Frecuencia y factores asociados a la inercia tera¬péutica en inicio de insulinización en pacientes con Diabetes Mellitus II en el Hospital José Carrasco Arteaga, Cuenca, 2018 / Frequency and associated factors with therapeutic inertia at the start of insulin therapy in patients with Diabetes Mellitus II, Hospital José Carrasco Arteaga. Cuenca, 2018

INTRODUCCIÓN: La Diabetes Mellitus II es un problema sanitario a nivel mundial, sin excepción en nuestro país. El tratamiento farmacológico de la DM2 se basa en un esquema escalonado, que varía según las necesidades del paciente y el desarrollo de la enfermedad, así como del control glucémico del mismo. El retraso en la intensificación del tratamiento o el inicio de la insulinización, hecho que se conoce como inercia terapéutica, obedece a diferentes factores atribuibles tanto al paciente, como al sistema sanitario, aumentando el riesgo de complicaciones crónicas, tanto micro como macrovasculares. MATERIALES Y MÉTODOS: Se realizó un estudio observacional, transversal, descriptivo y de correlación. Se estudiaron 422 pacientes de consulta externa de Endocrinología y Medicina Interna del Hospital "José Carrasco Arteaga" en el año 2018, con diagnóstico de Diabetes Mellitus II que recibieron como tratamiento dos antidiabéticos orales; con el objetivo de conocer la frecuencia y factores asociados a la inercia terapéutica en estos pacientes. La recolección de datos se realizó a partir de las historias clínicas de los pacientes, en un formulario diseñado para el estudio. El análisis fue hecho en el programa SPSS v.25, aplicando estadística descriptiva y de correlación con la prueba Chi-cuadrado, con un nivel de confianza del 95%. RESULTADOS: El 59.2% de la muestra estudiada tenía 65 años o más, 54.7% fueron mujeres, 46.7% tenía sobrepeso y 36% obesidad. El 96.7% tenía tres o más años de evolución de la enfermedad, 63.7% presentaron control glucémico adecuado. La comorbilidad más frecuente fue la hipertensión arterial, que se presentó en el 61.6%. El 87% tenía Metformina más Glibenclamida como tratamiento. El 86.3% se encontraban recibiendo su actual tratamiento por más de tres meses. La inercia terapéutica se presentó en el 25.8%, y de estos casos, la inercia se relacionó con el personal de salud en el 75.2%. CONCLUSIÓN: Se presentó inercia terapéutica en el 25.8% de la muestra. La mayoría de las inercias terapéuticas están relacionadas con el personal de salud. No se encontró asociación estadísticamente significativa de la ocurrencia de la inercia terapéutica con la edad, el sexo, el nivel de instrucción, las comorbilidades, el estado nutricional o el tiempo de evolución de la DMII.(au)

BACKGROUND: Diabetes Mellitus II is a global health issue, with no exception in Ecuador. The pharmacological treatment of DM2 is based on a stepped scheme, which varies according to the patients' needs, the disease course, and the glycaemic control. The delay in the treatment intensification or the insulin initiation, known as therapeutic inertia, is caused by different factors attributable to both the patient and the health care systems, increasing the risk of both micro and macrovascular chronic complications. METHODS: we carried out an observational, cross-sectional, descriptive and correlation study. 422 patients from the Endocrinology and Internal Medicine outpatient clinic of "Hospital José Carrasco Arteaga" in 2018, with DM2 diagnosis, who received two oral antidiabetic drugs as treatment were studied; with the purpose of identifying the frequency and associated factors with therapeutic inertia in these patients. Data was collected from medical records in a form designed for this study. The data analysis was made in the SPSS v.25 software, applying descriptive statistics and correlation statistics with Chi-square test, with a confidence level of 95%. RESULTS: 59.2% of the sample was 65 years or older, 54.7% were women, 46.7% were overweight and 36% were obese. 96.7% had three or more years of diagnosis of the disease, 63.7% had adequate glycaemic control. The most frequent comorbidity was hypertension, which occurred in 61.6% patients. 87% were using Metformin plus Glibenclamide as treatment. 86.3% were receiving their current treatment for more than three months. Therapeutic inertia presented in 25.8% of the sample, and of these cases, inertia was related to health personnel in 75.2%. CONCLUSION: therapeutic inertia presented in 25.8% of the sample. Most of the therapeutic inertias were related to the health personnel. No significant statistically association was found between the occurrence of therapeutic inertia with age, sex, educational level, comorbidities, nutritional status or years of evolution of DMII.(au)

