Comparative Effectiveness Study to Assess Immediate versus Conditional Antibiotic Treatment for Urinary Tract Infection in Women

Abstract

“A comparative effectiveness design has been specifically chosen so that the effectiveness of the two treatment strategies can be directly compared, rather than the pure drug efficacy.”

A planned comparative effectiveness study, outlined in BMC Infectious Disease, is looking to see if ibuprofen can reduce the use of antibiotics in sufferers of urinary tract infection (UTI). Primary care guidelines recommend that uncomplicated urinary tract infections are treated with antibiotics. Although antibiotics are effective in the clinical care of individuals, their ongoing use is leading to increased resistance rates in the population. This study is looking to combat this issue by investigating a combinational treatment method that could reduce the dose of antibiotics required in patients.

This study is a randomized-controlled, double-blind, double-dummy, multicenter trial that assesses the comparative effectiveness of immediate versus conditional antibiotic therapy in uncomplicated UTI. A comparative effectiveness design has been specifically chosen so that the effectiveness of the two treatment strategies can be directly compared, rather than the pure drug efficacy.

Women between the ages of 18 and 65 will be screened and enrolled from general practices who present with at least one of the typical symptoms of UTI: dysuria or frequency/urgency of micturition. The study investigators are aiming to enroll 494 patients from 45 general practices in Lower Saxony (Germany), over an 18-month recruitment period. The participants will be divided into two groups: one will receive immediate antibiotic therapy with fosfomycin trometamol 1 × 3 g (standard treatment); the second group will receive initial symptomatic treatment with ibuprofen 3 × 400 mg for 3 days. The participants in the group receiving ibuprofen will only be provided with antibiotics if they require them. This will include situations where their symptoms persist or worsen.

The investigators have defined a combined primary end point by choosing the number of all antibiotic prescriptions regardless of the medical indication from day 0–28, and the disease burden as a weighed sum of the daily total symptom scores from day 0–7. In light of this, the researchers have highlighted two outcomes they want to prove to declare their findings positive: superiority of the conditional antibiotic treatment with regards to the first primary end point, and noninferiority of this treatment method with regards to the second primary end point.

– Written by Jonathan Wilkinson

Source: Gaynor I, Hummers-Prader E, Kochen M et al. Immediate versus conditional treatment of uncomplicated urinary tract infection – a randomized-controlled comparative effectiveness study in general practices. BMC Infect. Dis. 12, 146 (2012).

Herd immunity results in reduced human papillomavirus infections in nonvaccinated teenagers

Human papillomavirus (HPV) is the most common sexually transmitted agent in the world. There are approximately 130 HPV types and, of those, HPV 16 and 18 are associated with high oncogenic risk and are responsible for the significant majority of cervical cancers.

While HPV-infection prevalence varies with age, a sharp increase in prevalence is associated with sexual debut. Accordingly, a high burden of HPV infection is seen in adolescents and during the reproductive years.

“… results are promising in that they suggest that vaccine introduction could substantially reduce rates of cervical cancer in this community in the future.”

In their recent study, a group led by Jessica Kahn, a physician in the division of Adolescent Medicine, Cincinnati Children's Hospital Medical Center, Cincinnati (OH, USA), analyzed HPV prevalence rates prior to and after introduction of the vaccine to females between the ages of 11 and 26 years, which occurred from June 2006 in accordance with the recommendation of the US Advisory Committee on Immunization Practices.

Kahn and colleagues recruited young women 13–16 years of age from primary care clinics in Cincinnati who had sexual contact but were not vaccinated against HPV. In the period 2006–2007 a total of 368 young women were recruited and in the period 2009–2010 a total of 409 women of the same age were recruited. However, more than half of young women in the latter group (termed the postvaccination group) had received at least one dose of the HPV vaccine.

“Infection with the types of HPV targeted by the vaccine decreased in vaccinated young women by 69%,” explained Kahn of the findings. “Two of these HPV types, HPV-16 and HPV-18, cause approximately 70% of cervical cancer. Thus, the results are promising in that they suggest that vaccine introduction could substantially reduce rates of cervical cancer in this community in the future.”

Of interest, in addition to observing a high decrease in vaccine-type HPV infection in vaccinated participants, a substantial decrease of 49% was seen in unvaccinated participants. The researchers believe that this is the first published study to demonstrate a substantial decrease in HPV infection in a community setting along with the first to indicate herd protection.

In addition, Kahn notes that that the reduction in vaccine-type HPV infection prevalence among participants considered vaccinated was “especially remarkable,” considering that participants were sexually experienced, had been exposed to vaccination-type HPV prior to vaccination and, in some cases, had only received one dose of the vaccine.

Cost–effectiveness models had already agreed that vaccination of females alone is more cost effective than vaccination of both sexes and it had been hypothesized that in countries, such as Australia, where high vaccine uptake is seen, the protective effects of herd immunity could be anticipated but that in countries with low uptake, such as the USA, vaccination of males may be required to gain this effect.

“… the reduction in vaccine-type human papillomavirus infection prevalence among participants considered vaccinated was ‘especially remarkable‘…”

These recent findings reopen this debate; however, Kahn takes care to note that because this study was relatively small, in a single city and included mainly young, black women of which a high proportion had Medicaid insurance, more representative samples will be needed to confirm these findings.

