Forecasting telecommunications data with linear models

For telecommunication companies to successfully manage their business, companies rely on mapping future trends and usage patterns. However, the evolution of telecommunications technology and systems in the provision of services renders imperfections in telecommunications data and impinges on a company’s’ ability to properly evaluate and plan their business. ITU Recommendation E.507 provides a selection of econometric models for forecasting these trends. However, no specific guidance is given. This paper evaluates whether simple extrapolation techniques in Recommendation E.507 can generate accurate forecasts. Standard forecast error statistics—mean absolute percentage error, median absolute percentage error and percentage better—show the ARIMA, Holt and Holt-D models provide better forecasts than a random walk and other linear extrapolation methods

Predictors of functional dependency in Parkinson’s disease

Financial disclosures/conflicts of interest: Dr Macleod was funded by a Clinical Academic Fellowship from the Chief Scientist Office of the Scottish Government and received grant funding from Parkinson’s UK, the Wellcome Trust, University of Aberdeen, and NHS Grampian endowments relating to this research. Dr Counsell received grant funding from Parkinson’s UK, National Institute for Health Research, the Scottish Chief Scientist Office, the BMA Doris Hillier award, RS Macdonald Trust, the BUPA Foundation, NHS Grampian endowments and SPRING relating to this research. We declare we have no conflicts of interest. Financial support: This study was funded by Parkinson’s UK, the Scottish Chief Scientist Office, NHS Grampian endowments, the BMA Doris Hillier award, RS Macdonald Trust, the BUPA Foundation, and SPRING.  Peer reviewedPublisher PD

Caesarean section and risk of unexplained stillbirth in subsequent pregnancy

Background Caesarean section is associated with an increased risk of disorders of placentation in subsequent pregnancies, but effects on the rate of antepartum stillbirth are unknown. We aimed to establish whether previous caesarean delivery is associated with an increased risk of antepartum stillbirth. Methods We linked pregnancy discharge data from the Scottish Morbidity Record (1980–98) and the Scottish Stillbirth and Infant Death Enquiry (1985–98). We estimated the relative risk of antepartum stillbirth in second pregnancies using time-to-event analyses. Findings For 120 633 singleton second births, there were 68 antepartum stillbirths in 17 754 women previously delivered by caesarean section (2–39 per 10 000 women per week) and 244 in 102879 women previously delivered vaginally (1·44; p<0·001). Risk of unexplained stillbirth associated with previous caesarean delivery differed significantly with gestational age (p=0·04); the excess risk was apparent from 34 weeks (hazard ratio 2·23 [95% Cl 1·48–3·36]). Risk was not attenuated by adjustment for maternal characteristics or outcome of the first pregnancy (2·74 [1·74–4·30]). The absolute risk of unexplained stillbirth at or after 39 weeks' gestation was 1·1 per 1000 women who had had a previous caesarean section and 0·5 per 1000 in those who had not. The difference was due mostly to an excess of unexplained stillbirths among women previously delivered by caesarean section. Interpretation Delivery by caesarean section in the first pregnancy could increase the risk of unexplained stillbirth in the second. In women with one previous caesarean delivery, the risk of unexplained antepartum stillbirth at or after 39 weeks' gestation is about double the risk of stillbirth or neonatal death from intrapartum uterine rupture

Efficacy of Liver Transplantation in Patients with Primary Biliary Cirrhosis

No controlled trials have been performed to assess the efficacy of liver transplantation. Because of the marked improvement in survival after liver transplantation since 1981, random assignment of patients to a control group not undergoing transplantation is considered clinically inappropriate. To assess the efficacy of liver transplantation in patients with primary biliary cirrhosis, we compared survival in 161 patients with this diagnosis who had undergone a liver transplantation with survival in patients with the same diagnosis who had been treated conservatively. The comparison was performed with use of a recently developed statistical technique, the Mayo model. All patients had undergone liver transplantation between March 1980 and June 1987 and were followed for a median of 25 months. Three months after liver transplantation, the Kaplan–Meier survival probabilities in the recipients were substantially higher than the Mayo-model “simulated-control” survival probabilities (P<0.001). At two years, the Kaplan–Meier survival probability was 0.74, whereas the mean Mayo-model survival probability was 0.31. The patients who were at low risk according to the Mayo model had the best probability of survival after liver transplantation; however, patients at all risk levels who had undergone liver transplantation had higher probabilities of survival than those who had not. We conclude that liver transplantation is an efficacious treatment in patients with advanced primary biliary cirrhosis. (N Engl J Med 1989; 320:1709–13.), LIVER transplantation has been accepted clinically as a lifesaving treatment in various end-stage liver diseases, including primary biliary cirrhosis.1,2 However, no controlled trials have been performed to evaluate the efficacy of this procedure. Indeed, because there has been a marked improvement since 1981 in survival after transplantation, random assignment of patients with advanced liver disease to a nontransplantation control group is considered to be clinically inappropriate. At the Mayo Clinic, a Cox regression model for predicting the probability of survival in patients with conservatively treated primary biliary cirrhosis has been developed.3 To provide control data for assessing the efficacy of…. © 1989, Massachusetts Medical Society. All rights reserved

Incidence, risk factors and causes of death in an HIV care programme with a large proportion of injecting drug users.

