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1.
Trauma Violence Abuse ; : 15248380241241018, 2024 Apr 27.
Article in English | MEDLINE | ID: mdl-38676377

ABSTRACT

The impact of caregiving on caregivers' mental health is typically considered within the caregiver stress and burden literature; however, more recently, research has investigated the experience of post-traumatic stress symptoms (PTSS) in caregivers. As an emerging area of research, it is timely to conduct a scoping review to map the existing literature in relation to PTSS among adult caregivers of children and adults with neurodevelopmental disorders (NDD), neurocognitive disorders, and psychiatric disorders. The scoping review was conducted using Preferred Reporting Items of Systematic Reviews and Meta-Analyses Extension for Scoping Reviews guidelines and Arksey and O'Malley's five-stage methodology framework. Published and unpublished gray literature between 2005 and 2022 was included in the scoping review. Nine thousand one hundred and twenty-five studies were originally identified for screening and 22 studies were selected for inclusion in the final review. Trauma and PTSS experienced by NDD caregivers were related to news breaking, NDD diagnosis, and behavioral issues, whereas caregivers of individuals with psychosis reported aggression and violence as traumatic events. Studies showed that up to half of caregivers reported PTSS, although no conclusions could be drawn about prevalence rates. A wide variety of tools measuring PTSS were used across the 22 studies. Many symptoms of PTSS were reported by caregivers, and cognitive appraisals were associated with PTSS in caregivers. The findings highlight the importance of recognizing the impact of trauma in caregiver mental health and the potential value of using traumatic stress frameworks with these populations. Research should be expanded to establish prevalence rates and to examine the long-term impact of trauma on caregiving as caregivers and care recipients age.

2.
Sleep Breath ; 28(1): 231-239, 2024 Mar.
Article in English | MEDLINE | ID: mdl-37548919

ABSTRACT

PURPOSE: The objective was to determine if alteration in airflow induced by negative pressure (NP) applied to participants' upper airways during wakefulness, is related to obstructive sleep apnea (OSA) severity as determined by the apnea-hypopnea index (AHI). METHODS: Adults 18 years of age or greater were recruited. All participants underwent overnight polysomnography to assess their apnea-hypopnea index (AHI). While awake, participants were twice exposed, orally, to -3 cm H2O of NP for five full breaths. The ratio of the breathing volumes of the last two breaths during NP exposure to the last two breaths prior to NP exposure was deemed the NP ratio (NPR). RESULTS: Eighteen participants were enrolled. A strong relationship between the AHI and the exponentially transformed NPR (ExpNPR) for all participants was observed (R2 = 0.55, p < 0.001). A multivariable model using the independent variable ExpNPR, age, body mass index and sex accounted for 81% of variability in AHI (p = 0.0006). A leave-one-subject-out cross-validation analysis revealed that predicted AHI using the multivariable model, and actual AHI from participants' polysomnograms, were strongly related (R2 = 0.72, p < 0.001). CONCLUSION: We conclude that ExpNPR, was strongly related to the AHI, independently of demographic factors known to be related to the AHI.


Subject(s)
Sleep Apnea, Obstructive , Wakefulness , Adult , Humans , Sleep Apnea, Obstructive/diagnosis , Polysomnography , Respiratory Physiological Phenomena , Nose
3.
BMJ Open ; 12(11): e058118, 2022 11 16.
Article in English | MEDLINE | ID: mdl-36385025

