Subcutaneous edema as a potential cause of catheter failure in older inpatients receiving peripheral parenteral nutrition.

Malnutrition is a common problem among hospitalized older patients. Peripheral parenteral nutrition (PN) can improve patient outcomes but can also lead to complications that affect future treatment. Older inpatients, in particular, are expected to be prone to these catheter-related complications. However, the impact of peripheral PN on older inpatients has been rarely investigated. In the current study, the impact of PN on short peripheral catheters (SPCs) was evaluated by comparing signs and symptoms at the time of catheter removal between 22 patients with PN and 27 without. In addition to external clinical assessment, sonographic investigations of the SPC site were performed. The prevalence of external signs and symptoms of complications was similar between the patients (all P > 0.05). However, subcutaneous edema was found by ultrasound in > 80% of patients with PN, compared with 55.6% of those without PN (P = 0.051). Unlike cases without PN, all patients with PN who presented with external signs and symptoms developed subcutaneous edema (P = 0.022). Multivariate analysis demonstrated that administration of PN was independently associated with subcutaneous edema (adjusted odds ratio = 6.88, 95% confidence interval = 1.083-75.486, P = 0.040). For several decades, phlebitis has been the primary focus of complications related to peripheral PN in clinical settings. However, our results imply that peripheral PN causes subcutaneous edema, which can lead to catheter failure in older inpatients. This study contributes to understanding the etiology of catheter failure during peripheral PN in this population.

Association between culture and the preference for, and perceptions of, 11 routes of medicine administration: A survey in 21 countries and regions.

Medicines can be taken by various routes of administration. These can impact the effects and perceptions of medicines. The literature about individuals' preferences for and perceptions of the different routes of administration is sparse, but indicates a potential influence of culture. Our aim was to determine: (i) any association between one's culture and one's preferred route of medicine administration and (ii) individual perceptions of pain, efficacy, speed of action and acceptability when medicines are swallowed or placed in the mouth, under the tongue, in the nose, eye, ear, lungs, rectum, vagina, on the skin, or areinjected. A cross-sectional, questionnaire-based survey of adults was conducted in 21 countries and regions of the world, namely, Tunisia, Ghana, Nigeria, Turkey, Ethiopia, Lebanon, Malta, Brazil, Great Britain, United States, India, Serbia, Romania, Portugal, France, Netherlands, Japan, South Korea, Hong Kong, mainland China and Estonia, using the Inglehart-Welzel cultural map to ensure coverage across all cultures. Participants scored the pain/discomfort, efficacy, speed of onset and acceptability of the different routes of medicine administration and stated their preferred route. Demographic information was collected. A total of 4435 participants took part in the survey. Overall, the oral route was the most preferred route, followed by injection, while the rectal route was the least preferred. While the oral route was the most preferred in all cultures, the percentage of participants selecting this route varied, from 98% in Protestant Europe to 50% in the African-Islamic culture. A multinomial logistic regression model revealed a number of predictors for the preferred route. Injections were favoured in the Baltic, South Asia, Latin America and African-Islamic cultures while dermal administration was favoured in Catholic Europe, Baltic and Latin America cultures. A marked association was found between culture and the preference for, and perceptions of the different routes by which medicines are taken. This applied to even the least favoured routes (vaginal and rectal). Only women were asked about the vaginal route, and our data shows that the vaginal route was slightly more popular than the rectal one.

Community Pharmacists' Experiences and Attitudes towards the Provision of Sexual and Reproductive Health Services: An International Survey.

Access to comprehensive sexual and reproductive health (SRH) services remains a challenge worldwide. Describing community pharmacists' SRH services in countries with different scopes of practice will aid in understanding how pharmacists view their roles and how to support them in providing needed services. A cross-sectional web-based survey was administered to pharmacists working in community pharmacies in Japan, Thailand, and Canada. The survey covered 7 SRH categories: pregnancy tests, ovulation tests, contraception, emergency contraception, sexually transmitted and blood-borne infections, maternal and perinatal health, and general sexual health. Descriptive statistics were used to analyze the data. A total of 922 eligible responses were included in the analysis (Japan = 534, Thailand = 85, and Canada = 303). Most Thai and Canadian participants reported dispensing hormonal contraceptives (Thailand = 99%, Canada = 98%) and emergency contraceptive pills (Thailand = 98%, Canada = 97%). Most Japanese participants provided patient education on barrier contraceptives for men (56%) and information on the safety of medications in pregnancy (74%) and breastfeeding (76%). The majority of participants expressed interest in additional training and expanding their roles in SRH. Sharing international experiences can guide challenges faced by the evolution of pharmacists' practice in SRH. Providing pharmacists support could help their readiness for this role.

