Incidence of influenza virus infection among pregnant women: a systematic review.

BACKGROUND: The World Health Organization (WHO) considers pregnant women to be a risk group for severe influenza disease. We conducted a systematic review to evaluate influenza disease incidence in pregnant women in order to inform estimates of influenza vaccine impact for low-resource countries. METHODS: We performed electronic literature searches, targeting studies on the following outcomes in pregnant women: attack rate, hospitalization rate, intensive care unit admission rate, mortality rate, and disability-adjusted life years lost. Only original studies published in peer-reviewed journals that had laboratory confirmation for influenza virus infection and included population-based incidence rates with denominator data were included. We summarized study characteristics in descriptive tables and outcome-specific Forest plots. We generated summary incidence rates using random effects models and assessed statistical heterogeneity by visual examination of Forest plots, and by χ 2 and I2 tests. RESULTS: We identified 1543 articles, of which nine articles met the study inclusion criteria. Five were case series, three were cohort studies, and one was a randomized controlled trial. Eight studies were from high-income countries, and one was from an upper middle-income country. Six studies reported results for pandemic influenza, and three reported seasonal influenza. Statistical heterogeneity was high for all outcomes, and methodologies and duration of surveillance varied considerably among studies; therefore, we did not perform meta-analyses. CONCLUSIONS: Study quality was very low according to GRADE criteria. More data on influenza disease incidence in pregnant women, particularly in low- and middle-income countries and for seasonal influenza disease, are needed to inform public health decision-making.

Early Engagement in HIV Research: Evaluation of the Penn CFAR Scholars Program Aimed at Increasing Diversity of the HIV/AIDS Workforce.

BACKGROUND: Demographic diversity is not represented in the HIV/AIDS workforce. Engagement of underrepresented trainees as early as high school may address this disparity. METHODS: We established the Penn Center for AIDS Research (CFAR) Scholars Program, a mentored research experience for underrepresented minority (URM) trainees spanning educational stages from high school to medical school. The program provides participants with tailored educational programming, professional skill building, and mentored research experiences. We conducted qualitative interviews with scholar, mentor, and leadership groups to evaluate the program's impact. RESULTS: Eleven participants were selected to partake in 1 of 5 existing mentored research programs as CFAR scholars. Scholars attended an 8-week HIV Seminar Series that covered concepts in the basic, clinical, behavioral, and community-based HIV/AIDS research. Program evaluation revealed that scholars' knowledge of HIV pathophysiology and community impact increased because of these seminars. In addition, they developed tangible skills in literature review, bench techniques, qualitative assessment, data analysis, and professional network building. Scholars reported improved academic self-efficacy and achieved greater career goal clarity. Areas for improvement included clarification of mentor-mentee roles, expectations for longitudinal mentorship, and long-term engagement between scholars. Financial stressors, lack of social capital, and structural racism were identified as barriers to success for URM trainees. CONCLUSION: The Penn CFAR Scholars Program is a novel mentored research program that successfully engaged URM trainees from early educational stages. Barriers and facilitators to sustained efforts of diversifying the HIV/AIDS workforce were identified and will inform future program planning.

The cost effectiveness of bisphosphonates for the prevention and treatment of osteoporosis: a structured review of the literature.

