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COMMENTARY: Organizational Improvements to Enhance Modern Clinical Epidemiology


COMMENTARY: The Importance of Biodiversity to Medicine


CLINICAL REVIEW: Pregnancy and Fertility Following Bariatric Surgery: A Systematic Review

Context  Use of bariatric surgery has increased dramatically during the past 10 years, particularly among women of reproductive age.

Objectives  To estimate bariatric surgery rates among women aged 18 to 45 years and to assess the published literature on pregnancy outcomes and fertility after surgery.

Evidence Acquisition  Search of the Nationwide Inpatient Sample (1998-2005) and multiple electronic databases (Medline, EMBASE, Controlled Clinical Trials Register Database, and the Cochrane Database of Reviews of Effectiveness) to identify articles published between 1985 and February 2008 on bariatric surgery among women of reproductive age. Search terms included bariatric procedures, fertility, contraception, pregnancy, and nutritional deficiencies. Information was abstracted about study design, fertility, and nutritional, neonatal, and pregnancy outcomes after surgery.

Evidence Synthesis  Of 260 screened articles, 75 were included. Women aged 18 to 45 years accounted for 49% of all patients undergoing bariatric surgery (>50 000 cases annually for the 3 most recent years). Three matched cohort studies showed lower maternal complication rates after bariatric surgery than in obese women without bariatric surgery, or rates approaching those of nonobese controls. In 1 matched cohort study that compared maternal complication rates in women after laparoscopic adjustable gastric band surgery with obese women without surgery, rates of gestational diabetes (0% vs 22.1%, P < .05) and preeclampsia (0% vs 3.1%, P < .05) were lower in the bariatric surgery group. Findings were supported by 13 other bariatric cohort studies. Neonatal outcomes were similar or better after surgery compared with obese women without laparoscopic adjustable gastric band surgery (7.7% vs 7.1% for premature delivery; 7.7% vs 10.6% for low birth weight, P < .05; 7.7% vs 14.6% for macrosomia, P < .05). No differences in neonatal outcomes were found after gastric bypass compared with nonobese controls (26.3%-26.9% vs 22.4%-20.2% for premature delivery, P = not reported [1 study] and = .43 [1 study]; 7.7% vs 9.0% for low birth weight, P = not reported [1 study]; and 0% vs 2.6%-4.3% for macrosomia, P = not reported [1 study and P = .28 [1 study]). Findings were supported by 10 other studies. Studies regarding nutrition, fertility, cesarean delivery, and contraception were limited.

Conclusion  Rates of many adverse maternal and neonatal outcomes may be lower in women who become pregnant after having had bariatric surgery compared with rates in pregnant women who are obese; however, further data are needed from rigorously designed studies.



REVIEW: Risk of Venous Thromboembolism With the Angiogenesis Inhibitor Bevacizumab in Cancer Patients: A Meta-analysis

Context  Venous thromboembolism is one of the leading causes of morbidity and mortality in patients with cancer. Concerns have arisen regarding the risk of venous thromboembolism with the novel antiangiogenic agent bevacizumab, a recombinant humanized monoclonal antibody to vascular endothelial growth factor that is widely used in cancer treatment. Currently, the role of bevacizumab in venous thromboembolism is controversial.

Objective  To assess the overall risk of venous thromboembolism associated with the use of bevacizumab, a systematic review and meta-analysis of published randomized controlled trials was performed.

Data Sources  The databases of PubMed and Web of Science were searched for articles published in the English language from January 1966 until January 2008 and abstracts presented at American Society of Clinical Oncology conferences held between January 2000 and January 2008 were searched to identify relevant clinical trials.

Study Selection and Data Extraction  Eligible studies included prospective randomized controlled trials in which standard antineoplastic therapy was used with and without bevacizumab and data on venous thromboembolism were available. Summary incidence rates, relative risks (RRs), and 95% confidence intervals (CIs) were calculated using random-effects or fixed-effects models based on the heterogeneity of included studies.

Data Synthesis  A total of 7956 patients with a variety of advanced solid tumors from 15 randomized controlled trials were identified and included for analysis. Among those patients receiving bevacizumab, the summary incidences of all-grade and high-grade venous thromboembolism were 11.9% (95% CI, 6.8%-19.9%) and 6.3% (95% CI, 4.8%-8.3%), respectively. Patients treated with bevacizumab had a significantly increased risk of venous thromboembolism with an RR of 1.33 (95% CI, 1.13-1.56; P < .001) compared with controls. The risk was significantly increased for both all-grade and high-grade venous thromboembolism. In addition, the risk was similarly increased for bevacizumab at 2.5 mg/kg per week (low dose; RR, 1.31 [95% CI, 1.08-1.60]; P = .007) and 5 mg/kg per week (high dose; RR, 1.31 [95% CI, 1.02-1.68]; P = .04).

Conclusion  The use of bevacizumab was significantly associated with an increased risk of developing venous thromboembolism in cancer patients receiving this drug.



ORIGINAL CONTRIBUTION: Genetic Alterations Associated With Cryptorchidism

Context  Cryptorchidism is the most frequent congenital birth defect in male children and represents an important risk factor for infertility and testicular cancer. Major regulators of testicular descent are the hormones insulin-like factor 3 (INSL3) and testosterone, and disruption of these pathways might cause cryptorchidism.

Objective  To determine the frequency of genetic alterations in cryptorchidism.

Design and Setting  Case-control study in 2 departments of pediatric surgery in Italy between January 2003 and March 2005.

Patients  Six hundred male infants with cryptorchidism. Boys were followed up for 2 to 3 years (through January 2008) and orchidopexy was performed in those who were persistently cryptorchid. We analyzed 300 noncryptorchid male children aged 1 to 4 years as controls.

Main Outcome Measures  Karyotype anomalies and INSL3, INSL3 receptor, and androgen receptor gene mutations.

Results  The frequency of genetic alterations in boys with cryptorchidism was low (17/600 [2.8%; 95% confidence interval {CI}, 1.7%-4.5%]) and was significantly higher in participants with persistent cryptorchidism (16/303 [5.3%; 95% CI, 3.0%-8.4%]; P = .001) and those with bilateral cryptorchidism (10/120 [8.3%; 95% CI, 4.1%-14.8%]; P = .001) than in controls (1/300 [0.3%; 95% CI, 0.1%-0.8%]). Boys with persistent cryptorchidism had a 17-fold greater odds of having a genetic alteration (odds ratio, 16.7; 95% CI, 2.2-126.5). The most common genetic findings in those with cryptorchidism were 8 cases of Klinefelter syndrome and 5 cases of mutations in the INSL3 receptor gene. Genetic alterations were not found in boys with low birth weight or low gestational age, who had frequent spontaneous descent of the testes.

Conclusion  In a small percentage of the study population, there was a statistically significant association between bilateral and persistent cryptorchidism and genetic alterations, including Klinefelter syndrome and INSL3 receptor gene mutations.


 
 


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