Relationship between airflow limitation in response to upper airway negative pressure during wakefulness and obstructive sleep apnea severity.

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.

What do specialist mental health professionals think of the mental health services for people with intellectual disabilities in Singapore?

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.

Rehabilitation interventions in Rett syndrome: a scoping review.

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.

Unmasking the Struggle: A Scoping Review Exploring Post-Traumatic Stress Symptoms in Caregivers of Individuals with Neurodevelopmental, Psychiatric and Neurocognitive Disorders.

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.

Serotonin directly stimulates cortisol secretion from the interrenals in goldfish.

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.

Protocol for scoping review study to map out the existing research in relation to post-traumatic stress symptoms among caregivers of individuals with neurodevelopmental, psychiatric and neurocognitive disorders.

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.

Nucleotide Composition of Ultra-Conserved Elements Shows Excess of GpC and Depletion of GG and CC Dinucleotides.

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.

Family carers' experiences of providing care for their adult relative with intellectual disabilities and mental health problems in Singapore.

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.

Analysis of Common SNPs across Continents Reveals Major Genomic Differences between Human Populations.

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.

Services for people with intellectual disabilities and mental health problems in Singapore: perspectives from mainstream mental health professionals.

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.

A phase II trial of a soy beverage for subjects without clinical disease with rising prostate-specific antigen after radical radiation for prostate cancer.

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.

Adult neurodevelopmental services in Singapore: A sociodemographic and clinical profile at a tertiary psychiatric hospital.

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.

Genetic and genomic resources to study natural variation in Brassica rapa.

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.

Does neoadjuvant hormone therapy improve outcome in prostate cancer patients receiving radiotherapy after radical prostatectomy?

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.

Diagnosis of Obstructive Sleep Apnea during Wakefulness Using Upper Airway Negative Pressure and Machine Learning.

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.

What is the optimal duration of androgen deprivation therapy in prostate cancer patients presenting with prostate-specific antigen levels > 20 ng/ml?

PURPOSE: To evaluate the optimal duration of androgen deprivation therapy (ADT) in patients with prostate cancer treated with external beam radiotherapy (EBRT), who present with PSA levels > 20 ng/mL. METHODS AND MATERIALS: A total of 307 patients presenting with a PSA > 20 ng/ml were treated with EBRT and ADT. The cohort was divided into four groups according to the duration of ADT: Group 1 received < 6 months (n = 71), group 2 received 6-12 months (n = 80), group 3 received 12-24 months (n = 72), and group 4 received > 24 months (n = 84) of ADT. The endpoints analyzed were biochemical control (bNED), overall survival (OS) and cause-specific survival (CSS). Statistical analysis was conducted using Kaplan-Meier estimates and Cox regression models. RESULTS: Compared to patients who received < 6 months of ADT, patients treated with 12-24 months or > 24 months of ADT experienced significantly improved bNED (p = 0.01 and p < 0.0001, respectively). Cause-specific survival with ADT durations 12-24 and > 24 months were significantly higher compared to < 6 months (p < 0.007 and 0.024, respectively). Overall survival with ADT durations > 24 months was also significantly higher compared to < 6 months (p = 0.0025). CONCLUSIONS: The present analysis supports the hypothesis that longer durations of ADT improves bNED, CSS and OS in patients presenting with a PSA > 20 ng/ml.

Hemoglobin levels do not predict biochemical outcome for localized prostate cancer treated with neoadjuvant androgen-suppression therapy and external-beam radiotherapy.

PURPOSE: To investigate whether hemoglobin (Hb) levels affect outcome in men with localized prostate adenocarcinoma (LPA) treated with neoadjuvant androgen-suppression therapy (NAST) and external-beam radiotherapy (EBRT). METHODS AND MATERIALS: A total of 563 men with LPA treated with NAST (median: 5.3 months) and EBRT who had Hb levels during treatment were retrospectively reviewed. Patient, tumor, and treatment variables, including the following Hb variables, were subjected to univariate and multivariable analyses to identify factors that predict biochemical control (bNED) and overall survival (OS): pre-EBRT Hb, Hb nadir during EBRT, and change in Hb from pre-EBRT to nadir during EBRT. RESULTS: Median PSA follow-up was 4.25 years. Forty-nine percent of men were anemic during EBRT, with a median Hb of 13.4 g/dL, and 68% experienced a decline in Hb from pre-EBRT to during EBRT of median 0.6 g/dL. Five-year Nadir+2 bNED and OS rates were similar for anemic and nonanemic patients during EBRT. High percent-positive biopsies, PSA and Gleason score, and use of AA monotherapy predicted worse bNED. High stage and age predicted worse OS. Hb variables were not predictive of bNED or OS. CONCLUSIONS: Anemia is a common side effect of NAST and is usually mild. Hb levels, however, do not predict biochemical control or survival.

Prospective evaluation of the prevalence and severity of fatigue in patients with prostate cancer undergoing radical external beam radiotherapy and neoadjuvant hormone therapy.