Associated Factors for Target Blood Pressure Achievement after Triple Combination Therapy in Hypertensive Patients

BACKGROUND: The prevalence of hypertension reaches 29% in adults over 30 years of age in the Korean population; however, the control rate is merely 44%. The aim of this study was to investigate the associated factors for target blood pressure achievement after triple combination therapy in hypertensive patients. METHODS: From February 2016 to May 2018, 10 family physicians recruited 348 patients, who newly started a triple combination antihypertensive medication. Target blood pressure was defined as a systolic blood pressure (SBP) <140 mmHg and diastolic blood pressure (DBP) <90 mmHg after 6 months of triple combination therapy. Multivariate logistic regression analyses were performed to analyze the associated factors for target blood pressure achievement. RESULTS: Among the 348 study participants, 317 completed 6 months of treatment. The target achievement rate was 76.3% (242/317). The mean absolute difference and 95% confidence interval (CI) for the SBP and DBP were 10.8 mmHg (8.8 to 12.7) and 6.4 mmHg (5.1 to 7.8), respectively (P<0.05). The odds ratio (OR) for the target blood pressure achievement increased in those with college education or higher (OR, 2.69; 95% CI, 1.22–5.92), those with dyslipidemia (OR, 1.74; 95% CI, 1.01–2.99), and those who were satisfied with the medication (OR, 29.91; 95% CI, 3.70–241.92). CONCLUSIONS: The presence of dyslipidemia and patient's satisfaction with the medication were associated with target blood pressure achievement in our analyses. Our findings suggest the importance of patient's factor in the control of blood pressure.

Methods to improve the treatment of antitumor angiogenesis / 肿瘤

Abnormal vessel and function are hallmarks of cancer, and they contribute to cancer progression and migration. Angiogenesis has become an attractive target for drug therapy, and several regulatory and signaling molecules governing angiogenesis are of interest. Angiogenesis inhibitors, intending to block tumor's blood supply and provide survival benefits for cancer patients, may fuel tumor progression and treatment resistance. Actionable strategies to improve clinical efficacy of angiogenesis inhibitors include vascular mimicry regulation, tumor vessel normalization, seeking predictive factors, multi-targeted drugs development and combinational therapeutics. Moreover, strategies aiming at alleviating tumor hypoxia while improving perfusion may enhance the outcome of antiangiogenic therapy. Angiogenesis inhibitors offer an avenue for the development of cancer therapy.

Irinotecan Monotherapy Versus Irinotecan-Based Combination as Second-Line Chemotherapy in Advanced Gastric Cancer: A Meta-Analysis / Journal of the Korean Cancer Association, 대한암학회지

PURPOSE: A meta-analysis was conducted to examine the question of whether combination regimens are more effective than monotherapy as a second-line chemotherapy in advanced gastric cancer. MATERIALS AND METHODS: The MEDLINE and the EMBASE databases and the Cochrane Central Register for Controlled Trials were searched using appropriate keywords. Only randomized controlled trials were eligible. RESULTS: Taxane-based study is rare; thus, four irinotecan-based studies were finally included in the meta-analysis. Out of 661 patients, 331 patients were assigned to combination therapy and 330 to monotherapy. Cisplatin or fluoropyrimidine (S-1 or 5-fluorouracil) was used as a combination partner to irinotecan. The pooled hazard ratio (HR) for overall survival (OS) and for progression-free survival (PFS) was 0.938 (95% confidence interval [CI], 0.796 to 1.104; p=0.442) and 0.815 (95% CI, 0.693 to 0.958; p=0.013). In subgroup analysis according to previous exposure to a partner agent, the PFS benefit of combination was observed only in the partially exposed group (HR, 0.784; 95% CI, 0.628 to 0.980; p=0.032). CONCLUSION: Second-line irinotecan-based combination was not associated with increased OS, but with PFS benefit, which seemed particularly significant for patients receiving combination with a new agent.