Community pharmacists' provision of sexual and reproductive health services: A cross-sectional study in Alberta, Canada.

BACKGROUND: In many countries, pharmacists' scope of practice enables the delivery of professional pharmacy services related to sexual and reproductive health (SRH). Studies exploring practices and perspectives regarding a wide range of SRH professional pharmacy services and the extent to which pharmacists are involved in prescribing or administering injections are limited. OBJECTIVES: This study aimed to explore SRH professional pharmacy services provided by pharmacists, evaluate pharmacists' self-reported confidence in providing SRH education and determine preferences for additional training. METHODS: A cross-sectional Web-based survey was administered to pharmacists working in community pharmacies in Alberta, Canada. The survey was sent via e-mail and was open for 8 weeks between June and August 2020. Descriptive statistics were used to analyze the data. RESULTS: Most of the 303 participants were female (66%) and received their first pharmacy degree in Canada (69%). Approximately two-thirds had additional prescribing authorization (APA), and 97% had injections authorization; 90% and 94% of participants reported administering injectable contraceptives and human papillomavirus vaccine, respectively, and more than 95% renewed prescriptions for oral contraceptives. Of the participants with APA, approximately 40% reported providing initial prescribing services for contraceptive products. Overall, participants reported confidence in providing SRH education for most topics. Most selected topics for additional training were related to sexually transmitted and blood-borne infections; sexual health concerns of lesbian, gay, bisexual, transgender, queer or questioning; and abortion medications. CONCLUSION: Pharmacists in Alberta reported providing a wide range of SRH services and are interested in expanding their SRH role. These findings highlight opportunities to improve access and reduce inequities in the delivery of SRH services through community pharmacies. However, pharmacists' training needs should be considered.

Association between Cerebral Infarction Risk and Medication Adherence in Atrial Fibrillation Patients Taking Direct Oral Anticoagulants.

Direct oral anticoagulants (DOACs) are available for nonvalvular atrial fibrillation patients. The advantage of DOACs is that regular anticoagulation monitoring is not required. However, adherence to the recommended regimen is essential. We investigated the association between medication adherence and the risk of cerebral infarction in patients taking DOACs. Patients admitted to any of the participating hospitals for cerebral infarction from September 2018 to February 2020 and prescribed DOACs before admission were defined as the case group, and patients hospitalized for diseases other than cerebral infarction, except for bleeding disorders, and prescribed DOACs before admission were defined as the control group. A nested case-control study was adapted, and 58 and 232 patients were included in the case and control groups, respectively. Medication adherence was assessed by the pharmacists through standardized interviewing. The adjusted odds ratio for the risk of cerebral infarction for low-adherence patients (<80% adherence rate) against good-adherence patients (100% adherence rate) was 9.69 (95% confidence interval, 3.86-24.3; p < 0.001). The patients' age and other background characteristics were not found to be risk factors for cerebral infarction. In conclusion, low adherence is a risk factor for cerebral infarction in patients taking DOACs. Pharmacists should focus on maintaining ≥80% adherence to DOAC therapy to prevent cerebral infarction.

Reproductive Health Services: Attitudes and Practice of Japanese Community Pharmacists.

The provision of sexual and reproductive health (SRH) services is an important part of a community pharmacist's role in many countries. However, such services are not traditionally provided by pharmacists in Japan. We surveyed the practice and attitudes regarding the provision of SRH services among Japanese community pharmacists with a focus on reproductive health (RH) topics. The participants were asked about the provision of RH services, attitudes toward their role as SRH providers, and self-reported confidence in providing education to patients on RH topics. We obtained 534 effective responses. About half of the participants reported providing RH services, and only 21% were involved in dispensing emergency contraception pills. Although the proportion of pharmacists providing education on these topics was considerably lower, about 80% recognized the importance of their role as SRH advisors. Confidence in providing patient education about RH topics depended on their experience in providing such services. Most participants were interested in additional SRH training (80%). Our results suggest that training programs could help to expand Japanese community pharmacists' roles as SRH providers and increase their confidence in the education of patients. This study provides useful insights to expand pharmacists' roles in Japan as providers of comprehensive SRH services.

