Number Needed to Treat (or Harm)

The effect of a treatment versus controls may be expressed in relative or absolute terms. For rational decision-making, absolute measures are more meaningful. The number needed to treat, the reciprocal of the absolute risk reduction, is a powerful estimate of the effect of a treatment. It is particularly useful because it takes into account the underlying risk (what would happen without the intervention?). The number needed to treat tells us not only whether a treatment works but how well it works. Thus, it informs health care professionals about the effort needed to achieve a particular outcome. A number needed to treat should be accompanied by information about the experimental intervention, the control intervention against which the experimental intervention has been tested, the length of the observation period, the underlying risk of the study population, and an exact definition of the endpoint. A 95% confidence interval around the point estimate should be calculated. An isolated number needed to treat is rarely appropriate to summarize the usefulness of an intervention; multiple numbers needed to treat for benefit and harm are more helpful. Absolute risk reduction and number needed to treat should become standard summary estimates in randomized controlled trial

Prevention of Bloodstream Infections With Central Venous Catheters Treated With Anti-Infective Agents Depends on Catheter Type and Insertion Time: Evidence From a Meta-Analysis

Objective: To test the evidence that the risk of infection related to central venous catheters (CVCs) is decreased by anti-infective coating or cuffing. Design: Systematic review of randomized, controlled trials comparing anti-infective with inactive (control) CVCs. Interventions: Average insertion times were taken as a measurement of the length of insertion. Dichotomous data were combined using a fixed effect model and expressed as odds ratio (OR) with 95% confidence interval (CI95). Results: Two trials on antibiotic coating (343 CVCs) had an average insertion time of 6 days; the risk of BSI decreased from 5.1% with control to 0% with anti-infective catheters. There were no trials with longer average insertion times. In three trials on silver collagen cuffs (422 CVCs), the average insertion time ranged from 5 to 8.2 days (median, 7 days); the risk of BSI was 5.6% with control and 3.2% with anti-infective catheters. In another trial on silver collagen cuffs (101 CVCs), the average insertion time was 38 days; the risk of BSI was 3.7% with control and 4.3% with anti-infective catheters. In five trials on chlorhexidine-silver sulfadiazine coating (1,269 CVCs), the average insertion time ranged from 5.2 to 7.5 days (median, 6 days); the risk of BSI decreased from 4.1% with control to 1.9% with anti-infective catheters. In five additional trials on chlorhexidine-silver sulfadiazine coating (1,544 CVCs), the average insertion time ranged from 7.8 to 20 days (median, 12 days); the risk of BSI was 4.5% with control and 4.2% with anti-infective catheters. Conclusions: Antibiotic and chlorhexidine-silver sulfadiazine coatings are anti-infective for short (approximately 1 week) insertion times. For longer insertion times, there are no data on antibiotic coating, and there is evidence of lack of effect for chlorhexidine-silver sulfadiazine coating. For silver-impregnated collagen cuffs, there is evidence of lack of effect for both short- and long-term insertio

Mortality with upper gastrointestinal bleeding and perforation: effects of time and NSAID use

<p>Abstract</p> <p>Background</p> <p>Some people who suffer an upper gastrointestinal bleed or perforation die. The mortality rate was estimated at 12% in studies published before 1997, but a systematic survey of more recent data is needed. Better treatment is likely to have reduced mortality. An estimate of mortality is helpful in explaining to patients the risks of therapy, especially with NSAIDs.</p> <p>Methods</p> <p>A systematic review of studies published before 1997, and between 1997 and 2008. Any study architecture was acceptable if it reported on cases who died from any cause of upper gastrointestinal bleed or perforation. Analyses were conducted separately for all cases, and those prescribed NSAID or aspirin.</p> <p>Results</p> <p>Information was available for 61,067 cases (81% published since 1997) of whom 5,001 died. The mortality rate in all cases fell significantly, from 11.6% (95% confidence interval, 11.0 to 12.2) in pre-1997 studies to 7.4% (7.2 to 7.6) in those published since 1997. In 5,526 patients taking NSAID or aspirin, mortality increased, from 14.7% (13.6 to 15.8) before 1997 to 20.9% (18.8 to 22.9) since 1997.</p> <p>Conclusion</p> <p>Upper gastrointestinal bleed or perforation still carries a finite risk of death. Differences in study architecture, population characteristics, risk factors, definition of mortality, and reporting of outcomes impose limitations on interpreting effect size. Data published since 1997 suggest that mortality in patients suffering from an upper gastrointestinal bleed or perforation has fallen to 1 in 13 overall, but remains higher at about 1 in 5 in those exposed to NSAID or aspirin.</p

