Treatment of Demodex-associated inflammatory skin conditions: A systematic review.

Bacterial folliculitis, rosacea, and other common skin conditions have been linked to infestation by Demodex mites (human demodicosis). Currently, there is little guidance for treatment of inflammatory conditions associated with demodicosis. Thus, the objective of this review is to evaluate the efficacy and safety of treatments utilized for Demodex infestation. PubMed (1946 to January 2019) and Embase (1947 to January 2019) were searched with the following term combinations: Demodex mites, Demodex folliculitis, demodicosis, Demodex folliculorum, or Demodex brevis and articles evaluating treatment of body surface colonization with Demodex mites were included. Common interventions used for Demodex infestation include metronidazole-based therapies, permethrin, benzoyl benzoate, crotamiton, lindane, and sulfur. Short courses of metronidazole taken orally have shown efficacy in reducing Demodex density. Additionally, topical administration of permethrin daily or twice daily was shown to be efficacious across multiple studies. Crotamiton and benzyl benzoate were also efficacious treatments. Several therapies were associated with mild-to-moderate skin irritation. Due to limited data, no standard of care can be identified at this time. Efficacious treatment options may include permethrin, crotamiton, benzyl benzoate, and oral metronidazole; however, long-term efficacy has not been established.

Nanocellulose in tissue engineering and bioremediation: mechanism of action.

Nanocellulose are nano-sized components which are biodegradable, biocompatible and renewable. It offers mechanical strength and chemical stability in plants and bacteria. The environmental contamination is reduced by employing various bioremediation techniques which usesmicroorganisms like algae, bacteria and fungi as bio-adsorbents. The bio adsorbent property of nanocellulose contribute more for the bioremediation methods and the detailed study of its mechanism and application is essential which is discussed here. The mechanism happening between the contaminant and nanocellulose adsorbent should be explored in detail in order to develop effective new bioremediation strategies. Nanocellulose structural functionalization helps to modify the nanocellulose structure based on which it can be utilized for specific functions. Exploring the mechanisms that contribute to the implementation of nanocellulose in tissue engineering helps for further developments and advancement in the biomedical application of nanocellulose. Not much studies are available that elucidate and study the basic steps involved in the biomedical and environmental usage of nanocellulose. This review has focussed on the basic mechanisms involved in the use of nanocellulose in tissue engineering and bioremediation processes.

Assessing the Economic Value of Pharmacy Resident Participation in an Investigational Drug Service.

PURPOSE: Completion of postgraduate residency training gives pharmacists an opportunity to gain advanced practice experience, yet the availability of these positions is often limited. Through participation in an investigational drug service (IDS), residency programs may be able to expand learning experiences while demonstrating a financial benefit to the institution. The purpose of this assessment is to examine the economic value generated by pharmacy resident involvement within an IDS. METHODS: This was a single-center retrospective record review. All resident dispensations within the IDS from January 1, 2016, to December 31, 2017, were evaluated for cost avoidance, revenue, and waived revenue. Cost avoidance was defined as the cost of medications the institution would have incurred had the sponsor not provided therapies free of charge. Medical center contract acquisition costs were used to determine cost avoidance. Total economic value accounted for the personnel costs of resident dispensations. Descriptive statistics were utilized for all assessments. RESULTS: A total of 444 resident dispensations occurred during the study period on 15 IDS protocols. The total cost avoidance for resident dispensations was US$144 898. Total revenue for these dispensations was US$1424, and waived revenue fees totaled US$17 625. After accounting for the personnel cost of dispensations by the residents, the total economic value of resident participation in the IDS was US$159 150. CONCLUSION: Resident participation in the IDS contributed economic value to the institution. The IDS provides a unique learning experience for the pharmacy residents, cost savings for the institution, and supports the advancement of patient care.

Prevalence of diabetes mellitus and HIV/AIDS among tuberculosis patients in Kerala.

