Analysis of patients' request to switch from a generic drug to the original drug in external prescriptions.

BACKGROUND: Generic drugs are heavily promoted in Japan. The aim of this retrospective single-center study was to clarify whether the frequency and reason that patients request a switch from a generic drug to the original drug differ according to therapeutic category and dosage form. METHODS: This study was performed at Chiba University Hospital. Prescription inquiries about 121 generic drugs from community pharmacies over a 3-year period (from July 2014 to June 2017) were analyzed. RESULTS: Approximately 30% of the requests were related to the efficacy, safety, and comfort of the generic drug. The most cited motive was "patient's desire with no reason given" at 44.5%. According to multiple logistic regression analysis, therapeutic categories and dosage forms were associated with the requests. The median request frequency differed according to therapeutic category and dosage form. The frequency was highest for "agents affecting the central nervous system" and "tablets and capsules", respectively. Among the therapeutic categories, "agents affecting the central nervous system" had the highest median number of requests related to "decreased effectiveness"; "cardiovascular agents" had the highest median number of requests related to "physician's instruction"; and "agents for the epidermis" had the highest median number of requests related to "uncomfortable to use". Among dosage forms, the odds ratio for patients' original drug request for "liniment and patch" was about 1.5 times that for "tablets and capsules". "Liniment and patch" had the highest median frequency of requests related to "decreased effectiveness", "uncomfortable to use", and "patient's desire with no reason given". CONCLUSIONS: The request frequency and reason differed according to therapeutic category and dosage form. Pharmacists should advise each patient properly about the choice and switching of drug brands, taking into account the therapeutic category and dosage form, especially liniments and patches.

A multicenter, randomized controlled trial comparing the identification rate of stigmata of recent hemorrhage and rebleeding rate between early and elective colonoscopy in outpatient-onset acute lower gastrointestinal bleeding: study protocol for a randomized controlled trial.

BACKGROUND: The clinical benefit of early colonoscopy within 24 h of arrival in patients with severe acute lower gastrointestinal bleeding (ALGIB) remains controversial. This trial will compare early colonoscopy (performed within 24 h) versus elective colonoscopy (performed between 24 and 96 h) to examine the identification rate of stigmata of recent hemorrhage (SRH) in ALGIB patients. We hypothesize that, compared with elective colonoscopy, early colonoscopy increases the identification of SRH and subsequently improves clinical outcomes. METHODS: This trial is an investigator-initiated, multicenter, randomized, open-label, parallel-group trial examining the superiority of early colonoscopy over elective colonoscopy (standard therapy) in ALGIB patients. The primary outcome measure is the identification of SRH. Secondary outcomes include 30-day rebleeding, success of endoscopic treatment, need for additional endoscopic examination, need for interventional radiology, need for surgery, need for transfusion during hospitalization, length of stay, 30-day thrombotic events, 30-day mortality, preparation-related adverse events, and colonoscopy-related adverse events. The sample size will enable detection of a 9% SRH rate in elective colonoscopy patients and a SRH rate of ≥ 26% in early colonoscopy patients with a risk of type I error of 5% and a power of 80%. DISCUSSION: This trial will provide high-quality data on the benefits and risks of early colonoscopy in ALGIB patients. TRIAL REGISTRATION: UMIN-CTR Identifier, UMIN000021129 . Registered on 21 February 2016; ClinicalTrials.gov Identifier, NCT03098173 . Registered on 24 March 2017.

Pseudomonas aeruginosa overexpression system of nitric oxide reductase for in vivo and in vitro mutational analyses.

Membrane-integrated nitric oxide reductase (NOR) reduces nitric oxide (NO) to nitrous oxide (N2O) with protons and electrons. This process is essential for the elimination of the cytotoxic NO that is produced from nitrite (NO2-) during microbial denitrification. A structure-guided mutagenesis of NOR is required to elucidate the mechanism for NOR-catalyzed NO reduction. We have already solved the crystal structure of cytochrome c-dependent NOR (cNOR) from Pseudomonas aeruginosa. In this study, we then constructed its expression system using cNOR-gene deficient and wild-type strains for further functional study. Characterizing the variants of the five conserved Glu residues located around the heme/non-heme iron active center allowed us to establish how the anaerobic growth rate of cNOR-deficient strains expressing cNOR variants correlates with the in vitro enzymatic activity of the variants. Since bacterial strains require active cNOR to eliminate cytotoxic NO and to survive under denitrification conditions, the anaerobic growth rate of a strain with a cNOR variant is a good indicator of NO decomposition capability of the variants and a marker for the screening of functionally important residues without protein purification. Using this in vivo screening system, we examined the residues lining the putative proton transfer pathways for NO reduction in cNOR, and found that the catalytic protons are likely transferred through the Glu57 located at the periplasmic protein surface. The homologous cNOR expression system developed here is an invaluable tool for facile identification of crucial residues in vivo, and for further in vitro functional and structural studies.

