山田 成樹

統合失調症の服薬アドヒアランス不良の問題を改善する方策として持効性注射剤(Long-acting injection:LAI)が挙げられるが、その普及率は低い。そこで、paliperidone持効性注射剤(PLAI)に対する統合失調症患者215名の受け入れ態度を調査し、患者の背景因子がPLAIの受け入れ態度に及ぼす影響について調査を行った。その結果、40.9%の患者がPLAIを試してみたいと回答し、その主な理由は「4週間に1回投与される方が楽だから」であった。外来患者の中でrisperidone LAI使用患者のPLAIの受け入れ率は経口抗精神病薬使用患者のそれより有意に高かった。さらに、PLAIの受け入れ率とSAI-J(病識の評価)および使用中の抗精神病薬のchlorpromazine換算値との間にそれぞれ正の相関が認められ、服薬確認されていると認識している入院患者のPLAIの受け入れ率は認識していない患者のそれより有意に高かった。これらのことから、PLAIの受け入れには病識や通院間隔、服薬の負担が影響することが明らかとなった。(著者抄録)

第二世代抗精神病薬(SGA)は統合失調症のみならず、患者の症状や状態により双極性障害への適応外使用も行われることは少なくない。このため、適正なインフォームド・コンセント(IC)の実施が求められている。そこで、精神科外来を受診したSGAを服薬している106名の双極性障害の患者を対象に、SGAに関する説明文書を用いたICが患者の服薬に対する満足度や服薬態度にどのような影響を及ぼすかについて調査を行った。その結果、多くの患者が抗精神病薬の効果と副作用に関する説明文書を用いた十分なICを受けていない現状が明らかとなり、説明文書を用いたICは患者の薬に対する満足度や服薬態度に悪影響を及ぼすことはなく、患者側からはむしろその必要性が求められた。さらに、IC後の患者の薬に対する満足度が高いほど服薬継続意思が高かったことから、治療のリスクとベネフィットについての十分な説明に加え、患者の意見を尊重するSDM(Shared Decision Making)の実践が重要となる。(著者抄録)

Objective: The purpose of this study was to clarify the importance of therapeutic drug monitoring (TDM) at acute care hospitals using Diagnosis Procedure Combination (DPC) data.<br>Methods: We used DPC data from about 3,500,000 inpatients at about 950 acute care hospitals.  The investigation period was from July 2010 to December 2010.  Patients were divided into 2 groups: TDM intervention (n=22,012); and non-TDM intervention (n=26,400).  We compared the clinical indicators (length of hospital stay, payment based on performance and drug costs) and use of antimicrobials.<br>Results: TDM intervention was carried out in 45.5% patients for whom an anti-MRSA agent was prescribed.  The duration of anti-MRSA agent administration was significantly longer in the TDM intervention group than in the non-TDM intervention group.  The total daily cost of anti-MRSA agents was significantly lower in the TDM intervention group than in the non-TDM intervention group.<br>Conclusion: Our results suggest that TDM intervention is often performed for seriously ill patients who require continuous treatment.  TDM intervention may prevent adverse reactions as a result of adjusting the dosage of the anti-MRSA agent.

Background: Patients with end-stage renal disease (ESRD) have symptoms related to severe anemia, edema, and heart failure. Although dialysis improves ESRD syndromes, the optimum timing for initiation of dialysis is unclear. Recent observational studies have suggested that early commencement of dialysis can be harmful. Given that early dialysis may increase the risk of death, avoiding an early start to dialysis is recommended. Patients with diabetic nephropathy (DN) may have risk factors for early dialysis. However, the risk factors for early dialysis are unclear in ESRD patients with DN. The aim of this study was to elucidate the risk factors for early initiation of dialysis in patients with DN and ESRD. Methods: From April 2009 to December 2012, we identified Japanese DN patients with an estimated glomerular filtration rate of less than 15 mL/minute/1.73 m(2). The patients were divided into late or early dialysis groups based on the timing of start of dialysis. Results: We evaluated 52 patients who commenced dialysis during the observation period, including 33 in the late dialysis group and 19 in the early dialysis group. There was a significant association between early dialysis and age &gt;= 65 years (odds ratio 4.59). The incidence of pneumonia before starting dialysis was significantly higher in elderly patients than in nonelderly patients. Conclusion: Our findings suggest that elderly patients with DN and ESRD have an increased risk of early initiation of dialysis, and occurrence of pneumonia is also associated with early dialysis. To avoid early commencement of dialysis, booster pneumococcal vaccination could be useful in elderly DN patients with ESRD.

