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*

BACKGROUND: Despite the recommendation of inhaled corticosteroids (ICSs) plus long-acting beta 2-agonist (LABA) and leukotriene receptor antagonist (LTRA) or ICS/LTRA as stepwise approaches in asthmatic children, there is a lack of published systematic review comparing the efficacy and safety of the two therapies in children and adolescents aged 4 to 18 years. This study aimed to compare the safety and efficacy of salmeterol/fluticasone (SFC) vs. montelukast (MON), or combination of montelukast and fluticasone (MFC) in children and adolescents aged 4 to 18 years with bronchial asthma. METHODS: A systematic search was conducted in MEDLINE, EMBASE, the Cochrane Library, China BioMedical Literature Database, Chinese National Knowledge Infrastructure, VIP Database for Chinese Technical Periodical, and Wanfang for randomized controlled trials (RCTs) published from inception to May 24, 2021. Interventions are as follows: SFC vs. MON, or combination of MFC, with no limitation of dosage or duration. Primary and secondary outcome measures were as follows: the primary outcome of interest was the risk of asthma exacerbation. Secondary outcomes included risk of hospitalization, pulmonary function, asthma control level, quality of life, and adverse events (AEs). A random-effects (I2 ≥ 50%) or fixed-effects model (I2 < 50%) was used to calculate pooled effect estimates, comparing the outcomes between the intervention and control groups where feasible. RESULTS: Of the 1006 articles identified, 21 studies met the inclusion criteria with 2643 individuals; two were at low risk of bias. As no primary outcomes were similar after an identical treatment duration in the included studies, meta-analysis could not be performed. However, more studies favored SFC, instead of MON, owing to a lower risk of asthma exacerbation in the SFC group. As for secondary outcome, SFC showed a significant improvement of peak expiratory flow (PEF)%pred after 4 weeks compared with MFC (mean difference [MD]: 5.45; 95% confidence interval [CI]: 1.57-9.34; I2 = 95%; P = 0.006). As for asthma control level, SFC also showed a higher full-controlled level (risk ratio [RR]: 1.51; 95% CI: 1.24-1.85; I2 = 0; P < 0.001) and higher childhood asthma control test score after 4 weeks of treatment (MD: 2.30; 95% CI: 1.39-3.21; I2 = 72%; P < 0.001) compared with MFC. CONCLUSIONS: SFC may be more effective than MFC for the treatment of asthma in children and adolescents, especially in improving asthma control level. However, there is insufficient evidence to make firm conclusive statements on the use of SFC or MON in children and adolescents aged 4 to 18 years with asthma. Further research is needed, particularly a combination of good-quality long-term prospective studies and well-designed RCTs. PROSPERO REGISTRATION NUMBER CRD42019133156.
Acetates ; Administration, Inhalation ; Adolescent ; Adrenal Cortex Hormones/therapeutic use* ; Albuterol/therapeutic use* ; Anti-Asthmatic Agents/therapeutic use* ; Asthma/drug therapy* ; Child ; Cyclopropanes ; Drug Therapy, Combination ; Fluticasone/therapeutic use* ; Humans ; Quinolines ; Salmeterol Xinafoate/therapeutic use* ; Sulfides

Recent studies have shown that the chemokine receptor CXCR3 and its ligand CXCL10 in the dorsal root ganglion mediate itch in experimental allergic contact dermatitis (ACD). CXCR3 in the spinal cord also contributes to the maintenance of neuropathic pain. However, whether spinal CXCR3 is involved in acute or chronic itch remains unclear. Here, we report that Cxcr3 mice showed normal scratching in acute itch models but reduced scratching in chronic itch models of dry skin and ACD. In contrast, both formalin-induced acute pain and complete Freund's adjuvant-induced chronic inflammatory pain were reduced in Cxcr3 mice. In addition, the expression of CXCR3 and CXCL10 was increased in the spinal cord in the dry skin model induced by acetone and diethyl ether followed by water (AEW). Intrathecal injection of a CXCR3 antagonist alleviated AEW-induced itch. Furthermore, touch-elicited itch (alloknesis) after compound 48/80 or AEW treatment was suppressed in Cxcr3 mice. Finally, AEW-induced astrocyte activation was inhibited in Cxcr3 mice. Taken together, these data suggest that spinal CXCR3 mediates chronic itch and alloknesis, and targeting CXCR3 may provide effective treatment for chronic pruritus.
Acetamides ; therapeutic use ; Animals ; Chemokine CXCL10 ; metabolism ; Chloroquine ; toxicity ; Chronic Disease ; Cyclopropanes ; adverse effects ; Dehydration ; complications ; Dinitrofluorobenzene ; adverse effects ; Disease Models, Animal ; Formaldehyde ; toxicity ; Freund's Adjuvant ; toxicity ; Mice ; Mice, Inbred C57BL ; Mice, Knockout ; Motor Activity ; drug effects ; Pain ; chemically induced ; Pruritus ; chemically induced ; pathology ; Pyrimidines ; therapeutic use ; Receptors, CXCR3 ; antagonists & inhibitors ; genetics ; metabolism ; Skin ; pathology ; Spinal Cord ; drug effects ; metabolism ; pathology ; Time Factors ; p-Methoxy-N-methylphenethylamine ; toxicity

