BACKGROUND: Central nervous system (CNS) symptoms after efavirenz (EFV) treatment in people living with human immunodeficiency virus (HIV) could persist and impact their quality of life. We assessed the impact of EFV-based regimen replacement with elvitegravir/cobicistat/emtricitabine/tenofovir alafenamide (E/C/F/TAF), which is considered an alternative option for subjects who do not tolerate EFV. Most specifically, we assessed the safety and the efficacy of E/C/F/TAF and its effects on the participants' neuropsychiatric toxicity symptoms in a real-life setting. METHODS: A prospective cohort study was conducted among virologic suppressed HIV-positive participants receiving EFV-based regimens with ongoing CNS toxicity ≥ grade 2. The participants were switched to single-pill combination regimens E/C/F/TAF and followed up for 48 weeks. The neuropsychiatric toxicity symptoms were measured using a CNS side effects questionnaire, as well as the Hospital Anxiety and Depression Scale and the Pittsburgh Sleep Quality Index. The primary outcome measure was the proportion of participants experiencing grade 2 or higher CNS toxicity after EFV switch off at weeks 12, 24, and 48. Secondary endpoints included virologic and immunological responses and the effect on fasting lipids at week 48 after switch. RESULTS: One hundred ninety-six participants (96.9% men, median age: 37.5 years, median: 3.7 years on prior EFV-containing regimens) were included in the study. Significant improvements in anxiety and sleep disturbance symptoms were observed at 12, 24, and 48 weeks after switching to E/C/F/TAF (P < 0.05). No significant change in depression symptom scores was observed. At 48 weeks after switch, HIV viral load <50 copies/mL was maintained in all of the participants, median fasting lipid levels were moderately increased (total cholesterol [TC]: 8.2 mg/dL, low-density lipoprotein cholesterol [LDL-C]: 8.5 mg/dL, high-density lipoprotein cholesterol [HDL-C]: 2.9 mg/dL, and triglyceride (TG): 1.6 mg/dL, and the TC:HDL-C ratio remained stable. CONCLUSIONS The single-pill combination regimens E/C/F/TAF is safe and well tolerated. This study reveals that switching from EFV to E/C/F/TAF significantly reduces neuropsychiatric toxicity symptoms in people living with HIV with grade 2 or higher CNS complaints.
Adenine/therapeutic use* ; Adult ; Alanine ; Alkynes ; Anti-HIV Agents/adverse effects* ; Benzoxazines ; Central Nervous System ; Cobicistat/therapeutic use* ; Cyclopropanes ; Drug Combinations ; Emtricitabine/therapeutic use* ; Female ; HIV Infections/drug therapy* ; Humans ; Male ; Prospective Studies ; Quality of Life ; Quinolones ; Sleep Quality ; Tenofovir/analogs & derivatives*

Adenine/analogs & derivatives* ; Anti-HIV Agents/therapeutic use* ; Cobicistat/therapeutic use* ; Drug Combinations ; Emtricitabine/therapeutic use* ; HIV ; HIV Infections/drug therapy* ; Humans ; Postoperative Complications ; Quinolones ; Viral Load

Although surgery is the mainstay of local treatment for skin cancer, definitive radiation therapy (RT) has been also applied for patients who are unable to tolerate surgery. Definitive RT regimens usually consist of daily treatment for 4–7 weeks. Such protracted daily RT regimens, however, would not be feasible for non-compliant patients or patients who are unable to make multiple daily trips for weeks. Without treatment, however, skin cancers can continuously progress and cause distressing symptoms. A cyclical hypofractionated RT (QUAD Shot: 14 Gy in 4 fractions, twice-daily treatments with 6 hours interval on 2 consecutive days) can be a practical RT regimen for those patients. In this report, we present the successful treatment course of repeated QUAD Shots in a 79-year-old patient with neglected skin cancer that was disfiguring his face yet declined definitive surgery and protracted RT. We also evaluated and compared biologically equivalent doses between QUAD Shots and conventionally fractionated protracted RT regimens.
Aged ; Elvitegravir, Cobicistat, Emtricitabine, Tenofovir Disoproxil Fumarate Drug Combination ; Humans ; Skin Neoplasms ; Skin

