Susan Ross

Cancer risk with tumor necrosis factor alpha (TNF) inhibitors: Meta-analysis of randomized controlled trials of adalimumab, etanercept, and infliximab using patient level data

Uncertain short‐ and long‐term cancer risks with anti‐TNF therapies is a concern, and led to a recent black box warning. This meta‐analysis, requested by the European Medicines Agency, aimed at better assessing short‐term risks by using meta‐analytic techniques based on individual patient data from all corporate‐sponsored randomized controlled trials (RCTs) of adalimumab, etanercept, and infliximab.

Less-Tight versus Tight Control of Hypertension in Pregnancy

BACKGROUND The effects of less-tight versus tight control of hypertension on pregnancy complications are unclear. METHODS We performed an open, international, multicenter trial involving women at 14 weeks 0 days to 33 weeks 6 days of gestation who had nonproteinuric preexisting or gestational hypertension, office diastolic blood pressure of 90 to 105 mm Hg (or 85 to 105 mm Hg if the woman was taking antihypertensive medications), and a live fetus. Women were randomly assigned to less-tight control (target diastolic blood pressure, 100 mm Hg) or tight control (target diastolic blood pressure, 85 mm Hg). The composite primary outcome was pregnancy loss or high-level neonatal care for more than 48 hours during the first 28 postnatal days. The secondary outcome was serious maternal complications occurring up to 6 weeks post partum or until hospital discharge, whichever was later. RESULTS Included in the analysis were 987 women; 74.6% had preexisting hypertension. The primary-outcome rates were similar among 493 women assigned to less-tight control and 488 women assigned to tight control (31.4% and 30.7%, respectively; adjusted odds ratio, 1.02; 95% confidence interval [CI], 0.77 to 1.35), as were the rates of serious maternal complications (3.7% and 2.0%, respectively; adjusted odds ratio, 1.74; 95% CI, 0.79 to 3.84), despite a mean diastolic blood pressure that was higher in the less-tight-control group by 4.6 mm Hg (95% CI, 3.7 to 5.4). Severe hypertension (≥160/110 mm Hg) developed in 40.6% of the women in the less-tight-control group and 27.5% of the women in the tight-control group (P<0.001). CONCLUSIONS We found no significant between-group differences in the risk of pregnancy loss, high-level neonatal care, or overall maternal complications, although less-tight control was associated with a significantly higher frequency of severe maternal hypertension. (Funded by the Canadian Institutes of Health Research; CHIPS Current Controlled Trials number, ISRCTN71416914; ClinicalTrials.gov number, NCT01192412.).

A Randomized Trial of Planned Cesarean or Vaginal Delivery for Twin Pregnancy

BACKGROUND Twin birth is associated with a higher risk of adverse perinatal outcomes than singleton birth. It is unclear whether planned cesarean section results in a lower risk of adverse outcomes than planned vaginal delivery in twin pregnancy. METHODS We randomly assigned women between 32 weeks 0 days and 38 weeks 6 days of gestation with twin pregnancy and with the first twin in the cephalic presentation to planned cesarean section or planned vaginal delivery with cesarean only if indicated. Elective delivery was planned between 37 weeks 5 days and 38 weeks 6 days of gestation. The primary outcome was a composite of fetal or neonatal death or serious neonatal morbidity, with the fetus or infant as the unit of analysis for the statistical comparison. RESULTS A total of 1398 women (2795 fetuses) were randomly assigned to planned cesarean delivery and 1406 women (2812 fetuses) to planned vaginal delivery. The rate of cesarean delivery was 90.7% in the planned-cesarean-delivery group and 43.8% in the planned-vaginal-delivery group. Women in the planned-cesarean-delivery group delivered earlier than did those in the planned-vaginal-delivery group (mean number of days from randomization to delivery, 12.4 vs. 13.3; P=0.04). There was no significant difference in the composite primary outcome between the planned-cesarean-delivery group and the planned-vaginal-delivery group (2.2% and 1.9%, respectively; odds ratio with planned cesarean delivery, 1.16; 95% confidence interval, 0.77 to 1.74; P=0.49). CONCLUSIONS In twin pregnancy between 32 weeks 0 days and 38 weeks 6 days of gestation, with the first twin in the cephalic presentation, planned cesarean delivery did not significantly decrease or increase the risk of fetal or neonatal death or serious neonatal morbidity, as compared with planned vaginal delivery. (Funded by the Canadian Institutes of Health Research; ClinicalTrials.gov number, NCT00187369; Current Controlled Trials number, ISRCTN74420086.).

The effect of anemia treatment on selected health-related quality-of-life domains: a systematic review.

