Risk Factors for Non-Adherence to Medications That Affect Surgery: A Retrospective Study in Japan.

Purpose: Data on risk factors for non-adherence to doctors' and pharmacists' instructions to discontinue medications prior to surgery are lacking. This study aimed to identify characteristics and risk factors for such non-adherent patients. Patients and Methods: Data (including patient age, sex, prescription medications, comorbidities, presence of roommate at home, and number of days between receiving instruction and surgery) of 887 patients who used medications affecting surgery at a university hospital from April 2017 to March 2020 were retrospectively evaluated. The primary endpoint was to investigate the rate of non-adherence and to explore independent risk factors for non-adherence (with age categorized as ≥65 [versus <65] years). Secondary endpoints included analysis of limited number of departments subgroup and a sensitivity analysis (with age categorized as ≥75 [versus <75] years) to confirm the robustness of the primary endpoint results. Independent risk factors for non-adherence were identified using logistic regression analysis. Results: The non-adherence rate was 11.4% (n=101/887), median age (interquartile range) at admission was 73 (70-79) years, and proportion of male patients was 81.2% (n=82). The main analysis adjusted for age ≥65 (versus <65) years showed age as a risk factor for increased non-adherence (adjusted odds ratio: 2.1, 95% confidence interval: 1.09-4.05; p=0.027). However, analyses adjusted for departments (other than urology, gynecology, and breast surgery, with a large sex bias in hospitalized patients) and for age ≥75 (versus <75) years showed no such risk. Conclusion: Age ≥65 years was associated with a higher risk of non-adherence to medications that should be discontinued before surgery. It is important for doctors and pharmacists to ensure that patients at high risk for non-adherence are aware of the importance of adherence. Our findings may help identify patients at high risk for non-adherence to such medications.

Effects of arsenic compounds on growth, cell-cycle distribution and apoptosis of tretinoin-resistant human promyelocytic leukemia cells.

BACKGROUND/AIM: The effects of inorganic and organic arsenicals on proliferation, cell-cycle distribution, and apoptosis of all-transretinoic acid (ATRA)-resistant human promyelocytic leukemia HL-60 (HL-60-R2) cells were herein investigated. MATERIALS AND METHODS: Cell proliferation was examined by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay. Cell-cycle distribution and apoptotic cells were analyzed by flow cytometry. RESULTS: The 50% inhibitory concentrations (IC50 values) for As2O3 against proliferation of HL-60 and HL-60-R2 cells were 12.2 and 7.2 µM, while those for arsenate were >200 and 62.1 µM, respectively. In contrast, organic methylarsinic acid, dimethylarsonic acid, trimethylarsine oxide, and tetramethylarsonium did not exert any inhibitory effects even at 200 µM. As2O3 and arsenate increased the proportion of apoptotic cells dose-dependently at a concentration range of 5-200 µM. As2O3 did not activate caspase 3/7 in HL-60 and HL-60-R2 cells. CONCLUSION: As2O3 and arsenate inhibit cell proliferation, affect cell-cycle distribution, and induce apoptosis of ATRA-resistant HL-60-R2 cells. The apoptosis-inducing mechanism appears not to be mediated through caspase3/7.

Evaluation of renal adverse effects of combination anti-retroviral therapy including tenofovir in HIV-infected patients.

PURPOSE: In order to maintain plasma HIV-RNA concentration in HIV-infected patients, below the detection limit combination anti-retroviral therapy (cART) are used. Although the nucleoside/nucleotide reverse transcriptase inhibitor, tenofovir disoproxil fumarate (TDF) is a first-line drug commonly used, it is associated with renal dysfunction. Nevertheless, only few clinical studies have focused on TDF in combination with new anti-HIV drugs, including the protease inhibitor (PI) darunavir (DRV), or the integrase strand transfer inhibitor (INSTI) raltegravir (RAL). Here we report the influence of such cART involving TDF on renal function. METHODS: We retrospectively investigated 68 patients under cART that included TDF between November 2004 and May 2012. We used hospital records to establish each patient's background and characteristics, CD4 cell count, plasma HIV-RNA concentration, drug combinations, renal function, and anti-retrovial therapy history. RESULTS: In all patients who had received cART, the plasma HIV-RNA concentration had fallen to less than 40 copies/mL by week 24 after the start of the therapy, and an increase in the CD4 cell count was observed. For each drug used in combination with TDF, the plasma HIV-RNA concentration and CD4 cell count showed a similar trend. After week 12, the estimated glomerular filtration rate (eGFR) had significantly decreased in all patients. The eGFR was significantly lower in those received PI on week 24 and in those received INSTI on week 12. The eGFR was significantly reduced in PI group who received atazanavir + ritonavir (ATV/RTV) on week 60. The eGFR in the DRV/RTV group tended to decrease. The eGFR in the PI and ATV/RTV group was significantly lower than in the efavirenz (EFV) group on week 96. CONCLUSION: It selecting drugs to include in combination therapy of HIV-infected patients, consideration should be given to the risk of renal dysfunction. There is a need to monitor renal function when TDF is combined with ATV/RTV, DRV/RTV or RAL.