BACKGROUND: Dual regimen with dolutegravir plus cobicistat-boosted darunavir (DTG/DRV/c) is reasonable alternative option for patients with existing resistance and/or intolerance to nucleoside reverse transcriptase inhibitors (NRTIs). MATERIAL AND METHODS: All patients who switched to DTG/DRV/c among treatment-experienced patients with human immunodeficiency virus (HIV) in a tertiary university hospital were selected. We analyzed the effectiveness, safety, and tolerability based on serial laboratory data and clinical findings. The primary endpoint was defined as the proportion of patients with plasma HIV RNA below 50 copies/mL at week 48 after switch. Secondary endpoints included evaluation of safety and tolerability. RESULTS: Thirty-one patients were retrospectively analyzed. The main reasons for the change to DTG/DRV/c were treatment failure in 13 patients (41.9%), simplification in 12 patients (38.7%), and adverse drug reaction in 6 patients (19.4%). Among the 13 patients who switched owing to treatment failure, the proportion of patients in whom the viral loads were suppressed to less than 50 copies/mL increased from 0% at baseline to 45% at 4 weeks, 50% at 12 weeks, 50% at 24 weeks, and 66.7% at 48 weeks. HIV virus levels decreased and CD4⁺ T cell counts increased during the follow-up period. In non-treatment failure patients (18 patients), the levels of viral suppression and CD4⁺ T cells were maintained. There were no significant differences in renal function, liver function, glucose levels, and lipid profile before and after regimen changes. The tolerability was very good: 30 patients (96.8%) tolerated the drugs well and only 1 patient discontinued owing to no improvement in renal insufficiency. Two patients (6.4%) in treatment failure group failed to reach viral suppression. CONCLUSION: The use of DTG/DRV/c in HIV treatment-experienced patients appears to be a very good regimen for switch therapy that is effective and well tolerated, without significant adverse drug reaction.
Cell Count ; Cobicistat ; Darunavir* ; Drug-Related Side Effects and Adverse Reactions ; Follow-Up Studies ; Glucose ; HIV* ; Humans ; Humans* ; Liver ; Plasma ; Renal Insufficiency ; Retrospective Studies ; Reverse Transcriptase Inhibitors ; RNA ; T-Lymphocytes ; Treatment Failure ; Viral Load

BACKGROUND: Dual regimen with dolutegravir plus cobicistat-boosted darunavir (DTG/DRV/c) is reasonable alternative option for patients with existing resistance and/or intolerance to nucleoside reverse transcriptase inhibitors (NRTIs). MATERIAL AND METHODS: All patients who switched to DTG/DRV/c among treatment-experienced patients with human immunodeficiency virus (HIV) in a tertiary university hospital were selected. We analyzed the effectiveness, safety, and tolerability based on serial laboratory data and clinical findings. The primary endpoint was defined as the proportion of patients with plasma HIV RNA below 50 copies/mL at week 48 after switch. Secondary endpoints included evaluation of safety and tolerability. RESULTS: Thirty-one patients were retrospectively analyzed. The main reasons for the change to DTG/DRV/c were treatment failure in 13 patients (41.9%), simplification in 12 patients (38.7%), and adverse drug reaction in 6 patients (19.4%). Among the 13 patients who switched owing to treatment failure, the proportion of patients in whom the viral loads were suppressed to less than 50 copies/mL increased from 0% at baseline to 45% at 4 weeks, 50% at 12 weeks, 50% at 24 weeks, and 66.7% at 48 weeks. HIV virus levels decreased and CD4⁺ T cell counts increased during the follow-up period. In non-treatment failure patients (18 patients), the levels of viral suppression and CD4⁺ T cells were maintained. There were no significant differences in renal function, liver function, glucose levels, and lipid profile before and after regimen changes. The tolerability was very good: 30 patients (96.8%) tolerated the drugs well and only 1 patient discontinued owing to no improvement in renal insufficiency. Two patients (6.4%) in treatment failure group failed to reach viral suppression. CONCLUSION: The use of DTG/DRV/c in HIV treatment-experienced patients appears to be a very good regimen for switch therapy that is effective and well tolerated, without significant adverse drug reaction.
Cell Count ; Cobicistat ; Darunavir* ; Drug-Related Side Effects and Adverse Reactions ; Follow-Up Studies ; Glucose ; HIV* ; Humans ; Humans* ; Liver ; Plasma ; Renal Insufficiency ; Retrospective Studies ; Reverse Transcriptase Inhibitors ; RNA ; T-Lymphocytes ; Treatment Failure ; Viral Load