ABSTRACT

INTRODUCTION: The challenges of providing caregiving that impacts the caregiver have been attributed to high levels of intensity and physical strain, burden and distress. This is likely to include emotional and psychological distress as manifested in post-traumatic stress symptoms (PTSS). As this is a new area of investigation among caregivers of individuals with neurodevelopmental, neurocognitive and psychiatric disorders, the extent of the literature for PTSS in these groups of caregivers is limited and unclear. This scoping review aims to map the existing research focusing on key concepts and identifying gaps in relation to PTSS among these caregivers. METHODS AND ANALYSIS: The scoping review will be guided by Arksey and O'Malley's proposed 5-stage framework. A search for published and unpublished grey literature between years 2005 to 2020 in the electronic databases of CINAHL, SCOPUS, PsychInfo, OVID PubMed and ProQuest Dissertation, and Thesis Global electronic databases was conducted using keywords to identify relevant studies. Articles will be limited to the English language. Endnote 20 software will be used to eliminate duplicates, and results will be exported into Abstrackr for the review screening process consisting of two stages: title and abstract reviews and full-text reviews. Selection process of eligible studies will follow the recommendations in the Preferred Reporting Items of Systematic Reviews and Meta-Analyses Extension for Scoping Reviews checklist. A data chart will be used to capture relevant information from all included studies, and results will be presented in tabular form and in a narrative report. ETHICS AND DISSEMINATION: This scoping review consists of reviewing and collecting data from publicly available materials and hence does not require ethics approval. The scoping review results will be disseminated via publications in peer-reviewed journals and conference presentations. The results will also guide the design of a mixed method research study to examine the extent of trauma symptomatology and potentially traumatising experiences, and how they relate to the mental health of caregivers of adults with intellectual and developmental disability from different cultural backgrounds.


Subject(s)
Problem Behavior , Stress Disorders, Post-Traumatic , Adult , Humans , Caregivers , Systematic Reviews as Topic , Neurocognitive Disorders , Review Literature as Topic
4.
Genes (Basel) ; 13(11)2022 11 07.
Article in English | MEDLINE | ID: mdl-36360290

ABSTRACT

The public UCNEbase database, comprising 4273 human ultra-conserved noncoding elements (UCNEs), was thoroughly investigated with the aim to find any nucleotide signals or motifs that have made these DNA sequences practically unchanged over three hundred million years of evolution. Each UCNE comprises over 200 nucleotides and has at least 95% identity between humans and chickens. A total of 31,046 SNPs were found within the UCNE database. We demonstrated that every human has over 300 mutations within 4273 UCNEs. No association of UCNEs with non-coding RNAs, nor preference of a particular meiotic recombination rate within them were found. No sequence motifs associated with UCNEs nor their flanking regions have been found. However, we demonstrated that UCNEs have strong nucleotide and dinucleotide sequence abnormalities compared to genome averages. Specifically, UCNEs are depleted for CC and GG dinucleotides, while GC dinucleotides are in excess of 28%. Importantly, GC dinucleotides have extraordinarily strong stacking free-energy inside the DNA helix and unique resistance to dissociation. Based on the adjacent nucleotide stacking abnormalities within UCNEs, we conjecture that peculiarities in dinucleotide distribution within UCNEs may create unique 3D conformation and specificity to bind proteins. We also discuss the strange dynamics of multiple SNPs inside UCNEs and reasons why these sequences are extraordinarily conserved.


Subject(s)
Chickens , Nucleotides , Humans , Animals , Nucleotides/genetics , Base Sequence , Genome , DNA/genetics
5.
Genes (Basel) ; 13(8)2022 08 18.
Article in English | MEDLINE | ID: mdl-36011383

ABSTRACT

Common alleles tend to be more ancient than rare alleles. These common SNPs appeared thousands of years ago and reflect intricate human evolution including various adaptations, admixtures, and migration events. Eighty-four thousand abundant region-specific alleles (ARSAs) that are common in one continent but absent in the rest of the world have been characterized by processing 3100 genomes from 230 populations. Also computed were 17,446 polymorphic sites with regional absence of common alleles (RACAs), which are widespread globally but absent in one region. A majority of these region-specific SNPs were found in Africa. America has the second greatest number of ARSAs (3348) and is even ahead of Europe (1911). Surprisingly, East Asia has the highest number of RACAs (10,524) and the lowest number of ARSAs (362). ARSAs and RACAs have distinct compositions of ancestral versus derived alleles in different geographical regions, reflecting their unique evolution. Genes associated with ARSA and RACA SNPs were identified and their functions were analyzed. The core 100 genes shared by multiple populations and associated with region-specific natural selection were examined. The largest part of them (42%) are related to the nervous system. ARSA and RACA SNPs are important for both association and human evolution studies.


