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\"Model life tables provide ways of deriving accurate mortality schedules or predicting future trends from scanty data. In settings where accurate data are unavailable, these provide invaluable tools for estimating mortality conditions among populations. Constructing model life tables requires the availability of accurate empirical life tables that depict the different patterns of age-specific risks of death in the populations covered. Starting in the early 1960s, a number of field-based research stations were established to collect longitudinal data on births, deaths and migrations, covering some geographic areas in sub-Saharan Africa and Asia. In the late 1990s, these research sites teamed up to form an international network, INDEPTH.

Non-ST-elevation myocardial infarction (NSTEMI) and unstable angina pectoris are frequent causes of hospital admission in the elderly. However, clinical trials targeting this population are scarce, and these patients are less likely to receive treatment according to guidelines. We aimed to investigate whether this population would benefit from an early invasive strategy versus a conservative strategy. In this open-label randomised controlled multicentre trial, patients aged 80 years or older with NSTEMI or unstable angina admitted to 16 hospitals in the South-East Health Region of Norway were randomly assigned to an invasive strategy (including early coronary angiography with immediate assessment for percutaneous coronary intervention, coronary artery bypass graft, and optimum medical treatment) or to a conservative strategy (optimum medical treatment alone). A permuted block randomisation was generated by the Centre for Biostatistics and Epidemiology with stratification on the inclusion hospitals in opaque concealed envelopes, and sealed envelopes with consecutive inclusion numbers were made. The primary outcome was a composite of myocardial infarction, need for urgent revascularisation, stroke, and death and was assessed between Dec 10, 2010, and Nov 18, 2014. An intention-to-treat analysis was used. This study is registered with ClinicalTrials.gov, number NCT01255540. During a median follow-up of 1·53 years of participants recruited between Dec 10, 2010, and Feb 21, 2014, the primary outcome occurred in 93 (40·6%) of 229 patients assigned to the invasive group and 140 (61·4%) of 228 patients assigned to the conservative group (hazard ratio [HR] 0·53 [95% CI 0·41–0·69], p=0·0001). Five patients dropped out of the invasive group and one from the conservative group. HRs for the four components of the primary composite endpoint were 0·52 (0·35–0·76; p=0·0010) for myocardial infarction, 0·19 (0·07–0·52; p=0·0010) for the need for urgent revascularisation, 0·60 (0·25–1·46; p=0·2650) for stroke, and 0·89 (0·62–1·28; p=0·5340) for death from any cause. The invasive group had four (1·7%) major and 23 (10·0%) minor bleeding complications whereas the conservative group had four (1·8%) major and 16 (7·0%) minor bleeding complications. In patients aged 80 years or more with NSTEMI or unstable angina, an invasive strategy is superior to a conservative strategy in the reduction of composite events. Efficacy of the invasive strategy was diluted with increasing age (after adjustment for creatinine and effect modification). The two strategies did not differ in terms of bleeding complications. Norwegian Health Association (ExtraStiftelsen) and Inger and John Fredriksen Heart Foundation.

Background. Previous reports suggest that community-acquired pneumonia (CAP) is associated with an enhanced risk of cardiovascular complications. However, a contemporary and comprehensive characterization of this association is lacking. Methods. In this multicenter study, 1182 patients hospitalized for CAP were prospectively followed for up to 30 days after their hospitalization for this infection. Study endpoints included myocardial infarction, new or worsening heart failure, atrial fibrillation, stroke, deep venous thrombosis, cardiovascular death, and total mortality. Results. Three hundred eighty (32.2%) patients experienced intrahospital cardiovascular events (CVEs) including 281 (23.8%) with heart failure, 109 (9.2%) with atrial fibrillation, 89 (8%) with myocardial infarction, 11 (0.9%) with ischemic stroke, and 1 (0.1%) with deep venous thrombosis; 28 patients (2.4%) died for cardiovascular causes. Multivariable Cox regression analysis showed that intrahospital Pneumonia Severity Index (PSI) class (hazard ratio [HR], 2.45, P = .027; HR, 4.23, P < .001; HR, 5.96, P < .001, for classes III, IV, and V vs II, respectively), age (HR, 1.02, P = .001), and preexisting heart failure (HR, 1.85, P < .001) independently predicted CVEs. One hundred three (8.7%) patients died by day 30 postadmission. Thirty-day mortality was significantly higher in patients who developed CVEs compared with those who did not (17.6% vs 4.5%, P < .001). Multivariable Cox regression analysis showed that intrahospital CVEs (HR, 5.49, P < .001) independently predicted 30-day mortality (after adjustment for age, PSI score, and preexisting comorbid conditions). Conclusions. CVEs, mainly those confined to the heart, complicate the course of almost one-third of patients hospitalized for CAP. More importantly, the occurrence of CVEs is associated with a 5-fold increase in CAP-associated 30-day mortality.

