SummaryBackgroundStudies evaluating titration of antihypertensive medication using self-monitoring give contradictory findings and the precise place of telemonitoring over self-monitoring alone is unclear. The TASMINH4 trial aimed to assess the efficacy of self-monitored blood pressure, with or without telemonitoring, for antihypertensive titration in primary care, compared with usual care.MethodsThis study was a parallel randomised controlled trial done in 142 general practices in the UK, and included hypertensive patients older than 35 years, with blood pressure higher than 140/90 mm Hg, who were willing to self-monitor their blood pressure. Patients were randomly assigned (1:1:1) to self-monitoring blood pressure (self-montoring group), to self-monitoring blood pressure with telemonitoring (telemonitoring group), or to usual care (clinic blood pressure; usual care group). Randomisation was by a secure web-based system. Neither participants nor investigators were masked to group assignment. The primary outcome was clinic measured systolic blood pressure at 12 months from randomisation. Primary analysis was of available cases. The trial is registered with ISRCTN, number ISRCTN 83571366.Findings1182 participants were randomly assigned to the self-monitoring group (n=395), the telemonitoring group (n=393), or the usual care group (n=394), of whom 1003 (85%) were included in the primary analysis. After 12 months, systolic blood pressure was lower in both intervention groups compared with usual care (self-monitoring, 137·0 [SD 16·7] mm Hg and telemonitoring, 136·0 [16·1] mm Hg vs usual care, 140·4 [16·5]; adjusted mean differences vs usual care: self-monitoring alone, −3·5 mm Hg [95% CI −5·8 to −1·2]; telemonitoring, −4·7 mm Hg [–7·0 to −2·4]). No difference between the self-monitoring and telemonitoring groups was recorded (adjusted mean difference −1·2 mm Hg [95% CI −3·5 to 1·2]). Results were similar in sensitivity analyses including multiple imputation. Adverse events were similar between all three groups.InterpretationSelf-monitoring, with or without telemonitoring, when used by general practitioners to titrate antihypertensive medication in individuals with poorly controlled blood pressure, leads to significantly lower blood pressure than titration guided by clinic readings. With most general practitioners and many patients using self-monitoring, it could become the cornerstone of hypertension management in primary care.FundingNational Institute for Health Research via Programme Grant for Applied Health Research (RP-PG-1209-10051), Professorship to RJM (NIHR-RP-R2-12-015), Oxford Collaboration for Leadership in Applied Health Research and Care, and Omron Healthcare UK.

The use of self-monitoring of blood pressure, with or without telemonitoring, to guide therapy decisions by physicians for patients with hypertension has been recently demonstrated to reduce blood pressure compared with using clinic monitoring (usual care). However, both the cost-effectiveness of these strategies compared with usual care, and whether the additional benefit of telemonitoring compared with self-monitoring alone could be considered value for money, are unknown. This study assessed the cost-effectiveness of physician titration of antihypertensive medication using self-monitored blood pressure, with or without telemonitoring, to make hypertension treatment decisions in primary care compared with usual care. A Markov patient-level simulation model was developed taking a UK Health Service/Personal Social Services perspective. The model adopted a lifetime time horizon with 6-month time cycles. At a willingness to pay of £20 000 per quality-adjusted life year, self-monitoring plus telemonitoring was the most cost-effective strategy (£17 424 per quality-adjusted life year gained) compared with usual care or self-monitoring alone (posting the results to the physician). However, deterministic sensitivity analysis showed that self-monitoring alone became the most cost-effective option when changing key assumptions around long-term effectiveness and time horizon. Overall, probabilistic sensitivity analysis suggested that self-monitoring regardless of transmission modality was likely to be cost-effective compared with usual care (89% probability of cost-effectiveness at £20 000/quality-adjusted life year), with high uncertainty as to whether telemonitoring or self-monitoring alone was the most cost-effective option. Self-monitoring in clinical practice is cost-effective and likely to lead to reduced cardiovascular mortality and morbidity.

