Comprehensive Systematic Review of long-term opioids in women with chronic non cancer pain and associated reproductive dysfunction (hypothalmic-pituitary-gonadal axis disruption)

A comprehensive systematic literature review of reproductive side effects in women aged 18 to 55 years treated with opioids for 1 month or longer for chronic noncancer pain. A search of 7 databases including EMBASE and Medline was undertaken (October 2014 and a limited rerun April 2016). The search contained key words for opioids (generic and specific drug names) and side effects (generic and specific reproductive). Titles were screened using predefined criteria by a single reviewer and abstracts and full texts by 2 independent reviewers. A total of 10,684 articles were identified and 12 full texts (cohort [n 5 1], case–control [n 5 4], crosssectional [n 5 4], case series [n 5 1], and case report [n 5 2] with a maximum of 41 cases in 1 article) were included covering 3 different modes of administration: oral (n 5 6), intrathecal (n 5 5), and transdermal (n 5 1). Amenorrhoea occurred in 23% to 71% of those receiving oral or intrathecal opioids. Decreased libido was seen in 61% to 100%. Of the 10 studies that undertook hormonal assays, only 2 studies showed a statistically significant decrease in hormone levels. This review supports the view that there is a potential relationship between the use of long-term opioids in women and reproductive side effects. The evidence is however weak and the mode of administration, duration, type, and dose of opioid might influence associations. Although hormone levels were statistically significant in only 2 studies, women exhibited clinically important symptoms (decreased libido and altered menstrual cycle). Further investigation is required with larger cohorts and analysis of different delivery methods

Evidence for strategies that improve recruitment and retention of adults aged 65 years and over in randomised trials and observational studies: a systematic review

Background: adults aged ≥65 years are often excluded from health research studies. Lack of representation reduces generalisability of treatments for this age group. Objective: to evaluate the effectiveness of strategies that improve recruitment and retention of adults aged ≥65 in observational studies and randomised controlled trials (RCTs). Methods: searches conducted in 10 databases for RCTs of recruitment and retention strategies in RCTs or observational studies. Two reviewers screened abstracts and full-text articles for eligibility and extracted data. Studies without separate data for adults aged ≥65 were discarded. Risk of bias assessed using the Cochrane Risk of Bias tool. Results were synthesised narratively. Results: thirty-two studies were included in the review (n = 75,444). Twelve studies had low risk of bias, of which 10 had successful strategies including: Opt-out versus opt-in increased recruitment (13.6% (n = 261)-18.7% (n = 36) difference; two studies); Advance notification increased retention (1.6% difference, OR 1.45; 95% CI 1.01, 2.10, one study (n = 2,686); 9.1% difference at 4 months, 1.44; 1.08, 1.92, one study (n = 753)); Hand-delivered versus postal surveys increased response (25.1% difference; X2 = 11.40, P < 0.01; one study (n = 139)); Open randomised design versus blinded RCT increased recruitment (1.56; 1.05, 2.33) and retention (13.9% difference; 3.1%, 24.6%) in one study (n = 538). Risk of bias was high/unclear for studies in which incentives or shorter length questionnaires increased response. Discussion: in low risk of bias studies, few of the strategies that improved participation in older adults had been tested in ≥1 study. Opt-out and advance notification strategies improved recruitment and retention, respectively, although an opt-out approach may have ethical limitations. Evidence from single studies limits the generalisability of other strategies