The TARGIT-A trial compared risk-adapted radiotherapy using single-dose targeted intraoperative radiotherapy (TARGIT) versus fractionated external beam radiotherapy (EBRT) for breast cancer. We report 5-year results for local recurrence and the first analysis of overall survival. TARGIT-A was a randomised, non-inferiority trial. Women aged 45 years and older with invasive ductal carcinoma were enrolled and randomly assigned in a 1:1 ratio to receive TARGIT or whole-breast EBRT, with blocks stratified by centre and by timing of delivery of targeted intraoperative radiotherapy: randomisation occurred either before lumpectomy (prepathology stratum, TARGIT concurrent with lumpectomy) or after lumpectomy (postpathology stratum, TARGIT given subsequently by reopening the wound). Patients in the TARGIT group received supplemental EBRT (excluding a boost) if unforeseen adverse features were detected on final pathology, thus radiotherapy was risk-adapted. The primary outcome was absolute difference in local recurrence in the conserved breast, with a prespecified non-inferiority margin of 2·5% at 5 years; prespecified analyses included outcomes as per timing of randomisation in relation to lumpectomy. Secondary outcomes included complications and mortality. This study is registered with ClinicalTrials.gov, number NCT00983684. Patients were enrolled at 33 centres in 11 countries, between March 24, 2000, and June 25, 2012. 1721 patients were randomised to TARGIT and 1730 to EBRT. Supplemental EBRT after TARGIT was necessary in 15·2% [239 of 1571] of patients who received TARGIT (21·6% prepathology, 3·6% postpathology). 3451 patients had a median follow-up of 2 years and 5 months (IQR 12–52 months), 2020 of 4 years, and 1222 of 5 years. The 5-year risk for local recurrence in the conserved breast was 3·3% (95% CI 2·1–5·1) for TARGIT versus 1·3% (0·7–2·5) for EBRT (p=0·042). TARGIT concurrently with lumpectomy (prepathology, n=2298) had much the same results as EBRT: 2·1% (1·1–4·2) versus 1·1% (0·5–2·5; p=0·31). With delayed TARGIT (postpathology, n=1153) the between-group difference was larger than 2·5% (TARGIT 5·4% [3·0–9·7] vs EBRT 1·7% [0·6–4·9]; p=0·069). Overall, breast cancer mortality was much the same between groups (2·6% [1·5–4·3] for TARGIT vs 1·9% [1·1–3·2] for EBRT; p=0·56) but there were significantly fewer non-breast-cancer deaths with TARGIT (1·4% [0·8–2·5] vs 3·5% [2·3–5·2]; p=0·0086), attributable to fewer deaths from cardiovascular causes and other cancers. Overall mortality was 3·9% (2·7–5·8) for TARGIT versus 5·3% (3·9–7·3) for EBRT (p=0·099). Wound-related complications were much the same between groups but grade 3 or 4 skin complications were significantly reduced with TARGIT (four of 1720 vs 13 of 1731, p=0·029). TARGIT concurrent with lumpectomy within a risk-adapted approach should be considered as an option for eligible patients with breast cancer carefully selected as per the TARGIT-A trial protocol, as an alternative to postoperative EBRT. University College London Hospitals (UCLH)/UCL Comprehensive Biomedical Research Centre, UCLH Charities, National Institute for Health Research Health Technology Assessment programme, Ninewells Cancer Campaign, National Health and Medical Research Council, and German Federal Ministry of Education and Research.

