The effect of older age on treatment outcomes in women with advanced ovarian cancer receiving chemotherapy: An NRG-Oncology/Gynecologic Oncology Group (GOG-0182-ICON5) ancillary study.

OBJECTIVE: To assess the effect of age on overall survival (OS) in women with ovarian cancer receiving chemotherapy. Secondary objectives were to describe the effect of age on treatment compliance, toxicities, progression free survival (PFS), time from surgery to chemotherapy, and rates of optimal cytoreduction. METHODS: Women enrolled in GOG 0182-ICON5 with stage III or IV epithelial ovarian cancer (EOC) who underwent surgery and chemotherapy between 2001 and 2004 were included. Patients were divided into ages <70 and ≥ 70 years. Baseline characteristics, treatment compliance, toxicities, and clinical outcomes were compared. RESULTS: We included a total of 3686 patients, with 620 patients (16.8%) ≥ 70 years. OS was 37.2 months in older compared to 45.0 months in younger patients (HR 1.21, 95% CI, 1.09-1.34, p < 0.001). Older patients had an increased risk of cancer-specific-death (HR 1.16, 95% CI, 1.04-1.29) as well as non-cancer related deaths (HR 2.78, 95% CI, 2.00-3.87). Median PFS was 15.1 months in older compared to 16.0 months in younger patients (HR 1.10, 95% CI, 1.00-1.20, p = 0.056). In the carboplatin/paclitaxel arm, older patients were just as likely to complete therapy and more likely to develop grade ≥ 2 peripheral neuropathy (35.7 vs 19.7%, p < 0.001). Risk of other toxicities remained equal between groups. CONCLUSIONS: In women with advanced EOC receiving chemotherapy, age ≥ 70 was associated with shorter OS and cancer specific survival. Older patients receiving carboplatin and paclitaxel reported higher rates of grade ≥ 2 neuropathy but were not more likely to suffer from other chemotherapy related toxicities. Clintrials.gov: NCT00011986.

Identification of Patients With Ovarian Cancer Experiencing the Highest Benefit From Bevacizumab in the First-Line Setting on the Basis of Their Tumor-Intrinsic Chemosensitivity (KELIM): The GOG-0218 Validation Study.

PURPOSE: In patients with high-grade ovarian cancer, predictors of bevacizumab efficacy in first-line setting are needed. In the ICON-7 trial, a poor tumor intrinsic chemosensitivity (defined by unfavorable modeled cancer antigen-125 [CA-125] ELIMination rate constant K [KELIM] score) was a predictive biomarker. Only the patients with high-risk disease (suboptimally resected stage III, or stage IV) exhibiting unfavorable KELIM score < 1.0 had overall survival (OS) benefit from bevacizumab (median: 29.7 v 20.6 months; hazard ratio [HR], 0.78). An external validation study in the GOG-0218 trial was performed. METHODS: In GOG-0218, 1,873 patients were treated with carboplatin-paclitaxel ± concurrent-maintenance bevacizumab/placebo. Patient KELIM values were calculated with CA-125 kinetics during the first 100 chemotherapy days by the Lyon University team. The association between KELIM score (favorable ≥ 1.0, or unfavorable < 1.0) and bevacizumab benefit for progression-free survival (PFS)/OS was independently assessed by NGR-GOG using univariate/multivariate analyses. RESULTS: KELIM was assessable in 1,662 patients with ≥ 3 CA-125 available values. An unfavorable KELIM score was associated with bevacizumab benefit compared with placebo (PFS: HR, 0.70; 95% CI, 0.59 to 0.82; OS: HR, 0.87; 95% CI, 0.73 to 1.03), whereas a favorable KELIM was not (PFS: HR, 0.96; 95% CI, 0.79 to 1.17; OS: HR, 1.11; 95% CI, 0.89 to 1.39). The highest benefit was observed in patients with a high-risk disease exhibiting unfavorable KELIM, for PFS (median: 9.1 v 5.6 months; HR, 0.64; 95% CI, 0.53 to 0.78), and for OS (median: 35.1 v 29.1 months; HR, 0.79; 95% CI, 0.65 to 0.97). CONCLUSION: This GOG-0218 trial investigation validates ICON-7 findings about the association between poor tumor chemosensitivity and benefit from concurrent-maintenance bevacizumab, suggesting that bevacizumab may mainly be effective in patients with poorly chemosensitive disease. Bevacizumab may be prioritized in patients with a high-risk and poorly chemosensitive disease to improve their PFS/OS (patient KELIM score calculator available on the Biomarker Kinetics website).

