Optimizing Survivorship Care Services for Asian Adolescent and Young Adult Cancer Survivors: A Qualitative Study.

Purpose: With an increasing focus on developing survivorship services tailored for adolescent and young adult (AYA) cancer survivors, incorporation of viewpoints from both survivors and health care professionals (HCPs) is important. This study aims to explore the perceptions of current and prospective survivorship services from both groups in Singapore to propose service design and delivery strategies. Methods: Focus group discussions with 23 AYA cancer survivors between the ages of 16 and 39 years at diagnosis and 18 HCPs were conducted in National Cancer Centre Singapore (NCCS) and Singapore Cancer Society (SCS). All focus group discussions were transcribed verbatim. Deductive thematic analysis was performed according to the components of a design thinking model: empathizing with AYA survivors, defining care gaps, proposing services, and implementation strategies. Results: AYA survivors preferred age-specific services that are aligned with their personal goals. Current survivorship care failed to address the needs of survivors' dependents (caregivers and children) and to consider the utility of each service temporally. Prospective services should clarify disease disclosure obligation in job search and introduce a care navigator. Key implementation strategies included (1) training HCPs on communication techniques with AYA, (2) selecting engagement platforms that complement survivors' information-seeking behavior, (3) improving outreach to survivors through appropriate branding and publicity, and (4) consolidating services from multiple providers. Conclusions: The design of survivorship care services for AYA survivors should be systematic in its conceptualization process and employ implementation strategies. The coordination of the wide spectrum of services warrants a concerted effort by cancer centers, community partners, and the government.

Use of single-question screening for erectile dysfunction: a study of at-risk Asian men in primary health care.

This study assesses the validity of a single-question screener for erectile dysfunction (ED) in men at risk in comparison to a standard validated tool - the five-item version of the International Index of Erectile Function (IIEF-5). A total of 174 men with at least one risk factor for ED were studied, with 58.0% and 10.9% of the study respondents meeting the criteria for their erectile impairment by IIEF-5 and single-question screener respectively. Our results suggest that in spite of high feasibility, a simplified, single-question screener has low sensitivity in capturing ED prevalence, even in an at-risk population, within the Asian context.

Endogenous hydrogen sulfide insufficiency as a predictor of sexual dysfunction in aging rats.

OBJECTIVE: Our earlier studies showed that endogenous hydrogen sulfide (H(2)S) pathway contributed significantly to erectile function. In this study, we tested the hypothesis that age-dependent changes in the bioavailability of H(2)S increased the risk of erectile dysfunction (ED). METHODS: Young, adult (3-month) and older (18-month) male Sprague-Dawley rats (n = 6-8/group) were treated daily with sodium hydrosulfide hydrate (NaHS), DL-propargylglycine, sildenafil or l-NAME for 10 weeks. Subsequent to cavernous nerve electrical stimulation, intracavernosal pressure (ICP) responses were determined, and the samples were collected and processed for hormonal (plasma) and gaseous parameters (plasma and erectile corpus cavernosum [CC]) using standard assay protocols. RESULTS: Aging significantly reduced the ICP response (35.9 ± 2.0 mmHg vs. 45.2 ± 1.9 mmHg in young controls), which was countered by NaHS (53.5 ± 6.0) or sildenafil (52.8 ± 9.8) treatment. In these rats, marked increments to testosterone (T) or estradiol resulted from NaHS supplementation. Similar to age-dependent decline in NO, the plasma and CC level of H(2)S was significantly lower in senescent rats when compared with young animals (p < 0.05). CONCLUSION: Our results confirm that ED with aging may be linked to a derangement in the H(2)S pathway accompanied by low T levels. It is likely that a pharmacologic intervention delivering H(2)S will provide additional benefits to sexual function from an improved T milieu.

Effects of hydrogen sulfide on erectile function and its possible mechanism(s) of action.

