OBJECTIVE: This study aimed to provide efficacy and safety information on the use of erenumab for prevention of episodic and chronic migraines. METHODS: The keywords “Erenumab and migraine” were used to search the PubMed database to then compile efficacy and safety data for erenumab. Data from relevant Phase 2 and Phase 3 clinical trials were analyzed, using RevMan for statistical analysis. RESULTS: Three clinical trials (one Phase 2 and two Phase 3 studies) were retrieved. All three trials used the same primary endpoint (change from baseline in monthly migraine days (CBMD)) to evaluate efficacy and safety of erenumab use for prevention of episodic and chronic migraines. Subcutaneous doses of erenumab (70 or 140 mg) were administered monthly in each trial, for 3 months (Studies 2, and 3) or 6 months (Study 1). The mean differences in CBMD in the 70 mg and 140 mg erenumab arms were −1.36 and −1.98, respectively, compared to that in the placebo arm. Some adverse events, such as nasopharyngitis and upper respiratory tract infection, were reported, but no differences in safety between erenumab and placebo were found to be significant. CONCLUSIONS: Erenumab showed superior efficacy in prevention of migraines compared to placebo. However, additional information regarding the long-term safety of erenumab should be collected. Therefore, post-marketing surveillance for adverse events is needed.
Arm ; Migraine Disorders ; Nasopharyngitis ; Respiratory Tract Infections

PURPOSE: Replication-competent adenoviruses (Ads) are promising new modalities for the treatment of cancer. Selective replication of a viral agent in tumor may lead to improved efficacy over non-replicating Ads due to viral multiplication, lysis of the infected cancer cell and spread to surrounding cells. In our previous studies it was shown that the E1B 55 kD-deleted Ad (YKL-1) exhibits tumor specific replication and cell lysis, but with reduced cytolytic effects compared to the wild type adenovirus (Int J Cancer 2000;88: 454-463). Thus, improving the potency of oncolytic Ads remains an important goal for cancer gene therapy. To increase the oncolytic ability of YKL-1, an adenovirus death protein (ADP) gene was reintroduced under the control of a CMV or MLP promoter at the E3 region of the YKL-1, generating an YKL-cADP and YKL-mADP, respectively. MATERIALS AND METHODS: The in vitro cytolytic effect of ADP expressing Ads was evaluated by MTT assay, and the induction of apoptosis by ADP expressing Ads was examined by TUNEL analysis. Finally, the antitumor effect of ADP expressing Ads was demonstrated in C33A xenograft tumor model. RESULTS: The YKL-cADP exerted a markedly enhanced cytolytic effect against H460 and SK-Hep1 cancer cell lines. The TUNEL assay indicated that the ADP-mediated cytotoxicity was largely driven by apoptosis. Finally, the YKL-cADP showed a superior antitumor effect than the YKL-1 or YKL-mADP in C33A xenografts. CONCLUSION: These lines of evidence demonstrate that the YKL-cADP induces efficient cell lysis, which is critical for the addition of therapeutic value to replicating Ads in cancer gene therapy.
Adenosine Diphosphate ; Adenoviridae* ; Apoptosis ; Cell Line ; Genes, Neoplasm ; Heterografts ; In Situ Nick-End Labeling

In order to solve the problems of traditional teaching model for medical statistics based on theoretical lecture, we developed new teaching model for medical statistics. The model was consisted of theoretical and practical lecture for 2nd grade of premedical students, Ewha Womans University. For theoretical lecture, we introduced basic concepts of medical statistics, data description and social survey method with questionnaire development. For practical lecture, we introduced the whole process from the selection for research topic to sampling, survey, data analysis, and report writing. Although students participated this class pointed out some trivial problems, they gave positive evaluation, particularly on practical lecture. We think this new model will be a good model and let medical students have ability to do medical research through basic knowledge and practical skill.
Surveys and Questionnaires ; Female ; Humans ; Linear Energy Transfer ; Schools, Medical* ; Statistics as Topic ; Students, Medical ; Students, Premedical ; Writing

