Propensity score analysis in the Genetic Analysis Workshop 17 simulated data set on independent individuals

Genetic Analysis Workshop 17 provided simulated phenotypes and exome sequence data for 697 independent individuals (209 case subjects and 488 control subjects). The disease liability in these data was influenced by multiple quantitative traits. We addressed the lack of statistical power in this small data set by limiting the genomic variants included in the study to those with potential disease-causing effect, thereby reducing the problem of multiple testing. After this adjustment, we could readily detect two common variants that were strongly associated with the quantitative trait Q1 (C13S523 and C13S522). However, we found no significant associations with the affected status or with any of the other quantitative traits, and the relationship between disease status and genomic variants remained obscure. To address the challenge of the multivariate phenotype, we used propensity scores to combine covariates with genetic risk factors into a single risk factor and created a new phenotype variable, the probability of being affected given the covariates. Using the propensity score as a quantitative trait in the case-control analysis, we again could identify the two common single-nucleotide polymorphisms (C13S523 and C13S522). In addition, this analysis captured the correlation between Q1 and the affected status and reduced the problem of multiple testing. Although the propensity score was useful for capturing and clarifying the genetic contributions of common variants to the disease phenotype and the mediating role of the quantitative trait Q1, the analysis did not increase power to detect rare variants

Breast cancer surface receptors predict risk for developing brain metastasis and subsequent prognosis

Determining the status of breast cancer surface receptors (estrogen receptor, progesterone receptor, HER2/neu) has become routine in the care of patients with this disease and has proven to be helpful in guiding treatment. For this reason, breast cancer has become a model for molecularly guided therapy in solid tumors. Emerging data support that these receptors are associated with risk for developing brain metastases. Additionally, once brain metastases have occurred these receptors may also correlate with prognosis

Hospitalisations at the end of life: using a sentinel surveillance network to study hospital use and associated patient, disease and healthcare factors

<p>Abstract</p> <p>Background</p> <p>Hospital deaths following several hospital admissions or long hospital stays may be indicative of a low quality of dying. Although place of death has been extensively investigated at population level, hospital use in the last months of life and its determinants have been studied less often, especially in Europe and with a general end-of-life patient population. In this study we aim to describe hospital use in the last three months of life in Belgium and identify associated patient, disease and healthcare factors.</p> <p>Methods</p> <p>We conducted a retrospective registration study (13 weeks in 2004) with the Belgian Sentinel Network of General Practitioners, an epidemiological surveillance system representative of all GPs in Belgium, covering 1.75% of the total Belgian patient population. All registered non-sudden or expected deaths of patients (aged one year or older) at the GPs' practices were included. Bivariate and regression analyses were performed.</p> <p>Results</p> <p>The response rate was 87%. The GPs registered 319 deaths that met inclusion criteria. Sixty percent had been hospitalised at least once in the last three months of life, for a median of 19 days. The percentage of patients hospitalised increased exponentially in the last weeks before death; one fifth was admitted in the final week of life. Seventy-two percent of patients hospitalised at least once in the final three months died in hospital. A palliative treatment goal, death from cardiovascular diseases, the expression of a wish to die in an elderly home and palliative care delivery by the GP were associated with lower hospitalisation odds.</p> <p>Conclusion</p> <p>Hospital care plays a large role in the end of patients' lives in Belgium, especially in the final weeks of life. The result is a high rate of hospital deaths, showing the institutionalised nature of dying. Patients' clinical conditions, the expression of preferences and also healthcare characteristics such as being treated as a palliative care patient, seem to be associated with hospital transfers. It is recommended that hospitalisation decisions are only made after careful consideration. Short admissions in the final days of life should be prevented in order to make dying at home more feasible.</p