INTRODUCTION: It is estimated that 10 million people fall ill with Tuberculosis (TB) every year worldwide. TB continues to be in the top 10 causes of death globally with India being the home to the world's largest number of TB patients. One of the major factors attributing to this is the presence of comorbidities such as Diabetes Mellitus and HIV/AIDS. AIM: The aim of this study was to determine the prevalence of comorbidities such as Diabetes mellitus & HIV/AIDS among the newly diagnosed TB patients in Kerala in 2019 and also to determine the factors associated with it. MATERIALS AND METHODS: A cross-sectional study was carried out using the secondary data from NIKSHAY portal. There were a total of 16,527 cases of pulmonary and extrapulmonary TB cases reported from 14 districts of Kerala from January to September 2019. Using a checklist, data regarding the age, gender, type of case, Type of patient, site of disease, drug resistance were collected separately for TB patients suffering from Diabetes mellitus and HIV/AIDS. The data was then entered into Excel sheet and was analyzed using SPSS version 23. RESULTS: Out of the total 16,527 study population, most of the patients were elderly above the age of 60 years (28.6%). The prevalence of Diabetes mellitus (22.6%) was higher among TB patients when compared to HIV/AIDS (1.2%). Males in the age group between 50-59 years were found to be significantly associated with TB- Diabetes Mellitus comorbidities. Diabetes was significantly associated with Pulmonary TB patients, while HIV/AIDS was significantly associated with extrapulmonary TB. CONCLUSION: Both Diabetes Mellitus and HIV/AIDS are comorbidities that have a strong impact on the diagnosis and management of Tuberculosis patients. Therefore, there is an urgent need to prevent these comorbidities from occurring along with the implementation of early diagnosis and appropriate management strategies. This study is of prime importance especially among Primary care Physicians who are treating TB patients on routine basis. They are particularly important in TB control since they are usually the first to meet a TB suspect, before diagnosis occurs. Both HIV/AIDS and Diabetes mellitus are immunocompromised conditions and these comorbidities can affect the treatment outcomes of TB. Primary care physicians are essential in detecting TB suspects and treating them, thus contribute significantly to reducing the burden of TB.

Extenuation of in utero toxic effects of MeHg in the developing neurons by Fisetin via modulating the expression of synaptic transmission and plasticity regulators in hippocampus of the rat offspring.

The neurotoxic environmental contaminant, methylmercury (MeHg), has shown to have detrimental effects on the developing brain when exposed during gestation. We have shown in our earlier studies that gestational administration of 3,3',4',7-Tetrahydroxyflavone or Fisetin reduces the toxic effects of MeHg in the developing rat brain. The current study has pivoted to study the mechanism behind the mitigating action of Fisetin against prenatal MeHg exposure induced neurotoxicity. Negligible data is available about the toxicity targets of MeHg in the developing brain. Studies have exhibited that MeHg exposure cause toxic effects on synaptic transmission and plasticity in the offspring brain. Hence, we aimed to study the effect of Fisetin on MeHg induced alterations in the expressions of regulatory genes and proteins involved in synaptic plasticity and transmission. Pregnant rats were grouped according to the type of oral administration as, (i) Control, (ii) MeHg (1.5 mg/kg b. w.), (iii) MeHg + Fisetin (30 mg/kg b. w.) and (iv) Fisetin (30 mg/kg b. w). Maternal administration of Fisetin prevented MeHg exposure induced downregulation of neurogranin (Nrgn), dendrin (Ddn), Syntaxin 1 A (Stx1a), Lin-7 homolog A (Lin7a), Complexin-2 (Cplx2) and Exocyst complex component 8 (Exoc8) genes in the offspring rat. Fisetin also prevented MeHg exposure induced downregulation of brain derived neurotrophic factor (BDNF), Glial-cell derived neurotrophic factor (GDNF) protein expressions and hampered reactive astrogliosis in the hippocampus of F1 generation rats. Hence, through this study, we conclude that Fisetin modulates the expression of regulatory genes and proteins involved in synaptic transmission and plasticity and extenuates MeHg neurotoxicity in the developing rat brain.

Economic outcomes associated with an investigational drug service within a Veterans Affairs health care system.

