Christine E. Kistler, Katharine A. Kirby, et al. Long-term Outcome Following Positive Fecal Occult Blood Test Results in Older Adults. Arch Intern Med. 2011;171(15):1344-1351.

In the United States, older adults have low rates (fewer than 60%) of follow-up colonoscopy after a positive fecal occult blood test (FOBT) result. The long-term outcomes of these real world practices and their associated benefits and burdens are unknown.

To inform how clinical practice could improve to maximize the net benefit of FOBT screening and follow-up in older adults.

Longitudinal cohort study of 212 patients 70 years or older with a positive FOBT result at 4 Veteran 
Affairs (VA) facilities in 2001 and followed up through 2008. We determined the frequency of downstream outcomes duringthe7years of follow-up, including procedures, colonoscopic findings, outcomes of treatment, complications, and mortality based on chart review and national VA and Medicare data. 
Net burden or benefit from screening and follow-up was determined according to each patient’s life expectancy. Life expectancy was classified into 3 categories: Best (age, 70-79 years and Charlson-Deyo comorbidity index [CCI], 0), average, and worst (age, 70-84 years and CCI, >=4 or age, >=85 years and CCI, >=1).

56 % of patients received follow-up colonoscopy (118 of 212), which found 34 significant adenomas and 6 cancers. 10% experienced complications from colonoscopy or cancer treatment (12 of 118). 46 % of those without follow-up colonoscopy died of other causes within 5 years of FOBT (43 of 94), while 3% (3 of 94) died of colorectal cancer within 5 years (Figure1). 87% of patients with worst life expectancy experienced a net burden from screening (26 of30) as did 70% with average life expectancy (92 of 131) and 65% with best life expectancy (35 of 51) (P=.048 for trend) (Figure2).

Over a 7-year period, older adults with best life expectancy were less likely to experience a net burden from current screening and follow-up practices than are those with worst life expectancy. The net burden could be decreased by better targeting FOBT screening and follow-up to healthy older adults.




※Charlson-Deyo comorbidity index (Wikipedia)
The Charlson co-morbidity index predicts the ten-year mortality for a patient who may have a range of co-morbid conditions such as heart disease, AIDS, or cancer (a total of 22 conditions). Each condition is assigned with a score of 1,2,3 or 6 depending on the risk of dying associated with this condition. Then the scores are summed up and given a total score which predicts mortality.
The clinical conditions and scores are as follow: 1 each: Myocardial infarct, congestive heart failure, peripheral vascular disease, dementia, cerebrovascular disease, chronic lung disease, connective tissue disease, ulcer, chronic liver disease. 2 each: Hemiplegia, moderate or severe kidney disease, diabetes, diabetes with complication, tumor, leukemia, lymphoma. 3 each: Moderate or severe liver disease. 6 each: Malignant tumor, metastasis, AIDS.
For a physician, it is helpful in knowing how aggressively to treat a condition. For example, a patient may have cancer, but also heart disease and diabetes so severe that the costs and risks of the treatment outweigh the short term benefit from treatment of the cancer.
Since patients often do not know how severe their conditions are, originally to calculate the index nurses were supposed to go through the patient’s chart and determine whether the patient had a particular condition. Subsequent studies have adapted it to a questionnaire for patients.
The original citation follows: Charlson ME, Pompei P, Ales KL, MacKenzie CR (1987). A new method of classifying prognostic comorbidity in longitudinal studies: development and validation. J Chron Dis, 40(5): 373-383.


Do you want to know the natural history of headache?


Magnitude, impact, and stability of primary headache subtypes: 30 year prospective Swiss cohort study.
Merikangas KR, Cui L, Richardson AK, Isler H, Khoromi S, Nakamura E, Lamers F, Rossler W, Ajdacic-Gross V, Gamma A, Angst J.
BMJ. 2011 Aug 25;343:d5076. doi: 10.1136/bmj.d5076.



To determine the prevalence, impact, and stability of different subtypes of headache in a 30 year prospective follow-up study of a general population sample.


Prospective cohort study.

Canton of Zurich, Switzerland.

591 people aged 19-20 from a cohort of 4547 residents of Zurich, Switzerland, interviewed seven times across 30 years of follow-up.

<Main outcome measures>

Prevalence of headache; stability of the predominant subtype of headache over time; and age of onset, severity, impact, family history, use of healthcare services, and drugs for headache subtypes.