Subject(s)
Genomics , Polymorphism, Single Nucleotide , Africa , Alleles , Humans , Polymorphism, Single Nucleotide/genetics , Selection, Genetic
6.
Res Dev Disabil ; 126: 104241, 2022 Jul.
Article in English | MEDLINE | ID: mdl-35504125

ABSTRACT

BACKGROUND: Families in Singapore are primarily involved in the care of their relatives with intellectual disabilities and the study aimed to explore their experiences taking care of their relatives with intellectual disabilities and mental health problems. METHOD: Nine unpaid family carers were interviewed. The interviews were analysed using Interpretative Phenomenological Analysis. RESULTS: Analysis revealed four themes 1) Making sense of behaviours; 2) Staff are the experts; 3) Public reaction and 4) Worries and hopes for the future. CONCLUSIONS: Family carers found it difficult to identify and manage the mental health symptoms of their relatives and sought help from specialist mental health professionals. They were satisfied with the specialist services and found psychotropic medication helpful to reduce the symptoms. Family carers expressed worries about their relative not being accepted by the public and did not make future care plans. More resources are needed to increase accessibility of specialist mental health services for people with intellectual disabilities. It is recommended for service providers to collaborate with family carers and provide them with resources and skills to empower them to care for their relatives with intellectual disabilities.


Subject(s)
Caregivers , Intellectual Disability , Adult , Caregivers/psychology , Humans , Intellectual Disability/psychology , Mental Health , Qualitative Research , Singapore
7.
J Intellect Disabil ; 26(4): 972-989, 2022 Dec.
Article in English | MEDLINE | ID: mdl-34427139

ABSTRACT

BACKGROUND: This research aimed to investigate the views and experiences of specialist mental health professionals working with adults with intellectual disabilities and mental health problems in Singapore in order to gain insight into the functioning of the local specialist intellectual disability mental health service and how it may be improved. METHODS: Eight staff members from specialist service were interviewed. The transcriptions of the interviews were analysed using thematic analysis. RESULTS: Analysis revealed four themes (1) Identifying their roles; (2) Ensuring continuity of care; (3) Disempowerment of service users and (4) Improving clinical practice. CONCLUSIONS: Participants identified the challenges they faced working with this population. They highlighted the importance of building therapeutic relationships during the treatment process and discussed the stigma that people with intellectual disabilities face in the community. Recommendations and implications are discussed in relation to service provision, improving staff knowledge and recruiting more staff to work in this field.


Subject(s)
Intellectual Disability , Mental Health Services , Adult , Humans , Intellectual Disability/psychology , Singapore , Mental Health , Qualitative Research
8.
Int J Dev Disabil ; 67(5): 371-380, 2021.
Article in English | MEDLINE | ID: mdl-34570836

ABSTRACT

Background: Generic mental health staff often have contact with people with intellectual disabilities when they access mainstream mental health services. To date, there has not been any research conducted in non-western countries to explore their views. This paper investigates the views and experiences of mainstream mental health professionals regarding the mental health services for people with intellectual disabilities in Singapore. Methods: Eight staff members from generic mental health services were interviewed. Thematic analysis was used to identify main themes. Findings: The main themes are related to their work experiences, perceptions of people with intellectual disabilities, ideal staff characteristics and service recommendations. Conclusions: Participants identified a lack of experience and knowledge when working with this population. They highlighted the challenges they face promoting choice and autonomy for people with intellectual disabilities. The discussion includes recommendations for improving staff knowledge through training opportunities, consideration of non-pharmacological approaches and early collaboration with caregivers during the treatment process.

9.
Plant Direct ; 4(12): e00285, 2020 Dec.
Article in English | MEDLINE | ID: mdl-33364543

ABSTRACT

The globally important crop Brassica rapa, a close relative of Arabidopsis, is an excellent system for modeling our current knowledge of plant growth on a morphologically diverse crop. The long history of B. rapa domestication across Asia and Europe provides a unique collection of locally adapted varieties that span large climatic regions with various abiotic and biotic stress-tolerance traits. This diverse gene pool provides a rich source of targets with the potential for manipulation toward the enhancement of productivity of crops both within and outside the Brassicaceae. To expand the genetic resources available to study natural variation in B. rapa, we constructed an Advanced Intercross Recombinant Inbred Line (AI-RIL) population using B. rapa subsp. trilocularis (Yellow Sarson) R500 and the B. rapa subsp. parachinensis (Cai Xin) variety L58. Our current understanding of genomic structure variation across crops suggests that a single reference genome is insufficient for capturing the genetic diversity within a species. To complement this AI-RIL population and current and future B. rapa genomic resources, we generated a de novo genome assembly of the B. rapa subsp. trilocularis (Yellow Sarson) variety R500, the maternal parent of the AI-RIL population. The genetic map for the R500 x L58 population generated using this de novo genome was used to map Quantitative Trait Loci (QTL) for seed coat color and revealed the improved mapping resolution afforded by this new assembly.