Intratympanic Steroid and Oral Diuretics Combination Therapy for Acute Low Frequency Sensorineural Hearing Loss without Vertigo / 대한이비인후과학회지

BACKGROUND AND OBJECTIVES: The effectiveness of intratympanic dexamethasone injections (ITD) alone is compared against the combination therapy of ITD and oral diuretics as treatments for acute low frequency sensorineural hearing loss (LFHL) without vertigo. SUBJECTS AND METHOD: A total of 36 patients, with LFHL 0.05). For subjective symptoms, there were no statistically significant differences in the improvement rate in either group (combination 58.8% vs. ITD only 63.2%, p>0.05). In pure tone audiometry, the improvement rate of the combination group was not significantly different from that of the ITD only group (76.5% vs. 73.7%, p>0.05). There was a significant correlation between the complete recovery rate and duration of symptoms. CONCLUSION: ITD alone is an effective treatment modality for LFHL within 1 month after onset. Diuretics have no additive effect for the recovery of hearing in patients with acute LFHL without vertigo.

Effects of combination therapy of docetaxel with selenium on the human breast cancer cell lines MDA-MB-231 and MCF-7

PURPOSE: The anticancer property and cytoprotective role of selenium in chemotherapy have been reported. However, the combination effects of selenium on chemotherapy for advanced breast cancer have not yet been clearly defined. The purpose of this study was to investigate the combined effects of selenium on chemotherapy using docetaxel on breast cancer cell lines. METHODS: Under adherent culture conditions, two breast cancer cell lines, MDA-MB-231 and MCF-7, were treated with docetaxel at 500pM and selenium at 100nM, 1microM, or 10microM. Changes in cell growth, cell cycle duration, and degree of apoptosis after 72 hours in each treated group were evaluated. RESULTS: In the MDA-MB-231 cells, the combination therapy group (docetaxel at 500pM plus selenium at 10microM) showed a significantly decreased percentage of cell growth (15% vs. 28%; P = 0.004), a significantly increased percentage of late apoptosis (63% vs. 26%; P = 0.001), and an increased cell cycle arrest in the G2/M phase (P = 0.001) compared with the solitary docetaxel therapy group. Isobologram analysis demonstrated the synergistic effect of the combination therapy in the MDA-MB-231 cells. However, in the MCF-7 cells, no significant differences in the percentage of cell growth apoptosis, the percentage of apoptosis, and the pattern of cell cycle arrest were noted between the combination therapy groups and the solitary docetaxel therapy group. CONCLUSION: Our in vitro study indicated that the combination of selenium with docetaxel inhibits cell proliferation through apoptosis and cell arrest in the G2/M phase in MDA-MB-231 breast cancer cells.

In vitro antimicrobial activity of cefsulodin and kanamycin in combinations.

Background: Infectious diseases are the greatest challenge of the world. The main failure in the treatment of infectious diseases is development of antibiotic resistance by the infective agents. Combination drug therapy is proposed to be more successful to contain diseases. But before the selection of combination of antibiotics, it is important to determine interaction of such antibiotics. Two antibiotics may have either synergistic or antagonistic action. In this study it was designed to find out the Minimum Inhibitory Concentration (MIC), and Minimum Bactericidal Concentration (MBC), which is usually used for the quantitative assessment of bacterial sensitivity to antibiotics. Methods: Checkerboard titration in microtitre trays used for this assay, and Fractional Inhibitory Concentration (FIC) and Fractional Bactericidal Concentration (FBC) measured to identify the type of interaction between the two antibiotics. Cefsulodin (Cef) and Kanamycin (Kan) were used against Escherechia coli (Esch. coli) and Staphylococcus aureus (Staph. aureus) to determine the efficacy of these antibiotics in combination. Results: MIC of cefsulodin and kanamycin against Staph. aureus was 3.125 and 3.125 respectively. MIC of Cef for Esch. coli was 6.25 and for Kan 50. FIC for Staph. aureus was 1. FIC for Esch. coli was different in different antibiotic concentrations and the least value was 0.37. There was no bactericidal effect of these antibiotics in combination against these organisms. Conclusion: Combination of two drugs cefsulodin and kanamycin showed synergistic action against Esch. coli and additive against Staph. aureus. So combined drug therapy can be used for better treatment with low toxicity, broad spectrum activity, and prevent emergence of drug resistance organism.

