilical cord blood, placental tissue, meconium, umbilical cord tissue, and neonatal hair present surrogate options to quantify and characterize fetal drug exposure. These sampling methods can be applied to all therapeutics including small molecule drugs, large molecule drugs, conjugated nanoparticles, and chemical exposures. Alternative approaches to determine PK have been explored, including physiologically based PK modeling, in vitro methods, and traditional animal models. These alternative approaches along with convenience sampling of tissue or fluid biospecimens can address challenges in studying maternal-fetal pharmacology. In this narrative review, we 1) present an overview of the current understanding of maternal-fetal drug exposure; 2) discuss biospecimen-guided sampling design and methods for measuring fetal drug concentrations throughout gestation; and 3) propose methods for advancing pharmacology research in the maternal-fetal population.

Modulation of Hepatic Functions by Chicory (Cichorium intybus L.) Extract: Preclinical Study in Rats.

The liver is important in detoxifying organisms from xenobiotics, supporting immune functions, and metabolizing lipids and glucose. In addition, a growing number of drug-induced liver injuries and diseases associated with liver dysfunction make the development of phytodrugs targeting multiple liver functions particularly crucial. Therefore, we investigated the effects of a novel chicory extract prepared from aerial parts of the wild Cichorium intybus L. plant (CE) on liver enzymes and on lipid and glucose metabolism in rats with acute liver injury or hyperlipidemia. A single subcutaneous injection of mercury chloride induced an acute liver injury. Hyperlipidemia was induced by a single intraperitoneal injection of Tween-80 or by feeding rats with cholesterol and mercazolil for 28 days. Under varying regimens, the experimental rats received 100 mg/kg b.w. or 500 mg/kg b.w. of CE. CE treatment ameliorated acute liver injury by reducing liver enzyme activity, bilirubin, glucose, and lipid levels. Treatment of hyperlipidemic rats with CE effectively reduced serum lipid and glucose levels. The data obtained in this study suggest that chicory-based phytodrugs may be used to effectively treat acute liver injury and for the prophylaxis or treatment of diseases such as hyperlipidemia, type 2 diabetes, and metabolic syndrome. Clinical trials are needed to prove the effectiveness of chicory extract in human patients.

Mapping the Evidence for Opioid-Mediated Changes in Malignancy and Chemotherapeutic Efficacy: Protocol for a Scoping Review.

BACKGROUND: Numerous reports contend opioids can augment or inhibit malignancy. At present, there is no consensus on the risk or benefit posed by opioids on malignancy or chemotherapeutic activity. Distinguishing the consequences of opioid use from pain and its management is challenging. Additionally, opioid concentration data is often lacking in clinical studies. A scoping review approach inclusive of preclinical and clinical data will improve our understanding of the risk-benefit relationship concerning commonly prescribed opioids and cancer and cancer treatment. OBJECTIVE: The aim of the study is to map diverse studies spanning from preclinical to clinical regarding opioids with malignancy and its treatment. METHODS: This scoping review will use the Arksey six stages framework to (1) identify the research question; (2) identify relevant studies; (3) select studies meeting criteria; (4) extract and chart data; (5) collate, summarize, and report results; and (6) conduct expert consultation. An initial pilot study was undertaken to (1) parameterize the extent and scale of existing data for an evidence review, (2) identify key factors to be extracted in systematic charting efforts, and (3) assess opioid concentration as a variable for its relevance to the central hypothesis. Six databases will be searched with no filters: MEDLINE, Embase, CINAHL Complete, Cochrane Library, Biological Sciences Collection, and International Pharmaceutical Abstracts. Trial registries will include ClinicalTrials.gov, Cochrane CENTRAL, International Standard Randomised Controlled Trial Number Registry, European Union Clinical Trials Register, and World Health Organization International Clinical Trials Registry. Eligibility criteria will include preclinical and clinical study data on opioids effects on tumor growth or survival, or alteration on the antineoplastic activity of chemotherapeutics. We will chart data on (1) opioid concentration from human subjects with cancer, yielding a "physiologic range" to better interpret available preclinical data; (2) patterns of opioid exposure with disease and treatment-related patient outcomes; and (3) the influence of opioids on cancer cell survival, as well as opioid-related changes to cancer cell susceptibility for chemotherapeutics. RESULTS: This scoping review will present results in narrative forms as well as with the use of tables and diagrams. Initiated in February 2021 at the University of Utah, this protocol is anticipated to generate a scoping review by August 2023. The results of the scoping review will be disseminated through scientific conference proceedings and presentations, stakeholder meetings, and by publication in a peer-reviewed journal. CONCLUSIONS: The findings of this scoping review will provide a comprehensive description of the consequences of prescription opioids on malignancy and its treatment. By incorporating preclinical and clinical data, this scoping review will invite novel comparisons across study types that could inform new basic, translational, and clinical studies regarding risks and benefits of opioid use among patients with cancer. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): PRR1-10.2196/38167.

