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1.
J Subst Use Addict Treat ; 160: 209306, 2024 May.
Article in English | MEDLINE | ID: mdl-38296033

ABSTRACT

INTRODUCTION: Methadone and buprenorphine are effective and safe treatments for opioid use disorder (OUD) and also reduce overdose and all-cause mortality. Identifying and reaching providers of medication for opioid use disorder (MOUD) has proven difficult for prospective patients and researchers. OBJECTIVES: To assess the accuracy of government-maintained lists of Arizona (AZ) providers prescribing MOUD, and the extent to which these providers are accessible for treatment. METHODS: A two-phase study used a listing of 2376 AZ MOUD providers obtained from the U.S. Drug Enforcement Administration and the Substance Abuse and Mental Health Services Administration. Phase 1 assessed the accuracy of the listing using internet confirmatory research from May-October 2022. Phase 2 used the resulting list of 838 providers to assess provider availability, type of MOUD treatment provided, and accepted payment through secret shopper calls between November 16 and 30, 2022. RESULTS: Just over half (52.2 %, n = 1240) of providers were removed from the original listing during Phase 1. One quarter (25.9 %) were no longer in practice. Among the 833 eligible for the secret shopper Phase 2 study, 36.6 % (n = 307) were reached and identified as providing MOUD. A vast majority (88.1 %) of MOUD providers indicating treatment type were accepting new patients, however methadone was identified far more frequently than was likely permitted or provided for OUD. Providers were 5.5 times more likely to accept new patients if they accepted cash payment for services, and 4.9 times more likely if they accepted Medicaid. Rural areas remained underserved. CONCLUSIONS: The active population of MOUD providers is far smaller than surmised. DEA and SAMHSA provider listings are not sufficiently accurate for survey research sampling. Other means of representative sampling will need to be devised, and trusted lists of providers for prospective patients should be promoted, publicly available, and regularly maintained for accuracy. Providers that offer treatment should assure that public-facing staff have basic information about the practice, the treatment offered, and conditions for taking new patients. Concerted efforts must assure rural access at the most local levels to reduce patient travel burden.


Subject(s)
Buprenorphine , Methadone , Opiate Substitution Treatment , Opioid-Related Disorders , Humans , Arizona , Methadone/therapeutic use , Buprenorphine/therapeutic use , Opioid-Related Disorders/drug therapy , Opioid-Related Disorders/epidemiology , Health Services Accessibility , Analgesics, Opioid/therapeutic use , United States , Physicians
3.
Ir Med J ; 115(5): 596, 2022 05 25.
Article in English | MEDLINE | ID: mdl-35696231

ABSTRACT

Aim Orthostatic Hypotension (OH) is an indicator of deteriorating autonomic dysfunction. Adherence to BP and OH measurement guidelines in an inpatient specialist palliative care unit (SPCU) was unknown. Compliance of BP and OH measurement in an advanced cancer cohort was audited. Methods A retrospective analysis of four consecutive months of patients admitted with an advanced cancer diagnosis to the inpatient SPCU was conducted. Data was obtained from 168 clinical records, and audited against current institutional clinical standards. Results Falls risk screening including BP and OH measurements were not measured on admission in 19% (n=32) cases as recommended by institutional guidelines. Where falls risks were identified in 94 (69%) patients only 71 (76%) of these had completed risk assessments. OH testing was incomplete or not conducted in 59% (n=42) of risk assessments. This had patient care and safety implications e.g. under-reporting falls risk. In addition, institutional guidelines were inflexible in clinical practice specific to a palliative care cohort of patient. Conclusions Institutional guidelines need regular reviewing. In cases where a healthcare professional determines it is inappropriate to perform an assessment, we recommend a modification to the tools allowing for recording of this decision. OH is an underestimated reality in hospice populations and the impact on hospice services is worthy of further study.