BACKGROUND: An investigational drug service (IDS) has a foundational role in ensuring the safe and efficient management of investigational drugs. The objective of this assessment is to determine economic value of an IDS within a Veterans Affairs health care system. METHODS: This assessment was a single-center retrospective record review. Study protocols managed by the IDS over a 2-year period were evaluated for cost avoidance, revenue, and waived revenue. Cost avoidance was defined as the cost savings generated when a research subject received sponsor-provided treatment in place of a therapy that would have been otherwise funded by the institution. Revenue from fees charged to investigators and waived revenue based on the standardized IDS fee schedule were also totaled. The total economic value to the institution accounted for the personnel costs of the IDS. RESULTS: Twenty-three investigational study protocols managed by the IDS resulted in economic outcomes. The total cost avoidance during the two-year period was $482,627.33. The total revenue and waived revenue associated with the IDS was $16,822 and $54,200, respectively. Oncology protocols had the highest contribution to the outcomes of cost avoidance and revenue and mental health protocols had the highest contribution for waived revenue. The overall economic value of the IDS to the institution was $393,649.33. CONCLUSIONS: Over a two-year period, the IDS demonstrated a substantial economic value that was largely driven by cost avoidance. Revenue generation from fees charged to investigators and cost savings to the investigator through waived revenue also contributed economic benefits to the institution.

Clinical Profile and Short Term Outcome of Adult Patients with Acute Myeloid Leukemia.

Acute myeloid leukemia has a poor outcome because of early deaths, high relapse rate and financial constraints. Our hospital provides care free of cost and this study assesses the short term outcome of acute myeloid leukemia in adults. The study was done from September 2013 to May 2015. All patients above 18 years of age were included. Cytarabine infusion 100 mg/m2 daily for 7 days and Daunorubicin 60 mg/m2 daily for 3 days was used for induction chemotherapy followed by three cycles of high dose cytarabine as post-remission therapy. One hundred and two patients were included in the study. 48% were males. The median age was 41 years. There was an intention to treat in 84 patients. 13 patients died before chemotherapy and 71 patients (57 non AML M3) received induction chemotherapy. 82% of them had a Eastern Cooperative Oncology Group performance score of ≤ 2. 28 (of 57 non AML M3) patients were alive after post-remission therapy (with 39% deaths during induction phase) and 15 of them were in remission after a median follow up of nine months. The overall event free survival at the end of the study was 22% (16 out of 71). Altogether, 63 out of 84 patients had died. Sepsis was considered as the cause of death in 46% of the patients, but the isolation of causative organism was limited (20%). The treatment outcomes of AML are poor at our centre and the current standard of care needs a significant improvement.

Economic Outcomes Associated with Safety Interventions by a Pharmacist-Adjudicated Prior Authorization Consult Service.

BACKGROUND: The establishment of a formulary management system ensures that health care professionals work together in an integrated patient care process to promote clinically sound, safe, and cost-effective medication therapy. Pharmacists have a foundational role within this system. A pharmacist-adjudicated prior authorization drug request (PADR) consult service has the potential to optimize drug therapy by decreasing medication misuse, minimizing adverse drug events (ADEs), and preventing medication errors. OBJECTIVES: To (a) determine cost avoidance associated with pharmacist-adjudicated PADR safety interventions within the Durham Veterans Affairs Health Care System and (b) evaluate cost savings associated with pharmacist-adjudicated PADRs not approved due to a safety intervention, evaluate cost avoidance and direct cost savings based on clinical specialty of pharmacist adjudicating PADR, and characterize severity of avoided ADEs. METHODS: Pharmacist-adjudicated PADRs not approved between July 1, 2016, and June 30, 2017, because of safety interventions were retrospectively reviewed. Cost avoidance was determined by multiplying the probability of ADE occurrence in the absence of PADR safety intervention by the estimated cost avoided based on the type of intervention. Direct cost savings was calculated by totaling the cost of requested medications not approved for each PADR and subtracting the cost of recommended alternative therapies and cost of pharmacist PADR review. All potential ADEs avoided were reviewed by a panel of 3 clinical pharmacists to validate ADE classification and ADE probability and severity scores. Descriptive statistics were used for all analyses. RESULTS: Of the 910 PADRs that were not approved during the study period, 96 met inclusion criteria. Pharmacist-adjudicated PADR safety interventions resulted in a total cost avoidance of $24,485.34 (mean = $255.06) and a direct cost savings of $288,695.63 (mean = $3,007.25). The practice settings of anticoagulation and infectious diseases PADRs resulted in the largest contribution to cost avoidance and direct cost savings, respectively. Prevented ADEs were classified as major for 64.6% of the PADRs. CONCLUSIONS: Pharmacist-adjudicated PADR safety reviews resulted in substantial economic benefit and prevention of major ADEs. This analysis supports the pharmacist's role in a formulary management system to optimize medication therapy. DISCLOSURES: This research did not receive any specific grant from funding agencies in the public, commercial, or not-for profit sectors. The authors have nothing to disclose.

