Real-world treatment outcome of direct-acting antivirals and patient survival rates in chronic hepatitis C virus infection in Eritrea.

Reliable real-world data on direct acting anti-retroviral (DAA) uptake and treatment outcomes are lacking for patients with hepatitis C virus (HCV) in sub-Saharan Africa. This study provides data on HCV DAA-based treatment outcomes, mortality, loss-to-follow up, and associated factors among patients in Eritrea. A multicenter retrospective observational cohort study was conducted in two tertiary hospitals in Asmara, Eritrea. A structured checklist was used to collect data from patient's cards. Descriptive and inferential statistics used included means (± Standard deviation (SD), medians (Interquartile range (IQR), chi-squire (χ2), Kaplan-Meier estimates, and multivariate Cox proportional hazard models. A total of 238 patients with median age of 59 years (IQR 50-69 years) were enrolled in the study. Out of the 227 patients initiated on treatment, 125 patients had viral load measurements at 12 weeks after end of treatment (EOT) whereas 102 patients had no viral load measurements at 12 weeks EOT. Among the patients with HCV RNA data post-EOT 12, 116 (92.8%) had sustained viral response (SVR). The prevalence of death and loss-to-follow up (LTFU) were (7.5%, 95% CI 1.7-4.1) and 67 (28.1%, 95% CI 22.3-33.9) translating into an incidence of 1.1 (95% CI 0.8-1.5) per 10,000 person days. Independent predictors of LTFU included the enrollment year (2020: aHR = 2.2, 95% CI 1-4.7; p value = 0.04); Hospital (Hospital B: aHR = 2.2, 95% CI 1-4.7; p value = 0.03) and the FIB-4 score (FIB-Score < 1.45: aHR = 3.7, 95% CI 1.2-11.5; p value = 0.02). The SVR rates achieved in this cohort were high. However, high LTFU and high mortality driven largely by late presentation and suboptimal population screening/case finding, were uncovered. These challenges can be addressed by test-and-treat programs that simultaneously prioritize programmatic screening, decentralization of care, and better patient tracking in the HCV care cascade.

Isolated Asymptomatic Fetal Intracardiac Mass: A Case of Rhabdomyoma.

Introduction: Fetal cardiac rhabdomyoma is one of the rare benign cardiac masses which is commonly associated with the tuberous sclerosis complex (TSC). Though mostly fetal cardiac rhabdomyoma is asymptomatic it may lead to life-threatening conditions like outflow obstruction, arrhythmias, hydrops fetalis, or sudden fetal death. Case Report: We are reporting an isolated, asymptomatic fetal intra-cardiac mass (rhabdomyoma) that was discovered at 32 weeks of gestation and was followed as an outpatient until 39 weeks plus one day, at which point a cesarean section was performed. After delivery, the child underwent evaluations at the 1st day, 7th day, 30th day, 7th month, and 12th month of age. Following a checkup, the child's anthropometric and neurobehavioral growth were both healthy. Except for the tumor, which was neither growing nor shrinking in size, none of the clinical diagnostic criteria for tuberous sclerosis complex were met for this child up to the age of one year. Conclusion: The most common primary benign fetal cardiac tumor is cardiac rhabdomyoma, which is usually associated with tuberous sclerosis. In developing nations where it is challenging to obtain MRIs and genetic studies, and in a similar patient like ours with no other features of tuberous sclerosis, the child needs to be followed in the future, bearing in mind that tuberous sclerosis manifestations will continue to develop over a patient's lifetime.

Providers' knowledge on postpartum intrauterine contraceptive device (PPIUCD) service provision in Amhara region public health facility, Ethiopia.

INTRODUCTION: Postpartum intrauterine contraceptive devices (PP-IUCD) are one type of post-partum family planning method, which can be provided to a post-partum woman starting from the placental delivery time (within 10 minutes), or within the first 48 hours of postpartum period. In most developing countries, delivery time is the primary opportunity for women to access post-partum family planning methods, especially for those living in remote areas. Hence, this study assesses providers' knowledge on postpartum intrauterine contraceptive device service provision. METHODS: A facility-based cross-sectional study was conducted in Amhara region health center and hospitals. Health providers surveyed included obstetricians, gynecologists, general practitioners, emergency surgical officers, health officers, midwives and nurses from September 18, 2015 to December18, 2016. Simple random sampling was used to select 864 subjects. Data were collected by using a structured self-administered questionnaire and observing the facility. Multilevel analysis was done to see factors associated with outcome. RESULTS: A total of 197 health facilities and 864 providers are included in the final analysis. Of the total providers 524 (60.6%) were from a health center. The mean age (±SD) of participants was 27.8 years (±5.4). The number of providers with good knowledge accounted for 253 of those surveyed (29.3%). The proportion of good knowledge among trained PP-IUCD providers was 35.7% (those who scored above average), and 27.9% was untrained about PP-IUCD. A considerable heterogeneity was observed between health facilities for each indicator of provider's knowledge. Gender differences were observed as the mean knowledge score deference on PP-IUCD by 0.4 points (ß = -0.41; -0.72, -0.10) when the participant was female. Having experience of regular counseling of pregnant women increases PP-IUCD knowledge score by 0.97. (ß = 0.97; 95% CI: 0.48, 1.47). Where the health facility requested clients to purchase the IUCD themselves, the mean knowledge score decreased by 0.47 points compared with free of charge at the facility level (ß = -0.47; 95%CI: -0.87, -0.07). CONCLUSION: Our findings showed that providers' knowledge about postpartum IUCD was low in the Amhara region public health facility. The lowest knowledge score was noted among nurses, health Officers, midwives, and general practice professionals. Factors associated with providers' knowledge on PP-IUCD are the status of health facility, female sex, training on PP-IUCD, regular counseling of pregnant women, and unavailability of IUCD service.