Osteoporotic fragility fractures constitute a significant public health concern. The lifetime risk of any osteoporotic fracture is very high (40-50% in women and 13-22% in men). Fractures are associated with significant mortality and morbidity and represent a substantial economic burden to society. Bisphosphonates (alendronate, etidronate, risedronate and ibandronate) are indicated for the treatment and prevention of osteoporosis but are costly compared with other treatments, such as vitamin D and calcium. Our search identified 23 studies evaluating the cost effectiveness of bisphosphonate therapy for the treatment and prevention of fragility fractures; these studies were from five geographical areas and employed a variety of comparators and assumptions. We identified 11 studies investigating bisphosphonates in women with low bone mineral density (BMD) [T-score >2.5 standard deviations {SDs} below normal {mean} peak values for young adults] and previous fractures, five studies investigating bisphosphonates in women with low BMD and no previous fracture, one study of bisphosphonates in women with osteopenia, five studies involving screening and two studies of bisphosphonates in special populations (women initiating corticosteroid treatment and men). In women with low BMD and previous fractures, bisphosphonate therapy was most cost effective in populations aged > or =70 years and was unlikely to be cost effective in populations aged < or =50 years. There was uncertainty concerning the cost effectiveness of bisphosphonates in such populations aged 60-69 years. In women with low BMD without previous fractures, treatment with alendronate or risedronate appeared to be cost effective across countries (UK, US, Denmark), but there was some uncertainty about the cost effectiveness of etidronate in patients in the highest age groups. Identifying risk factors for fractures through means such as spine radiographs to detect vertebral deformities improves the cost effectiveness of treatment. In women with osteopenia, alendronate therapy may be cost effective in women with a T-score of -2.4SD in the US. Screening for low BMD and treatment with alendronate or etidronate appears to be cost effective in postmenopausal women in general and in women with rheumatoid arthritis initiating corticosteroid therapy. Alendronate therapy without screening was also shown to be potentially cost effective in certain at-risk male populations, as well as in women initiating corticosteroid therapy after the age of 40 years. Decision makers in the US, UK and Sweden should consider funding the use of bisphosphonates for the prevention and treatment of osteoporosis in women aged >70 years, particularly if they have other risk factors for fracture. Further studies are required to make more definitive conclusions in other countries and patient populations. Screening strategies for low BMD followed by bisphosphonate treatment should also be considered in the general female population aged >65 years in the UK and US and in patients with rheumatoid arthritis initiating corticosteroid therapy.

Incidence of laboratory-confirmed influenza disease among infants under 6 months of age: a systematic review.

OBJECTIVES: The aim of this systematic review was to assess incidence rates of laboratory-confirmed influenza (LCI) outcomes among infants under 6 months of age. DESIGN: Systematic literature search and review of indexed studies in PubMed, EMBASE, the Cochrane Library and CINAHL Plus from inception to 19 April 2017. SETTING: Population-based estimates from community or hospital settings. PARTICIPANTS: Infants under 6 months of age. PRIMARY AND SECONDARY OUTCOME MEASURES: LCI illness in ambulatory care settings, LCI hospitalisation, LCI intensive care unit admission and LCI death. Only studies with population-based incidence data were included. RESULTS: We identified 27 primary studies, 11 of which were from the USA, four were from other non-US high-income settings and the remaining were from lower-middle-income or upper-middle-income countries. Most studies (n=23) assessed incidence of LCI hospitalisation, but meta-analysis to pool study-specific rates was not possible due to high statistical and methodological heterogeneity. Among US studies, the reported incidence of LCI hospitalisation ranged from 9.3 to 91.2 per 10 000 infants under 6 months for seasonal influenza, while the only US-based estimate for pandemic H1N1 influenza was 20.2 per 10 000 infants. Reported rates for LCI hospitalisation for seasonal influenza from other countries ranged from 6.2 to 73.0 per 10 000 infants under 6 months, with the exception of one study with an estimated rate of 250 per 10 000 infants. No events were reported in five of the nine studies that evaluated LCI death among infants under 6 months. CONCLUSION: Our review of published studies found limited data on LCI outcomes for infants under 6 months, particularly from non-US settings. Globally representative and reliable incidence data are necessary to fully evaluate influenza disease burden and the potential impact of maternal influenza immunisation programme on morbidity and mortality in young infants.

Endocrine therapy initiation from 2001 to 2008 varies by age at breast cancer diagnosis and tumor size.