Beyond Sedlis-A novel histology-specific nomogram for predicting cervical cancer recurrence risk: An NRG/GOG ancillary analysis.

PURPOSE: The Sedlis criteria define risk factors for recurrence warranting post-hysterectomy radiation for early-stage cervical cancer; however, these factors were defined for squamous cell carcinoma (SCC) at an estimated recurrence risk of ≥30%. Our study evaluates and compares risk factors for recurrence for cervical SCC compared with adenocarcinoma (AC) and develops histology-specific nomograms to estimate risk of recurrence and guide adjuvant treatment. METHODS: We performed an ancillary analysis of GOG 49, 92, and 141, and included stage I patients who were surgically managed and received no neoadjuvant/adjuvant therapy. Multivariable Cox proportional hazards models were used to evaluate independent risk factors for recurrence by histology and to generate prognostic histology-specific nomograms for 3-year recurrence risk. RESULTS: We identified 715 patients with SCC and 105 with AC; 20% with SCC and 17% with AC recurred. For SCC, lymphvascular space invasion (LVSI: HR 1.58, CI 1.12-2.22), tumor size (TS ≥4 cm: HR 2.67, CI 1.67-4.29), and depth of invasion (DOI; middle 1/3, HR 4.31, CI 1.81-10.26; deep 1/3, HR 7.05, CI 2.99-16.64) were associated with recurrence. For AC, only TS ≥4 cm, was associated with recurrence (HR 4.69, CI 1.25-17.63). For both histologies, there was an interaction effect between TS and LVSI. For those with SCC, DOI was most associated with recurrence (16% risk); for AC, TS conferred a 15% risk with negative LVSI versus a 25% risk with positive LVSI. CONCLUSIONS: Current treatment standards are based on the Sedlis criteria, specifically derived from data on SCC. However, risk factors for recurrence differ for squamous cell and adenocarcinoma of the cervix. Histology-specific nomograms accurately and linearly represent risk of recurrence for both SCC and AC tumors and may provide a more contemporary and tailored tool for clinicians to base adjuvant treatment recommendations to their patients with cervical cancer.

Sexual Pleasure and Healthcare Settings: Focusing on Pleasure to Improve Healthcare Delivery and Utilization.

Sexual pleasure is best attained through facilitating access to the highest standard of health. Today global data show a persistent high burden of sexual health issues. Yet, pleasure remains a sensitive, stigmatized, and unspoken topic in healthcare services. This article examines how to incorporate a value for pleasure into healthcare services, grounded in the assumption that pleasure is a fundamental reason why people have sex and that acknowledging this can support people in creating safer, more pleasurable sexual experiences. Drawing upon examples from the literature and field experience, this article explores how to better address pleasure in healthcare settings.

Male song sparrows have elevated testosterone in response to neighbors versus strangers.

Upon hearing a conspecific signal, animals must assess their relationship with the signaller and respond appropriately. Territorial animals usually respond more aggressively to strangers than neighbors in a phenomenon known as the "dear enemy effect". This phenomenon likely evolved because strangers represent a threat to an animal's territory tenure and parentage, whereas neighbors only represent a threat to an animal's parentage because they already possess a territory (providing territory boundaries are established and stable). Although the dear enemy effect has been widely documented using behavioral response variables, little research has been conducted on the physiological responses of animals to neighbors versus strangers. We sought to investigate whether the dear enemy effect is observed physiologically by exposing territorial male song sparrows (Melospiza melodia) to playback simulating a neighbor or a stranger, and then collecting blood samples to measure plasma testosterone levels. We predicted that song sparrows would exhibit increased testosterone levels after exposure to stranger playback compared to neighbor playback, due to the role testosterone plays in regulating aggression. Contrary to our prediction, we found that song sparrows had higher testosterone levels after exposure to neighbor playback compared to stranger playback. We discuss several explanations for our result, notably that corticosterone may regulate the dear enemy effect in male song sparrows and this may inhibit plasma testosterone. Future studies will benefit from examining corticosterone in addition to testosterone, to better understand the hormonal underpinnings of the dear enemy effect.

