Evaluating a shared care pathway intervention for people receiving chemotherapy to reduce post-treatment unplanned hospital presentations: a randomised controlled trial.

PURPOSE: The aim of this randomised controlled trial (RCT) was to explore whether a community nursing intervention for outpatients receiving systemic therapy reduced unplanned hospital presentations and improved physical and psychosocial health outcomes over the first three cycles of treatment compared to a control group receiving standard care. METHODS: The number of and reasons for unplanned presentations were obtained for 170 intervention and 176 control group adult patients with solid tumours starting outpatient chemotherapy. Poisson regression was used to compare the number of presentations between the intervention and control groups. Patients self-completed the Hospital Anxiety and Depression Scale, the Cancer Behavior Inventory and the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire core 30 (EORTC QLQ-C30) at the start of the first four cycles. Linear regression techniques were used to compare quality of life outcomes. RESULTS: The reduction in unplanned presentations in the intervention group relative to the control group was 12% (95% CI, - 25%, 37%; P = 0.48). At the start of cycle 4, there was no difference in anxiety (difference = 0.47 (95% CI, - 0.28, 1.22; P = 0.22)), depression (difference = 0.57 (95% CI, - 0.18, 1.31; P = 0.13)) or EORTC QLQ-C30 summary score (difference = 0.16 (95% CI, - 2.67, 3.00; P = 0.91)). Scores for self-efficacy as measured by the Cancer Behavior Inventory were higher in the intervention group (difference = 4.3 (95% CI, 0.7, 7.9; P = 0.02)). CONCLUSION: This RCT did not demonstrate a benefit in reducing unplanned presentations to hospital. The trial identified improved cancer-based self-efficacy in patients receiving the intervention. TRIAL REGISTRATION: Registered at Australian and New Zealand Clinical Trials Registry: ACTRN12614001113640, registered 21/10/2014.

Emotional Processing of Imaginal Exposures Predicts Symptom Improvement: Therapist Ratings Can Assess Trajectory in Prolonged Exposure for Posttraumatic Stress Disorder.

Research on mechanisms of change in prolonged exposure therapy (PE), an evidence-based treatment for posttraumatic stress disorder (PTSD), is ongoing. Two putative mechanisms of change are engagement during imaginal exposure and trauma-related belief change. The PE Therapist Questionnaire (PETQ), a novel measure based on the emotional processing theory underlying PE, was developed as a practical tool for therapists to use to assess (a) patient engagement during imaginal exposures and (b) perspective shifts during postimaginal processing. Patients (N = 151) at a U.S. Veterans Affairs medical center PTSD specialty clinic completed self-report measures of PTSD and depression symptoms prior to sessions. Study therapists (n = 17) completed the PETQ postsession. Rational construction and psychometric analyses suggested a two-component solution for the PETQ: imaginal and processing. The imaginal factor did not relate to PTSD and depression symptoms. The processing factor correlated with current and next-session PTSD and depression symptoms, with medium effect sizes, rs = -.41 to -.45, ps < .001. Controlling for current-session PTSD and depression, a higher level of processing predicted lower next-session PTSD severity, with a small effect size, ß = -.38, p < .04. Postexposure emotional processing, which supports positive changes in maladaptive trauma-related beliefs and tolerance of emotional distress, predicted future symptom improvement, highlighting the importance of processing components in PE. Further, the use of therapist observations may offer ancillary methods less influenced by correlation of within-patient subjective ratings and concomitant risk of construct overlap in mechanisms research.

Redemption in a single low point story longitudinally predicts well-being: The incremental validity of life story elements.

OBJECTIVE: Extending research on the incremental validity of life story variables and the importance of particular kinds of story contexts, this paper tested the hypothesis that a single theme (narrative redemption) in a specific life story episode (the low point-or an episode that challenges the self) can predict well-being, above and beyond covariates. METHOD: Two samples, an emerging adult (N = 144) and a late midlife sample (N = 158), provided life story episodes with different life story collection methods (written and interview) and completed self-report measures concurrently and longitudinally. RESULTS: The findings indicated that low point redemption was associated concurrently and longitudinally with well-being when controlling for the Big Five factors of Extraversion and Neuroticism and narrative word count. These associations held for three months among emerging adults and four years among late midlife adults. Aggregating redemption in high and low points did not improve the concurrent or longitudinal association between redemption and well-being. CONCLUSIONS: The findings demonstrate the capacity of elements in a single challenging episode of the life story to predict well-being.

