ContextTumor necrosis factor (TNF) plays an important role in host defense and tumor growth control. Therefore, anti-TNF antibody therapies may increase the risk of serious infections and malignancies.ObjectiveTo assess the extent to which anti-TNF antibody therapies may increase the risk of serious infections and malignancies in patients with rheumatoid arthritis by performing a meta-analysis to derive estimates of sparse harmful events occurring in randomized trials of anti-TNF therapy.Data SourcesA systematic literature search of EMBASE, MEDLINE, Cochrane Library, and electronic abstract databases of the annual scientific meetings of both the European League Against Rheumatism and the American College of Rheumatology was conducted through December 2005. This search was complemented with interviews of the manufacturers of the 2 licensed anti-TNF antibodies.Study SelectionWe included randomized, placebo-controlled trials of the 2 licensed anti-TNF antibodies (infliximab and adalimumab) used for 12 weeks or more in patients with rheumatoid arthritis. Nine trials met our inclusion criteria, including 3493 patients who received anti-TNF antibody treatment and 1512 patients who received placebo.Data ExtractionData on study characteristics to assess study quality and intention-to-treat data for serious infections and malignancies were abstracted. Published information from the trials was supplemented by direct contact between principal investigators and industry sponsors.Data SynthesisWe calculated a pooled odds ratio (Mantel-Haenszel methods with a continuity correction designed for sparse data) for malignancies and serious infections (infection that requires antimicrobial therapy and/or hospitalization) in anti-TNF–treated patients vs placebo patients. We estimated effects for high and low doses separately. The pooled odds ratio for malignancy was 3.3 (95% confidence interval [CI], 1.2-9.1) and for serious infection was 2.0 (95% CI, 1.3-3.1). Malignancies were significantly more common in patients treated with higher doses compared with patients who received lower doses of anti-TNF antibodies. For patients treated with anti-TNF antibodies in the included trials, the number needed to harm was 154 (95% CI, 91-500) for 1 additional malignancy within a treatment period of 6 to 12 months. For serious infections, the number needed to harm was 59 (95% CI, 39-125) within a treatment period of 3 to 12 months.ConclusionsThere is evidence of an increased risk of serious infections and a dose-dependent increased risk of malignancies in patients with rheumatoid arthritis treated with anti-TNF antibody therapy. The formal meta-analysis with pooled sparse adverse events data from randomized controlled trials serves as a tool to assess harmful drug effects.

/pdf/anti-tnf-antibody-therapy-in-rheumatoid-arthritis-and-the-4pipx1jwuu.pdf

Anti-TNF Antibody Therapy in Rheumatoid Arthritis and the Risk of Serious Infections and Malignancies: Systematic Review and Meta-analysis of Rare Harmful Effects in Randomized Controlled Trials

https://research.vu.nl/ws/files/2902143/267402.pdf

How to measure comorbidity: a critical review of available methods

ContextProlonged calorie restriction increases life span in rodents. Whether prolonged calorie restriction affects biomarkers of longevity or markers of oxidative stress, or reduces metabolic rate beyond that expected from reduced metabolic mass, has not been investigated in humans.ObjectiveTo examine the effects of 6 months of calorie restriction, with or without exercise, in overweight, nonobese (body mass index, 25 to <30) men and women.Design, Setting, and ParticipantsRandomized controlled trial of healthy, sedentary men and women (N = 48) conducted between March 2002 and August 2004 at a research center in Baton Rouge, La.InterventionParticipants were randomized to 1 of 4 groups for 6 months: control (weight maintenance diet); calorie restriction (25% calorie restriction of baseline energy requirements); calorie restriction with exercise (12.5% calorie restriction plus 12.5% increase in energy expenditure by structured exercise); very low-calorie diet (890 kcal/d until 15% weight reduction, followed by a weight maintenance diet).Main Outcome MeasuresBody composition; dehydroepiandrosterone sulfate (DHEAS), glucose, and insulin levels; protein carbonyls; DNA damage; 24-hour energy expenditure; and core body temperature.ResultsMean (SEM) weight change at 6 months in the 4 groups was as follows: controls, −1.0% (1.1%); calorie restriction, −10.4% (0.9%); calorie restriction with exercise, −10.0% (0.8%); and very low-calorie diet, −13.9% (0.7%). At 6 months, fasting insulin levels were significantly reduced from baseline in the intervention groups (all P<.01), whereas DHEAS and glucose levels were unchanged. Core body temperature was reduced in the calorie restriction and calorie restriction with exercise groups (both P<.05). After adjustment for changes in body composition, sedentary 24-hour energy expenditure was unchanged in controls, but decreased in the calorie restriction (−135 kcal/d [42 kcal/d]), calorie restriction with exercise (−117 kcal/d [52 kcal/d]), and very low-calorie diet (−125 kcal/d [35 kcal/d]) groups (all P<.008). These “metabolic adaptations” (~ 6% more than expected based on loss of metabolic mass) were statistically different from controls (P<.05). Protein carbonyl concentrations were not changed from baseline to month 6 in any group, whereas DNA damage was also reduced from baseline in all intervention groups (P <.005).ConclusionsOur findings suggest that 2 biomarkers of longevity (fasting insulin level and body temperature) are decreased by prolonged calorie restriction in humans and support the theory that metabolic rate is reduced beyond the level expected from reduced metabolic body mass. Studies of longer duration are required to determine if calorie restriction attenuates the aging process in humans.Trial RegistrationClinicalTrials.gov Identifier: NCT00099151

/pdf/effect-of-6-month-calorie-restriction-on-biomarkers-of-3ylslte4h4.pdf

Effect of 6-month calorie restriction on biomarkers of longevity, metabolic adaptation, and oxidative stress in overweight individuals: a randomized controlled trial.