BACKGROUND:There is considerable scientific interest in associations between protracted low-dose exposure to ionizing radiation and the occurrence of specific types of cancer. METHODS:Associations between ionizing radiation and site-specific solid cancer mortality were examined among 308,297 nuclear workers employed in France, the United Kingdom, and the United States. Workers were monitored for external radiation exposure and follow-up encompassed 8.2 million person-years. Radiation–mortality associations were estimated using a maximum-likelihood method and using a Markov chain Monte Carlo method, the latter used to fit a hierarchical regression model to stabilize estimates of association. RESULTS:The analysis included 17,957 deaths attributable to solid cancer, the most common being lung, prostate, and colon cancer. Using a maximum-likelihood method to quantify associations between radiation dose- and site-specific cancer, we obtained positive point estimates for oral, esophagus, stomach, colon, rectum, pancreas, peritoneum, larynx, lung, pleura, bone and connective tissue, skin, ovary, testis, and thyroid cancer; in addition, we obtained negative point estimates for cancer of the liver and gallbladder, prostate, bladder, kidney, and brain. Most of these estimated coefficients exhibited substantial imprecision. Employing a hierarchical model for stabilization had little impact on the estimated associations for the most commonly observed outcomes, but for less frequent cancer types, the stabilized estimates tended to take less extreme values and have greater precision than estimates obtained without such stabilization. CONCLUSIONS:The results provide further evidence regarding associations between low-dose radiation exposure and cancer.

Individual patient data from two randomised trials comparing neoadjuvant chemotherapy with upfront debulking surgery in advanced tubo-ovarian cancer were analysed to examine long-term outcomes for patients and to identify any preferable therapeutic approaches for subgroup populations. We did a per-protocol pooled analysis of individual patient data from the European Organisation for Research and Treatment of Cancer (EORTC) 55971 trial (NCT00003636) and the Medical Research Council Chemotherapy Or Upfront Surgery (CHORUS) trial (ISRCTN74802813). In the EORTC trial, eligible women had biopsy-proven International Federation of Gynecology and Obstetrics (FIGO) stage IIIC or IV invasive epithelial tubo-ovarian carcinoma. In the CHORUS trial, inclusion criteria were similar to those of the EORTC trial, and women with apparent FIGO stage IIIA and IIIB disease were also eligible. The main aim of the pooled analysis was to show non-inferiority in overall survival with neoadjuvant chemotherapy compared with upfront debulking surgery, using the reverse Kaplan-Meier method. Tests for heterogeneity were based on Cochran's Q heterogeneity statistic. Data for 1220 women were included in the pooled analysis, 670 from the EORTC trial and 550 from the CHORUS trial. 612 women were randomly allocated to receive upfront debulking surgery and 608 to receive neoadjuvant chemotherapy. Median follow-up was 7·6 years (IQR 6·0–9·6; EORTC, 9·2 years [IQR 7·3–10·4]; CHORUS, 5·9 years [IQR 4·3–7·4]). Median age was 63 years (IQR 56–71) and median size of the largest metastatic tumour at diagnosis was 8 cm (IQR 4·8–13·0). 55 (5%) women had FIGO stage II–IIIB disease, 831 (68%) had stage IIIC disease, and 230 (19%) had stage IV disease, with staging data missing for 104 (9%) women. In the entire population, no difference in median overall survival was noted between patients who underwent neoadjuvant chemotherapy and upfront debulking surgery (27·6 months [IQR 14·1–51·3] and 26·9 months [12·7–50·1], respectively; hazard ratio [HR] 0·97, 95% CI 0·86–1·09; p=0·586). Median overall survival for EORTC and CHORUS patients was significantly different at 30·2 months (IQR 15·7–53·7) and 23·6 months (10·5–46·9), respectively (HR 1·20, 95% CI 1·06–1·36; p=0·004), but was not heterogeneous (Cochran's Q, p=0·17). Women with stage IV disease had significantly better outcomes with neoadjuvant chemotherapy compared with upfront debulking surgery (median overall survival 24·3 months [IQR 14·1–47·6] and 21·2 months [10·0–36·4], respectively; HR 0·76, 95% CI 0·58–1·00; p=0·048; median progression-free survival 10·6 months [7·9–15·0] and 9·7 months [5·2–13·2], respectively; HR 0·77, 95% CI 0·59–1·00; p=0·049). Long-term follow-up data substantiate previous results showing that neoadjuvant chemotherapy and upfront debulking surgery result in similar overall survival in advanced tubo-ovarian cancer, with better survival in women with stage IV disease with neoadjuvant chemotherapy. This pooled analysis, with long-term follow-up, shows that neoadjuvant chemotherapy is a valuable treatment option for patients with stage IIIC–IV tubo-ovarian cancer, particularly in patients with a high tumour burden at presentation or poor performance status. National Cancer Institute and Vlaamse Liga tegen kanker (Flemish League against Cancer).