Cost-Effectiveness of Human Papillomavirus Vaccination and Cervical Cancer Screening in Women Older Than 30 Years in the United States

What is the problem and what is known about it so far? Cervical cancer is cancer of the cervix (the lower part of the uterus or womb). Infection with human papillomavirus (HPV), a common sexually transmitted virus, is a cause of cervical cancer. People can get HPV from intimate sexual contact with a person already infected with HPV. Many sexually active women get infected with HPV, but the risk for cervical cancer in the United States is low. Papanicolaou (Pap) smears are used to screen for cervical cancer. Screening for cancer means looking for cancer before a person has symptoms. To perform a Pap smear, doctors use a swab during an internal examination of the vagina to take a sample of cells from the cervix to look at under a microscope. Having a Pap smear every 1 to 3 years helps prevent cervical cancer by finding it at early, treatable stages. It is also possible to test for HPV, and experts are trying to determine the best way to combine HPV and Pap tests in cervical cancer screening. Some doctors test women for HPV only if the Pap smear shows abnormal cells that are not clearly cancerous. Other doctors use both tests together for all women older than 30 years, because cervical cancer is very rare before age 30 years. A vaccine to prevent infection with HPV types 16 and 18, which are 2 types most commonly linked to cervical cancer, is recommended for girls and young women aged 11 to 26 years. However, many women have already been exposed to HPV by this age. Because the vaccine does not treat HPV, the value of the vaccine in older women is questionable. Still, the vaccine makers are trying to get the U.S. Food and Drug Administration to approve the vaccine for older women. Why did the researchers do this particular study? To see whether the costs of giving the HPV vaccine to women older than 30 years are likely to be worth the benefits. Who was studied? The researchers did not study actual patients. They used computer models to simulate what would happen to a hypothetical group of women in the United States, aged 35 to 45 years. How was the study done? The researchers used information from studies to estimate what the associated costs and health benefits would be if women aged 35 to 45 years received HPV vaccination in addition to screening with Pap smears and HPV testing. What did the researchers find? Adding HPV vaccination to regular cervical cancer screening for women 35 to 45 years of age costs well over $116,950 to $381,590 per quality-adjusted life-year saved. This amount is more than persons in the United States typically consider to be good value for health care. What were the limitations of the study? This study was conducted by using a computer model and was based on many assumptions that reflect the uncertainty in currently available information. What are the implications of the study? Women older than 30 years should continue to receive recommended cervical cancer screening with Pap smears and HPV testing. The benefits of HPV vaccination for this age group are small, and the value is less than what is commonly accepted for health care interventions in the United States.


Second-Stage Labor Duration in Nulliparous Women: Relationship to Maternal and Perinatal Outcomes
Objective: The purpose of this study was to assess maternal and perinatal outcomes as a function of second-stage labor duration. Study Design: We assessed outcomes in nulliparous laboring women who were enrolled in a trial of fetal pulse oximetry. Results: Of 5341 participants, 4126 women reached the second stage of labor. As the duration of the second stage increased, spontaneous vaginal delivery rates declined, from 85% when the duration was Ͻ1 hour to 9% when it was Ͼ or ϭ5 hours. Adverse maternal outcomes that were associated significantly with the duration of the second stage of labor included chorioamnionitis (overall rate, 3.9%), third-or fourth-degree perineal laceration (overall rate, 8.7%), and uterine atony (overall rate, 3.9%). Odds ratios for each additional hour of the second stage of labor ranged from 1.3-1.8. Among individual adverse neonatal outcomes, only admission to a neonatal intensive care unit was associated significantly with second stage duration (odds ratio, 1.4). Conclusion: The second stage of labor does not need to be terminated for duration alone.

Multicenter Randomized Trial of Cerclage for Preterm Birth Prevention in High-Risk Women With Shortened Midtrimester Cervical Length
Objective: The objective of the study was to assess cerclage to prevent recurrent preterm birth in women with short cervix. Study Design: Women with prior spontaneous preterm birth less than 34 weeks were screened for short cervix and randomly assigned to cerclage if cervical length was less than 25 mm. Results: Of 1014 women screened, 302 were randomized; 42% of women not assigned and 32% of those assigned to cerclage delivered less than 35 weeks (Pϭ.09). In planned analyses, birth less than 24 weeks (Pϭ.03) and perinatal mortality (Pϭ.046) were less frequent in the cerclage group. There was a significant interaction between cervical length and cerclage. Birth less than 35 weeks (Pϭ.006) was reduced in the less than 15 mm stratum with a null effect in the 15-24 mm stratum. Conclusion: In women with a prior spontaneous preterm birth less than 34 weeks and cervical length less than 25 mm, cerclage reduced previ-

Multilevel Predictors of Inconsistent Condom Use Among Adolescent Mothers
Objectives: We used Bronfenbrenner's ecological systems theory to identify factors that predicted never or sometimes using condoms in a multiethnic cohort of adolescent mothers.