Effect of As2 O3 and paclitaxel on the proliferation of A549 cell and ectopic tumor growth of nude mice / 中国生化药物杂志

Objective To evaluate the effect of As2O3 combined with paclitaxel(PTX)on the treatment of lung cancer.Methods The anti-proliferation efficiency of As2 O3 combined with PTX was evaluated by MTT assay.Tumor spheroids were used to evaluate anti-tumor ability of As2 O3 combined with PTX.Transmission electron microscope (TEM)were used to observe the apoptosis morphous.A549 cell were xenografted in mice to establish the animal model,and the nude mices were devided into four groups,saline group,As2 O3 group,PTX group and As2 O3 +PTX group.The animal model were used to evaluate the effect of anti-tumor.The tumor size of every group were measured.HE was used to observe the apoptosis of cancer cells. Results The cell inhibition rate of A549 cell were(3.35 ±0.21)%,(47.55 ±2.25)%,(64.64 ±3.35)%and(84.58 ±3.76)%after treatment with saline,As2O3,PTX and As2O3combined with PTX after 48h respectively(P<0.01).The early apoptosis rate of cancer cells were 0.26%,9.7%, 17.8% and 42.5% for saline group,As2 O3 group,PTX and As2 O3 +PTX group respectively(P<0.01 ).The final tumor spheroid volumes in saline group increased 1.36 times after 7 days.The final tumor spheroid volumes reduced to(77.35 ±2.31)%,(61.68 ±2.44)% and(44.85 ±3.34)% in As2O3,PTX and As2O3 combined with PTX group respectively(P<0.01).The inhibition of lung cancer in vitro demonstrated the inhibition rate of tumor growth compared with saline group were(22.4 ±4.5)%,(39.5 ±6.2)% and(69.5 ±7.3)% for As2O3,PTX and As2O3 +PTX,respectively(P<0.01 ).Conclusion As2 O3 combined with PTX can effectively inhibit the proliferation of A549 cells and ectopic tumor growth in nude mice and it may be a potentially effective treatment for lung cancer.

Antihypertensive drug combinations

Hypertension has a diverse pathophysiology. Theoretically, one drug is not sufficient to control high blood pressure (BP) in most hypertension. Therefore, the combination of two or more drugs with different mechanisms is needed to meet the target BP. In setting the target BP, a low-dose combination of two drugs with different mechanisms has greater efficacy and safety than a higher dose of one drug. Recent clinical trials and hypertension guidelines from different parts of the world report that the combination of renin-angiotensin system inhibitors with calcium channel antagonists or diuretics is generally recommended but combinations including beta-blockers, rarely so. However, if even a combination of three drugs all with different mechanisms, each at full dose does not control the BP, then a beta-blocker and/or other antihypertensive drug should be considered. Rarely, an interventional procedure such as renal sympathetic denervation has been applied, but evidence supporting such therapies remains limited.

