ResearchPad - drugs https://www.researchpad.co Default RSS Feed en-us © 2020 Newgen KnowledgeWorks <![CDATA[Promoting healthy aging: intervening with diet, drugs, or exercise]]> https://www.researchpad.co/article/elastic_article_14072 <![CDATA[Comparability of modern contraceptive use estimates between a face-to-face survey and a cellphone survey among women in Burkina Faso]]> https://www.researchpad.co/article/elastic_article_13849 The proliferation of cell phone ownership in Sub-Saharan Africa (SSA) presents the opportunity to collect public health indicators at a lower cost compared to face-to-face (FTF) surveys. This analysis assesses the equivalence of modern contraceptive prevalence estimates between a nationally representative FTF survey and a cell phone survey using random digit dialing (RDD) among women of reproductive age in Burkina Faso.MethodsWe analyzed data from two surveys conducted in Burkina Faso between December 2017 and May 2018. The FTF survey conducted by Performance Monitoring and Accountability (PMA2020) comprised a nationally representative sample of 3,556 women of reproductive age (15–49 years). The RDD survey was conducted using computer-assisted telephone interviewing and included 2,379 women of reproductive age.ResultsCompared to FTF respondents, women in the RDD sample were younger, were more likely to have a secondary degree and to speak French. RDD respondents were more likely to report using modern contraceptive use (40%) compared to FTF respondents (26%) and the difference remained unchanged after applying post-stratification weights to the RDD sample (39%). This difference surpassed the equivalence margin of 4%. The RDD sample also produced higher estimates of contraceptive use than the subsample of women who owned a phone in the FTF sample (32%). After adjusting for women’s sociodemographic factors, the odds of contraceptive use were 1.9 times higher (95% CI: 1.6–2.2) in the RDD survey compared to the FTF survey and 1.6 times higher (95% CI: 1.3–1.8) compared to FTF phone owners.ConclusionsModern contraceptive prevalence in Burkina Faso is over-estimated when using a cell phone RDD survey, even after adjusting for a number of sociodemographic factors. Further research should explore causes of differential estimates of modern contraceptive use by survey modes. ]]> <![CDATA[A screening of the MMV Pathogen Box® reveals new potential antifungal drugs against the etiologic agents of chromoblastomycosis]]> https://www.researchpad.co/article/elastic_article_13863 Chromoblastomycosis (CBM) is a chronic subcutaneous mycosis caused by traumatic implantation of many species of black fungi. Due to the refractoriness of some cases and common recurrence of CBM, a more effective and less time-consuming treatment is mandatory. The aim of this study was to identify compounds with in vitro antifungal activity in the Pathogen Box® compound collection against different CBM agents. Synergism of these compounds with drugs currently used to treat CBM was also assessed. An initial screening of the drugs present in this collection at 1 μM was performed with a Fonsecaea pedrosoi clinical strain according to the EUCAST protocol. The compounds with activity against this fungus were also tested against other seven etiologic agents of CBM (Cladophialophora carrionii, Phialophora verrucosa, Exophiala jeanselmei, Exophiala dermatitidis, Fonsecaea monophora, Fonsecaea nubica, and Rhinocladiella similis) at concentrations ranging from 0.039 to 10 μM. The analysis of potential synergism of these compounds with itraconazole and terbinafine was performed by the checkerboard method. Eight compounds inhibited more than 60% of the F. pedrosoi growth: difenoconazole, bitertanol, iodoquinol, azoxystrobin, MMV688179, MMV021013, trifloxystrobin, and auranofin. Iodoquinol produced the lowest MIC values (1.25–2.5 μM) and MMV688179 showed MICs that were higher than all compounds tested (5 - >10 μM). When auranofin and itraconazole were tested in combination, a synergistic interaction (FICI = 0.37) was observed against the C. carrionii isolate. Toxicity analysis revealed that MMV021013 showed high selectivity indices (SI ≥ 10) against the fungi tested. In summary, auranofin, iodoquinol, and MMV021013 were identified as promising compounds to be tested in CBM models of infection.