Dying at home in Belgium: a descriptive GP interview study

<p>Abstract</p> <p>Background</p> <p>While increasing attention is being paid to enabling terminal patients to remain at home until death, limited information is available on the circumstances in which people at home actually die. Therefore this study aims to describe patient characteristics, functional and cognitive status and physical and psychological symptom burden in the last three months of life among Belgian patients dying at home, according to their GPs.</p> <p>Methods</p> <p>In 2005, a nationwide and retrospective interview study with GPs took place on people dying at home in Belgium as reported by Sentinel Network of GPs in Belgium. GPs registered all deaths (patients aged 1 year or more) weekly and were interviewed about all patients dying non-suddenly at home, using face-to-face structured interviews.</p> <p>Results</p> <p>Interviews were obtained on 205 patients (90% response rate). Between the second and third month before death, 55% were fully invalid or limited in self-care. In the last week of life, almost all were fully invalid. Fifty four percent were unconscious at some point during the last week; 46% were fully conscious. Most frequently reported symptoms were lack of energy, lack of appetite and feeling drowsy. Conditions most difficult for GPs to manage were shortness of breath, lack of energy and pain.</p> <p>Conclusions</p> <p>Many people dying at home under the care of their GPs in Belgium function relatively well until the last week of life and cognitive status seems to be preserved until the end in many cases. However, symptoms which GPs find difficult to control still manifest in many patients in the final week of life.</p

Minor Protease Inhibitor Mutations at Baseline Do Not Increase the Risk for a Virological Failure in HIV-1 Subtype B Infected Patients

BACKGROUND: Minor protease inhibitor (PI) mutations often exist as polymorphisms in HIV-1 sequences from treatment-naïve patients. Previous studies showed that their presence impairs the antiretroviral treatment (ART) response. Evaluating these findings in a larger cohort is essential. METHODS: To study the impact of minor PI mutations on time to viral suppression and time to virological failure, we included patients from the Swiss HIV Cohort Study infected with HIV-1 subtype B who started first-line ART with a PI and two nucleoside reverse transcriptase inhibitors. Cox regression models were performed to compare the outcomes among patients with 0 and ≥ 1 minor PI mutation. Models were adjusted for baseline HIV-1 RNA, CD4 cell count, sex, transmission category, age, ethnicity, year of ART start, the presence of nucleoside reverse transcriptase inhibitor mutations, and stratified for the administered PIs. RESULTS: We included 1199 patients of whom 944 (78.7%) received a boosted PI. Minor PI mutations associated with the administered PI were common: 41.7%, 16.1%, 4.7% and 1.9% had 1, 2, 3 or ≥ 4 mutations, respectively. The time to viral suppression was similar between patients with 0 (reference) and ≥ 1 minor PI mutation (multivariable hazard ratio (HR): 1.1 [95% confidence interval (CI): 1.0-1.3], P = .196). The time to virological failure was also similar (multivariable HR:.9 [95% CI:.5-1.6], P = .765). In addition, the impact of each single minor PI mutation was analyzed separately: none was significantly associated with the treatment outcome. CONCLUSIONS: The presence of minor PI mutations at baseline has no effect on the therapy outcome in HIV infected individuals

Predictors of dying at home for patients receiving nursing services in Japan: A retrospective study comparing cancer and non-cancer deaths

<p>Abstract</p> <p>Background</p> <p>The combined effects of the patient's and the family's preferences for death at home have in determining the actual site of death has not been fully investigated. We explored this issue on patients who had been receiving end-of-life care from Visiting Nurse Stations (VNS). In Japan, it has been the government's policy to promote end-of-life care at home by expanding the use of VNS services.</p> <p>Methods</p> <p>A retrospective national survey of a random sample of 2,000 out of the 5,224 VNS was made in January 2005. Questionnaires were mailed to VNS asking the respondents to fill in the questionnaire for each patient who had died either at home or at the hospital from July to December of 2004. Logistic regression analysis was respectively carried out to examine the factors related to dying at home for cancer and non-cancer patients.</p> <p>Results</p> <p>We obtained valid responses from 1,016 VNS (50.8%). The total number of patients who had died in the selected period was 4,175 (cancer: 1,664; non-cancer: 2,511). Compared to cancer patients, non-cancer patients were older and had more impairment in activities of daily living (ADL) and cognitive performance, and a longer duration of care. The factor having the greatest impact for dying at home was that of both the patient and the family expressing such preferences [cancer: OR (95% CI) = 57.00 (38.79-83.76); non-cancer: OR (95% CI) = 12.33 (9.51-15.99)]. The Odds ratio was greater compared with cases in which only the family had expressed such a preference and in which only the patient had expressed such a preference. ADL or cognitive impairment and the fact that their physician was based at a clinic, and not at a hospital, had modest effects on dying at home.</p> <p>Conclusions</p> <p>Dying at home was more likely when both the patient and the family had expressed such preferences, than when the patient alone or the family alone had done so, in both cancer and non-cancer patients. Health care professionals should try to elicit the patient's and family's preferences on where they would wish to die, following which they should then take appropriate measures to achieve this outcome.</p