Subject(s)
Hypotension, Orthostatic , Neoplasms , Accidental Falls/prevention & control , Blood Pressure/physiology , Humans , Hypotension, Orthostatic/diagnosis , Hypotension, Orthostatic/epidemiology , Hypotension, Orthostatic/etiology , Neoplasms/complications , Retrospective Studies
4.
Am J Addict ; 30(4): 305-315, 2021 07.
Article in English | MEDLINE | ID: mdl-33378137

ABSTRACT

BACKGROUND AND OBJECTIVES: Buprenorphine's high-binding affinity as a partial µ-opioid agonist displaces preexisting full agonists causing precipitated withdrawal, which requires most individuals starting buprenorphine to endure moderate withdrawal prior to induction to avoid precipitated withdrawal. A novel approach called microinduction has emerged to remove this prerequisite. Our aim is to review the literature on these alternative approaches. METHODS: Using keywords including buprenorphine, buprenorphine/naloxone, transdermal buprenorphine, suboxone, microinduction, microdosing, rapid induction, buprenorphine-dosing protocol, the authors searched PubMed/Medline, EMBASE, PsycINFO, PsychARTICLES, and Scopus databases from the date of inception through April 30, 2020, which yielded 1726 results, which, in turn, after manual exclusion for irrelevant content and publication in languages other than English, generated a total of 18 papers. RESULTS: On the basis of 18 papers included in this review, 63 patients were successfully transitioned to buprenorphine using different microdosing techniques, primarily in the inpatient setting. From the available data, patients were transitioned from a variety of opioids over a range of dosing without significant withdrawal, and initial doses ranged most frequently from 0.2 to 0.5 mg. While the timeframe for the various schedules ranged from 3 to 112 days, most transitioned over a period of 4 to 8 days, and most participants completed the cross titration at 8 to 16 mg. DISCUSSION AND CONCLUSIONS: The growing literature demonstrates some initial promise for alternative induction models, specifically targeting patients averse to withdrawal, patients prescribed opioids for chronic pain, patients on high-dose methadone, and patients using illicit or pharmaceutical fentanyl. SCIENTIFIC SIGNIFICANCE: This manuscript provides a review of the existing literature to help clinicians better understand the approaches to microdosing of buprenorphine in various clinical settings and populations. (Am J Addict 2020;00:00-00).


Subject(s)
Buprenorphine/administration & dosage , Naloxone/administration & dosage , Drug Administration Schedule , Humans
5.
Acad Psychiatry ; 44(3): 320-323, 2020 Jun.
Article in English | MEDLINE | ID: mdl-31828674

ABSTRACT

OBJECTIVE: The study's objectives were to assess the psychotherapy interests and needs of psychiatry residents, to develop a psychotherapy didactic curriculum for psychiatry residents on the inpatient service, and to evaluate residents' self-reported understanding and confidence with skills-based interventions. METHODS: Psychiatry residents within a major metro region in the Northeast were asked if they would voluntarily participate in a survey to assess their interest and skills. Based on the results of this survey, the authors devised an 8-week course for seventeen residents on the inpatient unit. Topics included general cognitive behavioral therapy (CBT), sleep hygiene, behavioral activation, dialectical behavioral therapy (DBT), mind-body skills, and motivational interviewing. Residents completed post-course questionnaires on comprehension and confidence in providing psychotherapy skills using 5-point Likert scales. RESULTS: Participants (N = 39) reported a strong interest in learning psychotherapy and in education focused on inpatient skills-based interventions. At the end of the course, 12/17 (70.6%) participants provided feedback to indicate that 9/12 (75%) respondents experienced increased confidence in therapy skills, 10/12 (83.3%) reported a basic understanding of skills-based psychotherapy, and 10/12 (83.4%) believed they could teach at least one new technique. CONCLUSION: Psychiatry residents in this study overwhelmingly requested additional training focused on skills relevant to inpatient service, and the curriculum the authors developed led to a subjective self-reported understanding of and confidence in providing these psychotherapy skills on the inpatient unit. These very preliminary results suggest that provision of increased skills-based psychotherapy training for inpatient psychiatry residents is important and beneficial within resident education.