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<![CDATA[Placental transfer of Letermovir &amp; Maribavir in the <i>ex vivo</i> human cotyledon perfusion model. New perspectives for <i>in utero</i> treatment of congenital cytomegalovirus infection]]> https://www.researchpad.co/article/elastic_article_11236 Congenital cytomegalovirus infection can lead to severe sequelae. When fetal infection is confirmed, we hypothesize that fetal treatment could improve the outcome. Maternal oral administration of an effective drug crossing the placenta could allow fetal treatment. Letermovir (LMV) and Maribavir (MBV) are new CMV antivirals, and potential candidates for fetal treatment.MethodsThe objective was to investigate the placental transfer of LMV and MBV in the ex vivo method of the human perfused cotyledon. Term placentas were perfused, in an open-circuit model, with LMV or MBV at concentrations in the range of clinical peak plasma concentrations. Concentrations were measured using ultraperformance liquid chromatography coupled with tandem mass spectrometry. Mean fetal transfer rate (FTR) (fetal (FC) /maternal concentration), clearance index (CLI), accumulation index (AI) (retention of each drug in the cotyledon tissue) were measured. Mean FC were compared with half maximal effective concentrations of the drugs (EC50(LMV) and EC50(MBV)).ResultsFor LMV, the mean FC was (± standard deviation) 1.1 ± 0.2 mg/L, 1,000-fold above the EC50(LMV). Mean FTR, CLI and AI were 9 ± 1%, 35 ± 6% and 4 ± 2% respectively. For MBV, the mean FC was 1.4 ± 0.2 mg/L, 28-fold above the EC50(MBV). Mean FTR, CLI and AI were 10 ± 1%, 50 ± 7% and 2 ± 1% respectively.ConclusionsDrugs’ concentrations in the fetal side should be in the range for in utero treatment of fetuses infected with CMV as the mean FC was superior to the EC50 for both molecules. ]]> <![CDATA[Substantial improvement of tetraene macrolide production in <i>Streptomyces diastatochromogenes</i> by cumulative drug resistance mutations]]> https://www.researchpad.co/article/elastic_article_7861 Tetraene macrolides remain one of the most reliable fungicidal agents as resistance of fungal pathogens to these antibiotics is relatively rare. The modes of action and biosynthesis of polyene macrolides had been the focus of research over the past few years. However, few studies have been carried out on the overproduction of polyene macrolides. In the present study, cumulative drug-resistance mutation was used to obtain a quintuple mutant G5-59 with huge tetraene macrolide overproduction from the starting strain Streptomyces diastatochromogenes 1628. Through DNA sequence analysis, the mutation points in the genes of rsmG, rpsL and rpoB were identified. Additionally, the growth characteristic and expression level of tetrRI gene (belonging to the large ATP binding regulator of LuxR family) involved in the biosynthesis of tetraene macrolides were analyzed. As examined with 5L fermentor, the quintuple mutant G5-59 grew very well and the maximum productivity of tetramycin A, tetramycin P and tetrin B was as high as 1735, 2811 and 1500 mg/L, which was 8.7-, 16- and 25-fold higher than that of the wild-type strain 1628, respectively. The quintuple mutant G5-59 could be useful for further improvement of tetraene macrolides production at industrial level.

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<![CDATA[Abrogation of pathogenic attributes in drug resistant <i>Candida auris</i> strains by farnesol]]> https://www.researchpad.co/article/elastic_article_7651 Candida auris, a decade old Candida species, has been identified globally as a significant nosocomial multidrug resistant (MDR) pathogen responsible for causing invasive outbreaks. Biofilms and overexpression of efflux pumps such as Major Facilitator Superfamily and ATP Binding Cassette are known to cause multidrug resistance in Candida species, including C. auris. Therefore, targeting these factors may prove an effective approach to combat MDR in C. auris. In this study, 25 clinical isolates of C. auris from different hospitals of South Africa were used. All the isolates were found capable enough to form biofilms on 96-well flat bottom microtiter plate that was further confirmed by MTT reduction assay. In addition, these strains have active drug efflux mechanism which was supported by rhodamine-6-G extracellular efflux and intracellular accumulation assays. Antifungal susceptibility profile of all the isolates against commonly used drugs was determined following CLSI recommended guidelines. We further studied the role of farnesol, an endogenous quorum sensing molecule, in modulating development of biofilms and drug efflux in C. auris. The MIC for planktonic cells ranged from 62.5–125 mM, and for sessile cells was 125 mM (4h biofilm) and 500 mM (12h and 24h biofilm). Furthermore, farnesol (125 mM) also suppresses adherence and biofilm formation by C. auris. Farnesol inhibited biofilm formation, blocked efflux pumps and downregulated biofilm- and efflux pump- associated genes. Modulation of C. auris biofilm formation and efflux pump activity by farnesol represent a promising approach for controlling life threatening infections caused by this pathogen.