Predictive Value of the Cardio-Ankle Vascular Index for Cardiovascular Events in Patients at Cardiovascular Risk.

Background Arterial stiffness is an important predictor of cardiovascular events; however, indexes for measuring arterial stiffness have not been widely incorporated into routine clinical practice. This study aimed to determine whether the cardio-ankle vascular index (CAVI), based on the blood pressure-independent stiffness parameter ß and reflecting arterial stiffness from the origin of the ascending aorta, is a good predictor of cardiovascular events in patients with cardiovascular disease risk factors in a large prospective cohort. Methods and Results This multicenter prospective cohort study, commencing in May 2013, with a 5-year follow-up period, included patients (aged 40‒74 years) with cardiovascular disease risks. The primary outcome was the composite of cardiovascular death, nonfatal stroke, or nonfatal myocardial infarction. Among 2932 included patients, 2001 (68.3%) were men; the mean (SD) age at diagnosis was 63 (8) years. During the median follow-up of 4.9 years, 82 participants experienced primary outcomes. The CAVI predicted the primary outcome (hazard ratio, 1.38; 95% CI, 1.16‒1.65; P<0.001). In terms of event subtypes, the CAVI was associated with cardiovascular death and stroke but not with myocardial infarction. When the CAVI was incorporated into a model with known cardiovascular disease risks for predicting cardiovascular events, the global χ2 value increased from 33.8 to 45.2 (P<0.001), and the net reclassification index was 0.254 (P=0.024). Conclusions This large cohort study demonstrated that the CAVI predicted cardiovascular events. Registration URL: https://www.clinicaltrials.gov; Unique identifier: NCT01859897.

Perspectives on Continuing Education Programs for Foundation-Level Drugstore Pharmacists in Japan.

BACKGROUND: Continuing education (CE) is important for developing and updating pharmacists' knowledge, skills, and attitudes. CE programs should be developed according to social requirements but also based on personal requirements depending on the sectors the pharmacists work in. This research aims to explore perspectives on CE programs for foundation-level drugstore pharmacists in Japan. METHOD: Foundation-level drugstore pharmacists were asked what CE programs or training they needed to develop patient care or customer satisfaction. RESULTS: We obtained 417 opinions (multiple answers were allowed) in 280 responses from 460 pharmacists (male: 245 and female: 215). The products and goods about which drugstore pharmacists wanted to learn covered a wide range. They wanted to learn about taping skills, tests, and products and devices related to care of the elderly. Taping skill would be quite unique for drugstore pharmacists. For special populations, they wanted knowledge and skills related to pregnancy tests and the safe use of medication by pregnant or lactating women. CONCLUSION: Drugstore pharmacists in Japan have different CE and continuing professional development (CPD) requirements from community pharmacists. The benefits of CE programs meeting pharmacists' requirements should be evaluated in future research.

Outcome of pitavastatin versus atorvastatin therapy in patients with hypercholesterolemia at high risk for atherosclerotic cardiovascular disease.

BACKGROUND: There has been no report about outcome of pitavastatin versus atorvastatin therapy in high-risk patients with hypercholesterolemia. METHODS: Hypercholesterolemic patients with one or more risk factors for atherosclerotic diseases (n = 664, age = 65, male = 54%, diabetes = 76%, primary prevention = 74%) were randomized to receive pitavastatin 2 mg/day (n = 332) or atorvastatin 10 mg/day (n = 332). Follow-up period was 240 weeks. The primary end point was a composite of cardiovascular death, sudden death of unknown origin, nonfatal myocardial infarction, nonfatal stroke, transient ischemic attack, or heart failure requiring hospitalization. The secondary end point was a composite of the primary end point plus clinically indicated coronary revascularization for stable angina. RESULTS: The mean low-density lipoprotein cholesterol (LDL-C) level at baseline was 149 mg/dL. The mean LDL-C levels at 1 year were 95 mg/dL in the pitavastatin group and 94 mg/dL in the atorvastatin group. There were no differences in LDL-C levels between both groups, however, pitavastatin significantly reduced the risk of the primary end point, compared to atorvastatin (pitavastatin = 2.9% and atorvastatin = 8.1%, HR, 0.366; 95% CI 0.170-0.787; P = 0.01 by multivariate Cox regression) as well as the risk of the secondary end point (pitavastatin = 4.5% and atorvastatin = 12.9%, HR = 0.350; 95%CI = 0.189-0.645, P = 0.001). The results for the primary and secondary end points were consistent across several prespecified subgroups. There were no differences in incidence of adverse events between the statins. CONCLUSION: Pitavastatin therapy compared with atorvastatin more may prevent cardiovascular events in hypercholesterolemic patients with one or more risk factors for atherosclerotic diseases despite similar effects on LDL-C levels.

