Comparison of persistence and adherence between fixed-dose combinations and two-pill combinations in Japanese patients with type 2 diabetes

Objective: To compare treatment patterns, persistence and adherence between fixed-dose combinations (FDCs) and two-pill combinations (TPCs) of oral antidiabetic drug (OAD) classes in Japanese patients with type 2 diabetes mellitus (T2DM) using administrative claims databases (Japan Medical Data Center [JMDC] and Medical Data Vision [MDV]).

Methods: This was a retrospective, longitudinal cohort analysis conducted between 2011 and 2015, in patients with T2DM receiving OADs as FDC or TPC. Outcomes included prescribing patterns, treatment persistence and adherence.

Results: Data from 3474 and 3066 patients receiving FDCs, and 4325 and 5192 patients receiving TPCs from the JMDC and MDV databases, respectively, was extracted. The most common OAD combination received by over half of all patients was dipeptidyl peptidase-4 inhibitor (DPP-4i) + thiazolidinediones (TZDs) (64.1% [JMDC] and 70.5% [MDV]). Overall, 12-month persistence rates were higher in patients receiving FDCs compared with TPCs (70.4 vs. 66.2% [JMDC], 75.6 vs. 55.7% [MDV]). In the JMDC population receiving FDCs or TPCs, persistence rates were highest with DPP-4i schedules (67.5–83.5%). Median time to discontinuation was significantly longer with biguanide?+?TZD, and DPP-4i?+?TZD FDC schedules (p < .05) than TPC; adherence rates were ≥80% across all antidiabetic drug classes in both database populations.

Conclusions: Persistence with and adherence to OADs in Japanese patients with T2DM were greater with FDCs than with TPCs, which may suggest increased patient satisfaction due to reduced treatment burden. Further studies are warranted to investigate the impact of adherence and persistence of FDCs of OADs on glycemic control.     

Asian variant of intravascular large B cell lymphoma causes patients to frequently develop the syndrome of inappropriate antidiuretic hormone secretion

The Asian variant of intravascular large B cell lymphoma is a special type of intravascular lymphoma with hemophagocytic syndrome and hypercytokinemia including interleukin-6, which stimulates antidiuretic hormone synthesis in the hypothalamus. We present here that the syndrome of inappropriate antidiuretic hormone secretion frequently occurs in patients with the Asian variant of intravascular large B cell lymphoma. The syndrome of inappropriate antidiuretic hormone secretion was found in eight of 118 (6.8%) lymphoma patients at the first diagnosis. Although there were six (5.1%) among 118 lymphoma patients with the Asian variant of intravascular large B cell lymphoma, four of the six patients (66.7%) developed the syndrome of inappropriate antidiuretic hormone secretion. In four patients with the Asian variant of intravascular large B cell lymphoma with the syndrome of inappropriate antidiuretic hormone secretion, elevated serum interleukin-6 and low sodium levels were almost normalized after chemotherapy. The Asian variant of intravascular large B cell lymphoma patients frequently develop the syndrome of inappropriate antidiuretic hormone secretion, and interleukin-6 might play a role in the occurrence of this disease. We should pay attention to hyponatremia caused by the syndrome of inappropriate antidiuretic hormone secretion in patients with the Asian variant of intravascular large B cell lymphoma.     

Extremely early onset of ranitidine action on human histamine H2 receptors expressed in HEK293 cells

BACKGROUND/AIMS: Histamine H2 receptor antagonists are considered to exert their effects on gastric acid secretion more rapidly than proton pump antagonists. However, there are no reports concerning the direct interaction of a histamine H2 receptor antagonist with the human H2 receptor in terms of onset of action. This study aims to characterize how rapidly famotidine and ranitidine, the most widely used histamine H2 receptor antagonists, interact with the human histamine H2 receptor. METHODS: HEK293 cell lines, stably expressing human histamine H2 receptors, were obtained. The dose- and time-dependent effects of famotidine and ranitidine on [3H]-tiotidine binding and histamine-stimulated cAMP production were analyzed. RESULTS: Ranitidine inhibited both [3H]-tiotidine binding and histamine-stimulated cAMP production more promptly than did famotidine. Inhibition of histamine-stimulated cAMP production by Cmax doses of famotidine (20 mg p.o.) and ranitidine (150 mg p.o.) peaked by 15 and 2 min, respectively. [3H]-tiotidine binding was not saturated by 60 min at the famotidine Cmax, while the ranitidine Cmax had produced saturation by 15 min. CONCLUSION: Ranitidine inhibits the human histamine H2 receptor very rapidly.     