INTRODUCTION: The current pharmacotherapy for erectile dysfunction (ED) relies significantly on the use of phosphodiesterase type 5 (PDE5) inhibitors, but quite a proportion of ED patients are resistant to this therapy, necessitating a search for an alternative treatment. We reviewed available published data to analyze current evidence of hydrogen sulfide (H(2) S) as a novel pharmacotherapeutic agent with supportive role in sexual function. AIM: To discuss the role of H(2) S in erectile function, its possible mechanism of action, and how this knowledge may be exploited for therapeutic use. METHODS: Pubmed and Medline search was conducted to identify original articles and reviews. MAIN OUTCOME MEASURES: Data from peer-reviewed publications. RESULTS: Animal studies using different species, including in vitro study done in humans, show evidence of H(2) S's pro-erectile effects. The mechanism behind is still unclear, but evidence in literature points out the involvement of K(+) (ATP) channel, modulation of protein with anti-erectile effects, as well as involvement of the nitrergic pathway through a complex cross-talk. A new drug called H(2) S-donating sildenafil (ACS6), which incorporated an H(2) S-donating moiety in sildenafil, has been developed. While more studies are still needed, this heralded a new pharmacotherapeutical approach, which is multipronged in nature. CONCLUSIONS: Given the mounting evidence of H(2) S's role in erectile function and how it appears to achieve its pro-erectile effects through different mechanisms, H(2) S represents a potentially important treatment alternative or adjunct to PDE5 inhibitors.

Endocrine milieu and erectile dysfunction: is oestradiol-testosterone imbalance, a risk factor in the elderly?

Oestrogens are not exclusive to the female gender but occur in moderate circulating levels of 25-70 pg ml⁻¹ in men, compared to 44-153 pg ml⁻¹ in women. Arising from aromatisation of testosterone (T), oestrogen is considered to have many opposing physiological functions and the progressive T decline in the aging male is associated with relative and/or absolute increase in serum oestradiol (E2). Sexual disinterest and erectile dysfunction (ED) in the elderly may well be due to pathophysiological E2-T imbalance; the altered hormonal ratio may also explain the higher incidence of ED in hyperestrogenism or following exposure to environmental/plant oestrogens.

Experimental models for the study of female and male sexual function.

INTRODUCTION: Significant progress has been made in the understanding of physiological and pharmacological mechanisms of human sexual functioning through preclinical research in animal models. AIM: To provide an evidence-based documentation of the experimental models evaluating male and female sexual function for useful clinical translation. METHODS: Consensus discussion over the past 18 months leading to summarized views of seven experts from six countries. MAIN OUTCOME MEASURE: Report was based on the critical analysis of scientific information available in literature and subcommittee presentations, discussions, and exchanges of ideas and feedback. RESULTS: Fundamental research in animal models has led to considerable understanding of the physiological mechanisms underlying desire, arousal, genital, and other sexual responses and the design of rational pharmacological treatments for certain sexual dysfunctions in the male and female. Tissue and cellular in vitro systems have provided critical information on the in vivo interactions and modulations in the presence and absence of chemical, biological, vascular, neurologic, endocrine, and genetic inputs. The animal models seem indispensable for elucidating the biophysiological and etiopathological aspects of male and female sexual disorders. CONCLUSIONS: Useful insights into the human experience have been derived from basic research in ways that are far more difficult to obtain in humans, both scientifically and ethically. The animal model with a good predictive value can be used as a successful preclinical tool so long as the functional end points are homologous or analogous. The key issue is whether further evaluations are warranted to extrapolate the results in a clinical setting.

Initial characterization of hydrogen sulfide effects in female sexual function.