The average one year prevalences of subtypes of headache were 0.9% (female:male ratio of 2.8) for migraine with aura, 10.9% (female:male ratio of 2.2) for migraine without aura, and 11.5% (female:male ratio of 1.2) for tension-type headache. Cumulative 30 year prevalences of headache subtypes were 3.0% for migraine with aura, 36.0% for migraine without aura, and 29.3% for tension-type headache. Despite the high prevalence of migraine without aura, most cases were transient and only about 20% continued to have migraine for more than half of the follow-up period. 69% of participants with migraine and 58% of those with tension-type headache manifested the same predominant subtype over time. However, the prospective stability of the predominant headache subtypes was quite low, with substantial crossover among the subtypes and no specific ordinal pattern of progression. A gradient of severity of clinical correlates and service use was present across headache subtypes; the greatest effect was for migraine with aura followed by migraine without aura, and then tension-type headache and unclassified headaches.


These findings highlight the importance of prospective follow-up of people with headache. The substantial longitudinal overlap among subtypes of headache shows the developmental heterogeneity of headache syndromes. Studies of the causes of headache that apply diagnostic nomenclature based on distinctions between discrete headache subtypes may not capture the true nature of headache in the general population.





R.K. Albert , et al. Azithromycin for Prevention of Exacerbations of COPD. The NEW ENGLAND JOURNAL of MEDISINE. 2011;8.25: 689-698.





増悪リスクは高いが、聴覚障害・安静時頻脈は認めず,補正 QT 間隔延長の明確なリスクを有しない COPD 患者を対象にアジスロマイシンによって増悪の頻度が低下するかどうかを検討することを目的として無作為化試験を行った。


1,577 例をスクリーニングし、その中で 1,142 例(72%)を1 年にわたり標準の治療とアジスロマイシン 250 mg/日を投与する群(570 例)とプラセボを投与する群(572 例)に無作為に割り付けた。1 年間の追跡を完了した患者の割合はアジスロマイシン群 89%,プラセボ群 90%であった。初回増悪までの期間の中央値は、アジスロマイシン群で 266 日(95%信頼区間 [CI] 227~313)に対し、プラセボ群では 174 日(95% CI 143~215)だった(P<0.001)。増悪の頻度は,アジスロマイシン群で患者・年あたり 1.48 回であったのに対し、プラセボ群では患者・年あたり 1.83 回であり(P=0.01)アジスロマイシン群における患者・年あたりの COPD 急性増悪発生のハザード比は 0.73(95% CI 0.63~0.84)であった(P<0.001)。St. George 呼吸器質問票(0~100 で,スコアが低いほど機能が良好であることを示す)のスコア改善はアジスロマイシン群のほうがプラセボ群よりも大きく(低下の平均 [±SD] 2.8±12.8 対 0.6±11.4,P=0.004),最小有意差である 4 単位以上の低下がみられた患者の割合は、アジスロマイシン群で 43%であったのに対し、プラセボ群では 36%であった(P=0.03)。聴力低下はアジスロマイシン群でプラセボ群よりも多く認められた(25% 対 20%,P=0.04)。また、気道におけるマクロライド耐性菌は優位に上昇(81%対41%)したが、肺炎発症には関与しなかった。


特定の COPD 患者では,標準治療に加えてアジスロマイシンを 1 年間連日服用することで,増悪の頻度が低下し QOL が改善したが、ごく一部の患者で聴力低下が生じた。この介入によって微生物の薬剤耐性パターンが変化する可能性があるが、それによる影響は不明である。






Effect of high flow oxygen on mortality in chronic obstructive pulmonary disease patients in prehospital setting: randomised controlled trial; BMJ 2010;341:c5462

クラスターランダム化比較試験。研究期間中にRoyal Hobart Hospitalに入院したCOPD急性増悪の患者で、救急救命士の治療を受けていた405名を対象とした。
 患者数   (A)226名 (B)179名
 COPD患者数(A)117名 (B)97名
 全死亡率  (A)9%(21名) (B)4%(7名)
 COPD患者の死亡率(A)9%(11名) (B)2%(2名)
 全患者    Relative risk 0.42 (95%信頼区間 0.20-0.89; P=0.02)
 COPD患者  Relative risk 0.22 (95%信頼区間 0.05-0.91; P=0.04)




Adriana Buitrago-Lopez et al: Chocolate consumption and cardiometabolic disorders: systematic review and meta-analysis. BMJ 2011; 343:d4488



To evaluate the association of chocolate consumption with the risk of developing cardiometabolic disorders.


Systematic review and meta-analysis of randomised controlled trials and observational studies.

<Data sources>

Medline, Embase, Cochrane Library, PubMed, CINAHL, IPA, Web of Science, Scopus, Pascal, reference lists of relevant studies to October 2010, and email contact with authors.