BACKGROUND Anemia is a reduction in the oxygen-carrying capacity of red blood cells that results in a variety of symptoms, including dyspnea, headaches, light-headedness, and fatigue. Although anemia has been associated with reduced health-related quality of life (HRQoL), its treatment has not yet been consistently shown to improve HRQoL. OBJECTIVE This systematic review of the literature was conducted to determine whether the treatment of anemia improves HRQoL domains, regardless of the type of underlying disease. METHODS Data for this review were drawn from the clinical trial databases from 2 previous systematic literature reviews of erythropoiesis-stimulating protein treatment for renal insufficiency- and cancer-related anemia, both spanning the period January 1, 1980, through December 31, 2001. MEDLINE, Cancerlit, and Current Contents/Clinical Medicine were searched using the combined terms erythropoietin, kidney failure, neoplasms, and anemia. The reference lists of all identified articles were searched manually for additional relevant papers. The review included prospective studies that reported both HRQoL and hematocrit (Hct) in patients with cancer or renal insufficiency who received treatment for anemia with an erythropoiesis-stimulating protein. HRQoL was categorized by domain (overall, energy/fatigue, physical, activity); changes in HRQoL domains were expressed as effect sizes and meta-analyzed, as were correlation coefficients. The effects on HRQoL of dropout rate, study duration, baseline Hct, and change in Hct were examined in meta-regression analyses. RESULTS Sixteen studies each were identified in patients with renal insufficiency (N = 2253) and patients with cancer (N = 10,695). The treated groups included 11,710 patients, and the control groups included 1238 patients. The baseline Hct in all treated groups averaged 26.0%: 28.3% in the group with cancer and 24.4% in the group with renal insufficiency. The mean improvement in Hct from baseline to the end of treatment was 8.3% (range, 1.0%-16.5%) in treated patients and 1.0% (range, 0.0%-3.3%) in controls. The Hct changes were similar in treated patients with cancer and treated patients with renal insufficiency, as was the HRQoL effect size (0.43). Dropout rate and study duration were not significant predictors of HRQoL changes, but change in Hct was a significant predictor in both conditions. Meta-analysis of the correlation coefficients, adjusting for HRQoL domains, showed a consistent and significant positive correlation between change in Hct and change in HRQoL (P < 0.001). CONCLUSION The consistency in both direction and magnitude of effect across many studies and thousands of patients supports the hypothesis that treatment of anemia with erythropoiesis-stimulating protein improves selected HRQoL domains in patients with renal insufficiency- or cancer-related anemia.

Omeprazole plus antibiotics in the eradication of Helicobacter pylori infection: a meta-regression analysis of randomized, controlled trials.

This article presents a meta-regression analysis of published studies of omeprazole plus antibiotics (amoxicillin, clarithromycin, or an imidazole derivative) in the treatment of Helicobacter pylori. Eligible studies were all randomized, controlled trials published through April 1996 with 10 or more patients receiving omeprazole plus antibiotics for 5 or more days and testing for H. pylori eradication 4 weeks or more after treatment. Probability of eradication was calculated for each treatment arm, and logistic regression was performed using study characteristics as covariates. Seventy-four studies involving 117 treatment arms with 4,769 patients were identified. The eradication rate was 76% for omeprazole plus clarithromycin and 65% for omeprazole plus amoxicillin dual regimens (P <.0001). Eradication rates for triple regimens were 82%, omeprazole plus amoxicillin plus clarithromycin; 83%, omeprazole plus amoxicillin plus imidazole; and 89%, omeprazole plus clarithromycin plus imidazole. In a multiple logistic regression analysis, significant factors were antibiotic, disease, omeprazole dose, and whether treatment was followed by maintenance omeprazole. A systematic overview of the best available evidence suggests that dual therapy with omeprazole plus clarithromycin is superior to omeprazole plus amoxicillin. Triple therapy is better than dual therapy. Treatment works better on ulcers than on nonulcer dyspepsia. Higher doses of omeprazole give better results. Additional trials exploring higher omeprazole doses for varying durations as well as cost, side effects, and compliance trade-offs with efficacy are recommended.

Factors associated with adverse perinatal outcome in the Term Breech Trial

BACKGROUND In the Term Breech Trial, the risk of adverse perinatal outcome was lower with planned cesarean section versus planned vaginal birth. We undertook secondary analyses to determine factors associated with adverse perinatal outcome. STUDY DESIGN By using multiple logistic regression analyses, we determined the effect of prelabor cesarean section, cesarean section during early labor, cesarean section during active labor versus vaginal birth, and other factors, on adverse perinatal outcome. For 1384 fetuses delivered after labor, we determined the effect of variables associated with labor on adverse perinatal outcome. RESULTS The risk of adverse perinatal outcome was lowest with prelabor cesarean section (odds ratio [OR]=0.13) and highest with vaginal birth. For those delivered after labor, labor augmentation (P=.007), birth weight less than 2.8 kg (P=.003), and longer time between pushing and delivery (P<.001) increased the risk, whereas the presence of an experienced clinician at delivery (P=.004) reduced the risk of adverse perinatal outcome. CONCLUSION Breech infants at term are best delivered by prelabor cesarean section.