Subject(s)
Curriculum , Internship and Residency , Needs Assessment , Psychiatry/education , Psychotherapy/education , Cognitive Behavioral Therapy , Education, Medical, Graduate , Humans , Inpatients , Motivational Interviewing , Pilot Projects , Surveys and Questionnaires
6.
Support Care Cancer ; 26(10): 3353-3364, 2018 Oct.
Article in English | MEDLINE | ID: mdl-29961146

ABSTRACT

Fatigue is one of the most common and debilitating cancer symptoms, and is associated with impaired quality of life. The exact pathophysiology of cancer-related fatigue (CRF) is poorly understood, but in any individual, it is likely multifactorial and involves inter-related cytokine, muscular, neurotransmitter, and neuroendocrine changes. Underlying CRF mechanisms proposed include central and peripheral hypotheses. Central mechanisms include hypotheses about cytokine dysregulation, hypothalamic-pituitary-adrenal-axis disruption, circadian rhythm disruption, serotonin, and vagal afferent nerve function while peripheral mechanisms include hypotheses about adenosine triphosphate and muscle contractile properties. Currently, these hypotheses are largely based on evidence from other conditions in which fatigue is characteristic. The purpose of this article is to provide a narrative review of the literature and present the current controversies in the pathophysiology of CRF, particularly in relation to central and peripheral hypotheses for CRF. An understanding of pathophysiology may facilitate direct and simple therapeutic interventions for those with cancer.


Subject(s)
Fatigue/physiopathology , Neoplasms/complications , Quality of Life/psychology , Humans
8.
Intern Med J ; 47(3): 280-283, 2017 Mar.
Article in English | MEDLINE | ID: mdl-27658500

ABSTRACT

BACKGROUND: In recent years, there has been a significant increase in the number of cancer treatments that have become available. However, it has remained difficult to choose the most appropriate time to cease active therapy in individual patients. AIMS: To determine the proportion of patients being treated with palliative intent who received systemic anticancer treatment in the last 30 days of life. METHODS: This is a retrospective cohort study conducted within the Melbourne Oncology Group at Cabrini Hospital. Patients managed with palliative intent who died between 1 January 2014 and 30 June 2014 were included. Outcomes measured were the percentage of patients who received systemic anticancer treatment in the last 30 days of life, palliative care referral status, Emergency Department presentations, hospital admissions and place of death. RESULTS: A total of 80 patients was included in the study. Of these patients, 21 (26%) received systemic anticancer treatment in the last 30 days of life. There was no statistically significant difference between patients who received treatment in the last month of life and those who did not in terms of the number of patients who were referred to palliative care, presented to an Emergency Department, were admitted to hospital or died in an acute ward. CONCLUSION: Although over a quarter of patients dying from advanced cancer received anticancer treatment in the last month of life, these patients did not present acutely to hospital more often and had the same extent of palliative care team involvement.


Subject(s)
Hospitals, Private , Neoplasms/therapy , Palliative Care/organization & administration , Terminal Care/organization & administration , Terminally Ill , Aged , Aged, 80 and over , Australia/epidemiology , Female , Hospitalization , Hospitals, Private/organization & administration , Humans , Male , Middle Aged , Neoplasms/mortality , Palliative Care/statistics & numerical data , Prevalence , Quality of Life , Retrospective Studies , Terminal Care/statistics & numerical data , Terminally Ill/psychology , Terminally Ill/statistics & numerical data
9.
J Assist Reprod Genet ; 33(12): 1615-1620, 2016 Dec.
Article in English | MEDLINE | ID: mdl-27639996

ABSTRACT

With the improvement of long-term cancer survival rates, growing numbers of female survivors are suffering from treatment-related premature ovarian insufficiency (POI). Although pre-treatment embryo and oocyte storage are effective fertility preservation strategies, they are not possible for pre-pubertal girls or women who cannot delay treatment. In these cases, the only available treatment option is ovarian cortex cryopreservation and subsequent re-implantation. A 32-year-old woman had ovarian cortex cryopreserved 10 years previously before commencing high-dose chemotherapy and undergoing a haematopoietic stem cell transplant for recurrent adult Wilms tumour, which resulted in POI. She underwent laparoscopic orthotopic transplantation of cryopreserved ovarian cortex to the original site of biopsy on the left ovary. She ovulated at 15 and 29 weeks post-re-implantation with AMH detectable, then rising, from 21 weeks, and conceived naturally following the second ovulation. The pregnancy was uncomplicated and a healthy male infant was born by elective Caesarean section at 36+4 weeks gestation. This is the first report of ovarian cortex re-implantation in the UK. Despite the patient receiving low-risk chemotherapy prior to cryopreservation and the prolonged tissue storage duration, the re-implantation resulted in rapid restoration of ovarian function and natural conception with successful pregnancy.