Therapy of Infections due to Carbapenem-Resistant Gram-Negative Pathogens

The prevalence of carbapenem-resistant gram-negative bacterial pathogens (CRGNs) has increased dramatically during the last 10 years, but the optimal treatment for CRGN infections is not well established due to the relative scarcity of robust clinical data. The polymyxins remain the most consistently active agents against CRGNs in vitro. Tigecycline, based on its in vitro antibacterial spectrum, could also be considered as a therapeutic option in the treatment of infections caused by certain CRGNs. Other agents, including aminoglycosides, rifampin, trimethoprim-sulfamethoxazole, fosfomycin and fluoroquinolones, could be considered as monotherapy or combination therapy against CRGNs in appropriate contexts, as combination therapy with two or more in vitro active drugs appears to be more effective than monotherapy based on some clinical data. Several promising new agents are in late-stage clinical development, including ceftolozane-tazobactam, ceftazidime-avibactam and plazomicin. Given the shortage of adequate treatment options, containment of CRGNs should be pursued through implementation of adequate infection prevention procedures and antimicrobial stewardship to reduce the disease burden and prevent future outbreaks of CRGNs.

In vitro Synergism between Chloroquine and Antibiotics against Orientia tsutsugamushi

BACKGROUND: To investigate whether chloroquine enhances the effect of antibiotics against Orientia tsutsugamushi, the causative organism of scrub typhus, we compared the effect of antibiotics in combination with chloroquine with the effect of antibiotics alone in vitro. MATERIALS AND METHODS: The Boryong or AFSC-4 strain was inoculated into ECV304 cells, and incubated in medium containing doxycycline (4 microg/mL), rifampin (4 microg/mL), azithromycin (0.5 microg/mL), chloroquine (1 microg/mL), and each of these antibiotics in combination with chloroquine for 7 d. Immunofluorescence (IF) staining for O. tsutsugamushi was performed 4 hr and 7 d after inoculation of the bacteria, and IF-positive foci were enumerated. RESULTS: Chloroquine inhibited the growth of O. tsutsugamushi by 15.5%. In combination with chloroquine, the antimicrobial effects increased by 4.4% for doxycycline (a 92.9% reduction of bacterial numbers for doxycycline versus a 97.3% reduction for doxycycline plus chloroquine), 4.6% for rifampin (90.0% versus 94.6%), and 8.3% for azithromycin (86.9% versus 95.2%). The antimicrobial effect of the antibiotics alone was significantly different compared to the combined effect of antibiotics and chloroquine (Wilcoxon signed-rank test, P = 0.001). CONCLUSIONS: The combined use of chloroquine with an antibiotic for the treatment of O. tsutsugamushi infections may be useful for increasing the efficacy of the antibiotics.

Detection of plasma clozapine concentration in psychosis disorder inpatients receiving comedications / 第二军医大学学报

Objective To investigate the effect of valgus comedications on the plasma concentration of clozapnnercLZ) in inpatients with psychis disorder. Methods High performance iiquid chromatography (HPLC) was used to analyze serum CLZand norclozapine (N-CLZ) concentrations in 571 psychis patients. The nnfluence of commedication on plasma CLZ concentration was analyzed udng SPSS 17. 0 software while considesing the dosage of CLZ and the comedications with 12 drugs most often used in combmation with CLZ. Results The CLZ dosage, plasma CLZ concentration and plasma N-CLZ concentration in the comedication group were signiticancly lower than those nn pure CLZ group (P<0. 01). The CLZ dosage in groups of comedications with donazepam, paroxetine, venlafaxnne, aripiprazole, quetiaprne and tispetidone were signiticancly lower than that of pure CLZ group (P<0. 05, P<0. 01). Comedication with donazepam, iithium carbonate, valproate and quetiaprne signiticanclydecreased the plasma concentration of CLZ (P<0. 05, P<0. 01). Comedication with donazepam, iithium carbonate, valproate, sertraHne, quetiaprne and tispetidone signiticantiy decreased the plasma concentration of N-CLZ (P<0.05, P<0. 01). Spearman's correlation analytis found that therewere signiticant positive corrclations among any two of dosageCLZ, concentration of CLZ and concentration of N-CLZ in CLZ group (P<0. 05, P<0. 01). Conclusion Some commonly-used antipsychotics have impact on plasma CLZ concentration. Drug monitoring and dosage regulation of CLZ should be stressed among patients comedicated with clozapine combined with other antipsychotics, so as to timely regulate the dosage of CLZ.

