Study protocol of a phase 1 clinical trial establishing the safety of intrapleural administration of liposomal curcumin: curcumin as a palliative treatment for malignant pleural effusion (IPAL-MPE).

INTRODUCTION: This is a phase 1, open-label, single-centre, uncontrolled, dose-escalation study to evaluate the feasibility, tolerability and pharmacokinetic profiles of a single dose of liposomal curcumin, administered via an existing tunnelled indwelling pleural catheter (TIPC) directly to the tumour site in individuals with diagnoses of malignant pleural effusion. Primarily, we aim to determine a maximum tolerated dose of liposomal curcumin administered via this method. METHODS AND ANALYSIS: We will use a 3+3 expanded cohort for predefined dose-escalation levels or until a predefined number of dose-limiting toxicities are reached. Participants will be administered a single dose of liposomal curcumin (LipoCurc, SignPath Pharma) via their existing TIPC as a sequential enrolling case series with the following dose cohorts: 100, 200 and 300 mg/m2. Primary endpoints are determination of the maximum tolerated dose within the predetermined dose range, and determination of the feasibility of intrapleural administration of liposomal curcumin via an existing TIPC. Secondary endpoints include determination of the safety and tolerability of intrapleural administration of liposomal curcumin, median overall survival, effects on quality of life and on feelings of breathlessness, and the pharmacokinetics and concentrations of curcumin from the plasma and the pleural fluid. Important inclusion criteria include age ≥18 years, an existing TIPC, a pleural biopsy or pleural fluid cytology-proven diagnosis of malignant pleural effusion and for whom no antitumour therapy of proven benefit is available or has been previously declined, eastern cooperative group performance status <2. ETHICS AND DISSEMINATION: The study protocol has been approved by the Southern Adelaide Local Health Network Human Research Ethics Committee (HREC) (approval number: HREC/20/SAC/11). Study results will be published in peer-reviewed journals, and presented at conferences, in field of medical oncology and respiratory medicine. TRIAL REGISTRATION NUMBER: ACTRN12620001216909. PROTOCOL VERSION NUMBER: V.1.0.

Is Bigger Really Better? Comparison of Ultraportable Handheld Ultrasound with Standard Point-of-Care Ultrasound for Evaluating Safe Site Identification and Image Quality prior to Pleurocentesis.

BACKGROUND: Pleural effusions remain a common medical problem which often requires diagnostic pleurocentesis to determine the underlying cause. Pleurocentesis is a frequently performed procedure worldwide with improved safety using ultrasound (US) technology. OBJECTIVES: This prospective, single-center study evaluated the use of an ultraportable handheld (UPHH) US compared with standard point-of-care (SPOC) US in determining a safe site for pleurocentesis. In addition, US image quality and factors impacting on image quality were assessed using both UPHH and SPOC US. METHODS: Paired US assessments were performed by thoracic physicians using UPHH and SPOC US on patients with unilateral pleural effusions to determine a safe site for pleurocentesis (defined as >2 cm of pleural fluid, >2 cm from a solid organ/diaphragm, and <7 cm chest wall depth). Distance measurements for key structures and image quality scores (using a 5-point Likert rating scale) were obtained at the time of US assessment. Factors affecting image quality were analyzed using univariate analysis. RESULTS: In 52 of the 54 included patients (96.3%), UPHH US was able to identify a safe site for pleurocentesis. Distance measurements between UPHH and SPOC US were not statistically different (all <0.5 cm with values of p > 0.05), but image quality was reduced in UPHH compared with SPOC US by 1 point on a 5-point Likert rating scale (p < 0.002). Increasing body mass index was associated with a reduction in image quality in both UPHH and SPOC US (all p < 0.01). CONCLUSIONS: Although image quality was lower in UPHH than SPOC US, a safe site was found in 96.3% of patients, which suggests that UPHH US may be a useful tool for diagnostic pleuro-centesis when SPOC US is not available (http://www.anzctr.org.au/, Australia New Zealand Clinical Trials Registry, No. ACTRN12618001592235).

Perceived Partner Responsiveness Mediates the Association Between Sexual and Marital Satisfaction: A Daily Diary Study in Newlywed Couples.

Sexuality is an integral part of intimate relationships, yet surprisingly little is known about how and for whom sexuality matters. The present research investigated the interplay of sexual and non-sexual factors that contribute to relationship satisfaction. Specifically, we tested the hypothesis that the association between sexual satisfaction and marital satisfaction is mediated by a non-sexual factor-namely, perceived partner responsiveness (PPR). Additionally, we tested the role of gender as a possible moderator of this mediated association. Thirty-four newlywed couples completed diaries with each spouse reporting their sexual satisfaction, marital satisfaction, and PPR every day for 30 days. We tested our predictions at both the person level (i.e., the mean level across 30 days) and the daily level. At the person level, we found that sexual satisfaction and PPR separately predicted marital satisfaction. Moreover, the effect of sexual satisfaction on marital satisfaction was partially mediated by PPR. No gender differences emerged at this level. At the daily level, we found similar support for partial mediation. However, at this level, gender did serve as a moderator. The stronger mediation found for women was driven by a stronger association between sexual satisfaction and PPR for women than for men. This study joins a growing literature highlighting the role of PPR in dyadic relationships.

The effects of similarity in sexual excitation, inhibition, and mood on sexual arousal problems and sexual satisfaction in newlywed couples.