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<![CDATA[Managing possible serious bacterial infection of young infants where referral is not possible: Lessons from the early implementation experience in Kushtia District learning laboratory, Bangladesh]]> https://www.researchpad.co/article/elastic_article_7649 Serious infections account for 25% of global newborn deaths annually, most in low-resource settings where hospital-based treatment is not accessible or feasible. In Bangladesh, one-third of neonatal deaths are attributable to serious infection; in 2014, the government adopted new policy for outpatient management of danger signs indicating possible serious bacterial infections (PSBI) when referral was not possible. We conducted implementation research to understand what it takes for a district health team to implement quality outpatient PSBI management per national guidelines.MethodsPSBI management was introduced as part of the Comprehensive Newborn Care Package in 2015. The study piloted this package through government health systems with limited partner support to inform scale-up efforts. Data collection included facility register reviews for cases seen at primary level facilities; facility readiness and provider knowledge and skills assessments; household surveys capturing caregiver knowledge of newborn danger signs and care-seeking for newborn illness; and follow-up case tracking, capturing treatment adherence and outcomes. Analysis consisted of descriptive statistics.ResultsOver the 15-month implementation period, 1432 young infants received care, of which 649 (45%) were classified as PSBI. Estimated coverage of care-seeking increased from 22% to 42% during the implementation period. Although facility readiness and providers’ skills increased, providers’ adherence to guidelines was not optimal. Among locally managed PSBI cases, 75% completed the oral antibiotic course and 15% received the fourth day follow-up. Care-seeking remained high among private providers (95%), predominantly village health doctors (over 80%).ConclusionsFacility readiness, including health care provider knowledge and skills were strengthened; future efforts should focus on improving provider adherence to guidelines. Social and behavior change strategies targeting families and communities should explore shifting care-seeking from private, possibly less-qualified providers. Strategies to improve private sector management of PSBI cases and improved linkages between private and public sector providers could be explored. ]]> <![CDATA[Virulence factors and antibiograms of <i>Escherichia coli</i> isolated from diarrheic calves of Egyptian cattle and water buffaloes]]> https://www.researchpad.co/article/elastic_article_8462 Diarrhea caused by Escherichia coli in calves is an important problem in terms of survivability, productivity and treatment costs. In this study, 88 of 150 diarrheic animals tested positive for E. coli. Of these, 54 samples had mixed infection with other bacterial and/or parasitic agents. There are several diarrheagenic E. coli pathotypes including enteropathogenic E. coli (EPEC), Shiga-toxin producing E. coli (STEC), enterotoxigenic E. coli (ETEC) and necrotoxigenic E. coli (NTEC). Molecular detection of virulence factors Stx2, Cdt3, Eae, CNF2, F5, Hly, Stx1, and ST revealed their presence at 39.7, 27.2, 19.3, 15.9, 13.6, 9.0, 3.4, and 3.4 percent, respectively. As many as 13.6% of the isolates lacked virulence genes and none of the isolate had LT or CNF1 toxin gene. The odds of isolating ETEC from male calves was 3.6 times (95% CI: 1.1, 12.4; P value = 0.042) that of female calves, whereas the odds of isolating NTEC from male calves was 72.9% lower (95% CI: 91.3% lower, 15.7% lower; P value = 0.024) than that in females. The odds of isolating STEC in winter was 3.3 times (95% CI: 1.1, 10.3; P value = 0.037) that of spring. Antibiograms showed 48 (54.5%) of the isolates to be multi-drug resistant. The percent resistance to tetracycline, streptomycin, ampicillin, and trimethoprim-sulfamethoxazole was 79.5, 67.0, 54.5, and 43.0, respectively. Ceftazidime (14.8%), amoxicillin-clavulanic acid (13.6%) and aztreonam (11.3%) showed the lowest resistance, and none of the isolates was resistant to imipenem. The results of this study can help improve our understanding of the epidemiological aspects of E. coli infection and to devise strategies for protection against it. The prevalence of E. coli pathotypes can help potential buyers of calves to avoid infected premises. The antibiograms in this study emphasizes the risks associated with the random use of antibiotics.