<Study selection>

Randomised trials and cohort, case-control, and cross sectional studies carried out in human adults, in which the association between chocolate consumption and the risk of outcomes related to cardiometabolic disorders were reported.

<Data extraction>
Data were extracted by two independent investigators, and a consensus was reached with the involvement of a third. The primary outcome was cardiometabolic disorders, including cardiovascular disease (coronary heart disease and stroke), diabetes, and metabolic syndrome. A meta-analysis assessed the risk of developing cardiometabolic disorders by comparing the highest and lowest level of chocolate consumption.


From 4576 references seven studies met the inclusion criteria (including 114 009 participants). None of the studies was a randomized trial, six were cohort studies, and one a cross sectional study. Large variation was observed between these seven studies for measurement of chocolate consumption, methods, and outcomes evaluated. Five of the seven studies reported a beneficial association between higher levels of chocolate consumption and the risk of cardiometabolic disorders. The highest levels of chocolate consumption were associated with a 37% reduction in cardiovascular disease (relative risk 0.63 (95% confidence interval 0.44 to 0.90)) and a 29% reduction in stroke compared with the lowest levels.


Based on observational evidence, levels of chocolate consumption seem to be associated with a substantial reduction in the risk of cardiometabolic disorders. Further experimental studies are required to confirm a potentially beneficial effect of chocolate consumption.





Julia Hippisley-Cox.Development and validation of risk prediction algorithm (QThrombosis) to estimate future risk of venous thromboembolism: prospective cohort study.BMJ 2011;343:d4656 doi: 10.1136/bmj.d4656







Prospective open cohort study
  Calibration(較正)とdiscrimination(識別)を測定するため、validation cohortを用いた。


QReserchデータベース上のイングランドとウェールズにある564か所の家庭医(general practices)



Derivation cohort(解析群):
割り付け 2,598,829人-exclusion=2,314,701人が対象。

Validation cohort(検証群):

割り付け 1,354,517人-exclusion=1,240,602人が対象。
Baselineのcharacteristic ⇒ Table1参照



このモデルは良く較正されていると言える。(well calibrated) ⇒ Table3


R2 statistic:女性においては33%、男性においては34%

D statistic:女性では1.43、男性では1.45であった。
ROC statistic:両性別で0.75であった。



QThrombosisR risk calculator






Effect of intensive glucose lowering treatment on all cause mortality, cardiovascular death, and microvascular events in type 2 diabetes: meta-analysis of randomised controlled trials
 BMJ 2011;343:d4169 doi: 10.1136/bmj.d4169













結果はrisk ratio(99%信頼区間)として報告した。統計学的異質性はカイ二乗検定など。fixed effect modelで統合した。厳密な血糖降下治療と通常のコントロールの比較は、fixed effect modelで評価した。かくRCTの質はJadad scoreで評価した。


13の研究が採用された。34533人の患者のうち、18315人が厳密な血糖降下治療をうけ、16218人が通常の治療を受けた。厳密な血糖降下治療は全死亡に大きな影響はもたらさなかった(RR:1.04、99%信頼区間:0.91?1.19)。心血管系死亡も同様であった(1.11、0.86?1.43)。しかし、厳密な血糖降下治療は、非致死的なAMIを減少させた(0.85、0.74?0.96、P<0.001)。また微量アルブミン尿も減少させた(0.90、0.85?0.96、P<0.001)。しかし重症な低血糖が2倍だった(2.33、1.62?3.36、P<0.001)。5年間で、1人の心筋梗塞を防ぐために117人?150人の治療が必要。微量アルブミン尿も同様に32人?142人の治療が必要。しかしこれをすると、15人?52人に1人の割合で毎年重症な低血糖が起きる(NNH=15?52)。質の高い研究(Jadad scoreで3点以上)に限ると、うっ血性心不全の危険性が47%増加する。 






Memantine Treatment in Patients With Moderate to Severe Alzheimer Disease Already Receiving Donepezil  A Randomized Controlled Trial JAMA 2004 Jan 21;Vol291,No.3:317-324



Memantine is a low- to moderate-affinity, uncompetitive N-methyl-Daspartate receptor antagonist. Controlled trials have demonstrated the safety and efficacy of memantine monotherapy for patients with moderate to severe Alzheimer disease(AD) but no controlled trials of memantine in patients receiving a cholinesterase inhibitor have been performed.

Objective  To compare the efficacy and safety of memantine vs placebo in patients with moderate to severe AD already receiving stable treatment with donepezil.

<Design, Setting, and Participants>

A randomized, double-blind, placebo controlled clinical trial of 404 patients with moderate to severe AD and Mini-Mental State Examination scores of 5 to 14, who received stable doses of donepezil, conducted at 37 US sites between June 11, 2001, and June 3, 2002. A total of 322 patients (80%) completed the trial.