Plasma Concentrations of Brain-derived Neurotrophic Factor in Patients Undergoing Minor Surgery: A Randomized Controlled Trial

We measured perioperative plasma concentrations of brain-derived neurotrophic factor (BDNF), a major mediator of synaptic plasticity in the central nervous system, in males, 30-65 years old, undergoing lumbar or cervical discotomy. Patients were randomly allocated to a general anesthetic with propofol induction and maintenance or with thiopental induction and isoflurane maintenance. BDNF plasma concentrations were measured before induction (baseline), 15min after induction but before start of surgery, at skin closure, in the post-anesthetic care unit, and 24h postoperatively. Data from 26 patients (13 in each group) were analyzed. At each time point, BDNF plasma concentrations showed large variability. At baseline, concentrations were 631±337 (mean±SD)pgml−1 in the propofol group and were 549±512pgml−1 in the thiopental-isoflurane group (P=0.31). At 15min, concentrations significantly decreased in the propofol group (247±219pgml−1, P=0.0012 compared with baseline) but remained unchanged in the thiopental-isoflurane group (597±471pgml−1, P=0.798 compared with baseline). At skin closure and in the post-anesthetic care unit, concentrations were not different from baseline in both groups. At 24h, concentrations significantly decreased below baseline in both groups (propofol: 232±129pgml−1, P=0.0015; thiopental-isoflurane: 253±250pgml−1, P=0.016). In the propofol group, there was a weak but statistically significant positive correlation (R 2=0.38, P=0.026) between the duration of surgery and BDNF plasma concentrations at skin closure. These data suggest that in males undergoing elective minor surgery, BDNF plasma concentrations show a specific pattern that is influenced by the anesthetic technique and, possibly, by the duration of surger

Is It Always Unethical to Use a Placebo in a Clinical Trial?

Background to the debate: Placebos are used in trials to conceal whether a treatment is being given or not and hence to control for the psychosomatic effects of offering treatment. Placebo-controlled trials are controversial. Critics of such trials argue that if a proven effective therapy exists, a placebo should not be used. But proponents argue that placebo trials are still crucial to prove the efficacy and safety of many treatments

Treatment of established postoperative nausea and vomiting: a quantitative systematic review

BACKGROUND: The relative efficacy of antiemetics for the treatment of postoperative nausea and vomiting (PONV) is poorly understood. METHODS: Systematic search (MEDLINE, Embase, Cochrane Library, bibliographies, any language, to 8.2000) for randomised comparisons of antiemetics with any comparator for the treatment of established PONV. Dichotomous data on prevention of further nausea and vomiting, and on side effects were combined using a fixed effect model. RESULTS: In seven trials (1,267 patients), 11 different antiemetics were tested without placebos; these data were not further analysed. Eighteen trials (3,809) had placebo controls. Dolasetron 12.5–100 mg, granisetron 0.1–3 mg, tropisetron 0.5–5 mg, and ondansetron 1–8 mg prevented further vomiting with little evidence of dose-responsiveness; with all regimens, absolute risk reductions compared with placebo were 20%–30%. The anti-nausea effect was less pronounced. Headache was dose-dependent. Results on propofol were contradictory. The NK(1) antagonist GR205171, isopropyl alcohol vapor, metoclopramide, domperidone, and midazolam were tested in one trial each with a limited number of patients. CONCLUSIONS: Of 100 vomiting surgical patients receiving a 5-HT(3) receptor antagonist, 20 to 30 will stop vomiting who would not have done so had they received a placebo; less will profit from the anti-nausea effect. There is a lack of evidence for a clinically relevant dose-response; minimal effective doses may be used. There is a discrepancy between the plethora of trials on prevention of PONV and the paucity of trials on treatment of established symptoms. Valid data on the therapeutic efficacy of classic antiemetics, which have been used for decades, are needed