Optimal clinical assessment strategies for chemotherapy-induced peripheral neuropathy (CIPN): a systematic review and Delphi survey.

BACKGROUND/PURPOSE: Chemotherapy-induced peripheral neuropathy (CIPN) is a prominent side effect of the treatment of cancer. Despite this frequent complication, there has been no comprehensive review and quality appraisal of CIPN assessments. The purpose of this study is to provide a definitive quality appraisal of CIPN assessment strategies for clinical use. METHODS: Relevant studies were identified through database searches of Medline, Embase, CINAHL, and Cochrane. CIPN assessment strategies from included articles were extracted and initially rated by an oncologist and neurophysiologist according to criteria related to assessment depth, comprehensiveness, appropriateness, and reliability. The six highest scoring assessment strategies were the focus of a two-round Delphi survey of a working party of 32 physicians, nurses, and consumers to achieve consensus on the highest rated assessments for each criterion. RESULTS: The database search yielded 117 distinct CIPN assessments that were extracted from 2373 articles. Three patient-reported outcome surveys and three clinician-based assessments were included in the Delphi survey. No consensus was generated regarding the best overall CIPN assessment, although good (≥70%) consensus was achieved regarding the best assessment within each criterion. The Participant Neurotoxicity Questionnaire (PNQ) was rated the highest overall and patient-reported outcome (PRO) assessment, while the Total Neuropathy Score clinical version (TNSc) was the highest rated clinician-based assessment. CONCLUSIONS: A diverse range of CIPN assessments currently exists. While several assessments assess CIPN symptoms with adequate comprehensiveness, depth, language, and feasibility, the consensus 'gold standard' clinical assessment remains to be established.

'Shadowing' as a management strategy for chemotherapy outpatient primary support persons.

Despite growing numbers of patients with cancer receiving chemotherapy in outpatient settings and the corresponding increase in care demands on family and close friends, little is known about the experiences of those informal carers supporting people with cancer during their chemotherapy trajectories. Using an interpretivist theoretical framework, this study explored the experiences of primary support persons of chemotherapy outpatients through in-depth interviews with 17 participants nominated as their primary support persons by people receiving chemotherapy at a large tertiary hospital in Australia. The study demonstrates that primary support persons of chemotherapy outpatients face distinct challenges, being at the frontline of treatment and managing side effects with minimal support at home. This role involves sensitive provision of complex medical and social care in circumstances that profoundly challenge the everyday worlds of both patient and carer. From the moment of diagnosis, informal carers in this context face the 'double whammy' of needing to 'manage' the cancer diagnosis experience as well as the chemotherapy trajectory experience. This study points to the significant level of responsibility that primary support persons take on, and the extent to which patients and clinicians rely on their support and management skills. It also points, however, to the lack of recognition they receive for assuming this role, and their sense of frustration in the face of this invisibility. The conceptualisation of the informal carer role as a 'shadowing' role explicitly represents the protective, vigilant, but almost invisible, support role described by the participants in this study.

PATTERNS OF CHANGE IN RESPONSE TO PROLONGED EXPOSURE: IMPLICATIONS FOR TREATMENT OUTCOME.

BACKGROUND: Assessment of response to Prolonged Exposure (PE) suggests some patients may experience discontinuous change involving sudden symptom reductions and/or temporary exacerbations. The current study looked to (1) isolate profiles of PE response among treatment-seeking veterans and (2) identify factors associated with unique patterns of change. METHODS: Archival records were examined for veterans receiving PE through a specialty Veterans Affairs Medical Center (VAMC) clinic (N = 109). Latent profile analysis was used to extract response trajectories defined by change in weekly PTSD Checklist (PCL) scores. Associations with provider status (staff vs. intern), setting (in-person vs. telehealth), initial severity (PTSD; depression), and eventual treatment gains were examined. RESULTS: Three profiles were observed. Rapid Responders (18.3%) evidenced sharp reductions at Week 2 and again between Weeks 5 and 6. Linear Responders (40.4%) demonstrated gradual reductions throughout the 10-week assessment window. Delayed Responder (41.3%) scores were relatively stable over the evaluation period although final session outcomes indicated reliable change (PCLΔ > 10) in 40% of patients. Profiles were similar with respect to provider status, treatment setting, and initial symptom severity. Rapid Responders evidenced lower final session scores relative to Linear (g = 1.13) and Delayed (g = 1.85) groups, with Linear Responders reporting lower end scores than Delayed Responders (g = 1.02). CONCLUSIONS: Anticipating patterns of recovery and their association with therapeutic outcome is of immense clinical value. Sudden gains emerged as a strong predictor of enhanced response. Data also suggest potential benefits of extending standard intervention for patients who fail to demonstrate an immediate response to PE.

