Transcript PowerPoint - 埼玉医科大学総合医療センター 内分泌・糖尿病内科

Journal Club
Tisha R. Joy, MD; Alaa Monjed, MD; Guang Yong Zou, PhD; Robert A. Hegele,
MD; Charlotte G. McDonald, MD, MSc; and Jeffrey L. Mahon, MD, MSc
N-of-1 (Single-Patient) Trials for Statin-Related Myalgia
Intern Med. 2014;160(5):301-310-310
Beuschlein F1, Fassnacht M, Assié G, Calebiro D, Stratakis CA, Osswald A,
Ronchi CL, Wieland T, Sbiera S, Faucz FR, Schaak K, Schmittfull A,
Schwarzmayr T, Barreau O, Vezzosi D, Rizk-Rabin M, Zabel U, Szarek E, Salpea
P, Forlino A, Vetro A, Zuffardi O, Kisker C, Diener S, Meitinger T, Lohse MJ,
Reincke M, Bertherat J, Strom TM, Allolio B.
Constitutive Activation of PKA Catalytic Subunit in Adrenal Cushing's Syndrome.
N Engl J Med. 2014 Feb 26. [Epub ahead of print]
2014年3月13日 8:30-8:55
８階 医局
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
Single-patient trials, also known as n-of-1 trials and
individual-patient trials, have the potential to address these
critiques. Single-patient trials are multiple-period crossover
experiments comparing two or more treatments within
individual patients. Unlike parallel-group RCTs, single-patient
trials can be used to estimate individual treatment effects
directly. This allows single-patient trials to identify the best
treatment for each individual patient and, thereby serving as
a promising clinical decision tool for individual patients in the
spirit of patient-centered outcomes research (PCOR).
J Clin Epidemiol. 2013 Aug;66(8 Suppl):S21-8.
N-of-1 trials (single-patient, randomized, multiple crossover,
blinded comparisons of an active treatment vs. placebo) are
the most effective way to limit these biases in individual
patients because each patient serves as his or her own
control
Drs. Joy, McDonald, and Mahon: Western University, Schulich School of
Medicine and Dentistry, 268 Grosvenor Street, London, Ontario N6A 4V2,
Canada.
Dr. Monjed: Al-hejra Street, PO Box 463, Makkah, Saudi Arabia.
Dr. Zou: Robarts Clinical Trials, PO Box 5015, 100 Perth Drive, London,
Ontario N6A 5K8, Canada.
Dr. Hegele: Vascular Biology, Robarts Research Institute, 1511 Richmond
Street North, London, Ontario N6A 5B7, Canada.
Ann Intern Med. 2014;160(5):301-310-310. doi:10.7326/M13-1921
Background: Statin-related myalgia is
difficult to distinguish from other conditions
causing myalgia and may often lead to
statin discontinuation.
Objective: To compare the effect of statin
rechallenge with placebo in patients with
prior statin-related myalgia and to determine
whether patients resumed statin therapy
after evaluating the results.
Setting: Tertiary care lipid clinic.
Patients: Patients with prior statin-related myalgia
with or without mild elevation of creatine kinase
levels.
Intervention: Rechallenge with the statin that was
previously associated with myalgia within 3 weeks of
open-label use versus matching placebo.
Measurements: Weekly visual analogue scale
(VAS) scores for myalgia and specific symptoms
(VAS myalgia score and symptom-specific VAS
score, respectively), pain interference scores, and
pain severity scores were recorded during the 3week periods when patients were receiving placebo
or statin. The primary outcome was the VAS myalgia
score (range, 0 to 100 mm).
The VAS myalgia scores for patients 1 to 8 are
presented according to each treatment period
(active [solid circle, solid line] and placebo
[solid square, dotted line]). A full n-of-1 trial
consisted of 6 treatment periods (3 active and 3
placebo). Treatment periods were 3 wk in
duration. The VAS myalgia scores were
completed at the end of each week in the
treatment periods. Higher VAS myalgia scores
signify greater muscle pain. Patient 6 crossed
over early during treatment period 1, resulting
in only 2 VAS myalgia scores for that period.
Patient 7 forgot to complete 1 of 3 VASs for
myalgia in treatment period 6, and patient 8
discontinued the n-of-1 trial after completing 5
treatment periods. VAS visual analogue scale.
For the PSS, the patients showed statistically greater discomfort during statin
treatment versus placebo, but the mean difference did not meet the
prespecified clinically significant difference of 1 point.
Results: Eight patients (mean age, 66 years [SD,
8 years]; 88% women, all with high 10-year
Framingham cardiovascular risk) participated in
n-of-1 trials. Seven patients completed 3
treatment pairs, and 1 completed 2 treatment
pairs. For each n-of-1 trial, no statistically
significant differences were seen between statin
and placebo in the VAS myalgia score, symptomspecific VAS score, pain interference score, and
pain severity score. Five patients resumed openlabel statin treatment, with a median posttrial
follow-up of 10 months.
Limitation: Results are limited by the small
sample size and cannot be extended to
patients with longer onset of myalgia after
statin initiation.
Conclusion: In selected patients with a
history of statin-related myalgia whose
symptoms are difficult to evaluate, n-of-1
trials may be a useful method for
determining statin tolerability.