原発性骨粗鬆症患者における新規ビスホスホネート(BP)製剤ミノドロネート(MIN)の臨床効果について検討した。新たに骨粗鬆症と診断した100例を、無作為にMIN投与群とアレンドロネート(ALN)投与群に割り付けた。TRACP-5bは、投与開始4週後より両群間において最小有意変化(MSC)を超える低下がみられた。血清NTXは、投与開始24週後より両群間においてMSCを超える低下がみられた。有害事象の発生率は、MIN群24%、ALN群22%で、継続不可となった症例はMIN群4例、ALN群7例で、自己中断などにより継続不可となった症例を含めると、48週継続率はそれぞれMIN群60%、ALN群60%であった。BP製剤の副作用としての膿部不快感がMIN群4例、ALN群4例、腹部膨満感がMIN群のみ3例、腹痛がMIN群1例、ALN群1例であったが、ALN群の腹部不快感1例を除き治療は継続した。

Background/Aims: Adiponectin is an adipocyte-derived protein with antiatherogenic properties. Chronic kidney disease (CKD) is one of the risk factors for cardiovascular disease. We investigated the potential association between adiponectin and carotid arteriosclerosis in patients with predialysis CKD. Methods: We enrolled 95 CKD patients without dialysis and 81 non-CKD patients. Intima-media thickness (IMT) and plaque score (PS) in the common carotid artery were measured using an ultrasound system. Carotid arteriosclerosis was defined as IMT &gt; 1.2 mm and/or PS &gt; 5.0 mm. Results: The prevalence of CKD was independently associated with carotid arteriosclerosis after adjustment for other risk factors. Higher adiponectin levels were observed in CKD patients compared with non-CKD patients. Adiponectin levels were not independently correlated with the presence of carotid arteriosclerosis in all subjects. To evaluate the association between adiponectin and carotid arteriosclerosis among a CKD population, we divided the CKD patients into 2 groups according to a cutoff level of adiponectin determined by ROC analysis. The prevalence of carotid arteriosclerosis was significantly higher in the low-adiponectin group than in the high-adiponectin group among CKD patients. After adjusting for other risk factors, low levels of adiponectin were independently correlated with carotid arteriosclerosis in CKD patients. Conclusion: Our data document that adiponectin is associated with increased risk of carotid atherosclerosis in a predialysis CKD population. Copyright (C) 2011 S. Karger AG, Basel

Background and objectives: Cardiac failure is directly affected by left ventricular (LV) dysfunction, and particularly LV systolic dysfunction is strongly associated with survival in ESRD patients. The aim of this study was to determine the prognostic value of reduced LV ejection fraction (LVEF) measured at the time of initiation of hemodialysis (HD) in incident HD patients. Design, setting, participants, & measurements: 1254 consecutive ESRD patients who electively started HD therapy were screened by echocardiography within 1 month after its inception. They were divided into five groups according to LVEF levels with a decrease of 0.1 each and were followed up for up to 7 years. Survival was examined with the Kaplan-Meier method and compared using the log-rank test. Results: Among the 1254 patients, LVEF levels &gt;= 0.6, 0.5 to 0.6, 0.4 to 0.5, 0.3 to 0.4, and &lt;0.3 were seen in 842 (67.1%), 247 (19.7%), 107 (8.5%), 41 (3.3%), and 17 (1.4%) patients, respectively. On Kaplan-Meier analysis, 7-year event-free rates from cardiovascular death were 84.2, 83.7, 73.6, 59.4, and 30.9% in order of groups with decreasing LVEF of 0.1 each, respectively. Seven-year event-free rates from all-cause death were 69.2, 61.7, 57.1, 45.9, and 23.1% in the respective groups. Even after adjustment for other risk factors, decreasing LVEF was a strong independent predictor for cardiovascular death. Conclusions: Reduced LVEF on starting HD therapy could stratify risk of cardiovascular and all-cause mortality in ESRD patients. Screening by echocardiography at start of HD therapy might be recommended to predict prognosis in patients with ESRD. Clin J Am Soc Nephrol 5: 1793-1798, 2010. doi: 10.2215/CJN.00050110