Slaughtering sacred cows: six institutional obstacles to advances in family planning.

In order to capitalise on new opportunities to advance contraceptive and reproductive health choices globally, organisations working in these fields will need to overcome six institutional obstacles. These are: (i) committee management; (ii) over-medicalisation; (iii) fear of risk and controversy; (iv) conferences, meetings, and symposia; (v) obsession with coordination; and (vi) fear of sex. The reproductive health community will require energy, innovative approaches, and a sharp focus on service delivery to address these hurdles that will otherwise slow down and misdirect programmatic momentum.

Three-year cost-effectiveness model for non-animal stabilized hyaluronic acid and dextranomer copolymer compared with sacral nerve stimulation after conservative therapy for the management of fecal incontinence.

BACKGROUND: Two new therapies for fecal incontinence (FI) are now available: non-animal stabilized hyaluronic acid and dextranomer copolymer (NASHA/Dx) and sacral nerve stimulation (SNS). PURPOSE: This study aimed to determine the cost-effectiveness of NASHA/Dx compared with SNS and conservative therapy (CT) for the treatment of FI after CT failure. METHODS: Decision tree models with Markov subbranches were developed to compare all direct costs and outcomes during a 3-year period from the viewpoint of the US third-party payer. Costs (in 2013 US dollars) of devices, medical and surgical care, and hospitalization were included. Outcomes included quality-adjusted life-years (QALYs) and incontinence-free days (IFDs). Both costs and outcomes were discounted at an annual rate of 3%. The incremental cost-effectiveness ratio was calculated for each outcome. One-way and probabilistic sensitivity analyses were performed to examine robustness of results and model stability. A budget impact analysis was also undertaken to estimate the potential cost and savings of NASHA/Dx for a payer with 1,000,000 covered lives. RESULTS: For the 3-year cost-effectiveness models, the expected cost was $9053 for CT, $14,962 for NASHA/Dx, and $33,201 for SNS. The numbers of QALYs were 1.769, 1.929, and 2.004, respectively. The numbers of IFDs were 128.8, 267.6, and 514.8, respectively. The incremental cost-effectiveness ratios per additional IFD gained were $42.60 for NASHA/Dx vs CT, $73.76 for SNS vs NASHA/Dx, and $62.55 for SNS vs CT. The incremental costs per QALY gained were $37,036 for NASHA/Dx vs CT, $244,509 for SNS vs NASHA/Dx, and $103,066 for SNS vs CT. The budget impact analysis evaluated the financial effect on the health care system of the use of NASHA/Dx and SNS. For the scenarios evaluated, when all of the patients receive NASHA/Dx, the net annual effect to the health care payer budget ranged from $571,455 to $2,857,275. When all of the patients receive SNS, the net annual effect to the health care payer budget ranged from $1,959,323 to $9,796,613. CONCLUSION: Both NASHA/Dx and SNS have produced significant improvements in FI symptoms for affected patients. NASHA/Dx is a cost-effective and more efficient use of resources for the treatment of FI when compared with SNS. The budget impact analysis suggests that although reimbursement for NASHA/Dx treatment initially adds costs to the health care system, it is significantly less expensive than SNS for patients who are candidates for either treatment.

Using the Internet and social media to promote condom use in Turkey.