Antimicrobial Susceptibility of Stenotrophomonas maltophilia Isolates from Korea, and the Activity of Antimicrobial Combinations against the Isolates

The aim of this study was to determine antimicrobial susceptibility of recent clinical Stenotrophomonas maltophilia isolates from Korea, and to compare the activity levels of several combinations of antimicrobials. A total of 206 non-duplicate clinical isolates of S. maltophilia was collected in 2010 from 11 university hospitals. Antimicrobial susceptibility testing was performed using the Clinical Laboratory Standards Institute agar dilution method. In vitro activity of antimicrobial combinations was tested using the checkerboard method. The susceptibility rates to trimethoprim-sulfamethoxazole and minocycline were 96% and 99%, respectively. The susceptibility rate to levofloxacin was 64%. All of four antimicrobial combinations showed synergy against many S. maltophilia isolates. A combination of trimethoprim-sulfamethoxazole plus ticarcillin-clavulanate was most synergistic among the combinations. None of the combinations showed antagonistic activity. Therefore, some of the combinations may be more useful than individual drugs in the treatment of S. maltophilia infection. Further clinical studies are warranted to validate our in vitro test results.

High efficacy of adefovir and entecavir combination therapy in patients with nucleoside-refractory hepatitis B / 대한간학회지

BACKGROUND/AIMS: Newly developed and potent antiviral agents suffer from the problem of drug resistance. Multidrug resistance is a major impediment in the treatment of patients with chronic hepatitis B (CHB). In line with American Association for the Study of Liver Diseases guidelines, adefovir dipivoxil (ADV) add-on therapy is recommended in the case of lamivudine resistance, while tenofovir disoproxil fumarate (TDF) is recommended for ADV or entecavir (ETV) resistance. TDF is currently not available in Korea. ADV+ETV combination therapy may be a viable alternative to TDF in patients with either ADV or ETV resistance. However, the efficacy of ADV+ETV combination therapy in patients with CHB and multidrug resistance is unclear. This study investigated the efficacy of ADV+ETV combination therapy in patients with multidrug resistance. METHODS: Twenty-five patients were enrolled and were administered ADV+ETV combination therapy for at least 6 months. Blood was drawn at baseline and at 3, 6, 9, and 12 months after commencing treatment, and the following blood parameters were analyzed: alanine transaminase, hepatitis B e-antigen (HBeAg), anti-hepatitis B e-antigen, and hepatitis B virus (HBV) DNA levels. The initial virological response (IVR) was defined as an HBV DNA level of or =5.0 log) dropped from 76% at baseline to only 5% after 6 months of treatment. The biochemical response rate during the first 6 months was 71%. HBeAg was lost in 2 patients (10%). CONCLUSIONS: ADV+ETV combination therapy induced a good IVR in CHB patients who were refractory to more than 2 antiviral agents. This regimen may be a good alternative to TDF in Korea, where that drug is not available.