The development of a foundation-level pharmacy competency framework: An analysis of country-level applicability of the Global Competency Framework.

BACKGROUND: The importance and usefulness of competency frameworks (CFs) in pharmacy professional development is recognised globally. However, there is no national CF for pharmacists in Japan yet. OBJECTIVE: This study was conducted to measure the level of relevance of behavioural statements of the International Pharmaceutical Federation (FIP) Global Competency Framework (GbCF) to Japanese foundation-level pharmacy practice, aiming for developing a national framework for foundation-level pharmacists in Japan. METHODS: A cross-sectional, anonymous, online self-completed survey was conducted during June and July 2018 in Japan. The questionnaire was adopted from the GbCF, translated into Japanese. A snowballing sampling approach was used. The relevance levels of the GbCF items were assessed by using 4-point Likert scales, and analysed by descriptive and inferential methods. RESULTS: A total 604 useable responses were included in analyses. High levels of relevance levels were found in two clusters ('pharmaceutical public health' and 'pharmaceutical care'), while the other two clusters ('organisation and management' and 'professional/personal') showed significantly low relevance (relevance = 89.6%, 82.5%, 59.6%, and 67.9%, respectively). The study found little engagement of the academic sector with framework, while the industry sector showed relevance to all clusters evenly. Regarding years working in sectors, there was no progression of relevance in 'organisation and management' and 'professional/personal' competencies during foundation years as well as very little professional/personal development. CONCLUSIONS: The study revealed specific competencies and behaviours which require modifications to adapt the GbCF into the Japanese pharmacy practice environment. This is a key step towards the development of a national framework, illustrating current Japanese foundation-level pharmacy practice compared with global standards. The findings will be used as a base for developing a framework for foundation-level pharmacists in Japan and address concerns such as pharmacist preparedness to advance in management roles and limited personal and professional development.

Background characteristics and postoperative outcomes of insufficient weight loss after laparoscopic sleeve gastrectomy in Japanese patients.

AIM: Laparoscopic sleeve gastrectomy (LSG) is becoming popular in Japan, but insufficient weight loss is often observed in patients after LSG. We investigated the effect of LSG on obesity-related comorbidities and identified the background characteristics of Japanese patients with insufficient weight loss after LSG. METHODS: In this multi-institutional retrospective study at 10 certified bariatric institutions, 322 Japanese patients who underwent LSG with a follow-up period of more than 2 years were analyzed. Anthropometry, obesity-related comorbidities and psychosocial background data were collected. Weight loss was expressed as 2-year percent total weight loss (%TWL). RESULTS: Mean age, body weight, body mass index (BMI) and glycated hemoglobin were 46.9 years, 119.2 kg, 43.7 kg/m2 and 7.1%, respectively. Prevalence of mental disorders was 26.3%. Mean BMI declined to 30.3 kg/m2 at 2 years and %TWL was 29.9%. Improvements in the markers and prevalence of obesity-related comorbidities were observed. Remission rates of diabetes, dyslipidemia and hypertension were 75.6%, 59.7% and 41.8%, respectively. %TWL at the respective cut-off level of diabetes remission was 20.8%. Lower remission rates of diabetes in patients with %TWL <20%, and less calorie restriction and higher prevalence of mental disorders (46.9%) in patients with %TWL <15% were observed. Frequencies of %TWL <15% and <20% were 6.5% and 18.5%, respectively. CONCLUSION: %TWL 20% was a candidate cut-off point of insufficient weight loss for diabetes remission after LSG, and mental disorders might be relevant to intractable obesity in Japanese patients.

Retrospective cohort study of the efficacy and safety of dabigatran: real-life dabigatran use including very low-dose 75 mg twice daily administration.