Objectives  To identify factors influencing mortality in an HIV programme providing care to large numbers of injecting drug users (IDUs) and patients co-infected with hepatitis C (HCV). Methods  A longitudinal analysis of monitoring data from HIV-infected adults who started antiretroviral therapy (ART) between 2003 and 2009 was performed. Mortality and programme attrition rates within 2 years of ART initiation were estimated. Associations with individual-level factors were assessed with multivariable Cox and piece-wise Cox regression. Results  A total of 1671 person-years of follow-up from 1014 individuals was analysed. Thirty-four percent of patients were women and 33% were current or ex-IDUs. 36.2% of patients (90.8% of IDUs) were co-infected with HCV. Two-year all-cause mortality rate was 5.4 per 100 person-years (95% CI, 4.4-6.7). Most HIV-related deaths occurred within 6 months of ART start (36, 67.9%), but only 5 (25.0%) non-HIV-related deaths were recorded during this period. Mortality was higher in older patients (HR = 2.50; 95% CI, 1.42-4.40 for ≥40 compared to 15-29 years), and in those with initial BMI < 18.5 kg/m(2) (HR = 3.38; 95% CI, 1.82-5.32), poor adherence to treatment (HR = 5.13; 95% CI, 2.47-10.65 during the second year of therapy), or low initial CD4 cell count (HR = 4.55; 95% CI, 1.54-13.41 for <100 compared to ≥100 cells/μl). Risk of death was not associated with IDU status (P = 0.38). Conclusion  Increased mortality was associated with late presentation of patients. In this programme, death rates were similar regardless of injection drug exposure, supporting the notion that satisfactory treatment outcomes can be achieved when comprehensive care is provided to these patients

Pulsatile luteinizing hormone disruption in depression

Two independent groups recently published data comparing pulsatile luteinizing hormone (LH) release between depressed and control women. Despite similar populations and LH sampling frequency, they reached different conclusions: Meller et al. [Am. J. Psych. 154 (1997) 1454] found disruption of normal LH pulsatility in depressed women, whereas Young et al. [Arch. Gen. Psych. 57 (2000) 1157] did not. To resolve this discrepancy, the current study applies a single, well-established statistical method, spectral analysis, to the two data sets and concludes that both depressed populations display significantly altered LH pulsatile release.NIMH MH50030Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/49487/2/YoungandGrambsch.pd

Risk stratification of patients with nodal involvement in upper tract urothelial carcinoma: value of lymph-node density

To determine the risk factors associated with clinical outcome in patients with lymph node (LN)-positive urothelial carcinoma of the upper urinary tract (UTUC) treated with radical nephroureterectomy (RNU) and lymphadenectomy, focusing on the concept of LN density (LND). PATIENTS AND METHODS Patients undergoing RNU with regional lymphadenectomy were identified through multi-institutional databases. All pathology slides were re-evaluated by genitourinary pathologists unaware of the clinical data. The exposure variable used was LND (continuously coded and that of all possible thresholds) with recurrence-free and disease-specific survival (DSS) serving as the outcome measures. RESULTS Of 432 patients undergoing RNU with lymphadenectomy, 135 (31%) had LN metastases. Within a median follow-up of 4.1 years, 90 of the 135 patients with LN metastases (68%) had disease recurrence and 76 (58%) died from UTUC. The mean (sem) 5-year recurrence-free and DSS probabilities were 27 (4)% and 33 (5)%, respectively. The median (range) LND was 50 (3–100)%. The most informative threshold for LND in relation to outcome was 30%. In multivariable analyses that adjusted for the effects of tumour stage and grade, patients with a LND of ≥30% were at greater risk of both cancer recurrence, with 5-year rates of 25 (5)% vs 38 (8)% (hazard ratio 1.8, P  = 0.021) and mortality, with 5-year rates of 30 (6)% vs 48 (9)% (1.7, P  = 0.032) compared to those with a LND of <30%. Our results are primarily limited by a lack of standardization in the lymphadenectomy template. CONCLUSION We evaluated the concept of LND for the first time in UTUC. LND provides additional prognostic information in patients with node-positive disease after RNU. The use of LND in clinical trials might provide an additional insight into the value of LN dissection in patients undergoing RNU.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/75412/1/j.1464-410X.2008.07988.x.pd