Analysis of K-<Emphasis Type="Italic">ras</Emphasis> Codon 12 Mutation in Flat and Nodular Variants of Serrated Adenoma in the Colon

PURPOSE: The developmental process of serrated adenomas is obscure, and the importance of genetic alterations has not been elucidated clearly. The possibility that the developmental process and genetic alterations of serrated adenomas could differ from those of ordinary tubular adenomas was explored in this work. METHODS: Serrated adenomas were obtained by endoscopic resection (n = 57) and divided into two groups: flat (n = 10) and nodular (n = 47). Mutation of the K-ras gene was analyzed by enriched polymerase chain reaction–enzyme-linked mini-sequence assay, which can detect not only the presence of a mutation but also the mutation type of K-ras codon 12 with high sensitivity. Methylation-specific polymerase chain reaction was performed with specific primers for the DNA repair gene O6-methylguanine-DNA methyltransferase. RESULTS: Serrated adenomas located in the rectum were more likely to have a K-ras mutation (9/12, 75 percent), whereas serrated adenomas of the flat type were less likely to have one (1/10, 10 percent). Furthermore, nodular serrated adenomas that occurred in the rectum possessed a high frequency of K-ras gene codon 12 point mutation (8/10, 80 percent) despite an overall frequency of 46.8 percent (22/47). A mutation of the K-ras codon 12 gene was detected in 23 (40.4 percent) of 57 serrated adenomas. Three types of point mutations of codon 12 were detected, with the mutation of GAT being observed most frequently. CONCLUSIONS: This study shows that development of nodular serrated adenomas may depend on the mutation of the K-ras codon 12 gene, whereas development of flat serrated adenomas may not. Additionally, serrated adenomas that occur in the rectum are closely related to the mutation of the K-ras codon 12 gene. K-ras mutations in serrated adenomas may be unaffected by the epigenetic silencing of O6-methylguanine-DNA methyltransferase by promoter hypermethylation.     

Comparison of the effects of cilnidipine and amlodipine on ambulatory blood pressure.

Cilnidipine is a novel and unique 1,4-dydropyridine derivative calcium antagonist that exerts potent inhibitory actions not only on L-type but also on N-type voltage-dependent calcium channels. Blockade of the neural N-type calcium channel inhibits the secretion of norepinephrine from peripheral neural terminals and depresses sympathetic nervous system activity. The purpose of this study was to assess the effect of cilnidipine and amlodipine on ambulatory blood pressure (BP) levels. We performed 24-h ambulatory BP monitoring before and after once-daily use of cilnidipine (n=55) and amlodipine (n=55) in 110 hypertensive patients. Both drugs significantly reduced clinic and 24-h systolic BP (SBP) and diastolic BP (DBP) (p < 0.005). However, the reductions of 24-h (-1.19+/-6.78 vs. 1.55+/-6.13 bpm, p=0.03), daytime (-1.58+/-6.72 vs. 1.68+/-7.34 bpm, p=0.02) and nighttime (-1.19+/-5.72 vs. 1.89+/-6.56 bpm, p=0.01) pulse rate (PR) were significantly greater in the cilnidipine group than the amlodipine group. There was no correlation between the degree of daytime SBP change and that of daytime PR change after amlodipine treatment (r=-0.08, n.s.), but there was a significant negative correlation between the degree of daytime SBP change and that of day-time PR change after cilnidipine treatment (r=-0.27, p<0.05). N-type calcium channel blockade by cilnidipine may not cause reflex tachycardia, and may be useful for hypertensive treatment.     

Role of case presentation for teaching and learning activities

In most clinical teaching settings, case presentation is the most frequently used teaching and learning activity. From an educational viewpoint, the two important roles of case presentations are the presenter's reflective opportunity and the clinician educator's clues to diagnose the presenter. When a presenter prepares for a case presentation, he/she has to organize all the information collected from a patient. The presenter sometimes does not recall what to ask or to examine with relation to pertinent differential diagnoses while seeing a patient, and afterward he/she might note that more information should have been collected. He/she is able to note the processes by reflection-on-action and improve the processes the next time. Such a reflective process is the most important role of case conference for a presenter. When a clinician has a consultation with a patient, early problem representation determines the quality of differential diagnoses. Clinicians make a "big picture" while listening to the patient (sometimes only a glance is enough to diagnose a patient) as problem representation to narrow down clinical areas to ask questions. If the early problem representation is far from the optimal direction, the possibility of misdiagnosis will be higher. To correct the cognitive processes that lead to misdiagnosis, disclosure of uncertainty will be the key. If the teaching environment among residents or young clinicians is too competitive, some might feel reluctant to disclose incorrect reasoning processes to their peers. Or, if a clinician educator is too authoritative, students may hide key information from the educator. The educator should construct the best environment for students to be able to disclose such uncertainty. The main role of clinician educators is to facilitate and evaluate case presentations and to suggest points for improvement. Neher et al's "five microskills" are a typical example of these processes, after a short presentation of an outpatient case. Yet, for an inpatient or for formal discussion, a longer version presentation is used. To improve the clinical reasoning processes of the presenter, the short presentation has several advantages: (1) shortening the presentation requires abstraction of information, possibly leading to better problem representation; (2) it is time-efficient; and (3) it stimulates more informal interactions with the facilitator and the audience. In clinical settings, a presenter uses his/her time for the preparation of case presentations to reflect on the information he/she has collected. The facilitator should know how to improve case presentations to diagnose and improve the presenter. The advantages of the short presentation should be emphasized.     