PURPOSE: Roflumilast is the only oral phosphodiesterase 4 inhibitor approved to treat chronic obstructive pulmonary disease (COPD) patients [post-bronchodilator forced expiratory volume in 1 second (FEV1) <50% predicted] with chronic bronchitis and a history of frequent exacerbations. This study evaluated the efficacy and safety of roflumilast in Korean patients with COPD and compared the efficacy based on the severity of airflow limitation. MATERIALS AND METHODS: A post-hoc subgroup analysis was performed in Korean COPD patients participating in JADE, a 12-week, double-blinded, placebo-controlled, parallel-group, phase III trial in Asia. The primary efficacy endpoint was the mean [least-squares mean adjusted for covariates (LSMean)] change in post-bronchodilator FEV1 from baseline to each post-randomization visit. Safety endpoints included adverse events (AEs) and changes in laboratory values, vital signs, and electrocardiograms. RESULTS: A total of 260 Korean COPD patients were recruited, of which 207 were randomized to roflumilast (n=102) or placebo (n=105) treatment. After 12 weeks, LSMean post-bronchodilator FEV1 increased by 43 mL for patients receiving roflumilast and decreased by 60 mL for those taking placebo. Adverse events were more common in the roflumilast group than in the placebo group; however, the types and frequency of AEs were comparable to those reported in previous studies. CONCLUSION: Roflumilast significantly improved lung function with a tolerable safety profile in Korean COPD patients irrespective of the severity of airflow limitation.
Aged ; Aminopyridines/*therapeutic use ; *Asian Continental Ancestry Group ; Benzamides/*therapeutic use ; Cyclopropanes/therapeutic use ; Double-Blind Method ; Female ; Humans ; Male ; Middle Aged ; Phosphodiesterase 4 Inhibitors/*therapeutic use ; Pulmonary Disease, Chronic Obstructive/*drug therapy/*ethnology/physiopathology ; Republic of Korea ; Respiratory Function Tests ; Treatment Outcome

cAMP-specific phosphodiesterase type 4 (PDE4) is one of the hot targets for treatment of inflammatory diseases. PDE4 inhibitors can suppress inflammation by increasing the concentration of cAMP in inflammatory cells. The efficacy and safety evaluations of several PDE4 inhibitors are currently carried on in clinical trials, for example GSK256066 in asthma, roflumilast and GSK256066 in chronic obstructive pulmonary disease, tetomilast in inflammatory bowel disease, and apremilast in dermatitis and arthritis etc. This article reviews the recent progress on PDE4-targeted therapy for inflammatory diseases.
Aminopyridines ; pharmacology ; Aminoquinolines ; pharmacology ; Arthritis ; drug therapy ; Asthma ; drug therapy ; Benzamides ; pharmacology ; Cyclopropanes ; pharmacology ; Dermatitis ; drug therapy ; Humans ; Inflammation ; drug therapy ; Inflammatory Bowel Diseases ; drug therapy ; Phosphodiesterase 4 Inhibitors ; pharmacology ; Pulmonary Disease, Chronic Obstructive ; drug therapy ; Sulfones ; pharmacology ; Thalidomide ; analogs & derivatives ; pharmacology ; Thiazoles ; pharmacology