Connexin32 protects against vascular inflammation by modulating inflammatory cytokine expression by endothelial cells.

Gap junctions (GJs) play an important role in vascular function, stability, and homeostasis in endothelial cells (ECs), and GJs are comprised of members of the connexin (Cx) family. GJs of vascular ECs are assembled from Cx37, Cx40, and Cx43, and we showed that ECs also express Cx32. In this study, we investigated a potential role for Cx32 during vascular inflammation. Expression of Cx32 mRNA and protein by human umbilical venous ECs (HUVECs) decreased following treatment with tumor necrosis factor (TNF)-α, but lipopolysaccharide (LPS) and interleukin (IL)-1ß did not affect Cx32 expression. Intracellular transfer of an inhibitory anti-Cx32 monoclonal antibody significantly enhanced TNF-α-induced monocyte chemotactic protein (MCP)-1 and IL-6 expression, but overexpression of Cx32 abrogated TNF-α-induced MCP-1 and IL-6 expression. LPS treatment of Cx32 knock-out mice significantly increased the serum concentrations of TNF-α, interferon-γ, IL-6 and MCP-1, compared to wild-type littermate mice. These data suggest that Cx32 protects ECs from inflammation by regulating cytokine expression and plays an important role in the maintenance of vascular function.

Connexin32 is expressed in vascular endothelial cells and participates in gap-junction intercellular communication.

Endothelial cells (ECs) play many roles in vascular biology, including control of blood pressure, blood clotting, atherosclerosis, angiogenesis, and inflammation. Gap junctions (GJs) are channel-like assemblies of connexin (Cx) family proteins that connect neighboring cells and modulate and synchronize their intracellular environments by the transfer of intracellular mediators. It has been reported that vascular ECs express Cx37, Cx40, and Cx43, but not Cx32. Here, we showed that Cx32 mRNA and protein are expressed in various cultured human ECs. We confirmed Cx32 expression in blood vessel ECs using wild-type and Cx32 knock-out mice. We observed that dye transfer between cultured ECs through gap junctions is suppressed by an anti-Cx32 monoclonal antibody. These findings suggest that vascular ECs express Cx32, which participates in endothelial gap-junction intercellular communication.

[Correlation between the SF-8 health status questionnaire and JRQLQ in patients with Japanese cedar pollinosis].

BACKGROUND: It is reported that the health-related quality of life (HRQL) is an important outcome in the Japanese Cedar Pollinosis (JCP) treatment. In Japan, the disease-specific Japan Rhino-conjunctivitis Quality of Life Questionnaire (JRQLQ) and the generic SF-36 Health Survey (SF-36) has been used. The aim of this study is to investigate more profitable QOL by using both the disease-specific questionnaire and the non-disease-specific questionnaire together. METHODS: 411 patients with JCP who visited 10 ENT clinics in Osaka from March 14 to March 26 (peak pollen season) in 2005 were questioned, and 240 patients were engaged in this study as subjects. In this study, the QOL scores were evaluated using the JRQLQ and SF-8 Health Survey (Japanese Version), a new, even shorter generic health survey. RESULTS: Using factor analysis and the correlation matrix, we showed that the disease-specific and the general health instrument covered a different half the total measurable HRQL. There was some correlation between the SF-8 items with the JRQLQ domains. There was little correlation between the SF-8 items and symptom scores, while, there was high correlation between the JRQLQ and symptom scores. The "Usual daily activities" domain in the JRQLQ correlated with any rhinoconjunctivitis symptoms. CONCLUSION: Both JRQLQ and SF-8 can be used to assess the quality of life of patients with JCP. Each instrument measures the aspects of the HRQL that hardly overlaps. For an assessment of the HRQL in JCP that is complete and responsive both instruments should be employed together.

[Quality of life in patients with Japanese cedar pollinosis: using the SF-8 health status questionnaire (Japanese version)].

