Tests for 2 x 2 Tables in Clinical Trials

Five standard tests are compared: chi-squared, Fisher\u27s exact, Yates’ correction, Fisher’s exact mid-p, and Barnard’s. Yates’ is always inferior to Fisher’s exact. Fisher’s exact is so conservative that one should look for alternatives. For certain sample sizes, Fisher’s mid-p or Barnard’s test maintain the nominal alpha and have superior power

Use of implantable cardioverter-defibrillators for primary prevention in older patients: A systematic literature review and meta-analysis

Background: Randomized clinical trials (RCTs) have demonstrated the efficacy of implantable cardioverter-defibrillators (ICDs) in reducing sudden cardiac death (SCD) in specific patient populations. However, patients ≥ 65 years were under-represented in these trials and the overall benefit of ICDs may be diminished in older patients due to competing risks for death. We evaluate the published data on ICD efficacy at reducing all-cause mortality in patients ≥ 65 years and in patients ≥ 75 years. Methods: We searched MEDLINE to identify RCTs and observational studies of ICDs that provided age-based outcome data for primary prevention of SCD. The primary endpoint was mortality evaluated by a meta-analysis of the RCTs using a random-effects model. Secondary endpoints included operative mortality, long-term complications and quality of life. Results: The enrollment of patients ≥ 65 years in RCTs was limited (range: 33% in DEFINITE to 56% in MUSTT). Combining data from four RCTs (n = 3,562) revealed that primary prevention ICD therapy is efficacious in reducing all-cause mortality in patients ≥ 65 years (HR 0.66; 95% CI 0.50–0.87; test of heterogeneity: X2 = 5.26; p = 0.15). For patients ≥ 75 years, combining data from four RCTs (n = 579) revealed that primary prevention ICD therapy remains efficacious in reducing all-cause mortality (HR 0.73; 95% CI 0.51–0.974; p = 0.03). There appears to be no difference in ICD-related, operative, in-hospital, or long- -term complications among older patients compared to younger patients, although it remains unclear if older patients have a better quality of life with an ICD than younger patients. Conclusions: Although the overall evidence regarding ICD efficacy in patients ≥ 65 years is limited and divergent, and the evidence available for patients ≥ 75 years is even more sparse, our meta-analysis suggests that primary prevention ICDs may be beneficial in older patients. Our findings need to be validated by future studies, particularly ones examining ICD complications and quality of life. (Cardiol J 2011; 18, 5: 503–514

Transforming Verbal Counts in Reports of Qualitative Descriptive Studies Into Numbers

Reports of qualitative studies typically do not offer much information on the numbers of respondents linked to any one finding. This information may be especially useful in reports of basic, or minimally interpretive, qualitative descriptive studies focused on surveying a range of experiences in a target domain, and its lack may limit the ability to synthesize the results of such studies with quantitative results in systematic reviews. Accordingly, the authors illustrate strategies for deriving plausible ranges of respondents expressing a finding in a set of reports of basic qualitative descriptive studies on antiretroviral adherence and suggest how the results might be used. These strategies have limitations and are never appropriate for use with findings from interpretive qualitative studies. Yet they offer a temporary workaround for preserving and maximizing the value of information from basic qualitative descriptive studies for systematic reviews. They show also why quantitizing is never simply quantitative

Zastosowanie wszczepialnych kardiowerterów- -defibrylatorów w profilaktyce pierwotnej u pacjentów w podeszłym wieku. Systematyczny przegląd piśmiennictwa i metaanaliza

Wstęp: W randomizowanych badaniach klinicznych (RCT) wykazano skuteczność zastosowania wszczepialnych kardiowerterów-defibrylatorów (ICD) w zapobieganiu nagłym zgonom sercowym (SCD) w określonych grupach chorych. Jednak w badaniach tych oceniano niewielkie grupy chorych ≥ 65. roku życia, a całkowite korzyści z wszczepienia ICD wśród starszych pacjentów mogą być ograniczone ze względu na zwiększone ryzyko zgonu. Na podstawie aktualnego piśmiennictwa oceniono, na ile wszczepienie ICD zmniejsza ryzyko zgonu z jakiejkolwiek przyczyny u pacjentów ≥ 65. roku życia oraz w wieku ≥ 75 lat. Metody: Danych z RCT oraz badań obserwacyjnych oceniających profilaktykę pierwotną SCD, w zależności od wieku, poszukiwano w bazie MEDLINE. Za pierwszorzędowy punkt końcowy przyjęto śmiertelność ocenianą w metaanalizach lub RCT z zastosowaniem modelu ″random-effects″. Za drugorzędowe punkty końcowe przyjęto śmiertelność związaną z zabiegiem operacyjnym, powikłania odległe oraz jakość życia (QoL). Wyniki: Do RCT nie włączano zbyt licznych grup pacjentów ≥ 65. roku życia (od 33% badanej populacji w badaniu DEFINITE do 56% w badaniu MUSTT). Na podstawie zsumowanych danych z 4 RCT (n = 3562) wykazano, że wszczepienie ICD w profilaktyce pierwotnej skutecznie zapobiega śmiertelności całkowitej u chorych w wieku ≥ 65 lat [współczynnik hazardu (HR): 0,66; 95% przedział ufności (CI): 0,50–0,87; test niejednorodności X2 = 5,26; p = 0,15). U pacjentów ≥ 75. roku życia zsumowane dane z 4 badań RCT (n = 579) również potwierdziły skuteczność ICD w profilaktyce pierwotnej w zapobieganiu śmiertelności całkowitej (HR: 0,73; 95% CI: 0,51–0,974; p = 0,03). Wydaje się, że powikłania związane z ICD, z zabiegiem operacyjnym, wewnątrzszpitalne oraz odległe nie różnią się istotnie w grupach pacjentów w podeszłym wieku w porównaniu z młodszymi chorymi, jednak pozostaje niejasne, czy u starszych osób wszczepienie ICD poprawia jakość życia bardziej niż u młodszych chorych. Wnioski: Choć dane dotyczące skuteczności ICD u pacjentów ≥65. roku życia są ograniczone i rozbieżne, a dostępne informacje na temat chorych w wieku ≥ 75 lat — jeszcze bardziej niepełne, wyniki niniejszej metaanalizy sugerują, że pacjenci w podeszłym wieku mogą odnieść korzyści z wszczepienia ICD w ramach profilaktyki pierwotnej. Rezultaty autorów metaanalizy powinny zostać zweryfikowane w kolejnych badaniach, zwłaszcza oceniających powikłania związane z ICD oraz jakość życia