Subject(s)
Fertility Preservation , Hematopoietic Stem Cell Transplantation , Pregnancy Complications, Neoplastic , Wilms Tumor/therapy , Adult , Cryopreservation , Female , Gametogenesis/genetics , Humans , Live Birth , Neoplasm Recurrence, Local/pathology , Neoplasm Recurrence, Local/therapy , Oocytes/growth & development , Oocytes/pathology , Ovary/growth & development , Ovary/pathology , Pregnancy , United Kingdom , Wilms Tumor/complications , Wilms Tumor/pathology
10.
Int Psychogeriatr ; 27(7): 1071-87, 2015 Jul.
Article in English | MEDLINE | ID: mdl-25633917

ABSTRACT

BACKGROUND: Four constructs are encompassed by the term "falls-related psychological concerns" (FrPC); "fear of falling" (FOF), "falls-related self-efficacy" (FSe), "balance confidence" (BC) and "outcome expectancy" (OE). FrPC are associated with negative consequences including physical, psychological, and social. Identifying factors associated with FrPC could inform interventions to reduce these concerns. METHODS: Sixty-two empirical papers relating to psychological factors associated with FrPC in community-dwelling older people (CDOP) were reviewed. Four levels of evidence were used when evaluating the literature: good, moderate, tentative, and none. RESULTS: Evidence that anxiety predicted FOF, BC, and OE was tentative. Moderate evidence was found for anxiety predicting FSe. Good evidence was found for depression predicting FSe. Moderate evidence was found for depression predicting both FOF and BC. No evidence was found for depression predicting OE. Tentative evidence was found for FSe predicting depression. Good and moderate evidence was found for quality of life (QoL) being predicted by FOF and BC respectively. Tentative evidence was found for FSe predicting QoL. Moderate evidence was found for QoL predicting both FSe and BC. No evidence was found for QoL predicting FOF. Good and moderate evidence was found for activity avoidance/restriction (AA/AR) being predicted by FOF and FSe respectively. Tentative evidence was found for BC and OE predicting AA/AR, as well as for AA/AR predicting FOF. Moderate evidence for activity level (AL) predicting FOF was identified, however the evidence of this predicting FSe and BC was tentative. Evidence for FOF, FSe, and BC predicting AL was tentative as was evidence to suggest FOF predicted coping. CONCLUSIONS: Mixed evidence has been found for the association of psychological factors in association with FrPCs. Future research should employ theoretically grounded concepts, use multivariate analysis and longitudinal designs.


Subject(s)
Accidental Falls/statistics & numerical data , Aging/psychology , Anxiety/diagnosis , Depression/diagnosis , Fear/psychology , Aged , Aged, 80 and over , Female , Geriatric Assessment , Humans , Independent Living , Male , Middle Aged , Postural Balance , Psychiatric Status Rating Scales , Psychology , Quality of Life , Self Efficacy
11.
Circulation ; 130(15): 1254-61, 2014 Oct 07.
Article in English | MEDLINE | ID: mdl-25200210

ABSTRACT

BACKGROUND: Many clinical trials use composite end points to reduce sample size, but the relative importance of each individual end point within the composite may differ between patients and researchers. METHODS AND RESULTS: We asked 785 cardiovascular patients and 164 clinical trial authors to assign 25 "spending weights" across 5 common adverse events comprising composite end points in cardiovascular trials: death, myocardial infarction, stroke, coronary revascularization, and hospitalization for angina. We then calculated end point ratios for each participant's ratings of each nonfatal end point relative to death. Whereas patients assigned an average weight of 5 to death, equal or greater weight was assigned to myocardial infarction (mean ratio, 1.12) and stroke (ratio, 1.08). In contrast, clinical trialists were much more concerned about death (average weight, 8) than myocardial infarction (ratio, 0.63) or stroke (ratio, 0.53). Both patients and trialists considered revascularization (ratio, 0.48 and 0.20, respectively) and hospitalization (ratio, 0.28 and 0.13, respectively) as substantially less severe than death. Differences between patient and trialist end point weights persisted after adjustment for demographic and clinical characteristics (P<0.001 for all comparisons). CONCLUSIONS: Patients and clinical trialists did not weigh individual components of a composite end point equally. Whereas trialists are most concerned about avoiding death, patients place equal or greater importance on reducing myocardial infarction or stroke. Both groups considered revascularization and hospitalization as substantially less severe. These findings suggest that equal weights in a composite clinical end point do not accurately reflect the preferences of either patients or trialists.