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<![CDATA[Adherence to antiretroviral therapy and associated factors among Human immunodeficiency virus positive patients accessing treatment at Nekemte referral hospital, west Ethiopia, 2019]]> https://www.researchpad.co/article/elastic_article_7637 Antiretroviral therapy has a remarkable clinical effect in reducing the progress of Acquired Immune Deficiency Syndrome. The clinical outcome of Anti-Retroviral therapy depends on strict adherence. Poor adherence reduces the effectiveness of antiretroviral therapy and increases viral replication. With changes in service delivery over time and differences in socio-demographic status from region to region, it is essential to measure adherence. Therefore, this study aimed to assess adherence to antiretroviral therapy and its associated factors among HIV/AIDS patients accessing treatment at Nekemte referral hospital, West Ethiopia.MethodsInstitutional based cross-sectional study was conducted on 311 HIV/AIDS patients from March 01 to March 30, 2019. The study participants were selected by a simple random sampling method and interviewed using structured questionnaires. Bivariable logistic regression was conducted to find an association between each independent variable and adherence to antiretroviral medication. Multivariable logistic regression was used to find the independent variables which best predict adherence. The statistical significance was measured using odds ratio at a 95% confidence interval with a p-value of less than 0.05.ResultsOut of a total of 311 patients sampled, 305 were participated in the study, making a response rate of 98.07%. From these 305 study participants,73.1% (95% CI = 68.2, 78.0) were adherent to their medication. Having knowledge about HIV and its treatment (AOR = 8.24, 95% CI: 3.10, 21.92), having strong family/social support (AOR = 6.21, 95% CI: 1.39, 27.62), absence of adverse drug reaction (AOR = 5.33, 95% CI: 1.95, 14.57), absence of comorbidity of other chronic diseases (AOR = 5.72, 95% CI: 1.91, 17.16) and disclosing HIV status to the family (AOR = 5.08, 95% CI: 2.09, 12.34) were significantly associated with an increased likelihood of adherence to antiretroviral medication.ConclusionThe level of adherence to antiretroviral therapy was found low compared to WHO recommendation. The clinician should emphasize reducing adverse drug reaction, detecting and treating co-morbidities early, improving knowledge through health education, and encouraging the patients to disclose their HIV status to their families. ]]> <![CDATA[Incidence and determinants of Implanon discontinuation: Findings from a prospective cohort study in three health zones in Kinshasa, DRC]]> https://www.researchpad.co/article/elastic_article_7634 Kinshasa is Africa's third largest city and one of the continent’s most rapidly growing urban areas. PMA2020 data showed that Kinshasa has a modern contraceptive prevalence of 26.5% among married women in 2018. In Kinshasa’s method mix, the contraceptive implant recently became the dominant method among contraceptive users married and in union. This study provides insight into patterns of implant use in a high-fertility setting by evaluating the 24-month continuation rate for Implanon NXT and identifying the characteristics associated with discontinuation.MethodologyThis community-based, prospective cohort study followed 531 Implanon users aged 18–49 years at 6, 12 and 24 months. The following information was collected: socio-demographic characteristics, Method Information Index (MII) and contraceptive history. The main outcome variable for this study was implant discontinuation. The incidence rate of discontinuation is presented as events per 1000 person/months (p-m), from the date of enrolment. The Cox proportional hazards modelling was used to measure predictors of discontinuation.ResultsA total of 9158.13 p-m were available for analysis, with an overall incidence rate of 9.06 (95% CI: 9.04–9.08) removals per 1000 p-m. Of nine possible co-variates tested, the likelihood of discontinuation was higher among women who lived in military camps, had less than three children, never used injectables or implants in the past, had experienced heavy/prolonged bleeding, and whose MII score was less than 3.ConclusionIn addition to four client characteristics that predicted discontinuation, we identified one programmatic factor: quality of counseling as measured by the Method Information Index. Community providers in similar contexts should pay more attention to clients having less than three children, new adopters, and to clients living military camps as underserved population, where clients have less access to health facilities. More targeted counselling and follow-up is needed, especially on bleeding patterns. ]]> <![CDATA[Chitosan-propolis nanoparticle formulation demonstrates anti-bacterial activity against Enterococcus faecalis biofilms]]> https://www.researchpad.co/article/5989db50ab0ee8fa60bdc122