Condoms are an important contraceptive method in Turkey, used by one in three couples using modern methods. However, withdrawal remains the most common form of contraception, resulting in many unwanted pregnancies. To address this issue and increase condom use in Turkey, DKT International, a social marketing enterprise, leveraged the high use of the Internet and social networking to help build Fiesta, a premium condom brand, and promote sales and condom use. By utilising a wide range of digital platforms--a new website, Facebook page, Google Adwords, an e-newsletter, viral marketing, banner ads and involving bloggers--Fiesta achieved strong recognition among the target audience of sexually active young people, though far more men than women. Retail audits, Internet analysis and sales performance suggest that using the Internet was instrumental in establishing Fiesta. Sales reached 4.3 million condoms (of which 8% were sold online) in the first 18 months. In contrast, Kiss, a far more inexpensive DKT condom, launched at the same time but with no digital campaign, sold 2.6 million. With the growing availability and use of the Internet and social media globally, family planning organizations should consider incorporating these technologies into their educational, outreach and marketing programmes.

Prescription opioid use among patients seeking treatment for opioid dependence.

OBJECTIVE: This study was designed to assess non-medical prescription opioid use among a sample of opioid dependent participants. METHODS: A cross-sectional survey was conducted with a convenience sample of patients hospitalized for medical management of opioid withdrawal. We collected data related to participant demographics, socio-economic characteristics, the age of first opioid use, types of opioids preferred, and routes of administration. We also asked participants to describe how they first began using opioids and how their use progressed over time. RESULTS: Among the 75 participants, the mean age was 32 years (SD: +/- 11, range: 18-70), 49 (65%) were men, 58 (77%) considered themselves to be "white," 55 (74%) had a high school diploma or equivalent, and 39 (52%) were unemployed. All of these participants considered themselves to be "addicted." Thirty-one (41%) felt that their addiction began with "legitimate prescriptions," 24 (32%) with diverted prescription medications, and 20 (27%) with "street drugs" from illicit sources; however, 69 (92%) had reported purchasing opioids "off the street" at some point in time. Thirty-seven (49%) considered heroin to be their current preferred drug, and 43 (57%) had used drugs intravenously. CONCLUSIONS: We found that many treatment-seeking opioid dependent patients first began using licit prescription drugs before obtaining opioids from illicit sources. Later, they purchased heroin, which they would come to prefer because it was less expensive and more effective than prescription drugs.

Electrical foot stimulation: a potential new method of deep venous thrombosis prophylaxis.

The purpose of this study was to compare venous blood flow velocity of intermittent pneumatic compression to electrical stimulation of the foot. A prospective randomized controlled study of 40 healthy volunteers was conducted. Subjects were seated for 4 hours during which they received electrical stimulation of the sole of the foot or intermittent pneumatic compression of the foot... Short-term electrical foot stimulation is at least as effective as foot intermittent pneumatic compression in increasing popliteal and femoral blood flow velocity. [corrected] Popliteal and femoral venous blood flow velocities were measured via Doppler ultrasonography. Blood flow velocity in the nonstimulated or noncompressed lower extremity served as a simultaneous control. For both the femoral and popliteal veins, the electrical foot stimulation group exhibited a greater increase in blood flow velocity than the intermittent pneumatic compression group. Electrical foot stimulation was noninferior relative to standard intermittent pneumatic compression. Specifically, this result of a greater increase in blood flow velocity is achieved at time = 120 minutes for the femoral vein (t = 2.70; p = .005) and time = 120 (t = 2.75; p = .004) and 240 (t = 2.27; p = .014) minutes for the popliteal vein. Short-term electrical foot stimulation is at least as effective as knee-high intermittent pneumatic compression in increasing popliteal and femoral blood flow velocity. Electrical foot stimulation has the potential to be an effective method of deep venous thrombosis prophylaxis.

Self-help program components and linkage to aftercare following inpatient detoxification.