Subject(s)
Angina, Unstable , Clinical Trials as Topic/psychology , Endpoint Determination/psychology , Health Personnel/psychology , Myocardial Infarction , Patients/psychology , Stroke , Aged , Aged, 80 and over , Angina, Unstable/mortality , Angina, Unstable/prevention & control , Data Collection , Female , Hospitalization , Humans , Male , Myocardial Infarction/mortality , Myocardial Infarction/prevention & control , Patient Preference , Patient-Centered Care , Percutaneous Coronary Intervention , Risk Factors , Stroke/mortality , Stroke/prevention & control
12.
Rev Sci Instrum ; 85(2): 023101, 2014 Feb.
Article in English | MEDLINE | ID: mdl-24593343

ABSTRACT

The high output voltages from piezoelectric transformers are currently being used to accelerate charged particle beams for x-ray and neutron production. Traditional methods of characterizing piezoelectric transformers (PTs) using electrical probes can decrease the voltage transformation ratio of the device due to the introduction of load impedances on the order of hundreds of kiloohms to hundreds of megaohms. Consequently, an optical diagnostic was developed that used the photoelastic and electro-optic effects present in piezoelectric materials that are transparent to a given optical wavelength to determine the internal stress and electric field. The combined effects of the piezoelectric, photoelastic, and electro-optic effects result in a time-dependent change the refractive indices of the material and produce an artificially induced, time-dependent birefringence in the piezoelectric material. This induced time-dependent birefringence results in a change in the relative phase difference between the ordinary and extraordinary wave components of a helium-neon laser beam. The change in phase difference between the wave components was measured using a set of linear polarizers. The measured change in phase difference was used to calculate the stress and electric field based on the nonlinear optical properties, the piezoelectric constitutive equations, and the boundary conditions of the PT. Maximum stresses of approximately 10 MPa and electric fields of as high as 6 kV/cm were measured with the optical diagnostic. Measured results were compared to results from both a simple one-dimensional (1D) model of the piezoelectric transformer and a three-dimensional (3D) finite element model. Measured stresses and electric fields along the length of an operating length-extensional PT for two different electrical loads were within at least 50 % of 3D finite element simulated results. Additionally, the 3D finite element results were more accurate than the results from the 1D model for a wider range of electrical load impedances under test.

13.
Ir J Med Sci ; 182(2): 283-6, 2013 Jun.
Article in English | MEDLINE | ID: mdl-22983882

ABSTRACT

BACKGROUND: Sarcoidosis is a multisystem granulomatous disease of unknown origin with pulmonary and extrapulmonary manifestations. Worldwide it is most often diagnosed in the third and fourth decades and most often affects Swedish, Danish and black patients. The association between malignancy and sarcoidosis has not been conclusively proven. Cancer can eventually occur in patients who have an established diagnosis of sarcoidosis for example, in sarcoidosis-lymphoma syndrome. Sarcoidosis can also subsequently develop in an oncology patient. There are multiple obstacles to confirming epidemiologically the linkage between sarcoidosis and malignancy. Histological verification and clinical acumen are needed to avoid misdiagnosis. The 18 fluorodeoxyglucose (18-FDG) PET has failed to provide a non invasive diagnostic method to differentiate neoplasia from benign sarcoid lesions and tissue diagnosis is essential before commencing a new therapeutic intervention in patients with lymphoma. METHODS: We report 3 cases of co-diagnosis of sarcoidosis and lymphoma that were seen in an oncology unit in Drogheda, Co. Louth. RESULTS: Our patients varied in the temporal association between the diagnosis of sarcoidosis and lymphoma as well as their demographic characteristics. CONCLUSION: These cases help to demonstrate the need for careful clinical, histological and radiological assessment.