Intravenous buspirone for the prevention of postoperative nausea and vomiting

Rationale: Buspirone, a partial 5HT1A agonist and D2 and D3 antagonist, has shown promising antiemetic efficacy when given parenterally in animal models, but its efficacy for the prevention of postoperative nausea and vomiting (PONV) is unknown. Objective: To study the efficacy and dose-responsiveness of intravenous buspirone for the prevention of PONV. Methods: A randomised, double-blind, placebo-controlled study was performed in adults at moderate to high PONV risk undergoing surgery with a general anaesthetic. Patients were randomised to receive an intravenous dose of buspirone (0.3, 1.0, 2.0, 3.0mg) or placebo at the end of surgery. The primary endpoint was the cumulative 24-h PONV incidence (i.e. any nausea and/or vomiting). Vomiting included retching. Nausea was defined as a score of ≥4 on an 11-point verbal rating scale running from zero (no nausea) to ten (the worst nausea imaginable). Results: A total of 257 patients received the study drug and fulfilled the criteria for inclusion in the primary efficacy and safety analyses. With placebo, the mean 24-h PONV incidence was 49.0% (90% confidence interval [CI] 37.5-60.5%). With buspirone, that incidence ranged from a mean of 40.8% (29.3-52.4%) in the 1mg arm to 58.0% (46.5-69.5%) in the 0.3mg arm (P > 0.05 for all comparisons). There was no difference between placebo and buspirone at any dose for any other efficacy endpoint, nor in the number or severity of adverse events or any other safety measures. Conclusion: We were unable to show that intravenous single-dose buspirone, at the tested dose-range, was effective at preventing PONV in surgical adult patients. The present study emphasises the difficulty in extrapolating from animal models of emesis to clinical efficacy in PON

More insight into the fate of biomedical meeting abstracts: a systematic review

BACKGROUND: It has been estimated that about 45% of abstracts that are accepted for presentation at biomedical meetings will subsequently be published in full. The acceptance of abstracts at meetings and their fate after initial rejection are less well understood. We set out to estimate the proportion of abstracts submitted to meetings that are eventually published as full reports, and to explore factors that are associated with meeting acceptance and successful publication. METHODS: Studies analysing acceptance of abstracts at biomedical meetings or their subsequent full publication were searched in MEDLINE, OLDMEDLINE, EMBASE, Cochrane Library, CINAHL, BIOSIS, Science Citation Index Expanded, and by hand searching of bibliographies and proceedings. We estimated rates of abstract acceptance and of subsequent full publication, and identified abstract and meeting characteristics associated with acceptance and publication, using logistic regression analysis, survival-type analysis, and meta-analysis. RESULTS: Analysed meetings were held between 1957 and 1999. Of 14945 abstracts that were submitted to 43 meetings, 46% were accepted. The rate of full publication was studied with 19123 abstracts that were presented at 234 meetings. Using survival-type analysis, we estimated that 27% were published after two, 41% after four, and 44% after six years. Of 2412 abstracts that were rejected at 24 meetings, 27% were published despite rejection. Factors associated with both abstract acceptance and subsequent publication were basic science and positive study outcome. Large meetings and those held outside the US were more likely to accept abstracts. Abstracts were more likely to be published subsequently if presented either orally, at small meetings, or at a US meeting. Abstract acceptance itself was strongly associated with full publication. CONCLUSIONS: About one third of abstracts submitted to biomedical meetings were published as full reports. Acceptance at meetings and publication were associated with specific characteristics of abstracts and meetings