INTRODUCTION: Despite the importance of sexuality for romantic relationships, there has been little research attention to individual differences and dyadic variables, including couple similarity, and their association with sexual problems and satisfaction. AIM: The current study examined the effects of the propensity for sexual inhibition and sexual excitation scales (SIS/SES) and the effects of different mood states on sexuality (Mood and Sexuality Questionnaire [MSQ]), at both the individual and the dyad level, on sexual arousal problems and sexual satisfaction. METHODS: Similarity in SIS/SES and MSQ was measured in a nonclinical sample of 35 newlywed couples and operationally defined as the within-couple, z-transformed correlations between the two partners' item responses. MAIN OUTCOME MEASURES: Sexual arousal problems were assessed using self-report measures (Demographic and Sexual History Questionnaire) and focused on the past 3 months. Sexual satisfaction was assessed using the Global Measure of Sexual Satisfaction. RESULTS: Regression analyses revealed that greater similarity in the effects of anxiety and stress on sexuality was associated with more reported sexual arousal problems of wives. In contrast, the husbands' sexual arousal problems were related only to their own higher SIS1 scores. Higher SES scores predicted lower sexual satisfaction for both husbands and wives. Wives who reported strong positive mood effects on their sexuality indicated greater sexual satisfaction, while husbands who were more similar to their wives in the effect of positive moods on sexuality indicated greater sexual satisfaction. CONCLUSIONS: The findings show that, above and beyond one's own sexual propensities, similarity in various aspects of sexuality predicts sexual problems (more so in women) and sexual satisfaction (in both men and women).

Attentional and affective processing of sexual stimuli in women with hypoactive sexual desire disorder.

Hypoactive sexual desire disorder (HSDD) is the most common sexual problem in women. From an incentive motivation perspective, HSDD may be the result of a weak association between sexual stimuli and rewarding experiences. As a consequence, these stimuli may either lose or fail to acquire a positive meaning, resulting in a limited number of incentives that have the capacity to elicit a sexual response. According to current information processing models of sexual arousal, sexual stimuli automatically activate meanings and if these are not predominantly positive, processes relevant to the activation of sexual arousal and desire may be interrupted. Premenopausal U.S. and Dutch women with acquired HSDD (n = 42) and a control group of sexually functional women (n = 42) completed a single target Implicit Association Task and a Picture Association Task assessing automatic affective associations with sexual stimuli and a dot detection task measuring attentional capture by sexual stimuli. Results showed that women with acquired HSDD displayed less positive (but not more negative) automatic associations with sexual stimuli than sexually functional women. The same pattern was found for self-reported affective sex-related associations. Participants were slower to detect targets in the dot detection task that replaced sexual images, irrespective of sexual function status. As such, the findings point to the relevance of affective processing of sexual stimuli in women with HSDD, and imply that the treatment of HSDD might benefit from a stronger emphasis on the strengthening of the association between sexual stimuli and positive meaning and sexual reward.

Sexual desire, sexual arousal and hormonal differences in premenopausal US and Dutch women with and without low sexual desire.

The interaction between women's hormonal condition and subjective, physiological, and behavioral indices of desire or arousal remains only partially explored, in spite of frequent reports from women about problems with a lack of sexual desire. The present study recruited premenopausal women at two sites, one in the United States and the other in the Netherlands, and incorporated various measures of acute changes in sexual desire and arousal. A sample of 46 women who met criteria for Hypoactive Sexual Desire Disorder (HSDD) was compared to 47 women who experienced no sexual problems (SF). Half of each group used oral contraceptives (OCs). The specific goal was to investigate whether there is a relationship between women's hormone levels and their genital and subjective sexual responsiveness. Background demographics and health variables, including oral contraceptive (OC) use, were recorded and hormones (total testosterone (T), free testosterone (FT), SHBG, and estradiol) were analyzed along with vaginal pulse amplitude and self-report measures of desire and arousal in response to sexual fantasy, visual sexual stimuli, and photos of men's faces. Self-reported arousal and desire were lower in the HSDD than the SF group, but only for women who were not using oral contraceptives. Relationships between hormones and sexual function differed depending on whether a woman was HSDD or not. In line with prior literature, FT was positively associated with physiological and subjective sexual arousal in the SF group. The HSDD women demonstrated the opposite pattern, in that FT was negatively associated with subjective sexual responsiveness. The findings suggest a possible alternative relationship between hormones and sexual responsiveness in women with HSDD who have characteristics similar to those in the present study.

Marital satisfaction and communication behaviors during sexual and nonsexual conflict discussions in newlywed couples: a pilot study.

The way couples communicate during conflict discussions has been found to be a reliable predictor of marital satisfaction. However, in previous research, there has been little experimental control over the selection of topics. The present study examined, in a sample of 15 newlywed couples, whether affective displays during the discussion of a sexual and a nonsexual conflict topic differentially predict current marital satisfaction. Communication behaviors were coded using an adaptation of the Specific Affect Coding System, resulting in composite "negative behavior" and "positive behavior" categories. Data were analyzed using multilevel modeling. Negative behaviors displayed during the nonsexual conflict discussions were not significantly related to concurrent self-reported relationship satisfaction. In contrast, for wives, negative behaviors displayed during the discussion of a sexual problem were significantly related to lower levels of relationship satisfaction. For the sexual and nonsexual conflict discussions, positive behaviors were positively associated with relationship satisfaction, although this effect did not reach statistical significance. Overall, the authors' findings emphasize the importance of incorporating sexual variables in the study of marriage. Furthermore, their study represents an important step in recognizing that marital research benefits from an examination of specific topics of conflict as a factor to consider in studies of marital functioning.