BACKGROUND: The number of patients with Japanese cedar pollinosis (JCP) is increasing, and now, has extended up to about 15% of the Japanese. It is reported that the QOL is an important outcome in the JCP treatment. This study aimed to evaluate the QOL in patients with JCP by means of the SF-8 Health Survey (Japanese Version), a new, even shorter generic health survey. METHODS: 411 patients with JCP who visited 10 ENT clinics in Osaka from March 14 to March 26 (peak pollen season) were questioned, and 204 patients without any treatments in this season were engaged in this study as subjects. In this study, the QOL scores were evaluated using the SF-8. This is an 8-item version of the SF-36 that yields a comparable 8-dimension health profile and comparable estimates of summary scores for the physical and mental components of health. RESULTS: The QOL score depressed in the patients with JCP compared with healthy subjects (Japanese national norms). Both Mental Component Score (MCS) and Physical Component Score (PCS) scores decreased more in females than in males. In females, MCS were significantly lower than national norms. The older the patients were, the lower PCS scores were showed. The severity of nasal symptoms influenced the PCS scores. CONCLUSION: These results showed the tendency similar to the early studies using SF-36 questionnaire. The sensitivity of SF-8 in the individual is not better than that of other specific QOL questionnaires, but SF-8 can be answered in a short time compared with other questionnaires including SF-36. We suggested that SF-8 become a useful questionnaire in the future.

[Willingness to pay for Japanese cedar pollinosis: comparison between pollination and non-pollination seasons].

Allergic rhinitis is not fatal illness, but its high prevalence and several symptoms result in substantial medical cost. There is increasing interest in the use of economic evaluations in healthcare; therefore, we investigated patients' willingness to pay (WTP) for prevention and cure from Japanese cedar pollinosis (JCP), and compared WTP values assessed in non-pollination season (June 1998) and pollination season (February-March 2003). Japanese economic woes got worse in 2003 than in 1998. Patients were randomly selected from ENT clinical sites in Osaka, 175 and 645 patients completed WTP questionnaire in 1998 and 2003, respectively. WTP value was lower in 2003 than in 1998, which related to part-time employees and housewives' reducing WTP. Declining WTP value did not associated with the differences in patient characteristics between 1998 and 2003 including age, duration of disease, nasal symptom severity and comorbid condition. These results show that we have to take employment status into account in economic evaluations. Decline in WTP for JCP in 2003 was strongly affected by Japanese sluggish economy, and the WTP seemed to be stable value in individual patients.

Measurement of quality of life during different clinical phases of Japanese cedar pollinosis.

OBJECTIVE: To assess Quality of Life (QOL) scores in patients with Japanese cedar (Cryptomeria japonica, CJ) pollinosis. METHODS: QOL was measured intraseasonally and extraseasonally in patients (n = 69) using the Medical Outcomes Study Short-Form Health Survey, and compared with healthy control subjects (n = 50). The differences in intraseasonal QOL scores between short and long disease duration groups were studied. The relation of intraseasonal QOL scores to nose symptoms was evaluated using Spearman's rank correlation. RESULTS: Significant decrease was observed in two of eight QOL items in intraseasonal measurements of patients. These QOL impairments improved extraseasonally. Scores for emotional problems in patients with long disease duration were less impaired than those with short disease duration. QOL scores in patients correlated poorly with the severity of nasal symptom. CONCLUSIONS: This is the first study to report QOL impairment in CJ pollinosis. Based on the findings long disease duration may improve emotional problems, and the correlation between disease severity and QOL is low.

[Willingness to pay and quality of life in patients with Japanese-cedar pollinosis].

Seasonal allergic rhinitis (SAR) is one of the world's most common health problems because it's a high-cost, high-prevalence disease. In this study, we investigated patients' willingness to pay (WTP) for prevention and cure from most common SAR, Japanese-cedar pollinosis. Two hundred and forty patients with Japanese-cedar pollinosis, who visited 4 clinics in Osaka and were measured QOL by the SF-36 Questionnaire (Japanese version) during pollen season, were mailed WTP questionnaire in off-season in 1998. Completed questionnaires were sent back by 175 patients. Most patients (83.5%) were willing to pay less than 10,000 yen. Patients with longer duration of disease or severer nasal symptom tended to be more willing to pay. In contrast, no association was found between WTP and sex, age, occupation and comorbid condition. There were significant impairments in five of eight QOL dimensions in patients of Much-WTP in comparison with Less-WTP. Patients with mild symptom had significant higher medication cost than those with less mild symptom. We conclude that effective treatment, even if it costs much, can satisfy patients and may help to reduce indirect costs as well as to lessen the impact of Japanese-cedar pollinosis on QOL for both patient and society.