1. Journal Club 埼玉医科大学 総合医療センター 内分泌・糖尿病内科 Department of Endocrinology and Diabetes, Saitama Medical Center, Saitama Medical University 松田 昌文 Matsuda, Masafumi 2011 年 9 月 1 日 8:30-8:55 ８階 医局 Bell CM, Brener SS, Gunraj N, Huo C, Bierman AS, Scales DC, Bajcar J, Zwarenstein M, Urbach DR. Association of ICU or hospital admission with unintentional discontinuation of medications for chronic diseases. JAMA. 2011 Aug 24;306(8):840-7. Jenkins DJ, Jones PJ, Lamarche B, Kendall CW, Faulkner D, Cermakova L, Gigleux I, Ramprasath V, de Souza R, Ireland C, Patel D, Srichaikul K, Abdulnour S, Bashyam B, Collier C, Hoshizaki S, Josse RG, Leiter LA, Connelly PW, Frohlich J. Effect of a dietary portfolio of cholesterol-lowering foods given at 2 levels of intensity of dietary advice on serum lipids in hyperlipidemia: a randomized controlled trial. JAMA. 2011 Aug 24;306(8):831-9.

2. Departments of Health Policy, Management, and Evaluation (Drs Bell, Bierman, Zwarenstein, and Urbach and Ms Brener), Medicine (Drs Bell and Bierman and Ms Brener), and Surgery (Dr Urbach), Keenan Research Centre in Li Ka Shing Knowledge Institute at St Michael’s Hospital (Dr Bell and Ms Brener), Interdepartmental Division of Critical Care (Dr Scales), Lawrence S. Bloomberg Faculty of Nursing (Dr Bierman), Leslie Dan Faculty of Pharmacy (Dr Bajcar), Centre for Patient Safety (Dr Bell), and University Health Network (Dr Urbach), University of Toronto, Toronto, Ontario, Canada; Institute for Clinical Evaluative Sciences, Toronto, Ontario, Canada (Drs Bell, Bierman, Scales, Zwarenstein, and Urbach and Mss Gunraj and Huo); and Departments of Critical Care Medicine (Dr Scales) and Pharmacy (Dr Bajcar), Sunnybrook Health Sciences Centre, Toronto, Ontario, Canada. JAMA. 2011;306(8):840-847

3. Context Patients discharged from acute care hospitals may be at risk for unintentional discontinuation of medications prescribed for chronic diseases. The intensive care unit (ICU)may pose an even greater risk because of the focus on acute events and the presence of multiple transitions in care. Objective To evaluate rates of potentially unintentional discontinuation of medications following hospital or ICU admission.

4. Design, Setting, and Patients A population-based cohort study using administrative records from 1997 to 2009 of all hospitalizations and outpatient prescriptions in Ontario, Canada; it included 396,380 patients aged 66 years or older with continuous use of at least 1 of 5 evidence-based medication groups prescribed for long-term use: (1) statins, (2) antiplatelet/anticoagulant agents, (3) levothyroxine, (4) respiratory inhalers, and (5) gastric acid–suppressing drugs. Rates of medication discontinuation were compared across 3 groups: patients admitted to the ICU, patients hospitalized without ICU admission, and nonhospitalized patients (controls). Odds ratios (ORs) were calculated and adjusted for patient demographics, clinical factors, and health services use. Main Outcome Measures The primary outcome was failure to renew the prescription within 90 days after hospital discharge.

5. aged 66 years or older who had at least 1 year of continuous medication use in at least 1 of 5 medication groups: (1)statins; (2)antiplatelet or anticoagulant agents; (3)levothyroxine; (4)respiratory inhalers; and (5)gastric acid–suppressing drugs This time frame was selected because previous research suggests that patients who are nonadherent to their prescribed medication regimen for chronic diseases typically stop using their medications within the first few months. (1)patients who were discharged after a hospitalization that included an ICU admission; (2)patients who were discharged after a hospitalization that did not include an ICU admission; and (3)patients who were not hospitalized (controls) 3 distinct cohorts: linked administrative records between 1997 and 2009 of all hospitalizations in Ontario, Canada

