Second-sky.com

Financial Disclosures: None reported.
ondary efficacy end points; changes from baseline on these 1. Kaplan SA, Roehrborn CG, Rovner ES, Carlsson M, Bavendam T, Guan Z. Toltero-
measures confirmed the efficacy of combination therapy.
dine and tamsulosin for treatment of men with lower urinary tract symptoms and Moreover, it was not surprising to see a large placebo effect; overactive bladder: a reandomized controlled trial. JAMA. 2006;296:2319-2328.
2. Yoshimura K, Arai Y, Ichioka K, Terada N, Matsuta Y, Okubo K. Symptom-
this is common in clinical trials in overactive bladder, lower specific quality of life in patients with benign prostatic hyperplasia. Int J Urol. 2002; urinary tract symptoms, and BPH. It likely reflects a com- bination of unilateral regression to the mean, training ef- In Reply: We agree with Dr Chai that overactive bladder
fects associated with the use of bladder diaries, and true pla- likely plays a greater role in urinary urgency and urgency incontinence than does BPH. Regarding the comments of Finally, treatment cost is a complicated issue and be- Mr Bell and Dr Amarshi, over-the-counter decongestants yond the scope of this study. Such an analysis would have and antihistamines were not prohibited, which is the to consider costs associated with ineffective monotherapy, convention in ␣-receptor antagonist and antimuscarinic surgery, preoperative evaluation (including urodynam- clinical trials. No potential interactions with these prod- ics), and postoperative costs, as well as dual pharmaco- ucts are described in the tamsulosin or tolterodine extended release prescribing information, and we are Steven A. Kaplan, MD
unaware of any evidence suggesting that their efficacy is [email protected]
compromised by these products. We did conduct medica- Weill Cornell Medical College
tion reconciliation to assess compliance. Unused medica- New York, NY
tion was recorded at each visit or upon early termination.
Claus G. Roehrborn, MD
Patients who took at least 80% of their study medication University of Texas Southwestern Medical Center
We disagree with Drs Young and Subramonian that the Eric S. Rovner, MD
issues they raise preclude conclusions about the efficacy of Medical University of South Carolina
Charleston
combination therapy in men with lower urinary tract symp- Tamara Bavendam, MD
toms including overactive bladder. They state that the study Zhonghong Guan, MD, PhD
was underpowered to detect differences between mono- Pfizer Inc
therapy and combination therapy. We explicitly stated that New York, NY
our purpose was to compare combination therapy vs pla-cebo in men who met research criteria for BPH and over- Financial Disclosures: Drs Bavendam and Guan report that they are employed by
Pfizer Inc. Dr Kaplan reports that he is a paid consultant, speaker, and meeting
active bladder, based on the hypothesis that this unique popu- participant for Pfizer; a consultant for Astellas, GlaxoSmithKline, Allergan, and Sa- lation may simultaneously experience lower urinary tract nofi; a speaker for Sanofi Aventis; and a principal investigator for the National In-stitute of Diabetes and Digestive and Kidney Diseases. Dr Roehrborn reports that symptoms of prostatic and nonprostatic origin. The mono- he is a paid consultant, speaker, and meeting participant for Pfizer; a consultant therapy groups were included not as active controls but to for GlaxoSmithKline, Sanofi Aventis, and Lilly ICOS; and a study investigator forLilly ICOS. Dr Rovner reports that he is a paid consultant, speaker, meeting par- investigate monotherapy efficacy relative to placebo and to ticipant, and study investigator for Pfizer; a consultant for Allergan and Esprit; a identify factors that may predict response to monotherapy speaker for Astellas and Esprit; and a study investigator for Allergan and Q-Med.
(to be assessed in future subanalyses).
1. Scarpa RM. Lower urinary tract symptoms: what are the implications for the
We disagree that patient selection was biased toward those patients? Eur Urol. 2001;40(suppl 4):12-20.
2. Belal M, Abrams P. Noninvasive methods of diagnosing bladder outlet obstruc-
with overactive bladder–related (storage) symptoms. Al- tion in men, II: noninvasive urodynamics and combination of measures. J Urol.
though storage symptoms are associated with greater bother 2006;176:29-35.