– Written by Lauren Constable

Sources: Goldstone SE, Vuocolo S. A prophylactic quadrivalent vaccine for the prevention of infection and disease related to HPV-6, −11, −16 and −18. Expert Rev. Vaccines 11(4), 395–406 (2012); Press release: HPV vaccine reduces infection, even in unvaccinated: www.eurekalert.org/pub_releases/2012–07/cchm-hvr070512.php

Study reports link between childbearing at an older age and decreased risk of endometrial cancer

Findings published recently in the American Journal of Epidemiology have provided support for the notion that childbearing at an older age may be linked with a reduced risk of endometrial cancer. Compared with women who last gave birth under 25 years of age, the study reported a 44% decrease in the risk of endometrial cancer in women who last gave birth at the age of 40 years or older.

The study – suggested to be the largest of its kind performed to date – consisted of a pooled analysis of four cohort studies and 13 case–control analyses within the Epidemiology of Endometrial Cancer Consortium. Notably, the data encompassed over 8500 cases of endometrial cancer and more than 16,500 controls.

Having taken into account known risk factors for endometrial cancer, the authors examined the effect of increasing age at last birth on cancer risk. This approach revealed a strong link between childbearing at an older age and diminished risk of endometrial cancer.

As noted by Veronica Setiawan, first author of the study: “We found that the lower risk of endometrial cancer continued for older mothers across different age-at-diagnosis groups, including under 50, 50–59, 60–69 and over 70, which shows that the protection persists for many years.”

“While childbearing at an older age previously has been associated with a lower risk of endometrial cancer, the size of this study definitively shows that late age at last birth is a significant protective factor after taking into account other factors known to influence the disease – bodyweight, number of kids and oral contraceptive use,” emphasized Setiawan.

– Written by Edward Parker

Sources: Setiawan VW, Pike MC, Karageorgi S et al.; the Australian National Endometrial Cancer Study Group. Age at last birth in relation to risk of endometrial cancer: pooled analysis in the Epidemiology of Endometrial Cancer Consortium. Am. J. Epidemiol. 176(4), 269–278 (2012); Keck School of Medicine news release: http://keck.usc.edu/en/About/Administrative_Offices/Office_of_Public_Relations_and_Marketing/News/Detail/2012__pr_and_markteing__summer__setiawan_epidemiology_072312

In brief …

Risk of cervical precancer and cancer among HIV-infected women with normal cervical cytology and no evidence of oncogenic HPV infection. Keller MJ, Burk RD, Xie X. JAMA 308(4), 362–369 (2012). A new study investigated the risk of cervical precancer or cancer in HIV-infected women and HIV-uninfected women who at baseline had a normal Pap test result and were negative for oncogenic human papillomavirus. Participants included 420 HIV-infected women and 279 HIV-uninfected women with normal cervical cytology at enrollment, and the primary analysis was truncated at 5 years of follow-up. It was found that the 5-year cumulative incidence cervical precancer or cancer was similar in HIV-infected women and HIV-uninfected women who were cytologically normal and oncogenic human papillomavirus-negative at enrollment.

Diabetes mellitus and sexual function in middle-aged and older women. Copeland KL, Brown JS, Creasman JM. Obstet. Gynecol. 120(2 Pt 1), 331–340 (2012). Researchers have examined the relationship between diabetes and sexual function in middle-aged and older women. Sexual function was examined in a cross-sectional cohort of 2270 ethnically diverse women aged 40–80 years using questionnaires. It was concluded that diabetic women, compared with nondiabetic women, are more likely to report low overall sexual satisfaction. Insulin-treated diabetic women also appear at higher risk for problems such as difficulty with lubrication and orgasm. Prevention of end-organ complications may be important in preserving sexual activity and function in diabetic women.

Chemicals in personal care products may be linked to diabetes in women

A study published recently in the journal Environmental Health Perspectives has proposed that urinary phylates could be associated with diabetes and diabetes-related risk factors among women, potentially due to the use of personal care products. The work was performed at Brigham and Women's Hospital (MA, USA).

Phthalates are endocrine-disrupting chemicals that are commonly found in personal care products such as moisturizers, nail polishes, soaps, hair sprays and perfumes. This study aimed to explore the association between urinary phthalate metabolite concentrations and diabetes among women in a cross-sectional study.

The researchers analyzed urinary concentrations of phthalates in 2350 women aged between 20 and 80 years, who participated in the National Health and Nutrition Examination Survey. A secondary analysis was conducted in women without diabetes to evaluate the association between phthalate metabolite concentrations and fasting blood glucose, insulin resistance (homeostatic model assessment) and hemoglobin A1c. All results were adjusted for urinary creatinine, sociodemographic and dietary factors, and body size.

It was found that women with higher levels of phthalates in their urine were more likely to have diabetes. Women who had the highest levels of the chemicals monobenzyl phthalate and monoisobutyl phthalate had almost twice the risk of diabetes compared with women with the lowest levels of those chemicals. In addition, women with higher than median levels of the chemical mono-(3-carboxypropyl) phthalate had approximately a 60% increased risk of diabetes. Also, women with moderately high levels of the chemicals mono-n-butyl phthalate and di-2-ethylhexyl phthalate had approximately a 70% increased risk of diabetes.

Lead author of the study, Tamara James-Todd, said that “This is an important first step in exploring the connection between phthalates and diabetes … we know that in addition to being present in personal care products, phthalates also exist in certain types of medical devices and medication that is used to treat diabetes and this could also explain the higher level of phthalates in diabetic women. So overall, more research is needed.”

The authors believe that future prospective studies are needed to further explore these associations to determine whether phthalate exposure can alter glucose metabolism and increase the risk of insulin resistance and diabetes.

– Written by Sam Rose

Source: James-Todd T, Stahlhut R, Meeker JD et al. Urinary phthalate metabolite concentrations and diabetes among women in the National Health and Nutrition Examination Survey (NHANES) 2001–2008. Environ. Health Perspect. doi:10.1289/ehp.1104717 (2012) (Epub ahead of print).