pH-Sensitive Polymeric Nanoparticles Fabricated by Dispersion Polymerization for the Delivery of Bioactive Agents.

BACKGROUND: Development of pH-responsive nanoparticles capable of rapid degradation in the acidic environments in the endosomes and lysosomes of tumor tissues but relatively more stable in the physiological pH (pH 7.4) is desirable. OBJECTIVE: To show that the number of methoxy groups on the benzene ring of benzaldehyde bisacrylate acetal crosslinkers should affect the rate of hydrolysis of the crosslinkers and in vitro availability of the drug loaded into the nanoparticles. METHOD: Three pH-sensitive acetal crosslinkers were synthesized and characterized by 1H NMR, 13C NMR, FT-IR and high resolution mass spectroscopy (HR-MS). The nanoparticles were fabricated by free-radical dispersion polymerization method. Hydrolysis studies were carried out on the crosslinkers and nanoparticles; drug release studies were done on docetaxel-loaded nanoparticles at pH 5.0 and pH 7.4. The statisitical experimental design was randomized complete block design followed by analyses of variance with F-test of significance. Pairwise comparison test was used to locate specific differences among parameters of the crosslinkers and the nanopaticles. RESULTS: Scanning electron micrographs showed the formation of spherical particles. Particle size analysis showed that the nanoparticles are within nanosize range with negative zeta potential. Data showed that the rate of hydrolysis and drug release were faster at pH 5.0 compared to pH 7.4. Hydrolysis and drug release studies were dependent on the structure of the acetals: Di(2-methacryloyloxyethoxy)- [2,4,6-trimethoxyphenyl] methane crosslinker showed the fastest rate of hydrolysis, followed by di(2- methacryloyloxyethoxy)-[2,4-dimethoxyphe-nyl] methane and di(2-methacryloyloxyethoxy)-[4-methoxyphenyl] methane. CONCLUSION: The pH-responsive nanoparticles are suitable for the delivery of bioactive agents, especially anticancer drugs.

N-Butanoyl-N-(3-chloro-1,4-dioxonaph-thalen-2-yl)butanamide.

In the title compound, C18H18ClNO4, the imide group with its two alkyl substituents is approximately perpendicular to the plane of the naphtho-quinone ring system [dihedral angle = 78.5 (1)°]. Further, the imide carbonyl groups are oriented in an anti sense. In the crystal, the substituted naphtho-quinone rings form π-π stacks in the a-axis direction [perpendicular centroid-centroid distance = 3.209 (2) Šand slippage = 4.401 Å].

An Integrated Model for Patient Care and Clinical Trials (IMPACT) to support clinical research visit scheduling workflow for future learning health systems.

We describe a clinical research visit scheduling system that can potentially coordinate clinical research visits with patient care visits and increase efficiency at clinical sites where clinical and research activities occur simultaneously. Participatory Design methods were applied to support requirements engineering and to create this software called Integrated Model for Patient Care and Clinical Trials (IMPACT). Using a multi-user constraint satisfaction and resource optimization algorithm, IMPACT automatically synthesizes temporal availability of various research resources and recommends the optimal dates and times for pending research visits. We conducted scenario-based evaluations with 10 clinical research coordinators (CRCs) from diverse clinical research settings to assess the usefulness, feasibility, and user acceptance of IMPACT. We obtained qualitative feedback using semi-structured interviews with the CRCs. Most CRCs acknowledged the usefulness of IMPACT features. Support for collaboration within research teams and interoperability with electronic health records and clinical trial management systems were highly requested features. Overall, IMPACT received satisfactory user acceptance and proves to be potentially useful for a variety of clinical research settings. Our future work includes comparing the effectiveness of IMPACT with that of existing scheduling solutions on the market and conducting field tests to formally assess user adoption.