Methods:
We interviewed adolescent mothers within 48 hours of delivery and surveyed them 6 and 12 months after delivery (nϭ636). We used multinomial logistic regression to identify individual-, dyad-, family-, and peer and community-level factors associated with never or sometimes using versus always using condoms during intercourse at 12 months postpartum.
Results: Pregnancy status, partner refusal to use condoms, intimate partner violence, and race/ethnicity predicted both never and sometimes using condoms. Condom use 6 months earlier and church attendance also predicted never using condoms, whereas maternal monitoring was an additional predictor for sometimes using condoms.

Conclusions:
Overlapping yet distinct risk profiles predicted never or sometimes using versus always using condoms. Factors from multiple levels of influence affected the condom use behaviors of adolescent mothers indicating that multilevel interventions are needed to promote safer sexual practices among these young women. Van

The Second Time Around: Reproductive Performance After Repetitive Versus Primary Surgery for Endometriosis
After repetitive surgery for recurrent endometriosis, 20 of 89 (22%) women achieved spontaneous pregnancy, compared with 165 of 411 (40%) after first-line procedure (adjusted incidence rate ratio, 0.51; 95% confidence interval, 0.32 to 0.82), and the 12-and 24-month cumulative pregnancy rates were 14% and 26% in the former group compared with 32% and 38% in the latter. Among infertile patients at baseline, 13 of 67 (19%) conceived after reoperation compared with 98 of 290 (34%) after primary surgery (adjusted incidence rate ratio, 0.55; 95% confidence interval, 0.30 to 0.99), and the 12-and 24-month cumulative pregnancy rates were 13% and 22% in the former group and 25% and 30% in the latter.

A Multicenter, Randomized Trial of Treatment for Mild Gestational Diabetes
Background: It is uncertain whether treatment of mild gestational diabetes mellitus improves pregnancy outcomes. Methods: Women who were in the 24th to 31st week of gestation and who met the criteria for mild gestational diabetes mellitus (i.e., an abnormal result on an oral glucose-tolerance test but a fasting glucose level below 95 mg per deciliter [5.3 mmol per liter]) were randomly assigned to usual prenatal care (control group) or dietary intervention, self-monitoring of blood glucose, and insulin therapy, if necessary (treatment group). The primary outcome was a composite of stillbirth or perinatal death and neonatal complications, including hyperbilirubinemia, hypoglycemia, hyperinsulinemia, and birth trauma. Results: A total of 958 women were randomly assigned to a study group-485 to the treatment group and 473 to the control group. We observed no significant difference between groups in the frequency of the composite outcome (32.4% and 37.0% in the treatment and control groups, respectively; Pϭ0.14). There were no perinatal deaths. However, there were significant reductions with treatment as compared with usual care in several prespecified secondary outcomes, including mean birth weight (3302 vs. 3408 g), neonatal fat mass (427 vs. 464 g), the frequency of large-for-gestational-age infants (7.1% vs. 14.5%), birth weight greater than 4000 g (5.9% vs. 14.3%), shoulder dystocia (1.5% vs. 4.0%), and cesarean delivery (26.9% vs. 33.8%). Treatment of gestational diabetes mellitus, as compared with usual care, was also associated with reduced rates of preeclampsia and gestational hypertension (combined rates for the two conditions, 8.6% vs. 13.6%; Pϭ0.01). Conclusions: Although treatment of mild gestational diabetes mellitus did not significantly reduce the frequency of a composite outcome that included stillbirth or perinatal death and several neonatal complications, it did reduce the risks of fetal overgrowth, shoulder dystocia, cesarean delivery, and hypertensive disorders.

Moderate Hypothermia to Treat Perinatal Asphyxial Encephalopathy
Background: Whether hypothermic therapy improves neurodevelopmental outcomes in newborn infants with asphyxial encephalopathy is uncertain. Methods: We performed a randomized trial of infants who were less than 6 hours of age and had a gestational age of at least 36 weeks and perinatal asphyxial encephalopathy. We compared intensive care plus cooling of the body to 33.5 degrees C for 72 hours and intensive care alone. The primary outcome was death or severe disability at 18 months of age. Prespecified secondary outcomes