Propolis obtained from bee hives is a natural substance with antimicrobial properties. It is limited by its insolubility in aqueous solutions; hence ethanol and ethyl acetate extracts of Malaysian propolis were prepared. Both the extracts displayed antimicrobial and anti-biofilm properties against Enterococcus faecalis, a common bacterium associated with hospital-acquired infections. High performance liquid chromatography (HPLC) analysis of propolis revealed the presence of flavonoids like kaempferol and pinocembrin. This study investigated the role of propolis developed into nanoparticles with chitosan for its antimicrobial and anti-biofilm properties against E. faecalis. Bacteria that grow in a slimy layer of biofilm are resistant to penetration by antibacterial agents. The use of nanoparticles in medicine has received attention recently due to better bioavailability, enhanced penetrative capacity and improved efficacy. A chitosan-propolis nanoformulation was chosen based on ideal physicochemical properties such as particle size, zeta potential, polydispersity index, encapsulation efficiency and the rate of release of the active ingredients. This formulation inhibited E. faecalis biofilm formation and reduced the number of bacteria in the biofilm by ~90% at 200 μg/ml concentration. When tested on pre-formed biofilms, the formulation reduced bacterial number in the biofilm by ~40% and ~75% at 200 and 300 μg/ml, respectively. The formulation not only reduced bacterial numbers, but also physically disrupted the biofilm structure as observed by scanning electron microscopy. Treatment of biofilms with chitosan-propolis nanoparticles altered the expression of biofilm-associated genes in E. faecalis. The results of this study revealed that chitosan-propolis nanoformulation can be deemed as a potential anti-biofilm agent in resisting infections involving biofilm formation like chronic wounds and surgical site infections.

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<![CDATA[Dalcetrapib Reduces Risk of New-Onset Diabetes in Patients With Coronary Heart Disease]]> https://www.researchpad.co/article/N32959076-708b-4063-8edf-816fe24890d1

OBJECTIVE

Incident type 2 diabetes is common among patients with recent acute coronary syndrome and is associated with an adverse prognosis. Some data suggest that cholesteryl ester transfer protein (CETP) inhibitors reduce incident type 2 diabetes. We compared the effect of treatment with the CETP inhibitor dalcetrapib or placebo on incident diabetes in patients with recent acute coronary syndrome.

RESEARCH DESIGN AND METHODS

In the dal-OUTCOMES trial, 15,871 patients were randomly assigned to treatment with dalcetrapib 600 mg daily or placebo, beginning 4–12 weeks after an acute coronary syndrome. Absence of diabetes at baseline was based on medical history, no use of antihyperglycemic medication, and hemoglobin A1c and serum glucose levels below diagnostic thresholds. Among these patients, incident diabetes after randomization was defined by any diabetes-related adverse event, new use of antihyperglycemic medication, hemoglobin A1c ≥6.5%, or a combination of at least two measurements of serum glucose ≥7.0 mmol/L (fasting) or ≥11.1 mmol/L (random).

RESULTS

At baseline, 10,645 patients (67% of the trial cohort) did not have diabetes. During a median follow-up of 30 months, incident diabetes was identified in 403 of 5,326 patients (7.6%) assigned to dalcetrapib and in 516 of 5,319 (9.7%) assigned to placebo, corresponding to absolute risk reduction of 2.1%, hazard ratio of 0.77 (95% CI 0.68–0.88; P < 0.001), and a need to treat 40 patients for 3 years to prevent 1 incident case of diabetes. Considering only those with prediabetes at baseline, the number needed to treat for 3 years to prevent 1 incident case of diabetes was 25. Dalcetrapib also decreased the number of patients who progressed from normoglycemia to prediabetes and increased the number who regressed from diabetes to no diabetes.

CONCLUSIONS

In patients with a recent acute coronary syndrome, incident diabetes is common and is reduced substantially by treatment with dalcetrapib.

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<![CDATA[Efficacy and Safety of Liraglutide 3.0 mg in Individuals With Overweight or Obesity and Type 2 Diabetes Treated With Basal Insulin: The SCALE Insulin Randomized Controlled Trial]]> https://www.researchpad.co/article/N17ac9936-3fe4-430d-beaf-90ce59ac8a86

OBJECTIVE

Most individuals with type 2 diabetes also have obesity, and treatment with some diabetes medications, including insulin, can cause further weight gain. No approved chronic weight management medications have been prospectively investigated in individuals with overweight or obesity and insulin-treated type 2 diabetes. The primary objective of this study was to assess the effect of liraglutide 3.0 mg versus placebo on weight loss in this population.

RESEARCH DESIGN AND METHODS

Satiety and Clinical Adiposity—Liraglutide Evidence (SCALE) Insulin was a 56-week, randomized, double-blind, placebo-controlled, multinational, multicenter trial in individuals with overweight or obesity and type 2 diabetes treated with basal insulin and ≤2 oral antidiabetic drugs.