Antitrypanosomal activities and cytotoxicity of some novel imido-substituted 1,4-naphthoquinone derivatives.

The antitrypanosomal activities, cytotoxicity, and selectivity indices of eleven imido-substituted 1,4-naphthoquinone derivatives and nifurtimox have been studied. Compared to nifurtimox (IC(50) = 10.67 µM), all the imido-naphthoquinone analogs (IMDNQ1-IMDNQ11) are more potent on Trypanosoma cruzi with IC50 values ranging from 0.7 µM to 6.1 µM (p < 0.05). Studies of the cytotoxic activities of these compounds on a Balb/C 3T3 mouse fibroblast cell line revealed that four of these compounds, IMDNQ1, IMDNQ2, IMDNQ3, and IMDNQ10 displayed selectivity indices of 60.25, 53.97, 31.83, and 275.3, respectively, rendering them significantly (p < 0.05) more selective in inhibiting the parasite growth than nifurtimox (selectivity index = 10.86).

Cytotoxic effects of N-(3-chloro-1,4-dioxo 1,4-dihydro-naphthalen-2-yl)-benzamide on androgen-dependent and -independent prostate cancer cell lines.

BACKGROUND: Worldwide among men, prostate cancer ranks third in cancer occurrence and sixth in cancer mortality. A number of 1, 4-naphthoquinone derivatives have been identified that possess significant pharmacological effects associated with antitumor activities. In this study, the in vitro effects of N-(3-chloro-1,4-dioxo 1,4-dihydro-naphthalen-2-yl)-benzamide (NCDDNB) were evaluated on androgen-dependent (CWR-22) and androgen-independent (PC-3, DU-145) human prostate cancer cell lines, and on a normal bone marrow cell line (HS-5). Specifically, the in vitro activity of this compound on cell cycle regulation and apoptosis was evaluated. MATERIALS AND METHODS: Established methods of cell viability, cell cycle, Western blot and apoptosis were used. RESULTS: The effect of NCDDNB on CWR-22, PC-3, DU-145 and HS-5 cells revealed significant anti-tumor activities with IC(50)s, of 2.5, 2.5, 6.5, and 25 muM respectively. The results of cell cycle analysis showed that NCDDNB arrested PC-3, DU-145, and CWR-22 cells in the G(1)-phase of the cell cycle. The compound showed no effect on the cell cycle progression in the HS-5 bone marrow cell line. These findings were further validated using Western blot analysis. NCDDNB showed the greatest amount of apoptosis in the androgen-independent PC-3 cells in a time-dependent manner with the apoptotic apex at day 5 of treatment. Furthermore, NCDDNB induced-apoptosis in DU-145 and CWR-22 cells peaked at day 3 of treatment. CONCLUSION: Although the mechanism of action of this compound has not been completely elucidated, the effect on the cell cycle and the induction of apoptosis in different prostate cancer cell lines prompted us to carry out a more in-depth preclinical evaluation. This study suggests that NCDDNB may have an impact on treatment of prostate cancer while protecting the bone marrow.

Synthesis of 3-[(N-carboalkoxy)ethylamino]-indazole-dione derivatives and their biological activities on human liver carbonyl reductase.

A series of indazole-dione derivatives were synthesized by the 1,3-dipolar cycloaddition reaction of appropriate substituted benzoquinones or naphthoquinones and N-carboalkoxyamino diazopropane derivatives. These compounds were evaluated for their effects on human carbonyl reductase. Several of the analogs were found to serve as substrates for carbonyl reductase with a wide range of catalytic efficiencies, while four analogs display inhibitory activities with IC(50) values ranging from 3-5 microM. Two of the inhibitors were studied in greater detail and were found to be noncompetitive inhibitors against both NADPH and menadione with K(I) values ranging between 2 and 11 microM. Computational studies suggest that conformation of the compounds may determine whether the indazole-diones bind productively to yield product or nonproductively to inhibit the enzyme.

Secure, obligated and coordinated collaboration in health care for the patient-centered medical home.

In the patient-centered medical home, PCMH, patient care is overseen by a primary care physician leading a team of health care providers, who collaborate to optimize treatment. To facilitate interactions in PCMH, secure collaboration will be needed to: control access to information; dictate who can do what when; and promote sharing and concurrent access. This contrasts approaches such as the National Institute of Standard and Technology (NIST) role-based access control (RBAC), where the emphasis is on controlling access and separating responsibilities. This paper investigates secure collaboration within an application such as PCMH, through: a futuristic scenario for patient care; proposed collaboration extensions to the NIST RBAC standard with a fine-grained obligated mechanism and workflow; and a prototype of PCMH via the Google Wave real-time collaboration platform.

Biological evaluation of 2,3-dichloro-5,8-dimethoxy-1,4-naphthoquinone as an anti-breast cancer agent.