Troponin T and quantitative ST-segment depression offer complementary prognostic information in the risk stratification of acute coronary syndrome patients

OBJECTIVES Our primary objective was to examine the prognostic relationship between baseline quantitative ST-segment depression (ST ↓) and cardiac troponin T (cTnT) elevation. The secondary objectives were to: 1) examine whether ST ↓ provided additional insight into therapeutic efficacy of glycoprotein IIb/IIIa therapy similar to that demonstrated by cTnT and 2) explore whether the time to evaluation impacted on each marker's relative prognostic utility. BACKGROUND The relationship between the baseline electrocardiogram (ECG) and cTnT measurements in risk-stratifying patients presenting with acute coronary syndromes (ACS) has not been evaluated comprehensively. METHODS The study population consisted of 959 patients enrolled in the cTnT substudy of the Platelet IIb/IIIa Antagonism for the Reduction of Acute coronary syndrome events in a Global Organization Network (PARAGON)-B trial. Patients were classified as having no ST ↓ (n = 387), 1 mm ST ↓ (n = 433), and ST ↓ ≥2 mm (n = 139). Forty-percent (n = 381) were classified as cTnT-positive based on a definition of ≥0.1 ng/ml. RESULTS Six-month death/(re)myocardial infarction rates were 8.4% among cTnT-negative patients with no ST ↓ and 26.18% among cTnT-positive patients with ST ↓ ≥2 mm. On ECGs done after 6 h of symptom onset, ST ↓ ≥2 mm was associated with higher risk compared to its presence on ECGs done earlier (odds ratio [OR] 7.3 vs. 2.1). In contrast, the presence of elevated cTnT within 6 h of symptom was associated with a higher risk of adverse events compared with elevations after 6 h (OR 2.4 vs. 1.5). CONCLUSIONS Quantitative ST ↓ and cTnT status are complementary in assessing risk among ACS patients and both should be employed to determine prognosis and assist in medical decision making

Relation between dose of loop diuretics and outcomes in a heart failure population: Results of the ESCAPE Trial

We examined the relation of maximal in-hospital diuretic dose to weight loss, changes in renal function, and mortality in hospitalised heart failure (HF) patients

Perioperative Bridging Anticoagulation in Patients with Atrial Fibrillation

BACKGROUND: It is uncertain whether bridging anticoagulation is necessary for patients with atrial fibrillation who need an interruption in warfarin treatment for an elective operation or other elective invasive procedure. We hypothesized that forgoing bridging anticoagulation would be noninferior to bridging with low-molecular-weight heparin for the prevention of perioperative arterial thromboembolism and would be superior to bridging with respect to major bleeding. METHODS: We performed a randomized, double-blind, placebo-controlled trial in which, after perioperative interruption of warfarin therapy, patients were randomly assigned to receive bridging anticoagulation therapy with low-molecular-weight heparin (100 IU of dalteparin per kilogram of body weight) or matching placebo administered subcutaneously twice daily, from 3 days before the procedure until 24 hours before the procedure and then for 5 to 10 days after the procedure. Warfarin treatment was stopped 5 days before the procedure and was resumed within 24 hours after the procedure. Follow-up of patients continued for 30 days after the procedure. The primary outcomes were arterial thromboembolism (stroke, systemic embolism, or transient ischemic attack) and major bleeding. RESULTS: In total, 1884 patients were enrolled, with 950 assigned to receive no bridging therapy and 934 assigned to receive bridging therapy. The incidence of arterial thromboembolism was 0.4% in the no-bridging group and 0.3% in the bridging group (risk difference, 0.1 percentage points; 95% confidence interval [CI], -0.6 to 0.8; P=0.01 for noninferiority). The incidence of major bleeding was 1.3% in the no-bridging group and 3.2% in the bridging group (relative risk, 0.41; 95% CI, 0.20 to 0.78; P=0.005 for superiority). CONCLUSIONS: In patients with atrial fibrillation who had warfarin treatment interrupted for an elective operation or other elective invasive procedure, forgoing bridging anticoagulation was noninferior to perioperative bridging with low-molecular-weight heparin for the prevention of arterial thromboembolism and decreased the risk of major bleeding. (Funded by the National Heart, Lung, and Blood Institute of the National Institutes of Health; BRIDGE ClinicalTrials.gov number, NCT00786474.)