RESULTS

Individuals were randomized to liraglutide 3.0 mg (n = 198) or placebo (n = 198), combined with intensive behavioral therapy (IBT). At 56 weeks, mean weight change was −5.8% for liraglutide 3.0 mg versus −1.5% with placebo (estimated treatment difference −4.3% [95% CI −5.5; −3.2]; P < 0.0001). With liraglutide 3.0 mg, 51.8% of individuals achieved ≥5% weight loss versus 24.0% with placebo (odds ratio 3.41 [95% CI 2.19; 5.31]; P < 0.0001). Liraglutide 3.0 mg was associated with significantly greater reductions in mean HbA1c and mean daytime glucose values and less need for insulin versus placebo, despite a treat-to-glycemic-target protocol. More hypoglycemic events were observed with placebo than liraglutide 3.0 mg. No new safety or tolerability issues were observed.

CONCLUSIONS

In individuals with overweight or obesity and insulin-treated type 2 diabetes, liraglutide 3.0 mg as an adjunct to IBT was superior to placebo regarding weight loss and improved glycemic control despite lower doses of basal insulin and without increases in hypoglycemic events.

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<![CDATA[Oxycodone versus morphine for cancer pain titration: A systematic review and pharmacoeconomic evaluation]]> https://www.researchpad.co/article/N5c0f7a4c-4090-42ec-ba95-57e120b0c99c

Objective

To evaluate the efficacy, safety and cost-effectiveness of Oxycodone Hydrochloride Controlled-release Tablets (CR oxycodone) and Morphine Sulfate Sustained-release Tablets (SR morphine) for moderate to severe cancer pain titration.

Methods

Randomized controlled trials meeting the inclusion criteria were searched through Medline, Cochrane Library, Pubmed, EMbase, CNKI,VIP and WanFang database from the data of their establishment to June 2019. The efficacy and safety data were extracted from the included literature. The pain control rate was calculated to eatimate efficacy. Meta-analysis was conducted by Revman5.1.4. A decision tree model was built to simulate cancer pain titration process. The initial dose of CR oxycodone and SR morphine group were 20mg and 30mg respectively. Oral immediate-release morphine was administered to treat break-out pain. The incremental cost-effectiveness ratio was performed with TreeAge Pro 2019.

Results

19 studies (1680 patients)were included in this study. Meta-analysis showed that the pain control rate of CR oxycodone and SR morphine were 86% and 82.98% respectively. The costs of CR oxycodone and SR morphine were $23.27 and $13.31. The incremental cost-effectiveness ratio per unit was approximate $329.76. At the willingness-to-pay threshold of $8836, CR oxycodone was cost-effective, while the corresponding probability of being cost-effective at the willingness-to-pay threshold of $300 was 31.6%. One-way sensitivity analysis confirmed robustness of results.

Conclusions

CR oxycodone could be a cost-effective option compared with SR morphine for moderate to severe cancer pain titration in China, according to the threshold defined by the WHO.

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<![CDATA[Gender norms and mass deworming program access in Comé, Benin: A qualitative assessment of gender-associated opportunities and challenges to achieving high mass drug administration coverage]]> https://www.researchpad.co/article/N0cbc3c85-9c5e-43fe-983c-4afc7d1b8db3

The World Health Organization’s Neglected Tropical Disease Roadmap has accelerated progress towards eliminating select neglected tropical diseases (NTDs). This momentum has catalyzed research to determine the feasibility of interrupting transmission of soil-transmitted helminths (STH) using community-wide mass drug administration (MDA). This study aims to identify potential gender-specific facilitators and barriers to accessing and participating in community-wide STH MDA, with the goal of ensuring programs are equitable and maximize the probability of interrupting STH transmission. This research was conducted prior to the launch of community-wide MDA for STH in Comé, Benin. A total of 10 focus group discussions (FGDs) were conducted separately among 40 men, 38 women, and 15 community drug distributors (CDDs). Salient themes included: both men and women believe that community-wide MDA would reduce the financial burden associated with self-treatment, particularly for low income adults. Community members believe MDA should be packaged alongside water, sanitation, and other health services. Women feel past community-wide programs have been disorganized and are concerned these distributions will be similar. Women also expressed interest in increased engagement in the implementation of future community-based public health programs. Men often did not perceive themselves to be at great risk for STH infection and did not express a high demand for treatment. Finally, the barriers discussed by CDDs generally did not align with gender-specific concerns, but rather represented concerns shared by both genders. A door-to-door distribution strategy for STH MDA is preferred by women in this study, as this platform empowers women to participate as health decision makers for their family. In addition, involving women in planning and implementation of community-wide programs may help to increase treatment coverage and compliance.