Examination of Complementary Medicine for Treating Urinary Tract Infections Among Pregnant Women and Children.

Urinary tract infections (UTIs) are a significant clinical problem that pregnant women and children commonly experience. Escherichia coli is the primary causative organism, along with several other gram-negative and gram-positive bacteria. Antimicrobial drugs are commonly prescribed to treat UTIs in these patients. Conventional treatment can range from using broad-spectrum antimicrobial drugs for empirical or prophylactic therapy or patient-tailored therapy based on urinary cultures and sensitivity to prospective antibiotics. The ongoing emergence of multi-drug resistant pathogens has raised concerns related to commonly prescribed antimicrobial drugs such as those used routinely to treat UTIs. Consequently, several natural medicines have been explored as potential complementary therapies to improve health outcomes in patients with UTIs. This review discusses the effectiveness of commonly used natural products such as cranberry juice/extracts, ascorbic acid, hyaluronic acid, probiotics, and multi-component formulations intended to treat and prevent UTIs. The combination of natural products with prescribed antimicrobial treatments and use of formulations that contained high amounts of cranberry extracts appear to be most effective in preventing recurrent UTIs (RUTIs). The incorporation of natural products like cranberry, hyaluronic acid, ascorbic acid, probiotics, Canephron® N, and Cystenium II to conventional treatments of acute UTIs or as a prophylactic regimen for treatment RUTIs can benefit both pregnant women and children. Limited information is available on the safety of natural products in these patients' populations. However, based on limited historical information, these remedies appear to be safe and well-tolerated by patients.

Intrauterine growth restriction alters T-lymphocyte cell number and dual specificity phosphatase 1 levels in the thymus of newborn and juvenile rats.

Intrauterine growth restricted (IUGR) infants have increased susceptibility to infection associated with higher risk of illness and death. Dual specificity phosphatase 1 (DUSP1), which is transcribed in the thymus, increases in quantity as T cells mature and differentiate into CD4+ cells. Little is known about how IUGR affects DUSP1 levels and T-cell subpopulations over time. We hypothesized that IUGR would decrease cell count, CD4+ and CD8+ subpopulations of T lymphocytes, and DUSP1 levels in IUGR rat thymus and spleen. Bilateral uterine artery ligation produced IUGR rats. Thymus and spleen were harvested at P0 and P21. Flow cytometry was used to compare CD4+ and CD8+ lymphocyte populations. Real-time RT-PCR and Western blotting were used to determine DUSP1 quantity. IUGR significantly decreased total cell count in P0 and P21 IUGR male and female thymus. IUGR significantly increased CD4+ cells in IUGR P0 males and females, significantly decreased CD4+ cells in P21 female thymus, and significantly altered DUSP1 levels in the IUGR female thymus at P0 and P21, although it is not yet known whether the change in DUSP1 levels is due to a change in the level per cell or to a change in cellular composition of the thymus.

Valuable Hepatoprotective Plants - How Can We Optimize Waste Free Uses of Such Highly Versatile Resources?