In vitro Efficacy of Antibiotic Combinations against Orientia tsutsugamushi

BACKGROUND: Occasionally, combinations of antibiotics are used for the treatment of scrub typhus. However, the effectiveness of such combined therapies has rarely been evaluated. To date, no experimental studies have been performed; only 1 clinical study has assessed the efficacy of combined doxycycline and rifampin therapy. To elucidate the efficacies of other antibiotic combinations, we performed an experiment to evaluate the in vitro efficacy of antibiotic combinations against Orientia tsutsugamushi. MATERIALS AND METHODS: O. tsutsugamushi strain Boryong was inoculated into the ECV304 cell line. The infected cells were cultured in antibiotic-containing media for 3-5 days and stained with FS15, a monoclonal antibody reacting against the linear epitope on the 56-kDa major outer membrane protein of O. tsutsugamushi. Thereafter, antimicrobial susceptibility was measured by flow cytometry and expressed as a growth index (total mass of Orientia). The growth indices of doxycycline (0.1 microg/mL), azithromycin (0.1 microg/mL), rifampin (0.0125 microg/mL), cefotaxime (2 and 20 microg/mL), and their various combinations (doxycycline+cefotaxime, doxycycline+rifampin, azithromycin+cefotaxime, and rifampin+cefotaxime) were measured. The above mentioned antibiotic concentrations, except for that of cefotaxime, represent the minimal inhibitory concentrations of each antibiotic. RESULTS: The growth indices of doxycycline (4.67% and 0.52%), rifampin (2.35% and 0.26%), and azithromycin (7.54%) were within the range of full suppression of O. tsutsugamushi; in contrast, cefotaxime (87.60%) was in effective. The growth indices of doxycycline+rifampin were 0.10% and 0.10%, which were similar to those obtained with doxycycline or rifampin alone. The growth indices of doxycycline+cefotaxime were 3.99% and 3.65% in low-dose cefotaxime (2 microg/mL), and 3.69% and 4.40% in high-dose cefotaxime (20 microg/mL). The growth indices of rifampin+cefotaxime (2.19% and 2.19% at 2 microg/mL; 1.84% and 2.04% at 20 microg/mL cefotaxime) were similar to those obtained with rifampin alone (2.35% and 0.26%). Azithromycin+cefotaxime (11.06-14.63%) showed higher growth indices than azithromycin alone; this suggests that this combination may be antagonistic. Conclusions: The anti-Orientia efficacies of doxycycline+rifampin, doxycycline+cefotaxime, and rifampin+cefotaxime were not antagonistic. The efficacy of the azithromycin+cefotaxime combination needs to be confirmed by more sensitive methods to exclude the possibility of antagonistic interactions between the antibiotics.

In vitro Efficacy of Antibiotic Combinations against Orientia tsutsugamushi

BACKGROUND: Occasionally, combinations of antibiotics are used for the treatment of scrub typhus. However, the effectiveness of such combined therapies has rarely been evaluated. To date, no experimental studies have been performed; only 1 clinical study has assessed the efficacy of combined doxycycline and rifampin therapy. To elucidate the efficacies of other antibiotic combinations, we performed an experiment to evaluate the in vitro efficacy of antibiotic combinations against Orientia tsutsugamushi. MATERIALS AND METHODS: O. tsutsugamushi strain Boryong was inoculated into the ECV304 cell line. The infected cells were cultured in antibiotic-containing media for 3-5 days and stained with FS15, a monoclonal antibody reacting against the linear epitope on the 56-kDa major outer membrane protein of O. tsutsugamushi. Thereafter, antimicrobial susceptibility was measured by flow cytometry and expressed as a growth index (total mass of Orientia). The growth indices of doxycycline (0.1 microg/mL), azithromycin (0.1 microg/mL), rifampin (0.0125 microg/mL), cefotaxime (2 and 20 microg/mL), and their various combinations (doxycycline+cefotaxime, doxycycline+rifampin, azithromycin+cefotaxime, and rifampin+cefotaxime) were measured. The above mentioned antibiotic concentrations, except for that of cefotaxime, represent the minimal inhibitory concentrations of each antibiotic. RESULTS: The growth indices of doxycycline (4.67% and 0.52%), rifampin (2.35% and 0.26%), and azithromycin (7.54%) were within the range of full suppression of O. tsutsugamushi; in contrast, cefotaxime (87.60%) was in effective. The growth indices of doxycycline+rifampin were 0.10% and 0.10%, which were similar to those obtained with doxycycline or rifampin alone. The growth indices of doxycycline+cefotaxime were 3.99% and 3.65% in low-dose cefotaxime (2 microg/mL), and 3.69% and 4.40% in high-dose cefotaxime (20 microg/mL). The growth indices of rifampin+cefotaxime (2.19% and 2.19% at 2 microg/mL; 1.84% and 2.04% at 20 microg/mL cefotaxime) were similar to those obtained with rifampin alone (2.35% and 0.26%). Azithromycin+cefotaxime (11.06-14.63%) showed higher growth indices than azithromycin alone; this suggests that this combination may be antagonistic. Conclusions: The anti-Orientia efficacies of doxycycline+rifampin, doxycycline+cefotaxime, and rifampin+cefotaxime were not antagonistic. The efficacy of the azithromycin+cefotaxime combination needs to be confirmed by more sensitive methods to exclude the possibility of antagonistic interactions between the antibiotics.