Antiproliferative and apoptosis-inducing effects of lipophilic vitamins on human melanoma A375 cells in vitro.

The effects of six lipophilic vitamins: tretinoin (ATRA), vitamin D(3) (VD(3)), VE, VK(1), VK(3), and VK(5) on cell proliferation and apoptosis in human A375 melanoma cells were investigated. VD(3), VK(3), and VK(5) were found to inhibit cell proliferation significantly at concentration ranges of 10-100 µmol/L (p<0.01), while the other vitamins did not show inhibitory effects at 100 µmol/L. VK(3) and VK(5) showed the strongest effects with IC(50) values of less than 10 µmol/L. Dacarbazine slightly inhibited the proliferation of A375 cells at a concentration range of 25-100 µmol/L, but the effects were not statistically significant. VK(3) and VK(5) increased annexin-V positive apoptotic cells, as well as activating caspase-3, in A375 cells. Our findings showed that VD(3), VK(3,) and VK(5) inhibited the growth of dacarbazine resistant human melanoma cells, while ATRA, VE, and VK(1) had little effect on the cell growth. The effects of VK(3) and VK(5) were observed at concentrations lower than 10 µmol/L, which are suggested to have resulted from apoptosis-induction in the melanoma cells.

Effects of inorganic and organic arsenic compounds on growth and apoptosis of human T-lymphoblastoid leukemia cells.

BACKGROUND/AIM: To investigate the effects of inorganic and organic arsenic compounds on human T-lymphoblastoid leukemia cells. MATERIALS AND METHODS: Cell proliferation was analyzed by 3-(4,5-dimethylthiazol-2-yl)-2,5¬diphenyltetrazolium bromide (MTT) assay. Apoptotic cell morphology was examined by cell staining with Hoechst 33342. Cellular caspase-3/7 activities were measured after arsenic treatment. RESULTS: The inhibitory concentration by 50% (IC(50)) values of As(2)O(3) towards MOLT-4 and daunorubicin- resistant MOLT-4/DNR cell proliferation were 0.87 and 0.92 µM, while the values for arsenic acid were 69.1 and 116.6 µM, respectively. These arsenic compounds also inhibited mitogen-induced proliferation of human peripheral blood mononuclear cells. Six organic arsenic compounds did not inhibit leukemia cell proliferation. As(2)O(3) and arsenic acid induced apoptotic cell morphology and increased caspase-3/7 activity in the leukemia cells. Ascorbic acid and buthionine sulfoxide enhanced, while N-acetyl-L-cysteine abated, the suppressive effects of inorganic arsenic compounds on leukemia cell proliferation. CONCLUSION: As(2)O(3) and arsenic acid inhibit proliferation and induce apoptosis in MOLT-4 and daunorubicine-resistant MOLT-4/DNR cells via glutathione-depletion and subsequent caspase-3/7 activation. Organic arsenic compounds have no inhibitory activity on the leukemia cell proliferation. Inorganic arsenic compounds are suggested as useful agents for treatment of T-lymphoblastoid leukemia.

Antiproliferative and anti-invasive effects of inorganic and organic arsenic compounds on human and murine melanoma cells in vitro.

OBJECTIVES: For patients with advanced melanoma, no treatment options are available at present that provide either sufficient response rates or a significant prolongation of overall survival. The present study examines the effects of two inorganic and six organic arsenic compounds on cell proliferation and cell invasion of melanoma cells in vitro. METHODS: The effects of arsenic compounds on proliferation of human melanoma A375 cells and murine melanoma B16F10 cells were examined by MTT assay and 5-bromo-2'-deoxyuridine (BrdU) incorporation assay, and the effects of the compounds on cell invasion were examined by the Boyden chamber invasion assay. The amounts of active matrix metalloproteinase (MMP)-2 and pro-MMP-2 in the culture supernatant of A375 cells were determined by an MMP-2 activity assay system. KEY FINDINGS: Arsenate and arsenic trioxide (As(2) O(3) ) inhibited the proliferation of A375 and B16F10 cells significantly at concentration ranges of 0.1-20µg/ml (P<0.001), while the organic compounds arsenobetaine, arsenocholine, dimethylarsinic acid, methylarsonic acid, tetramethylarsonium and trimethylarsine oxide did not show any inhibitory effects even at 20µg/ml. Cell invasion of A375 and B16F10 cells through a layer of collagen IV was significantly inhibited by 0.1-20 µg/ml of arsenate or As(2) O(3) (P<0.05), while the organic compounds did not inhibit cell invasion. Arsenate or As(2) O(3) at 0.2-10µg/ml significantly inhibited the amount of active MMP-2 and pro-MMP-2 secreted into the A375 cell culture supernatant (P<0.05). CONCLUSIONS: Our findings show that the inorganic arsenic compounds arsenate and As(2) O(3) inhibit cell proliferation and prevent the invasive properties of melanoma cells, possibly by decreasing MMP-2 production from the cells.