Subject(s)
Lymphoma/complications , Sarcoidosis/complications , Adult , Female , Humans , Lung/pathology , Lymph Nodes/pathology , Lymphoma/diagnosis , Male , Middle Aged , Sarcoidosis/diagnosis
14.
Article in English | MEDLINE | ID: mdl-21623495

ABSTRACT

Acrylamide concentrations in prune products--baby strained prunes (range = 75-265 µg kg(-1)), baby apple/prune juice (33-61 µg kg(-1)), prune juice (186-916 µg kg(-1)) and prunes (58-332 µg kg(-1))--on the Canadian market were determined. The formation of acrylamide in a simulated plum juice was also investigated under 'drying conditions' in an open vessel at temperatures <100°C for 24 h and under 'wet conditions' in a closed vessel at a temperature of 120°C for 1 h. Acrylamide was produced in a simulated plum juice under 'drying conditions' in amounts comparable with those found in prunes and prune juices. Acrylamide was not produced in simulated plum juice under 'wet conditions' in a closed vessel at temperature of 120°C for 1 h, but under the same condition an authentic prune juice doubled its acrylamide concentration. Formation of acrylamide in prune products was attributed to the presence of asparagine and sugars in the starting materials.


Subject(s)
Acrylamide/analysis , Beverages/analysis , Food Contamination , Food Handling/methods , Fruit/chemistry , Models, Chemical , Prunus/chemistry , Acrylamide/chemistry , Asparagine/chemistry , Canada , Food Contamination/prevention & control , Fructose/chemistry , Hot Temperature/adverse effects , Humans , Infant , Infant Food/analysis , Reproducibility of Results
15.
Haemophilia ; 17(3): 407-11, 2011 May.
Article in English | MEDLINE | ID: mdl-21382134

ABSTRACT

Previous studies have suggested that development of inhibitors in previously treated patients (PTPs) may be attributable to a switch in factor VIII (FVIII) therapeutic product. Consequently, it is widely recognized that inhibitor development must be assessed in PTPs following the introduction of any new FVIII product. Following a national tender process in 2006, all patients with haemophilia A in Ireland changed their FVIII treatment product en masse to a plasma and albumin-free recombinant full-length FVIII product (ADVATE(®)). In this study, we retrospectively reviewed the case records of Irish PTPs to evaluate risk of inhibitor formation following this treatment switch. One hundred and thirteen patients participated in the study. Most patients (89%) had severe haemophilia. Only one of 96 patients with no inhibitor history developed an inhibitor. Prior to the switch in his recombinant FVIII (rFVIII) treatment of choice, this child had only experienced three exposure days (EDs). Consequently, in total he had only received 6 EDs when his inhibitor was first diagnosed. In keeping with this lack of de novo inhibitor development, we observed no evidence of any recurrent inhibitor formation in any of 16 patients with previously documented inhibitors. Similarly, following a previous en masse switch, we have previously reported that changing from a Chinese hamster ovary cell-produced to a baby hamster kidney cell-produced rFVIII was also associated with a low risk of inhibitor formation in PTPs. Our cumulative findings from these two studies clearly emphasizes that the risk of inhibitor development for PTPs following changes in commercial rFVIII product is low, at least in the Irish population.


Subject(s)
Autoantibodies/analysis , Blood Coagulation Factor Inhibitors/blood , Factor VIII/immunology , Factor VIII/therapeutic use , Hemophilia A/drug therapy , Adolescent , Adult , Child , Child, Preschool , Hemophilia A/blood , Humans , Recombinant Proteins/blood , Retrospective Studies , Serum Albumin , Young Adult
16.
Hum Reprod ; 21(1): 285-94, 2006 Jan.
Article in English | MEDLINE | ID: mdl-16172147