10.
Dev Med Child Neurol ; 62(8): 906-916, 2020 08.
Article in English | MEDLINE | ID: mdl-32472972

ABSTRACT

AIM: To summarize existing interventions and their outcomes in Rett syndrome (RTT) rehabilitation and identify gaps in the literature. METHOD: Five databases (Ovid MEDLINE, Ovid Embase Classic, Ovid PsycINFO, EBSCO CINAHL Plus, and ProQuest ERIC) were systematically searched up to 23rd July 2018 for studies describing rehabilitation interventions. Data on study participants, design, and outcomes were extracted. RESULTS: Sixty-two articles were included in the final review. Evidence consistently demonstrated that females with RTT can improve their gross motor, fine motor, and communicative skills with rehabilitation. All 11 interventions targeting gross motor function, namely ambulation, achieved functional improvements. Twenty of 24 articles describing fine motor rehabilitation studies succeeded in decreasing stereotypies, improving functional hand use, and/or reducing self-injurious behaviors. Twenty-one of 22 studies describing communication interventions succeeded in training choice-making, communicative language, or socialization behavior. Other key findings include the positive interplay between physical and communicative rehabilitation outcomes, and the ability of females with RTT to improve their cognitive abilities during intervention. INTERPRETATION: Rehabilitation can impact the daily lives of females with RTT and their caregivers in clinically meaningful ways.


Subject(s)
Rett Syndrome/rehabilitation , Humans , Quality of Life , Recovery of Function , Treatment Outcome
11.
Asia Pac Psychiatry ; 12(2): e12388, 2020 Jun.
Article in English | MEDLINE | ID: mdl-32291970

ABSTRACT

INTRODUCTION: The Adult Neurodevelopmental Service in Singapore is the first service of its kind in South-East Asia for adults with intellectual disability (ID) and/or autism spectrum disorder (ASD). However, few studies have documented and compared the sociodemographic characteristics and clinical needs of this subpopulation group. METHODS: Initial assessments conducted from 1 January 2015 to 31 December 2016 were retrospectively reviewed for this descriptive study. RESULTS: A total of 272 patients were included in the study (mean age 28.3 ± 11.5; 200 males, 72 females). Adults with ID comprised the largest percentage (52.9%), followed by those with ASD (30.2%), and then those with co-occurring ASD and ID (16.9%). The ASD subgroup had the highest proportion of individuals with employment, postsecondary school education, functional capabilities, and a psychiatric disorder. In comparison, adults with only ID and adults with co-occurring ASD and ID shared similar lower levels of education and employment, and had a higher proportion of individuals with epilepsy and aggressive behavior. DISCUSSION: In this study, adults with ASD had a unique social profile with different clinical needs compared to adults with only ID or to adults with co-occurring ASD and ID. Adults with only ID and those with co-occurring ASD shared many of the same social characteristics and high clinical needs. The analysis of these profiles will be useful in developing services that better meet the needs of this complex group.


Subject(s)
Autism Spectrum Disorder/epidemiology , Educational Status , Employment/statistics & numerical data , Intellectual Disability/epidemiology , Adult , Comorbidity , Female , Hospitals, Psychiatric/statistics & numerical data , Humans , Male , Middle Aged , Retrospective Studies , Singapore/epidemiology , Tertiary Care Centers/statistics & numerical data , Young Adult
12.
Annu Int Conf IEEE Eng Med Biol Soc ; 2019: 1605-1608, 2019 Jul.
Article in English | MEDLINE | ID: mdl-31946203

ABSTRACT

Background and Rational: Obstructive Sleep Apnea (OSA) is a common disorder, affecting almost 10% of adults, but very underdiagnosed. This is largely due to limited access to overnight sleep testing using polysomnography (PSG). Our goal was to distinguish OSA from healthy individual using a simple maneuver during wakefulness in combination with machine learning methods. Methods: Participants have undergone an overnight PSG to determine their ground truth OSA severity. Separately, they were asked to breathe through a nasal mask or a mouth piece through which negative pressure (NP) was applied, during wakefulness. Airflow waveforms were acquired and several features were extracted and used to train various classifiers to predict OSA. Results and Discussion: The performance of each classifier and experimental setup was calculated. The best results were obtained using Random Forest classifier for distinguishing OSA from healthy individuals with a very good area under the curve of 0.80. To the best of our knowledge, this is the first study to deploy machine learning and NP with promising path to diagnose OSA during wakefulness.