A Comparison of Human Narrative Coding of Redemption and Automated Linguistic Analysis for Understanding Life Stories.

The majority of life narrative research is performed using trained human coders. In contrast, automated linguistic analysis is oft employed in the study of verbal behaviors. These two methodological approaches are directly compared to determine the utility of automated linguistic analysis for the study of life narratives. In a study of in-person interviews (N = 158) and a second study of life stories collected online (N = 242), redemption scores are compared to the output of the Linguistic Inquiry and Word Count (Pennebaker, Francis & Booth, 2001). Additionally, patterns of language are found using exploratory principal components analysis. In both studies, redemption scores are modestly correlated with some LIWC categories and unassociated with the components. Patterns of language do not replicate across samples, indicating that the structure of language does not extend to a broader population. Redemption scores and linguistic components are independent predictors of life satisfaction up to 3 years later. These studies converge on the finding that human-coded redemption and automated linguistic analysis are complementary and nonredundant methods of analyzing life narratives, and considerations for the study of life narratives are discussed.

Rituximab for subcutaneous delivery: Clinical management principles from a nursing perspective.

Nurses play an integral role in administering treatments to patients with non-Hodgkin's lymphomas. Intravenous (IV) rituximab was approved by the Australian Therapeutic Goods Administration in 1998, and a novel subcutaneous (SC) formulation was approved in 2014. Fixed-dose SC rituximab is highly concentrated; co-formulation with a fully human recombinant vorhyaluronidase alfa enzyme helps overcome the physiological barriers of the SC space, facilitating drug dispersion. Despite a different pharmacokinetic profile to the IV preparation, SC rituximab demonstrates a comparable efficacy/safety profile. Most frequently occurring rituximab-related adverse events include neutropenia, nausea and constipation, and administration-related reactions are more frequent with the SC preparation. Compared with IV, SC delivery reduces treatment times and nurse workload, and patients report greater comfort and convenience. This article sets out nursing considerations for optimal administration of SC rituximab, including premedication, drug handling/preparation, injection technique, after-care and management of adverse events, particularly administration-related reactions.

Prevalence and correlates of posttrauma distorted beliefs: evaluating DSM-5 PTSD expanded cognitive symptoms in a national sample.

The fifth edition of the Diagnostic and Statistical Manual of Mental Disorders (DSM-5; American Psychiatric Association [APA], 2013) modified the diagnostic criteria for posttraumatic stress disorder (PTSD), including expanding the scope of dysfunctional, posttrauma changes in belief (symptoms D2-persistent negative beliefs and expectations about oneself or the world, and D3-persistent distorted blame of self or others for the cause or consequences of the traumatic event). D2 and D3 were investigated using a national sample of U.S. adults (N = 2,498) recruited from an online panel. The prevalence of D2 and D3 was substantially higher among those with lifetime PTSD than among trauma-exposed individuals without lifetime PTSD (D2: 74.6% vs 23.9%; D3: 80.6% vs 35.7%). In multivariate analyses, the strongest associates of D2 were interpersonal assault (OR = 2.39), witnessing interpersonal assault (OR = 1.63), gender (female, OR = 2.11), and number of reported traumatic events (OR = 1.88). The strongest correlates of D3 were interpersonal assault (OR = 3.08), witnessing interpersonal assault (OR = 1.57), gender (female, OR = 2.30), and number of reported traumatic events (OR = 1.91). The findings suggested the expanded cognitive symptoms in the DSM-5 diagnostic criteria better capture the cognitive complexity of PTSD than those of the DSM-IV.

The prevalence and correlates of supportive care needs in testicular cancer survivors: a cross-sectional study.