Many patients fail to initiate aftercare for addictive disease rehabilitation following detoxification. This study of 136 inpatients compared characteristics of those who initiated aftercare (behavior therapy or self-help programs) during the week following discharge with those who did not. Among this group of patients, 77% (91/119) linked to aftercare. Self-help treatment related components were associated with increased aftercare treatment attendance rates and included: having a copy of the "12 Steps" (81% vs. 46%, P = .002), having read self-help literature (73% vs. 42%, P = .007), and having telephone numbers of self-help program members (50% vs. 18%, P = .008). Those who initiated aftercare treatment were also more likely to have remained abstinent from drugs and alcohol (81% vs. 39%, P < .001). Having self-help treatment related components was associated with increased rates of aftercare attendance following hospital inpatient detoxification.

The epidemiologic association between opioid prescribing, non-medical use, and emergency department visits.

INTRODUCTION: Since the 1990s prescriptions for and the non-medical use of opioids have increased. This study examines associations between opioid prescribing, non-medical use, and emergency department (ED) visits. METHODS: Data were abstracted from four federally sponsored, nationally representative, annual surveys (National Hospital Ambulatory Medical Care Survey, National Ambulatory Medical Care Survey, National Survey on Drug Use and Health, and Drug Abuse Warning Network). RESULTS: For hydrocodone and oxycodone, associations between prescribing and non-medical use, and prescribing and ED visits were statistically significant (p-values < 0.04) and strongly associated (correlation coefficient range 0.73 to 0.87). Male gender, White race, and age > or = 35 were all statistically significant (p-values < 0.0001) predictors of receiving a hydrocodone or oxycodone-containing prescription. CONCLUSION: The increased number of prescriptions written for hydrocodone and oxycodone between 1995 and 2004 was associated with similar increases in non-medical use and the number of ED visits during this time period.

A randomized trial of extended buprenorphine detoxification for opioid dependency.

OBJECTIVE: : The objective of this study was to determine whether additional "take-home" medication after inpatient opioid detoxification would lead to improved rates of subsequent treatment initiation and abstinence. METHODS: : We randomly assigned 60 inpatients to a 7-day or 37-day extension of sublingual buprenorphine/naloxone after hospitalization. Follow-up telephone interviews were conducted approximately 5 weeks after discharge. The primary outcomes were abstinence, initiation of aftercare outpatient counseling, and initiation of self-help meeting attendance. RESULTS: : Of the 30 participants in each group, outcome data were obtained for 25 (83%) in the 7-day extension group and 27 (90%) in the 37-day extension group. There was not a significant difference in the rates of abstinence (53% versus 41%) or initiation of self-help (57% versus 54%) between the 7-day and 37-day groups, respectively. Of those in the 7-day group, 15 (65%) initiated outpatient treatment compared with 21 (88%) of those assigned to the 37-day group. Although not significant in unadjusted analysis (P = 0.093), this difference was significant in regression analysis when controlling for a history of intravenous drug use (P = 0.034). Among all participants, individual characteristics at the time of hospital admission (eg, age of first drug use, previous history of intravenous drug, type of health insurance) were predictive of outcomes. CONCLUSIONS: : In this preliminary study, additional medication beyond a week after inpatient detoxification was not associated with clinically important improvements in rates of abstinence or treatment initiation. Baseline patient characteristics seem to affect these clinical outcomes after hospitalization.

Fruity, fun and safe: creating a youth condom brand in Indonesia.

DKT Indonesia, a social marketing enterprise, undertook research among young people in Indonesia to develop a strategy to heighten understanding of safer sex and increase the availability and use of condoms among sexually active youth. The centerpiece of this campaign was the launch in 2003 of Fiesta condoms, with a range of flavours, colours, shapes and pricing aimed to appeal to young people. Working with key commercial and NGO partners, distribution has focused on places where young people often congregate and shop. The campaign relies heavily on the media, including TV commercials, radio talk shows, print media and mobile text messaging. DKT has also partnered with MTV, the Staying Alive campaign and other NGO and private sector partners to educate young people on a range of reproductive and sexual health issues. Based on retail audits and focus group discussions, the Fiesta brand has been a success. In three years, it has gained a 10% share of the condom market and helped to increase overall condom sales by 22%. Young people identify Fiesta as "their" brand and have started to use Fiesta condoms in significant numbers.