Humans used plants for thousand of years as food, drugs, or fuel to keep homes warm. People commonly used fruits and roots, and other parts of the plant were often wasted. This review aims to discuss the potential of rational stem-to-stern use of three highly versatile and valuable plants with hepatoprotective properties. Milk thistle (Silybum marianum L. Gaertn.), artichoke (Cynara cardunculus), and chicory (Cichorium intybus L.) have well-characterized hepatoprotective properties. These plants have been chosen since liver diseases are significant diseases of concern worldwide, and all parts of plants can be potentially utilized. Artichoke and chicory are commonly used as food or dietary supplements and less often as phytodrugs. Various dietary supplements and phytodrugs prepared from milk thistle (MT) fruits/seeds are well-known to consumers as remedies supporting liver functions. However, using these plants as functional food, farm animal feed, is not well-described in the literature. We also discuss bioactive constituents present in various parts of these plants, their pharmacological properties. Distinct parts of MT, artichoke, and chicory can be used to prepare remedies and food for humans and animals. Unused plant parts are potentially wasted. To achieve waste-free use of these and many other plants, the scientific community needs to analyze the complex use of plants and propose strategies for waste-free technologies. The government must stimulate companies to utilize by-products. Another problem associated with plant use as a food or source of phytodrug is the overharvesting of wild plants. Consequently, there is a need to use more active cultivation techniques for plants.

Effects of a new thyrotropic drug isolated from Potentilla alba on the male reproductive system of rats and offspring development.

BACKGROUND: The dysfunction of the thyroid gland is a common medical condition. Nowadays, patients frequently use medicinal herbs as complementary or alternative options to conventional drug treatments. These patients may benefit from treatment of thyroid dysfunctions with Potentilla alba L. preparations. While it has been reported that Potentilla alba preparations have low toxicity, nothing is known about their ability to affect reproductive functions in patients of childbearing age. METHODS: Male Wistar rats were orally treated with a thyrotrophic botanical drug, standardized Potentilla alba Dry Extract (PADE), at doses 8 and 40 times higher than the median therapeutic dose recommended for the clinical trials, for 60 consecutive days. Male Wistar rats receiving water (H2O) were used as controls. After completing treatment, half of the PADE-treated and control males were used to determine PADE gonadotoxicity, and the remaining half of PADE-treated and control males were mated with intact females. Two female rats were housed with one male for two estrus cycles. PADE effects on fertility and fetal/offspring development were evaluated. RESULTS: Herein, we report that oral treatment of male Wistar rats with PADE before mating with intact females instigated marked effects on male reproductive organs. Treatment significantly decreased the motility of the sperm and increased the number of pathological forms of spermatozoa. Additionally, a dose-dependent effect on Leydig cells was observed. However, these PADE effects did not significantly affect male fertility nor fetal and offspring development when PADE-treated males were mated with intact females. CONCLUSIONS: PADE treatment of male rates negatively affected sperm and testicular Leydig cell morphology. However, these changes did not affect male fertility and offspring development. It is currently not known whether PADE treatment may affect human male fertility and offspring development. Therefore, these results from an animal study need to be confirmed in humans. Results from this animal study can be used to model the exposure-response relationship and adverse outcomes in humans.

Treatment optimization of maintenance immunosuppressive agents in pediatric renal transplant recipients.

Introduction: Graft survival in pediatric kidney transplant patients has increased significantly within the last three decades, correlating with the discovery and utilization of new immunosuppressants as well as improvements in patient care. Despite these developments in graft survival for patients, there is still improvement needed, particularly in long-term care in pediatric patients receiving grafts from deceased donor patients. Maintenance immunosuppressive therapies have narrow therapeutic indices and are associated with high inter-individual and intra-individual variability.Areas covered: In this review, we examine the impact of pharmacokinetic variability on renal transplantation and its association with age, genetic polymorphisms, drug-drug interactions, drug-disease interactions, renal insufficiency, route of administration, and branded versus generic drug formulation. Pharmacodynamics are outlined in terms of the mechanism of action for each immunosuppressant, potential adverse effects, and the utility of pharmacodynamic biomarkers.Expert opinion: Acquiring abetter quantitative understanding of immunosuppressant pharmacokinetics and pharmacodynamic components should help clinicians implement treatment regimens to maintain the balance between therapeutic efficacy and drug-related toxicity.