OBJECTIVE: This cross-sectional study aimed to identify the prevalence and correlates of supportive care needs in testicular cancer (TC) survivors. METHODS: Men who had completed active anti-cancer treatment for TC between 6 months and 5 years previously showing no evidence of recurrence were recruited from 14 Australian cancer centers (September 2009-February 2011). Participants completed a self-report questionnaire measuring sociodemographics, disease, and treatment information, supportive care needs (CaSUN), psychological distress (DASS21) and health-related quality of life (HRQoL; SF36v2). RESULTS: Of the 486 eligible TC survivors invited to participate, 244 completed the questionnaire. Sixty-six percent reported one or more unmet supportive care needs. The mean number of unmet needs was 4.73 (SD = 7.0, Range = 0-34). The most common unmet needs related primarily to existential survivorship issues (e.g., life stress) and relationships (e.g., sex life). Younger age and presence of chronic illness other than TC were significantly associated with higher number of unmet needs. The number of unmet needs was more highly correlated with psychological distress and HRQoL than unmet need strength. CONCLUSIONS: The majority of TC survivors reported one or more unmet needs. Unmet needs regarding existential survivorship issues were frequently reported by TC survivors despite their favorable prognosis. Relationships unmet needs were less prevalent but still more common than in breast and gynecological cancer survivors. These findings appear to be related to the young age of TC survivors. As a higher number of unmet needs is significantly associated with psychological morbidity and impaired HRQoL, interventions addressing this constellation of issues are needed.

Nurse-led supportive care management: a 6-month review of the role of a nurse practitioner in a chemotherapy unit.

OBJECTIVES: This case study evaluates the oncology nurse practitioner (NP) role in a chemotherapy unit. BACKGROUND: The NP works in the cancer centre of a major metropolitan public hospital. The NP role was established in the chemotherapy unit in 2007. The NP reviews all patients that have an unscheduled presentation to the unit, with symptoms relating either to their disease or treatment. METHODS: All unscheduled occasions of service provided by the NP in the chemotherapy unit over 6 months were recorded. Data were collected on patient demographic characteristics, medical problems and reason for presentation. Data on duration of care, interventions and outcomes administered by the NP were captured. RESULTS: There were 87 occasions of service (72 patients) during the study period. Nausea, vomiting or dehydration were the most common presenting problems and most presenting problems were moderate or severe (n = 73, 84%). The median time to review for the NP was 5 min and nearly all consultations (n = 83, 96%) took 30 min or less. Following NP consultation, most occasions of service did not require subsequent hospital admission (n = 52, 60%), medical advice (n = 61, 70%) or medical review (n = 75, 86%). CONCLUSIONS: The NP is a valuable asset to a busy department, increasing access to timely and appropriate healthcare for patients on chemotherapy.

Invoking Uncertainty: Parents' Accounts for Intrusions on Medical Authority in Pediatric Neurology.

In pediatric medical visits, parents may assume the role of co-caregiver with clinicians. At times, parents challenge physicians' authority to determine diagnoses and treatments for their children. The present study uses conversation analysis to examine parents' accounts for their intrusions on medical authority in a corpus of 35 video-recorded pediatric neurology visits for overnight video-electroencephalogram monitoring. I show how parents can exploit their legitimate role as carers to challenge medical authority. Through invoking uncertainty in contexts where they have somehow challenged medical authority, parents can account for their conduct in ways that elide direct conflict with physicians and thereby minimize damage to the physician-family partnership.

Individual symptom reduction and post-treatment severity: Varying levels of symptom amelioration in response to prolonged exposure for post-traumatic stress disorder.