Recent Update on Fixed Combinations of Antihypertensive Agents

The amlodipine/atorvastatin single tablet has been shown to improve patients' achievement of national guideline recommended blood pressure and lipid target levels and exhibits a safety profile consistent with the parent com-pounds. The single tablet formulation has the potential to improve adherence and decrease prescription costs. These potential benefits are associated with important implications because hypertensive patients with additional risk factors represent a large proportion of those at risk for cardiovascular events. Combination low-dose drug treatment increases efficacy and reduces adverse effects. Fixed low-dose combination drug treatment increases efficacy and reduces adverse effects. This combination has greater potency and a similar side effect profile to monotherapy and represents a highly effective approach for attaining goal blood pressure levels using a therapeutic strategy that very effectively lowers blood pressure, is well-tolerated, and minimizes increasing doses of monotherapy-induced metabolic effects.

The Rationale and Effect of Antipsychotics Combination Therapy / 대한정신약물학회지

Up to the present date, the principle of antipsychotics treatment in patients with schizophrenia is antipsychotics monotherapy. The reasons for the drug monotherapy may be associated with the fact that typical antipsychotics were assumed to have similar mechanism of action and that combination use of more than two antipsychotics would offer no benefit over that of monotherapy with the agents. However, because the newer `atypical' antipsychotics have the notable features in their diverse pharmacologic action and lower adverse event profiles, many practitioners have an interest in using the combination therapy. Some patients with schizophrenia and schizoaffective disorder have no response to atypical antipsychotics and the studies increasingly reported that the antipsychotics combinations improve the symptom profiles of psychotic patients. Thus, the antipsychotic combination therapy is an additional option in treatment-resistant psychotic patients. These combination therapies are commonly used in clinical practice, but we are in lack of the evidence of the rationale and background of this practice. Since most studies for antipsychotics combination therapy are open trial or retrospective study, we need the further prospective clinical studies with double-blind, placebo-controlled design in order to definitively determine the effectiveness of such practice.

A Case of Intractable Hiccup Controlled by Combination Drug Therapy with Levosulpiride, Omeprazole and Baclofen

No abstract available.

Quantitative analyses of the combined effects of nano red elemental selenium and glucurolactone on forming liver fibrosis induced by CCl4 in rats / 中国药理学通报

AIM: To observe the combined effects of nano red elemental selenium (Nse) and glucurolactone (Glu) on forming liver fibrosis in rats, and to search for a low dose of Nse with therapeutic effect. METHODS: According to the weighted modification method, six compound-dose groups and 2 control groups were set. The rats were given (sc) CCl4 for 10 wk, and the administration began at 4 wk. The indices related to acute liver damage were determined 3 wk after the administration, and to chronic liver damage 6 wk after the administration. RESULTS: At the stage of acute liver damage and within the therapeutic duration of 3 wk, Nse should be used at a larger dose in combination with Glu. Theoretical analysis showed that Nse 200 μg·kg-1 alone was available by the weighted modification method. However, in the combination of Nse and Glu for the chronic liver injury, Nse should be given at a low dose. There was a synergism between Nse and Glu, and some compound-dose groups showed the preventive and therapeutic effect, especially in a dose of Nse 100 μg·kg-1 + Glu 60 mg·kg-1. But theoretical analysis exhibited that Nse 100 μg · kg-1 + Glu 60 mg·kg-1 (ig) might be an optimal combination. CONCLUSION: The combination of Nse and Glu has significant effect in prevention and treatment of the live fibrosis in rats, and it can decrease dose of Nse used.