BACKGROUND: Breast cancer is the most frequent cancer and the second leading cause of cancer deaths in women today. A number of 1,4-naphthoquinone derivatives have been found to possess significant pharmacological effects associated with marked antimicrobial and antitumor activities. In the present study, the in vitro effect of 2,3-dichloro-5,8-dimethoxy-1,4-naphthoquinone (DCDMNQ) was evaluated on estrogen-positive MCF-7 and estrogen-negative MDA-MB-436 and Hs-578T human breast cancer cell lines. Moreover, the in vitro activity of this compound on cell cycle regulation and apoptosis were evaluated. MATERIALS AND METHODS: Established methods of cell viability, cell cycle, Western blot and apoptosis were used. RESULTS: The effect of DCDMNQ on MCF-7, MDA-MB-436 and Hs-578T cells revealed significant antitumor activities with IC(50)s, of 0.6 +/- 0.02, 1.4 +/- 0.25 and 3.1 +/- 0.4 microM respectively. Cell cycle analysis showed that DCDMNQ inhibited progression through the cell cycle in MCF-7 and MDA-MB-436 cell lines in a time-dependent manner. DCDMNQ arrested cells in the S-phase of the cell cycle with the greatest proportion of cells in the S-phase by day 5. This cell-cycle arrest was corroborated by inhibition of topoisomerase I induced by DCDMNQ. These findings were further validated using Western blot analysis of retinoblastoma protein time-dependent phosphorylation. Furthermore, DCDMNQ induced apoptosis in both estrogen-positive and -negative cell lines in a time-dependent manner. However, the highest percentages of apoptotic cells were observed in the MDA-MB-436 cell line. CONCLUSION: Although the mechanism of action of DCDMNQ has not been completely elucidated, it appears that this compound can inhibit topoisomerase I in a concentration-dependent manner. These promising results to explore novel naphthoquinone analogues as potential breast cancer agents. This study suggests that DCDMNQ may have an impact on treatment of estrogen-positive and -negative breast cancer while protecting the bone marrow.

2-Chloro-3-(4-chloro-benzamido)-1,4-naphthoquinone.

The naphthoquinone ring is almost perpendicular [dihedral angle 71.02 (3)°] to the phenyl group of the title compound, C(17)H(9)Cl(2)NO(3), while the dihedral angle between the amide group and the 4-chloro-phenyl ring is 21.9 (2)°. The conformation of the N-H and C=O bonds are anti to each other. N-H⋯Cl hydrogen bonds link the mol-ecules into chains in the a-axis direction. In addition, these chains are linked by weak inter-molecular C-H⋯O inter-actions.

Cytotoxicity of 2,3-dichloro-5,8-dimethoxy-1,4-naphthoquinone in androgen-dependent and -independent prostate cancer cell lines.

BACKGROUND: Prostate cancer ranks third worldwide in cancer incidence and sixth in cancer mortality among men. A number of 1,4-naphthoquinone derivatives have been found to possess significant pharmacological effects associated with marked antimicrobial and antitumor activities. In the present study the in vitro effect of 2,3-dichloro-5,8-dimethoxy-1,4-naphthoquinone (DCDMNQ) was evaluated on androgen-dependent (LNCaP, CWR-22) and androgen-independent (PC-3. DU-145) human prostate cancer cell lines, and/or a normal bone marrow cell line (HS-5). Moreover, the in vitro activity of this compound on cell cycle regulation and apoptosis was evaluated. MATERIALS AND METHODS: Established methods of cell viability, cell cycle, Western blot and apoptosis were used. RESULTS: The effect of DCDMNQ on LNCaP, CWR-22, PC-3, DU-145 and HS-5 cells revealed significant anti-tumor activities with IC50s, of 1, 3. 1.5, 3 and 10 microM respectively. Cell cycle analysis showed that DCDMNQ inhibited progression through the cell cycle in PC-3 and DU-145 cell lines in a time-dependent manner. The result for the CWR-22 cell line showed that DCDMNQ arrested cells in the G -phase of the cell cycle with the greatest proportion of cells in the G1-phase by day 5; however, the LNCaP cell line was inconsistent. The compound showed no effect on the cell cycle progression in the bone marrow HS-5 cell line. These findings were further validated using Western blot analysis. Furthermore, DCDMNQ induced apoptosis in the androgen-independent cells, preferentially over that of the androgen-dependent cell lines, in a time-dependent manner. CONCLUSION: Although the mechanism of action of this compound has not been completely elucidated, the effect on the cell cycle and the induction of apoptosis in different prostate cancer cell lines prompted us to carry out a more in-depth preclinical evaluation of it. This study suggests that DCDMNQ may have an impact on treatment of prostate cancer while protecting the bone marrow.