ABSTRACT

BACKGROUND: The combination of etonogestrel implants with injectable testosterone decanoate was investigated as a potential male contraceptive. METHODS: One hundred and thirty subjects were randomly assigned to three treatment groups, all receiving two etonogestrel rods (204 mg etonogestrel) and 400 mg testosterone decanoate either every 4 weeks (group I, n = 42), or every 6 weeks (group II, n = 51) or 600 mg testosterone decanoate every 6 weeks (group III, n = 37) for a treatment period of 48 weeks. RESULTS: One hundred and ten men completed 48 weeks of treatment. Sperm concentrations of <1 x 10(6)/ml were achieved in 90% (group I), 82% (group II) and 89% (group III) of subjects by week 24. Suppression was slower in group II, which also demonstrated more frequent escape from gonadotrophin suppression than groups I and III. Peak testosterone concentrations remained in the normal range throughout in all groups. Mean trough testosterone concentrations were initially subphysiological but increased into the normal range during treatment. Mean haemoglobin levels increased in group I, and a non-significant increase in weight and decline in high-density lipoprotein cholesterol was observed in all groups. Fourteen subjects discontinued treatment due to adverse events. CONCLUSIONS: Subcutaneous etonogestrel implants in combination with injectable testosterone decanoate resulted in profound suppression of spermatogenesis that could be maintained for up to 1 year. Efficacy of suppression was less in group II, probably due to inadequate testosterone dosage. This combination has potential as a long-acting male hormonal contraceptive.


Subject(s)
Contraceptive Agents, Male/administration & dosage , Delayed-Action Preparations/administration & dosage , Desogestrel/administration & dosage , Spermatozoa/drug effects , Testosterone/analogs & derivatives , Administration, Cutaneous , Adolescent , Adult , Behavior/drug effects , Contraceptive Agents, Male/adverse effects , Delayed-Action Preparations/adverse effects , Desogestrel/adverse effects , Follicle Stimulating Hormone/blood , Humans , Luteinizing Hormone/blood , Male , Middle Aged , Sperm Count , Testosterone/administration & dosage , Testosterone/adverse effects , Testosterone/blood
17.
Hum Reprod ; 19(11): 2658-67, 2004 Nov.
Article in English | MEDLINE | ID: mdl-15333595

ABSTRACT

BACKGROUND: Combined testosterone and progestogen preparations are a promising approach to male hormonal contraception. We investigated the effect of s.c. etonogestrel with depot testosterone on spermatogenesis in normal men over a period of 48 weeks. METHODS: Fifteen healthy men received three s.c. 68 mg etonogestrel implants. Testosterone pellets (400 mg) were administered at 12 weekly intervals. RESULTS: Nine men completed 48 weeks of treatment. Four subjects chose to discontinue after 6 months, one man withdrew from the study early for personal reasons and one was withdrawn due to illness. Sperm concentrations of <1 x 10(6)/ml were achieved in all men by 16 weeks of treatment. All men became azoospermic, although the time to achieve this varied from 8 to 28 weeks. Azoospermia was maintained in eight of the nine men treated for 48 weeks, one subject showing partial recovery from 40 weeks. Testosterone levels remained in the physiological range throughout. Treatment did not result in weight gain, change in body composition or decline in high-density lipoprotein cholesterol concentrations. CONCLUSIONS: The combination of three etonogestrel implants with depot testosterone results in rapid and consistent suppression of spermatogenesis. This can be maintained for up to 1 year and may therefore be a suitable approach for a long-acting male hormonal contraceptive.


Subject(s)
Contraceptive Agents, Male/administration & dosage , Contraceptive Agents, Male/adverse effects , Desogestrel/administration & dosage , Desogestrel/adverse effects , Oligospermia/chemically induced , Testosterone/administration & dosage , Testosterone/adverse effects , Adolescent , Adult , Body Composition/drug effects , Desogestrel/blood , Dose-Response Relationship, Drug , Drug Implants , Epitestosterone/blood , Epitestosterone/urine , Follicle Stimulating Hormone/blood , Hemoglobins/analysis , Humans , Inhibins/blood , Lipids/blood , Luteinizing Hormone/blood , Male , Oligospermia/metabolism , Sexual Behavior/drug effects , Sperm Count , Spermatogenesis/drug effects , Testosterone/blood
18.
Clin Endocrinol (Oxf) ; 58(4): 506-12, 2003 Apr.
Article in English | MEDLINE | ID: mdl-12641635