BACKGROUND: Dabigatran is a direct thrombin inhibitor and an anticoagulant that is prescribed to prevent ischemic stroke and systemic embolism in non-valvular atrial fibrillation. Dabigatran (150 mg twice daily) is non-inferior to warfarin for the prevention of stroke and systemic embolism. A dose reduction to 110 mg twice daily should be considered for patients with decreased renal function, elderly patients, and those with a history of gastrointestinal bleeding. A small number of patients are prescribed 75 mg twice daily; however, excessive dose reduction below that indicated on the package insert may decrease the effectiveness of dabigatran. In this study, we investigated the incidence of thromboembolic events and hemorrhagic complications in patients receiving different doses of dabigatran, including patients receiving the very low-dose of 75 mg twice daily. METHODS: Five hospitals in Meguro and Setagaya areas of Tokyo were included in this study. The subjects were patients receiving dabigatran in the hospitals from March 2011 to February 2014. Thromboembolic events (stroke, systemic embolism, and transient cerebral ischemic attack) and hemorrhagic complications occurring before December 2014 were retrospectively evaluated. RESULTS: A total of 701 subjects received dabigatran during the study period: 187 patients (26.7%) received 150 mg twice daily (normal dose), 488 patients (69.6%) received 110 mg twice daily (low-dose), and 26 patients (3.7%) received 75 mg twice daily (very low-dose). Thromboembolism occurred in 4 (2.1%), 11 (2.3%), and 3 patients (11.5%), in the normal dose, low-dose, and very low-dose groups, respectively. The odds ratio of the 75 mg dose to the 150 and 110 mg doses was 5.73 (95% CI, 1.55-21.2; p = 0.009), and the incidence with the 75 mg dose was higher than that with the other doses. Although the number of events was limited, it should be noted that 3 patients in the very low-dose group had thromboembolic events. CONCLUSIONS: The results suggest that sufficient anticoagulation efficacy may not be maintained when the dabigatran dose is excessively reduced to 75 mg twice daily.

An Analysis of the Relationship between the Learning Process and Learning Motivation Profiles of Japanese Pharmacy Students Using Structural Equation Modeling.

Pharmacy students in Japan have to maintain strong motivation to learn for six years during their education. The authors explored the students’ learning structure. All pharmacy students in their 4th through to 6th year at Josai International University participated in the survey. The revised two factor study process questionnaire and science motivation questionnaire II were used to assess their learning process and learning motivation profiles, respectively. Structural equation modeling (SEM) was used to examine a causal relationship between the latent variables in the learning process and those in the learning motivation profile. The learning structure was modeled on the idea that the learning process affects the learning motivation profile of respondents. In the multi-group SEM, the estimated mean of the deep learning to learning motivation profile increased just after their clinical clerkship for 6th year students. This indicated that the clinical experience benefited students’ deep learning, which is probably because the experience of meeting with real patients encourages meaningful learning in pharmacy studies.

Effect of practical training on the learning motivation profile of Japanese pharmacy students using structural equation modeling.

PURPOSE: To establish a model of Japanese pharmacy students' learning motivation profile and investigate the effects of pharmaceutical practical training programs on their learning motivation. METHODS: The Science Motivation Questionnaire II was administered to pharmacy students in their 4th (before practical training), 5th (before practical training at clinical sites), and 6th (after all practical training) years of study at Josai International University in April, 2016. Factor analysis and multiple-group structural equation modeling were conducted for data analysis. RESULTS: A total of 165 students participated. The learning motivation profile was modeled with 4 factors (intrinsic, career, self-determination, and grade motivation), and the most effective learning motivation was grade motivation. In the multiple-group analysis, the fit of the model with the data was acceptable, and the estimated mean value of the factor of 'self-determination' in the learning motivation profile increased after the practical training programs (P= 0.048, Cohen's d= 0.43). CONCLUSION: Practical training programs in a 6-year course were effective for increasing learning motivation, based on 'self-determination' among Japanese pharmacy students. The results suggest that practical training programs are meaningful not only for providing clinical experience but also for raising learning motivation.

Probucol suppresses initiation of chronic hemodialysis therapy and renal dysfunction-related death in diabetic nephropathy patients: Sakura study.