11. Results Patients admitted to the hospital (n=187 912) were more likely to experience potentially unintentional discontinuation of medications than controls (n=208 468) across all medication groups examined. The adjusted ORs (AORs) ranged from 1.18 (95% CI, 1.14-1.23) for discontinuing levothyroxine in 12.3% of hospitalized patients (n=6831) vs 11.0% of controls (n=7114) to an AOR of 1.86 (95% CI, 1.77- 1.97) for discontinuing antiplatelet/anticoagulant agents in 19.4% of hospitalized patients (n=5564) vs 11.8% of controls (n=2535). With ICU exposure, the AORs ranged from 1.48 (95% CI, 1.39-1.57) for discontinuing statins in 14.6% of ICU patients (n=1484) to an AOR of 2.31 (95% CI, 2.07-2.57) for discontinuing antiplatelet/ anticoagulant agents in 22.8% of ICU patients (n=522) vs the control group. Admission to an ICU was associated with an additional risk of medication discontinuation in 4 of 5 medication groups vs hospitalizations without an ICU admission. One-year follow-up of patients who discontinued medications showed an elevated AOR for the secondary composite outcome of death, emergency department visit, or emergent hospitalization of 1.07 (95% CI, 1.03-1.11) in the statins group and of 1.10 (95% CI, 1.03-1.16) in the antiplatelet/anticoagulant agents group.

12. Conclusions Patients prescribed medications for chronic diseases were at risk for potentially unintentional discontinuation after hospital admission. Admission to the ICU was generally associated with an even higher risk of medication discontinuation.

13. Message/Comments 入院中に ICU に入る状態になった場合に， 慢性疾患の管理に用いられた薬物が中断と なるケースが結構ある。 死亡や救急入院がスタチンや抗血小板剤や 抗凝固薬の中断で増加していた！ （甲状腺薬、気管支の薬、胃薬では差がな かった！？） 日本では？ このような解析であると（処 方継続忘れでなく）中断できた例が良かっ たりする可能性もあるが。

15. Clinical Nutrition and Risk Factor Modification Center (Drs Jenkins, Kendall, Faulkner, de Souza, Bashyam, Josse, and Leiter and Mr Ireland and Mss Patel, Srichaikul, and Abdulnour) and Department of Medicine (Drs Jenkins, Josse, and Leiter), St Michael’s Hospital, Toronto, Ontario; Departments of Nutritional Sciences (Drs Jenkins, Kendall, Faulkner, de Souza, Bashyam, Josse, and Leiter and Mr Ireland and Mss Patel and Srichaikul) and Medicine (Drs Jenkins, Josse, and Leiter), University of Toronto, Toronto, Ontario; Richardson Center for Functional Foods and Nutraceuticals, University of Manitoba, Winnipeg (Drs Jones and Ramprasath); Institute of Nutraceuticals and Functional Foods, Laval University, Quebec City, Quebec (Dr Lamarche and Ms Gigleux); Department of Pathology and Laboratory Medicine, University of British Columbia, Vancouver (Dr Frohlich and Mss Cermakova, Collier, and Hoshizaki); Department of Clinical Epidemiology and Biostatistics, McMaster University, Hamilton, Ontario (Dr de Souza); Institute of Medical Science, University of Toronto, Toronto, Ontario (Ms Abdulnour); and Keenan Research Center of the Li Ka Shing Knowledge Institute, St Michael’s Hospital, Toronto, Ontario (Drs Jenkins, Josse, Leiter, and Connelly), Canada. JAMA. 2011;306(8):831-839

16. Context Combining foods with recognized cholesterol-lowering properties (dietary portfolio) has proven highly effective in lowering serum cholesterol under metabolically controlled conditions. Objective To assess the effect of a dietary portfolio administered at 2 levels of intensity on percentage change in low- density lipoprotein cholesterol (LDL-C) among participants following self-selected diets.