Bioelectrical impedance phase angle as a prognostic indicator in breast cancer

<p>Abstract</p> <p>Background</p> <p>Bioelectrical impedance analysis (BIA) is an easy-to-use, non-invasive, and reproducible technique to evaluate changes in body composition and nutritional status. Phase angle, determined by bioelectrical impedance analysis (BIA), detects changes in tissue electrical properties and has been hypothesized to be a marker of malnutrition. Since malnutrition can be found in patients with breast cancer, we investigated the prognostic role of phase angle in breast cancer.</p> <p>Methods</p> <p>We evaluated a case series of 259 histologically confirmed breast cancer patients treated at Cancer Treatment Centers of America. Kaplan Meier method was used to calculate survival. Cox proportional hazard models were constructed to evaluate the prognostic effect of phase angle independent of stage at diagnosis and prior treatment history. Survival was calculated as the time interval between the date of first patient visit to the hospital and the date of death from any cause or date of last contact/last known to be alive.</p> <p>Results</p> <p>Of 259 patients, 81 were newly diagnosed at our hospital while 178 had received prior treatment elsewhere. 56 had stage I disease at diagnosis, 110 had stage II, 46 had stage III and 34 had stage IV. The median age at diagnosis was 49 years (range 25 – 74 years). The median phase angle score was 5.6 (range = 1.5 – 8.9). Patients with phase angle <= 5.6 had a median survival of 23.1 months (95% CI: 14.2 to 31.9; n = 129), while those > 5.6 had 49.9 months (95% CI: 35.6 to 77.8; n = 130); the difference being statistically significant (p = 0.031). Multivariate Cox modeling, after adjusting for stage at diagnosis and prior treatment history found that every one unit increase in phase angle score was associated with a relative risk of 0.82 (95% CI: 0.68 to 0.99, P = 0.041). Stage at diagnosis (p = 0.006) and prior treatment history (p = 0.001) were also predictive of survival independent of each other and phase angle.</p> <p>Conclusion</p> <p>This study demonstrates that BIA-derived phase angle is an independent prognostic indicator in patients with breast cancer. Nutritional interventions targeted at improving phase angle could potentially lead to an improved survival in patients with breast cancer.</p

Utilization of acute and long-term care in the last year of life: comparison with survivors in a population-based study

Background. It is well-known that the use of care services is most intensive in the last phase of life. However, so far only a few determinants of end-of-life care utilization are known. The aims of this study were to describe the utilization of acute and long-term care among older adults in their last year of life as compared to those not in their last year of life, and to examine which of a broad range of determinants can account for observed differences in care utilization. Methods. Data were used from the Longitudinal Aging Study Amsterdam (LASA). In a random, age and sex stratified population-based cohort of 3107 persons aged 55 ? 85 years at baseline and representative of the Netherlands, follow-up cycles took place at 3, 6 and 9 years. Those who died within one year directly after a cycle were defined as the "end-of-life group" (n = 262), and those who survived at least three years after a cycle were defined as the "survivors". Utilization of acute and long-term care services, including professional and informal care, were recorded at each cycle, as well as a broad range of health-related and psychosocial variables. Results. The end-of-life group used more care than the survivors. In the younger-old this difference was most pronounced for acute care, and in the older-old, for long-term care. Use of both acute and long-term home care in the last year of life was fully accounted for by health problems. Use of institutional care at the end of life was partly accounted for by health problems, but was not fully explained by the determinants included. Conclusion. This study shows that severity of health problems are decisive in the explanation of the increase in use of care services towards the end-of-life. This information is essential for an appropriate allocation of professional health care to the benefit of older persons themselves and their informal caregivers. © 2009 Pot et al; licensee BioMed Central Ltd