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<![CDATA[Streptococcal H2O2 inhibits IgE-triggered degranulation of RBL-2H3 mast cell/basophil cell line by inducing cell death]]> https://www.researchpad.co/article/Nadf2e0c3-9608-4100-a6fa-f03310d30959

Mast cells and basophils are central players in allergic reactions triggered by immunoglobulin E (IgE). They have intracellular granules containing allergic mediators (e.g., histamine, serotonin, inflammatory cytokines, proteases and β-hexosaminidase), and stimulation by IgE-allergen complex leads to the release of such allergic mediators from the granules, that is, degranulation. Mast cells are residents of mucosal surfaces, including those of nasal and oral cavities, and play an important role in the innate defense system. Members of the mitis group streptococci such as Streptococcus oralis, are primary colonizers of the human oral cavity. They produce hydrogen peroxide (H2O2) as a by-product of sugar metabolism. In this study, we investigated the effects of streptococcal infection on RBL-2H3 mast cell/basophil cell line. Infection by oral streptococci did not induce degranulation of the cells. Stimulation of the RBL-2H3 cells with anti-dinitrophenol (DNP) IgE and DNP-conjugated human serum albumin triggers degranulation with the release of β-hexosaminidase. We found that S. oralis and other mitis group streptococci inhibited the IgE-triggered degranulation of RBL-2H3 cells. Since mitis group streptococci produce H2O2, we examined the effect of S. oralis mutant strain deficient in producing H2O2, and found that they lost the ability to suppress the degranulation. Moreover, H2O2 alone inhibited the IgE-induced degranulation. Subsequent analysis suggested that the inhibition of degranulation was related to the cytotoxicity of streptococcal H2O2. Activated RBL-2H3 cells produce interleukin-4 (IL-4); however, IL-4 production was not induced by streptococcal H2O2. Furthermore, an in vivo study using the murine pollen-induced allergic rhinitis model suggested that the streptococcal H2O2 reduces nasal allergic reaction. These findings reveal that H2O2 produced by oral mitis group streptococci inhibits IgE-stimulated degranulation by inducing cell death. Consequently, streptococcal H2O2 can be considered to modulate the allergic reaction in mucosal surfaces.

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<![CDATA[Proteomic analysis of protein composition of rat hippocampus exposed to morphine for 10 days; comparison with animals after 20 days of morphine withdrawal]]> https://www.researchpad.co/article/N2838fdc6-dc33-429a-ba0d-e2e831e6a950

Opioid addiction is recognized as a chronic relapsing brain disease resulting from repeated exposure to opioid drugs. Cellular and molecular mechanisms underlying the ability of organism to return back to the physiological norm after cessation of drug supply are not fully understood. The aim of this work was to extend our previous studies of morphine-induced alteration of rat forebrain cortex protein composition to the hippocampus. Rats were exposed to morphine for 10 days and sacrificed 24 h (groups +M10 and −M10) or 20 days after the last dose of morphine (groups +M10/−M20 and −M10/−M20). The six altered proteins (≥2-fold) were identified in group (+M10) when compared with group (−M10) by two-dimensional fluorescence difference gel electrophoresis (2D-DIGE). The number of differentially expressed proteins was increased to thirteen after 20 days of the drug withdrawal. Noticeably, the altered level of α-synuclein, β-synuclein, α-enolase and glyceraldehyde-3-phosphate dehydrogenase (GAPDH) was also determined in both (±M10) and (±M10/−M20) samples of hippocampus. Immunoblot analysis of 2D gels by specific antibodies oriented against α/β-synucleins and GAPDH confirmed the data obtained by 2D-DIGE analysis. Label-free quantification identified nineteen differentially expressed proteins in group (+M10) when compared with group (−M10). After 20 days of morphine withdrawal (±M10/−M20), the number of altered proteins was increased to twenty. We conclude that the morphine-induced alteration of protein composition in rat hippocampus after cessation of drug supply proceeds in a different manner when compared with the forebrain cortex. In forebrain cortex, the total number of altered proteins was decreased after 20 days without morphine, whilst in hippocampus, it was increased.