Fisetin impedes developmental methylmercury neurotoxicity via downregulating apoptotic signalling pathway and upregulating Rho GTPase signalling pathway in hippocampus of F1 generation rats.

Methyl mercury is a teratogenic and neurodevelopmental toxicant in the environment. MeHg affects several biological pathways critical for brain development. The present study validated the effect of Fisetin on developmental MeHg exposure induced alterations in mitochondrial apoptotic pathway and Rho GTPase mRNA expressions in hippocampus of F1 generation rats. Pregnant Wistar rats were grouped as Group I : administered with vehicle control, Group II: MeHg (1.5 mg/kg b.w), Group III: MeHg + Fisetin (10 mg/kg b.w), Group IV: MeHg + Fisetin (30 mg/kg b.w), Group V: MeHg + Fisetin (50 mg/kg b.w), Group VI: MeHg + Fisetin (70 mg/kg b.w), Group VII: Fisetin (30 mg/kg b.w) alone. Fisetin reduced mercury accumulation in offspring brain. In hippocampus, Fisetin preserved mitochondrial total thiol status, glutathione antioxidant system, mitochondrial metabolic integrity and respiratory chain activity. Fisetin ameliorated apoptotic signals by preventing Cytochrome c release, down regulating ERK 1/2 and Caspase 3 gene expression. Fisetin also upregulated mRNA expressions of RhoA/Rac1/Cdc42 in hippocampus. Predominant effect of Fisetin was to reduce mercury accumulation in offspring brain there by diminishing the toxic effect of MeHg. Hence we showed that, gestational intake of Fisetin (30 mg/kg b.w.) impedes developmental MeHg neurotoxicity by regulating mitochondrial apoptotic and Rho GTPase signalling molecules and by reducing the mercury accumulation in hippocampus of F1 generation rats.

Methylmercury exposure develops atherosclerotic risk factors in the aorta and programmed cell death in the cerebellum: ameliorative action of Celastrus paniculatus ethanolic extract in male Wistar rats.

Methylmercury (MeHg) is a bioaccumulative global environmental contaminant present in fishes and seafood. MeHg is the methylated form of mercury emitted from diverse anthropogenic and natural sources. MeHg is accumulated in the aquatic environment and eventually reaches human system via food chain by biomagnification. We have reported previously that the neurotoxic effect of MeHg in rat cerebellum is mitigated by the administration of an ayurvedic medicinal plant, Celastrus paniculatus ethanolic extract. The present study has focussed to further explore the mechanism of action of Celastrus paniculatus against MeHg-induced neurotoxicity in the cerebellum. We have also inspected the effect of Celastrus paniculatus (CP) against MeHg-induced atherosclerotic risk factors like alterations in antioxidant levels, aortic lipid profile, and aortic histology by MeHg in the largest vasculature, aorta, which are the initiating factors of cardiovascular diseases. Male Wistar rats were divided as (i) control, (ii) MeHg (5 mg/kg b.w.), (iii) MeHg + CP (200 mg/kg b.w.), and (iv) CP alone (200 mg/kg b.w.). All were given orally for 21 days. In cerebellum Celastrus paniculatus, there were increased mitochondrial electron transport chain (p < 0.05) activity, reduced cytochrome c release (p < 0.05), and caspase 3 mRNA expression (p < 0.05). In the aorta, MeHg-induced oxidative stress, lipid profile changes, and endothelial denudation were ameliorated by Celastrus paniculatus. Hence, we conclude that Celastrus paniculatus protects against MeHg toxicity by inhibiting mitochondrial cytochrome c/caspase 3 apoptotic pathway in the cerebellum and reducing the development of atherosclerotic risk factors in the aorta.