ContextLaparoscopic-assisted colectomy (LAC) has emerged as the preferred minimally
invasive surgical strategy for diseases of the colon. The safety and efficacy
of LAC for colon cancer are unknown, and the nature and magnitude of any quality-of-life
(QOL) benefit resulting from LAC for colon cancer is also unknown.ObjectiveTo compare short-term QOL outcomes after LAC vs open colectomy for colon
cancer.Design, Setting, and ParticipantsMulticenter, randomized controlled trial (Clinical Outcomes of Surgical
Therapy [COST]). Between September 1994 and February 1999, 37 of 48 centers
provided data for the QOL component of the trial for 449 consecutive patients
with clinically resectable colon cancer.Main Outcome MeasuresScores on the Symptoms Distress Scale (SDS), Quality of Life Index,
and a single-item global rating scale at 2 days, 2 weeks, and 2 months postoperative;
duration of postoperative in-hospital analgesic use; and length of stay.ResultsOf 449 patients, 428 provided QOL data. In an intention-to-treat analysis
comparing SDS pain intensity, SDS summary, QOL Index summary, and global rating
scale scores at each time point, the only statistically significant difference
observed between groups was the global rating scale score for 2 weeks postsurgery.
The mean (median) global rating scale scores for 2 weeks postsurgery were
76.9 (80) for LAC vs 74.4 (75) for open colectomy (P
= .009). While in the hospital, patients assigned to LAC required fewer days
of both parenteral analgesics compared with patients assigned to open colectomy
(mean [median], 3.2 [3] vs 4.0 [4] days; P<.001)
and oral analgesics (mean [median], 1.9 [1] vs 2.2 [2] days; P = .03).ConclusionOnly minimal short-term QOL benefits were found with LAC for colon cancer
compared with standard open colectomy. Until ongoing trials establish that
LAC is as effective as open colectomy in preventing recurrence and death from
colon cancer, this procedure should not be offered to patients with colon
cancer.

https://jamanetwork.com/journals/jama/articlepdf/194570/JOC10604.pdf

Short-term Quality-of-Life Outcomes Following Laparoscopic-Assisted Colectomy vs Open Colectomy for Colon Cancer: A Randomized Trial

CONTEXT
Laparoscopic-assisted colectomy (LAC) has emerged as the preferred minimally invasive surgical strategy for diseases of the colon. The safety and efficacy of LAC for colon cancer are unknown, and the nature and magnitude of any quality-of-life (QOL) benefit resulting from LAC for colon cancer is also unknown.


OBJECTIVE
To compare short-term QOL outcomes after LAC vs open colectomy for colon cancer.


DESIGN, SETTING, AND PARTICIPANTS
Multicenter, randomized controlled trial (Clinical Outcomes of Surgical Therapy [COST]). Between September 1994 and February 1999, 37 of 48 centers provided data for the QOL component of the trial for 449 consecutive patients with clinically resectable colon cancer.


MAIN OUTCOME MEASURES
Scores on the Symptoms Distress Scale (SDS), Quality of Life Index, and a single-item global rating scale at 2 days, 2 weeks, and 2 months postoperative; duration of postoperative in-hospital analgesic use; and length of stay.


RESULTS
Of 449 patients, 428 provided QOL data. In an intention-to-treat analysis comparing SDS pain intensity, SDS summary, QOL Index summary, and global rating scale scores at each time point, the only statistically significant difference observed between groups was the global rating scale score for 2 weeks postsurgery. The mean (median) global rating scale scores for 2 weeks postsurgery were 76.9 (80) for LAC vs 74.4 (75) for open colectomy (P =.009). While in the hospital, patients assigned to LAC required fewer days of both parenteral analgesics compared with patients assigned to open colectomy (mean [median], 3.2 [3] vs 4.0 [4] days; P<.001) and oral analgesics (mean [median], 1.9 [1] vs 2.2 [2] days; P =.03).


CONCLUSION
Only minimal short-term QOL benefits were found with LAC for colon cancer compared with standard open colectomy. Until ongoing trials establish that LAC is as effective as open colectomy in preventing recurrence and death from colon cancer, this procedure should not be offered to patients with colon cancer.

Short-term Quality-of-Life Outcomes Following Laparoscopic-Assisted Colectomy vs Open Colectomy for Colon Cancer

Externalities in hospitals and physician adoption of a new surgical technology: an exploratory analysis.

https://www.archives-pmr.org/article/0003-9993(94)90273-9/pdf

Four methods for characterizing disability in the formation of function related groups.

https://www.archives-pmr.org/article/S0003-9993(98)90001-6/pdf

JoséJ. Escarce

Papers

Externalities in hospitals and physician adoption of a new surgical technology: an exploratory analysis.

Four methods for characterizing disability in the formation of function related groups.

Diagnostic coding and medical rehabilitation length of stay: Their relationship☆☆☆