Timely Follow-up of Abnormal Diagnostic Imaging Test Results in an Outpatient Setting: Are Electronic Medical Records Achieving Their Potential?
Background: Given the fragmentation of outpatient care, timely follow-up of abnormal diagnostic imaging results remains a challenge. We hypothesized that an electronic medical record (EMR) that facilitates the transmission and availability of critical imaging results through either automated notification (alerting) or direct access to the primary report would eliminate this problem. Methods: We studied critical imaging alert notifications in the outpatient setting of a tertiary care Department of Veterans Affairs facility from November 2007 to June 2008. Tracking software determined whether the alert was acknowledged (ie, health care practitioner/provider [HCP] opened the message for viewing) within 2 weeks of transmission; acknowledged alerts were considered read. We reviewed medical records and contacted HCPs to determine timely follow-up actions (eg, ordering a follow-up test or consultation) within 4 weeks of transmission. Multivariable logistic regression models accounting for clustering effect by HCPs analyzed predictors for 2 outcomes: lack of acknowledgment and lack of timely follow-up. Results: Of 123 638 studies (including radiographs, computed tomographic scans, ultrasonograms, magnetic resonance images, and mammograms), 1196 images (0.97%) generated alerts; 217 (18.1%) of these were unacknowledged. Alerts had a higher risk of being unacknowledged when the ordering HCPs were trainees (odds ratio [OR], 5.58; 95% confidence interval [CI], 2.86 -10.89) and when dual-alert (Ͼ1 HCP alerted) as opposed to single-alert communication was used (OR, 2.02; 95% CI, 1.22-3.36). Timely follow-up was lacking in 92 (7.7% of all alerts) and was similar for acknowledged and unacknowledged alerts (7.3% vs 9.7%; Pϭ.22). Risk for lack of timely follow-up was higher with dual-alert communication (OR, 1.99; 95% CI, 1.06 -3.48) but lower when additional verbal communication was used by the radiologist (OR, 0.12; 95% CI, 0.04 -0.38). Nearly all abnormal results lacking timely follow-up at 4 weeks were eventually found to have measurable clinical impact in terms of further diagnostic testing or treatment. Conclusions: Critical imaging results may not receive timely follow-up actions even when HCPs receive and read results in an advanced, integrated electronic medical record system. A multidisciplinary approach is needed to improve patient safety in this area.

A Randomized Study on the Effect of Weight Loss on Obstructive Sleep Apnea Among Obese Patients With Type 2 Diabetes: The Sleep AHEAD Study
Background: The belief that weight loss improves obstructive sleep apnea (OSA) has limited empirical support. The purpose of this 4-center study was to assess the effects of weight loss on OSA over a 1-year period.

Methods:
The study included 264 participants with type 2 diabetes and a mean (SD) age of 61.2 (6.5) years, weight of 102.4 (18.3) kg, body mass index (BMI) (calculated as weight in kilograms divided by height in meters squared) of 36.7 (5.7), and an apneahypopnea index (AHI) of 23.2 (16.5) events per hour. The participants were randomly assigned to either a behavioral weight loss program developed specifically for obese patients with type 2 diabetes (intensive lifestyle intervention [ILI]) or 3 group sessions related to effective diabetes management (diabetes support and education [DSE]).

Results:
The ILI participants lost more weight at 1 year than did DSE participants (10.8 kg vs 0.6 kg; PϽ.001).
Relative to the DSE group, the ILI intervention was associated with an adjusted (SE) decrease in AHI of 9.7 (2.0) events per hour (PϽ.001). At 1 year, more than 3 times as many participants in the ILI group than in the DSE group had total remission of their OSA, and the prevalence of severe OSA among ILI participants was half that of the DSE group. Initial AHI and weight loss were the strongest predictors of changes in AHI at 1 year (PϽ.01). Participants with a weight loss of 10 kg or more had the greatest reductions in AHI. Conclusions: Physicians and their patients can expect that weight loss will result in significant and clinically relevant improvements in OSA among obese patients with type 2 diabetes. Trial Registration clinicaltrials.gov Identifier: NCT00194259.

Comparative Efficacy of Inactivated and Live Attenuated Influenza Vaccines
Background: The efficacy of influenza vaccines may vary from year to year, depending on a variety of factors, and may differ for inactivated and live attenuated vaccines.

Methods:
We carried out a randomized, double-blind, placebo-controlled trial of licensed inactivated and live attenuated influenza vaccines in healthy adults during the 2007-2008 influenza season and estimated the absolute and relative efficacies of the two vaccines.
Results: A total of 1952 subjects were enrolled and received study vaccines in the fall of 2007. Influenza activity occurred from January through April 2008, with the circulation of influenza types A (H3N2) (about 90%) and B (about 9%). Absolute efficacy against both types of influenza, as measured by isolating the virus in culture, identifying it on real-time polymerasechain-reaction assay, or both, was 68% (95% confidence interval [CI], 46 to 81) for the inactivated vaccine and 36% (95% CI, 0 to 59) for the live attenuated vaccine. In terms of relative efficacy, there was a 50% (95% CI, 20 to 69) reduction in laboratory-confirmed influenza among subjects who received inactivated vaccine as compared with those given live attenuated vaccine. The absolute efficacy against the influenza A virus was 72% (95% CI, 49 to 84) for the inactivated vaccine and 29% (95% CI, -14 to 55) for the live attenuated vaccine, with a relative efficacy of 60% (95% CI, 33 to 77) for the inactivated vaccine. Conclusions: In the 2007-2008 season, the inactivated vaccine was efficacious in preventing laboratory-confirmed symptomatic influenza A (predominately H3N2) in healthy adults. The live attenuated vaccine also prevented influenza illnesses but was less efficacious. NCT00538512.) 2009 Massachusetts Medical Society