Many patients evince significant post-traumatic stress disorder (PTSD) symptoms after a dose of an evidence-based treatment (EBT) for PTSD. Little research systematically addresses if individual PTSD symptoms are more or less resistant to change through an EBT for PTSD or have greater or lesser post-treatment severity levels. Two studies within VA medical centers provided data. Study 1 (n = 81) was drawn from a randomized clinical trial of Prolonged Exposure (PE), an EBT for PTSD. Study 2 (n = 225) was drawn from two PTSD specialty clinics employing PE. Symptoms were assessed pre- and post-treatments via semi-structured clinician interview (Study 1) and patient self-report (Studies 1 and 2). Most individual symptoms reduced about the same amount through the course of treatment except for avoidance, which showed greater reductions. High heterogeneity in post-treatment symptom severity was found with troubled sleep and hypervigilance displaying above average levels, and traumatic amnesia, foreshortened future, and flashbacks displaying below average levels. Method of symptom measurement had a modest impact on results, as semi-structured clinical interview results were moderately more differentiated than self-report measures. Results were generally consistent between an efficacy (i.e., extremely high, potentially artificial methodological control) and effectiveness (i.e., relatively more real world) context. Primary limitation is analysis of single items on semi-structured clinician interview and patient self-report scale when psychometric validation studies did not interpret measures this way. Moreover, DSM-IV criteria for PTSD were assessed. EBT augmentation and new treatment development should focus on further reducing both PTSD symptoms in general and on the specific symptoms of troubled sleep and hypervigilance, which persist to a greater degree. (PsycInfo Database Record (c) 2023 APA, all rights reserved).

Chemotherapy outpatients' unplanned presentations to hospital: a retrospective study.

GOAL OF WORK: This descriptive, retrospective study sought to identify the nature and magnitude of chemotherapy outpatients' unplanned presentations and admissions to the emergency department and/or cancer centre at a large metropolitan tertiary hospital, and to explore the antecedents to those presentations. PATIENTS AND METHODS: Retrospective data were collected for outpatients who made an unplanned presentation to a large metropolitan hospital in Sydney, Australia between October 1, 2006 and September 30, 2007. Detailed information was collected for those who had received cytotoxic chemotherapy at the hospital's cancer centre within the 6 months prior to the unplanned presentation to hospital. Demographic and explanatory variables were identified, including: reasons for presentation, cancer diagnosis, chemotherapy regimens, and position in the chemotherapy trajectory. MAIN RESULTS: The Cancer Institute NSW figures indicate that each year approximately 518 outpatients are treated with chemotherapy at the participating cancer centre. During the study period, 316 cancer outpatients made 469 unplanned presentations to either the Cancer Centre or the hospital emergency department. Of those outpatients presented, 233 (73.7%) had received chemotherapy in the previous 6 months and made a total of 363 presentations. Of these 363 presentations, 253 (69.7%) occurred within 4 weeks of receiving chemotherapy. The majority of presentations by those who had received chemotherapy in the previous 6 months resulted in hospital admission (87.6%) for a median length of stay of 5 days. The most frequent presentation symptoms were nausea and/or vomiting (45.2%), pain (27%), fever and/or febrile neutropenia (23.4%), shortness of breath (19.3%), dehydration (12.1%), anaemia (8.8%), fatigue (8.8%), diarrhoea (8.8%), and anxiety and/or depression (5.5%). CONCLUSIONS: Chemotherapy outpatients have significant unmet needs following treatment, indicating an urgent need for improved continuity of care and better integration of primary and tertiary health care services.

Perceptions of Patients with Primary Nonadherence to Statin Medications.

BACKGROUND: Despite emphasis on efforts to prevent cardiovascular disease (CVD), 13% to 34% of people never fill a prescribed statin (primary nonadherence). This study determined perceptions of adults with primary nonadherence to statins. METHODS: Ten focus groups were conducted with 61 adults reporting primary nonadherence to statins (93% without known CVD). Participants were recruited from an academic medical center and nationwide Internet advertisements. RESULTS: Major themes related to primary nonadherence were 1) desire to pursue alternatives before starting a statin (eg, diet and/or exercise, dietary supplements), 2) worry about risks and adverse effects of statins, 3) perceptions of good personal health (suggesting that a statin was not needed), and 4) doubt about the benefits of statins in the absence of disease. Additional themes included mistrust of the pharmaceutical industry, mistrust of prescribing providers, inadequate provider communication about statins, and negative prior experiences with medication. Although rare, a few patients said that high cholesterol does not require treatment if it is genetic. One third noted during focus group discussions that they did not communicate their decision not to take a statin to providers. CONCLUSIONS: Adults with primary nonadherence to statins describe seeking alternatives, avoiding perceived risks of statins, poor acceptance/understanding of CVD risk estimates, and doubts about the benefits of statins. Many do not disclose their decisions to providers, thus highlighting the need for provider awareness of the potential for primary nonadherence at the point of prescribing, and the need for future work to develop strategies to identify patients with potential primary nonadherence.

Generativity, the big five, and psychosocial adaptation in midlife adults.