Subject(s)
Sleep Apnea, Obstructive , Wakefulness , Humans , Machine Learning , Polysomnography , Sleep Apnea, Obstructive/diagnosis , Trachea
13.
Oncoimmunology ; 3: e29243, 2014.
Article in English | MEDLINE | ID: mdl-25114831

ABSTRACT

Standard cancer treatments trigger immune responses that may influence tumor control. The nature of these responses varies depending on the tumor and the treatment modality. We previously reported that radiation and androgen-deprivation therapy (ADT) induce tumor-associated autoantibody responses in prostate cancer patients. This follow-up analysis was conducted to assess the relationship between autoantibody responses and clinical outcome. Patients with non-metastatic prostate cancer received external beam radiation therapy (EBRT) plus neoadjuvant and concurrent androgen deprivation. Treatment-induced autoantibodies were detected in almost a third of patients receiving combinatorial ADT and EBRT. Unexpectedly, patients that developed autoantibody responses to tumor antigens had a significantly lower 5-year biochemical failure-free survival (BFFS) than patients that did not develop an autoantibody response. Thus, tumor-reactive autoantibodies may be associated with increased risk of biochemical failure and immunomodulation to prevent autoantibody development may improve BFFS for select, high-risk prostate cancer patients receiving both ADT and EBRT.

14.
Gen Comp Endocrinol ; 192: 246-55, 2013 Oct 01.
Article in English | MEDLINE | ID: mdl-24013027

ABSTRACT

While serotonin (5-HT) can stimulate the hypothalamic-pituitary-interrenal stress axis in fish, the specific site(s) of 5-HT action are poorly understood. In this study, goldfish (Carassius auratus) were injected intraperitoneally with either saline or the 5-HT1A/7 receptor agonist 8-OH-DPAT at a dose of 100 or 400 µg/kg body weight and sampled 1.5 and 8 h post-injection. Relative to unhandled controls, the saline and 100 µg/kg 8-OH-DPAT treatments elicited similar transient 5- to 7-fold increases in plasma cortisol and the 400 µg/kg 8-OH-DPAT dosage resulted in a sustained 16-fold increase in cortisol levels. Although the 5-HT1A receptor is expressed in the brain preoptic area (POA), the pituitary and the head kidney, neither the saline nor the 8-OH-DPAT treatments affected the mRNA abundance of POA corticotropin-releasing factor and pituitary pro-opiomelanocortin or plasma adrenocorticotropic hormone (ACTH) levels. To assess the direct actions of 5-HT on cortisol secretion relative to those of ACTH, head kidney tissue were superfused with 10(-7)M 5-HT, ACTH or a combined 5-HT/ACTH treatment. Overall, the ACTH and 5-HT/ACTH treatments resulted in higher peak cortisol and total cortisol release than in the 5-HT treatment but the response time to peak cortisol release was shorter in the combined treatment than in either the 5-HT or ACTH alone treatments. Both 8-OH-DPAT and cisapride, a 5-HT4 receptor agonist, also stimulated cortisol release in vitro and their actions were reversed by selective 5-HT1A and 5-HT4 receptor antagonists, respectively. Finally, double-labeling with anti-tyrosine hydroxylase and anti-5-HT revealed that the chromaffin cells of the head kidney contain 5-HT. Thus, in goldfish, 5-HT can directly stimulate cortisol secretion from the interrenals via multiple 5-HT receptor subtypes and the chromaffin cells may be involved in the paracrine regulation of cortisol secretion via 5-HT.