Participants were randomized to receive memantine (starting dose 5 mg/d, increased to 20 mg/d, n=203) or placebo (n=201) for 24 weeks.

<Main Outcome Measures>

Change from baseline on the Severe Impairment Battery (SIB), a measure of cognition, and on a modified 19-item AD Cooperative Study? Activities of Daily Living Inventory (ADCS-ADL19). Secondary outcomes included a Clinician’s Interview-Based Impression of Change Plus Caregiver Input (CIBIC-Plus), the Neuropsychiatric Inventory, and the Behavioral Rating Scale for Geriatric Patients (BGP Care Dependency Subscale).


The change in total mean (SE) scores favored memantine vs placebo treatment for SIB (possible score range, 0-100), 0.9 (0.67) vs ?2.5 (0.69), respectively (P_.001); ADCS-ADL19 (possible score range, 0-54), ?2.0 (0.50) vs ?3.4 (0.51), respectively (P=.03); and the CIBIC-Plus (possible score range, 1-7), 4.41 (0.074) vs 4.66 (0.075), respectively (P=.03). All other secondary measures showed significant benefits of memantine treatment. Treatment discontinuations because of adverse events for memantine vs placebo were 15 (7.4%) vs 25 (12.4%), respectively.


In patients with moderate to severe AD receiving stable doses of donepezil, memantine resulted in significantly better outcomes than placebo on measures of cognition, activities of daily living, global outcome, and behavior and was well tolerated. These results, together with previous studies, suggest that memantine represents a new approach for the treatment of patients with moderate to severe AD.





Leslee L. Subak, M.D.,  Weight Loss to Treat Urinary Incontinence in Overweight and Obese Women N Engl J Med 2009 360;5 jan 29, 481-490



Obesity is an established and modifiable risk factor for urinary incontinence, but conclusive evidence for a beneficial effect of weight loss on urinary incontinence is lacking.


Researchers randomly assigned 338 overweight and obese women with at least 10 urinary incontinence episodes per week to an intensive 6-month weight-loss program that included diet, exercise, and behavior modification (226 patients) or to a structured education program (112 patients).


The mean (±SD) age of the participants was 53±11 years. The body-mass index (BMI) (the weight in kilograms divided by the square of the height in meters) and the weekly number of incontinence episodes as recorded in a 7-day diary of voiding were similar in the intervention group and the control group at baseline (BMI, 36±6and 36±5, respectively; incontinence episodes, 24±18 and 24±16, respectively). The women in the intervention group had a mean weight loss of 8.0% (7.8 kg), as compared with 1.6% (1.5 kg) in the control group (P<0.001). After 6 months, the mean weekly number of incontinence episodes decreased by 47% in the intervention group, as compared with 28% in the control group (P = 0.01). As compared with the control group, the intervention group had a greater decrease in the frequency of stress incontinence episodes (P = 0.02), but not of urge-incontinence episodes (P = 0.14).A higher proportion of the intervention group than of the control group had a clinically relevant reduction of 70% or more in the frequency of all incontinence episodes (P<0.001), stress-incontinence episodes (P = 0.009), and urge-incontinence episodes(P = 0.04).

 A 6-month behavioral intervention targeting weight loss reduced the frequency of self-reported urinary-incontinence episodes among overweight and obese women as compared with a control group. A decrease in urinary incontinence may be another benefit among the extensive health improvements associated with moderate weight reduction. 




Sertraline or mirtazapine for depression in dementia (HTA-SADD): a randomised, multicentre, double-blind, placebo-controlled trial. The Lancet, Volume 378, Issue 9789, Pages 403 – 411, 30 July 2011.

うつ症状を示すアルツハイマー病患者に、選択的セロトニン再取り込み阻害薬(SSRI)のセルトラリン、ノルアドレナリン作動性・特異的セロトニン作動性抗うつ薬(NaSSA)のミルタザピン、偽薬のいずれかを投与した無作為化試験の結果が、Lancet誌2011年7月18日号に掲載された。英London King’s CollegeのSube Banerjee氏らによると、13週後と39週後のうつ症状の変化において、どちらの抗うつ薬にも偽薬を上回る利益は見られず、有害事象発生率は高かった。


現状では、主要学会は抗うつ薬の認知症患者への適用を支持しており、セルトラリンなどが第1選択として処方されている。高齢化が進む先進国では、認知症患者のうつは臨床的に重要な領域であると考えた英National Institute of Health Research (NIHR)は、著者らに臨床試験の実施を依頼した。













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