ABSTRACT

OBJECTIVE: Synthetic gestogens in combination with testosterone have potential as a male hormonal contraceptive, predominantly acting by augmenting suppression of gonadotrophin secretion. Little is known, however, of the effects of gestogens in the male. Gestogens have affinity for both androgen and progesterone receptors but the relative contribution of action at these two receptors in gonadotrophin suppression remains unclear. In this study the effects of progesterone, with no significant androgen-receptor affinity are compared to desogestrel, a synthetic gestogen with relatively low affinity for the androgen receptor, on gonadotrophin secretion in normal men. DESIGN: Subjects received either 50 mg progesterone intramuscularly (i.m.) or 300 micro g desogestrel orally daily for 7 days. Frequent blood sampling over 12 h was undertaken before and after drug administration. GnRH [100 micro g intravenously (i.v.)] was administered 2 h before the end of the frequent sampling period. SUBJECTS: Twenty healthy men were randomly allocated to the two treatment groups. RESULTS: Both progesterone and desogestrel administration resulted in decreases in the concentration of both LH and FSH secretion, as well as testosterone. Analysis of the pulsatile nature of LH secretion indicated that both treatments reduced LH pulse amplitude, and that progesterone reduced LH pulse frequency. Progesterone, but not desogestrel, treatment also reduced the increase in LH secretion in response to GnRH. CONCLUSIONS: The effects of progesterone were at least as marked as those of a maximally effective dose of desogestrel. As progesterone has negligible affinity for the androgen receptor, these results are compatible with the suppressive effects of synthetic 19-norgestogens on gonadotrophin secretion in the male being mediated via the progesterone receptor, with its androgenicity contributing minimally to gonadotrophin suppression.


Subject(s)
Desogestrel , Gonadotropins, Pituitary/blood , Hormones , Progesterone , Receptors, Progesterone/drug effects , Administration, Oral , Adolescent , Adult , Contraceptive Agents, Male/pharmacology , Depression, Chemical , Follicle Stimulating Hormone/blood , Gonadotropin-Releasing Hormone , Humans , Inhibins/blood , Injections, Intramuscular , Luteinizing Hormone/blood , Male , Testosterone/blood
19.
Mar Pollut Bull ; 42(10): 873-8, 2001 Oct.
Article in English | MEDLINE | ID: mdl-11693641

ABSTRACT

Imposex, the phenomenon in which induced male sex characteristics are superimposed on normal females, still occurs widely in the gastropod Thais orbita from Port Philip Bay, and its incidence is greatest in areas that have high boating and shipping activities. Compared to 1992, both the extent and severity of imposex has reduced. By inference, this means that pollution by tributyltin (TBT) in Port Phillip Bay has decreased and that the bans limiting its use to vessels greater than 25 m in length, in place since 1989, have been effective. However, TBT pollution is still an issue at locations that are adjacent to major ports, such as the Port of Melbourne, where TBT from large ships and ship maintenance activities continues to pollute fish habitats. It is anticipated that the incidence of imposex, and therefore TBT pollution, will continue to decrease in Port Phillip Bay as long as the bans currently in place continue to be observed. If the trends observed in the present study continue, then it is unlikely, with the notable exception of commercial ports, that TBT will pose a threat to the health of fish habitats in Port Phillip Bay.


Subject(s)
Mollusca/anatomy & histology , Trialkyltin Compounds/adverse effects , Water Pollutants, Chemical/adverse effects , Animals , Australia , Environmental Monitoring , Female , Gonads/abnormalities , Incidence , Male , Mollusca/drug effects , Oceans and Seas , Sex Characteristics , Ships , Trialkyltin Compounds/analysis , Water Pollutants, Chemical/analysis
20.
Dermatology ; 202(1): 1-3, 2001.
Article in English | MEDLINE | ID: mdl-11244219

ABSTRACT

Females with Turner's syndrome (TS) have a markedly increased number of cutaneous nevi. While this is a well-recognized risk factor for cutaneous melanoma (CM), the incidence of this tumor in TS and the implications for our understanding of nevi and melanoma have not previously been considered. Here we report a case of an anorectal melanoma in a woman with TS and a review of the literature. Overall, there appears to be a lower than expected incidence of CM. Possible explanations are discussed and in particular the possible relationship between sex hormones and melanoma development as these girls fail to undergo normal pubertal development. Further study of this syndrome may provide important insights into the genetic factors involved in normal melanocyte and nevus development, the potential influence of sex hormones on melanoma development and the relationship between the presence of nevi and the risk of developing CM.


Subject(s)
Melanoma/complications , Nevus/complications , Skin Neoplasms/complications , Turner Syndrome/complications , Adult , Female , Humans , Melanoma/pathology , Nevus/pathology , Skin Neoplasms/pathology
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