3. Pleil AM, Coyne KS, Reese PR, Jumadilova Z, Rovner ES, Kelleher CJ. The vali-
and impact on quality of life, voiding symptoms are also both- dation of patient-rated global assessments of treatment benefit, satisfaction, and ersome and reduce quality of life.1 Thus, it is unlikely that willingness to continue–the BSW. Value Health. 2005;8(suppl 1):S25-S34.
this inclusion criterion introduced selection bias. A mean 4. van Leeuwen JH, Castro R, Busse M, Bemelmans BL. The placebo effect in the
pharmacologic treatment of patients with lower urinary tract symptoms. Eur Urol.
maximum urinary flow rate of 12.9 mL/s does not neces- sarily indicate that patients were not obstructed.2 Interna-tional Prostate Symptom Scores on the storage subscale and Frail Older Adults and Palliative Care
the prevalence of overactive bladder were likely higher inour study than in the general population of men with lower To the Editor: In their Perspectives on Care at the Close of
urinary tract symptoms because our intention was to in- Life, Drs Boockvar and Meier1 discuss palliative care for frail clude only men who met standard research criteria for BPH older adults and state that “relief of discomfort and en- hancement of quality of life is highly appropriate.” They rec- We also disagree that using the Perception of Treatment ommend considering megestrol as a treatment and cite Benefit question as the primary end point caused us to over- Reuben et al2; however, that study did not find a statisti- estimate efficacy. This measure has been validated in pa- cally significant effect of megestrol acetate on serum albu- tients with overactive bladder.3 Bladder diary variables and min levels or clinical end points, such as weight, func- International Prostate Symptom Scores were included as sec- tional status, or health-related quality of life. They also cite 2007 American Medical Association. All rights reserved.
(Reprinted) JAMA, March 21, 2007—Vol 297, No. 11 1193
Yeh et al,3 who found no difference in weight change until 3. Penninx BW, Pluijm SM, Lips P, et al. Late-life anemia is associated with in-
creased risk of recurrent falls. J Am Geriatr Soc. 2005;53:2106-2111.
months after treatment was stopped, no difference in de- 4. Dharmarajan TS, Avula S, Norkus EP. Anemia increases risk for falls in hospi-
pression scores, and a 3-point difference on a 99-point scale talized older adults: an evaluation of falls in 362 hospitalized, ambulatory, long- of sense of well-being. As Boockvar and Meier note, the drug term care, and community patients. J Am Med Dir Assoc. 2006;7:287-293.
5. Steinberg KE. Anemia and falls. J Am Med Dir Assoc. 2006;7:327.
is toxic. I believe that the current best evidence indicates 6. Zakai NA, Katz R, Hirsch C, et al. A prospective study of anemia status, hemo-
that megestrol has no role in the care, palliative or other- globin concentration, and mortality in an elderly cohort: the Cardiovascular HealthStudy. Arch Intern Med. 2005;165:2214-2220.
Thomas E. Finucane, MD
To the Editor: Drs Boockvar and Meier1 offered perspec-
[email protected]
tives on palliative care. As they appropriately identified, Division of Geriatric Medicine and Gerontology
among all of the other maladies seen at the end of life, the Johns Hopkins Bayview Medical Center
loss of independence in function of activities of daily living Baltimore, Md
(ADL) is a cruel component in the deterioration of a per- Financial Disclosures: None reported.
1. Boockvar KS, Meier DE. Palliative care for frail older adults: “there are things I
A patient in palliative care is vulnerable and will rely can’t do anymore that I wish I could . . . ” JAMA. 2006;296:2245-2253.
heavily on the physician for direction of care and recom- 2. Reuben DB, Hirsch SH, Zhou K, Greendale GA. The effects of megestrol ac-
etate suspension for elderly patients with reduced appetite after hospitalization: a
mendations for a dignified end-of-life experience. Al- phase II randomized clinical trial. J Am Geriatr Soc. 2005;53:970-975.
though the authors did include recommendations for reha- 3. Yeh SS, Wu SY, Lee TP, et al. Improvement in quality-of-life measures and stimu-
bilitation and physical therapy in their suggestions for how lation of weight gain after treatment with megestrol acetate oral suspension ingeriatric cachexia: results of a double-blind, placebo-controlled study. J Am Geri- to address skill decline, they did not mention occupational therapy, a profession whose job definition is based on en- To the Editor: Many symptoms and consequences of ane-
suring enhancement or maintenance of the highest pos- mia, especially late-life anemia, are similar to those charac- sible level of independence in a patient’s ADL. Occupa- terizing frailty (fatigue, weakness, and impaired physical and tional therapists’ education includes both physical and cognitive performance).1 In Table 1 of their discussion of psychosocial rehabilitation. As a patient’s clinical status be- palliative care for frail older adults, Drs Boockvar and Meier2 comes progressively worse, and rehabilitation efforts to re- summarized operational definitions, assessment, and treat- store biomechanical skills become less effective, occupa- ment methods for common symptoms of frailty. Anemia was tional therapists may offer ideas and training in adaptive listed as a remediable cause of fatigue but not as an under- methods and equipment to help maintain some level of in- lying cause of falls. Although the association between ane- dependence and dignity in the patient’s daily routine.
mia and increased risk of falls among elderly individuals has Daniel Cormican, OT/L
been recognized,3,4 anemia associated with long-term con- [email protected]
ditions other than renal disease may not be treated aggres- Peggy A. Seidman, MD
sively or considered in risk assessments for falls.5 The ac- Stony Brook University School of Medicine
Stony Brook, NY
cepted definition of anemia (hemoglobin Ͻ12 g/dL inwomen; Ͻ13 g/dL in men) may no longer be clinically valid Financial Disclosures: None reported.
for elderly individuals.6 Symptoms of nonanemic iron deple- 1. Boockvar KS, Meier DE. Palliative care for frail older adults: “there are things I
tion (serum ferritin Յ50 ng/mL [Յ112 pmol/L]) also may can’t do anymore that I wish I could . . . ” JAMA. 2006;296:2245-2253.
be misinterpreted as age-related frailty and remain un-treated.