BACKGROUND: There exists a treatment challenge with periungual warts. Topical immunotherapy with diphenylcyclopropenone (DPCP) has recently been reported to be an effective treatment for recalcitrant warts, including periungual types. OBJECTIVE: We aimed to evaluate the effectiveness and preference of topical immunotherapy with DPCP in treating periungual warts. METHODS: Twenty-seven patients with periungual warts who were treated with DPCP immunotherapy (2007 through 2010; Dongguk University Ilsan Hospital, Goyang, Korea) were retrospectively recruited. Other treatment modalities were also used in some patients. Lesions were grouped into the types according to the following locations: proximal nail fold, lateral nail fold and hyponychium. Total and group clearance rates as well as treatment periods according to location and disease duration were evaluated. A patient questionnaire was performed to assess the satisfaction for the treatments in those who received multiple therapies. RESULTS: Total success rates were 85% (by subjects) and 91% (by individual lesions). Success rate and treatment period for proximal nail fold type seemed more desirable than other locations. Success rate decreased and treatment period increased as disease duration increased. The questionnaire revealed a significantly higher satisfaction rate for DPCP immunotherapy than for cryotherapy and pulsed-dye laser. CONCLUSION: Topical immunotherapy with DPCP is an effective and preferred method in the treatment of periungual warts.
Cryotherapy ; Cyclopropanes ; Humans ; Immunotherapy* ; Retrospective Studies ; Warts* ; Surveys and Questionnaires

No abstract available.
Aged ; Anti-Bacterial Agents/pharmacology/therapeutic use ; Asian Continental Ancestry Group ; Bacterial Proteins/genetics/*metabolism ; China ; Cilastatin/therapeutic use ; Citrobacter freundii/drug effects/*enzymology/isolation & purification ; Drug Combinations ; Drug Resistance, Multiple, Bacterial ; Humans ; Imipenem/therapeutic use ; Male ; Microbial Sensitivity Tests ; Plasmids/*metabolism ; Respiratory Tract Infections/*diagnosis/drug therapy/microbiology ; beta-Lactamases/genetics/*metabolism

OBJECTIVES: The purpose of this study was to evaluate the risk indicators of periodontal disease in a representative sample of Korean adults aged between 18 and 44 years. METHODS: Data of 6,485 adults were derived from the Fourth Korean National Health and Nutrition Examination Survey, which was conducted from 2007 to 2009. Demographic, socioeconomic, and oral health-related behavioral data were collected as independent variables. The Community Periodontal Index (CPI) was used as a dependent variable. The chi-square test and logistic regression analysis were performed to identify the relationship between the CPI and the other variables. RESULTS: Multiple logistic regression analysis revealed that periodontal pocket formation (4 mm or more) was related with sex, age, and income level, irrespective of whether the mother engaged in economic activities in childhood, smoking experience, dental flossing, and use of interdental brushes. The subjects in the lowest-income quartile and those who were current smokers had a higher risk of pocket formation (odds ratios, 1.43 and 1.74, respectively) than those in the highest-income quartile and those who had no smoking experience, respectively. CONCLUSIONS: This study confirmed various risk indicators of periodontal disease in Korean adults, using Korean national survey data. Smoking cessation, dental flossing, and efforts to decrease socioeconomic inequality should be encouraged to decrease the risk of periodontal disease.
Adult ; Aged ; Cyclopropanes ; Dental Devices, Home Care ; Humans ; Indoles ; Logistic Models ; Mothers ; Nutrition Surveys ; Periodontal Diseases ; Periodontal Index ; Periodontal Pocket ; Smoke ; Smoking ; Smoking Cessation ; Socioeconomic Factors

Fibromyalgia syndrome (FMS) is characterized by chronic widespread pain and various accompanying symptoms including fatigue, sleep disturbances, and cognitive dysfunction. While the etiology of fibromyalgia is unclear, accumulating data suggest that disordered central pain processing likely plays a role in the pathogenesis of symptoms. Although the 1990 American College of Rheumatology (ACR) classification criteria for FMS were originally developed for research purposes and were not intended for clinical diagnosis, the criteria have become the de facto diagnostic criteria in clinical settings. Recently, an improved clinical case definition for FMS was proposed by ACR in 2010 to overcome several limitations of 1990 ACR criteria. Further studies are needed to assess the acceptance, reliability, and validity of the new criteria in epidemiologic and clinical studies. Many randomized controlled trials and meta-analyses confirm the therapeutic efficacy of pregabalin, duloxetine, and milnacipran, in the treatment of FMS. In view of the currently available evidence, a combination of pregabalin, duloxetine, or milnacipran as pharmacological interventions and aerobic exercise or CBT as non-pharmacological interventions seems most promising.
Cyclopropanes ; Exercise ; Fatigue ; Fibromyalgia ; gamma-Aminobutyric Acid ; Rheumatology ; Thiophenes ; Duloxetine Hydrochloride ; Pregabalin

No abstract available.
Cyclopropanes ; Melanoma