When stenting is applied to treat myocardial infarction, antiplatelet agents are administered to prevent thrombosis, which increases the risk of bleeding. Patients with myocardial infarction are also more likely to have osteoarthritis simultaneously, because both diseases occur frequently in elderly patients. Patients with osteoarthritis often use analgesics, especially nonsteroidal anti-inflammatory drugs (NSAIDs); hence, patients with both diseases use analgesics and antiplatelet agents simultaneously. The risk of bleeding increases with the use of antiplatelet agents and this is further increased when NSAIDs are added. We would like to report a case that reflects this situation. A 60-year-old man underwent stenting after ST-elevation myocardial infarction, and was treated with aspirin and clopidogrel. This patient also received a pelubiprofen prescription from another physician to treat osteoarthritis. After the patient took pelubiprofen twice, he found a bruise on his wrist and reported it to the pharmacist. It is unlikely that this is rare in community pharmacies, so pharmacists should pay careful attention to the concomitant administration of analgesics to patients receiving antiplatelet agents and should provide appropriate education to patients.
Aged ; Analgesics ; Anti-Inflammatory Agents, Non-Steroidal ; Aspirin ; Contusions ; Education ; Hemorrhage* ; Humans ; Middle Aged ; Myocardial Infarction ; Osteoarthritis ; Pharmacies ; Pharmacists ; Platelet Aggregation Inhibitors ; Prescriptions ; Stents ; Thrombosis ; Wrist

PURPOSE: This study has been planned to generate a replication-competent adenovirus which replicates in a cancer cell-specific manner, thus minimizing the side effects and toxicity of cancer gene therapy. MATERIALS AND METHODS: we have generated an E1B 19 kD attenuated recombinant adenoviruses, Ad-TERT-delta19 and Ad-mTERT-delta19, which encode E1A gene driven by the wild type hTERT and modified m-hTERT promoter containing additional c-myc and Sp1 binding sites in the backbone of Ad-deltaE1B19. The in vitro efficacy and specificity of the hTERT and m-hTERT promoter have been evaluated by the comparison of viral replication and cytopathic effect in cancer cells and normal cell lines. To assess anti-tumor effect and safety of hTERT or m-hTERT promoter driven replication competent adenoviruses, tumor regression after subcutaneous injection in subcutaneous C33A xenografts and lacZ expression after systemic injection in organs were examined. RESULTS: The activation of hTERT or m-hTERT promoter was significantly up-regulated only in hTERT-positive cells, but not in hTERT-negative cells. Moreover, the activity of m-hTERT promoter was substantially increased in hTERT-positive cancer cells, but not in hTERT-negative cells. While Ad-TERT-delta19 replicated in and induced cytopathic effect in cancer and in some normal cell lines, Ad-mTERT-delta19 enhanced viral replication and cytopathic effect in cancer cells only. Furthermore, the growth of established human cervical carcinoma in nude mice was significantly suppressed by intratumoral injection of Ad-mTERT-delta19. CONCLUSIONS: The use of m-hTERT promoter is not only useful in the regulation of therapeutic gene expression but also that replication-competent oncolytic adenovirus under the control of m-hTERT promoter may be a new promising tool for the treatment of human malignancies.
Adenoviridae* ; Animals ; Binding Sites ; Cell Line ; Gene Expression ; Genes, Neoplasm ; Heterografts ; Humans* ; Injections, Subcutaneous ; Mice ; Mice, Nude ; Sensitivity and Specificity ; Telomerase*

Pseudohypoparathyroidism (PHP) is a rare disorder caused by genetic and epigenetic aberrations in the GNAS complex locus resulting in impaired expression of stimulatory G protein (Gsα). PHP type Ib (PHP-Ib) is characterized by hypocalcemia and hyperphosphatemia due to renal resistance to the parathyroid hormone, and is distinguished from PHP-Ia by the absence of osteodystrophic features. An 11-yr-old boy presented with poor oral intake and cramping lower limb pain after physical activity. Laboratory studies revealed hypocalcemia, hyperphosphatemia, and increased parathyroid hormone levels. The GNAS complex locus was evaluated using the methylation-specific multiplex ligation-dependent probe amplification (MS-MLPA) assay. Gain of methylation in the NESP55 domain and loss of methylation in the antisense (AS) transcript, XL, and A/B domains in the maternal allele were observed. Consequently, we present a case of PHP-Ib diagnosed using MS-MLPA.
Alleles ; Epigenomics ; GTP-Binding Proteins ; Humans ; Hyperphosphatemia ; Hypocalcemia ; Lower Extremity ; Male ; Methylation* ; Motor Activity ; Multiplex Polymerase Chain Reaction ; Muscle Cramp ; Parathyroid Hormone ; Pseudohypoparathyroidism*

BACKGROUND: Hereditary breast and ovarian cancer syndrome (HBOC) is caused by pathogenic variants in BRCA and other cancer-related genes. We analyzed variants in BRCA gene and other cancer-related genes in HBOC patients to evaluate the clinical validity of next-generation sequencing (NGS) multi-gene panel testing. METHODS: The BRCA1/2 NGS testing was conducted for 262 HBOC patients. Multiplex ligation-dependent probe amplification and direct Sanger sequencing were performed for confirmation. Multi-gene panel testing was conducted for 120 patients who did not possess BRCA1/2 pathogenic variants but met the National Comprehensive Cancer Network criteria. RESULTS: Pathogenic variants in BRCA1/2 were detected in 30 HBOC patients (11.5%). Additionally, four out of the 120 patients possessed pathogenic variants by multi-gene panel testing (3.3%): MSH2 (c.256G>T, p.Glu86*), PMS2 (c.1687C>T, p.Arg563*), CHEK2 (c.546C>A, p.Tyr182*), and PALB2 (c.3351-1G>C). All the four patients had a family history of cancer. CONCLUSIONS Multi-gene panel testing could be a significant screening tool for HBOC patients, especially for those with a family history of cancer.