How can we improve the safe use of herbal medicine and other natural products? A clinical pharmacologist mission.

INTRODUCTION: Three major classes of natural products (NPs) for medicinal purposes or improving wellbeing are generally available in the US: conventional drugs of herbal origin, botanical drugs, and dietary supplements (DSs). Consumer consumption of DSs is growing annually. The U.S. FDA regulates conventional and botanical drugs for safety and efficacy; however, DSs are minimally regulated. AREAS COVERED: This article will: i) highlight the importance of NP as a significant source of prescription drugs; ii) discuss differences in the regulation of conventional drugs of NP product, botanical drugs, and DSs; iii) discuss the safety and efficacy of DSs and iv) make recommendations for improvement of safety for minimally regulated NPs. EXPERT OPINION: Toxicities associated with the use of NPs, including vitamins and DSs, are mainly due to excessive use and interactions with conventional drug(s) and may represent challenges for clinicians. Conventional and botanical-based prescription drugs are rarely associated with unknown toxicities. However, DSs are minimally regulated and can produce severe adverse effects. We believe that clinical pharmacologists can have a role in developing criteria for DS safety analysis. There is also the potential for a standardized NP stewardship program(s) and the development of NP policies and practices nationally and globally.

Supportive care medications coinciding with chemotherapy among children with hematologic malignancy.

Pharmacokinetic (PK) conflicts can arise between supportive care medications (SCM) and chemotherapy in children with hematologic malignancy (HM). In this retrospective study, medical records for children (28 days-18 years) diagnosed with HM and receiving an SCM antimicrobial were collected from a hospital network between 1 May 2000 and 31 December 2014. PK drug-gene associations were obtained from a curated pharmacogenomics database. Among 730 patients (median age of 7.5 (IQR 3.7-13.9) years), primarily diagnosed with lymphoid leukemia (52%), lymphoma (28%), or acute myeloid leukemia (16%), chemotherapy was administered in 2846 hospitalizations. SCM accounted for 90.5% (n = 448) of distinct drugs with 93% (n = 679) of children, receiving ≥5 different SCM/hospitalization. Same-day SCM/chemotherapeutic PK gene overlap occurred in 48.3% of hospitalizations and was associated with age (p = 0.026), number of SCM, HM subtype, surgery, and hematopoietic stem cell transplant (p < 0.0001). A high and variable SCM burden among children with HM receiving chemotherapy poses a risk for unanticipated PK conflicts.

Changing trends in IVIG use in pediatric patients: A retrospective review of practices in a network of major USA pediatric hospitals.

The use of immunoglobulins is gradually increasing. Intravenous immunoglobulins (IVIG) are used as replacement therapy for primary and secondary immune deficiencies, and as an anti-inflammatory and immunomodulatory medication for the treatment of neurologic, dermatologic, and rheumatologic diseases. The objective of this study was to analyze trends in the IVIG use in pediatric patients hospitalized to 47 US-based children's hospitals from 2007 to 2014. IVIG was used for the treatment of >2300 primary diagnoses in 53,648 unique patients. The number of IVIG admissions increased by 30.2% during the study period, while the mean rate of IVIG admissions/100,000 admissions increased only 5.8%. Most patients receiving IVIG were children and adolescents. IVIG was frequently used off-label or for the treatment of FDA-approved indications in children under two years of age and BMT patients <20 years of age. Primary immune deficiencies represented only 1.2% of all IVIG admissions. Pediatric patients with mucocutaneous lymph node syndrome (Kawasaki disease, KD) and idiopathic thrombocytopenic purpura (ITP) were two primary consumers of the IVIG. Another top-ranked indications were acute infectious polyneuritis (Guillain-Barré syndrome, GBS) and prophylaxis of infections in patients receiving antineoplastic chemotherapy. IVIG usage is a dynamic process guided by emerging evidence and FDA approval for new indications. IVIG was mostly prescribed for treatment of diseases with pathologic immune responses to foreign of self-antigens. These indications usually, require higher amounts of IVIG per admission. More studies are needed to understand whether IVIG treatments of off-label indications are effective and cost-efficient.