Subject(s)
8-Hydroxy-2-(di-n-propylamino)tetralin/pharmacology , Hydrocortisone/metabolism , Serotonin Receptor Agonists/pharmacology , Serotonin/pharmacology , Animals , Goldfish
15.
Radiother Oncol ; 107(3): 366-71, 2013 Jun.
Article in English | MEDLINE | ID: mdl-23726114

ABSTRACT

PURPOSE: After publication of EORTC-22863 trial, prolonged androgen deprivation therapy (ADT) combined with radiation therapy (RT) became standard policy for high-risk prostate cancer patients in British Columbia (BC) in 1997. We evaluated whether population-based survival improved after this policy change. PATIENTS AND METHODS: Two cohorts comprising all patients with T3-T4 prostate cancer treated with curative-intent RT in BC were reviewed. The Early cohort (n=730) was all patients treated between 1993 and 1995, and the Late cohort (n=584) was all patients treated between 1999 and 2001. The BC Cancer Registry, which collects data on survival, was linked to RT and pharmacy databases. Duration of ADT, age, stage, grade, presenting PSA, and Charlson comorbidity index (CCI; none=0, minor=1, major=2+), were abstracted from charts. RESULTS: Usage of ≥6 months and ≥18 months of neoadjuvant and adjuvant ADT increased from 14% and 1% to 97% and 59% (p<0.0001). Baseline characteristics were similar, except for lower Gleason score (G2-6: 45% vs. 20%, G7: 35% vs. 48%, G8-10: 19% vs. 32%; p<0.0001), higher T-stage (T4: 9% vs. 5%, p=0.004) and higher comorbidity (CCI 0: 62% vs. 71%, CCI 1: 26% vs. 20%, CCI 2+: 11% vs. 9%, p=0.002) in the Early cohort. Disease-specific survival adjusted for competing risks from other causes mortality was improved (90% vs. 86%, p=0.042). On multivariate analysis, the Late cohort was independently associated with improved 8-year overall survival (76% vs. 64%, p=0.0002). CONCLUSIONS: This population-based study demonstrated improved overall survival following a policy change to use of prolonged ADT with curative RT for patients with T3-T4 prostate cancer.


Subject(s)
Androgen Antagonists/therapeutic use , Prostatic Neoplasms/drug therapy , Aged , Aged, 80 and over , Cohort Studies , Humans , Male , Middle Aged , Neoplasm Grading , Prostatic Neoplasms/mortality , Prostatic Neoplasms/pathology , Prostatic Neoplasms/radiotherapy , Retrospective Studies
16.
Acupunct Med ; 29(3): 173-9, 2011 Sep.
Article in English | MEDLINE | ID: mdl-21666275

ABSTRACT

PURPOSE: A pilot study to document changes in symptoms after acupuncture or nurse-led supportive care in patients with incurable cancer. METHODS: Patients receiving palliative care with estimated survival of at least 3 months were screened with the Edmonton Symptom Assessment System (ESAS). Patients (n=20) with significant symptoms were randomised to receive weekly acupuncture or nurse-led supportive care for 4 weeks. ESAS scores were obtained before and after each treatment, and weekly for 6 weeks after treatment by telephone. RESULTS: 42 of 170 patients screened were eligible. 20 gave consent for recruitment. The compliance rate was 90% for acupuncture and 80% for nurse-led supportive care. Total symptom scores were reduced by an average of 22% after each acupuncture visit and by 14% after each supportive care visit. Compared with baseline, ESAS scores at the end of the follow-up period were reduced by 19% for the acupuncture arm and 26% for nurse-led supportive care. CONCLUSION: Patients appear to benefit from incorporating acupuncture in the treatment of advanced incurable cancer. Acupuncture was well tolerated with no significant or unexpected side effects. Acupuncture had an immediate effect on all symptoms, whereas nurse-led supportive care had a larger impact 6 weeks after the final session. Both interventions appear helpful to this population and warrant further study.