The study examines the extent to which 2 sets of personality variables-(1) dispositional traits (and their facets) within the Big Five taxonomy and (2) the adult developmental construct of generativity-are associated with psychosocial adaptation in midlife adults (N=128), conceived as the combination of individual well-being and positive societal involvements. Generativity is conceived as an adult's concern for and commitment to promoting the well-being of future generations. Multiple regression analyses showed that dispositional traits were more strongly associated with individual well-being than was generativity, but generativity was much more strongly associated with positive societal engagement than were the traits. Correlations between dispositional traits and generativity revealed that highly generative adults were elevated on most of the facets of Extraversion and Openness. For the other 3 traits, generativity was positively related to facets of competence, achievement striving, dutifulness, altruism, and trust and negatively related to vulnerability, anxiety, depressiveness, and modesty.

Sexual Desire among Veterans Receiving Prolonged Exposure Therapy for PTSD: Does Successful PTSD Treatment Also Yield Improvements in Sexual Desire?

Objective: People with posttraumatic stress disorder (PTSD) commonly report difficulties with sexual desire and other aspects of sexual functioning, but it is currently unknown if people who respond to psychotherapy for PTSD also report improvements in sexual desire. Method: One hundred and eighty-seven veterans with PTSD received prolonged exposure (PE) therapy at two outpatient PTSD specialty clinics and completed measures of PTSD symptoms (the PTSD Checklist - Military Version) and sexual desire (item 21 of the Beck Depression Inventory - Second Edition) repeatedly throughout the course of treatment. Results: The results of a conditional generalized mixed ordinal regression model showed a significant interaction between weeks in treatment and PTSD treatment response in predicting change in sexual desire across the course of treatment. Specifically, PTSD treatment responders reported improvement in sexual desire over the course of treatment, whereas nonresponders did not show changes in sexual desire over time. However, the effect of PTSD treatment response was no longer significant when accounting for severity of depression at the start of treatment. Participants reporting more severe depression at the start of treatment reported less improvement in sexual desire, regardless of PTSD symptom response. Conclusions: People with PTSD who respond to PE also report improvements in sexual desire over time, indicating that response to PE is associated with improved sexual desire, but the effect is complicated by the presence of co-occurring depression symptomatology.

Cardiac hypertrophy in mice with long-chain acyl-CoA dehydrogenase or very long-chain acyl-CoA dehydrogenase deficiency.

Cardiac hypertrophy is a common finding in human patients with inborn errors of long-chain fatty acid oxidation. Mice with either very long-chain acyl-coenzyme A dehydrogenase deficiency (VLCAD-/-) or long-chain acyl-coenzyme A dehydrogenase deficiency (LCAD-/-) develop cardiac hypertrophy. Cardiac hypertrophy, initially measured using heart/body weight ratios, was manifested most severely in LCAD-/- male mice. VLCAD-/- mice, as a group, showed a mild increase in normalized cardiac mass (8.8% hypertrophy compared with all wild-type (WT) mice). In contrast, LCAD-/- mice as a group showed more severe cardiac hypertrophy (32.2% increase compared with all WT mice). On the basis of a clear male predilection, we analyzed the role of dietary plant estrogenic compounds commonly found in mouse diets because of soy or alfalfa components providing natural phytoestrogens or isoflavones in cardioprotection of LCAD-/- mice. Male LCAD-/- mice fed an isoflavone-free test diet had more severe cardiac hypertrophy (58.1% hypertrophy compared with WT mice fed the same diet). There were no significant differences in the female groups fed any of the diets. Echocardiography measurement performed on male LCAD-deficient mice fed a standard diet at the age of approximately 3 months confirmed the substantial cardiac hypertrophy in these mice compared with WT controls. Left ventricular (LV) wall thickness of the interventricular septum and posterior wall was remarkably increased in LCAD-/- mice compared with that of WT controls. Accordingly, the calculated LV mass after normalization to body weight was increased by about 40% in the LCAD-/- mice compared with WT mice. In summary, we found that metabolic cardiomyopathy, expressed as hypertrophy, developed in mice because of either VLCAD deficiency or LCAD deficiency; however, LCAD deficiency was the most profound and seemed to be attenuated either by endogenous estrogen (in females) or by phytoestrogens present in the diet as isoflavones (in males).