Background: Percutaneous transluminal angioplasty (PTA) for femoropopliteal lesions in peripheral artery disease has been performed in patients undergoing hemodialysis as well as in the general population. Cilostazol, a selective inhibitor of phosphodiesterase 3, has been reported to reduce target lesion revascularization after PTA for femoropopliteal lesions in the general population. Objective: This study investigated the effects of cilostazol use on long-term patency after PTA in patients with femoropopliteal disease undergoing hemodialysis. Methods: fit this retrospective study, data from patients undergoing hemodialysis who underwent successful PTA for femoropopliteal disease, defined as a final luminal diameter stenosis &lt;30%, without angiographically Visual arterial dissection and no in-hospital complications, were included. One Study group received long-term treatment with oral cilostazol 100 mg BID after PTA; the control group did not. The duration of follow-tip was ! 6 years. The primary outcome of interest Was cumulative patency, as measured by the event-free rate 6 years after PTA, with event defined as restenosis of &gt;50% of the vessel diameter in femoropophreal lesions. Data on baseline characteristics, patency, and covariates (diabetes, hypertension, hyperlipidemia, smoking, coronary artery disease, critical limb ischemia, TransAtlantic Inter-Society Consensus classification, and stenting) were obtained from electronic medical records and tele-phone interviews with patients. To minimize the effects of selection bias for cilostazol administration, a propensity-matched analysis using Cox univariate and multivariate models including the previously mentioned covariates was conducted. The propensity, scores of the 2 groups were matched 1:1 (AUC = 0.69 [receiving operating characteristics analysis]). Data were obtained from electronic medical records and telephone interviews with patients by trained personnel who were blinded to treatment assignment. Results: A total of 358 consecutive lesions of 1,74 patients undergoing hemodialysis were Included (103 men, 7.1 women; mean [SD] age, 66 [11] years; cilostazol group, 61. patients, 121 lesions; control group, I 13 patients, 237 lesions). The mean duration of follow-Lip was 37 (27) months. The 6-year event-free rate of restenosis of &gt;50% of the vessel diameter was significantly higher in the cilostazol group than in the control group (72/121 [59.5%] vs 120/237 [50.6%,]; P = 0.005 [log-rank test]; hazard ratio [HR] = 0.63; 95% CI, 0.45-0.88; P = 0.008 [Cox univariate analysis]). Also, event-free rates of target lesion revascularization and limb amputation were significantly higher in the cilostazol group than in the control group (40/61 [65.6%] vs 57/113 [50.4%]; P = 0.013 [log-rank test] and 54161 [88.5%] vs 90/113 [79.6%]; P = 0.047 [log-rank test], respectively). On propensity score matching (105 lesions), the baseline characteristics were comparable between the 2 groups. The 6-year event-free rate of restenosis was significantly higher in the cilostazol group than in the control group (66/105 [62.9%] vs 52/105 [49.5%]; HR = 0.58; 95% CI, 0.38-0.88; P = 0.012 [Cox univariate analysis]). On propensity-matched (COX multivariate) analysis, cilostazol (HR = 0.51; 95% CI, 0.27-0.84; P = 0.008), age (HR = 1.01; 95% CI, 1.01-1.04; P = 0.031), and critical limb ischemia (HR = 2.21; 95% CI, 1.39-3.53; P = 0.001) were independent predictors of restenosis. None of the patients in the cilostazol group discontinued cilostazol treatment during the follow-up period. Four patients (6.6%) experienced mild headache. Conclusion: This study found that ill these patients with femoropopliteal lesions in peripheral artery disease who were undergoing hemodialysis, those treated with cilostazol 100 mg BID after PTA had a higher mean rate of cumulative patency after PTA than those in the control group. (Clin Ther. 2010;32:24-33) (C) 2010 Excerpta Medica Inc.