Effect of Gestational Intake of Fisetin (3,3',4',7-Tetrahydroxyflavone) on Developmental Methyl Mercury Neurotoxicity in F1 Generation Rats.

Methyl mercury (MeHg) is a developmental neurotoxin that causes irreversible cognitive damage in offspring of gestationally exposed mothers. Currently, no preventive drugs are established against MeHg developmental neurotoxicity. The neuroprotective effect of gestational administration of a flavanoid against in utero toxicity of MeHg is not explored much. Hence, the present study validated the effect of a bioactive flavanoid, fisetin, on MeHg developmental neurotoxicity outcomes in rat offspring at postnatal weaning age. Pregnant Wistar rats were simultaneously given MeHg (1.5 mg/kg b.w.) and two doses of fisetin (10 and 50 mg/kg b.w. in two separate groups) orally from gestational day (GD) 5 till parturition. Accordingly, after parturition, on postnatal day (PND) 24, weaning F1 generation rats were studied for motor and cognitive behavioural changes. Biochemical and histopathological changes were also studied in the cerebral cortex, cerebellum and hippocampus on PND 25. Administration of fisetin during pregnancy prevented behavioural impairment due to transplacental MeHg exposure in weaning rats. Fisetin decreased the levels of oxidative stress markers, increased enzymatic and non-enzymatic antioxidant levels and increased the activity of membrane-bound ATPases and cholinergic function in F1 generation rats. In light microscopic studies, fisetin treatment protected the specific offspring brain regions from significant morphological aberrations. Between the two doses of fisetin studied, 10 mg/kg b.w. was found to be more satisfactory and effective than 50 mg/kg b.w. The present study shows that intake of fisetin during pregnancy in rats ameliorated in utero MeHg exposure-induced neurotoxicity outcomes in postnatal weaning F1 generation rats.

Clostridium difficile infection: A brief update on emerging therapies.

PURPOSE: Established and investigational antibiotic, monoclonal antibody, vaccine, and microbe-based approaches to the prevention and treatment of Clostridium difficile infection (CDI) are reviewed. SUMMARY: CDI is increasingly prevalent in the United States and other countries, particularly among hospitalized patients and the elderly, who are at high risk for potentially fatal CDI-related enterotoxic diarrhea. Established therapies for CDI such as vancomycin and metronidazole (an off-label use) are limited by poor efficacy and high recurrence rates. An investigational antibiotic with potent in vitro activity against all C. difficile strains (including the hypervirulent BI/NAP1/027 strain) has yielded encouraging results in early clinical trials. Another promising approach involves the use of monoclonal antibodies with selective activity against toxins responsible for CDI-associated diarrhea; in a small Phase II clinical trial, a single monoclonal antibody infusion in combination with vancomycin or metronidazole therapy was more effective than antibiotic therapy alone in preventing CDI relapse. Other emerging approaches to CDI treatment and prophylaxis include the use of vaccines against C. difficile toxins (several C. difficile-targeted vaccines are under development in Europe and the United States); microbe-based strategies such as fecal microbiota transplants, "microbial ecosystem therapeutics," and probiotic supplements; and an investigational encapsulated form of ß-lactamase designed to prevent C. difficile colonization from progressing to CDI. CONCLUSION: The current antibiotic therapies for CDI, mainly vancomycin and (off-label) metronidazole and the newer agent fidaxomicin, have limitations with respect to efficacy, recurrence rates, and adverse effects, but a variety of promising approaches are emerging.