Antibiotic Treatment of Suspected and Confirmed Neonatal Sepsis Within 28 Days of Birth: A Retrospective Analysis.

Neonatal sepsis causes significant mortality and morbidity worldwide. Diagnosis is usually confirmed via blood culture results. Blood culture sepsis confirmation can take days and suffer from contamination and false negatives. Empiric therapy with antibiotics is common. This study aims to retrospectively describe and compare treatments of blood culture-confirmed and unconfirmed, but suspected, sepsis within the University of Utah Hospital system. Electronic health records were obtained from 1,248 neonates from January 1, 2006, to December 31, 2017. Sepsis was categorized into early-onset (≤3 days of birth, EOS) and late-onset (>3 and ≤28 days of birth, LOS) and categorized as culture-confirmed sepsis if a pathogen was cultured from the blood and unconfirmed if all blood cultures were negative with no potentially contaminated blood cultures. Of 1,010 neonates in the EOS cohort, 23 (2.3%) were culture-confirmed, most with Escherichia coli (42%). Treatment for unconfirmed EOS lasted an average of 6.1 days with primarily gentamicin and ampicillin while confirmed patients were treated for an average of 12.3 days with increased administration of cefotaxime. Of 311 neonates in the LOS cohort, 62 (20%) were culture-confirmed, most culturing coagulase negative staphylococci (46%). Treatment courses for unconfirmed LOS lasted an average of 7.8 days while confirmed patients were treated for an average of 11.4 days, these patients were primarily treated with vancomycin and gentamicin. The use of cefotaxime for unconfirmed EOS and LOS increased throughout the study period. Cefotaxime administration was associated with an increase in neonatal mortality, even when potential confounding factors were added to the logistic regression model (adjusted odds ratio 2.8, 95%CI [1.21, 6.88], p = 0.02). These results may not be generalized to all hospitals and the use of cefotaxime may be a surrogate for other factors. Given the low rate of blood culture positive diagnosis and the high exposure rate of empiric antibiotics, this patient population might benefit from improved diagnostics with reevaluation of antibiotic use guidelines.

Use of Herbal Medicine by Pregnant Women: What Physicians Need to Know.

About 80% of the consumers worldwide use herbal medicine (HMs) or other natural products. The percentage may vary significantly (7%-55%) among pregnant women, depending upon social status, ethnicity, and cultural traditions. This manuscript discusses the most common HMs used by pregnant women, and the potential interactions of HMs with conventional drugs in some medical conditions that occur during pregnancy (e.g., hypertension, asthma, epilepsy). It also includes an examination of the characteristics of pregnant HM consumers, the primary conditions for which HMs are taken, and a discussion related to the potential toxicity of HMs taken during pregnancy. Many cultures have used HMs in pregnancy to improve wellbeing of the mother and/or baby, or to help decrease nausea and vomiting, treat infection, ease gastrointestinal problems, prepare for labor, induce labor, or ease labor pains. One of the reasons why pregnant women use HMs is an assumption that HMs are safer than conventional medicine. However, for pregnant women with pre-existing conditions like epilepsy and asthma, supplementation of conventional treatment with HMs may further complicate their care. The use of HMs is frequently not reported to healthcare professionals. Providers are often not questioning HM use, despite little being known about the HM safety and HM-drug interactions during pregnancy. This lack of knowledge on potential toxicity and the ability to interact with conventional treatments may impact both mother and fetus. There is a need for education of women and their healthcare professionals to move away from the idea of HMs not being harmful. Healthcare professionals need to question women on whether they use any HMs or natural products during pregnancy, especially when conventional treatment is less efficient and/or adverse events have occurred as herbal-drug interactions could be the reason for these observations. Additionally, more preclinical and clinical studies are needed to evaluate HM efficacy and toxicity.