Subject(s)
Electroacupuncture , Neoplasms/therapy , Nursing Care , Palliative Care , Adult , Aged , Aged, 80 and over , Disease Management , Female , Humans , Male , Middle Aged , Pilot Projects
17.
Int J Radiat Oncol Biol Phys ; 81(5): e713-9, 2011 Dec 01.
Article in English | MEDLINE | ID: mdl-21277102

ABSTRACT

PURPOSE: To examine the impact of patient, disease, and treatment characteristics on survival outcomes in patients treated with neoadjuvant androgen deprivation therapy (ADT) and radical external-beam radiotherapy (RT) for clinically localized, extreme-risk prostate adenocarcinoma with a presenting prostate-specific antigen (PSA) concentration of >40 ng/ml. METHODS AND MATERIALS: A retrospective chart review was conducted of 64 patients treated at a single institution between 1991 and 2000 with ADT and RT for prostate cancer with a presenting PSA level of >40 ng/ml. The effects of patient age, tumor (presenting PSA level, Gleason score, and T stage), and treatment (total ADT duration and pre-RT PSA level) characteristics on rates of biochemical disease-free survival (bDFS), prostate cancer-specific survival (PCSS), and overall survival (OS) were examined. RESULTS: Median follow-up time was 6.45 years (range, 0.09-15.19 years). Actuarial bDFS, PCSS, and OS rates at 5 years were 39%, 87%, and 78%, respectively, and 17%, 64%, and 45%, respectively, at 10 years. On multivariate analysis, the pre-RT PSA level (≤0.1 versus >0.1 ng/ml) was the single most significant prognostic factor for bDFS (p=0.033) and OS (p=0.018) rates, whereas age, T stage, Gleason score, and ADT duration (≤6 versus >6 months) were not predictive of outcomes. CONCLUSION: In prostate cancer patients with high presenting PSA levels, >40 ng/ml, treated with combined modality, neoadjuvant ADT, and RT, the pre-RT PSA nadir, rather than ADT duration, was significantly associated with improved survival. This observation supports the use of neoadjuvant ADT to drive PSA levels to below 0.1 ng/ml before initiation of RT, to optimize outcomes for patients with extreme-risk disease.


Subject(s)
Adenocarcinoma/blood , Androgen Antagonists/therapeutic use , Prostate-Specific Antigen/blood , Prostatic Neoplasms/blood , Adenocarcinoma/drug therapy , Adenocarcinoma/mortality , Adenocarcinoma/pathology , Adenocarcinoma/radiotherapy , Aged , Aged, 80 and over , Chemotherapy, Adjuvant/methods , Disease-Free Survival , Humans , Male , Middle Aged , Multivariate Analysis , Neoplasm Grading , Neoplasm Staging , Prognosis , Prostatic Neoplasms/drug therapy , Prostatic Neoplasms/mortality , Prostatic Neoplasms/pathology , Prostatic Neoplasms/radiotherapy , Radiotherapy Dosage , Retrospective Studies
18.
Am J Clin Oncol ; 34(4): 350-5, 2011 Aug.
Article in English | MEDLINE | ID: mdl-20686404

ABSTRACT

OBJECTIVE: To evaluate tolerability and compliance to a walking exercise program and its effect on fatigue during and after radical external beam radiation therapy (EBRT) for prostate cancer. METHODS: A total of 50 subjects with prostate cancer undergoing EBRT over 6 to 8 weeks were prospectively accrued to an exercise intervention group, matched for age and clinical characteristics to 30 subjects in a historical control group who underwent EBRT with no specific exercise intervention. Starting 1 week before EBRT, exercise participants performed moderate-intensity walking targeting 60% to 70% age-predicted maximum heart rate, at least 20 min/d, 3 d/wk over 12 weeks. The Brief Fatigue Inventory was administered at baseline, mid-EBRT (week 3-4), end-EBRT (week 6-8), and 6 months post-EBRT. RESULTS: Of 50, 42 (84%) of exercise participants completed the walking program. There were no cardiovascular complications, musculoskeletal injuries, or other adverse events. A total of 89% subjects reported "Good-Excellent" satisfaction during and up to 6 months post-EBRT. Fatigue in control subjects escalated from baseline to end-EBRT, remaining high at 6 months post-EBRT (P[r] = 0.03). In contrast, mean total fatigue scores in exercise subjects were stable from baseline up to 6 months post-EBRT (P = 0.52). Trends for higher fatigue interference with quality of life were observed in the control group as compared with the exercise group. CONCLUSIONS: Moderate-intensity walking exercise during radical EBRT is safe and feasible. The high convenience and satisfaction ratings, in conjunction with the observed fatigue trends, indicate that this activity has the potential to attenuate fatigue and improve quality of life for patients with localized prostate cancer undergoing curative therapy.