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<![CDATA[Baloxavir treatment of ferrets infected with influenza A(H1N1)pdm09 virus reduces onward transmission]]> https://www.researchpad.co/article/Nca8f7add-a1d9-4373-9c77-344aec55ea94

Influenza viruses cause seasonal outbreaks and pose a continuous pandemic threat. Although vaccines are available for influenza control, their efficacy varies each season and a vaccine for a novel pandemic virus manufactured using current technology will not be available fast enough to mitigate the effect of the first pandemic wave. Antivirals can be effective against many different influenza viruses but have not thus far been used extensively for outbreak control. Baloxavir, a recently licensed antiviral drug that targets the influenza virus endonuclease, has been shown to reduce virus shedding more effectively than oseltamivir, a widely used neuraminidase inhibitor drug. Thus it is possible that treatment with baloxavir might also interrupt onward virus transmission. To test this, we utilized the ferret model, which is the most commonly used animal model to study influenza virus transmission. We established a subcutaneous baloxavir administration method in ferrets which achieved similar pharmacokinetics to the approved human oral dose. Transmission studies were then conducted in two different locations with different experimental setups to compare the onward transmission of A(H1N1)pdm09 virus from infected ferrets treated with baloxavir, oseltamivir or placebo to naïve sentinel ferrets exposed either indirectly in adjacent cages or directly by co-housing. We found that baloxavir treatment reduced infectious viral shedding in the upper respiratory tract of ferrets compared to placebo, and reduced the frequency of transmission amongst sentinels in both experimental setups, even when treatment was delayed until 2 days post-infection. In contrast, oseltamivir treatment did not substantially affect viral shedding or transmission compared to placebo. We did not detect the emergence of baloxavir-resistant variants in treated animals or in untreated sentinels. Our results support the concept that antivirals which decrease viral shedding could also reduce influenza transmission in the community.

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<![CDATA[Nosocomial transmission of extensively drug resistant Acinetobacter baumannii strains in a tertiary level hospital]]> https://www.researchpad.co/article/N9f3b656c-39ce-49ef-bced-db8369f1110d

Acinetobacter baumannii is an opportunistic infectious agent that affects primarily immunocompromised individuals. A. baumannii is highly prevalent in hospital settings being commonly associated with nosocomial transmission and drug resistance. Here, we report the identification and genetic characterization of A. baumannii strains among patients in a tertiary level hospital in Mexico. Whole genome sequencing analysis was performed to establish their genetic relationship and drug resistance mutations profile. Ten genetically different, extensively drug resistant strains were identified circulating among seven wards. The genetic profiles showed resistance primarily against aminoglycosides and beta-lactam antibiotics. Importantly, no mutants conferring resistance to colistin were observed. The results highlight the importance of implementing robust classification schemes for advanced genetic characterization of A. baumannii clinical isolates and simultaneous detection of drug resistance markers for adequate patient’s management in clinical settings.

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<![CDATA[Antibiotic use for Australian Aboriginal children in three remote Northern Territory communities]]> https://www.researchpad.co/article/N999fa4e6-a15c-456a-862e-2e1ce88316a9

Objective

To describe antibiotic prescription rates for Australian Aboriginal children aged <2 years living in three remote Northern Territory communities.

Design

A retrospective cohort study using electronic health records.

Setting

Three primary health care centres located in the Katherine East region.

Participants

Consent was obtained from 149 mothers to extract data from 196 child records. There were 124 children born between January 2010 and July 2014 who resided in one of the three chosen communities and had electronic health records for their first two years of life.

Main outcome measures

Antibiotic prescription rates, factors associated with antibiotic prescription and factors associated with appropriate antibiotic prescription.

Results

There were 5,675 Primary Health Care (PHC) encounters for 124 children (median 41, IQR 25.5, 64). Of the 5,675 PHC encounters, 1,542 (27%) recorded at least one infection (total 1,777) and 1,330 (23%) had at least one antibiotic prescription recorded (total 1,468). Children had a median five (IQR 2, 9) prescriptions in both their first and second year of life, with a prescription rate of 5.99/person year (95% CI 5.35, 6.63). Acute otitis media was the most common infection (683 records, 38%) and Amoxycillin was the most commonly prescribed antibiotic (797 prescriptions, 54%). Of the 1,468 recorded prescriptions, 398 (27%) had no infection recorded and 116 (8%) with an infection recorded were not aligned with local treatment guidelines.

Conclusion

Prescription rates for Australian Aboriginal children in these communities are significantly higher than that reported nationally for non-Aboriginal Australians. Prescriptions predominantly aligned with treatment guidelines in this setting where there is a high burden of infectious disease.

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