A special case of reduced rank models for identification and modelling of time varying effects in survival analysis

Flexible survival models are in need when modelling data from long term follow-up studies. In many cases, the assumption of proportionality imposed by a Cox model will not be valid. Instead, a model that can identify time varying effects of fixed covariates can be used. Although there are several approaches that deal with this problem, it is not always straightforward how to choose which covariates should be modelled having time varying effects and which not. At the same time, it is up to the researcher to define appropriate time functions that describe the dynamic pattern of the effects. In this work, we suggest a model that can deal with both fixed and time varying effects and uses simple hypotheses tests to distinguish which covariates do have dynamic effects. The model is an extension of the parsimonious reduced rank model of rank 1. As such, the number of parameters is kept low, and thus, a flexible set of time functions, such as b-splines, can be used. The basic theory is illustrated along with an efficient fitting algorithm. The proposed method is applied to a dataset of breast cancer patients and compared with a multivariate fractional polynomials approach for modelling time-varying effects. Copyright © 2016 John Wiley & Sons, Ltd

Inhibition of EGFR, HER2, and HER3 signalling in patients with colorectal cancer wild-type for BRAF, PIK3CA, KRAS, and NRAS (FOCUS4-D): a phase 2–3 randomised trial

Background: A substantial change in trial methodology for solid tumours has taken place, in response to increased understanding of cancer biology. FOCUS4 is a phase 2–3 trial programme testing targeted agents in patients with advanced colorectal cancer in molecularly stratified cohorts. Here, we aimed to test the hypothesis that combined inhibition of EGFR, HER2, and HER3 signalling with the tyrosine kinase inhibitor AZD8931 will control growth of all wild-type tumours. Methods: In FOCUS4-D, we included patients from 18 hospitals in the UK with newly diagnosed advanced or metastatic colorectal cancer whose tumour was wild-type for BRAF, PIK3CA, KRAS, and NRAS. After 16 weeks of first-line therapy, patients with stable or responding tumours were randomised to oral AZD8931 (40 mg twice a day) or placebo. Randomisation was done by minimisation with a random element of 20%, minimisation by hospital site, site of primary tumour, WHO performance status, 16-week CT scan result, number of metastatic sites, and first-line chemotherapy regimen. The primary outcome was progression-free-survival. CT scans were assessed by local radiologists according to Response Evaluation Criteria in Solid Tumors (RECIST), version 1.1. Preplanned interim analyses were assessed per protocol and were agreed using multiarm multistage (MAMS) trial design methodology triggered by occurrence of progression-free survival events in the placebo group. The final analysis was assessed by intention to treat. This trial is registered at , ISRCTN 90061546. Findings: Between July 7, 2014, and March 7, 2016, 32 patients were randomised to study treatment, 16 to AZD8931 and 16 to placebo. At the first preplanned interim analysis (March, 2016), the independent data monitoring committee (IDMC) recommended closure of FOCUS4-D because of a lack of activity. At the final analysis (Aug 1, 2016), 31 patients had had a progression-free survival event (15 with AZD8931 and 16 with placebo). Median progression-free survival was 3·48 months (95% CI 1·51–5·09) in the placebo group and 2·96 months (1·94–5·62) in the AZD8931 group. No progression-free survival benefit of AZD8931 compared with placebo was noted (hazard ratio [HR] 1·10, 95% CI 0·47–3·57; p=0·95). The most common grade 3 adverse event in the AZD8931 group was skin rash (three [20%] of 15 patients with available data vs none of 16 patients in the placebo group), and in the placebo group it was diarrhoea (one [7%] vs one [6%]). No grade 4 adverse events were recorded and no treatment-related deaths were reported. Interpretation: The MAMS trial design for FOCUS4 has shown efficiency and effectiveness in trial outcome delivery, informing the decision to proceed or stop clinical evaluation of a targeted treatment within a molecularly defined cohort of patients. The overarching FOCUS4 trial is now aiming to open a replacement arm in the cohort with all wild-type tumours. Funding: Medical Research Council (MRC) and National Institute for Health Research (NIHR) Efficacy and Mechanism Evaluation programme, Cancer Research UK, NIHR Clinical Trials Research Network, Health and Care Research Wales, and AstraZeneca