Primary Funding Source: Western
University, London, Ontario, Canada.
Message
スタチン関連筋痛症既往患者8人を対象に、ス
タチン治療再開の判断に対するN-of-1二重盲検
試験の有用性を検証。視覚的アナログスケール
の筋痛症スコアにおける、スタチンとプラセボ
の統計学的有意差はなかった。中央値10カ月の
追跡期間中に5人がスタチンを再開した。N-of-1
試験でスタチンへの忍容性を評価できる可能性
が示唆された。
Department of International Health (Human Nutrition), Johns Hopkins Bloomberg
School of Public Health, Baltimore, Maryland (Jones-Smith);
School of Public Health, University of California, Berkeley (Dow);
Independent consultant, Sacramento, California (Chichlowska).
JAMA. 2014;311(9):929-936. doi:10.1001/jama.2014.604
Importance Economic resources have been
inversely associated with risk of childhood
overweight/obesity. Few studies have evaluated
whether this association is a direct effect of
economic resources or is attributable to
unmeasured confounding or reverse causation.
American Indian–owned casinos have resulted in
increased economic resources for some tribes
and provide an opportunity to test whether these
resources are associated with overweight/obesity.
Objective To assess whether openings or
expansions of American Indian–owned casinos
were associated with childhood
overweight/obesity risk.
Design, Setting, and Participants We used repeated
cross-sectional anthropometric measurements from
fitness testing of American Indian children (aged 7-18
years) from 117 school districts that encompassed
tribal lands in California between 2001 and 2012.
Children in school districts encompassing American
Indian tribal lands that either gained or expanded a
casino were compared with children in districts with
tribal lands that did not gain or expand a casino.
Main Outcomes and Measures Per capita annual
income, median annual household income, percentage
of population in poverty, total population, child
overweight/obesity (body mass index [BMI] ≥85th ageand sex-specific percentile) and BMI z score.
a Data are expressed as mean
(SD) unless otherwise
indicated.
b Slot machines per capita
were calculated for each
school district in every year
and represent the number of
slot machines per single-race
American Indian living on
tribal lands within the school
district; places with zero slot
machines are included in the
estimate.
c Overweight/obesity was
defined as85th percentile for
age- and sex-specific body
mass index based on the
2000 Centers for Disease
Control and
Prevention/National Center
for Health Statistics (CDC)
growth charts.
d Based on 22 863
observations between years
2001 and 2012.
e Body mass index z score was
based on the age- and sex-
a The statistical models for body mass index z score are district fixed-effects linear regression models; the statistical models for
overweight/obesity are district fixed-effects linear probability models. In addition to including district fixed effects (ie, an indicator
variable for each district), all models also include indicator variables for each year, an ordered categorical variable for year to
provide a linear time trend, and interactions terms between district indicator variables and the linear time trend to allow the trend
in BMI z score/obesity to vary by district (coefficients are not shown). All models used robust standard errors that also correct for
correlated outcomes within individuals and school districts. Casino slot machines per capita were calculated for each school
district in every year and represent the number of slot machines per single-race American Indian living on tribal lands within the
school district. This number could change over time for each school district, depending on casino opening and expansion dates.
b Body mass index z scores were age- and sex-specific using the 2000 Centers for Disease Control and Prevention/National
Center for Health Statistics (CDC) growth charts.
c Overweight/obesity was defined as a having a body mass index z score85th percentile of the age- and sex-specific 2000 CDC
growth charts.
d P<.05.
Results Of the 117 school districts, 57 gained or expanded a
casino, 24 had a preexisting casino but did not expand, and 36
never had a casino. The mean slots per capita was 7 (SD, 12) and
the median was 3 (interquartile range [IQR], 0.3-8). Among
districts where a casino opened or expanded, the mean change in
slots per capita was 13 (SD, 19) and the median was 3 (IQR, 111). Forty-eight percent of the anthropometric measurements were
classified as overweight/obese (11 048/22 863). Every casino slot
machine per capita gained was associated with an increase in per
capita annual income (β = $541; 95% CI, $245-$836) and a
decrease in percentage in poverty (β = −0.6%; 95% CI, −1.1% to
−0.20%) among American Indians living on tribal lands. Among
American Indian children, every slot machine per capita gained
was associated with a decreased probability of overweight/obesity
by 0.19 percentage points (95% CI, −0.26 to −0.11 percentage
points) and a decrease in BMI z score (β = −0.003; 95% CI,
−0.005 to −0.0002).
Conclusions and Relevance In this
study, opening or expanding a casino
was associated with increased
economic resources and decreased
risk of childhood overweight/obesity.
Given the limitations of an ecological
study, further research is needed to
better understand the mechanisms
behind this association.
Message
米国で先住民所有のカジノの新設または拡
大と、先住民居留区の小児の過体重・肥満
リスクの関連を検証。先住民1人当たりのス
ロットマシン台数の増加は、1人当たり年間
所得の増加および貧困率の低下と関連した。
スロットの1台増加は、小児の過体重・肥満
率の0.19パーセントポイント低下および体
格指数Zスコアの低下と関連した。