In Reply: Dr Finucane rightly points out that the evidence
Although the causes of frailty and falls among elderly in- for megestrol benefit is very limited for older adults with dividuals are numerous and complex, it is important for cli- weight loss. Unfortunately, in many cases appetite and weight nicians to recognize that the physical and cognitive effects loss are high-priority concerns of patients or their families.
of anemia or low iron stores, even when hemoglobin and In this situation, it may be helpful for clinicians to explain hematocrit values are normal or near normal, can be dev- that the cause of weight loss usually is not starvation or in- astating to older persons. Ferritin levels and other under- adequate intake but poorly understood metabolic dysregu- lying causes of anemia should be investigated whenever in- lation. Clinicians may still feel pressured by patients or fami- explicable symptoms of frailty develop.
lies to offer any weight loss antidote available, and megestrolmay be appropriate to prescribe under these circum- Carol E. Bower, BSc
stances. Clinicians would be extrapolating from existing evi- [email protected]
dence of megestrol benefit in patients with cancer,1 many Manchester, Conn
of whom are older, frail, and receiving palliative care.
Financial Disclosures: None reported.
We concur with Ms Bower’s point about the potential con- 1. Eisenstaedt R, Penninx BW, Woodman RC. Anemia in the elderly: current un-
tribution of anemia to weakness, slowed performance, fa- derstanding and emerging concepts. Blood Rev. 2006;20:213-226.
tigue, and low physical activity in older adults. An attempt 2. Boockvar KS, Meier DE. Palliative care for frail older adults: “there are things I
can’t do anymore that I wish I could . . . ” JAMA. 2006;296:2245-2253.
to correct anemia may improve symptoms, although the evi- 1194 JAMA, March 21, 2007—Vol 297, No. 11 (Reprinted)
2007 American Medical Association. All rights reserved.
dence base for treatment approach and goals of therapy is 1. Berenstein EG, Ortiz Z. Megestrol acetate for the treatment of anorexia-
cachexia syndrome. Cochrane Database Syst Rev. 2005;(2):CD004310.
limited.2 We also concur with the point of Mr Cormican and 2. Eisenstaedt R, Penninx BW, Woodman RC. Anemia in the elderly: current un-
Dr Seidman about the potential value of referring older adults derstanding and emerging concepts. Blood Rev. 2006;20:213-226.
with functional limitations to an occupational therapist forevaluation and treatment.
Kenneth Boockvar, MD, MS
CORRECTION
[email protected]
Omission of Text in Financial Disclosures: In the Original Contribution entitled
James J. Peters VA Medical Center
“Tolterodine and Tamsulosin for Treatment of Men With Lower Urinary Tract Symp- Bronx, NY
toms and Overactive Bladder: A Randomized Controlled Trial” published in theNovember 15, 2006, issue of JAMA (2006;295:2319-2328), text in 2 sentences Diane Meier, MD
of the financial disclosure was inadvertently omitted. The sentence that read “Dr Mount Sinai School of Medicine
Roehrborn is also a consultant for GlaxoSmithKline, Sanofi Aventis, and Lilly ICOS, New York, NY
a consultant for Allergan and Esprit, a speaker for Astellas and Esprit, and a studyinvestigator for Allergan and Q-Med” should have read “Dr Roehrborn is also aconsultant for GlaxoSmithKline, Sanofi Aventis, and Lilly ICOS, and is a study in- Financial Disclosures: Dr Boockvar reported that he has received grant support
vestigator for Lilly ICOS. Dr Rovner is a paid consultant, speaker, meeting partici- from Pfizer Inc for an investigator-initiated research fellowship and award. Dr Meier pant, and study investigator for Pfizer; a consultant for Allergan and Esprit; a speaker for Astellas and Esprit; and a study investigator for Allergan and Q-Med.” Without books, history is silent, literature dumb, sci-ence crippled, thought and speculation at a stand-still. They are engines of change, windows on theworld, lighthouses erected in the sea of time.
2007 American Medical Association. All rights reserved.
(Reprinted) JAMA, March 21, 2007—Vol 297, No. 11 1195

Source: http://second-sky.com/docs/jama_anemia_ed_letter.pdf