Summary Background 80% of individuals with cancer will require a surgical procedure, yet little comparative data exist on early outcomes in low-income and middle-income countries (LMICs). We compared postoperative outcomes in breast, colorectal, and gastric cancer surgery in hospitals worldwide, focusing on the effect of disease stage and complications on postoperative mortality. Methods This was a multicentre, international prospective cohort study of consecutive adult patients undergoing surgery for primary breast, colorectal, or gastric cancer requiring a skin incision done under general or neuraxial anaesthesia. The primary outcome was death or major complication within 30 days of surgery. Multilevel logistic regression determined relationships within three-level nested models of patients within hospitals and countries. Hospital-level infrastructure effects were explored with three-way mediation analyses. This study was registered with ClinicalTrials.gov , NCT03471494 . Findings Between April 1, 2018, and Jan 31, 2019, we enrolled 15 958 patients from 428 hospitals in 82 countries (high income 9106 patients, 31 countries; upper-middle income 2721 patients, 23 countries; or lower-middle income 4131 patients, 28 countries). Patients in LMICs presented with more advanced disease compared with patients in high-income countries. 30-day mortality was higher for gastric cancer in low-income or lower-middle-income countries (adjusted odds ratio 3·72, 95% CI 1·70–8·16) and for colorectal cancer in low-income or lower-middle-income countries (4·59, 2·39–8·80) and upper-middle-income countries (2·06, 1·11–3·83). No difference in 30-day mortality was seen in breast cancer. The proportion of patients who died after a major complication was greatest in low-income or lower-middle-income countries (6·15, 3·26–11·59) and upper-middle-income countries (3·89, 2·08–7·29). Postoperative death after complications was partly explained by patient factors (60%) and partly by hospital or country (40%). The absence of consistently available postoperative care facilities was associated with seven to 10 more deaths per 100 major complications in LMICs. Cancer stage alone explained little of the early variation in mortality or postoperative complications. Interpretation Higher levels of mortality after cancer surgery in LMICs was not fully explained by later presentation of disease. The capacity to rescue patients from surgical complications is a tangible opportunity for meaningful intervention. Early death after cancer surgery might be reduced by policies focusing on strengthening perioperative care systems to detect and intervene in common complications. Funding National Institute for Health Research Global Health Research Unit.

Background Surgical site infection (SSI) is a worldwide problem which has morbidity, mortality and financial consequences. The incidence rate of SSI is high in Low-and Middle-Income countries (LMICs) compared to high income countries, and the costly surgical complication can raise the potential risk of financial catastrophe. Objective The aim of the study is to critically appraise studies on the cost of SSI in a range of LMIC studies and compare these estimates with a reference standard of high income European studies who have explored similar SSI costs. Methods A systematic review was undertaken using searches of two electronic databases, EMBASE and MEDLINE In-Process & Other Non-Indexed Citations, up to February 2019. Study characteristics, comparator group, methods and results were extracted by using a standard template. Results Studies from 15 LMIC and 16 European countries were identified and reviewed in full. The additional cost of SSI range

BackgroundUnprovoked first venous thromboembolism (VTE) is defined as VTE in the absence of a temporary provoking factor such as surgery, immobility and other temporary factors. Recurrent VTE in unprovoked patients is highly prevalent, but easily preventable with oral anticoagulant (OAC) therapy. The unprovoked population is highly heterogeneous in terms of risk of recurrent VTE.ObjectivesThe first aim of the project is to review existing prognostic models which stratify individuals by their recurrence risk, therefore potentially allowing tailored treatment strategies. The second aim is to enhance the existing research in this field, by developing and externally validating a new prognostic model for individual risk prediction, using a pooled database containing individual patient data (IPD) from several studies. The final aim is to assess the economic cost-effectiveness of the proposed prognostic model if it is used as a decision rule for resuming OAC therapy, compared with current standard treatment strategies.MethodsStandard systematic review methodology was used to identify relevant prognostic model development, validation and cost-effectiveness studies. Bibliographic databases (including MEDLINE, EMBASE and The Cochrane Library) were searched using terms relating to the clinical area and prognosis. Reviewing was undertaken by two reviewers independently using pre-defined criteria. Included full-text articles were data extracted and quality assessed. Critical appraisal of included full texts was undertaken and comparisons made of model performance. A prognostic model was developed using IPD from the pooled database of seven trials. A novel internal–external cross-validation (IECV) approach was used to develop and validate a prognostic model, with external validation undertaken in each of the trials iteratively. Given good performance in the IECV approach, a final model was developed using all trials data. A Markov patient-level simulation was used to consider the economic cost-effectiveness of using a decision rule (based on the prognostic model) to decide on resumption of OAC therapy (or not).ResultsThree full-text articles were identified by the systematic review. Critical appraisal identified methodological and applicability issues; in particular, all three existing models did not have external validation. To address this, new prognostic models were sought with external validation. Two potential models were considered: one for use at cessation of therapy (pre D-dimer), and one for use after cessation of therapy (post D-dimer). Model performance measured in the external validation trials showed strong calibration performance for both models. The post D-dimer model performed substantially better in terms of discrimination (c = 0.69), better separating high- and low-risk patients. The economic evaluation identified that a decision rule based on the final post D-dimer model may be cost-effective for patients with predicted risk of recurrence of over 8% annually; this suggests continued therapy for patients with predicted risks ≥ 8% and cessation of therapy otherwise.ConclusionsThe post D-dimer model performed strongly and could be useful to predict individuals’ risk of recurrence at any time up to 2–3 years, thereby aiding patient counselling and treatment decisions. A decision rule using this model may be cost-effective for informing clinical judgement and patient opinion in treatment decisions. Further research may investigate new predictors to enhance model performance and aim to further externally validate to confirm performance in new, non-trial populations. Finally, it is essential that further research is conducted to develop a model predicting bleeding risk on therapy, to manage the balance between the risks of recurrence and bleeding.Study registrationThis study is registered as PROSPERO CRD42013003494.FundingThe National Institute for Health Research Health Technology Assessment programme.