OBJECTIVE: To prospectively evaluate the prevalence and severity of fatigue and its impact on quality of life (QOL) during and after radical external beam radiotherapy (RT) for prostate cancer. METHOD AND MATERIALS: Twenty-eight men with prostate cancer undergoing RT over 6-8 consecutive weeks were prospectively accrued. The Brief Fatigue Inventory (BFI), a validated fatigue assessment tool, was administered at five time points: baseline (week 1), middle of RT (week 3-4), end of RT (last week of RT), and follow-up (median 6.5 weeks after RT). The BFI contained nine questions, each using 0-10 ratings to quantify fatigue severity and interference with six QOL domains. The prevalence of moderate-severe fatigue was plotted as a function of time. Mean sum and subscale scores at each time point were compared to baseline scores using Wilcoxon tests. Linear regression analyses were performed to assess associations between fatigue scores and age, tumor and treatment characteristics. RESULTS: The median age was 69 years (range 57-84), Gleason score 7 (range 6-10), and presenting PSA 9.0 ng/mL (range 2.5 ng/mL-103.0 ng/mL). Patients were treated once daily to a median dose of 74 Gy (range 60 Gy-78 Gy) over a median of 37 fractions (range 30-39). Hormone therapy was used in all patients (median duration 12.2 months). The prevalence of moderate-severe present fatigue increased from 7% at baseline to 8% at mid-RT and 32% at RT completion. Compared to baseline (mean score 11.5), fatigue increased significantly mid-RT (mean score 14.6, p = 0.03) and peaked at the end of RT (mean score 23.5, p = 0.001). Fatigue significantly interfered with walking ability, normal work, daily chores, and enjoyment of life only at the end of RT. After RT completion, fatigue improved but remained higher compared to baseline at 6.5 weeks of follow-up (mean score 15.0, p = 0.02). On linear regression analysis, age, Gleason score, PSA, T-stage, hormone therapy duration, RT dose and fractions were not significantly associated with mean fatigue scores. CONCLUSION: Patients undergoing 6-8 weeks of RT experienced significant fatigue adversely affecting QOL persisting after therapy completion. Since walking ability was not affected until the end of RT, a walking exercise intervention to combat fatigue is likely feasible and is being investigated.

Neoadjuvant hormone therapy and external-beam radiation for localized high-risk prostate cancer: the importance of PSA nadir before radiation.

PURPOSE: To examine the impact of various patient, disease, and treatment characteristics on outcome in patients treated with neoadjuvant hormone therapy (NAHT) and external-beam radiation therapy (EBRT) for clinically localized, high-risk prostate adenocarcinoma (initial prostate-specific antigen [PSA] level >20, Gleason score 8-10 or Stage > or = T3). METHODS AND MATERIALS: A retrospective chart review was conducted on 407 patients treated between 1991 and 2001 with NAHT and EBRT for high-risk prostate cancer. The effect of tumor (PSA level, Gleason score, and T stage) and treatment (NAHT duration, total-hormone duration, preradiation PSA) characteristics on rates of biochemical disease-free survival (bDFS), prostate cancer-specific survival, and overall survival were examined. RESULTS: Median follow-up time was 78 months (range: 5-140 months). Actuarial bDFS at 5 years was 52% (95% confidence interval [CI], 46% to 57%) for the entire group. On multivariate analysis, initial PSA level (p = 0.004), Gleason score (p = 0.005), and preradiation PSA level (p < 0.001) were predictive of bDFS, whereas age, T stage, duration of NAHT, and duration of total hormone therapy were not predictive of outcomes. Gleason score and preradiation PSA level were also predictive of prostate cancer-specific survival rates. CONCLUSION: Improved bDFS in patients with high-risk prostate cancer was associated with lower initial PSA level, lower Gleason score, and lower preradiation PSA level. The duration of NAHT did not have an impact on outcomes, but the preradiation PSA was an important predictor of bDFS in high-risk patients.

Do age and comorbidity impact treatment allocation and outcomes in limited stage small-cell lung cancer? a community-based population analysis.

PURPOSE: The effects of age and comorbidity on treatment and outcomes for patients with limited stage small-cell lung cancer (L-SCLC) are unclear. This study analyzes relapse and survival in a community-based population with L-SCLC according to age and comorbidity. METHODS: A retrospective review was performed on 174 patients with L-SCLC referred to the British Columbia Cancer Agency, Vancouver Island Centre, between January 1991 and December 1999. Patient and treatment characteristics, disease response, relapse, and survival were compared among three age cohorts: <65 years (n = 55, 32%), 65-74 years (n = 76, 44%), and > or =75 years (n = 43, 25%); and according to Charlson comorbidity scores 0, 1, and > or =2. Multivariate analysis was performed to identify independent prognostic factors associated with treatment response and survival. RESULTS: Patient factors that significantly differed with age were functional status classified by Eastern Cooperative Oncology Group performance status and number of comorbidities. Increasing age was significantly associated with fewer diagnostic scans. Combined modality chemoradiotherapy (CRT) was given in 86%, 66%, and 40% of patients ages <65, 65-74, and > or =75 years, respectively, (p <0.0001). Thoracic irradiation use was comparable among the age cohorts (p >0.05), but chemotherapy use varied significantly with less intensive regimens, fewer cycles, and lower total doses with advancing age (p <0.05). Prophylactic cranial irradiation (PCI) was used in 41 patients, only 3 of whom were age >70 years. Overall response rates to primary treatment significantly decreased with advancing age: 91%, 79%, and 74% in patients ages <65, 65-74, and > or =75 years, respectively (p = 0.014). Treatment toxicity and relapse patterns were similar across the age cohorts. Overall 2-year survival rates were significantly lower with advancing age: 37%, 22%, and 19% (p = 0.003), with corresponding median survivals of 17, 12, and 7 months among patients ages <65, 65-74, and > or =75 years, respectively. On multivariate analysis, age and Charlson comorbidity scores were not significantly associated with treatment response and survival. Independent prognostic factors favorably associated with survival were good performance status, normal lactate dehydrogenase, absence of pleural effusion, and > or =four cycles of chemotherapy. CONCLUSION: Increasing age was associated with decreased performance status and increased comorbidity. Older patients with L-SCLC were less likely to be treated with CRT, intensive chemotherapy, and PCI. Treatment response and survival rates were lower with advancing age, but this may be attributed to poor performance status and suboptimal treatment rather than age.