Unusual left ventricular dilatation without functional or biochemical impairment in normotensive extremely overweight Japanese professional sumo wrestlers

To explore the physiologic limit of left ventricular (LV) enlargement, we performed echocardiography and air displacement plethysmography to respectively assess LV dimension and function and the body composition of Japanese professional sumo wrestlers. After excluding subjects with cardiovascular disease, hypertension, plasma brain natriuretic peptide (BNP) > or =17.9 pg/ml, diabetes mellitus, or asthma, 331 subjects (mean +/- SD age, 21.6 +/- 3.7 years; height 179.2 +/- 5.3 cm; weight 1,17.9 +/- 21.5 kg; percent fat, 29.6 +/- 6.6%) were analyzed. LV end-diastolic dimension averaged 58.4 +/- 3.7 mm and was within the generally regarded normal limit (< or =54 mm) in 14.5% of subjects, but was > or =60 mm in 41.1% of subjects. LV septal and posterior wall thicknesses were 10.3 +/- 0.9 and 10.2 +/- 0.9 mm, respectively. Peak E- and A-wave velocities, E/A ratio, LV fractional shortening, and BNP were 96 +/- 16 and 51 +/- 13 cm/s, 2.0 +/- 0.7, 33.5 +/- 4.5%, and 3.1 +/- 3.7 pg/ml, respectively. LV end-diastolic dimension was not correlated with these indexes of LV function or with plasma BNP levels, but was significantly correlated with height, weight, body surface area, fat-free mass, and fat mass. These results show that among very large, highly trained, professional athletes, LV end-diastolic dimension frequently exceeds the traditionally accepted upper limit of normal for the general population. This increase in LV end-diastolic dimension may thus represent an extreme example of the physiologic adaptation of the athlete's heart.     

Clinical features of Japanese type 1 autoimmune hepatitis patients with zone III necrosis

Aim: In Caucasians in northern Europe and North America, type 1 autoimmune hepatitis is characterized by susceptibility to human leukocyte antigens DR3 and DR4, and patients with zone III necrosis more frequently have an acute onset of the disease and a lower frequency of cirrhosis than those without. In Japanese patients, however, type 1 autoimmune hepatitis is primarily associated with DR4, and there are almost no DR3-positive patients. Thus, the clinical features of Japanese patients with type 1 autoimmune hepatitis and zone III necrosis may be different from those reported previously for Caucasians. Methods: We investigated 160 consecutive patients with type 1 autoimmune hepatitis (20 males and 140 females; median age, 55 years; range, 16-79 years). Results: Forty-seven patients (29%) had zone III necrosis, and these patients had lower serum levels of albumin and higher serum levels of total bilirubin, aspartate aminotransferaseand alanine aminotransferase. Histologically, zone III necrosis was found more frequently in patients with acute hepatitis than in those with chronic hepatitis. However, there was no difference in the frequency of cirrhosis between patients with and without zone III necrosis. In addition, normalization of serum alanine aminotransferase levels within six months after the introduction of corticosteroid treatment was slightly more frequent in patients with zone III necrosis (95% vs. 88%). Conclusion: In Japanese patients, zone III necrosis may reflect not only acute autoimmune hepatitis, but also acute exacerbation of pre-existing chronic disease. Furthermore, patients with zone III necrosis may respond better to corticosteroid treatment than those without.     

Lectin staining of neoplastic and normal background colorectal mucosa in nonpolyposis and polyposis patients

A lectin histochemistry approach was adopted for comparative assessment of a colon cancer risk. Binding of Ulex europaeus agglutinin-I (UEA-I), peanut agglutinin (PNA), Griffonia simplicifolia agglutinin-II (GSA-II), and Dolichos biflorus agglutinin (DBA) was investigated in tumor and background tissue from a total of 34 adenoma and 44 cancer patients and compared with reaction patterns in control and familial adenomatous pplyposis (FAP) patients. Adenoma patients with UEA-I positive rectal mucosa were found to have a 33.3 percent familial history of large bowel cancer, which was significantly higher (P <0.05) than the respective 4.0 percent figure for patients with negative rectal mucosa. In the cancer patients, an even stronger correlation was noted, with a 63.2 percent UEA-I positive family history association being recorded, as opposed to 4.0 percent in the negative rectal mucosa patients (P <0.01). Thus, the results suggest that, apparently, normal rectal background mucosa of individuals genetically at high risk for colon and rectal cancer demonstrates a specific lectin binding ability similar to that of FAP patients and that the simple method using UEA-I staining of rectal biopsy specimens can be of practical use in identification of high-risk colorectal cancer.