INTRODUCTION: In our male animal models, hydrogen sulfide (H(2)S) displayed significant vasodilatory and smooth muscle relaxant effects suggestive of an endogenous physiological role in erectile process. AIM: In this first exploratory study, we aimed to identify the existence and mechanism of H(2)S pathway in female sexual physiology. METHODS: Vaginal and clitoral cavernosal smooth muscle strips from New Zealand white rabbits (N = 12) were exposed to stable H(2)S donor, sodium hydrosulfide hydrate (NaHS.xH(2)O, 100 microM-1.6 mM), in isometric tension studies. The NaHS responses were repeated after incubations with (i) N(omega)-nitro-L-arginine (50 microM), 1H-[1,2,4]oxadiazolo[4,3-a]quinoxalin-1-one (ODQ) (10 microM) or cis-N-[2-phenylcyclopentyl]-azacyclotridec-1-en-2-amine (MDL 12,330A) (10 microM); and (ii) potassium chloride medium (high K(+) 60 mM/low K(+) 10 mM), tetraethylammonium (10 mM) or glibenclamide (100 microM). Relaxant effect of NaHS was also compared with those of nitroglycerine (0.18-78.2 microM) and sildenafil (0.084-25.3 microM). Additionally, samples (N = 16) were collected for estimations of plasma and tissue H(2)S and expression levels of cystathionine gamma-lyase (CSE) and cystathionine beta-synthase (CBS) proteins. MAIN OUTCOME MEASURES: In vitro evidences for H(2)S formation and its physiopharmacological effects. RESULTS: NaHS produced significant concentration-dependent relaxation of vaginal and cavernosal smooth muscles with inhibitions by combination of ODQ and MDL 12,330A (26.4%), N(omega)-nitro-L-arginine (22.2%), high K(+) (15.1%) or glibenclamide (10.1%). Based on molar potency, NaHS was 18.3 and 6.3 times weaker than nitroglycerine and sildenafil, respectively. Quantitative assays indicated that plasma H(2)S level was 16.5 +/- 2.58 microM, and H(2)S was synthesized in the clitoral and vaginal smooth muscles (1.8 and 3.9 nmol/mg soluble protein compared with 26.5 nmol/mg in the liver: positive control). Similarly, western blotting identified the protein expression bands of CSE (44.5 kDa) and CBS (63 kDa) in these genital tissue samples. CONCLUSION: These pilot studies clearly indicate the smooth muscle relaxant effect of H(2)S in female genital tract, mediating through cyclic adenosine 3':5'-monophosphate, nitric oxide-cyclic guanosine monophosphate and K(+)(ATP) channels. Taken together with biochemical and molecular evidences for endogenous formation, H(2)S pathway could be a contributing factor in female sexual responses.

Hydrogen sulphide: a novel endogenous gasotransmitter facilitates erectile function.

INTRODUCTION: In a pilot study, we found that the novel gasotransmitter, hydrogen sulfide (H2S), had a vasodilatory and proerectile action on the cavernosum. In the present work, we explored the ability of the cavernosum to synthesize H2S and its mechanism on the cavernosal pathways. AIM: To evaluate the physiopharmacological responses and mechanism in the erectile function of H2S in rabbit cavernosum. METHODS: Rabbit corpus cavernosum (CC) smooth muscle tissue (N = 5) was homogenized and incubated with L-cysteine (10 mM) and pyridoxal 5'-phosphate (2 mM) to detect H2S formation. In isometric tension studies on rabbits (N = 12), the effect of sodium hydrogen sulfide (NaHS; stable H2S donor, 100 microM-3.2 mM) was evaluated on the relaxant and contractile pathways in the cavernous smooth muscle using standard pharmacological tools. MAIN OUTCOME MEASURES: In vitro evidences for cavernosal H2S formation and proerectile pharmacological effects. RESULTS: H2S was readily synthesized in the rabbit CC (2.1 +/- 0.4 nmol/mg protein). In organ bath studies, NaHS consistently relaxed the rabbit CC in a concentration-dependent manner. MDL 12,330A and 1-H-[1,2,4]-oxadiazolo-[4,3-a]-quinoxalin-1-one inhibited the NaHS relaxation by 22.5% and 14.7%, respectively. All three enzyme inhibitors (aminooxyacetic acid [AOAA], beta-cyanoalanine [beta-CA], and DL-propargylglycine [PAG][1 mM]) markedly increased the noradrenergic contractile neurotransmission of CC strips to field stimulation with minimal reversal by cysteine (1 mM) indicating the possible inherent inhibition of the relaxant H2S formation. AOAA, beta-CA, or PAG had no significant effect on nitrergic relaxation of noradrenaline-precontracted CC strips. CONCLUSION: These pioneering studies provide evidence for the endogenous formation of H2S and its proerectile relaxant effect on the cavernosum, with the possibility of involvement of the cyclic adenosine monophosphate pathway.

Possible role for the novel gasotransmitter hydrogen sulphide in erectile dysfunction--a pilot study.

Penile erectile tissue is a highly vascularised smooth muscle which hitherto has been an unexplored target for the neuromodulatory effect of hydrogen sulphide. In this study, intracavernous injection of sodium hydrogen sulphide to primates resulted in significant increases in penile length and cavernous pressure. In another set of experiments, administration of DL-propargylglycine (inhibitor of cystathionine gamma-lyase) to rats resulted in significant reduction in cavernous nerve stimulation-evoked perfusion pressure. Our pilot experiment suggests a possible role for endogenous hydrogen sulphide in erectile physiopharmacology through facilitation of nerve-mediated penile tumescence; this is confirmed by the inhibitory effect of propargylglycine on the proerectile pathway.