Brugada syndrome-like ST-segment elevation increase exacerbated by vomiting.

The patient was a 53 year-old male who had 3 syncopal episodes over a 6-month period. In the electrophysiological study, ventricular fibrillation (VF) was repeatedly induced by the ventricular extrastimulus method. Intravenous pilsicainide was administered, and the J-point and ST-segment in the right precordial leads became slightly elevated just following drug administration. Five min later, the patient experienced severe nausea and then vomited twice, at which point the electrocardiogram (ECG) showed increased elevation of the J-point and ST-segment. These ECG changes recovered to normal 30 min later. The cause of his syncope was strongly suspected to be related to the VF associated with Brugada syndrome. An interesting aspect of this case was the particular type of J-point and ST-segment elevation that was induced when the patient experienced nausea and vomiting. It is proposed that this phenomenon originated from the vagal stimulation associated with the nausea and vomiting.

Experimental study on the effectiveness and safety of radiofrequency catheter ablation with the cooled ablation system.

Experimental in vitro and in vivo studies were performed to assess the effectiveness and safety of the cooled-tip catheter and the Cooled Ablation System, which enables the creation of deeper and wider burn lesions in the myocardial tissue using radiofrequency current. This system was confirmed to consistently create large burns by cooling the catheter tip with circulating water within the catheter, even under unfavorable conditions. On the other hand, unfavorable effects, as a result of over burning, such as explosive vaporization within the tissue (the 'pop' phenomenon), tissue carbonization, coronary artery injury and lung injury were identified. 'Pop' was difficult to predict, but it is important to know how it can be avoided. No 'Pop' was seen without first observing an impedance decrease, thus it was considered safe to decrease the radiofrequency current if the impedance began to decrease. This system will be very effective for ablation of refractory arrhythmias, such as ventricular tachycardia or atrial flutter, but it is recommended that only experienced electrophysiologists use this system to avoid serious complications.

Electrocardiography subtraction method of detecting low-amplitude, high-frequency components (L-HFCs) within the QRS complex of patients with ventricular tachycardia.

A new method of extracting the low-amplitude and high-frequency components (L-HFCs) was developed and this study investigated its usefulness in 86 subjects: 28 normal subjects (group 1) and 58 patients with a previous myocardial infarction (MI). The patients were classified into 3 groups: group 2 with 38 patients without ventricular tachycardia (VT), group 3 with 13 patients with non-sustained VT, and group 4 with 7 patients with sustained VT. The new electrocardiography (ECG) subtraction method, using a mathematical filtering procedure, was used instead of conventional complex filtering. The continuous L-HFCs within the QRS complex were analyzed using a Z-lead recording. The duration of the continuous L-HFCs was significantly longer in group 4 than in groups 1 (p<0.0001), 2 (p<0.0001) or 3 (p<0.05) with all 3 filters. The ECG subtraction method is a powerful and useful new technique for identifying patients at risk for either sustained or non-sustained VT after MI, and overcomes several of the problems with the conventional signal-averaging method.

Clinical significance of the dispersion of the activation--recovery interval and recovery time as markers for ventricular fibrillation susceptibility in patients with Brugada syndrome.

Brugada syndrome (BS) is associated with sudden cardiac death and the markers for ventricular fibrillation (VF) remain unclear, so the activation-recovery interval (ARI) dispersion and recovery time (RT) dispersion were investigated as possible markers in 20 subjects with BS (BS group) and 22 healthy individuals (H group). The 20 BS subjects were divided into 8 cases with documented VF (BS-VF group), 3 of which had recurrences, and 12 without (BS-N group). The corrected dispersion measurements from the standard 12-lead ECG of the QT interval (QTcd), ARI (ARIcd) and RT (RTcd) were compared among the groups. There were significant differences noted between the BS-VF and BS-N groups for the ARIcd and the RTcd, but not for the QTcd. Further, there were critical differences, 150 ms(1/2), observed for the ARIcd and RTcd, and these were associated with a prolongation of the maximum ARI or RT, shortening of the minimum ARI or RT, and prolongation only of the maximum QT for the QTcd. Susceptibility to VF may be predicted by the ARIcd or RTcd in BS.