Pioglitazone is known to have antidiabetic effects through decreasing peripheral, hepatic and vascular insulin resistance by the stimulation of PPAR gamma. To address the possible genetic factors affecting the pharmacokinetics (PK) of pioglitazone, 27 male Korean volunteers were enrolled from two separate bioequivalence studies. Each subject was administered 15 mg pioglitazone and reference drug PK parameters were used. We used Illumina Human610 Quad v1.0 DNA Analysis BeadChip for whole genome SNPs analysis and whole genome genotyping data was processed by linear regression analysis for PK parameters. We found 35 significant SNPs (P < 0.0001) in C(max), 1,118 significant SNPs (P < 0.0001) in T(max) and 1,259 significant SNPs (P < 0.0001) in AUC(inf) from whole genome analysis. For clinical pharmacological purpose, we selected SNPs from several phase I and II drug metabolizing enzyme and analyzed PK parameters with genotypes. Four SNPs (rs7761731 and rs3799872 from CYP39A1; rs156697 from GSTO2; rs1558139 from CYP4F2) showed significant associations with pioglitazone C(max). In the T(max) group, seven SNPs from 3 genes (rs3766198 from CYP4B1; rs2270422 from GSTZ1; rs2054675, rs10500282, rs3745274, rs8192719, and rs11673270 from CYP2B6) had significant associations. In the AUC(inf) group, seven SNPs from 4 genes (rs11572204 from CYP2J2; rs4148280 from UGT2A1, rs4646422 from CYP1A1; rs3745274, rs8192719, rs11673270, and rs707265 from CYP2B6) showed significant associations with pioglitazone absorption. These results showed that genetic makeup could affect the PK parameters and these informations could be provide information for personalized pioglitazone therapy.
Absorption ; Cytochrome P-450 CYP1A1 ; DNA ; Elvitegravir, Cobicistat, Emtricitabine, Tenofovir Disoproxil Fumarate Drug Combination ; Genome ; Genotype ; Humans ; Insulin Resistance ; Linear Models ; Male ; Mass Screening* ; Pharmacogenetics ; Pharmacokinetics* ; Polymorphism, Genetic* ; Polymorphism, Single Nucleotide ; PPAR gamma ; Therapeutic Equivalency ; Volunteers

OBJECTIVE: To analyze the fatigue resistance, debonding force, and failure type of fiber-reinforced composite, polyethylene ribbon-reinforced, and braided stainless steel wire lingual retainers in vitro. METHODS: Roots of human mandibular central incisors were covered with silicone, mimicking the periodontal ligament, and embedded in polymethylmethacrylate. The specimens (N = 50), with two teeth each, were randomly divided into five groups (n = 10/group) according to the retainer materials: (1) Interlig (E-glass), (2) everStick Ortho (E-glass), (3) DentaPreg Splint (S2-glass), (4) Ribbond (polyethylene), and (5) Quad Cat wire (stainless steel). After the recommended adhesive procedures, the retainers were bonded to the teeth by using flowable composite resin (Tetric Flow). The teeth were subjected to 10,00,000 cyclic loads (8 Hz, 3 - 100 N, 45degrees angle, under 37 +/- 3degrees C water) at their incisoproximal contact, and debonding forces were measured with a universal testing machine (1 mm/min crosshead speed). Failure sites were examined under a stereomicroscope (x40 magnification). Data were analyzed by one-way analysis of variance. RESULTS: All the specimens survived the cyclic loading. Their mean debonding forces were not significantly different (p > 0.05). The DentaPreg Splint group (80%) showed the highest incidence of complete adhesive debonding, followed by the Interlig group (60%). The everStick Ortho group (80%) presented predominantly partial adhesive debonding. The Quad Cat wire group (50%) presented overlying composite detachment. CONCLUSIONS: Cyclic loading did not cause debonding. The retainers presented similar debonding forces but different failure types. Braided stainless steel wire retainers presented the most repairable failure type.
Adenine ; Adhesives ; Animals ; Carbamates ; Cats ; Collodion ; Composite Resins ; Deoxycytidine ; Drug Combinations ; Fatigue ; Humans ; Incidence ; Incisor ; Organophosphonates ; Periodontal Ligament ; Polyethylene ; Polyethylenes ; Polymethyl Methacrylate ; Quinolones ; Recurrence ; Retention (Psychology) ; Silicones ; Splints ; Stainless Steel ; Thiazoles ; Tooth ; Elvitegravir, Cobicistat, Emtricitabine, Tenofovir Disoproxil Fumarate Drug Combination