AIM: Probucol has antioxidant as well as cholesterol-lowering effects. We examined the effect of probucol on the progression of diabetic nephropathy. We named this study 'Sakura Study' after our hospital and city. METHODS: We performed a randomized, open trial on 162 type 2 diabetic patients with clinical albuminuria (urinary albumin excretion >300 mg/g creatinine). Eighty patients were assigned to probucol treatment (500 mg/day) and 82 patients to no probucol treatment. All patients were followed for five years. The primary outcome was the time to renal dysfunction events, defined as the initiation of chronic hemodialysis therapy and renal dysfunction-related death. RESULTS: Probucol decreased total cholesterol, HDL-cholesterol, and LDL-cholesterol compared to the control group. The serum creatinine increase rate was significantly lower (p= 0.015) in the probucol group (0.066 mg/dL/month) than in the non-probucol group (0.116 mg/dL/month). Renal dysfunction events occurred in 72 patients during this study. The 69 patients who were initiated on chronic hemodialysis comprised 42 in the non-probucol group and 27 in the probucol group. Three patients in the non-probucol group, but no patients in the probucol group died of renal dysfunction. The renal dysfunction event-free survival rate was significantly higher (log-rank: p= 0.02) in the probucol group than in the non-probucol group. CONCLUSION: Probucol suppressed the progression of diabetic nephropathy and renal dysfunction events.

Artificial Neural Network Modeling of Quality of Life of Cancer Patients: Relationships between Quality of Life Assessments, as Evaluated by Patients, Pharmacists, and Nurses.

AIM: The purpose of this study was to investigate the difference between the professional perspectives of pharmacists and nurses in Japan with regard to evaluation of the quality of life (QOL) of cancer patients. METHODS: A group of cancer hospital inpatients (n=15) were asked to rate the condition of their health and their QOL by filling in a questionnaire. On the same day, a group of pharmacists (n=8) and nurses (n=18) also evaluated patient QOL. Three-layered artificial neural network (ANN) architecture was used to model the relationship between the different QOL evaluations made by patients, pharmacists, and nurses. RESULTS: Although there was no statistical difference between the QOL scores obtained from pharmacists and nurses, the correlation between these scores was weak (0.1188). These results suggest that pharmacists and nurses evaluate the QOL of their patients from different perspectives, based on their respective profession. QOL parameters were modeled with an ANN using the scores, given by patients in answer to questions regarding health-related QOL as input variables. Both the predictive performance of the ANN and the robustness of the optimized model were acceptable. The response surfaces calculated by ANN modeling showed that pharmacists and nurses evaluate patient's QOL using different information and reasoning, which is likely related to the nature of their contact with the patients. CONCLUSION: Health professionals evaluate patient QOL from different perspectives, depending on their profession.

Contradictory effects of ß1- and α1- aderenergic receptor blockers on cardio-ankle vascular stiffness index (CAVI)--CAVI independent of blood pressure.

AIM: The cardio-ankle vascular stiffness index (CAVI) is a new parameter that reflects the stiffness of the aorta, femoral artery and tibial artery as a whole. One of its conspicuous features is that CAVI is independent of blood pressure at measuring time, theoretically. But, it has not been experimentally proved yet. For confirmation, pharmacological studies were performed comparing with brachial-ankle pulse wave velocity (baPWV). METHODS: Used drugs were a ß1-adrenoceptor blocker, metoprorol and an α1- adrenoceptor blocker doxazosin. Both were administered to 12 healthy volunteer men. CAVI and baPWV were measured every one hour for 6 hours using VaSera. RESULTS: When metoprolol (80 mg) was administered to 12 healthy volunteer men, systolic blood pressure decreased from 131.4 ± 4.5 to 118.3 ± 4.1 mmHg (mean ± SE) (p < 0.05) at the 3rd hour, and diastolic blood pressure decreased from 85.3 ± 4.0 to 75.3 ± 3.0 mm Hg (p < 0.05). baP-WV decreased from 13.93 ± 0.46 to 12.46 ± 0.49 m/sec (p < 0.05), significantly, but CAVI did not change (8.16 ± 0.29 to 8.24 ± 0.27) (p = 0.449). ΔbaPWV at each time was significantly correlated with both Δsystolic and Δdiastolic blood pressures, but ΔCAVI was not correlated with either Δblood pressure. When doxazosin (4 mg) was administered to the same men, systolic blood pressure decreased from 130.2 ± 4.6 to 117.2 ± 4.8 mmHg (p < 0.05) at the 3rd hour. Diastolic blood pressure also decreased from 85.1 ± 4.1 to 74.2 ± 3.9 mmHg (p < 0.05). baPWV decreased from 13.98 ± 0.68 to 12.25 ± 0.53 m/sec (p < 0.05), significantly. CAVI also decreased from 8.15 ± 0.28 to 7.18 ± 0.37 (p < 0.05), significantly. CONCLUSION: These results suggested that CAVI was not affected by blood pressure at the measuring time directly, but affected by the changes of contractility of smooth muscle cells.