PURPOSE: To evaluate tamoxifen and aromatase inhibitor (AI) initiation over time and by patient characteristics among women diagnosed with breast cancer in a community setting. METHODS: We conducted a retrospective cohort study of 1,501 women age ≥ 18 years diagnosed with stages I to II invasive, hormone receptor-positive breast cancer from 2001 to 2008 in an integrated delivery system. Using automated pharmacy dispensings, we determined endocrine therapy receipt within 12 months of diagnosis. We used generalized linear models to estimate adjusted relative risks (RRs) with 95% CIs for any endocrine therapy use (v none), tamoxifen use (v none), AI use (v none), and AIs first (v tamoxifen). Each model adjusted for age, stage, body mass index, tumor size, lymph node status, comorbidities, other treatment, and diagnosis year. RESULTS: Tamoxifen use was at its highest (56.9%) in 2001 and then decreased; AI use was lowest in 2001 (5.5%) and then peaked in 2005 (36.8%). In multivariate models, women age ≥ 65 years were less likely to use any endocrine therapy compared with women age 55 to 64 years (age 65 to 74 years: RR, 0.86; 95% CI, 0.78 to 0.96; age ≥ 75 years: RR, 0.71; 95% CI, 0.61 to 0.81). Women age ≥ 75 years were significantly less likely to begin AIs versus no treatment (RR, 0.46; 95% CI, 0.32 to 0.64) and versus tamoxifen (RR, 0.67; 95% CI, 0.46 to 0.97). Women with tumor sizes 1.0 to 1.9 cm and ≥ 2.0 cm were significantly more likely to use any endocrine therapy compared with women with tumor sizes < 1.0 cm (RR, 1.41; 95% CI, 1.23 to 1.61 and RR, 1.52; 95% CI, 1.27 to 2.81, respectively). CONCLUSION: Differential initiation over time, as well as by age and tumor size, suggests patient preferences and provider recommendations for endocrine therapy vary, despite guideline recommendations.

Concomitant use of cholinesterase inhibitors and anticholinergics: prevalence and outcomes.

OBJECTIVES: To determine the extent of concomitant use of cholinesterase inhibitor (ChI) and anticholinergic (ACh) medications and the clinical consequences of dual use in a population-based setting. DESIGN: Retrospective cohort study. SETTING: Group Health Cooperative and Kaiser Permanente Colorado. PARTICIPANTS: Five thousand six hundred twenty-five adults aged 50 and older who began new use of a ChI between 2000 and 2007. MEASUREMENTS: Rates and characteristics of concomitant ChI and ACh use and the association between dual use and the outcomes of death and nursing home placement (claim from a nursing home with no prior claims used as a proxy). RESULTS: Thirty-seven percent of ChI users also received AChs. Eleven percent of ChI users were concomitantly using two or more moderate to potent AChs. Median duration of this concomitant use was approximately 4 months, but a substantial proportion (25%) continued to use both medication classes simultaneously for longer than 12 months. In 23% of ChI users, AChs were being used at the time ChI therapy was initiated. The majority of this ACh use (77%) was not stopped once ChIs were started. No association was observed between concomitant use and risk of death or nursing home placement. CONCLUSION: These results should raise awareness about the prevalence and potential inappropriateness of concomitant use of ChIs and AChs and promote evaluations of practices intended to improve care standards.

Statin use and cancer risk: a comprehensive review.

IMPORTANCE OF THE FIELD: HMG-CoA inhibitors (statins), a class of drugs that reduce cholesterol, are used to manage and prevent coronary heart disease. They are among the most commonly prescribed drugs worldwide. Contrary to early concerns over the carcinogenicity of statins, a growing body of evidence suggests statins may in fact have a chemopreventive potential against cancer. AREAS COVERED IN THIS REVIEW: In this paper, we review evidence on the association between statin use and cancer risk. Specifically, we report on clinical trials and observational studies that measured all cancer or site-specific cancers of the breast, colorectal, lung, prostate and reproductive organs associated with statin use. WHAT THE READER WILL GAIN: An understanding of the evidence, including strengths and limitations, to support an association between statins and cancer. Information on the current state of the field and future directions are also discussed. TAKE HOME MESSAGE: Few strong or consistent associations between statins and cancer incidence overall or for any of the sites reviewed were detected. Data for any effects of statins on cancer prognosis and secondary prevention are lacking; with the exception of consistent evidence that statins are associated with reduced risk of advanced/aggressive prostate cancer. Statins appear safe in relation to cancer risk but any chemopreventive effect in humans remains to be established and should not be recommended outside the context of clinical trials. It is encouraging that numerous trials are ongoing. The prospect of reducing the incidence and burden of some of the most prevalent cancers with safe, affordable and tolerable medication that already reduces the risk of the leading cause of death and cardiovascular disease warrants further exploration in clinical trials and observational studies of prognosis and survival.