OBJECTIVES: The objective of this paper is to assess which wide type monitor configurations are preferred when physicians use an Electronic Medical Record (EMR) system in an outpatient clinic setting. METHODS: We selected three kinds of monitor configurations available for adoption at outpatient clinics with reference to monitor market trends. Fifteen attending physicians of the Seoul National University Bundang Hospital used each monitor configuration in their outpatient clinics. After completing the outpatient sessions, they selected the best monitor configuration for criteria described in five questionnaire items. We counted the number of votes and reviewed opinions of participants. RESULTS: The Wide Quad High Definition (WQHD) 27-inch single monitor configuration was most preferred for all questionnaire items. All participants answered that the WQHD 27-inch single monitor configuration was the best for desk space utilization. Eleven out of fifteen participants chose the WQHD 27-inch single monitor configuration as the most suitable monitor for outpatient practice. CONCLUSIONS: This study found that physicians preferred the WQHD 27-inch single monitor configuration in outpatient clinic settings. Healthcare organizations need to consider this finding when they purchase wide type monitors for EMR systems instead of the standard type monitor.
Adenine ; Adoption ; Ambulatory Care Facilities ; Carbamates ; Computer Terminals ; Delivery of Health Care ; Deoxycytidine ; Drug Combinations ; Electronic Health Records ; Electronics ; Electrons ; Elvitegravir, Cobicistat, Emtricitabine, Tenofovir Disoproxil Fumarate Drug Combination ; Humans ; Organophosphonates ; Organothiophosphorus Compounds ; Outpatients ; Personal Satisfaction ; Quinolones ; Thiazoles ; User-Computer Interface ; Surveys and Questionnaires

OBJECTIVE: To compare the differences in the second trimester Quad test markers in patients who subsequently developed preeclampsia depending on the disease onset time and the presence of fetal growth restriction (FGR). METHODS: A retrospective study was carried out on 66 women with severe preeclampsia and 345 controls who were delivered at Dong-A University hospital and Ilsin Christian Hospital from January 2006 to December 2008. Severe preeclampsia patients were grouped according to with (n=30) or without (n=36) FGR. Severe preeclampsia patients were also grouped according to early onset (n=16) or late onset (n=50) The levels of the second trimester human chorionic gonadotropin (hCG), inhibin-A, unconjugated estriol (uE3), alpha-fetoprotein (AFP) were compared in each group. RESULTS: In the pregnancies that subsequently developed severe preeclampsia, the second trimester hCG, inhibin-A and AFP were significantly higher than the controls. We found that levels of hCG, inhibin-A in severe preeclampsia complicated by FGR were significantly higher than those without FGR. We also found that levels of AFP and inhibin-A in early onset severe preeclampsia were significantly higher than late onset severe preeclampsia. CONCLUSION: The levels of second trimester Quad test markers in patients that subsequently developed severe preeclampsia were different according to with or without FGR and onset time.
Adenine ; alpha-Fetoproteins ; Carbamates ; Chorionic Gonadotropin ; Deoxycytidine ; Drug Combinations ; Estriol ; Female ; Fetal Development ; Humans ; Organophosphonates ; Pre-Eclampsia ; Pregnancy ; Pregnancy Trimester, Second ; Quinolones ; Retrospective Studies ; Thiazoles ; Elvitegravir, Cobicistat, Emtricitabine, Tenofovir Disoproxil Fumarate Drug Combination

Anterior open bite is a condition in which maxillary and mandibular incisors do not occlude at central occlusion. It is a vertical discrepancy of the jaws and dental arches that has many etiologic factors making it difficult in diagnosis, treatment and prediction of prognosis. One of the causes of open bite is abnormal size and shape of the tongue. Macroglossia, a condition in which tongue is oversized, is caused by several factors which are not clearly identifiable, and it may be a major factor of anterior and posterior open bite. Macroglossia is subdivided into true, functional and pseudomacroglossia depending on its relative size in the oral cavity. In this case report, a patient was diagnosed as skeletal Class II with pseudomacroglossia, and was treated with SARPE in order to expand the narrowed maxillary arch and quad helix for the mandibular arch. As a result the transverse deficiency was treated. In the adult patients where no skeletal growth is expected, SARPE has shown to be effective in treating maxillomandibular transverse discrepancies in which macroglossia was accompanied as in this case.
Adenine ; Adult ; Carbamates ; Dental Arch ; Deoxycytidine ; Drug Combinations ; Humans ; Incisor ; Jaw ; Macroglossia ; Mouth ; Open Bite ; Organophosphonates ; Palatal Expansion Technique ; Prognosis ; Quinolones ; Thiazoles ; Tongue ; Elvitegravir, Cobicistat, Emtricitabine, Tenofovir Disoproxil Fumarate Drug Combination