Subject(s)
Brachytherapy , Exercise , Prostatic Neoplasms/radiotherapy , Quality of Life , Aged , Aged, 80 and over , Fatigue/etiology , Fatigue/prevention & control , Humans , Male , Middle Aged , Pilot Projects , Prognosis , Prospective Studies
19.
Nutr Cancer ; 62(2): 198-207, 2010.
Article in English | MEDLINE | ID: mdl-20099194

ABSTRACT

Our objective was to evaluate the tolerability and effect of a daily soy beverage in prostate cancer patients with biochemical failure after radiotherapy. Patients with rising prostate-specific antigen (PSA) after radical radiation for prostate cancer were instructed to consume 500 ml of soy beverage daily for 6 mo. Tolerability of the soy beverage and compliance were assessed. PSA doubling times before and after the consumption of soy were compared. Thirty-four subjects were enrolled; 5 withdrew before 1 mo of soy for reasons unrelated to soy consumption. All remaining 29 subjects were included in the analysis. Mean consumption of the assigned soy beverage was 93%. Mild gastrointestinal upset (38%) not affecting soy consumption was the commonest side effect. PSA showed a declining trend in 4 patients (13.8%), and there was a > 100% prolongation of PSA doubling time in 8 patients (27.6%). However, PSA doubling time also showed a 50% or more shortening in 5 patients (17.2%). In our cohort of North American subjects, 6 mo of a daily soy beverage was well tolerated and was associated with a declining trend or more than 2 times prolongation of PSA doubling time in 41% of subjects. Confirmatory studies are warranted.


Subject(s)
Prostate-Specific Antigen/blood , Prostatic Neoplasms/radiotherapy , Prostatic Neoplasms/therapy , Soy Milk/administration & dosage , Aged , Aged, 80 and over , Humans , Isoflavones/administration & dosage , Kinetics , Male , Middle Aged , Prostatic Neoplasms/pathology , Testosterone/blood , Treatment Failure
20.
Can J Urol ; 16(2): 4541-52, 2009 Apr.
Article in English | MEDLINE | ID: mdl-19364426

ABSTRACT

PURPOSE: To assess outcome and predictive factors in men with prostate cancer who receive post radical prostatectomy (RP) radiotherapy (RT) either in the adjuvant or salvage setting, with or without neoadjuvant androgen deprivation therapy (NADT). METHODS: A retrospective analysis was performed on 175 patients with clinically localized prostate cancer treated with RP who subsequently received RT (dose range 50 Gy-68 Gy). Twenty-two patients received adjuvant RT (ART), 57 received NADT + ART, 15 received salvage RT (SRT), and 81 received NADT + SRT. Outcome was assessed by biochemical disease free survival (BDFS), prostate cancer specific survival and overall survival (OS). RESULTS: Although BDFS favored patients who received NADT with 5 year rates of 67%, 80%, 27% and 62% for the ART, NADT + ART, SRT, and NADT + SRT groups respectively; this was not a significant predictor on multivariable analysis. Significant independent predictive factors of improved BDFS were pre-RT PSA < or = 0.2 ng/ml, low Gleason score and positive surgical margins. Age and Gleason score were independent predictors of OS. CONCLUSIONS: Pre-RT PSA is an important predictor of outcome. NADT appears to benefit patients who presented with a pre-RT PSA > 0.2 ng/ml, particularly for patients receiving SRT. NADT can be considered for patients receiving RT after RP who present with a high pre-RT PSA but may not be necessary for patients without. Results of ongoing randomized studies such as RADICALS will also help clarify the role of hormone therapy in conjunction with RT.


Subject(s)
Adenocarcinoma/drug therapy , Adenocarcinoma/surgery , Androgen Antagonists/therapeutic use , Prostatic Neoplasms/drug therapy , Prostatic Neoplasms/surgery , Adenocarcinoma/mortality , Adenocarcinoma/radiotherapy , Aged , Humans , Male , Middle Aged , Neoadjuvant Therapy , Prostate-Specific Antigen/blood , Prostatectomy , Prostatic Neoplasms/mortality , Prostatic Neoplasms/radiotherapy , Radiotherapy Dosage , Radiotherapy, Adjuvant , Salvage Therapy , Treatment Outcome
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