PURPOSE: Bevacizumab±irinotecan is effective for treatment of recurrent malignant gliomas. However, the optimal duration of treatment has not been established. MATERIALS AND METHODS: Ninety-four consecutive patients with recurrent malignant glioma who were treated with bevacizumab at our institutions were identified. Patients who continued bevacizumab until tumor progression were enrolled in a late discontinuation (LD) group, while those who stopped bevacizumab before tumor progression were enrolled in an early discontinuation (ED) group. Landmark analyses were performed at weeks 9, 18, and 26 for comparison of patient survival between the two groups. RESULTS: Among 89 assessable patients, 62 (69.7%) and 27 (30.3%) patients were categorized as the LD and ED groups, respectively. According to landmark analysis, survival times from weeks 9, 18, and 26 were not significantly different between the two groups in the overall population. However, the LD group showed a trend toward increased survival compared to the ED group among responders. In the ED group, the median time from discontinuation to disease progression was 11.4 weeks, and none of the patients showed a definite rebound phenomenon. Similar median survival times after disease progression were observed between groups (14.4 weeks vs. 15.7 weeks, p=0.251). Of 83 patients, 38 (45.8%) received further therapy at progression, and those who received further therapy showed longer survival in both the LD and ED groups. CONCLUSION: In recurrent malignant glioma, duration of bevacizumab was not associated with survival time in the overall population. However, ED of bevacizumab in responding patients might be associated with decreased survival.
Bevacizumab* ; Disease Progression ; Glioblastoma ; Glioma* ; Humans

BACKGROUND: Although the importance of pharmaceutical care service has been growing to meet the needs of customers with the improvement of clinical and humanistic outcomes, there was not a systematic strategy to promote research in Korea. The aim of this study was to suggest the core agendas for pharmaceutical care services research and development (R&D) considering priorities. METHODS: Based on desk researches, we developed R&D agendas for the needs of improving pharmaceutical care services in the area of institution, community, and public health. To determine the priority of agendas in developing pharmaceutical care service, analytic hierarchy process (AHP) analysis was performed by the 14 experts. Criteria and subcriteria were assessed for significance by pairwise comparisons. Then, agendas were evaluated for importance according to each subcriteria, and rank ordered considering the weight calculated by multiplying the importance scores of the criteria and the subcriteria. RESULTS: We derived 25 agendas including 13 for institutional pharmaceutical care service, 8 for community pharmaceutical care service, and 4 for public-health related pharmaceutical care service. AHP model was constructed based on 4 criteria and 8 subcriteria by a hierarchical structure. From the AHP survey, the ‘Development of pharmaceutical care service for metabolic and chronic disease’ agenda accounted for the highest priority. CONCLUSION: We have developed the R&D agendas of the pharmaceutical care service which should be promoted. The results should be utilized by the government to nationally support the development of the standards and relevant regulations related to pharmaceutical care services in Korea.
Korea ; Pharmaceutical Services ; Public Health ; Social Control, Formal

In this study, we determined mode of action of a novel carbamoyloxy arylalkanoyl arylpiperazine compound (SKL-NP) on hyperpolarization-activated cyclic nucleotide-gated (HCN) channel currents (Ih) that plays important roles in neuropathic pain. In small or medium-sized dorsal root ganglion (DRG) neurons (<40 microm in diameter) exhibiting tonic firing and prominent Ih, SKL-NP inhibited Ih and spike firings in a concentration dependent manner (IC50=7.85 microM). SKL-NP-induced inhibition of Ih was blocked by pretreatment of pertussis toxin (PTX) and N-ethylmaleimide (NEM) as well as 8-Br-cAMP, a membrane permeable cAMP analogue. These results suggest that SKL-NP modulates Ih in indirect manner by the activation of a Gi-protein coupled receptor that decreases intracellular cAMP concentration. Taken together, SKL-NP has the inhibitory effect on HCN channel currents (I h) in DRG neurons of rats.
Animals ; Diagnosis-Related Groups ; Ethylmaleimide ; Fires ; Ganglia, Spinal ; Membranes ; Neuralgia ; Neurons ; Pertussis Toxin ; Rats ; Spinal Nerve Roots