Effectiveness of cervical cerclage for a sonographically shortened cervix: A systematic review and meta-analysis

OBJECTIVE The purpose of this study was to determine the effectiveness of cerclage for a shortened cervix on transvaginal ultrasound scanning in terms of the rates of preterm delivery and adverse neonatal and maternal outcomes. STUDY DESIGN Pre-MEDLINE and MEDLINE, EMBASE, and the Cochrane Library were searched for human studies that compared cerclage placement to no cerclage on the basis of transvaginal ultrasound findings of a short cervix (< or =2.5 cm). Two authors independently determined eligibility and abstracted data. Meta-analyses were conducted when possible. RESULTS Thirty-five studies were reviewed; 6 studies were eligible and were included in the analysis. There was no statistically significant effect of cerclage on the rates of preterm delivery (<37, <34, <32, and <28 weeks of gestation), preterm labor, neonatal mortality or morbidity, gestational age at delivery, or time to delivery. Birth weight was significantly higher with than without cerclage (P=.004). CONCLUSION The available evidence does not support cerclage for a sonographically detected short cervix. A randomized controlled trial is needed to determine whether this intervention will reduce adverse neonatal outcomes.

Effect of antenatal corticosteroids on fetal growth and gestational age at birth

OBJECTIVE: To estimate the effect of multiple courses of antenatal corticosteroids on neonatal size, controlling for gestational age at birth and other confounders, and to determine whether there was a dose–response relationship between number of courses of antenatal corticosteroids and neonatal size. METHODS: This is a secondary analysis of the Multiple Courses of Antenatal Corticosteroids for Preterm Birth Study, a double-blind randomized controlled trial of single compared with multiple courses of antenatal corticosteroids in women at risk for preterm birth and in which fetuses administered multiple courses of antenatal corticosteroids weighed less, were shorter, and had smaller head circumferences at birth. All women (n=1,858) and children (n=2,304) enrolled in the Multiple Courses of Antenatal Corticosteroids for Preterm Birth Study were included in the current analysis. Multiple linear regression analyses were undertaken. RESULTS: Compared with placebo, neonates in the antenatal corticosteroids group were born earlier (estimated difference and confidence interval [CI]: −0.428 weeks, CI −0.10264 to −0.75336; P=.01). Controlling for gestational age at birth and confounding factors, multiple courses of antenatal corticosteroids were associated with a decrease in birth weight (−33.50 g, CI −66.27120 to −0.72880; P=.045), length (−0.339 cm, CI −0.6212 to −0.05676]; P=.019), and head circumference (−0.296 cm, −0.45672 to −0.13528; P<.001). For each additional course of antenatal corticosteroids, there was a trend toward an incremental decrease in birth weight, length, and head circumference. CONCLUSION: Fetuses exposed to multiple courses of antenatal corticosteroids were smaller at birth. The reduction in size was partially attributed to being born at an earlier gestational age but also was attributed to decreased fetal growth. Finally, a dose–response relationship exists between the number of corticosteroid courses and a decrease in fetal growth. The long-term effect of these findings is unknown. CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov, www.clinicaltrials.gov, NCT00187382. LEVEL OF EVIDENCE: II

Planned caesarean section decreases the risk of adverse perinatal outcome due to both labour and delivery complications in the Term Breech Trial

Objective  To determine if the decreased risk of adverse perinatal outcome, with a policy of planned caesarean, in the Term Breech Trial, was due to a reduction of problems of labour, problems of delivery or unrelated problems.

Meta-analysis to assess the efficacy of interferon-α in patients with follicular non-Hodgkin's lymphoma

The authors wanted to determine whether adding interferon-&agr; (IFN-&agr;) to chemotherapy regimens, in either induction or maintenance settings, provides additional survival benefits in follicular non-Hodgkins lymphoma (NHL). A meta-analysis was performed based on published data from randomized controlled clinical trials involving nine separate study populations. Patients receiving IFN-&agr; (in either induction or maintenance therapy) had significantly increased 5-year and progression-free survival rates at 3 and 5 years compared with concurrent controls. The advantages of IFN-&agr; therapy were most marked in studies using anthracycline-containing induction chemotherapy; in these studies, patients who received IFN-&agr; had approximately 20% increased progression-free survival rates compared with controls and a lesser survival advantage. The available literature did not allow a determination of the relative benefit of IFN-&agr; in induction or maintenance treatments for NHL or a determination of the optimum duration of IFN-&agr; treatment. Although questions remain about its optimal use, IFN-&agr; appears to prolong survival time in patients with follicular NHL.