17. Design, Setting, and Participants A parallel-design study of 351 participants with hyperlipidemia from 4 participating academic centers across Canada (Quebec City, Toronto, Winnipeg, and Vancouver) randomized between June 25, 2007, and February 19, 2009, to 1 of 3 treatments lasting 6 months. Intervention Participants received dietary advice for 6 months on either a low−saturated fat therapeutic diet (control) or a dietary portfolio, for which counseling was delivered at different frequencies, that emphasized dietary incorporation of plant sterols, soy protein, viscous fibers, and nuts. Routine dietary portfolio involved 2 clinic visits over 6 months and intensive dietary portfolio involved 7 clinic visits over 6 months. Main Outcome Measures Percentage change in serum LDL-C.

18. CHD indicates coronary heart disease; LDL-C, low- density lipoprotein cholesterol. a The number of individuals that did not meet inclusion criteria included 218 with lipids not in study range, 109 with concurrent disorders, 15 with food allergies, 7 with acute and chronic infections, 5 with excess alcohol intake, 5 with high BMI, 4 who were premenopausal, 3 who did not stop taking statins, 2 with weight not stable, 1 with high family risk for cancer, 1 with concern about adherence to study diet, and 1 with a hostile attitude.

20. Abbreviations: BMI, body mass index, calculated as weight in kilograms divided by height in meters squared; CI, confidence interval; HDL-C, high-density lipoprotein cholesterol; LDL-C, low- density lipoprotein cholesterol; TC, total cholesterol. SI conversions: To convert TC, HDL-C, and LDL-C to mmol/L, multiply by 0.0259; and triglycerides to mmol/L, multiply by 0.0113. a P values for between-group differences used generalized linear model analysis of variance for continuous variables and Fisher exact test for categorical variables, in which the null hypothesis is that the portion of participants receiving each medication was the same across all treatments. b Included those participants of mixed race and those whose race/ethnicity could not be self- determined. c Participants who entered the study taking lipid-lowering drugs were required to discontinue them at least 2 weeks before randomization. d An additional participant started estrogen at week 12.

23. LDL-C indicates low-density lipoprotein cholesterol; TC, total cholesterol; HDL-C, high-density lipoprotein cholesterol. To convert LDL-C to mmol/L, multiply by 0.0259. Error bars indicate SE.

24. Results In the modified intention-to-treat analysis of 345 participants, the overall attrition rate was not significantly different between treatments (18% for intensive dietary portfolio, 23% for routine dietary portfolio, and 26% for control; Fisher exact test, P=.33). The LDL-C reductions from an overall mean of 171 mg/dL (95% confidence interval [CI], 168-174 mg/dL) were −13.8% (95% CI, −17.2% to −10.3%; P<.001) or −26 mg/dL (95% CI, −31 to −21 mg/dL; P<.001) for the intensive dietary portfolio; −13.1% (95% CI, −16.7% to −9.5%; P<.001) or –24 mg/dL (95% CI, −30 to −19 mg/dL; P<.001) for the routine dietary portfolio; and −3.0% (95% CI, −6.1% to 0.1%; P=.06) or −8 mg/dL (95% CI, −13 to −3 mg/dL; P=.002) for the control diet. Percentage LDL-C reductions for each dietary portfolio were significantly more than the control diet (P<.001, respectively).The 2 dietary portfolio interventions did not differ significantly (P=.66). Among participants randomized to one of the dietary portfolio interventions, percentage reduction in LDL- C on the dietary portfolio was associated with dietary adherence (r=−0.34, n=157, P<.001).

25. Conclusion Use of a dietary portfolio compared with the low−saturated fat dietary advice resulted in greater LDL- C lowering during 6 months of follow- up. Trial Registration clinicaltrials.gov Identifier: NCT00438425

26. Message/Comments LDL-C を低下させる食事療法介入は２回 （ 60,40 分）で 13% の低下効果があることが示 された。 ドロップアウトが 23% もあった。 ２回以上７回やってもあまり違いはなかった。 で、栄養指導はまぁ２回。スタチンはイベント 低下には必須？日本人ならもっとまじめにやる のできっと結果はもうすこしよいかもしれない が。