Quantitative analysis of crystalline pharmaceuticals in tablets by pattern-fitting procedure using X-ray diffraction pattern.

A pattern-fitting procedure using an X-ray diffraction pattern was applied to the quantitative analysis of binary system of crystalline pharmaceuticals in tablets. Orthorhombic crystals of isoniazid (INH) and mannitol (MAN) were used for the analysis. Tablets were prepared under various compression pressures using a direct compression method with various compositions of INH and MAN. Assuming that X-ray diffraction pattern of INH-MAN system consists of diffraction intensities from respective crystals, observed diffraction intensities were fitted to analytic expression based on X-ray diffraction theory and separated into two intensities from INH and MAN crystals by a nonlinear least-squares procedure. After separation, the contents of INH were determined by using the optimized normalization constants for INH and MAN. The correction parameter including all the factors that are beyond experimental control was required for quantitative analysis without calibration curve. The pattern-fitting procedure made it possible to determine crystalline phases in the range of 10-90% (w/w) of the INH contents. Further, certain characteristics of the crystals in the tablets, such as the preferred orientation, size of crystallite, and lattice disorder were determined simultaneously. This method can be adopted to analyze compounds whose crystal structures are known. It is a potentially powerful tool for the quantitative phase analysis and characterization of crystals in tablets and powders using X-ray diffraction patterns.

Tenomodulin is highly expressed in adipose tissue, increased in obesity, and down-regulated during diet-induced weight loss.

CONTEXT: Tenomodulin (TNMD), a putative angiogenesis inhibitor, is expressed in hypovascular connective tissues. Global gene expression scans show that the TNMD gene also is expressed in human adipose tissue and that its expression is regulated in response to weight reduction; however, more detailed information is lacking. OBJECTIVE: The aim of this study was to investigate TNMD tissue distribution and TNMD gene expression in human adipose tissue in relation to obesity and metabolic disease. DESIGN, PATIENTS, AND INTERVENTIONS: TNMD gene expression, tissue distribution, and TNMD gene expression in adipose tissue from different depots, from lean and obese subjects, and during diet-induced weight reduction were analyzed by DNA microarray and real-time PCR. MAIN OUTCOME MEASURE: We primarily measured TNMD gene expression. RESULTS: The TNMD gene was predominantly expressed in sc adipose tissue. TNMD gene expression was higher in sc than omental adipose tissue both in lean (P = 0.002) and obese subjects (P = 0.014). In both women and men, TNMD gene expression was significantly higher in the obese subjects compared to the lean subjects (P = 1.1 x 10(-26) and P = 0.010, respectively). In a multiple linear regression analysis, BMI was a significant independent predictor of TNMD gene expression. TNMD gene expression was down-regulated during diet-induced weight loss, with a 65% decrease after 18 wk of diet (P < 0.0001). CONCLUSIONS: We conclude that human adipose tissue TNMD gene expression is highly affected by obesity, adipose tissue location, and weight loss, indicating that TNMD may play a role in adipose tissue function.

Preparation of multiparticulate vaginal tablet using glyceryl monooleate for sustained progesterone delivery.

Most of the sustained release vaginal formulations are in the form of bioadhesive gels and tablets. Though proved efficient, their presence in the vagina for a longer time as a bulk produces discomfort and interference with body functioning including sexual activities. Hence, they lack complete patient compliance. In this study, multiparticulate vaginal tablets were prepared by utilizing progesterone (PRO) loaded dry powder precursor of cubic phase (DPPCP) of glyceryl monooleate (GMO). DPPCP were obtained by spray drying GMO with magnesium trisilicate (MTS) and have presented PRO sustained release in simulated vaginal fluid (SVF) for 14 hours. The effect of hydrophilic and hydrophobic tableting excipients on compression, phase, bioadhesion and drug release properties of prepared tablets was evaluated. The effervescent hydrophilic tablet (EHT) prepared with hydrophilic excipients showed rapid disintegration but, diminished sustaining ability owing to transformation into lamellar phase whereas the multiparticulate hydrophobic tablet (MHT) obtained from hydrophobic excipients presented both rapid disintegration and sustained release in SVF by virtue of cubic phase retention. During bioadhesivity testing, fast disintegration of MHT with formation of uniform and viscous bioadhesive layer on cow mucosa was observed even with a small volume of SVF. As MHT may not produce discomfort and interference, it will be preferred over bioadhesive gel or tablet.